FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Bozkurt, B Mann, DL AF Bozkurt, B Mann, DL TI Use of biomarkers in the management of heart failure - Are we there yet? SO CIRCULATION LA English DT Editorial Material DE editorials; heart failure; morbidity; mortality ID LEFT-VENTRICULAR DYSFUNCTION; BRAIN NATRIURETIC PEPTIDE; ENALAPRIL; SURVIVAL; THERAPY C1 Baylor Coll Med, Dept Med, Winters Ctr Heart Failure Res, Houston, TX 77030 USA. Houston Vet Adm Med Ctr, Houston, TX USA. Methodist Hosp, Houston, TX 77030 USA. RP Mann, DL (reprint author), Baylor Coll Med, Dept Med, Winters Ctr Heart Failure Res, MS 524,6565 Fannin, Houston, TX 77030 USA. OI Mann, Douglas /0000-0002-2516-0145 FU NHLBI NIH HHS [P50 HL-O6H, R01 HL58081-01, HL-42250-10/10, R01 HL61543-01] NR 12 TC 20 Z9 29 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 11 PY 2003 VL 107 IS 9 BP 1231 EP 1233 DI 10.1161/01.CIR.0000057608.97285.20 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 653ZM UT WOS:000181467000002 PM 12628938 ER PT J AU Ascherio, A Chen, H Schwarzschild, MA Zhang, SM Colditz, GA Speizer, FE AF Ascherio, A Chen, H Schwarzschild, MA Zhang, SM Colditz, GA Speizer, FE TI Caffeine, postmenopausal estrogen, and risk of Parkinson's disease SO NEUROLOGY LA English DT Article ID MESENCEPHALIC DOPAMINERGIC-NEURONS; CORONARY HEART-DISEASE; CLINICAL-DIAGNOSIS; COFFEE CONSUMPTION; CIGARETTE-SMOKING; WOMEN; ESTRADIOL; ACCURACY; ALCOHOL; 17-BETA-ESTRADIOL AB Background: Men who regularly consume caffeinated drinks have a lower risk of PD than do nondrinkers, but this relation has not been found in women. Because this sex difference could be due to hormonal effects, the authors examined prospectively the risk of PD according to use of postmenopausal hormones and caffeine intake among participants in the Nurses' Health Study. Methods: The study population comprised 77,713 women free of PD, stroke, or cancer at baseline, who were postmenopausal at baseline or reached menopause before the end of the study. During 18 years of follow-up the authors documented 154 cases of PD. Results: Overall, the risk of PD was similar in women using hormones and women who never used hormones (relative risk 1.02, 95% CI 0.69 to 1.52). Use of hormones, however, was associated with a reduced risk of PD among women with low caffeine consumption (RR 0.39, 95% CI 0.13 to 1.17), and with increased risk among women with high caffeine consumption (RR 2.44, 95% CI 0.75 to 7.86; p for interaction = 0.01). Among hormone users, women consuming six or more cups of coffee per day had a fourfold higher risk of PD (RR 3.92, 95% CI 1.49 to 10.34; p = 0.006) than did women who never drink coffee. Conclusions: These results suggest that caffeine reduces the risk of PD among women who do not use postmenopausal hormones, but increases risk among hormone users. Clinical trials of caffeine or estrogens in women should avoid the combined use of these agents. 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, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Ascherio, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009; OI Colditz, Graham/0000-0002-7307-0291; Chen, Honglei/0000-0003-3446-7779 FU NIEHS NIH HHS [ES10804]; NINDS NIH HHS [NS35624] NR 55 TC 114 Z9 116 U1 2 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 11 PY 2003 VL 60 IS 5 BP 790 EP 795 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 679XY UT WOS:000182948300011 PM 12629235 ER PT J AU Douglas, JG Bakris, GL Epstein, M Ferdinand, KC Ferrario, C Flack, JM Jamerson, KA Jones, WE Haywood, J Maxey, R Ofili, EO Sanders, E Schiffrin, EL Sica, DA Sowers, JR Vidt, DG AF Douglas, JG Bakris, GL Epstein, M Ferdinand, KC Ferrario, C Flack, JM Jamerson, KA Jones, WE Haywood, J Maxey, R Ofili, EO Sanders, E Schiffrin, EL Sica, DA Sowers, JR Vidt, DG CA Hypertension African Amer Working TI Management of high blood pressure in African Americans - Consensus statement of the hypertension in African Americans Working Group of the International Society on Hypertension in Blacks SO ARCHIVES OF INTERNAL MEDICINE LA English DT Review ID CONVERTING-ENZYME-INHIBITOR; HEALTH-CARE PROFESSIONALS; TO-MODERATE HYPERTENSION; LEFT-VENTRICULAR DYSFUNCTION; RANDOMIZED CONTROLLED TRIAL; PRACTICE GUIDELINES COMMITTEE; ASSOCIATION TASK-FORCE; COLLEGE-OF-CARDIOLOGY; CHRONIC HEART-FAILURE; END-POINT REDUCTION AB The purpose of this consensus statement is to offer primary care providers (including physicians, nurse practitioners, and physician assistants) a practical, evidence-based clinical tool for achieving blood pressure goals in African American patients. The need for specific recommendations for African Americans is highlighted by compelling evidence of a higher prevalence of hypertension and poorer cardiovascular and renal outcomes in this group than in white Americans. African Americans have disturbingly higher rates of cardiovascular mortality, stroke, hypertension-related heart disease, congestive heart failure, type 2 diabetes mellitus, hypertensive nephropathy, and end-stage renal disease (ESRD). C1 Case Western Reserve Univ, Dept Med, Sch Med, Cleveland, OH 44106 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ Miami, Sch Med, Miami, FL 33152 USA. Heartbeats Life Ctr, New Orleans, LA USA. Wake Forest Univ, Sch Med, Hypertens & Vasc Dis Ctr, Winston Salem, NC 27109 USA. Wayne State Univ, Sch Med, Detroit, MI USA. Univ Michigan, Hlth Syst, Ann Arbor, MI 48109 USA. S Texas Vet Hlth Syst, San Antonio, TX USA. Univ So Calif, Med Ctr, Los Angeles, CA USA. Natl Med Assoc Board Trustees, Los Angeles, CA USA. Morehouse Sch Med, Atlanta, GA 30310 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Clin Res Inst Montreal, Montreal, PQ H2W 1R7, Canada. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Douglas, JG (reprint author), Case Western Reserve Univ, Dept Med, Sch Med, Room W-165,10900 Euclid Ave, Cleveland, OH 44106 USA. NR 132 TC 258 Z9 261 U1 2 U2 13 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 MAR 10 PY 2003 VL 163 IS 5 BP 525 EP 541 DI 10.1001/archinte.163.5.525 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 655PH UT WOS:000181561000003 PM 12622600 ER PT J AU Patel, SR White, DP Malhotra, A Stanchina, ML Ayas, NT AF Patel, SR White, DP Malhotra, A Stanchina, ML Ayas, NT TI Continuous positive airway pressure therapy for treating sleepiness in a diverse population with obstructive sleep apnea - Results of a meta-analysis SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PLACEBO-CONTROLLED TRIAL; PROSPECTIVE PARALLEL TRIAL; DAYTIME SLEEPINESS; APNOEA/HYPOPNOEA SYNDROME; HYPOPNEA SYNDROME; APNEA/HYPOPNEA SYNDROME; CLINICAL-TRIALS; CPAP TREATMENT; NASAL-CPAP; ACCIDENTS AB Background: Although continuous positive airway pressure (CPAP) has become the standard of care in the treatment of obstructive sleep apnea (OSA), 2 systematic reviews have questioned its utility. Since the publication of these reviews, several randomized controlled trials' have been reported. We, therefore, performed a meta-analysis to assess the effect of CPAP on subjective and objective sleepiness. Methods: We conducted a thorough literature search to identify all published randomized controlled trials of CPAP in patients with OSA. Meta-analyses were performed using a random-effects model: Statistical heterogeneity was assessed using the Q statistic. Results: Twelve trials of CPAP in patients with OSA meeting our inclusion criteria were found. The Epworth Sleepiness Scale score was reported in 11 studies (706 patients). A meta-analysis found that CPAP reduced the Epworth Sleepiness Scale score an average of 2.94 points more than placebo (P < .001). The heterogeneity (Q(10) = 57.7, P < .001) between studies could not be explained by differences in sex composition, mean age, mean body mass index, or country of study. Trials recruiting subjects with severe OSA plus sleepiness (mean apnea-hypopnea index, greater than or equal to 30 events per hour; and mean Epworth Sleepiness Scale score, greater than or equal to 11) had a greater decrease in the Epworth Sleepiness Scale score than the other studies (4.75 vs 1.10; P < .001). Objective measures of sleepiness were reported in 8 trials (482 subjects). Continuous positive airway pressure increased sleep onset latency by 0.93 minute (P = .04) more than placebo. Conclusions: Continuous positive airway pressure therapy significantly improves subjective and objective measures of sleepiness in patients with OSA across a diverse range of populations. Patients with more severe apnea and sleepiness seem to benefit the most. C1 Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ayas, NT (reprint author), Vancouver Gen Hosp, Div Pulm Med, 2775 Heather St, Vancouver, BC V5Z 3J5, Canada. FU NHLBI NIH HHS [HL07633, HL48531, HL60292] NR 34 TC 214 Z9 221 U1 1 U2 12 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 MAR 10 PY 2003 VL 163 IS 5 BP 565 EP 571 DI 10.1001/archinte.163.5.565 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 655PH UT WOS:000181561000006 PM 12622603 ER PT J AU Hylek, EM Regan, S Henault, LE Gardner, M Chan, AT Singer, DE Barry, MJ AF Hylek, EM Regan, S Henault, LE Gardner, M Chan, AT Singer, DE Barry, MJ TI Challenges to the effective use of unfractionated heparin in the hospitalized management of acute thrombosis SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 02-05, 2001 CL SAN DIEGO, CALIFORNIA SP Soc Gen Internal Med ID MOLECULAR-WEIGHT HEPARIN; DEEP-VEIN THROMBOSIS; VENOUS THROMBOSIS; MYOCARDIAL-INFARCTION; SUBCUTANEOUS HEPARIN; PULMONARY-EMBOLISM; THERAPY; NOMOGRAM; PHARMACOKINETICS; ACHIEVE AB Background: Unfractionated heparin therapy is care intensive because of dose-response variability, and because of the necessity of constant intravenous infusion and frequent monitoring. We sought to assess the real-world course of transition from heparin to warfarin in hospitalized patients undergoing anticoagulation therapy for acute venous or arterial thrombosis at our medical center. Methods: Patients were retrospectively identified from July 1998 to December 1998. Data collected included initiation and maintenance doses of heparin, frequency of monitoring and dose adjustments, time to the therapeutic range, complications and interruptions of therapy, and characteristics of heparin-to-warfarin transition. Results: Of the 311 patients who met the study criteria during the 6-month period, 134 had venous thromboembolism, 122 had cerebral arterial thrombosis, and 55 had peripheral arterial thrombosis. Groups differed in use and magnitude of initial heparin bolus, frequency of monitoring, and time to the therapeutic range. Dose response to intravenous heparin was highly variable. Even when the activated partial thromboplastin time reached the therapeutic range of 55 to 85 seconds, the next 2 consecutive measurements remained in this range in only 29% of the patients. Patients received an average of 4 different heparin doses over the first 3 days of treatment, and the therapeutic range was maintained on each of 4 sequential days in only 7% of them. During the course of therapy, 54% of the patients had at least I prolonged interruption in heparin infusion, and 4.8% sustained a major hemorrhage. Overall, 20% of the patients met the currently recommended treatment guideline of 4 days or more of heparin and warfarin overlap, until the international normalized ratio is greater than 2.0 for 2 consecutive days. Conclusions: Multiple challenges to effective anticoagulation treatment with unfractionated heparin exist in the hospital setting. Strategies are needed to improve the overall quality of anticoagulant care, including the substitution of low-molecular-weight heparin for unfractionated heparin, where appropriate. C1 Massachusetts Gen Hosp, Div Gen Med, Clin Epidemiol Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hylek, EM (reprint author), Massachusetts Gen Hosp, Div Gen Med, Clin Epidemiol Unit, Dept Med, 9th Floor,50 Staniford St, Boston, MA 02114 USA. NR 20 TC 34 Z9 37 U1 0 U2 0 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 MAR 10 PY 2003 VL 163 IS 5 BP 621 EP 627 DI 10.1001/archinte.163.5.621 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 655PH UT WOS:000181561000014 PM 12622610 ER PT J AU Johnson, KM Alarcon, J Watts, DM Rodriguez, C Velasquez, C Sanchez, J Lockhart, D Stoner, BP Holmes, KK AF Johnson, KM Alarcon, J Watts, DM Rodriguez, C Velasquez, C Sanchez, J Lockhart, D Stoner, BP Holmes, KK TI Sexual networks of pregnant women with and without HIV infection SO AIDS LA English DT Article DE HIV-1; sexual network; pregnant women; Peru; heterosexual transmission ID HETEROSEXUAL TRANSMISSION; CONDOMS AB Objectives: To determine the relationship of HIV infection in pregnant women to sexual network size and other risk factors. Design: Case-control study of women attending the public maternity hospital in Lima, Peru. Methods: We interviewed 75 HIV-seropositive women, 41 of their most recent male partners, and two control groups totaling 137 uninfected pregnant women and 70 of their most recent male partners. Each woman's sexual network size was estimated through second and third-generation partnerships over the past year, 5 years and lifetime. Results: Few HIV-seropositive women reported behavioral risk factors for HIV infection, but 79% of male partners were HIV seropositive. Risk factors in male partners included sex with a female sex worker (FSW) or with another man (MSM). The mean 5-year sexual network sizes through the second generation (8.4 persons for HIV-seropositive women, and 2.5 and 1.9 for women in the two control groups) predicted HIV in the women, independently of her own number of partners. These differences were largely attributable to the number of partners reported by male partners. Using data from concurrent studies of FSW and MSM, estimates of 5-year sexual network sizes through the third-generation, excluding contacts with FSW which were protected by consistent condom use, were 672 persons for HIV-seropositive women, and 160 and 224 for women in the two control groups. Conclusions: HIV infection risk among pregnant women in Lima depends largely on their male partners' risk behaviors. Even monogamous women had very large sexual networks. (C) 2003 Lippincott Williams Wilkins. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Ctr AIDS & STD, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Nacl Mayor San Marcos, Inst Trop Med, San Marcos, TX USA. Minist Hlth, Inst Materno Perinatal, Limu, Peru. Minist Hlth, Program Control STDs & AIDS, Limu, Peru. Washington Univ, Sch Med, Dept Med, St Louis, MO 63130 USA. Washington Univ, Sch Med, Dept Anthropol, St Louis, MO 63130 USA. RP Johnson, KM (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Mailstop 111WOM,1660 S Columbian Way, Seattle, WA 98108 USA. OI Alarcon, Jorge/0000-0002-0800-2380 FU FIC NIH HHS [T22 TW00001]; NIAID NIH HHS [AI-27757] NR 21 TC 26 Z9 26 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 7 PY 2003 VL 17 IS 4 BP 605 EP 612 DI 10.1097/01.aids.0000050785.28043.b9 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 653KT UT WOS:000181434900016 PM 12598781 ER PT J AU Alarcon, JO Johnson, KM Courtois, B Rodriguez, C Sanchez, J Watts, DM Holmes, KK AF Alarcon, JO Johnson, KM Courtois, B Rodriguez, C Sanchez, J Watts, DM Holmes, KK TI Determinants and prevalence of HIV infection in pregnant Peruvian women SO AIDS LA English DT Article DE heterosexual transmission; risk factors; sexual behavior; South America ID IMMUNODEFICIENCY-VIRUS INFECTION; POPULATION; RISK AB Objectives: To determine age-specific seroprevalence, risk factors, and risk markers for heterosexually-acquired HIV infection among pregnant women. Design: Cross-sectional study of 12 436 consecutive pregnant women in Lima, Peru in 1996-1997. Methods: Standardized interviews, serologic tests for HIV and syphilis, bivariate and multivariate analysis. Results: HIV seropositivity was confirmed in 58 women (0.5%). Only 22.6% were married, and only 12% of HIV infected women reported greater than or equal to2 sex partners ever. In multivariate analyses HIV infection was associated with: short duration of current relationship; two risk behaviors of women themselves (early onset of sexual activity and number of past sexual relationships); women's perceptions of two risk behaviors of partners (partner is a 'womanizer,' and partner uses illegal drugs); inadequate prenatal care; and four additional risk factors or markers (history of sexually transmitted disease, tuberculosis, or abortion in the women; and diagnosis of HIV/AIDS in a partner). Conclusions: HIV infection was related both to women's own risk behaviors and to the perceived risk behaviors of their sexual partners. Underlying societal factors related to heterosexual HIV infection, including deferral of marriage, warrant further study. (C) 2003 Lippincott Williams Wilkins. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Nacl Mayor San Marcos, Inst Trop Med, Lima 14, Peru. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Ctr AIDS & STD, Seattle, WA 98195 USA. Inst Materno Perinatal Lima, Lima, Peru. Minist Hlth, Program AIDS & STD, Lima, Peru. USN, Med Res Ctr, Lima, Peru. RP Johnson, KM (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Mailstop 111WOM,1660 S Columbian Way, Seattle, WA 98108 USA. OI Alarcon, Jorge/0000-0002-0800-2380 FU NIAID NIH HHS [P30AI27757] NR 25 TC 36 Z9 39 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAR 7 PY 2003 VL 17 IS 4 BP 613 EP 618 DI 10.1097/01.aids.0000042973.95433.22 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 653KT UT WOS:000181434900017 PM 12598782 ER PT J AU Fan, ZS Beresford, PJ Oh, DY Zhang, D Lieberman, J AF Fan, ZS Beresford, PJ Oh, DY Zhang, D Lieberman, J TI Tumor suppressor NM23-H1 is a granzyme A-activated DNase during CTL-mediated apoptosis, and the nucleosome assembly protein SET is its inhibitor SO CELL LA English DT Article ID DIPHOSPHATE KINASE; NUCLEAR TRANSLOCATION; HISTONE ACETYLATION; IN-VIVO; FRAGMENTATION; TRANSCRIPTION; CLEAVAGE; REPAIR; TARGET; DEGRADATION AB Granzyme A (GzmA) induces a caspase-independent cell death pathway characterized by single-stranded DNA nicks and other features of apoptosis. A GzmA-activated DNase (GAAD) is in an ER associated complex containing pp32 and the GzmA substrates SET, HMG-2, and Ape1. We show that GAAD is NM23-H1, a nucleoside diphosphate kinase implicated in suppression of tumor metastasis, and its specific inhibitor (IGAAD) is SET. NM23-H1 binds to SET and is released from inhibition by GzmA cleavage of SET. After GzmA loading or CTL attack, SET and NM23-H1 translocate to the nucleus and SET is degraded, allowing NM23-H1 to nick chromosomal DNA. GzmA-treated cells with silenced NM23-H1 expression are resistant to GzmA-mediated DNA damage and cytolysis, while cells over-expressing NM23-H1 are more sensitive. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [AI45587] NR 50 TC 353 Z9 385 U1 2 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAR 7 PY 2003 VL 112 IS 5 BP 659 EP 672 DI 10.1016/S0092-8674(03)00150-8 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 653NW UT WOS:000181443600009 PM 12628186 ER PT J AU Yajnik, V Paulding, C Sordella, R McClatchey, AI Saito, M Wahrer, DCR Reynolds, P Bell, DW Lake, R van den Heuvel, S Settleman, J Haber, DA AF Yajnik, V Paulding, C Sordella, R McClatchey, AI Saito, M Wahrer, DCR Reynolds, P Bell, DW Lake, R van den Heuvel, S Settleman, J Haber, DA TI DOCK4, a GTPase activator, is disrupted during tumorigenesis SO CELL LA English DT Article ID REPRESENTATIONAL DIFFERENCE ANALYSIS; TUMOR-SUPPRESSOR GENE; E-CADHERIN; LYMPHOCYTE MIGRATION; BINDING-PROTEIN; PROSTATE-CANCER; CELL-MIGRATION; FREQUENT LOSS; ADHESION; COMPLEX AB We used representational difference analysis to identify homozygous genomic deletions selected during tumor progression in the mouse NF2 and TP53 tumor model. We describe a deletion targeting DOCK4, a member of the CDM gene family encoding regulators of small GTPases. DOCK4 specifically activates Rap GTPase, enhancing the formation of adherens junctions. DOCK4 mutations are present in a subset of human cancer cell lines; a recurrent missense mutant identified in human prostate and ovarian cancers encodes a protein that is defective in Rap1 activation. The engulfment defect of C. elegans mutants lacking the CDM gene ced-5 is rescued by wild-type DOCK4, but not by the mutant allele. Expression of wild-type, but not mutant, DOCK4 in mouse osteosarcoma cells with a deletion of the endogenous gene suppresses growth in soft agar and tumor invasion in vivo. DOCK4 therefore encodes a CDM family member that regulates intercellular junctions and is disrupted during tumorigenesis. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Med Sch, Gastrointestinal Unit, Charlestown, MA 02129 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RI van den Heuvel, Sander/B-8892-2011; Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 FU NCI NIH HHS [CA58596]; NIDDK NIH HHS [5T32DK07191]; NIGMS NIH HHS [GM63081] NR 59 TC 143 Z9 151 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAR 7 PY 2003 VL 112 IS 5 BP 673 EP 684 DI 10.1016/S0092-8674(03)00155-7 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 653NW UT WOS:000181443600010 PM 12628187 ER PT J AU Razzaque, MS Kumari, S Foster, CS Ahmed, AR AF Razzaque, MS Kumari, S Foster, CS Ahmed, AR TI Expression profiles of collagens, HSP47, TGF-beta 1, MMPs and TIMPs in epidermolysis bullosa acquisita SO CYTOKINE LA English DT Article DE conjunctiva; fibroblast; epidermolysis bullosa acquisita; collagen; HSP47; matrix metalloproteinases; tissue inhibitors of metalloproteinases ID HUMAN DIABETIC NEPHROPATHY; BINDING HEAT-SHOCK-PROTEIN-47; VII COLLAGEN; IN-SITU; MOLECULAR CHAPERONE; BASEMENT-MEMBRANE; MESSENGER-RNA; GLOMERULONEPHRITIS; PROTEIN; RAT AB Epidermolysis bullosa acquisita (EBA) is a chronic, uncommon, sub-epidermal blistering disease involving the skin and mucous membranes that heals with scar formation and milia. Collagens, matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are important components that play an essential role(s) in matrix remodeling during scar formation. However, the possible involvement of these components in EBA-induced scarring is not yet known. In the present study, we examined the expression profile of collagens, collagen-binding heat shock protein 47 (HSP47), MMPs and their inhibitory enzymes, TIMPs, in matrix remodeling during conjunctival scarring. The involvement of TGF-beta1, a fibrogenic factor, was also studied. Compared to the controls, an increased expression of type I collagen, type III collagen and HSP47 was detected in conjunctival biopsy sections of patient with EBA using immunohistochemistry. Similar increase in the expression of type I collagen, type III collagen and HSP47 was noted in conjunctival fibroblasts obtained from the patient with EBA. Up-regulation in the expression of MMP-1 and MMP-14 was also noted in conjunctival fibroblasts isolated from the patient with EBA, while no significant changes in the expression of MMP-3, MMP-8, MMP-9 and MMP-13 were seen. As for TIMPs, conjunctival fibroblasts isolated from the patient with EBA, grown in vitro, exhibited increased expression of TIMP-1, TIMP-2 and TIMP-3, when compared with fibroblasts grown from control conjunctival tissues, although the expression level varies with different molecules of the same family. Additionally, compared to the control conjunctival fibroblasts, an increased expression of TGF-beta1 was detected in fibroblasts isolated from the conjunctival tissues of patient with EBA. This study suggests that there is up-regulation in the production of collagens (type I and III), collagen-binding protein (HSP47), matrix degrading collagenases (MMP-1 and 14), and their inhibitory enzymes (TIMP-1, 2 and 3) during the process of conjunctival matrix remodeling in the patient with EBA. The presented data is preliminary and could serve as a basis for further studies to enhance our understanding about the molecular mechanisms of conjunctival scarring in patients with EBA. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol Immunol & Uveitis Serv, Boston, MA 02115 USA. RP Ahmed, AR (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA. NR 36 TC 8 Z9 13 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD MAR 7 PY 2003 VL 21 IS 5 BP 207 EP 213 DI 10.1016/S1043-4666(03)00034-6 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 687PX UT WOS:000183386700001 PM 12824005 ER PT J AU Beilharz, T Egan, B Silver, PA Hofmann, K Lithgow, T AF Beilharz, T Egan, B Silver, PA Hofmann, K Lithgow, T TI Bipartite signals mediate subcellular targeting of tail-anchored membrane proteins in Saccharomyces cerevisiae SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MITOCHONDRIAL OUTER-MEMBRANE; ENDOPLASMIC-RETICULUM MEMBRANE; CYTOCHROME B(5); IN-VIVO; YEAST; INSERTION; FUSION; TRANSLOCATION; MUTANTS; PATHWAY AB Tail-anchored proteins have an NH2-terminal cytosolic domain anchored to intracellular membranes by a single, COOH-terminal, transmembrane segment. Sequence analysis identified 55 tail-anchored proteins in Saccharomyces cerevisiae, with several novel proteins, including Prm3, which we find is required for karyogamy and is tail-anchored in the nuclear envelope. A total of six tail-anchored proteins are present in the mitochondrial outer membrane and have relatively hydrophilic transmembrane segments that serve as targeting signals. The rest, by far the majority, localize via a bipartite system of signals: uniformly hydrophobic tail anchors are first inserted into the endoplasmic reticulum, and additional segments within the cytosolic domain of each protein can dictate subsequent sorting to a precise destination within the cell. C1 Univ Melbourne, Russell Grimwade Sch Biochem & Mol Biol, Parkville, Vic 3010, Australia. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. MEMOREC Stoffel GmbH, Bioinformat Grp, D-50829 Cologne, Germany. RP Lithgow, T (reprint author), Univ Melbourne, Russell Grimwade Sch Biochem & Mol Biol, Parkville, Vic 3010, Australia. OI Beilharz, Traude/0000-0002-8942-9502 NR 38 TC 101 Z9 110 U1 2 U2 5 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 MAR 7 PY 2003 VL 278 IS 10 BP 8219 EP 8223 DI 10.1074/jbc.M212725200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 653ZK UT WOS:000181466800061 PM 12514182 ER PT J AU Wick, KR Werner, ED Langlais, P Ramos, FJ Dong, LQ Shoelson, SE Liu, F AF Wick, KR Werner, ED Langlais, P Ramos, FJ Dong, LQ Shoelson, SE Liu, F TI Grb10 inhibits insulin-stimulated insulin receptor substrate (IRS)-phosphatidylinositol 3-kinase/Akt signaling pathway by disrupting the association of IRS-1/IRS-2 with the insulin receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE KINASE DOMAIN; GROWTH-FACTOR RECEPTOR; FACTOR-I RECEPTORS; PLECKSTRIN HOMOLOGY; CATALYTIC ACTIVITY; BINDING-PROTEIN; SRC HOMOLOGY-2; SH2 DOMAINS; PHOSPHORYLATION; IRS-1 AB Grb10 has been proposed to inhibit or activate insulin signaling, depending on cellular context. We have investigated the mechanism by which full-length hGrb10gamma inhibits signaling through the insulin receptor substrate (IRS) proteins. Overexpression of hGrb10gamma in CHO/IR cells and in differentiated adipocytes significantly reduced insulin-stimulated tyrosine phosphorylation of IRS-1 and IRS-2. Inhibition occurred rapidly and was sustained for 60 min during insulin stimulation. In agreement with inhibited signaling through the IRS/PI 3-kinase pathway, we found hGrb10gamma to both delay and reduce phosphorylation of Akt at Thr(308) and Ser(173) in response to insulin stimulation. Decreased phosphorylation of IRS-1/2 may arise from impaired catalytic activity of the receptor, since hGrb10gamma directly associates with the IR kinase regulatory loop. However, yeast tri-hybrid studies indicated that full-length Grb10 blocks association between IRS proteins and IR, and that this requires the SH2 domain of Grb10. In cells, hGrb10gamma inhibited insulin-stimulated IRS-1 tyrosine phosphorylation in a dose-dependent manner, but did not affect IR catalytic activity toward Tyr(972) in the juxtamembrane region and Tyr(1158/1162/1163) in the regulatory domain. We conclude that binding of hGrb10gamma to IR decreases signaling through the IRS/PI 3-kinase/AKT pathway by physically blocking IRS access to IR. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Cell & Dev Biol, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Liu, F (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NIA NIH HHS [2T32AG00205-11]; NIDDK NIH HHS [DK43123, R01 DK52933] NR 42 TC 71 Z9 74 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 7 PY 2003 VL 278 IS 10 BP 8460 EP 8467 DI 10.1074/jbc.M208518200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 653ZK UT WOS:000181466800093 PM 12493740 ER PT J AU Neicu, T Shirato, H Seppenwoolde, Y Jiang, SB AF Neicu, T Shirato, H Seppenwoolde, Y Jiang, SB TI Synchronized moving aperture radiation therapy (SMART): average tumour trajectory for lung patients SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID BREATH-HOLD TECHNIQUE; RESPIRATION-GATED RADIOTHERAPY; DEEP INSPIRATION; CONTROL ABC; MOTION; IRRADIATION; CANCER; RADIOSURGERY; MOVEMENT; SYSTEM AB Synchronized moving aperture radiation therapy (SMART) is a new technique for treating mobile tumours under development at Massachusetts General Hospital (MGH). The basic idea of SMART is to synchronize the moving radiation beam aperture formed by a dynamic multileaf collimator (DMLC) with the tumour motion induced by respiration. SMART is based on the concept of the average tumour trajectory (ATT) exhibited by a tumour during respiration. During the treatment simulation stage, tumour motion is measured and the ATT is derived. Then, the original IMRT MLC leaf sequence is modified using the ATT to compensate for tumour motion. During treatment, the tumour motion is monitored. The treatment starts when leaf motion and tumour motion are synchronized at a specific breathing phase. The treatment will halt when the tumour drifts away from the ATT and will resume when the synchronization between tumour motion and radiation beam is re-established. In this paper, we present a method to derive the ATT from measured tumour trajectory data. We also investigate the validity of the ATT concept for lung tumours during normal breathing. The lung tumour trajectory data were acquired during actual radiotherapy sessions using a real-time tumour-tracking system. SMART treatment is simulated by assuming that the radiation beam follows the derived ATT and the tumour follows the measured trajectory. In simulation, the treatment starts at exhale phase. The duty cycle of SMART delivery was calculated for various treatment times and gating thresholds, as well as for various exhale phases where the treatment begins. The simulation results show that in the case of free breathing, for 4 out of 11 lung datasets with tumour motion greater than I cm from peak to peak, the error in tumour tracking can be controlled to within a couple of millimetres while maintaining a reasonable delivery efficiency. That is to say, without any breath coaching/control, the ATT is a valid concept for some lung tumours. However, to make SMART an efficient technique in general, it is found that breath coaching techniques are required. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Hokkaido Univ, Sch Med, Dept Radiat Med, Sapporo, Hokkaido 060, Japan. Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Radiotherapy, Amsterdam, Netherlands. RP Neicu, T (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RI Shirato, Hiroki/A-7068-2010 NR 25 TC 160 Z9 163 U1 3 U2 11 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 MAR 7 PY 2003 VL 48 IS 5 BP 587 EP 598 AR PII S0031-9155(03)57158-5 DI 10.1088/0031-9155/48/5/303 PG 12 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 662QG UT WOS:000181958500003 PM 12696797 ER PT J AU Pagani, FD DerSimonian, H Zawadzka, A Wetzel, K Edge, ASB Jacoby, DB Dinsmore, JH Wright, S Aretz, TH Eisen, HJ Aaronson, KD AF Pagani, FD DerSimonian, H Zawadzka, A Wetzel, K Edge, ASB Jacoby, DB Dinsmore, JH Wright, S Aretz, TH Eisen, HJ Aaronson, KD TI Autologous skeletal myoblasts transplanted to ischemia-damaged myocardium in humans - Histological analysis of cell survival and differentiation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review ID IMPROVES HEART FUNCTION; INFARCTED MYOCARDIUM; CARDIAC-MUSCLE; STEM-CELLS; CARDIOMYOPLASTY; CARDIOMYOCYTES; PERFORMANCE; REPAIR; REGENERATION; IMPLANTATION AB OBJECTIVES We report histological analysis of hearts from patients with end-stage heart disease who were transplanted with autologous skeletal myoblasts concurrent with left ventricular assist device (LVAD) implantation. BACKGROUND Autologous skeletal myoblast transplantation is under investigation as a means to repair infarcted myocardium. To date, there is only indirect evidence to suggest survival of skeletal muscle in humans. METHODS Five patients (all male; median age 60 years) with ischemic cardiomyopathy, refractory heart failure, and listed for heart transplantation underwent muscle biopsy from the quadriceps muscle. The muscle specimen was shipped to a cell isolation facility where myoblasts were isolated and grown. Patients received a transplant of 300 million cells concomitant with LVAD implantation. Four patients underwent LVAD explant after 68, 91, 141, and 191 days of LVAD support (three transplant, one LVAD death), respectively. One patient remains alive on LVAD support awaiting heart transplantation. RESULTS Skeletal muscle cell survival and differentiation into mature myofibers were directly demonstrated in scarred myocardium from three of the four explanted hearts using an antibody against skeletal muscle-specific myosin heavy chain. An increase in small vessel formation was observed in one of three patients at the site of surviving myotubes, but not in adjacent tissue devoid of engrafted cells. CONCLUSIONS These findings represent demonstration of autologous myoblast cell survival in human heart. The implanted skeletal myoblasts formed viable grafts in heavily scarred human myocardial tissue. These results establish the feasibility of myoblast transplants for myocardial repair in humans. (C) 2003 by the American College of Cardiology Foundation. C1 Univ Michigan, Sect Cardiac Surg, Heart Transplant Program, Ann Arbor, MI 48109 USA. Univ Michigan, Div Cardiol, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Temple Univ, Philadelphia, PA 19122 USA. Diacrin Inc, Charlestown, MA USA. RP Pagani, FD (reprint author), Univ Michigan, Sect Cardiac Surg, Heart Transplant Program, 2120 Taubman Ctr,Box 3480,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. OI Jacoby, David/0000-0003-2195-9512 NR 31 TC 291 Z9 330 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 5 PY 2003 VL 41 IS 5 BP 879 EP 888 DI 10.1016/S0735-1097(03)00081-0 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 650DU UT WOS:000181248000027 PM 12628737 ER PT J AU Grumbach, MM Biller, BMK Braunstein, GD Campbell, KK Carney, JA Godley, PA Harris, EL Lee, JKT Oertel, YC Posner, MC Schlechte, JA Wieand, HS AF Grumbach, MM Biller, BMK Braunstein, GD Campbell, KK Carney, JA Godley, PA Harris, EL Lee, JKT Oertel, YC Posner, MC Schlechte, JA Wieand, HS TI Management of the clinically inapparent adrenal mass ("incidentaloma") SO ANNALS OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT State of the Science Conference CY FEB 04-06, 2002 CL BETHESDA, MARYLAND AB The National Institutes of Health Consensus Development Program convened surgeons, endocrinologists, pathologists, biostatisticians, radiologists, oncologists, and other health care professionals, as well as members of the general public, to address the causes, prevalence, and natural history of clinically inapparent adrenal masses, or "incidentalomas"; the appropriate evaluation and treatment of such masses; and directions for future research. Improvements in abdominal imaging techniques have increased detection of adrenal incidentalomas, and because the prevalence of these masses increases with age, appropriate management of adrenal tumors will be a growing challenge in our aging society. To address six predetermined questions, the 12-member nonfederal, nonadvocate state-of-the-science panel heard presentations from 21 experts in adrenal incidentalomas and consulted a systematic review of medical literature on the topic provided by the Agency for Healthcare Research and Quality and an extensive bibliography developed by the National Library of Medicine. The panel recommended a 1-mg dexamethasone suppression test and measurement of plasma-free metanephrines for all patients with an adrenal incidentaloma; additional measurement of serum potassium and plasma aldosterone concentration-plasma renin activity ratio for patients with hypertension; and surgery for patients with biochemical evidence of pheochromocytoma, patients with tumors greater than 6 cm, and patients with tumors greater than 4 cm who also meet other criteria. The panel also advocated a multidisciplinary approach to managing adrenal incidentalomas. The statement is an independent report of the panel and is not a policy statement of the National Institutes of Health or the federal government. C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Cushings Support & Res Fdn, Boston, MA USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Mayo Clin, Rochester, MN USA. Univ N Carolina, Sch Med, Chapel Hill, NC 27515 USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. Washington Hosp Ctr, Washington, DC 20010 USA. Univ Chicago, Chicago, IL 60637 USA. Univ Iowa Hosp, Iowa City, IA USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA. RP Grumbach, MM (reprint author), NIH, Off Med Applicat Res, Bldg 31,Room 1B03,31 Ctr Dr MSC 2082, Bethesda, MD 20892 USA. NR 0 TC 436 Z9 456 U1 1 U2 15 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 MAR 4 PY 2003 VL 138 IS 5 BP 424 EP 429 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 650HJ UT WOS:000181257300009 PM 12614096 ER PT J AU Shimizu, N Petroni, BD Khatri, A Gardella, TJ AF Shimizu, N Petroni, BD Khatri, A Gardella, TJ TI Functional evidence for an intramolecular side chain interaction between residues 6 and 10 of receptor-bound parathyroid hormone analogues SO BIOCHEMISTRY LA English DT Article ID JUXTAMEMBRANE REGION; PTH/PTHRP RECEPTOR; LIGAND INTERACTION; ADENYLYL-CYCLASE; PTH-1 RECEPTOR; BINDING; PROTEIN; PEPTIDES; CONFORMATION; FRAGMENTS AB The N-terminal domain of PTH(1-34) is critical for PTH-1 receptor (P1R) activation and has been postulated to be alpha-helical when bound to the receptor. We investigated the possibility that the side chains of residues 6 (Gln) and 10 (Gln or Asn) of PTH analogues, which would align on the same face of the predicted alpha-helix, could interact and thereby contribute to the PTH/P1R interaction process. We utilized PTH(1-11), PTH(1-14), and PTH(1-34) analogues substituted with alanine at one or both of these positions and functionally evaluated the peptides in cell lines (HKRK-B7 and HKRK-B28) stably expressing the P1R, as well as in COS-7 cells transiently expressing either the P1R or a P1R construct that lacks the amino-terminal extracellular domain (P1R-DelNt). In HKRK-B7 cells, the single substitutions of Gln(6) --> Ala and Gln(10) --> Ala reduced the CAMP-stimulating potency of [Ala(3),Gln(10),Arg(11)]rPTH(1-11)NH2 similar to60- and similar to2-fold, respectively, whereas the combined Ala(6,10) substitution resulted in a similar to2-fold gain in potency, relative to the single Ala(6) substitution. Similar effects on P1R-mediated cAMP-signaling potency and P1R-binding affinity were observed for these substitutions in [Aib(1,3),Gln(10),Har(11),Ala(12),Trp(14)]-rPTH(1-14)NH2. Installation of a lactam bridge between the Lys(6) and the Glu(10) side chains of [Ala(3,12),- Lys(6),Glu(10),Har(11),Trp(14)]rPTH(1-14)NH2 increased signaling potency 6-fold, relative to the nonbridged linear analogue. Alanine substitutions at positions 6 and/or 10 of [Tyr(34)]hPTH(1-34)NH2 did not affect signaling potency nor binding affinity on the intact P1R; however, Ala(6) abolished PTH(1-34) signaling on P1R-DelNt, and this effect was reversed by Ala(10). The overall data support the hypothesis that the N-terminal portion of PTH is alpha-helical when bound to the activation domain of the PTH-1 receptor and they further suggest that intrahelical side chain interactions between residues 6 and 10 of the ligand can contribute to the receptor interaction process. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Gardella, TJ (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-11794] NR 35 TC 16 Z9 16 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 4 PY 2003 VL 42 IS 8 BP 2282 EP 2290 DI 10.1021/bi027237n PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 649EC UT WOS:000181193100004 PM 12600195 ER PT J AU Communal, C Huq, F Lebeche, D Mestel, C Gwathmey, JK Hajjar, RJ AF Communal, C Huq, F Lebeche, D Mestel, C Gwathmey, JK Hajjar, RJ TI Decreased efficiency of adenovirus-mediated gene transfer in aging cardiomyocytes SO CIRCULATION LA English DT Article DE aging; gene therapy; myocytes; viruses; receptors ID FAILING HEART; INTEGRINS; RECEPTOR; EXPRESSION; RATS; COXSACKIEVIRUS; MYOCARDITIS; APOPTOSIS; JUNCTION; SYSTEM AB Background-Aging is an independent risk factor for the development of cardiovascular disease. Clinical application of myocardial gene transfer may be best suited in the elderly. In vivo gene transfer by adenovirus is less efficient in aging myocardium. Methods and Results-When infected with adenovirus containing beta-galactosidase (beta-gal) and green fluorescent protein (GFP) driven by cytomegalovirus promoters in vitro, aging rat cardiac myocytes exhibit significantly lower infectivity and delayed transgene expression compared with adult controls. Abnormalities of viral internalization may be one mechanism accounting for this difference. To investigate this, we studied expression levels of the coxsackievirus and adenovirus receptor (CAR) as well as other potential integrins involved in the internalization of adenoviruses. CAR expression tended to be upregulated whereas among potential integrins, alpha(3)beta(1) was downregulated in aging cardiac myocytes. Blocking the beta(1) component of alpha(3)beta(1) further decreased infectivity, suggesting that the interaction between the penton base of the adenovirus and beta(1) maybe a crucial component of the viral entry mechanism. Conclusions-These results suggest that it is integrin-stimulated internalization rather than the adenovirus-CAR interaction that plays a vital role in adenoviral entry. The downregulation of integrins observed in senescent cells may be a key mechanism accounting for the decrease in viral infectivity seen in these cells. These findings have implications for the gene therapy treatment of myocardial failure in the elderly. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. Hop Lariboisiere, INSERM, U572, F-75475 Paris, France. RP Hajjar, RJ (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St,CNY-4, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [R01 HL049574-05, HL 49574, R01 HL049574-07, R01 HL049574-08, R01 HL049574-06S1, HL 57623, R01 HL049574-05S1, R01 HL049574-06] NR 21 TC 28 Z9 32 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 4 PY 2003 VL 107 IS 8 BP 1170 EP 1175 DI 10.1161/01.CIR.0000051467.31874.29 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 653ZL UT WOS:000181466900016 PM 12615797 ER PT J AU Sheeman, B Carvalho, P Sagot, I Geiser, J Kho, D Hoyt, MA Pellman, D AF Sheeman, B Carvalho, P Sagot, I Geiser, J Kho, D Hoyt, MA Pellman, D TI Determinants of S. cerevisiae dynein localization and activation: Implications for the mechanism of spindle positioning SO CURRENT BIOLOGY LA English DT Article ID CYTOPLASMIC DYNEIN; SACCHAROMYCES-CEREVISIAE; NUCLEAR MIGRATION; DYNACTIN COMPLEX; CELL-CYCLE; ASPERGILLUS-NIDULANS; INTERMEDIATE CHAIN; BUDDING YEAST; HEAVY-CHAIN; MOTOR AB Background: During anaphase in budding yeast, dynein inserts the mitotic Spindle across the neck between mother and daughter cells. The mechanism of dynein-dependent spindle positioning is thought to involve recruitment of dynein to the cell cortex followed by capture of astral microtubules (aMTs). Results: We report the native-level localization of the dynein heavy chain and characterize the effects of mutations in dynein regulators on its intracellular distribution. Budding yeast dynein displays discontinuous localization along aMTs, with enrichment at the spindle pole body and aMT plus ends. Loss of Bik1p (CLIP-170), the cargo binding domain of Bik1p, or Pac1p(LIS1) resulted in diminished targeting of dynein to aMTs. By contrast, loss of dynactin or a mutation in the second P loop domain of dynein resulted in an accumulation of dynein on the plus ends of aMTs. Unexpectedly, loss of Num1p, a proposed dynein cortical anchor, also resulted in selective accumulation of dynein on the plus ends of anaphase aMTs. Conclusions: We propose that, rather than first being recruited to the cell cortex, dynein is delivered to the cortex on the plus ends of polymerizing aMTs. Dynein may then undergo Num1p-dependent activation and transfer to the region of cortical contact. Based on the similar effects of loss of Num1p and loss of dynactin on dynein localization, we suggest that Num1 p might also enhance dynein motor activity or processivity, perhaps by clustering dynein motors. C1 Harvard Univ, Dept Pediat Hematol, Childrens Hosp, Dana Farber Canc Inst,Dept Pediat Oncol,Sch Med, Boston, MA 02115 USA. Western Michigan Univ, Dept Biol Sci, Kalamazoo, MI 49008 USA. Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. RP Pellman, D (reprint author), Harvard Univ, Dept Pediat Hematol, Childrens Hosp, Dana Farber Canc Inst,Dept Pediat Oncol,Sch Med, 44 Binney St, Boston, MA 02115 USA. EM david_pellman@dfci.harvard.edu OI Carvalho, Pedro/0000-0002-9691-5277 FU NIGMS NIH HHS [GM61345] NR 43 TC 162 Z9 163 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAR 4 PY 2003 VL 13 IS 5 BP 364 EP 372 AR PII S0960-9822(03)00013-7 DI 10.1016/S0960-9822(03)00013-7 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 652PT UT WOS:000181388100017 PM 12620184 ER PT J AU Luo, BH Springer, TA Takagi, J AF Luo, BH Springer, TA Takagi, J TI Stabilizing the open conformation of the integrin headpiece with a glycan wedge increases affinity for ligand SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SWISS-MODEL; BINDING; ACTIVATION; FIBRINOGEN; ANTIBODIES; ALPHA-5-BETA-1; CONFORMERS; REVEALS; DOMAIN AB The affinity of the extracellular domain of integrins for ligand is regulated by conformational changes signaled from the cytoplasm. Alternative types of conformational movement in the ligand binding headpiece have been proposed. In one study, electron micrograph image averages of the headpiece of integrin aVbeta3 show two different conformations. The open conformation of the headpiece is present when a ligand mimetic peptide is bound and differs from the closed conformation in the presence of an obtuse angle between the beta3 subunit hybrid and I-like domains. We tested the hypothesis that opening of the hybrid-l-like domain interface increases ligand-binding affinity by mutationally introducing an N-glycosylation site into it. Both beta3 and beta1 integrin glycan wedge mutants exhibit constitutively high affinity for physiological ligands. The data uniquely support one model of integrin activation and suggest that movement at the interface with the hybrid domain pulls down the C-terminal helix of the I-like domain and activates its metal ion-dependent adhesion site, analogously to activation of the integrin I domain. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Takagi, J (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-48675, P01 HL048675] NR 30 TC 101 Z9 101 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 4 PY 2003 VL 100 IS 5 BP 2403 EP 2408 DI 10.1073/pnas.0438060100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 652DR UT WOS:000181365000045 PM 12604783 ER PT J AU Ni, HY Yuen, PST Papalia, JM Trevithick, JE Sakai, T Fassler, R Hynes, RO Wagner, DD AF Ni, HY Yuen, PST Papalia, JM Trevithick, JE Sakai, T Fassler, R Hynes, RO Wagner, DD TI Plasma fibronectin promotes thrombus growth and stability in injured arterioles SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VON-WILLEBRAND-FACTOR; PLATELET-ADHESION; INTEGRIN ALPHA(IIB)BETA(3); GLANZMANNS-THROMBASTHENIA; VONWILLEBRAND-FACTOR; MICE LACKING; FACTOR-VIII; SUBENDOTHELIUM; FIBRINOGEN; DEFECTS AB Mice lacking both of the best-known platelet ligands, von Willebrand factor and fibrinogen, can still form occlusive thrombi in injured arterioles. The platelets of these animals accumulate excessive amounts of fibronectin (FN). These observations led us to examine the contribution of plasma FN (pFN) to thrombus formation. Inactivation of the FN gene in FN conditional knockout mice reduced pFN levels to <2% and platelet FN to approximate to20% of the levels in similarly treated control mice. The mice were then observed in a model of arterial injury to evaluate their capacity to form thrombi. The deficiency of pFN did not affect the initial platelet adhesion, but a delay of several minutes in thrombus formation was observed in the arterioles of pFN-deficient mice as compared with control mice. The thrombi that formed in the absence of pFN were stably anchored to the vessel wall but continuously shed platelets or small platelet clumps, thus slowing their growth significantly; the platelet/platelet cohesion was apparently diminished. Consequently the occlusion of pFN-deficient vessels was delayed, with the majority of vessels remaining patent at the end of the 40-min observation period. We conclude that, in addition to von Willebrand factor and fibrinogen, FN plays a significant role in thrombus initiation, growth, and stability at arterial shear rates and that deficiency in each of the three platelet ligands has its own specific impact on platelet plug formation. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. MIT, Howard Hughes Med Inst, Ctr Canc Res, Dept Biol, Cambridge, MA 02139 USA. Max Planck Inst Biochem, Dept Mol Med, D-82152 Martinsried, Germany. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RI Yuen, Peter/B-1954-2008; OI Yuen, Peter/0000-0001-9557-3909; Ni, Heyu/0000-0002-7621-2945 FU NHLBI NIH HHS [P01 HL056949, P01 HL066105, P01HL56949, R37 HL041002, R37HL41002] NR 29 TC 136 Z9 142 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 4 PY 2003 VL 100 IS 5 BP 2415 EP 2419 DI 10.1073/pnas.2628067100 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 652DR UT WOS:000181365000047 PM 12606706 ER PT J AU Dai, Y Kysela, B Hanakahi, LA Manolis, K Riballo, E Stumm, M Harville, TO West, SC Oettinger, MA Jeggo, PA AF Dai, Y Kysela, B Hanakahi, LA Manolis, K Riballo, E Stumm, M Harville, TO West, SC Oettinger, MA Jeggo, PA TI Nonhomologous end joining and V(D)J recombination require an additional factor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID STRAND BREAK REPAIR; DEPENDENT PROTEIN-KINASE; DNA-LIGASE-IV; HAMSTER OVARY CELL; ATAXIA-TELANGIECTASIA; SACCHAROMYCES-CEREVISIAE; RADIOSENSITIVITY; DEFICIENCY; CYCLE; LINE AB DNA nonhomologous end-joining (NHEJ) is the major pathway for repairing DNA double-strand breaks in mammalian cells. It also functions to carry out rearrangements at the specialized breaks introduced during V(D)J recombination. Here, we describe a patient with T-B- severe combined immunodeficiency, whose cells have defects closely resembling those of NHEJ-defective rodent cells. Cells derived from this patient show dramatic radiosensitivity, decreased double-strand break rejoining, and reduced fidelity in signal and coding joint formation during V(D)J recombination. Detailed examination indicates that the patient is defective neither in the known factors involved in NHEJ in mammals (Ku70, Ku80, DNA-dependent protein kinase catalytic subunit, Xrcc4, DNA ligase IV, or Artemis) nor in the Mre11/Rad50/Nbs1 complex, whose homologue in Saccharomyces cerevisiae functions in NHEJ. These results provide strong evidence that additional activities are crucial for NHEJ and V(D)J recombination in mammals. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Univ Sussex, Genome Damage & Stabil Unit, Brighton BN1 9RQ, E Sussex, England. Canc Res UK, London Res Inst, Clare Hall Labs, S Mimms EN6 3LD, Herts, England. Univ Klinikum Magdeburg, Inst Humangenet, D-39120 Magdeburg, Germany. Univ Arkansas, Sch Med, Div Allergy, Arkansas Childrens Hosp, Little Rock, AR 72202 USA. Univ Arkansas, Sch Med, Div Immunol, Arkansas Childrens Hosp, Little Rock, AR 72202 USA. Univ Arkansas, Sch Med, Div Rheumatol, Arkansas Childrens Hosp, Little Rock, AR 72202 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Oettinger, MA (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. OI West, Stephen/0000-0001-8848-9418 FU NIGMS NIH HHS [GM58026] NR 38 TC 126 Z9 131 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 4 PY 2003 VL 100 IS 5 BP 2462 EP 2467 DI 10.1073/pnas.0437964100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 652DR UT WOS:000181365000055 PM 12604777 ER PT J AU Paulding, CA Ruvolo, M Haber, DA AF Paulding, CA Ruvolo, M Haber, DA TI The Tre2 (USP6) oncogene is a hominoid-specific gene SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SEGMENTAL DUPLICATIONS; RAPID EVOLUTION; HUMAN GENOME; PROTEIN; SEQUENCES; DOMAIN; FAMILY AB Gene duplication and domain accretion are thought to be the major mechanisms for the emergence of novel genes during evolution. Such events are thought to have occurred at early stages in the vertebrate lineage, but genomic sequencing has recently revealed extensive amplification events during the evolution of higher primates. We report here that the Tre2 (USP6) oncogene is derived from the chimeric fusion of two genes, USP32 (NY-REN-60), and TBC1D3. USP32 is an ancient, highly conserved gene, whereas TBC1D3 is derived from a recent segmental duplication, which is absent in most other mammals and shows rapid amplification and dispersal through the primate lineage. Remarkably, the chimeric gene Tre2 exists only in the hominoid lineage of primates. This hominoid-specific oncogene arose as recently as 21-33 million years ago, after proliferation of the TBC1D3 segmental duplication in the primate lineage. In contrast to the broad expression pattern of USP32 and TBC1D3, expression of Tre2 is testis-specific, a pattern proposed for novel genes implicated in the emergence of reproductive barriers. The sudden emergence of chimeric proteins, such as that encoded by Tre2, may have contributed to hominoid speciation. C1 Massachusetts Gen Hosp, Ctr Canc, Genet Mol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Harvard Univ, Dept Anthropol, Cambridge, MA 02138 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Genet Mol Lab, CNY7,Bldg 149,13th St, Charlestown, MA 02129 USA. EM Haber@helix.mgh.harvard.edu FU NCI NIH HHS [CA84066] NR 28 TC 86 Z9 91 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 4 PY 2003 VL 100 IS 5 BP 2507 EP 2511 DI 10.1073/pnas.0437015100 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 652DR UT WOS:000181365000063 PM 12604796 ER PT J AU Bassing, CH Tillman, RE Woodman, BB Canty, D Monroe, RJ Sleckman, BP Alt, FW AF Bassing, CH Tillman, RE Woodman, BB Canty, D Monroe, RJ Sleckman, BP Alt, FW TI T cell receptor (TCR) alpha/delta locus enhancer identity and position are critical for the assembly of TCR delta and alpha variable region genes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CONTROLLING V(D)J RECOMBINATION; GERM-LINE TRANSCRIPTION; DEVELOPMENTAL REGULATION; TARGETED DELETION; CHAIN ENHANCER; BETA LOCUS; V-GENE; ACCESSIBILITY; REARRANGEMENT; ELEMENT AB T cell receptor (TCR) delta and alpha variable region genes are assembled from germ-line gene segments located in a single chromosomal locus in which TCRdelta segments are situated between TCRalpha segments. The TCRa enhancer (Ealpha) located at the 3' end of the TCRalpha/delta locus functions over a long chromosomal distance to promote TCRa rearrangement and maximal TCRdelta expression; whereas the TCRdelta enhancer (Edelta) is located among the TCRdelta segments and functions with additional element(s) to mediate TCRdelta rearrangement. We used gene-targeted mutation to evaluate whether the identity of Ealpha and the position of Edelta are critical for the developmental stage-specific assembly of TCR 5 and a variable region genes. Specific replacement of Ealpha with Edelta, the core Ealpha element (EalphaC), or the Ig heavy chain intronic enhancer (iEmu), all of which promote accessibility in the context of transgenic V(D)J recombination substrates, did not promote a significant level of TCRa rearrangement beyond that observed in the absence of Ealpha. Therefore, the identity and full complement of Ealpha-binding sites are critical for promoting accessibility within the TCRa locus. In the absence of the endogenous Edelta element, specific replacement of Ealpha with Edelta also did not promote TCRdelta rearrangement. However, deletion of intervening TCRalpha/delta locus sequences to restore the inserted Edelta to its normal chromosomal position relative to 5' sequences rescued TCRdelta rearrangement. Therefore, unlike Ealpha, Edelta lacks ability to function over the large intervening TCRalpha locus and/or Edelta function requires proximity to additional upstream element(s) to promote TCRdelta accessibility. C1 Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. RP Alt, FW (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. FU NIAID NIH HHS [R01 AI020047, AI20047-20, R37 AI020047] NR 54 TC 25 Z9 25 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 4 PY 2003 VL 100 IS 5 BP 2598 EP 2603 DI 10.1073/pnas.0437943100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 652DR UT WOS:000181365000078 PM 12604775 ER PT J AU Li, YZ Sun, XG LaMont, JT Pardee, AB Li, CJ AF Li, YZ Sun, XG LaMont, JT Pardee, AB Li, CJ TI Selective killing of cancer cells by beta-lapachone: Direct checkpoint activation as a strategy against cancer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DNA-DAMAGE; APOPTOSIS; PROLIFERATION; MECHANISM; EVENTS; E2F-1; CYCLE; DEATH; P53 AB Most chemotherapeutic drugs kill cancer cells by indirectly activating checkpoint-mediated apoptosis after creating nonselective damage to DNA or microtubules, which accounts for their toxicity toward normal cells. We seek to target cancer cells by directly activating checkpoint regulators without creating such damage. Here, we show that beta-lapachone selectively induces apoptosis in cancer cells without causing the death of nontransformed cells in culture. This unusual selectivity against cancer cells is preceded by activation of S-phase checkpoint and selective induction of E2F1, a regulator of checkpoint-mediated apoptosis. This study suggests direct checkpoint activation as a strategy against cancer. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gastroenterol, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Li, CJ (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Gastroenterol, 330 Brookline Ave, Boston, MA 02215 USA. NR 23 TC 112 Z9 114 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 4 PY 2003 VL 100 IS 5 BP 2674 EP 2678 DI 10.1073/pnas.0538044100 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 652DR UT WOS:000181365000091 PM 12598645 ER PT J AU Goldfine, AB Bouche, C Parker, RA Kim, C Kerivan, A Soeldner, JS Martin, BC Warram, JH Kahn, CR AF Goldfine, AB Bouche, C Parker, RA Kim, C Kerivan, A Soeldner, JS Martin, BC Warram, JH Kahn, CR TI Insulin resistance is a poor predictor of type 2 diabetes in individuals with no family history of disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BETA-CELL; GLUCOSE-TOLERANCE; PIMA-INDIANS; MELLITUS; OBESITY; HYPERINSULINEMIA; DYSFUNCTION; SENSITIVITY; RISK AB In normoglycemic offspring of two type 2 diabetic parents, low insulin sensitivity (S-I) and low insulin-independent glucose effectiveness (S-G) predict the development of diabetes one to two decades later. To determine whether low S-I, low S-G, or low acute insulin response to glucose are predictive of diabetes in a population at low genetic risk for disease, 181 normoglycemic individuals with no family history of diabetes (FH-) and 150 normoglycemic offspring of two type 2 diabetic parents (FH+) underwent i.v. glucose tolerance testing (IVGTT) between the years 1964-82. During 25 +/- 6 years follow-up, comprising 2,758 person years, the FH- cohort (54 +/- 9 years) had an age-adjusted incidence rate of type 2 diabetes of 1.8 per 1,000 person years, similar to that in other population-based studies, but significantly lower than 16.7 for the FH+ cohort. Even when the two study populations were subdivided by initial values of S-I and S-G derived from IVGTT's performed at study entry, there was a 10- to 20-fold difference in age-adjusted incidence rates for diabetes in the FH- vs. FH+ individuals with low S-I and low S-G. The acute insulin response to glucose was not predictive of the development of diabetes when considered independently or when assessed as a function of S-I, i.e., the glucose disposition index. These data demonstrate that low glucose disposal rates are robustly associated with the development of diabetes in the FH+ individuals, but insulin resistance per se is not sufficient for the development of diabetes in individuals without family history of disease and strongly suggest a familial factor, not detectable in our current measures of the dynamic responses of glucose or insulin to an IVGTT is an important risk factor for type 2 diabetes. Low S-I and low S-G, both measures of glucose disposal, interact with this putative familial factor to result in a high risk of type 2 diabetes in the FH+ individuals, but not in the FH- individuals. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Beth Israel Med Ctr, Biometr Ctr, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. FU NCRR NIH HHS [M01 RR001032, M01 RR01032]; NIDDK NIH HHS [P30 DK36836, K23 DK002795, R01-DK33201, R01 DK033201, R01-DK45935, P30 DK036836, K23-DK02795, R01 DK045935] NR 30 TC 64 Z9 64 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 4 PY 2003 VL 100 IS 5 BP 2724 EP 2729 DI 10.1073/pnas.0438009100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 652DR UT WOS:000181365000100 PM 12591951 ER PT J AU Bina, J Zhu, J Dziejman, M Faruque, S Calderwood, S Mekalanos, J AF Bina, J Zhu, J Dziejman, M Faruque, S Calderwood, S Mekalanos, J TI ToxR regulon of Vibrio cholerae and its expression in vibrios shed by cholera patients SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VIRULENCE GENE-EXPRESSION; MANNOSE-SENSITIVE HEMAGGLUTININ; BIOTYPE-SPECIFIC CONTROL; EL-TOR; COORDINATE EXPRESSION; REGULATORY CASCADE; COREGULATED PILUS; COLONIZATION; STRAINS; O139 AB Toxigenic Vibrio cholerae cause cholera, a severe diarrheal disease responsible for significant morbidity and mortality worldwide. Two determinants, cholera enterotoxin (CT) and toxin coregulated pilus (TCP) are critical factors responsible for this organism's virulence. The genes for these virulence determinants belong to a network of genes (the ToxR regulon) whose expression is modulated by transcriptional regulators encoded by the toxRS, tcpPH, and toxT genes. To define the ToxR regulon more fully, mutants defective in these regulatory genes were transcriptionally profiled by using V. cholerae genomic microarrays. This study identified 13 genes that were transcriptionally repressed by the toxT mutation (all involved in CT and TCP biogenesis),and 27 and 60 genes that were transcriptionally repressed by the tcpPH and toxRS mutations, respectively. During the course of this analysis, we validated the use of a genomic DNA-based reference sample as a means to standardize and normalize data obtained in different microarray experiments. This method allowed the accurate transcriptional profiling of V. cholerae cells present in stools from cholera patients and the comparison of these profiles to those of wild-type and mutant strains of V. cholerae grown under optimal conditions for CT and TCP expression. Our results suggest that vibrios present in cholera stools carry transcripts for these two virulence determinants, albeit at relatively low levels compared with optimal in vitro conditions. The transcriptional profile of vibrios present in cholera stools also suggests that the bacteria experienced conditions of anaerobiosis, iron limitation, and nutrient deprivation within the human gastrointestinal tract. C1 Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Int Ctr Diarrhoeal Dis Res, Genet Mol Lab, Dhaka 1212, Bangladesh. Massachusetts Gen Hosp, Dept Med, Infect Dis Unit, Boston, MA 02114 USA. RP Mekalanos, J (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, 200 Longwood Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [AI18045, R01 AI018045, R37 AI018045] NR 39 TC 116 Z9 129 U1 2 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 4 PY 2003 VL 100 IS 5 BP 2801 EP 2806 DI 10.1073/pnas.2628026100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 652DR UT WOS:000181365000113 PM 12601157 ER PT J AU Niquet, J Baldwin, RA Allen, SG Fujikawa, DG Wasterlain, CG AF Niquet, J Baldwin, RA Allen, SG Fujikawa, DG Wasterlain, CG TI Hypoxic neuronal necrosis: Protein synthesis-independent activation of a cell death program SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CYTOCHROME-C RELEASE; MITOCHONDRIAL PERMEABILITY TRANSITION; CNS MITOCHONDRIA; GLOBAL-ISCHEMIA; APOPTOSIS; HIPPOCAMPUS; EXPRESSION; INDUCTION; MECHANISM; SURVIVAL AB Hypoxic necrosis of dentate gyrus neurons in primary culture required the activation of an orderly cell death program independent of protein synthesis. Early mitochondrial swelling and loss of the mitochondrial membrane potential were accompanied by release of cytochrome c and followed by caspase-9-dependent activation of caspase-3. Caspase-3 and -9 inhibitors reduced neuronal necrosis. Calcium directly induced cytochrome c release from isolated mitochondria. Hypoxic neuronal necrosis may be an active process in which the direct effect of hypoxia on mitochondria may lead to the final common pathway of caspase-3-mediated neuronal death. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Expt Neurol Labs, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Brain Res Inst, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Niquet, J (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Res 151,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NINDS NIH HHS [NS13515, R01 NS013515] NR 35 TC 53 Z9 60 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 4 PY 2003 VL 100 IS 5 BP 2825 EP 2830 DI 10.1073/pnas.0530113100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 652DR UT WOS:000181365000117 PM 12606726 ER PT J AU Alonso, JM Stepanova, AN Solano, R Wisman, E Ferrari, S Ausubel, FM Ecker, JR AF Alonso, JM Stepanova, AN Solano, R Wisman, E Ferrari, S Ausubel, FM Ecker, JR TI Five components of the ethylene-response pathway identified in a screen for weak ethylene-insensitive mutants in Arabidopsis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAY; AUXIN-TRANSPORT; GENE; THALIANA; PROTEIN; ETHYLENE-INSENSITIVE3; ENCODES; FAMILY; ETR1; BIOSYNTHESIS AB Five ethylene-insensitive loci (wei1-wei5) were identified by using a low-dose screen for "weak" ethylene-insensitive mutants. wei1, wei2, and wei3 seedlings showed hormone insensitivity only in roots, whereas wei4 and wei5 displayed insensitivity in both roots and hypocotyls. The genes corresponding to wei1, wei4, and wei5 were isolated using a positional cloning approach. The wei1 mutant harbored a recessive mutation in TIR1, which encodes a component of the SCF protein ubiquitin ligase involved in the auxin response. wei4, a dominant mutant, resulted from a mutation in the ethylene receptor ER5, whereas wei5, a semidominant mutant, was caused by a mutation in the EIN3-related transcription factor gene EIL1. The simultaneous loss of functional WEI5/EIL1 and EIN3 nearly completely abolished the ethylene response in etiolated seedlings, and adult plants were highly susceptible to infection by the necrotrophic fungal pathogen Botrytis cinerea. Moreover, wei5/eil1 ein3 double mutants were able to fully suppress constitutive signaling caused by ctr1, suggesting a synergistic interaction among these gene products. Unlike previously known root ethylene-insensitive mutants, wei2 and wei3 were not affected in their response to auxin and showed a normal response to gravity. Genetic mapping studies indicate that wei2 and wei3 correspond to previously unidentified ethylene pathway genes that may control cell-elongation processes functioning at the intersection of the ethylene and auxin response pathways. C1 Salk Inst Biol Studies, Plant Biol Lab, La Jolla, CA 92037 USA. Michigan State Univ, Dept Energy, Plant Res Lab, E Lansing, MI 48824 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Ecker, JR (reprint author), Salk Inst Biol Studies, Plant Biol Lab, La Jolla, CA 92037 USA. EM ecker@salk.edu RI Ecker, Joseph/B-9144-2008; Alonso, Jose/K-6826-2014; OI Ecker, Joseph/0000-0001-5799-5895; Alonso, Jose/0000-0001-7087-1571; Solano, Roberto/0000-0001-5459-2417 FU NIGMS NIH HHS [GM48707, R01 GM048707, R37 GM048707] NR 32 TC 187 Z9 211 U1 2 U2 18 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 4 PY 2003 VL 100 IS 5 BP 2992 EP 2997 DI 10.1073/pnas.0438070100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 652DR UT WOS:000181365000146 PM 12606727 ER PT J AU Rooney, S Alt, FW Lombard, D Whitlow, S Eckersdorff, M Fleming, J Fugmann, S Ferguson, DO Schatz, DG Sekiguchi, J AF Rooney, S Alt, FW Lombard, D Whitlow, S Eckersdorff, M Fleming, J Fugmann, S Ferguson, DO Schatz, DG Sekiguchi, J TI Defective DNA repair and increased genomic instability in artemis-deficient murine cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE artemis; DNA repair; genomic instablility; telomere fusions; VDJ recombination ID DEPENDENT PROTEIN-KINASE; STRAND BREAK REPAIR; SEVERE COMBINED IMMUNODEFICIENCY; COMBINED IMMUNE-DEFICIENCY; PRE-B CELLS; END-JOINING PATHWAY; LIGHT CHAIN GENES; V(D)J RECOMBINATION; SCID MICE; CATALYTIC SUBUNIT AB In developing lymphocytes, the recombination activating gene endonuclease cleaves DNA between V, D, or J coding and recombination signal (RS) sequences to form hairpin coding and blunt RS ends, which are fused to form coding and RS joins. Nonhomologous end joining (NHEJ) factors repair DNA double strand breaks including those induced during VDJ recombination. Human radiosensitive severe combined immunodeficiency results from,lack of Artemis function, an NHEJ factor with in vitro endonuclease/exonuclease activities. We inactivated Artemis in murine embryonic stem (ES) cells by targeted mutation. Artemis deficiency results in impaired VDJ coding, but not RS, end joining. In addition, Artemis-deficient ES cells are sensitive to a radiomimetic drug, but less sensitive to ionizing radiation. VDJ coding joins from Artemis-deficient ES cells, which surpnisingly are distinct from the highly deleted joins consistently obtained from DNA-dependent protein kinase catalytic subunit-deficient ES cells, frequently lack deletions and often display large junctional palindromes, consistent with a hairpin coding end opening defect. Strikingly, Artemis-deficient ES cells have increased chromosomal instability including telomeric fusions. Thus, Artemis appears to be required for a subset of NHEJ reactions that require end processing. Moreover, Artemis functions as a genomic caretaker, most notably in prevention of translocations and telomeric fusions. As Artemis deficiency is compatible with human life, Artemis may also suppress genomic instability in humans. C1 Harvard Univ, Sch Med, Childrens Hosp, Ctr Blood Res,Howard Hughes Med Inst, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Mol Biophys & Biochem, Immunobiol Sect, New Haven, CT 06510 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Ctr Blood Res,Howard Hughes Med Inst, 300 Longwood Ave,Enders 861, Boston, MA 02115 USA. RI Schatz, David/A-6748-2013; OI Schatz, David/0000-0002-5669-1176; Sekiguchi, JoAnn/0000-0002-7178-4258 FU NCI NIH HHS [CA92625, P01 CA092625]; NHLBI NIH HHS [K08 HL067580, K08 HL67580-02]; NIAID NIH HHS [AI32524, AI35714, P01 AI035714, R01 AI032524, R37 AI032524] NR 78 TC 137 Z9 140 U1 1 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 MAR 3 PY 2003 VL 197 IS 5 BP 553 EP 565 DI 10.1084/jem.20021891 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 652ZU UT WOS:000181411400003 PM 12615897 ER PT J AU Hoen, M Golembiowski, M Guyot, E Deprez, V Caplan, D Dominey, PF AF Hoen, M Golembiowski, M Guyot, E Deprez, V Caplan, D Dominey, PF TI Training with cognitive sequences improves syntactic comprehension in agrammatic aphasics SO NEUROREPORT LA English DT Article DE agrammatism; aphasia; cognitive sequence; re-education; syntax ID CLOSED-CLASS WORDS; LANGUAGE; TASK AB A major open question in cognitive neuroscience concerns the modularity of language: does human language rely, in part, on neural processes that are not language specific? Such reliance would predict that learning should transfer between non-linguistic and linguistic domains via this common neural basis. To test this prediction, we studied effects of non-linguistic cognitive sequence training on syntactic comprehension of six left-hemisphere damaged aphasic patients. Syntactic comprehension impairment was quantified before and after 10 weeks of training on a non-linguistic sequence processing task. This task used a transformational rule specifically corresponding to the transformation required for understanding a particular type of sentence referred to as relativised. Non-linguistic sequencing improved significantly with training (day effect: F(9,45)=3.7, p<0.005). Moreover, a significant transfer of this improvement was observed for relativised, but not active nor passive sentences (pre-post x type interaction: F(2,10)=4.72, p < 0.05). The specificity of this transfer indicates that language relies partially on functional and neural processes that are not language specific. C1 Inst Cognit Sci, Sequential Cognit & Language Grp, CNRS, UMR 5015, F-69675 Bron, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Dominey, PF (reprint author), Inst Cognit Sci, Sequential Cognit & Language Grp, CNRS, UMR 5015, 67 Blvd Pinel, F-69675 Bron, France. EM dominey@isc.cnrs.fr RI Dominey, Peter/H-3832-2012; Hoen, Michel/C-7721-2012 OI Dominey, Peter/0000-0002-9318-179X; Hoen, Michel/0000-0003-2099-8130 NR 19 TC 31 Z9 31 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAR 3 PY 2003 VL 14 IS 3 BP 495 EP 499 DI 10.1097/00001756-200303030-00040 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 656ZW UT WOS:000181641800040 PM 12634511 ER PT J AU Lansing, RW Moosavi, SH Banzett, RB AF Lansing, RW Moosavi, SH Banzett, RB TI Measurement of dyspnea: word labeled visual analog scale vs. verbal ordinal scale SO RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY LA English DT Article DE control of breathing, air hunger; dyspnea, air hunger; mammals, humans; scales, verbal category, ordinal, visual analog ID AIR HUNGER; VENTILATED QUADRIPLEGICS; EXPERIMENTAL PAIN; SENSATION; HUMANS; P-CO2; BREATHLESSNESS; PULMONARY; INTENSITY; VOLUME AB We previously used a verbal ordinal rating scale to measure dyspnea. That scale was easy for subjects to use and the words provided consistency in ratings. We have recently developed a word labeled visual analog scale (LVAS) with labels placed by the subjects, retaining the advantages of a verbal scale while offering a continuous scale that generates parametric data. In a retrospective meta-analysis of data from 43 subjects, individuals differed little in their placement of words on the 100 mm LVAS (mean +/- S.D. for slight = 20 +/- 2.5 mm, moderate = 50 +/- 5 min and severe = 80 +/- 6 mm) and ratings were distributed uniformly along the scale. A significant stimulus -response correlation was obtained for both the LVAS (r(2) = 0.98) and for the verbal ordinal scale (Spearman r = 0.94). The resolution of the two scales differed only slightly. With meaningful verbal anchors, well-defined end-points, and clear instructions about the specific sensation to be rated, both scales provide valid measures of dyspnea. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Publ Hlth, Physiol Program, Boston, MA 02115 USA. Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Moosavi, SH (reprint author), Harvard Univ, Sch Publ Hlth, Physiol Program, 665 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL57916, HL46690] NR 32 TC 20 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-9048 J9 RESP PHYSIOL NEUROBI JI Respir. Physiol. Neuro. PD MAR 3 PY 2003 VL 134 IS 2 BP 77 EP 83 AR PII S1569-9048(02)00211-2 DI 10.1016/S1569-9048(02)00211-2 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 652YC UT WOS:000181407600001 PM 12609476 ER PT J AU Bao, G Tsourkas, A Santangelo, P AF Bao, G Tsourkas, A Santangelo, P TI Dual fret molecular beacons for gene detection in living cells SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 Georgia Inst Technol, Dept Biomed Engn, Atlanta, GA 30332 USA. Emory Univ, Atlanta, GA 30332 USA. Massachusetts Gen Hosp, MGH CMIR, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RI Tsourkas, Andrew/A-1074-2007 OI Tsourkas, Andrew/0000-0001-7758-1753 NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 195-IEC BP U982 EP U982 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917804615 ER PT J AU Panilaitis, B Glickstein, L Fuhrman, J Kaplan, DL AF Panilaitis, B Glickstein, L Fuhrman, J Kaplan, DL TI Toll-4 dependent adjuvant activity of emulsan. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LA SP Amer Chem Soc C1 Tufts Univ, Dept Chem & Biol Engn, Medford, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Tufts Univ, Dept Biol, Medford, MA 02155 USA. EM bpanilai@emerald.tufts.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 145-BIOT BP U207 EP U207 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PU UT WOS:000187917800835 ER PT J AU Zaari, N Rajagopalan, P Kim, SK Wong, JY AF Zaari, N Rajagopalan, P Kim, SK Wong, JY TI Microgradient mechanically-compliant polyacrylamide gels to probe cell response SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 225th National Meeting of the American-Chemical-Society CY MAR 23-27, 2003 CL NEW ORLEANS, LOUISIANA SP Amer Chem Soc C1 Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Cambridge, MA 02138 USA. EM sooyoung@bu.edu RI Wong, Joyce/F-3732-2011 OI Wong, Joyce/0000-0002-3526-6381 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR PY 2003 VL 225 MA 346-POLY BP U582 EP U582 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 761PW UT WOS:000187918003043 ER PT J AU Jackson, VA Palepu, A Szalacha, L Caswell, C Carr, PL Inui, T AF Jackson, VA Palepu, A Szalacha, L Caswell, C Carr, PL Inui, T TI "Having the right chemistry": A qualitative study of mentoring in academic medicine SO ACADEMIC MEDICINE LA English DT Article ID FACULTY AB Purpose. To develop a deeper understanding of mentoring by exploring lived experiences of academic medicine faculty members. Mentoring relationships are key to developing productive careers in academic medicine, but such alliances hold a certain "mystery." Method. Using qualitative techniques, between November 1999 and March 2000, the authors conducted individual telephone interviews of 16 faculty members about their experiences with mentoring. Interviews were taped and transcribed and authors identified major themes through multiple readings. A consensus taxonomy for classifying content evolved from comparisons of coding by four reviewers. Themes expressed by participants were studied for patterns of connection and grouped into broader categories. Results. Almost 98% of participants identified lack of mentoring as the first (42%) or second (56%) most important factor hindering career progress in academic medicine. Finding a suitable mentor requires effort and persistence. Effective mentoring necessitates a certain chemistry for an appropriate interpersonal match. Prized mentors have "clout," knowledge, and interest in the mentees, and provide both professional and personal support. In cross-gender mentoring, maintaining clear boundaries is essential for an effective relationship. Samegender or same-race matches between mentor and mentee were not felt to be essential. Conclusions. Having a mentor is critical to having a successful career in academic medicine. Mentees need to be diligent in seeking out these relationships and institutions need to encourage and value the work of mentors. Participants without formalized mentoring relationships should look to peers and colleagues for assistance in navigating the academic system. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Palliat Care, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ British Columbia, St Pauls Hosp, Div Gen Internal Med, Vancouver, BC V5Z 1M9, Canada. Brown Univ, Dept Educ, Providence, RI 02912 USA. New England Res Inst, Survey Res Ctr, Watertown, MA 02172 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Indiana Univ, Sch Med, Regenstrief Inst, Indianapolis, IN USA. RP Jackson, VA (reprint author), Dana Farber Canc Inst, 44 Binney St SW 411, Boston, MA 02115 USA. OI Palepu, Anita/0000-0002-7881-4800 NR 16 TC 166 Z9 169 U1 2 U2 7 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD MAR PY 2003 VL 78 IS 3 BP 328 EP 334 DI 10.1097/00001888-200303000-00020 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 653YW UT WOS:000181465500016 PM 12634219 ER PT J AU Bonner, LT AF Bonner, LT TI On bridging the gap SO ACADEMIC PSYCHIATRY LA English DT Editorial Material ID HEALTH-CARE C1 NW Network Mental Illness Res Educ & Clin Ctr, Dept Vet Affairs, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Bonner, LT (reprint author), VA Puget Sound Hlth Care Syst, MIRECC, S-116,1660 S Columbian Way, Seattle, WA 98108 USA. FU NIA NIH HHS [R01 AG18644] NR 5 TC 11 Z9 11 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD SPR PY 2003 VL 27 IS 1 BP 29 EP 30 DI 10.1176/appi.ap.27.1.29 PG 2 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 649NR UT WOS:000181215300005 PM 12824118 ER PT J AU Bostic, JQ Schlozman, S Pataki, C Ristuccia, C Beresin, EV Martin, A AF Bostic, JQ Schlozman, S Pataki, C Ristuccia, C Beresin, EV Martin, A TI From Alice Cooper to Marilyn Manson - The significance of adolescent antiheroes SO ACADEMIC PSYCHIATRY LA English DT Article ID HEAVY-METAL MUSIC; MEDIA; SUICIDE AB Every generation has icons attractive to adolescents and equally repugnant to adults. This article examines antihero characteristics, their appeal to adolescents, and how adults can respond to adolescents enamored of antiheroes. The stage personas of antiheroes champion rejection of the mainstream, assail adult constraints and expectations, explore frightening topics, and ultimately fulfill the adolescent fantasy of surviving alienation and emerging victorious over parents and peers. But antihero idolization also tests the adult's defenses. Adults, fearing loss of control and rejection by the adolescent, sometimes resort to primitive defenses mismatched to the developmental needs of the adolescent. Adults, as much as the adolescents, benefit from examining their individual reactions to the antihero and how their current relationship can accommodate this intrusion. The antihero phenomenon presents adults with an opportunity to model ways to think through that which is uncomfortable and to navigate together the adolescent's developmentally normative separation efforts. (Academic Psychiatry 2003; 27:54-62). C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Tufts Univ, Boston, MA 02111 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. Yale Child Study Ctr, New Haven, CT USA. RP Bostic, JQ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 15 Parkman St,WAC 725, Boston, MA 02114 USA. NR 23 TC 2 Z9 2 U1 2 U2 9 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD SPR PY 2003 VL 27 IS 1 BP 54 EP 62 DI 10.1176/appi.ap.27.1.54 PG 9 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 649NR UT WOS:000181215300010 PM 12824123 ER PT J AU Schellingerhout, D Lev, MH Bagga, RJ Rincon, S Berdichevsky, D Thangaraj, V Gonzalez, RG Alpert, NM AF Schellingerhout, D Lev, MH Bagga, RJ Rincon, S Berdichevsky, D Thangaraj, V Gonzalez, RG Alpert, NM TI Coregistration of head CT comparison studies: Assessment of clinical utility SO ACADEMIC RADIOLOGY LA English DT Article DE computed tomography (CT), image processing; diagnostic radiology, observer performance; head, CT ID IMAGE REGISTRATION; ALGORITHM; PET AB Rationale and Objectives. The authors evaluated the clinical utility of image coregistration in the interpretation of follow-up computed tomographic (CT) studies of the head. Materials and Methods. Fourteen patients with 34 intracranial lesions underwent follow-up head CT. The images were coregistered automatically with proprietary software on a standard personal computer, and all patient demographic data were removed. A neuroradiologist read the coregistered images several days after first reading the nonregistered images. The reading was repeated some months later to assess intraobserver variability, and a second reader was recruited so that interobserver variability also could be assessed. The interpretations of nonregistered images served as controls for the interpretations of coregistered images. Readers were asked to assess changes in lesion size quantitatively and to record the time it took to, evaluate each case. Differences in interpretation speed were evaluated with the t test. Univariate analysis was used to measure accuracy; mterpretations were compared with those of a nonblinded senior neuroradiologist, which served as the diagnostic standard. Intra- and interindividual variability were assessed with the kappa statistic. Results. The time needed to read the studies decreased by an average of 65.6% (P <.05), with statistically significant reductions for each reader. Coregistration also changed the interpretation results in 21.9% of cases. Coregistration increased the accuracy of reading, but not significantly. Intraobserver variability improved from 0.3554 to 0.7328 with coregistration, and interobserver variability improved from 0.2670 to 0.3309. Conclusion. Image coregistration is technically feasible and accurate. Coregistration of follow-up studies significantly reduces the time needed for comparison and interpretation. It does not detract from the accuracy of interpretation of follow-up studies and tends to decrease intra- and interobserver variability. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Integrated Med Imaging Syst, Waltham, MA USA. RP Schellingerhout, D (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 8 TC 11 Z9 11 U1 1 U2 1 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD MAR PY 2003 VL 10 IS 3 BP 242 EP 248 DI 10.1016/S1076-6332(03)80097-1 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 650DX UT WOS:000181248300002 PM 12643550 ER PT J AU Shin, Y Cho, HS Fukumoto, H Shimizu, T Shirasawa, T Greenberg, SM Rebeck, GW AF Shin, Y Cho, HS Fukumoto, H Shimizu, T Shirasawa, T Greenberg, SM Rebeck, GW TI A beta species, including IsoAsp23 A beta, in Iowa-type familial cerebral amyloid angiopathy SO ACTA NEUROPATHOLOGICA LA English DT Article DE Alzheimer's disease; mutation; isomerization; vascular dementia ID ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; PRESENILIN-1 MUTATION; BRITISH DEMENTIA; FIBRIL FORMATION; DUTCH TYPE; PEPTIDE; DEPOSITION; AGGREGATION; HEMORRHAGE AB Mutations within the Abeta sequence of the APPP gene are associated with familial forms of cerebral amyloid angiopathy (CAA). One mutation, Abeta D23N, was identified in a family in Iowa with a clinical history of early-onset dementia. We analyzed the pattern of Abeta deposition in the hippocampus of an individual with Iowa CAA. In addition to strong amyloid angiopathy, we found unusual diffuse Abeta deposits in the CA4, and in the parenchyma near arnyloid-laden vessels. ELISA of cortical brain extracts showed that Abeta40 was nearly 20-fold higher than Abeta42, in both soluble and insoluble fractions. We identified an Abeta antibody that recognized wild-type Abeta but riot Iowa Abeta. With this antibody, we found that wild-type Abeta was present in the Abeta deposits, but limited to the strongest deposits in the cerebrovasculature. Previous in vitro studies suggested that the presence of an asparagine at position 23 of Abeta favored formation of an isoAsp residue, which was associated with increased Abeta fibrillogenesis. Using isoAsp-specific antibodies in immunohistochemical studies, we examined the distribution of isoAsp Abeta in the Iowa brain. IsoAsp7 Abeta was present in both the parenchymal and vascular deposits, whereas isoAsp23 Abeta was present only in vascular deposits. These data suggest that alteration of Abeta Asn23 to isoAsp may be an important determinant in the deposition of Abeta in cerebral blood vessels. C1 Tokyo Metropolitan Inst Gerontol, Dept Mol Genet, Itabashi Ku, Tokyo 1730015, Japan. Massachusetts Gen Hosp, Alzheimers Res Lab, Charlestown, MA 02129 USA. RP Rebeck, GW (reprint author), Massachusetts Gen Hosp, Alzheimers Res Lab, 114 6th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [R03 AG19507] NR 47 TC 29 Z9 29 U1 0 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD MAR PY 2003 VL 105 IS 3 BP 252 EP 258 DI 10.1007/s00401-002-0639-0 PG 7 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 652BN UT WOS:000181359800009 PM 12557012 ER PT J AU Si, ZH Phan, N Kiprilov, E Sodroski, J AF Si, ZH Phan, N Kiprilov, E Sodroski, J TI Effects of HIV type 1 envelope glycoprotein proteolytic processing on antigenicity SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODY; PIG-TAILED MACAQUES; NEUTRALIZATION SENSITIVITY; CONFORMATIONAL-CHANGES; PERSISTENT INFECTION; LYMPHOCYTE DEPLETION; GP120 GLYCOPROTEIN; RECEPTOR-BINDING; ATOMIC-STRUCTURE AB Passaged simian-human immunodeficiency virus (SHIV)-HXBc2P 3.2 exhibits resistance to neutralization by most antibodies and soluble CD4 compared with the parental SHIV-HXBc2; these SHIVs are neutralized equivalently by 2G12 antibody. 2G12 antibody bound proteolytically processed, cell surface envelope glycoproteins from these viruses equivalently; by contrast, other antibodies bound less efficiently to HXBc2P 3.2 envelope glycoproteins than to HXBc2 envelope glycoproteins. We have examined the influence of proteolytic processing of the envelope glycoprotein precursor on antigenicity, comparing antibody binding to cleaved and uncleaved cell surface envelope glycoproteins and to uncleaved soluble trimeric envelope glycoproteins. All envelope glycoproteins bound neutralizing antibodies better than nonneutralizing antibodies, suggesting that their general topology is similar. Differences between cleaved HXBc2 and HXBc2P 3.2 envelope glycoproteins in binding a given antibody, which correlated with susceptibility to neutralization, were not evident in uncleaved envelope glycoproteins. These results indicate that proteolytic processing allows subtle but biologically important adjustments in the conformation of HIV-1 envelope glycoproteins. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div Aids, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. FU NIAID NIH HHS [AI31783, AI39420, AI42848] NR 64 TC 41 Z9 42 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAR PY 2003 VL 19 IS 3 BP 217 EP 226 DI 10.1089/088922203763315722 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 655KM UT WOS:000181551000007 PM 12689414 ER PT J AU Rumsfeld, JS Magid, DJ Plomondon, ME Sales, AE Grunwald, GK Every, NR Spertus, JA AF Rumsfeld, JS Magid, DJ Plomondon, ME Sales, AE Grunwald, GK Every, NR Spertus, JA TI History of depression, angina, and quality of life after acute coronary syndromes SO AMERICAN HEART JOURNAL LA English DT Article; Proceedings Paper CT 74th Annual Scientific Sessions of the American-Heart-Association CY NOV 11-14, 2001 CL ANAHEIM, CALIFORNIA SP Amer Heart Assoc ID SEROTONIN REUPTAKE INHIBITORS; MYOCARDIAL-INFARCTION; OF-LIFE; ARTERY DISEASE; FUNCTIONAL STATUS; UNSTABLE ANGINA; HEALTH; OUTPATIENTS; PROGNOSIS; MORTALITY AB Background Depression has been associated with higher mortality and morbidity rates after acute coronary syndromes (ACS), but little is known about the association between depression, angina burden, and quality of life. We evaluated the association between a history of depression and patient-reported angina frequency, physical limitation, and quality of life 7 months after discharge from the hospital for ACS. Methods Patients were enrolled in the Department of Veterans Affairs Access to Cardiology Study, a cohort study of all patients with acute myocardial infarction or unstable. angina who were discharged, from 24 Veterans Affairs medical centers between March 1998 and February 1999. Data from 1957 patients who completed a 7-month postdischarge Seattle Angina Questionnaire were analyzed. Multivariate logistic regression was used to evaluate a history of depression as an independent predictor of angina frequency, physical limitation, and quality of life 7 months after ACS, as measured with the Seattle Angina Questionnaire. Results A total of 526 patients (26.7%) had a history of depression. After adjustment for a wide array of demographic, cardiac, and comorbid factors, a history of depression was significantly associated with more frequent angina (odds ratio [OR] 2.40; 95 % CI 1.86-3.10, P < .001), greater physical limitation (OR 2.89, 95 % CI 2.17-3.86, P < .001), and worse quality of life (OR 2.84, 95 % CI 2.16-3.72, P < .001) after ACS. Conclusion We found a strong association between a history of depression and both heavier angina burden and worse health status after ACS. These findings further support the importance of depression as a risk marker for adverse outcomes after ACS. C1 Denver VA Med Ctr, Denver, CO 80206 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Colorado Permanente Med Grp, Denver, CO USA. Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Missouri, Kansas City, MO 64110 USA. RP Rumsfeld, JS (reprint author), Denver VA Med Ctr, 1055 Clermont St, Denver, CO 80206 USA. OI Sales, Anne/0000-0001-9360-3334 NR 32 TC 86 Z9 99 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAR PY 2003 VL 145 IS 3 BP 493 EP 499 DI 10.1067/mhj.2003.177 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 663QG UT WOS:000182015800020 PM 12660673 ER PT J AU Baker, LD Sambamurti, K Craft, S Cherrier, M Raskind, MA Stanczyk, FZ Plymate, SR Asthana, S AF Baker, LD Sambamurti, K Craft, S Cherrier, M Raskind, MA Stanczyk, FZ Plymate, SR Asthana, S TI 17 beta-estradiol reduces plasma A beta 40 for HRT-naive postmenopausal women with Alzheimer disease - A preliminary study SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article; Proceedings Paper CT International Meeting on Alzbeimers Disease and Related Disorders CY JUL, 2002 CL STOCKHOLM, SWEDEN ID ESTROGEN REPLACEMENT THERAPY; CENTRAL-NERVOUS-SYSTEM; BETA-AMYLOID PEPTIDES; CEREBROSPINAL-FLUID; PRECURSOR PROTEIN; CONTROLLED TRIAL; DOUBLE-BLIND; DEMENTIA; OVARIECTOMY; METABOLISM AB One mechanism to support the potentially ben, the brain for postmenopausal women potentially involves the hormone's ability to favorably alter the processing of amyloid-precursor protein (APP), believed to play an important role in the pathobiology of Alzheimer disease (AD). The authors evaluated the effects of estrogen administration on plasma concentration of one by-product of APP processing, Abeta40, for postmenopausal women with AD. Methods: In a placebo-controlled, double blind, parallel-group design study, 20 women were randomized to receive either 0.10 mg/day of transdermal 17beta-estradiol or a placebo for 8 weeks and were retrospectively evaluated as to whether basal levels of Abeta40 were affected by pre-study use of hormone replacement therapy (HRT). Blood samples were collected and cognitive tests were administered at baseline; at Weeks 3, 5, and 8 during treatment,and again 8 weeks after treatment termination. Results: For the group as a whole, plasma Abeta40 was not reliably reduced in response to short-term estradiol administration. For HRT-naive subjects, baseline Abeta40 concentrations were higher than those of previous HRT users, and controlled estradiol administration significantly reduced plasma Abeta40 by the end of the 8-week treatment period. Conclusions: These results provide preliminary clinical evidence to support an effect of estradiol on Abeta-processing for AD women who are HRT-naive. This finding suggests that the hormone may serve as an AA lowering agent for HRT-naive AD women, which may in turn, have ultimate ramifications for the progression of AD pathology. C1 Univ Wisconsin, Sch Med, Dept Med, Madison, WI 53705 USA. GRECC, LDB, SC, MAR,SRP, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Mayo Clin, Dept Pharmacol, Jacksonville, FL 32224 USA. Univ So Calif, Dept Obstet & Gynecol, Los Angeles, CA 90089 USA. William S Middleton Vet Affairs Hosp, GRECC, Madison, WI USA. RP Asthana, S (reprint author), Univ Wisconsin, Sch Med, Dept Med, 2870 Univ Ave,Suite 100, Madison, WI 53705 USA. NR 32 TC 19 Z9 22 U1 3 U2 4 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD MAR-APR PY 2003 VL 11 IS 2 BP 239 EP 244 DI 10.1176/appi.ajgp.11.2.239 PG 6 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 649LL UT WOS:000181209900014 PM 12611754 ER PT J AU Cuajungco, MP Leyne, M Mull, J Gill, SP Lu, WN Zagzag, D Axelrod, FB Maayan, C Gusella, JF Slaugenhaupt, SA AF Cuajungco, MP Leyne, M Mull, J Gill, SP Lu, WN Zagzag, D Axelrod, FB Maayan, C Gusella, JF Slaugenhaupt, SA TI Tissue-specific reduction in splicing efficiency of IKBKAP due to the major mutation associated with familial dysautonomia SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID POLYMERASE-II HOLOENZYME; REAL-TIME; GENE-EXPRESSION; ELONGATOR; COMPLEX; IKAP; VALIDATION; COMPONENT; PROTEIN; SUBUNIT AB We recently identified a mutation in the I-kappaB kinase associated protein (IKBKAP) gene as the major cause of familial dysautonomia (FD), a recessive sensory and autonomic neuropathy. This alteration, located at base pair 6 of the intron 20 donor splice site, is present on >99.5% of FD chromosomes and results in tissue-specific skipping of exon 20. A second FD mutation, a missense change in exon 19 (R696P), was seen in only four patients heterozygous for the major mutation. Here, we have further characterized the consequences of the major mutation by examining the ratio of wild-type to mutant (WT: MU) IKBKAP transcript in EBV-transformed lymphoblast lines, primary fibroblasts, freshly collected blood samples, and postmortem tissues from patients with FD. We consistently found that WT IKBKAP transcripts were present, albeit to varying extents, in all cell lines, blood, and postmortem FD tissues. Further, a corresponding decrease in the level of WT protein is seen in FD cell lines and tissues. The WT: MU ratio in cultured lymphoblasts varied with growth phase but not with serum concentration or inclusion of antibiotics. Using both densitometry and real-time quantitative polymerase chain reaction, we found that relative WT: MU IKBKAP RNA levels were highest in cultured patient lymphoblasts and lowest in postmortem central and peripheral nervous tissues. These observations suggest that the relative inefficiency of WT IKBKAP mRNA production from the mutant alleles in the nervous system underlies the selective degeneration of sensory and autonomic neurons in FD. Therefore, exploration of methods to increase the WT: MU IKBKAP transcript ratio in the nervous system offers a promising approach for developing an effective therapy for patients with FD. C1 Harvard Univ, Sch Med, Inst Human Genet, Boston, MA 02115 USA. Brigham & Womens Hosp, Collis Genome Lab, Boston, MA 02115 USA. NYU, Med Ctr, Dept Pathol, New York, NY 10016 USA. NYU, Med Ctr, Dept Pediat, New York, NY 10016 USA. Hadassah Univ Hosp, Dept Pediat, IL-91120 Jerusalem, Israel. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. RP Slaugenhaupt, SA (reprint author), Harvard Univ, Sch Med, Inst Human Genet, 77 Ave Louis Pasteur,HIM 422, Boston, MA 02115 USA. RI Cuajungco, Math/B-2647-2008; OI Cuajungco, Math/0000-0003-0749-9564; Lu, Weining/0000-0002-6570-3044 FU NICHD NIH HHS [N01-HD-8-3284]; NINDS NIH HHS [R01 NS036326, R01 NS36326] NR 42 TC 65 Z9 65 U1 2 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAR PY 2003 VL 72 IS 3 BP 749 EP 758 DI 10.1086/368263 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 648LJ UT WOS:000181152600026 PM 12577200 ER PT J AU Knight, EL Kramer, HM Curhan, GC AF Knight, EL Kramer, HM Curhan, GC TI High-normal blood pressure and microalbuminuria SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE high-normal blood pressure (BP); normal blood pressure (BP); blood pressure (BP); albuminuria; microalbuminuria; urinary protein ID URINARY ALBUMIN EXCRETION; CARDIOVASCULAR RISK-FACTORS; ESSENTIAL-HYPERTENSION; ALBUMIN/CREATININE RATIO; GENERAL-POPULATION; PREVALENCE; DYSFUNCTION; DISEASE; ADULTS; DAMAGE AB Background. High-normal blood pressure (BP) is associated with increased cardiovascular risk compared with optimal BB, but no study has specifically examined the association between high-normal BP and microalbuminuria, an established predictor of future cardiovascular events. Methods: This was a cross-sectional study of normotensive (systolic BP [SBP] < 140 mm Hg, diastolic BP [DBP] < 90 mm Hg) individuals without diabetes with no hypertension history enrolled in the Third National Health and Nutrition Examination Survey. BP was categorized as high normal (SBP, 130 to 139 mm Hg or DBP, 85 to 89 mm Hg), normal (SBP, 120 to 129 mm Hg or DBP, 80 to 84 mm Hg), and optimal (SBP < 120 mm Hg and DBP < 80 mm Hg). We also separately examined SBP, DBP, mean arterial pressure (MAP), and pulse pressure. Microalbuminuria was defined using sex-specific cutoff values (urine albumin-creatinine ratio greater than or equal to 17 and less than or equal to 250 mug/mg [greater than or equal to1.0 and less than or equal to528 mg/mmol] for men and greater than or equal to 25 and less than or equal to 355 mug/mg for women [greater than or equal to3 and less than or equal to40 mg/mmol]). We used multivariate logistic regression to analyze the association between different BP measurements and microalbuminuria. Results: Compared with optimal BP, high-normal BP was significantly associated with increased odds of microalbuminuria (odds ratio [OR], 2.13; 95% confidence interval [CI], 1.51 to 3.01). Similarly, MAP (OR, 1.41; 95% CI, 1.15 to 1.74 per 10-mm Hg increment), SBP (OR, 1.27; 95% CI, 1.09 to 1.48 per 10-mm Hg increment), and DBP (OR, 1.29; 95% CI, 1.06 to 1.57 per 10-mm Hg increment) were significantly associated with microalbuminuria. Conclusion: High-normal BP is significantly associated with microalbuminuria compared with optimal BP and may be a biomarker of the increased cardiovascular risk observed in this population. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Unit, Boston, MA USA. RP Knight, EL (reprint author), Nurses Hlth Study, Channing Lab, 3rd Floor,181 Longwood Ave, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK52866, T32DK0740-16, T32DK07791] NR 28 TC 64 Z9 73 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAR PY 2003 VL 41 IS 3 BP 588 EP 595 DI 10.1053/ajkd.2003.50120 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 651MP UT WOS:000181324000009 PM 12612982 ER PT J AU Kramer, HM Curhan, GC Singh, A AF Kramer, HM Curhan, GC Singh, A CA HELP Study Grp TI Permanent cessation of menses and postmenopausal hormone use in dialysis-dependent women: The HELP Study SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE menopause; women's health; estrogen; epidemiology ID SYSTEMIC LUPUS-ERYTHEMATOSUS; CORONARY HEART-DISEASE; REPLACEMENT THERAPY; UNITED-STATES; PULSE CYCLOPHOSPHAMIDE; NATURAL MENOPAUSE; RENAL-DISEASE; RISK FACTOR; AGE; SMOKING AB Background: Earlier onset of menopause is associated with an increased risk for cardiovascular disease, especially among women with surgical menopause. Information on age at or reasons for the permanent cessation of menses among women with end-stage renal disease (ESRD) remains limited, although cardiovascular disease accounts for more than half of all cardiovascular deaths in this population. Methods: We used data from the Hemodialysis and Estrogen Levels in Postmenopausal Patients Study to examine the reported age when menses permanently ceased, reasons for the permanent cessation of menses, and prevalence of surgical menopause. We also investigated the frequency of current and past postmenopausal hormone (PMH) use among dialysis-dependent women and their views toward PMH therapy. Results Among 238 postmenopausal hemodialysis-dependent women, median age when manses permanently ceased was 48 years. Permanent cessation of menses was attributed to natural causes in 65%, surgical reasons in 30% (16%, hysterectomy without bilateral oophorectomy; 14%, hysterectomy with bilateral oophorectomy), kidney failure in 2%, radiation or chemotherapy in 1%, and other causes in 2%. Among women with a history of bilateral oophorectomy, 71% became menopausal before the age of 35 years. Current and past PMH use was reported by 6% and 17% of the women, respectively, whereas 77% were never administered hormones. Only 2% stated a kidney doctor ever recommended PMH therapy, and 54% said they would not take PMHs if prescribed by their kidney doctor. Conclusion: Many women with ESRD experience surgical menopause before the age of 35 years, which may contribute to the excess cardiovascular mortality among women with ESRD. PMH use remains low among dialysis-dependent women. However, two randomized controlled trials have noted a significantly increased risk for cardiovascular events in women administered estrogen in combination with progestin. Thus, risks associated with PMH use may outweigh the benefits in a population with a very high rate of cardiovascular disease, such as postmenopausal hemodialysis-dependent women. C1 Brigham & Womens Hosp, Div Renal, Boston, MA 02114 USA. Loyola Univ, Med Ctr, Dept Med, Div Nephrol, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Prevent Med & Epidemiol, Maywood, IL 60153 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. Channing Labs, Boston, MA USA. RP Singh, A (reprint author), Brigham & Womens Hosp, Div Renal, 75 Francis St, Boston, MA 02114 USA. NR 33 TC 9 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAR PY 2003 VL 41 IS 3 BP 643 EP 650 DI 10.1053/ajkd.2003.50126 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 651MP UT WOS:000181324000015 PM 12612988 ER PT J AU Wang, Q Bernardini, J Piraino, B Fried, L AF Wang, Q Bernardini, J Piraino, B Fried, L TI Albumin at the start of peritoneal dialysis predicts the development of peritonitis SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE incidence; peritoneal dialysis (PD); peritonitis; albumin; hypoalbuminemia ID MORBIDITY; INDEX AB Background. Both Peritonitis and serum albumin level are associated with morbidity and mortality in peritoneal dialysis (PD) patients. Severe cases of peritonitis result in hypoalbuminemia. However, it is not clear whether hypoalbuminemia predicts the development of peritonitis. Methods: We performed a retrospective analysis of a prospectively collected database from six centers in western Pennsylvania and West Virginia. Incident PD patients with a Charlson Comorbidity Index (CCI) score at the start of PD therapy and serum albumin level measured within 30 days of initiation were selected. Poisson regression was used to analyze predictors of peritonitis. Results: Three hundred ninety-three patients had a CCI score and serum albumin level measured at the start of PD therapy. Overall peritonitis rate was 0.65 episodes/dialysis-year. Significant univariate predictors were albumin level (rate ratio [RR], 0.79 per 1-g/dL [10-g/L] increase; 95% confidence interval [CI], 0.65 to 0.95; P = 0.015), male sex (P = 0.003), and being dialyzed in the Veterans Administration (RR, 1.97; 95% Cl, 1.48 to 2.62; P < 0.001) or other center (RR, 1.68; 95% Cl, 1.92 to 5.62; P < 0.001). Although CCI score correlated inversely with albumin level (r = -0.305; P < 0.001), CCI score was only marginally predictive of peritonitis (P = 0.068). In multivariate analysis, predictors were albumin level (RR, 0.74; 95% Cl, 0.31 to 1.75; P = 0.002) and race (RR, 1.36; P = 0.024). Patients with an initial serum albumin level less than 2.9 g/dL (29 g/L) had a peritonitis rate of 1.5 episodes/dialysis-year compared with 0.6 episodes/ dialysis-year for patients with an initial serum albumin level of 2.9 g/dL or greater (P < 0.001). Conclusion Hypoalbuminemia at the start of PD therapy is an independent predictor of subsequent peritonitis. Intervention studies to decrease peritonitis risk in this high-risk subset of patients are needed. C1 Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA. Vet Adm Hosp, Vet Adm Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Fried, L (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, 4N167,Mailstop 111F-U,Univ Dr C, Pittsburgh, PA 15240 USA. OI Piraino, Beth/0000-0001-5061-0841 NR 17 TC 55 Z9 61 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAR PY 2003 VL 41 IS 3 BP 664 EP 669 DI 10.1053/ajkd.2003.50128 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 651MP UT WOS:000181324000018 PM 12612991 ER PT J AU Williams, ME AF Williams, ME TI New therapies for advanced glycation end product nephrotoxicity: Current challenges SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article; Proceedings Paper CT 11th International Congress on Nutrition and Metabolism in Renal Disease CY MAR 29-31, 2002 CL NAGOYA, JAPAN DE diabetic nephropathy; glycosylation; treatment ID EXPERIMENTAL DIABETIC NEPHROPATHY; AMINOGUANIDINE; ALBUMINURIA; TISSUE; RAGE; RAT AB Background: The role of advanced glycation end products (AGEs) in diabetic nephropathy has been developed during several years of research and increasingly complex AGE biochemistry. However, the structural diversity of AGE chemistry has created new challenges in the search for AGE-based inhibition therapies. Results: The challenges include the need to standardize measurements of serum and tissue AGE levels, identifying nephrotoxic AGE compounds, understanding the cell biological state of AGEs in the diabetic kidney, determining the mechanism of action of selective inhibition of the glycation cascade, and forming complementary therapies. Conclusion: Current challenges in the development of new therapies for AGE nephrotoxicity are reviewed. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Williams, ME (reprint author), 1 Joslin Pl, Boston, MA 02215 USA. NR 31 TC 22 Z9 26 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAR PY 2003 VL 41 IS 3 SU 1 BP S42 EP S47 DI 10.1053/ajkd.2003.50083 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 651RX UT WOS:000181336200011 PM 12612951 ER PT J AU Schaefer, PW Ozsunar, Y He, J Hamberg, LM Hunter, GJ Sorensen, AG Koroshetz, WJ Gonzalez, RG AF Schaefer, PW Ozsunar, Y He, J Hamberg, LM Hunter, GJ Sorensen, AG Koroshetz, WJ Gonzalez, RG TI Assessing tissue viability with MR diffusion and perfusion imaging SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Radiological-Society-North-American CY NOV 25-30, 2001 CL CHICAGO, ILLINOIS SP Radiologic Soc North Amer ID CEREBRAL BLOOD-FLOW; HYPERACUTE STROKE; ISCHEMIC PENUMBRA; WEIGHTED MRI; METABOLIC DISTURBANCES; SIGNAL INTENSITY; COEFFICIENT; VOLUME; BRAIN; EVOLUTION AB BACKGROUND AND PURPOSE: Diffusion- (DW) and perfusion-weighted (PW) MR imaging reflect neurophysiologic changes during stroke evolution. We sought to determine parameters that distinguish regions of brain destined for infarction from those that will survive despite hypoperfusion. METHODS: DW and PW images were obtained in 30 patients at 1-12 hours after symptom onset. Relative cerebral blood volume (rCBV), flow (rCBF), mean transit time (MTT), apparent diffusion coefficient (ADC), DW image signal intensity, and fractional anisotropy (FA) lesion-contralateral normal region ratios were obtained in the following regions: 1) infarct core with hyperintensity on DW image, abnormality on rCBF and MTT images, and follow-up abnormality; 2) infarcted penumbra with normal DW image, abnormal rCBF and MTT images, and follow-up abnormality; and 3) hypoperfused tissue that remained viable, with normal DW image, abnormal rCBF and MTT images, and normal follow-up. RESULTS: rCBF ratios for regions 1, 2, and 3 were 0.32 +/- 0.11, 0.46 +/- 0.13, and 0.58 +/- 0.12, respectively, and were significantly different. DW image intensity and ADC ratios were significantly different among all regions, but were more similar than rCBF ratios. rCBV and FA ratios were not significantly different between regions 2 and 3. No MTT ratios were significantly different. No region of interest with an rCBF ratio less than 0.36, an rCBV ratio less than 0.53, an ADC ratio less than 0.85, a DW image intensity ratio greater than 1.23, or an FA ratio greater than 1.10 remained viable. No region of interest with an rCBF ratio greater than 0.79 infarcted. CONCLUSIONS: Differences among mean ratios of three regions investigated were greatest for. the rCBF ratio. The rCBF ratio may be the most useful parameter in differentiating viable tissue that is likely to infarct without intervention, from tissue that will survive despite hypoperfusion. ADC, DW intensity, FA, and rCBV ratios may provide adjunctive information. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Neuroradiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Schaefer, PW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Neuroradiol, Gray B285,Fruit St, Boston, MA 02114 USA. NR 37 TC 85 Z9 91 U1 0 U2 1 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 MAR PY 2003 VL 24 IS 3 BP 436 EP 443 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 658WR UT WOS:000181744500026 PM 12637294 ER PT J AU Schorge, JO Lea, JS Garner, FO Duska, LR Miller, DS Coleman, RL AF Schorge, JO Lea, JS Garner, FO Duska, LR Miller, DS Coleman, RL TI Cervical adenocarcinoma survival among Hispanic and white women: A multicenter cohort study SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE cervical adenocarcinoma; cohort study; racial difference ID SQUAMOUS-CELL CARCINOMA; UNITED-STATES; INTERNATIONAL TRENDS; UTERINE CERVIX; CANCER; RACE; CARE; RADIOTHERAPY; BREAST AB OBJECTIVE: We compared the clinical outcome of cervical adenocarcinoma in Hispanic and white women to determine whether race was an independent predictor of survival. STUDY DESIGN: All women who were diagnosed with cervical adenocarcinoma at three institutions between 1982 and 2000 were identified. Medical records were reviewed retrospectively. Hispanic and white cohorts were matched 1:2 for age, stage of disease, date of diagnosis, tumor size, histologic subtype, grade, and invasive depth. RESULTS: The 65 Hispanic patients were more likely to be treated at the public hospital (71% vs 14%; P <.001) than the 122 matched white patients. Most Hispanic patients (72%) and white patients (76%) presented with early (stage IA-IIA), not advanced (IIB-IVB), disease. Early (81% vs 81%, P =.65), advanced (37% vs; 26%, P =.21), and overall 5-year survival rates (67% vs 68%, P =.57) were similar among Hispanic and white,patients, respectively. The relative risk of race on recurrence was 1.22 (95% Cl, 0.56-2.42) and on survival was 0.72 (95% Cl, 0.36-1.44). CONCLUSION: Hispanic race is not an independent predictor of survival in cervical adenocarcinoma. C1 UT Southwestern Med Ctr, Div Gynecol Oncol, Dept Obstet & Gynecol, Dallas, TX 75390 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Schorge, JO (reprint author), UT Southwestern Med Ctr, Div Gynecol Oncol, Dept Obstet & Gynecol, 5323 Harry Hines Blvd,J7-124, Dallas, TX 75390 USA. EM john.schorge@utsouthwestern.edu RI Miller, David/H-4604-2011 OI Miller, David/0000-0002-8215-5887 NR 20 TC 8 Z9 9 U1 0 U2 0 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 MAR PY 2003 VL 188 IS 3 BP 640 EP 644 DI 10.1067/mob.2003.96 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 658XH UT WOS:000181746000007 PM 12634634 ER PT J AU Kovac, SH Klapow, JC Kroenke, K Spitzer, RL Williams, JBW AF Kovac, SH Klapow, JC Kroenke, K Spitzer, RL Williams, JBW TI Differing symptoms of abused versus nonabused women in obstetric-gynecology settings SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the Society-of-Behavioral-Medicine CY APR 03-06, 2002 CL WASHINGTON, D.C. SP Soc Behav Med DE obstetrics-gynecology; abuse; symptom; patient health questionnaire ID INTIMATE PARTNER VIOLENCE; PRIMARY-CARE PRACTICE; DOMESTIC VIOLENCE; PREVALENCE; PHYSICIANS; EMERGENCY; VALIDITY; VICTIMS; UTILITY; MD AB OBJECTIVE: The purpose of this study was to document the prevalence rates of reported abuse in obstetric/gynecology settings and to characterize physical symptoms, function, and psychologic distress of women who report abuse. STUDY DESIGN: This was a descriptive study of 118 patients who reported physical or sexual abuse in the past year and 2800 patients who reported no abuse at seven obstetric/gynecology practices. The Patient Health Questionnaire measured psychiatric diagnoses, somatic complaints, and psychosocial stressors. The Medical Outcomes Study Short Form 20 assessed health status, and self-reported health care use was measured. RESULTS: Four percent of women reported recent abuse. Patients who reported abuse had more psychiatric diagnoses, more severe psychologic distress, more somatic symptoms, more psychosocial stressors, more physician visits, and poorer reported health status compared with nonreporters of abuse. CONCLUSION: Enhanced recognition of possible abuse through screening may identify women in need of intervention and help to reduce the need for continued medical intervention. C1 Birmingham Vet Aff Med Ctr, Targeted Res Enhancement Program, Birmingham, AL 35233 USA. Univ Alabama, Ctr Outcomes & Effectiveness Res & Educ, Birmingham, AL USA. Univ Alabama, Div Prevent Med, Birmingham, AL USA. Univ Alabama, Dept Psychol, Birmingham, AL USA. Univ Alabama, Dept Hlth Care Org & Policy, Birmingham, AL USA. Indiana Univ, Regenstrief Inst Hlth Care, Indianapolis, IN 46204 USA. Indiana Univ, Dept Med, Indianapolis, IN 46204 USA. New York State Psychiat Inst & Hosp, Biometr Res Dept, New York, NY 10032 USA. Columbia Univ, Dept Psychiat, New York, NY 10027 USA. RP Kovac, SH (reprint author), Birmingham Vet Aff Med Ctr, Targeted Res Enhancement Program, 700 19th St S, Birmingham, AL 35233 USA. EM skovac@dopm.uab.edu NR 25 TC 30 Z9 30 U1 1 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 MAR PY 2003 VL 188 IS 3 BP 707 EP 713 DI 10.1067/mob.2003.193 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 658XH UT WOS:000181746000018 PM 12634645 ER PT J AU Christoforidis, JB DeAngelo, DJ D'Amico, DJ AF Christoforidis, JB DeAngelo, DJ D'Amico, DJ TI Resolution of leukemic retinopathy following treatment with imatinib mesylate for chronic myelogenous leukemia SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To report a case of leukemic retinopathy before and after treatment with imatinib mesylate (formerly STI-571) for chronic myelogenous leukemia (CML). DESIGN: Interventional case report. METHODS: A 58-year old man diagnosed with stable phase CML (SP-CML) presented with blurry vision. Fundos, copy revealed several flame,shaped hemorrhages in the macular region in both eyes. One month after this initial visit, imatinib therapy was initiated. RESULTS: The patient noticed improvement in his visual as well as his medical symptoms; on repeat examination 6 months after the initial visit, the retinal hemorrhages had resolved and remained so after 18 months. CONCLUSIONS: Imatinib appears to be an effective treatment for SP-CML, and the improvement in visual and medical symptoms in our case report correlates with this. (C) 2003 by Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Ophthalmol, Boston, MA 02115 USA. RP D'Amico, DJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. NR 3 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 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAR PY 2003 VL 135 IS 3 BP 398 EP 400 DI 10.1016/S0002-9394(02)01964-5 PG 3 WC Ophthalmology SC Ophthalmology GA 650HT UT WOS:000181258100027 PM 12614767 ER PT J AU Lee, MS Goslee, TE Lessell, S AF Lee, MS Goslee, TE Lessell, S TI Ehrlichiosis optic neuritis SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID HUMAN GRANULOCYTIC EHRLICHIOSIS AB PURPOSE: To describe a case of ehrlichiosis optic neuritis. DESIGN: Single observational case report. METHODS: A 41-year-old woman with symptoms and clinical and imaging signs consistent with optic neuritis presented to a tertiary care academic center for comprehensive neuro,ophthalmic evaluation. Main outcome measures included preoptic and postoptic neuritis polyvalent ehrlichiosis titers and magnetic resonance imaging (MRI) of orbits with gadolinium. RESULTS: Ehrlichiosis titers drawn 11 days before onset of eye symptoms were negative. Titers drawn 7 days after symptoms began were positive. The optic nerve enhanced with gadolinium on MRI. CONCLUSIONS: Ehrlichiosis can cause optic neuritis and should be considered in patients with optic neuritis after a febrile, flu-like illness in an endemic area. (C) 2003 by Elsevier Science Inc. All rights reserved. C1 Cleveland Clin Fdn, Cole Eye Inst I32, Cleveland, OH 44195 USA. Upper Care Ophthalmol Inc, Falmouth, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Lee, MS (reprint author), Cleveland Clin Fdn, Cole Eye Inst I32, 9500 Euclid Ave, Cleveland, OH 44195 USA. NR 5 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 MAR PY 2003 VL 135 IS 3 BP 412 EP 413 DI 10.1016/S0002-9394(02)01945-1 PG 2 WC Ophthalmology SC Ophthalmology GA 650HT UT WOS:000181258100034 PM 12614774 ER PT J AU Stein, J Shafqat, S Doherty, D Frates, EP Furie, KL AF Stein, J Shafqat, S Doherty, D Frates, EP Furie, KL TI Family member knowledge and expectations for functional recovery after stroke SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE stroke; rehabilitation; health education; caregivers ID RANDOMIZED CONTROLLED TRIAL; EDUCATION; CARERS AB Objective: To assess the stroke knowledge and expectations for recovery among the family members of stroke patients in an acute rehabilitation hospital. Design: Survey study of 50 family members of stroke patients undergoing inpatient rehabilitation at a single urban rehabilitation hospital. Results: Sixty percent of participants were able to identify whether their family member had sustained a cerebral hemorrhage or infarct; 48% were able to identify at least one treatment provided to their family member for his or her stroke. The average length of stay predicted by participants closely matched the average patient length of stay. Participants tended to overestimate the functional abilities of their family member with a stroke, both on initial assessment and discharge. This overestimation was more substantial for discharge functional ability than for initial assessment. Participants were able to predict discharge location with substantial accuracy (82% agreement, kappa = 0.41). Conclusions: The knowledge of stroke etiology and functional outcome of family members of individuals undergoing rehabilitation after stroke shows significant limitations. Participants' ability to predict functional outcome on discharge was worse than their knowledge of current functional status. Participant predictions of length of stay and discharge disposition were areas of relative strength. Further efforts are needed to enhance the knowledge level of family members of patients undergoing rehabilitation after stroke. C1 Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. RP Stein, J (reprint author), Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, 125 Nashua St, Boston, MA 02114 USA. NR 12 TC 5 Z9 5 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD MAR PY 2003 VL 82 IS 3 BP 169 EP 174 DI 10.1097/01.PHM.0000052587.39623.74 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 648LQ UT WOS:000181153200003 PM 12595767 ER PT J AU Boninger, ML Cooper, RA Fitzgerald, SG Lin, J Cooper, R Dicianno, B Liu, B AF Boninger, ML Cooper, RA Fitzgerald, SG Lin, J Cooper, R Dicianno, B Liu, B TI Investigating neck pain in wheelchair users SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE wheelchair; neck pain; vibration ID SPINAL-CORD INJURIES; RISK-FACTORS; BACK; PREVALENCE; SATISFACTION; RELIABILITY; DISABILITY; DISORDERS; OPERATORS; HEALTH AB Objective: Despite the fact that wheelchair users are exposed to risk factors for neck and upper back pain (NP), little is known about the impact and possible diagnoses associated with NP. The purpose of this study was to examine the significance of NP in wheelchair users and to determine if a portion of the NP may be myofascial in origin. Design: Cross-sectional cohort study using questionnaires and physical exams to evaluate NP in a convenience sample of wheelchair users from the National Veteran's Wheelchair Games. Main outcome measures included reported NP, visual analog scale of neck complaints, Neck Disability Index, and physical examination findings of trigger points. Results: Sixty-six percent of subjects reported NP since becoming a wheelchair user and, 60% reported pain during the past month. Neither age nor length of time in a wheelchair was significantly different between those subjects who did and those subjects who did not report pain. Of those respondents who reported NP, 60% visited the doctor about the pain and 40% limited their daily activities due to the pain. Trigger-point palpation reproduced pain in 54% of those respondents who experienced pain in the past month (n = 34). Conclusion: This study provides a first step in defining the prevalence and significance of NP among wheelchair users. Clinicians who work with this population need to ask subjects about symptoms and consider a myofascial origin for that pain when considering treatment. C1 Univ Pittsburgh, Dept Phys Med & Rehabil, Human Engn Res Labs, Pittsburgh, PA USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Ctr Excellence Wheelchairs & Related Technol, Pittsburgh, PA 15206 USA. RP Boninger, ML (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Ctr Excellence Wheelchairs & Related Technol, 7180 Highland Dr,Bldg 4,2nd Floor E,151R-1, Pittsburgh, PA 15206 USA. OI Boninger, Michael/0000-0001-6966-919X; Dicianno, Brad/0000-0003-0738-0192 NR 30 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD MAR PY 2003 VL 82 IS 3 BP 197 EP 202 DI 10.1097/01.PHM.0000054217.17816.DD PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 648LQ UT WOS:000181153200008 PM 12595772 ER PT J AU Chang, HY Mashimo, H Goyal, RK AF Chang, HY Mashimo, H Goyal, RK TI Musings on the wanderer: What's new in our understanding of vago-vagal reflex? IV. Current concepts of vagal efferent projections to the gut SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE enteric nervous system; gastrointestinal motility; gastrointestinal secretions; gastrointestinal smooth muscle; neurotransmitters; parasympathetic nerves ID ESOPHAGEAL SPHINCTER PRESSURE; MIGRATING MOTOR COMPLEX; OPOSSUM; RAT; CONTRACTIONS; INNERVATION; NUCLEUS; DOGS AB Vagal efferents, consisting of distinct lower motor and preganglionic parasympathetic fibers, constitute the motor limb of vagally mediated reflexes. Arising from the nucleus ambiguus, vagal lower motor neurons (LMN) mediate reflexes involving striated muscles of the orad gut. LMNs provide cholinergic innervation to motor end plates that are inhibited by myenteric nitrergic neurons. Preganglionic neurons from the dorsal motor nucleus implement parasympathetic motor and secretory functions. Cholinergic preganglionic neurons form parallel inhibitory and excitatory vagal pathways to smooth muscle viscera and stimulate postganglionic neurons via nicotinic and muscarinic receptors. In turn, the postganglionic inhibitory neurons release ATP, VIP, and NO, whereas the excitatory neurons release ACh and substance P. Vagal motor effects are dependent on the viscera's intrinsic motor activity and the interaction between the inhibitory and excitatory vagal influences. These interactions help to explain the physiology of esophageal peristalsis, gastric motility, lower esophageal sphincter, and pyloric sphincter. Vagal secretory pathways are predominantly excitatory and involve ACh and VIP as the postganglionic excitatory neurotransmitters. Vagal effects on secretory functions are exerted either directly or via release of local mediators or circulating hormones. C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Ctr Swallowing & Motil Disorders, Boston, MA 02132 USA. RP Goyal, RK (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. FU NIDDK NIH HHS [DK 31092] NR 25 TC 75 Z9 75 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAR PY 2003 VL 284 IS 3 BP G357 EP G366 DI 10.1152/ajpgi.00478.2002 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 642WC UT WOS:000180827600002 PM 12576302 ER PT J AU Raybould, HE Glatzle, J Robin, C Meyer, JH Phan, T Wong, H Sternini, C AF Raybould, HE Glatzle, J Robin, C Meyer, JH Phan, T Wong, H Sternini, C TI Expression of 5-HT3 receptors by extrinsic duodenal afferents contribute to intestinal inhibition of gastric emptying SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE glucose; carbohydrate; monosaccharide; enterochromaffin cells; 5-hydroxytryptamine ID ENTEROCHROMAFFIN CELLS; SIGNALING MECHANISMS; RAT JEJUNUM; VAGAL; NEURONS; SECRETION; PIG; 5-HYDROXYTRYPTAMINE; SEROTONIN; PATHWAYS AB Intestinal perfusion with carbohydrates inhibits gastric emptying via vagal and spinal capsaicin-sensitive afferent pathways. The aim of the present study was to determine the role of 1) 5-hydroxytryptamine (5-HT)(3) receptors (5-HT3R) in mediating glucose-induced inhibition of gastric emptying and 2) 5-HT3R expression in vagal and spinal afferents in innervating the duodenum. In awake rats fitted with gastric and duodenal cannulas, perfusion of the duodenum with glucose (50 and 100 mg) inhibited gastric emptying. Intestinal perfusion of mannitol inhibited gastric emptying only at the highest concentration (990 mosm/kgH(2)O). Pretreatment with the 5-HT3R antagonist tropisetron abolished both glucose- and mannitol-induced inhibition of gastric emptying. Retrograde labeling of visceral afferents by injection of dextran-conjugated Texas Red into the duodenal wall was used to identify extrinsic primary afferents. Immunoreactivity for 5-HT3R, visualized with an antibody directed to the COOH terminus of the rat 5-HT3R, was found in >80% of duodenal vagal and spinal afferents. These results show that duodenal extrinsic afferents express 5-HT3R and that the receptor mediates specific glucose- induced inhibition of gastric emptying. These findings support the hypothesis that enterochromaffin cells in the intestinal mucosa release 5-HT in response to glucose, which activates 5-HT3R on afferent nerve terminals to evoke reflex changes in gastric motility. The primary glucose sensors of the intestine may be mucosal enterochromaffin cells. C1 Univ Calif Davis, Sch Vet Med, Dept Anat Physiol & Cell Biol, Davis, CA 95616 USA. Univ Calif Los Angeles, Sch Med, Vet Affairs Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr,Dept Med,Div Digest Dis, Los Angeles, CA 95616 USA. Univ Calif Los Angeles, Sch Med, Dept Neurobiol, Los Angeles, CA 95616 USA. RP Raybould, HE (reprint author), Univ Calif Davis, Sch Vet Med, Dept Anat Physiol & Cell Biol, 1321 Haring Hall, Davis, CA 95616 USA. FU NIDDK NIH HHS [DK 41004, DK 41301, DK 35740, DK 57037] NR 34 TC 84 Z9 88 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAR PY 2003 VL 284 IS 3 BP G367 EP G372 DI 10.1152/ajpgi.00292.2001 PG 6 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 642WC UT WOS:000180827600003 PM 12409280 ER PT J AU Kanakiriya, SKR Croatt, AJ Haggard, JJ Ingelfinger Jr Tang, SS Alam, J Nath, KA AF Kanakiriya, SKR Croatt, AJ Haggard, JJ Ingelfinger, JR Tang, SS Alam, J Nath, KA TI Heme: a novel inducer of MCP-1 through HO-dependent and HO-independent mechanisms SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE heme oxygenase; monocyte chemoattractant protein-1; iron; oxidant stress ID FACTOR-KAPPA-B; OXYGENASE-1 GENE ABLATION; TUBULAR EPITHELIAL-CELLS; LOW-DENSITY-LIPOPROTEIN; ACUTE-RENAL-FAILURE; ENDOTHELIAL-CELLS; OXIDATIVE STRESS; OXIDANT DAMAGE; IN-VIVO; HYDROGEN-PEROXIDE AB This study examined the effect of hemin on the expression of heme oxygenase-1 (HO-1) and monocyte chemoattractant protein-1 (MCP-1) in immortalized rat proximal tubular epithelial cells (IRPTCs). Hemin elicited a dose- and time-dependent induction of HO-1 and MCP-1 mRNA. HO activity contributed to MCP-1 mRNA expression at early time points (4-6 h) because inhibition of HO activity by zinc protoporphyrin (ZnPP) prevented hemin-induced expression of MCP-1 mRNA. Catalytically active intracellular iron was markedly increased in hemin-treated IRPTCs and contributed to the induction of HO-1 and MCP-1 mRNA because an iron chelator blocked hemin-induced upregulation of both genes, whereas a cell-permeant form of iron directly induced these genes. N-acetylcysteine completely blocked hemin-induced expression of HO-1 and MCP-1 mRNA, thereby providing added evidence for redox regulation of expression of these genes. The redox-sensitive transcription factor NF-kappaB was recruited in hemin-induced upregulation of MCP-1 because two different compounds that abrogate the activation of NF-kappaB (TPCK and BAY 11-7082) completely blocked hemin-induced upregulation of MCP-1 mRNA. In contrast to this HO-mediated induction of MCP-1 through redox-sensitive, iron-dependent, and NF-kappaB-involved pathways observed after 4-6 h, hemin also elicited a delayed induction of MCP-1 at 18 h through HO-independent pathways. We conclude that hemin is a potent inducer of MCP-1 in IRPTCs: HO-dependent, heme-degrading pathways lead to an early, robust, and self-remitting induction of MCP-1, whereas HO-independent mechanisms lead to a delayed expression of MCP-1. C1 Mayo Clin & Mayo Fdn, Div Nephrol, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. Alton Ochsner Med Fdn & Ochsner Clin, Dept Mol Genet, New Orleans, LA 70121 USA. RP Nath, KA (reprint author), Mayo Clin, 200 1st St SW,Guggenheim 542, Rochester, MN 55905 USA. EM nath.karl@mayo.edu RI Alam, Jawed/F-2596-2010 OI Alam, Jawed/0000-0001-6520-482X FU NHLBI NIH HHS [HL-48455, HL-55552]; NIDDK NIH HHS [DK-43135, DK-50835, DK-58950, R01-DK-47060] NR 65 TC 57 Z9 59 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAR PY 2003 VL 284 IS 3 BP F546 EP F554 DI 10.1152/ajprenal.00298.2002 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 640JZ UT WOS:000180686900016 PM 12556365 ER PT J AU Glatt, SJ Faraone, SV Tsuang, MT AF Glatt, SJ Faraone, SV Tsuang, MT TI Association between a functional catechol O-methyltransferase gene polymorphism and schizophrenia: Meta-analysis of case-control and family-based studies SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID CYCLING BIPOLAR DISORDER; HAPLOTYPE-RELATIVE-RISK; LINKAGE DISEQUILIBRIUM; RECEPTOR GENE; NO EVIDENCE; COMT GENE; SUSCEPTIBILITY; POPULATION; IDENTIFICATION; METAANALYSIS AB Objective: There is strong evidence for a genetic contribution to schizophrenia, but efforts to identify susceptibility genes have been largely unsuccessful because of the low power of individual studies. The authors' goal was to evaluate the collective evidence for an association between the Val158/108Met polymorphism of the catechol O-methyltransferase (COMT) gene and schizophrenia. Method: They performed separate metaanalyses of existing case-control and family-based association studies. Results: Overall, case-control studies showed no indication of an association between either allele and schizophrenia, and family-based studies found modest evidence implicating the Val allele in schizophrenia risk. The pooled analyses of studies from diverse geographical regions may have obscured ethnic differences in patterns of genetic risk for schizophrenia. Stratification of the studies by ethnicity of the subjects yielded evidence for an association with the Val allele in case-control studies of European samples and, especially, in family-based studies of European samples. Case-control and family-based studies of Asian samples produced mixed results and, overall, little evidence for association. Conclusions: The results of the two types of association studies diverged somewhat, but the evidence from the family-based studies, although based on fewer reports, may be more accurate. The Val allele may be a small but reliable risk factor for schizophrenia for people of European ancestry, but the influence of this polymorphism on risk in Asian populations remains unclear. These results call for more family-based studies to confirm the association between COMT and schizophrenia in European samples and to clarify its contribution to risk in Asian samples. They also suggest that case-control studies should use methods of genomic control to avoid being confounded by population stratification. C1 Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Brockton W Roxbury Vet Affairs Med Ctr, Psychiat Serv, Brockton, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Tsuang, MT (reprint author), Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, 74 Fenwood Rd, Boston, MA 02115 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH-59624, MH-60485] NR 48 TC 255 Z9 264 U1 0 U2 7 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 2003 VL 160 IS 3 BP 469 EP 476 DI 10.1176/appi.ajp.160.3.469 PG 8 WC Psychiatry SC Psychiatry GA 655MX UT WOS:000181557600008 PM 12611827 ER PT J AU Samaha, M Metson, R AF Samaha, M Metson, R TI Image-guided resection of fibro-osseous lesions of the skull base SO AMERICAN JOURNAL OF RHINOLOGY LA English DT Article ID PARANASAL SINUSES AB Background: Endoscopic resection of sinonasal fibro-osseous lesions remains a technical challenge because of the loss of anatomic landmarks and the frequent need to resect bone along the skull base. The purpose of this study was to evaluate the usefulness of image-guidance systems for the resection of these lesions. Methods: Endoscopic surgery was performed in 10 patients with fibro-osseous lesions of the sinuses and skull base (six fibrous dysplasias and four osteomas). Indications for surgical intervention were recurrent infection (7), facial pain (3), mucocele (1), and compressive optic neuropathy (1). All surgeries were performed with an image-guidance system, which included an integrated high-speed drill system. Results: Anatomic localization was accurate to within 1 mm when monitoring the depth of bone removal along the skull base. Complete resection of the fibro-osseous lesion was possible in six patients (60%) and partial removal was possible in four patients (40%). In the latter group, a margin of dysplastic bone was preserved along the ethmoid roof to prevent dural exposure. There were no intraoperative complications. Surgery resulted in resolution of infection and facial pain in nine patients (90%). Additional surgery was required in one patient (10%) who developed recurrent optic neuropathy because of continued dysplastic bone growth. Mean follow-up was 34 months (range, 13-67 months). Conclusion: Image-guidance technology appears to be ideally suited for the treatment of patients with fibro-osseous lesions of the sinonasal cavity. Real-time monitoring of the depth of bone removal relative to the skull base may enhance the safety and efficacy of such surgery. C1 Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Metson, R (reprint author), Zero Emerson Pl, Boston, MA 02114 USA. NR 9 TC 4 Z9 4 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1050-6586 J9 AM J RHINOL JI Am. J. Rhinol. PD MAR-APR PY 2003 VL 17 IS 2 BP 115 EP 118 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 677KV UT WOS:000182807400010 PM 12751708 ER PT J AU Smith, JJ Berlin, L AF Smith, JJ Berlin, L TI Malpractice issues in radiology - Medicare fraud and abuse SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID PHYSICIANS C1 Rush N Shore Med Ctr, Dept Radiol, Skokie, IL 60076 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Rush Med Coll, Chicago, IL 60612 USA. RP Berlin, L (reprint author), Rush N Shore Med Ctr, Dept Radiol, 9600 Gross Point Rd, Skokie, IL 60076 USA. NR 13 TC 1 Z9 1 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2003 VL 180 IS 3 BP 591 EP 595 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 648LT UT WOS:000181153400005 PM 12591659 ER PT J AU Harisinghani, MG Maher, MM Gervais, DA McGovern, F Hahn, P Jhaveri, K Varghese, J Mueller, PR AF Harisinghani, MG Maher, MM Gervais, DA McGovern, F Hahn, P Jhaveri, K Varghese, J Mueller, PR TI Incidence of malignancy in complex cystic renal masses (Bosniak category III): Should imaging-guided biopsy precede surgery? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CLASSIFICATION; CT AB OBJECTIVE. Complex indeterminate renal cystic masses (Bosmak type III) can have benign and malignant causes and have been traditionally considered surgical lesions. We sought to determine the incidence of malignancy and to assess a possible role for imaging-guided biopsy for this category of renal masses. MATERIALS AND METHODS. Three hundred ninety-seven renal biopsies were performed at our institution between 1991 and 2000. Between January 1997 and August 2000, 28 Bosniak category III lesions, based on established CT imaging criteria on helical CT scans, were identified for analysis. The incidence of malignancy based on surgical pathology or imaging follow-up and percentage of lesion proceeding to surgery, among these 28 lesions, was determined. The surgical results were correlated with the biopsy findings. RESULTS. Of the 28 biopsied category III lesions, 17 (60.7%) were malignant (16 renal cell carcinomas and one lymphoma), and 11 (39.3%) were benign (six hemorrhagic cysts, three inflammatory cysts, one metanephric adenoma, and one cystic oncocytoma). Seventeen of the 28 lesions (16 renal cell carcinomas and one inflammatory cyst) had surgical resection after the biopsy. All resected. lesions had pathologic diagnoses identical to the percutaneous imaging-guided biopsy results. The remaining 11 patients who had undergone nonsurgical biopsies had radiologic follow-up for a minimum of 1 year, with benign lesions showing no interval change. CONCLUSION. Renal biopsy and radiologic follow-up were useful in identifying nomnalignant lesions in complex cystic renal masses and avoided unnecessary surgery in 39% of patients. C1 Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Univ Toronto, Mt Sinai Hosp, Univ Hlth Network, Dept Med Imaging, Toronto, ON M5G 2M9, Canada. RP Harisinghani, MG (reprint author), Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent, 55 Fruit St, Boston, MA 02114 USA. NR 10 TC 84 Z9 86 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2003 VL 180 IS 3 BP 755 EP 758 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 648LT UT WOS:000181153400034 PM 12591691 ER PT J AU Lehtinen, JT Tingart, MJ Apreleva, M Ticker, JB Warner, JJP AF Lehtinen, JT Tingart, MJ Apreleva, M Ticker, JB Warner, JJP TI Anatomy of the superior glenoid rim - Repair of superior labral anterior to posterior tears SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article ID SLAP LESIONS AB Background: Successful placement of a fixation device on the superior glenoid rim during superior labrum repairs requires accurate knowledge of the glenoid rim anatomy. Purpose: To investigate the normal bony anatomy of the superior glenoid rim. Study Design: Descriptive anatomic study. Methods: Twenty cadaveric glenoid specimens were scanned to obtain cross-sectional images with peripheral quantitative computed tomography in three different positions, each perpendicular to the articular surface. Two straight lines were drawn along the interior bony margins of the articular surface and cortex, and image analysis software was used to calculate the angle between these lines. Three bony angles were measured. Results: The bony angles from the 10:30-, 12-, and 1:30-o'clock cross-sections were 55degrees +/- 5degrees, 64degrees +/- 5degrees, and 62degrees +/- 8degrees, respectively. The posterosuperior angle (at the 10:30-o'clock position) was statistically significantly lower than the superior and anterosuperior angles. Intraobserver variation was less than 3%. Conclusions: The most superior point of the glenoid rim (12-o'clock position) seems to provide the most bone stock for anchor insertion. The available bone support was found to decrease posteriorly on the glenoid rim. Clinical Relevance: During superior labral repairs, the anchor or fixation device should be inserted at approximately a 30degrees angle in relation to the articular surface for maximal bone support. (C) 2003 American Orthopaedic Society for Sports Medicine. C1 Beth Israel Deaconess Med Ctr, Orthoped Biomech Lab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Harvard Shoulder Serv, Boston, MA USA. Isl Orthopaed & Sports Med, Massapequa, NY USA. RP Apreleva, M (reprint author), Beth Israel Deaconess Med Ctr, Orthoped Biomech Lab, 330 Brookline Ave,RN 115, Boston, MA 02215 USA. NR 13 TC 11 Z9 11 U1 0 U2 1 PU AMER ORTHOPAEDIC SOC SPORT MED PI WALTHAM PA 230 CALVARY STREET, WALTHAM, MA 02154 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD MAR-APR PY 2003 VL 31 IS 2 BP 257 EP 260 PG 4 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 655WD UT WOS:000181574900017 PM 12642262 ER PT J AU Lee, KR Young, RH AF Lee, KR Young, RH TI The distinction between primary and metastatic mucinous carcinomas of the ovary - Gross and histologic findings in 50 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ovary; adenocarcinoma; mucinous carcinoma; metastases ID BORDERLINE TUMORS; INTESTINAL-TYPE; IMMUNOHISTOCHEMICAL ANALYSIS; CLINICOPATHOLOGICAL ANALYSIS; CARCINOEMBRYONIC ANTIGEN; DIFFERENTIAL-DIAGNOSIS; COLONIC-CARCINOMA; ADENOCARCINOMAS; CYTOKERATIN-20; ORIGIN AB The gross and routine microscopic features of 25 stage I primary mucinous ovarian carcinomas without clinical evidence of recurrence and 25 mucinous carcinomas metastatic to the ovaries were compared. Findings that were frequent in the latter and strongly favored a metastasis were: 1) bilaterality, 2) microscopic surface involvement by epithelial cells (surface implants), and 3) an infiltrative pattern of stromal invasion. Findings that were less frequent but present exclusively or almost exclusively in metastatic carcinomas were: 1) a nodular invasive pattern, 2) ovarian hilar involvement, 3) single cell invasion, 4) signet-ring cells, 5) vascular invasion, and 6) microscopic surface mucin. Findings that were frequent in, and strongly favored, primary ovarian carcinoma were: 1) an "expansile" pattern of invasion and 2) a complex papillary pattern. Findings that were less frequent but also favored a primary tumor were: 1) size >10 cm, 2) a smooth external surface, 3) benign-appearing and borderline-appearing areas, 4) microscopic cystic glands, and 5) necrotic luminal debris. Findings that did not distinguish the tumors were: 1) a cystic gross appearance, 2) gross solid, papillary, necrotic, or hemorrhagic areas, 3) nature of cyst contents (mucinous vs nonmucinous), 4) stromal mucin (pseudomyxoma ovarii), 5) cribriform, villous, or solid growth patterns, 6) focal area resembling typical colonic carcinoma, 7) goblet cells, or 8) tumor grade. Primary and metastatic mucinous ovarian carcinomas can be distinguished from each other in the great majority of cases based solely on their conventional histopathologic findings. Careful gross evaluation is also important with special attention paid to the external surface of the ovarian tumor(s) to detect abnormalities that have the features of surface implants on microscopic evaluation. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol,Div Womens & Perinatal Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA USA. RP Lee, KR (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol,Div Womens & Perinatal Pathol, 75 Francis St, Boston, MA 02115 USA. NR 30 TC 126 Z9 129 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAR PY 2003 VL 27 IS 3 BP 281 EP 292 DI 10.1097/00000478-200303000-00001 PG 12 WC Pathology; Surgery SC Pathology; Surgery GA 650CY UT WOS:000181245900001 PM 12604884 ER PT J AU Leaf, DA Macrae, HSH Grant, E Kraut, J AF Leaf, DA Macrae, HSH Grant, E Kraut, J TI Isometric exercise increases the size of forearm veins in patients with chronic renal failure SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE physical exercise; Cimino-Brescia fistula; hemodialysis; veins; renal failure ID HEMODIALYSIS AB Objectives: Delay in maturation or failure of maturation of Cimino-Brescia fistulae contributes to the significant vascular access-related morbidity of chronic hemodialysis patients. Increased size and capacitance of native veins before the formation of vascular access has been considered an important variable in the success rate of native fistulae. We evaluated whether a formal exercise program might alter the size of native veins. Methods: The effect of exercise on venous size was evaluated in 5 patients with severe chronic renal failure [glomerular filtration rate, 30.6 +/- 5.3 mL/min (mean +/- SD)]. Five male patients with a mean age of 57 +/- 9 years underwent a 6-week forearm exercise training program, involving nondominant arms, that included isometric hand-grip contractions to 25 to 35% of MVC lasting 40 to 120 seconds and repetitive squeezing of squash and racquet balls. Both the volume and intensity of exercise training was increased weekly based on strength measured by hand-grip dynamometer and on the patients' indicated level of comfort. Cephalic vessel size in both the nondominant (trained) and dominant (control) arms, with and without a tourniquet, were obtained using Doppler ultrasound before and after the 6-week exercise training program. Results: The size of the cephalic vein of the exercised arm increased significantly (P < 0.05) compared with the control arm when measured in both the absence (048 +/- 0.016 versus 0.024 +/- 0.023 cm(2)) and the presence of a tourniquet (0.056 +/- 0.022 versus 028 +/- 0.027 cm(2)). Conclusions: These findings indicate that a simple, incremental resistance, exercise-training program can cause a significant increase in the size of the cephalic vein commonly used in the creation of an arteriovenous fistula. The increase in size and resultant probable increase in blood flow might accelerate the maturation of native arteriovenous fistulae, thereby lessening the morbidity associated with vascular access. C1 Greater Los Angeles VA Healthcare Syst, Div Gen Med, Los Angeles, CA 90073 USA. Greater Los Angeles VA Healthcare Syst, Div Nephrol, Los Angeles, CA 90073 USA. Greater Los Angeles VA Healthcare Syst, Div Radiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Pepperdine Univ, Dept Sports Med, Malibu, CA 90265 USA. RP Leaf, DA (reprint author), Greater Los Angeles VA Healthcare Syst, Div Gen Med, 111G,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM david.leaf@med.va.gov NR 14 TC 20 Z9 22 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD MAR PY 2003 VL 325 IS 3 BP 115 EP 119 DI 10.1097/00000441-200303000-00003 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 659LF UT WOS:000181777600003 PM 12640286 ER PT J AU Collins, TC Beyth, RJ AF Collins, TC Beyth, RJ TI Process of care and outcomes in peripheral arterial disease SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Review DE process of care; outcomes; peripheral arterial disease ID CORONARY-HEART-DISEASE; LIMB-THREATENING ISCHEMIA; ANKLE-ARM INDEX; INTERMITTENT CLAUDICATION; RISK-FACTORS; VASCULAR-DISEASE; FEMORAL ATHEROSCLEROSIS; DEFINED POPULATION; OCCLUSIVE DISEASE; LOWER-EXTREMITIES AB Peripheral arterial disease (PAD) is a prevalent illness that most commonly affects patients older than 60 years. As the population ages, the prevalence of PAD and its associated, adverse outcomes will also increase. Adverse outcomes in PAD are either systemic (ie, cardiovascular events such as myocardial infarctions or strokes) or localized to the legs (ie, bypass surgery or amputation). Although much research has focused on adverse systemic outcomes in patients with PAD, less is known about those factors related to adverse limb events. The Centers for Disease Control and Prevention estimate that more than 100,000 amputations are performed in the United States each year. What remains to be determined is the association between how physicians manage patients with PAD (ie, process of care) and the development of adverse limb outcomes. Determining the association of the management of PAD with adverse limb outcomes will highlight those areas in which to focus to improve the quality of care for patients with this disease. Understanding the relationship between risk factors, process of care, and outcomes will be of importance to patients, clinicians, and policy makers.. The purpose of this article is to review the burden of PAD and to discuss the association of process of care with adverse limb outcomes in patients with PAD. C1 Houston VAMC, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Div Hlth Serv Res, Houston, TX 77030 USA. RP Collins, TC (reprint author), Houston VAMC, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd, Houston, TX 77030 USA. FU NIA NIH HHS [K08-AG00712] NR 78 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 EI 1538-2990 J9 AM J MED SCI JI Am. J. Med. Sci. PD MAR PY 2003 VL 325 IS 3 BP 125 EP 134 DI 10.1097/00000441-200303000-00005 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 659LF UT WOS:000181777600005 PM 12640288 ER PT J AU Koulmanda, M Qipo, A Chebrolu, S O'Neil, J Auchincloss, H Smith, RN AF Koulmanda, M Qipo, A Chebrolu, S O'Neil, J Auchincloss, H Smith, RN TI The effect of low versus high dose of streptozotocin in cynomolgus monkeys (Macaca fascilularis) SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE cynomolgus monkeys; diabetes; preclinical model; streptozotocin ID DIABETES-MELLITUS; PANCREATIC-ISLETS; RHESUS-MONKEYS; TRANSPLANTATION AB Streptozotocin (STZ) is often used to induce diabetes in animal models. However, morbidity associated with STZ and its ability to induce diabetes vary with different dosages among different animal species, including nonhuman primates. To find an optimal dose of STZ that would cause diabetes with minimal toxicity, we compared low and high doses of STZ. Male cynomolgus monkeys (3-6years old) were given a single dose of 100 mg/kg (high dose, 4 animals) or 55 mg/kg (low dose, 20 animals) of STZ. Blood glucose levels, intravenous glucose tolerance test (IVGTT), pancreatic biopsies, liver function tests (LFTs), liver biopsies, kidney function tests, and kidney biopsies were performed periodically. Animals from both groups developed diabetes within 24h after administration of STZ. Serum C-peptide levels in both groups decreased from 2 to 8 ng/mL before STZ to between 0.01 and 0.6ng/mL after STZ. Animals with the high dose of STZ developed transient vomiting within minutes after injection. During the first week after STZ injection, high-dose animals developed elevated LFTs, BUN and creatinine. In contrast, low-dose animals had normal liver and kidney function tests. Histological analysis showed that animals given the high dose of STZ developed marked steatosis of the liver and tubular injury in the kidneys, whereas animals given the low dose of STZ had normal-looking liver and kidney histology. The pancreatic islets in both groups were indistinguishable by immunoperoxidase staining for insulin, and showed either no insulin-positive cells or rare insulin-positive cells. Glucagon staining was normal. Over time, low-dose diabetic monkeys remained persistently hyperglycemic with negligible C-peptide stimulation by intravenous glucose. We conclude that low-dose STZ at 55mg/mL successfully induces diabetes in cynomolgus monkeys with minimal liver and kidney toxicity. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Islet Transplantat Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Islet Transplantat Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Joslin Diabet Ctr,Islet Transplantat Lab, Boston, MA 02114 USA. RP Koulmanda, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Islet Transplantat Lab, Boston, MA 02114 USA. FU NIDDK NIH HHS [P01 DK53087] NR 8 TC 57 Z9 62 U1 1 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAR PY 2003 VL 3 IS 3 BP 267 EP 272 DI 10.1034/j.1600-6143.2003.00040.x PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 660XD UT WOS:000181859500006 PM 12614280 ER PT J AU Martin, B Clapp, L Bialkowski, D Bridgeford, D Amponsah, A Lyons, L Beresford, TP AF Martin, B Clapp, L Bialkowski, D Bridgeford, D Amponsah, A Lyons, L Beresford, TP TI Compliance to supervised disulfiram therapy: A comparison of voluntary and court-ordered patients SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID ALCOHOLISM AB We hypothesized that court mandate would significantly enhance compliance with supervised disulfiram therapy. We conducted a twelve-week prospective study of outpatient compliance with court-ordered, monitored disulfiram treatment as compared to voluntary, monitored treatment. The court ordered group (n = 19) was significantly more compliant than the voluntary group (n = 22). Legally mandated subjects attended an average of 87% (+/- 21%) of scheduled visits, versus 42% (+/- 35%) for the group without court order. Court mandate roughly doubles the compliance rate of monitored disulfiram therapy, effectively enhancing clinic attendance during the first twelve weeks of treatment. C1 Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. RP Beresford, TP (reprint author), Denver Vet Affairs Med Ctr, 151,1055 Clermont St, Denver, CO 80220 USA. NR 19 TC 12 Z9 12 U1 2 U2 3 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD MAR PY 2003 VL 12 IS 2 BP 137 EP 143 DI 10.1080/10550490390201399 PG 7 WC Substance Abuse SC Substance Abuse GA 671MP UT WOS:000182468800004 PM 12746088 ER PT J AU Rollinson, DC Rathlev, NK Moss, M Killiany, R Sassower, KC Auerbach, S Fish, SS AF Rollinson, DC Rathlev, NK Moss, M Killiany, R Sassower, KC Auerbach, S Fish, SS TI The effects of consecutive night shifts on neuropsychological performance of interns in the emergency department: A pilot study SO ANNALS OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-Academic-Emergency-Medicine CY MAY 20-23, 1999 CL BOSTON, MASSACHUSETTS SP Soc Amer Emergency Med ID HOSPITALIZED-PATIENTS; ADVERSE EVENTS; SLEEP; WORK; PHYSICIANS AB Study objective: We obtain preliminary information on the neuropsychological performance of house officers at the beginning and end of a shift while they worked consecutive night shifts in the emergency department. Methods: We prospectively studied interns working 12-hour consecutive night shifts in an urban Level I trauma center ED. All consecutive non-emergency medicine interns rotating for 1 month were eligible except those older than 40 years and those with sleep disorders or depression (identified by using the Profile of Mood Scale, Sleep Diagnostic Questionnaire). We tested research subjects at the beginning of a day shift and at the beginning and end of night shifts 1 and 3 of 4 consecutive night shifts at times of estimated baseline wakefulness (10 Pm) and maximum fatigue (3 AM). We used 3 standardized neuropsychological tests: (1) Delayed Recognition Span Test (visual memory capacity); (2) Continuous Performance Test (attentional function, vigilance); and (3) Santa Ana Form Board Test (psychomotor speed, coordination). We analyzed data with mixed-model analysis, with research subject as a random effect. Results: Thirteen interns were eligible, and 1 declined. Twelve interns (6 men and 6 women; age range 25 to 35 years) were enrolled. The Delayed Recognition Span Test (number correct before first error) revealed significant deterioration from the beginning of the shift to the end of the shift (mean difference -2.2; 95% confidence interval -3.1 to -1.3). This represents an 18.5% decrease in visual memory capacity. There were no significant differences found for the other tests. Conclusion: Interns working nights demonstrated a significant reduction in visual memory capacity across the night shift. Research involving neuropsychological performance during night shifts in the ED is important. It might provide valuable insights into ways to improve our performance during night shifts. C1 Boston Univ, Med Ctr, Dept Emergency Med, Boston, MA 02215 USA. Boston Univ, Med Ctr, Dept Neurol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Anat, Boston, MA 02118 USA. Massachusetts Gen Hosp, Sleep Disorders Unit, Dept Neurol, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, Dept Biostat & Epidemiol, Boston, MA 02215 USA. RP Rollinson, DC (reprint author), Tufts Univ New England Med Ctr, Dept Emergency Med, 750 Washington St, Boston, MA 02111 USA. NR 19 TC 41 Z9 42 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD MAR PY 2003 VL 41 IS 3 BP 400 EP 406 DI 10.1067/mem.2003.77 PG 7 WC Emergency Medicine SC Emergency Medicine GA 651PT UT WOS:000181329700015 PM 12605209 ER PT J AU Earle, CC Grunfeld, E Coyle, D Cripps, MC Stern, HS AF Earle, CC Grunfeld, E Coyle, D Cripps, MC Stern, HS TI Cancer physicians' attitudes toward colorectal cancer follow-up SO ANNALS OF ONCOLOGY LA English DT Article DE colorectal cancer; costs; follow-up; physician survey ID FLUOROURACIL PLUS LEVAMISOLE; COLON-CANCER; ADJUVANT THERAPY; RANDOMIZED TRIAL; CARCINOEMBRYONIC ANTIGEN; COST-EFFECTIVENESS; CURATIVE SURGERY; RADICAL SURGERY; BREAST-CANCER; RESECTION AB Background: The optimal follow-up strategy for colorectal cancer is unknown. Materials and methods: We surveyed all Canadian radiation oncologists, medical oncologists and surgeons specializing in colorectal cancer to assess their recommendations for follow-up after potentially curative treatment, the beliefs and attitudes underlying these practices, and the cost implications of different follow-up strategies. Results: One hundred and sixty practitioners (58%) returned completed surveys. Most recommended clinical assessments every 3-4 months in the first 2 years including carcino-embryonic antigen testing, gradually decreasing in frequency over 5 years. Ninety per cent recommend a surveillance colonoscopy in the first year. The majority felt that specialist involvement in follow-up was important because of the increased opportunities for patients to contribute to research (76%) and teaching (73%). About half felt that specialists were more efficient at providing follow-up than primary care physicians, but these same physicians recommended significantly longer and more expensive follow-up routines on average than others. Primary care physicians were felt to be important allies, especially in managing the psychosocial concerns of patients. Conclusions: Surveillance practices are generally in keeping with published recommendations. Most specialists feel that they should remain involved in follow-up, but this may result in increased resource utilization. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, Div Populat Sci, Boston, MA 02115 USA. Univ Ottawa, Ottawa Reg Canc Ctr, Ottawa, ON, Canada. Univ Ottawa, Div Med Oncol, Ottawa, ON, Canada. Ottawa Hosp Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada. Univ Ottawa, Dept Surg, Ottawa, ON, Canada. RP Earle, CC (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, Div Populat Sci, 44 Binney St,454-STE 21-24, Boston, MA 02115 USA. NR 56 TC 21 Z9 21 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD MAR PY 2003 VL 14 IS 3 BP 400 EP 405 DI 10.1093/annonc/mdg101 PG 6 WC Oncology SC Oncology GA 670KK UT WOS:000182406700010 PM 12598345 ER PT J AU Grillo, HC AF Grillo, HC TI Development of tracheal surgery: A historical review. Part 2: Treatment of tracheal diseases SO ANNALS OF THORACIC SURGERY LA English DT Review ID POSTPNEUMONECTOMY SYNDROME; TRACHEOESOPHAGEAL FISTULA; IATROGENIC STENOSES; SLIDE TRACHEOPLASTY; PERICARDIAL PATCH; MANAGEMENT; RESECTION; CARCINOMA; REPAIR; AIRWAY C1 Massachusetts Gen Hosp, Div Gen Thorac Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Grillo, HC (reprint author), Massachusetts Gen Hosp, Div Gen Thorac Surg, Blake 1570,55 Fruit St, Boston, MA 02114 USA. NR 81 TC 30 Z9 33 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAR PY 2003 VL 75 IS 3 BP 1039 EP 1047 AR PII S0003-4975(02)04109-7 DI 10.1016/S0003-4975(02)04109-7 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 653NJ UT WOS:000181431100070 PM 12645751 ER PT J AU Doyle, PJ McNeil, MR Hula, WD AF Doyle, PJ McNeil, MR Hula, WD TI The Burden of Stroke Scale (BOSS): Validating patient-reported communication difficulty and associated psychological distress in stroke survivors SO APHASIOLOGY LA English DT Article ID QUALITY-OF-LIFE; HEALTH; SYMPTOMS AB Background: The Burden of Stroke Scale (BOSS) (Doyle et al., 2002) is a health-status assessment instrument designed to measure patient-reported difficulty in multiple domains of functioning, psychological distress associated with specific functional limitations, and general well-being in stroke survivors. Aims: This study was designed to examine the discriminative and concurrent validity of the BOSS Communication Difficulty (CD) and Communication-Associated Psychological Distress (CAPD) scales. A secondary purpose was to provide a preliminary examination of the relationships between the BOSS CD and CAPD scales and aspects of subjective well-being, including the frequency with which participants reported experiencing general positive and negative emotional states. Methods & Procedures: The BOSS was administered as a face-to-face interviewer-assisted survey to 281 medically stable, community-dwelling stroke survivors selected from five collaborating centres in the USA. Prior to administration of the BOSS, all subjects were rated for severity of communication impairment using the Boston Diagnostic Aphasia Examination (BDAE) Severity Rating Scale (Goodglass, Kaplan, & Baressi, 2001) and were administered Subtest 8 of the Revised Token Test (RTT), (McNeil & Prescott, 1978). The discriminant validity of the BOSS CD and CAPD scales was examined by comparing scores in stroke survivors with (N = 135) and without (N = 146) communication impairment, and within the communicatively impaired sample when classified according to BDAE ratings and RTT performance. Concurrent validity of the BOSS CD and CAPD scales was examined by correlating BOSS scores with BDAE ratings and RTT performance. Finally, correlations between the BOSS CAPD, BOSS CD, Positive Mood, and Negative Mood scales were calculated. Outcomes & Results: Statistical analyses revealed significant differences between communicatively impaired and non-communicatively impaired subjects on the BOSS CD and CAPD scales, as well as significant differences between communicatively impaired subjects of differing severity levels classified both by BDAE severity ratings and RTT performance. Correlational analyses revealed moderately strong relationships among the BOSS CD scale, BDAE severity ratings, and RTT performance. Finally, correlations among the BOSS CAPD, CD, Positive Mood, and Negative Mood scales revealed true covarying relationships of moderate strength between the BOSS CAPD and CD scales, and also between the CAPD and Negative Mood Scales. Conclusions: These findings provide preliminary support for the discriminant and construct validity of the BOSS Communication Difficulty (CD) and Communication Associated Distress (CAPD) Scales, and provide an empirical rationale for further research into the relationships between functional status, patient-reported health perceptions, and subjective well-being in stroke survivors with communication disorders. C1 VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr 132AH, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. RP Doyle, PJ (reprint author), VA Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr 132AH, 7180 Highland Dr, Pittsburgh, PA 15206 USA. NR 32 TC 27 Z9 28 U1 2 U2 7 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PD MAR PY 2003 VL 17 IS 3 BP 291 EP 304 DI 10.1080/02687030244000680 PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA 656MD UT WOS:000181610800005 ER PT J AU Clarke, P Tyler, KL AF Clarke, P Tyler, KL TI Reovirus-induced apoptosis: A minireview SO APOPTOSIS LA English DT Article DE apoptosis; caspases; death receptors; mitochondria; reovirus ID NF-KAPPA-B; ATTACHMENT PROTEIN SIGMA-1; STRUCTURAL BASIS; DEATH RECEPTORS; SIALIC-ACID; CANCER-CELLS; INHIBITION; ACTIVATION; BINDING; TRAIL AB Reoviruses infect a variety of mammalian hosts and serve as an important experimental system for studying the mechanisms of virus-induced injury. Reovirus infection induces apoptosis in cultured cells in vitro and in target tissues in vivo, including the heart and central nervous system (CNS). In epithelial cells, reovirus-induced apoptosis involves the release of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) from infected cells and the activation of TRAIL-associated death receptors (DRs) DR4 and DR5. DR activation is followed by activation of caspase 8, cleavage of Bid, and the subsequent release of pro-apoptotic mitochondrial factors. By contrast, in neurons, reovirus-induced apoptosis involves a wider array of DRs, including TNFR and Fas, and the mitochondria appear to play a less critical role. These results show that reoviruses induce apoptotic pathways in a cell and tissue specific manner. In vivo there is an excellent correlation between the location of viral infection, the presence of tissue injury and apoptosis, indicating that apoptosis is a critical mechanism by which disease is triggered in the host. These studies suggest that inhibition of apoptosis may provide a novel strategy for limiting virus-induced tissue damage following infection. C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Microbiol & Immunol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. RP Tyler, KL (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol B 182, 4200 E 9th Ave, Denver, CO 80262 USA. EM Ken.Tyler@uchsc.edu OI Tyler, Kenneth/0000-0003-3294-5888 FU NIA NIH HHS [1R01AG14071] NR 51 TC 54 Z9 55 U1 0 U2 5 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1360-8185 J9 APOPTOSIS JI Apoptosis PD MAR PY 2003 VL 8 IS 2 BP 141 EP 150 DI 10.1023/A:1022966508671 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 659GF UT WOS:000181768400003 PM 12766474 ER PT J AU Oaklander, AL Stocks, EA Mouton, PR AF Oaklander, AL Stocks, EA Mouton, PR TI Number of Langerhans immune cells in painful and non-painful human skin after shingles SO ARCHIVES OF DERMATOLOGICAL RESEARCH LA English DT Article DE CD1a; PGP9.5; skin biopsy; herpes zoster; postherpetic neuralgia ID POSTHERPETIC NEURALGIA; CUTANEOUS INNERVATION; MECHANICAL ALLODYNIA; DENDRITIC CELLS; HERPES-ZOSTER; NERVE-FIBERS; TNF-ALPHA; DENSITY; NEUROPATHIES; INVOLVEMENT AB During injury or inflammation, paracrine sensitization of peripheral sensory neurons by immune cells contributes to the sensation of pain. It is less clear whether this neural sensitization contributes to neuropathic pain after neural injury as well. Shingles (herpes zoster) is a common disease that leaves some patients with prolonged neuropathic pain known as postherpetic neuralgia (PHN). Sensitization of cutaneous neurons has been hypothesized to contribute to PHN. Langerhans cells (LC), the le macrophages of the skin, contact epidermal neurites and, when activated, synthesize molecules with the ability to sensitize axons. For these reasons, we examined morphological evidence for activation of LC in subjects with established PHN. We also evaluated the relationship between numbers of LC and nociceptive epidermal nerve endings; these are markedly reduced in PHN. We used design-based stereology to estimate the number of CD1a(+) LC in biopsies of painful and non-painful skin from ten adults with or without PHN after shingles on the torso. There were no differences in the number of LC in previously shingles-affected and normal-control skin biopsies. The number of LC also remained at normal levels in biopsies with near-loss of innervation from shingles. LC numbers were unrelated to the presence or severity of pain. These data suggest that neuropathic pain in established PHN is not associated with increased numbers of cutaneous macrophages, and that the number of cutaneous macrophages in skin from the human torso is independent of the number of epidermal nerve endings. C1 Johns Hopkins Med Inst, Dept Neurosci, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Pathol Neuropathol, Baltimore, MD 21205 USA. RP Oaklander, AL (reprint author), Massachusetts Gen Hosp, Nerve Injury Unit, Dept Anesthesiol, 55 Fruit St,Clin 3, Boston, MA 02114 USA. EM aoaklander@partners.org FU NIA NIH HHS [AG05146]; NIMH NIH HHS [MH 58981]; NINDS NIH HHS [NS10580, NS16735, NS 38377] NR 42 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-3696 J9 ARCH DERMATOL RES JI Arch. Dermatol. Res. PD MAR PY 2003 VL 294 IS 12 BP 529 EP 535 DI 10.1007/s00403-002-0362-7 PG 7 WC Dermatology SC Dermatology GA 666HH UT WOS:000182171200001 PM 12624778 ER PT J AU Tsao, H Bevona, C Goggins, W Quinn, T AF Tsao, H Bevona, C Goggins, W Quinn, T TI The transformation rate of moles (melanocytic nevi) into cutaneous melanoma - A population-based estimate SO ARCHIVES OF DERMATOLOGY LA English DT Article ID MALIGNANT-MELANOMA; DYSPLASTIC NEVI; RISK-FACTOR; SWEDISH POPULATION; PIGMENTED MOLES; MARKERS; NUMBER; ASSOCIATION; PRECURSORS; DIAGNOSIS AB Background: Moles, or melanocytic nevi, are both markers of an increased risk of cutaneous melanoma and direct precursor lesions. Recent strategies to reduce the burden of advanced disease have focused on early detection and ongoing surveillance of moles for malignant degeneration. Inherent in this approach is the notion that moles exhibit a certain risk of transformation into melanoma; however, this risk is unknown. Objective: To estimate the risk of moles transforming into cutaneous melanoma. Design: We first constructed a model of transformation based on the assumption that the minimal number of moles turning into cutaneous melanoma per year is roughly equivalent to the number of melanomas diagnosed each year with associated nevic components. The annual risk was then calculated as the number of mole-associated melanomas diagnosed in 1 year (stratified by 10-year age groups) divided by the number of moles in a the same 10-year age group. We also estimated the cumulative risk during the lifetime of an individual mole by using a modification of the standard tile table method. Results: The annual transformation rate of any single mole into melanoma ranges from 0.0005% or less (ie, less than or equal to1 in 200000) for both men and women younger than 40 years to 0.003% (about 1 in 33000) for men older than 60 years. The rate is similar between men and women younger than 40 years but becomes substantially higher or men older than 40 years. For a 20-year-old individual, the lifetime risk of any selected mole transforming into melanoma by age 80 years is approximately 0.03% (1 in 3164) for men and 0.009% (1 in 10 800) for women. Conclusions: The risk of any particular mole becoming melanoma is low, especially in younger individuals. However, since moles can disappear, ones that persist into old age have an increased risk of malignant degeneration. For young people with innumerable moles and no other associated risk factors, systematic excision of benign-appearing lesions would be of limited benefit. C1 Massachusetts Gen Hosp, Dept Dermatol, Melanoma Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Univ Kansas, Med Ctr, Div Dermatol, Kansas City, KS 66103 USA. Hong Kong Baptist Univ, Dept Math, Hong Kong, Hong Kong, Peoples R China. Pathol Serv Inc, Cambridge, MA USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Melanoma Ctr, Bartlett 622,48 Blossom St, Boston, MA 02114 USA. NR 28 TC 93 Z9 94 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD MAR PY 2003 VL 139 IS 3 BP 282 EP 288 DI 10.1001/archderm.139.3.282 PG 7 WC Dermatology SC Dermatology GA 655PJ UT WOS:000181561100004 PM 12622618 ER PT J AU Orr, SP Metzger, LJ Lasko, NB Macklin, ML Hu, FB Shalev, AY Pitman, RK AF Orr, SP Metzger, LJ Lasko, NB Macklin, ML Hu, FB Shalev, AY Pitman, RK CA Harvard Veterans Affairs Post Trau TI Physiologic responses to sudden, loud tones in monozygotic twins discordant for combat exposure - Association with posttraumatic stress disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 09-14, 2001 CL WAIKALOLA, HAWAII SP Amer Coll Neuropsychopharmacol ID TRAUMA SURVIVORS; VETERANS; RELIABILITY; REGISTRY; VALIDITY; NUCLEUS; SCALE; PTSD; WAR AB Background: Larger heart rate responses to sudden, loud (startling) tones represent one of the best-replicated psychophysiologic markers for posttraumatic stress disorder (PTSD). This abnormality may be a pretrauma vulnerability factor, ie, it may have been present prior to the event's occurrence and increased the individual's likelihood of developing PTSD on traumatic exposure. Alternately, it may be an acquired PTSD sign, ie, it may have developed after the traumatic exposure, along with the PTSD. Studying identical twins discordant for traumatic exposure offers an opportunity to resolve these competing origins. Methods: Subjects included pairs of Vietnam combat veterans and their non-combat-exposed, monozygotic twins. Combat veterans were diagnosed as having current PTSD (n=50) or non-PTSD (ie, never had),(n=53). All subjects listened to a series of 15 sudden, loud tone presentations while heart rate, skin conductance, and orbicularis oculi electromyogram responses were measured. Results: Consistent with previous reports, averaged heart rate responses to the tones were larger in Vietnam combat veterans with PTSD. These larger responses were not shared by their tion-combat-exposed co-twins, whose responses were similar to those of the non-PTSD combat veterans and their non-combat-exposed co-twins. This result remained significant after adjusting for a number of potentially confounding factors. Conclusions: The results suggest that larger heart rate responses to sudden, loud tones represent an acquired sign of PTSD rather than a familial vulnerability factor. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Vet Affairs Med Ctr, Res Serv, Manchester, NH USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA USA. Hadassah Univ Hosp, Dept Psychiat, IL-91120 Jerusalem, Israel. Vietnam Era Twin Registry, Hines, IL USA. RP Orr, SP (reprint author), Massachusetts Gen Hosp E, Psychiat Neurosci Program, CNY-9,Bldg 149,13th St, Boston, MA 02129 USA. FU NIMH NIH HHS [MH54636] NR 25 TC 96 Z9 97 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAR PY 2003 VL 60 IS 3 BP 283 EP 288 DI 10.1001/archpsyc.60.3.283 PG 6 WC Psychiatry SC Psychiatry GA 655UZ UT WOS:000181572200008 PM 12622661 ER PT J AU Toomey, R Lyons, MJ Eisen, SA Xian, H Chantarujikapong, S Seidman, LJ Faraone, SV Tsuang, MT AF Toomey, R Lyons, MJ Eisen, SA Xian, H Chantarujikapong, S Seidman, LJ Faraone, SV Tsuang, MT TI A twin study of the neuropsychological consequences of stimulant abuse SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; ABSTINENT COCAINE ABUSERS; ATTENTION-DEFICIT; ALCOHOL; TELEPHONE; MEMORY; WITHDRAWAL; IMPAIRMENT; DEPENDENCE; REGISTRY AB Background: Previous studies document neuropsychological deficits associated with stimulant abuse, but findings are inconsistent. Methods: We identified 50 twin pairs in which only I member had heavy stimulant abuse (cocaine and/or amphetamines) ending at least I year before the evaluation. The co-twin control research design controls for familial vulnerability and makes it easier to identify neuropsychological deficits that are consequences of stimulant abuse. Subjects were administered an extensive neuropsychological test battery organized into the following 5 functions: attention, executive functioning, motor skills, intelligence, and memory. Results: Multivariate tests showed that abusers performed significantly worse than nonabusers on functions of attention and motor skills. Within each of these functions, univariate tests showed that abusers performed significantly worse on certain tests of motor skills and attention. In contrast, abusers performed significantly better on one test of attention measuring visual vigilance. Within the abuser group, higher levels of stimulant use were largely uncorrelated with neuropsychological test scores, although a few significant correlations indicated better functioning with more stimulant use. Conclusions: With ideal controls, this study demonstrates that deficits in attention and motor skills persist after I year of abstinence from stimulant use and raises hypotheses regarding relative strengths on a vigilance task among abusers. RP Toomey, R (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bldg 149-912E,13th St, Boston, MA 02129 USA. RI Lyons, Michael/B-6119-2011; OI Lyons, Michael/0000-0001-6516-9219; Faraone, Stephen/0000-0002-9217-3982 FU NIDA NIH HHS [DA04604] NR 54 TC 48 Z9 48 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAR PY 2003 VL 60 IS 3 BP 303 EP 310 DI 10.1001/archpsyc.60.3.303 PG 8 WC Psychiatry SC Psychiatry GA 655UZ UT WOS:000181572200011 PM 12622664 ER PT J AU Pompl, PN Yemul, S Xiang, ZM Ho, L Haroutunian, V Purohit, D Mohs, R Pasinetti, GM AF Pompl, PN Yemul, S Xiang, ZM Ho, L Haroutunian, V Purohit, D Mohs, R Pasinetti, GM TI Caspase gene expression in the brain as a function of the clinical progression of Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID APOPTOTIC CELL-DEATH; NEUROFIBRILLARY TANGLE FORMATION; AMYLOID-BETA; IN-SITU; REGIONAL DISTRIBUTION; PRECURSOR PROTEIN; ENTORHINAL CORTEX; DNA FRAGMENTATION; PLAQUE-FORMATION; PLASMA-LEVELS AB Background: Caspase gene expression has previously been reported in terminal Alzheimer disease (AD) brain, but, currently, little is known about the temporal pattern of caspase gene expression relative to the onset and clinical progression of AD. Objective: To derive a profile of caspase gene expression and proapoptotic indexes as a function of the clinical and neuropathologic progression of AD dementia. Setting and Patients: Postmortem survey of nursing home patients characterized clinically by Clinical Dementia Rating (CDR) and neuropathologically by Consortium to Establish a Registry for Alzheimer's Disease criteria. Design and Outcome Measures: To assess messenger RNA expression of caspase-1, -2L, -2S, -3, -5, -6, -7, -8, and -9; apoptotic cell death by TUNEL assay; and poly (ADP-ribose) polymerase cleavage in postmortem brain tissue samples from cognitively normal (CDR 0), high risk of developing AD dementia (CDR 0.5), and severe dementia (CDR 5) cases. Results: Compared with CDR 0 cases, elevated messenger RNA expression of caspase-1 and caspase-7 in the entorhinal cortex of CDR 0.5 cases coincided with increased poly (ADP-ribose) polymerase cleavage but not apoptotic cell injury. In the entorhinal cortex of CDR 5 cases, we found elevation of caspase-1 -2L, -3, -5, -6, -7, -8, and -9 and a greater than 4-fold increase in TUNEL-positive cells. Caspase messenger RNA expression was closely associated with neurofibrillary tangle and, to a lesser extent; neuritic plaque density. Conclusions: Proapoptotic mechanisms may be at play early in the onset of AD (before overt signs of apoptosis) and maybe a conditional factor for later apoptotic cell injury or death. These data have relevance to potential therapeutic interventions for AD using selective caspase inhibitors. C1 Mt Sinai Sch Med, Neuroinflammat Res Labs, Dept Psychiat, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Pathol, New York, NY 10029 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, Dept Psychiat, Bronx, NY USA. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Neuroinflammat Res Labs, Dept Psychiat, 1 Gustave L Levy Pl, New York, NY 10029 USA. FU NIA NIH HHS [AG 02219] NR 59 TC 69 Z9 76 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAR PY 2003 VL 60 IS 3 BP 369 EP 376 DI 10.1001/archneur.60.3.369 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 655PM UT WOS:000181561500008 PM 12633148 ER PT J AU Bartzokis, G Cummings, JL Sultzer, D Henderson, VW Nuechterlein, KH Mintz, J AF Bartzokis, G Cummings, JL Sultzer, D Henderson, VW Nuechterlein, KH Mintz, J TI White matter structural integrity in healthy aging adults and patients with Alzheimer disease - A magnetic resonance imaging study SO ARCHIVES OF NEUROLOGY LA English DT Article ID MYELINATED NERVE-FIBERS; PRIMARY VISUAL-CORTEX; IN-VIVO EVALUATION; BRAIN IRON; OXIDATIVE STRESS; RHESUS-MONKEY; NITRIC-OXIDE; AGE; DEMENTIA; OLIGODENDROCYTES AB Background: Imaging and postmortem studies suggest that frontal lobe white matter (FLWM) volume expands until about the age of 44.6 years and then declines. Postmortem evidence indicates that the structural integrity of myelin sheaths deteriorates during normal aging, especially in late myelinating regions such as the frontal lobes. Objectives: To assess the integrity of FLWM by magnetic resonance imaging and, thus, to provide an important index of brain aging and its relationship to Alzheimer disease (AD). Design: Cross-sectional study. Setting: Two metropolitan university hospitals and AD research centers. Participants: Two hundred fifty-two healthy adults (127 men and 125 women), aged 19 to 82 years, and 34 subjects with AD (16 men and 18 women), aged 59 to 85 years. Main Outcome Measure: Calculated transverse relaxation rate (R-2) of the FLWM (an indirect measure of the structural integrity of white matter). Results: As expected from prior imaging data on FLWM volume, the quadratic function best represented the relationship between age and the FLWM R-2 (P<.001). In healthy individuals, the FLWM R-2 increased until the age of 38 years and then declined markedly with age. The R-2 of subjects with AD was significantly lower than that of a group of healthy control subjects who were of similar age and sex (P<.001). Conclusions: The R-2 change"s in white matter suggest that the healthy adult brain is in a constant state of change, roughly defined as periods of maturation continuing into middle age followed by progressive loss of myelin integrity. Clinically diagnosed AD is associated with more severe myelin breakdown. Noninvasive measures, such as the determination of the R-2, may have the potential to track prospectively the trajectory of deteriorating white matter integrity during normal aging and the development of AD and, thus, may be a useful marker for medication development aimed at the prevention of AD. C1 Univ Calif Los Angeles, Sch Med, Rush Alzheimers Dis Ctr, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Div Brain Mapping, Lab Neuroimaging, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Univ Arkansas Med Sci, Dept Geriatr, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Neurol, Little Rock, AR 72205 USA. RP Bartzokis, G (reprint author), Univ Calif Los Angeles, Sch Med, Rush Alzheimers Dis Ctr, Dept Neurol, 710 Westwood Plaza,Room 2-238, Los Angeles, CA 90095 USA. RI Bartzokis, George/K-2409-2013; Mintz, Jim/N-7385-2014 OI Mintz, Jim/0000-0002-8299-5851 FU NIA NIH HHS [AG 16570]; NIMH NIH HHS [MH-30911, MH-37705, MH-51928] NR 77 TC 212 Z9 222 U1 0 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAR PY 2003 VL 60 IS 3 BP 393 EP 398 DI 10.1001/archneur.60.3.393 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 655PM UT WOS:000181561500011 PM 12633151 ER PT J AU Krause, MHJ Xiong, J Gragoudas, ES Young, LHY AF Krause, MHJ Xiong, J Gragoudas, ES Young, LHY TI Treatment of experimental choroidal melanoma with an Nd : yttrium-lanthanum-fluoride laser at 1047 nm SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID PHOTODYNAMIC THERAPY; TRANSPUPILLARY THERMOTHERAPY; UVEAL MELANOMA; RABBIT MODEL; ESTABLISHMENT AB Objective: To evaluate the effect of a new infrared laser in the destruction of pigmented choroidal melanomas. Methods: B16F10 melanomas were implanted in the subchoroidal space of 64 rabbits (tumor height, 2.0-4.0 mm). Laser radiation from an Nd:yttrium-lanthanum-fluoride laser (1047 nm) was delivered as a focused (beam waist, 25 pm; irradiance, 100 kW/cm(2)) raster-scanned transpupillary beam. To investigate melanin heating, treatment with focused light was compared with collimated light (beam waist, 2 mm; irradiance, 16 W/cm(2)). Fine-wire thermocouples were implanted at the base of 3 tumors for in vivo temperature measurements. Untreated animals were used as controls. Results: Of 64 animals, 27 received a single treatment with focused 1047-nm light. The rate of complete tumor eradication was 91% (10 of 11 animals) at a dosage of 125 J/cm(2) and 75% (9/12) at 63 J/cm(2) to 87 J/cm(2). The eradication rate dropped to 25% (1 of 4) at 38 J/cm(2) or less (P<.001). Continuous tumor growth was observed in all animals treated with collimated radiation and in untreated controls. Temperature measurements indicated that tissue heating at the tumor base was more rapid at 1047 nm than at 805 nm. Conclusions: These data suggest that a single treatment with a focused, raster-scanned beam at 1047 nm may play a role in the destruction of pigmented choroidal melanoma. Focused irradiation at 1047 nm may provide more effective submillisecond heating of melanin than collimated irradiation, resulting in immediate photothermal disruption of tumor cells. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Laser Res Lab, Boston, MA 02114 USA. RP Young, LHY (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv, 243 Charles St, Boston, MA 02114 USA. EM lhyoung@meei.harvard.edu FU NEI NIH HHS [EY 10975] NR 19 TC 3 Z9 3 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAR PY 2003 VL 121 IS 3 BP 357 EP 363 PG 7 WC Ophthalmology SC Ophthalmology GA 653YP UT WOS:000181464900008 PM 12617706 ER PT J AU Christen, WG Manson, JE Glynn, RJ Gaziano, KM Sperduto, RD Buring, JE Hennekens, CH AF Christen, WG Manson, JE Glynn, RJ Gaziano, KM Sperduto, RD Buring, JE Hennekens, CH TI A randomized trial of beta carotene and age-related cataract in US physicians SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID CIGARETTE-SMOKING; ALPHA-TOCOPHEROL; SERUM CAROTENOIDS; VITAMIN-A; NUTRIENT CONCENTRATIONS; CARDIOVASCULAR-DISEASE; PLASMA-CONCENTRATIONS; ANTIOXIDANT VITAMINS; ALCOHOL-CONSUMPTION; NUCLEAR CATARACT AB Objective: To examine the development of age-related cataract in a trial of beta carotene supplementation in men. Design: Randomized, double-masked, placebo-controlled trial. Methods: Male US physicians aged 40 to 84 years (n = 22071) were randomly assigned to receive eitherbeta carotene (50 mg on alternate days) or placebo for 12 years. Main Outcome Measures: Age-related cataract and extraction of age-related cataract, defined as an incident, age-related lens opacity, responsible for a reduction in best-corrected visual acuity to 20/30 or worse, based on self-report confirmed by medical record review. Results: There was no difference between the beta carotene and placebo groups in the overall incidence of cataract (998 cases vs 1017 cases;,relative risk [RR], 1.00; 95% confidence interval [CI], 0.91-1.09) or cataract ex-traction (584 vs 593; RR, 1.00; 95% CI, 0.89-1.12). In subgroup analyses, the effect of beta carotene supplementation appeared to be modified by smoking status at baseline (P = .02). Among current smokers, there were 108 cases of cataract in the beta carotene group and 133 in the placebo group (RR, 0.74; 95% CI, 0.57-0.95). Among current nonsmokers, there was no significant difference in the number of cases in the 2 treatment groups (884 vs 881; RR, 1.03; 95% CI, 0.94-1.13). The results for cataract extraction appeared to be similarly modified by baseline smoking status (P = .05). Conclusions: Randomized trial data from a large population of healthy men indicate no overall benefit or harm of 12 years of beta carotene supplementation on cataract or cataract extraction. However, among current smokers at baseline, beta carotene appeared to attenuate their excess risk of cataract by about one fourth. C1 Brigham & Womens Hosp, Div Prevent Med, 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. Boston Healthcare Syst, Dept Vet Affairs, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. NEI, Bethesda, MD 20892 USA. Univ Miami, Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33152 USA. RP Christen, WG (reprint author), Brigham & Womens Hosp, Div Prevent Med, 900 Commonwealth Ave E,3rd Floor, Boston, MA 02215 USA. FU NCI NIH HHS [CA 40360, CA 34944, R01 CA097193]; NEI NIH HHS [EY 06633]; NHLBI NIH HHS [HL 26490, HL 34595] NR 51 TC 41 Z9 43 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAR PY 2003 VL 121 IS 3 BP 372 EP 378 PG 7 WC Ophthalmology SC Ophthalmology GA 653YP UT WOS:000181464900010 PM 12617708 ER PT J AU Kratz, A Lewandrowski, KB Siegel, A Sluss, PM Chun, KY Flood, JG Lee-Lewandrowski, E AF Kratz, A Lewandrowski, KB Siegel, A Sluss, PM Chun, KY Flood, JG Lee-Lewandrowski, E TI Effect of marathon running on total and free serum prostate-specific antigen concentrations SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID EARLY DIAGNOSIS; CANCER; HYPERPLASIA; EJACULATION; INCREASES; MEN AB Context.-Prostate-specific antigen (PSA) is an important tumor marker for the most frequently diagnosed cancer in the United States. A major limitation of this marker is falsely elevated results in patients who are found not to have prostate cancer. The effects of vigorous physical exertion on PSA concentrations are controversial. Objective.-To determine the effects of marathon running on PSA levels. Design.-Measurement of total and free PSA levels in the sera of participants in a marathon before and within 4 and 24 hours after the race. Results.-None of the participants had elevated total PSA levels before the race. Although we found no statistically significant changes in average total or free PSA concentrations at either time point, after the marathon, 2 (111%) of 18 runners had total PSA concentrations outside the standard reference range. Changes in total PSA levels did not correlate with age or prerace PSA concentrations. Free PSA levels were not statistically significantly changed after the race and did not allow a reliable determination of exercise-induced PSA elevations. Conclusions.-Although it may not be necessary for men to abstain from exercise involving running before blood draws for PSA analysis, elevated PSA concentrations may be observed in some individuals after participation in a major sporting event. In these cases, repeat measurements should be considered at a time significantly removed from such exercise. C1 Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. McLean Hosp, Dept Med, Belmont, MA 02178 USA. RP Lee-Lewandrowski, E (reprint author), Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, 55 Fruit St,GRB5 Chem, Boston, MA 02114 USA. NR 24 TC 8 Z9 8 U1 0 U2 2 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAR PY 2003 VL 127 IS 3 BP 345 EP 348 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 661XT UT WOS:000181915700014 PM 12653581 ER PT J AU Ferris, TG Wasserman, RC AF Ferris, TG Wasserman, RC TI Primary care and specialty care for US children - What is the right mix? SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Editorial Material C1 MassGen Hosp Children, Inst Hlth Policy, Boston, MA 02114 USA. RP Ferris, TG (reprint author), MassGen Hosp Children, Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. RI Wasserman , Richard/G-3775-2015 NR 7 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD MAR PY 2003 VL 157 IS 3 BP 219 EP 220 PG 2 WC Pediatrics SC Pediatrics GA 653KX UT WOS:000181435300002 PM 12622667 ER PT J AU Encke, J Putlitz, JZ Stremmel, W Wands, JR AF Encke, J Putlitz, JZ Stremmel, W Wands, JR TI CpG immuno-stimulatory motifs enhance humoral immune responses against hepatitis C virus core protein after DNA-based immunization SO ARCHIVES OF VIROLOGY LA English DT Article ID B SURFACE-ANTIGEN; IMMUNOSTIMULATORY DNA; GENETIC IMMUNIZATION; BACTERIAL-DNA; POTENT ENHANCER; VACCINES; VACCINATION; CONSTRUCTS; ADJUVANTS; MICE AB Chronic HCV infection is associated with a high morbidity and mortality rate, and currently a prophylactic or therapeutic vaccine is not available. DNA-based immunization is a powerful method to generate cellular and humoral immune responses. However, DNA immunization against HCV core results only in a weak humoral immune response demonstrated in several studies. Therefore, co-immunization with a novel adjuvant may enhance such potentially important immune responses. We examined whether unmethylated CpG motifs in the form of oligodeoxynucleotides (ODN) or E. coli DNA can act as adjuvants for a DNA vaccination approach, since CpG motifs have been shown to stimulate the innate immune system as well as B and T cell immune reactivity. The present study demonstrates that CpG motifs enhance in vivo antibody levels after DNA immunization against HCV core. However, despite some in vitro activity of CpG motifs, no enhancement of T cell responses in vivo was observed after immunization with HCV plasmid DNA and CpG motifs in mice. Our results suggest that co-immunization with CpG-ODN may strengthen humoral immune responses but show no potential effect as an adjuvant to induce cellular immunity against HCV core. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc,Mol Hepatol Lab, Charlestown, MA USA. RP Encke, J (reprint author), Univ Heidelberg, Dept Internal Med 4, Bergheimerstr 58, D-69115 Heidelberg, Germany. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-20169, AA-02666] NR 39 TC 18 Z9 21 U1 1 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PD MAR PY 2003 VL 148 IS 3 BP 435 EP 448 DI 10.1007/s00705-002-0935-y PG 14 WC Virology SC Virology GA 654JW UT WOS:000181494000002 PM 12607097 ER PT J AU Manfro, GG Netto, CA Pollack, M Mezzomo, KM Preffer, F Kradin, R AF Manfro, GG Netto, CA Pollack, M Mezzomo, KM Preffer, F Kradin, R TI Stress regulates the lymphocyte homing receptor CD62L (L-selectin) SO ARQUIVOS DE NEURO-PSIQUIATRIA LA English DT Article DE corticosteroids; interleukin-2; lymphocyte migration; adhesion molecules; panic disorder ID PANIC DISORDER; INTERLEUKIN-2; PROLIFERATION; ACTIVATION; CYTOKINE; ANXIETY; ATTACKS AB Based on a previous study showing that panic disorder patients had increased expression of naive phenotype lymphocytes (CD45RA+ and CD62L+), increased plasma cortisol, as well as decreased interleukin-2 (IL-2) production, we hypothesized that changes in the percentage of expression of these lymphocyte surface molecules could be related to the substances released by the hypothalamic-pituitary-adrenal (HPA) axis and possibly associated to panic disorder (cortisol, IL-2, serotonin and epinephrine). In order to study the altered expression, blood mononuclear cells of normal volunteers were stimulated with mitogen, in the presence of dexamethasone, IL-2, serotonin and epinephrin. CD62L is decreased by IL-2 in vitro. Serotonin and epinephrine did not promote changes in the expression of these surface molecules. The results of the ex vivo study are in agreement with a previous clinical study with panic patients. It could be suggested that stress is responsible for certain immunologic dysfunctions and new studies should be conducted. C1 Univ Fed Rio Grande Sul, Dept Bioquim, BR-90046900 Porto Alegre, RS, Brazil. Hosp Clin Porto Alegre, Serv Psiquiatria, Porto Alegre, RS, Brazil. Massachusetts Gen Hosp, Sch Med, Dept Pathol, Immunopathol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Psychopharmacol Unit, Boston, MA 02114 USA. Univ Fed Rio Grande Sul, Dept Psiquiatria & Med Legal, Porto Alegre, RS, Brazil. RI Manfro, Gisele/B-7020-2009 NR 26 TC 3 Z9 4 U1 0 U2 2 PU ASSOC ARQUIVOS DE NEURO- PSIQUIATRIA PI SAO PAULO SP PA PR AMADEU AMARAL 47/33, 01327-010 SAO PAULO SP, BRAZIL SN 0004-282X J9 ARQ NEURO-PSIQUIAT JI Arq. Neuro-Psiquiatr. PD MAR PY 2003 VL 61 IS 1 BP 20 EP 24 DI 10.1590/S0004-282X2003000100004 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 669DM UT WOS:000182336700004 PM 12715014 ER PT J AU Leopold, JA Zhang, YY Scribner, AW Stanton, RC Loscalzo, J AF Leopold, JA Zhang, YY Scribner, AW Stanton, RC Loscalzo, J TI Glucose-6-phosphate dehydrogenase overexpression decreases endothelial cell oxidant stress and increases bioavailable nitric oxide SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE glucose-6-phosphate dehydrogenase; oxidant stress; endothelium; nitric oxide; nitric oxide synthase ID SUPEROXIDE GENERATION; GLUTATHIONE LEVELS; OXIDATIVE STRESS; SYNTHASE; EXPRESSION; INHIBITION; GROWTH AB Objective-Glucose-6-phosphate dehydrogenase (G6PD), the principal source of NADPH, serves as an antioxidant enzyme to modulate the redox milieu and nitric oxide synthase activity. Deficient G6PD activity is associated with increased endothelial cell oxidant stress and diminished bioavailable nitric oxide (NO.). Therefore, we examined whether overexpression of G6PD would decrease reactive oxygen species accumulation and increase bioavailable NO. in endothelial cells. Methods and Results-Adenoviral-mediated gene transfer of G6PD increased G6PD expression, activity, and NADPH levels in bovine aortic endothelial cells (BAECs). BAECs overexpressing G6PD demonstrated a significant reduction in reactive oxygen species accumulation when exposed to hydrogen peroxide, xanthine-xanthine oxidase, or tumor necrosis factor-alpha compared with BAECs with basal levels of G6PD. BAECs overexpressing G6PD maintained intracellular glutathione stores when exposed to oxidants because of increased activity of glutathione reductase, an effect that was not observed in endothelial cells with normal G6PD activity. Overexpression of G6PD was also associated with enhanced nitric oxide synthase activity, resulting in elevated levels of cGMP, nitrate, and nitrite, and this response was increased after stimulation with bradykinin. Conclusions-Overexpression of G6PD in vascular endothelial cells decreases reactive oxygen species accumulation in response to exogenous and endogenous oxidant stress and improves levels of bioavailable NO.. C1 Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Leopold, JA (reprint author), Boston Univ, Sch Med, Whitaker Cardiovasc Inst, 700 Albany St,CABR W-507, Boston, MA 02118 USA. FU NHLBI NIH HHS [HL04399, HL58976, HL61795, P50 HL55993] NR 21 TC 94 Z9 99 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAR PY 2003 VL 23 IS 3 BP 411 EP 417 DI 10.1161/01.ATV.0000056744.26901.BA PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 655JY UT WOS:000181549400012 PM 12615686 ER PT J AU White, RF James, KE Vasterling, JJ Letz, R Marans, K Delaney, R Krengel, M Rose, F Kraemer, HC AF White, RF James, KE Vasterling, JJ Letz, R Marans, K Delaney, R Krengel, M Rose, F Kraemer, HC TI Neuropsychological screening for cognitive impairment using computer-assisted tasks SO ASSESSMENT LA English DT Article DE neuropsychological screening; diagnostic classification; recursive partitioning; regression trees; cognitive impairment; computerized testing ID EXPOSURE; VETERANS; TESTS AB The aim of this study was to validate a computer-assisted screening battery for classifying patients into two groups, those with and without cognitive impairment. Participants were all patients referred to the neuropsychology clinics at four VA medical centers during a I-Year period. Patients meeting the study inclusionary criteria (N = 252) were administered the Neurobehavioral Evaluation System-3 (NES3) computer-assisted battery. A detailed neuropsychological examination was carried out by an experienced neuropsychologist, who diagnosed the patient as cognitively impaired or not impaired. The neuropsychologist's diagnosis was the gold standard. Recursive partitioning analyses yielded several classification procedures using the NES3 data to predict the gold standard. These procedures produced a set of six NES3 tasks that provide good sensitivity and specificity inpredicting diagnosis. Sensitivity and specificity for the least random classification procedure were 0.87 and 0.67, respectively. The results suggest that computer-assisted screening methods are a promising means of triaging patients. C1 VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Boston, MA 02215 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. DVA Cooperat Studies Program, Portland, OR 97201 USA. Tulane Univ, Sch Med, New Orleans, LA 70118 USA. VA New Orleans Healthcare Syst, New Orleans, LA 70118 USA. Emory Univ, Atlanta, GA 30322 USA. Gaylord Hosp, Wallingford, CT USA. Salk Inst, San Diego, CA 92186 USA. Stanford Univ, Stanford, CA 94305 USA. RP White, RF (reprint author), VA Med Ctr, 116B-4,150 S Huntington Ave, Boston, MA 02310 USA. OI Krengel, Maxine/0000-0001-7632-590X; White, Roberta/0000-0002-2001-6646 NR 52 TC 21 Z9 21 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-1911 J9 ASSESSMENT JI Assessment PD MAR PY 2003 VL 10 IS 1 BP 86 EP 101 DI 10.1177/1073191102250185 PG 16 WC Psychology, Clinical SC Psychology GA 663VX UT WOS:000182028000010 PM 12675388 ER PT J AU Lopez, I Ayala, C Honrubia, V AF Lopez, I Ayala, C Honrubia, V TI Synaptophysin immunohistochemistry during vestibular hair cell recovery after gentamicin treatment SO AUDIOLOGY AND NEURO-OTOLOGY LA English DT Article DE hair cells; synaptophysin immunoreactivity; gentamicin ototoxicity ID CHINCHILLA CRISTA-AMPULLARIS; INNER-EAR; INNERVATION PATTERNS; NEUROTROPHIC FACTOR; SENSORY EPITHELIA; SYNAPTIC VESICLE; EFFERENT NEURONS; GUINEA-PIGS; END-ORGANS; SYNAPSIN-I AB In the present study, morphometric and immunohistochemical techniques were used to evaluate the degree of synaptic recovery in the chinchilla crista sensory epithelia during various post-gentamicin-treatment periods of hair cell loss and recovery. For this purpose, two groups of animals were treated with Gelfoams pellets impregnated with 50 mug of gentamicin implanted in the perilymphatic space within the otic capsule of the superior semicircular canal. Animals were sacrificed 1, 2 and 4 weeks after treatment. The degree of synaptic reinnervation was evaluated in the horizontal crista of the first group of animals using immunohistochemical techniques and antibodies against synaptophysin, a marker for synaptic reinnervation and synaptogenesis. Quantification of immunoreactivity in this group was made in the mid-region of the crista using the NIH 'Image' program. The second group of animals was used for quantification of the number of hair cells and supporting cells in the horizontal crista. In the normal sensory epithelium, synaptophysin immunoreactivity was found in the areas corresponding to the known distribution of afferent and efferent nerve terminals. Immunoreactivity was predominantly located within the afferent calyces of type I hair cells. No immunoreactivity was found in the supporting cells. Seven days after treatment there was a significant loss of hair cells and synaptophysin-stained area (SSA). In the mid-region of the crista the loss of synaptophysin immunoreactivity was quantitatively the greatest within the central zone of this region (93%) while the loss of hair cells was the smallest. These results suggest that afferent and efferent nerve terminals were also severely affected by the ototoxic treatment. Four weeks after treatment corresponding to the end of the recovery phase of gentamicin ototoxicity, there was a proportional increase in the number of hair cells and of the degree of SSA in the mid-region of the crista. The number of hair cells recovered to 58% with a recovery of SSA to 54% of normal. These results suggest that a greater fraction of synaptophysin expression within the sensory epithelium depends on the presence of afferent calyceal endings, which are greatly affected by gentamicin. Also, these results demonstrate a significant level of reinnervation of the newly regenerated hair cells, forecasting the potential for functionality of the regenerated hair cells. Copyright (C) 2003 S. Karger AG, Basel. C1 Univ Calif Los Angeles, Sch Med, Div Head & Neck Surg, Victor Goodhill Ear Ctr, Los Angeles, CA 90024 USA. Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Honrubia, V (reprint author), 10833 Conte Ave,62-129 CHS, Los Angeles, CA 90095 USA. OI Lopez, Ivan/0000-0001-5205-7293 FU NIDCD NIH HHS [DC02952, DC00008] NR 51 TC 6 Z9 8 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-3030 J9 AUDIOL NEURO-OTOL JI Audiol. Neuro-Otol. PD MAR-APR PY 2003 VL 8 IS 2 BP 80 EP 90 DI 10.1159/000069001 PG 11 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 660XE UT WOS:000181859600003 PM 12634456 ER PT J AU Garb, HN AF Garb, HN TI Observations on the validity of neuropsychological and personality assessment testing SO AUSTRALIAN PSYCHOLOGIST LA English DT Article ID RORSCHACH-COMPREHENSIVE-SYSTEM; CLINICAL-ASSESSMENT; PSYCHOLOGICAL-ASSESSMENT; DAUBERT STANDARD; NORMS; TESTIMONY; ACCURACY; PSYCHOPATHOLOGY; MISPERCEPTION; METAANALYSES AB The validity of neuropsychological testing is evaluated in the context of a growing controversy surrounding personality assessment, Claims made by a committee established by the American Psychological Association are disputed (e.g., that psychological tests are as valid as medical tests). Also, normative data for projective techniques and neuropsychological tests are contrasted. Normative data is not available for many projective techniques, and norms for the Rorschach Comprehensive System (Exner, 1993) have been seriously flawed. In contrast, norms for neuropsychological tests are widely available and fundamentally sound. Finally, with regard to the validity of judgments made by psychologists, results for projective techniques have been disappointing while results for neuropsychological tests have generally been positive. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. RP Garb, HN (reprint author), VA Pittsburgh Healthcare Syst, 116A-H,7180 Highland Dr, Pittsburgh, PA 15206 USA. NR 77 TC 0 Z9 0 U1 3 U2 8 PU AUSTRALIAN PSYCHOLOGICAL SOC PI CARLTON PA 1 GRATTAN STREET, CARLTON, VICTORIA 3053, AUSTRALIA SN 0005-0067 J9 AUST PSYCHOL JI Aust. Psychol. PD MAR PY 2003 VL 38 IS 1 BP 14 EP 21 DI 10.1080/00050060310001706977 PG 8 WC Psychology, Multidisciplinary SC Psychology GA 650HN UT WOS:000181257700003 ER PT J AU Stark, LJ Opipari, LC Spieth, LE Jelalian, E Quittner, AL Higgins, L Mackner, L Byars, K Lapey, A Stallings, VA Duggan, C AF Stark, LJ Opipari, LC Spieth, LE Jelalian, E Quittner, AL Higgins, L Mackner, L Byars, K Lapey, A Stallings, VA Duggan, C TI Contribution of behavior therapy to dietary treatment in cystic fibrosis: A randomized controlled study with 2-year follow-up SO BEHAVIOR THERAPY LA English DT Article ID INCREASING CALORIE CONSUMPTION; BODY-COMPOSITION; CHILDREN; INTERVENTION; ADHERENCE; PARENTS; GROWTH AB Behavioral intervention (BI) was compared to nutrition education (NE) to better understand the contribution of behavior therapy to nutrition management in children with cystic fibrosis (CF). Participants were 7 children between 6 and 12 years of age with weight for age percentiles ranging from the 3rd to the 27th. Families in each condition were seen for 7 sessions and provided the same nutrition information and calorie goals. The BI received training on child behavior management. Caloric intake across meals was evaluated via multiple baseline design. Results indicated that the BI had a greater increase in daily caloric intake (1,036 cal/day) and weight gain (1.42 kg) than the NE (408 cal/day, 0.78 kg). Improved caloric intake was maintained 2 years following treatment. C1 Univ Cincinnati, Childrens Hosp, Med Ctr, Coll Med,Div Psychol, Cincinnati, OH 45229 USA. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Brown Univ, Rhode Isl Hosp, Sch Med, Providence, RI 02903 USA. Univ Florida, Gainesville, FL 32611 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Univ Penn, Sch Med, Childrens Hosp, Philadelphia, PA 19104 USA. RP Stark, LJ (reprint author), Univ Cincinnati, Childrens Hosp, Med Ctr, Coll Med,Div Psychol, MLC 3015,3333 Burnet Ave, Cincinnati, OH 45229 USA. NR 29 TC 29 Z9 29 U1 0 U2 1 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 SPR PY 2003 VL 34 IS 2 BP 237 EP 258 DI 10.1016/S0005-7894(03)80015-1 PG 22 WC Psychology, Clinical SC Psychology GA 687ZJ UT WOS:000183406900007 ER PT J AU Zhao, HY Tian, W Xu, HS Cohen, DM AF Zhao, HY Tian, W Xu, HS Cohen, DM TI Urea signalling to immediate-early gene transcription in renal medullary cells requires transactivation of the epidermal growth factor receptor SO BIOCHEMICAL JOURNAL LA English DT Article DE heparin-binding epidermal growth factor; hypertonicity; metalloproteinase ID DIPHTHERIA-TOXIN RECEPTOR; PROTEIN-COUPLED RECEPTORS; SMOOTH-MUSCLE CELLS; DUCT MIMCD3 CELLS; FACTOR HB-EGF; METALLOPROTEINASE CLEAVAGE; INTEGRIN ALPHA-3-BETA-1; EXTRACELLULAR CALCIUM; EPITHELIAL-CELLS; TYROSINE KINASE AB Signalling by physiological levels of urea (e.g. 200 nM) in cells of the mammalian renal medulla is reminiscent of activation of a receptor tyrosine kinase. The epidermal growth factor (EGF) receptor may be transactivated by a variety of G-protein-coupled receptors, primarily through metalloproteinase-dependent cleavage of a membrane-anchored EGF precursor. In the murine inner medullary collecting duct (mIMCD3) cell line, urea (200 mM) induced prompt (1-5 min) tyrosine phosphorylation of the EGF receptor. Pharmacological inhibition of EGF receptor kinase activity with AG1478 or PD153035 blocked urea-inducible transcription and expression of the immediate-early gene, Egr-1. AG1478 blocked, either fully or partially, other hallmarks of urea signalling including Elk-l activation and extracellular signal-regulated kinase phosphorylation. EGF receptor kinase inhibition also blocked the cytoprotective effect of urea observed in the context of hypertonicity-inducible apoptosis. EGF receptor transactivation was likely to be attributable to metalloproteinase-dependent ectodomain shedding of an EGF receptor agonist because both specific and non-specific inhibitors of metalloproteinases blocked the urea effect. Heparin-binding EGF (HB-EGF), in particular, was implicated because the diphtheria toxin analogue and highly specific antagonist of HB-EGF, CRM197, also blocked urea-inducible transcription. In aggregate, these data indicate that signalling in response to Urea in renal medullary cells requires EGF receptor transactivation, probably through autocrine action of HB-EGF. C1 Oregon Hlth Sci Univ, Div Nephrol, Dept Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Dev & Cell Biol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. RP Cohen, DM (reprint author), Oregon Hlth Sci Univ, Div Nephrol, Dept Med, Mailcode PP262,3314 SW US Vet Hosp Rd, Portland, OR 97201 USA. NR 60 TC 11 Z9 11 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAR 1 PY 2003 VL 370 BP 479 EP 487 DI 10.1042/BJ20020565 PN 2 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 654BB UT WOS:000181471700013 PM 12466022 ER PT J AU Bartzokis, G Nuechterlein, KH Lu, PH Gitlin, M Rogers, S Mintz, J AF Bartzokis, G Nuechterlein, KH Lu, PH Gitlin, M Rogers, S Mintz, J TI Dysregulated brain development in adult men with schizophrenia: A magnetic resonance imaging study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; brain; development; myelin; MRI; white matter; gray matter ID CHILDHOOD-ONSET SCHIZOPHRENIA; PREFRONTAL GRAY-MATTER; HUMAN CEREBRAL-CORTEX; CORPUS-CALLOSUM SIZE; AGE-RELATED-CHANGES; WHITE-MATTER; EPISODE SCHIZOPHRENIA; NEUROLEPTIC-NAIVE; IN-VIVO; VOLUMES AB Background: Recent imaging evidence suggests that normal brain development/maturation of the frontal lobes and association areas is a well-regulated process consisting of continued myelination and expansion of white matter volumes into the late 40s accompanied by complementary reductions in gray matter volumes. The possibility that a dysregulation of this process may contribute to the syndrome of schizophrenia was investigated using magnetic resonance imaging. Methods: Fifty-two normal adult males and 35 males with schizophrenia underwent magnetic resonance imaging. Coronal images were acquired using pulse sequences that maximized myelin signal. The age-related change in the gray to white matter ratio was used as a measure of developmental dysregulation in the schizophrenic subjects and contrasted to the age-related changes of the normal control group. Results: Regression analyses on frontal and temporal gray to white matter ratio yielded highly significant interactions of diagnosis and age for both regions (p = .0003 and p =.01, respectively). In the normal group, both frontal and temporal gray to white matter ratios decreased significantly and linearly across the age range. In contrast, neither ratio showed meaningful age-related change in the schizophrenia group. Thus, differences in gray to white matter ratio between the groups increased markedly with age, driven primarily by the absence of a white matter volume expansion in the patient group. Conclusions: The absence of the normal complementary volume changes in the gray and white matter with age in the schizophrenic sample suggests that this dynamic developmental process is dysregulated in adult schizophrenic subjects. The importance of myelination to the continued maturation and normal functioning of the brain has implications for the diagnosis, treatment, and prognosis of schizophrenia. C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Alzheimers Dis Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Div Brain Mapping,Lab Neuroimaging, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat, Los Angeles, CA 90095 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. RP Bartzokis, G (reprint author), Univ Calif Los Angeles, Sch Med, Dept Neurol, Alzheimers Dis Ctr, 710 Westwood Plaza,RNRC,Room 2-238, Los Angeles, CA 90095 USA. RI Bartzokis, George/K-2409-2013 FU NIMH NIH HHS [MH-51928, MH-37705, MH-30911] NR 74 TC 83 Z9 86 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 2003 VL 53 IS 5 BP 412 EP 421 DI 10.1016/S0006-3223(03)01835-8 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 649RA UT WOS:000181220700006 PM 12614994 ER PT J AU Chan, GW Gorgun, G Miller, KB Foss, FM AF Chan, GW Gorgun, G Miller, KB Foss, FM TI Persistence of host dendritic cells after transplantation is associated with graft-versus-host disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE dendritic cells; transplant; graft-versus-host disease (GVHD); chimerism ID BONE-MARROW TRANSPLANTATION; BLOOD STEM-CELL; EXTRACORPOREAL PHOTOCHEMOTHERAPY; HEMATOLOGIC MALIGNANCIES; PREPARATIVE REGIMENS; CHIMERISM; DEPLETION; THERAPY; FUTURE; GVHD AB Graft-versus-host disease (GVHD) causes significant morbidity and mortality in patients undergoing allogeneic bone marrow transplantation following either a conventional or reduced-intensity preparative regimen. In a murine model, inactivation of host dendritic cells (DCs) was associated with a significant reduction in acute GVHD, suggesting that host DCs may play an important role in the pathogenesis of acute GVHD. The role of host DCs in the development of GVHD following allogeneic stem cell transplantation in humans, however, is unclear. We examined DC chimerism in patients with various hematologic malignancies who underwent a reduced-intensity preparative regimen of extracorporeal photophoresis, pentostatin, and reduced-dose total body irradiation (n = 21) or a conventional preparative regimen of cyclophosphamide and total body irradiation (n = 3). Full donor hematopoietic reconstitution was demonstrated in 19 of 21 patients who underwent a reduced-intensity preparative regimen and in all patients who underwent a conventional preparative regimen. Grade 0 to I acute GVHD and limited or no chronic GVHD were observed in 18 patients who underwent a reduced-intensity regimen and 1 patient who underwent a conventional regimen who achieved full donor DC chimerism at day +100 posttransplantation. In contrast, grade H to IV acute GVHD and extensive chronic GVHD were observed in the 2 patients who underwent a conventional regimen and the I patient who underwent a reduced-intensity regimen who had host rather than donor DC chimerism. The persistence of host DCs at day +100 posttransplantation is correlated with the development of severe acute and chronic GVHD (P = .001). Host DCs may represent a therapeutic target for reducing GVHD in allogeneic bone marrow transplants. (C) 2003 American Society for Blood and Marrow Transplantation. C1 Tufts Univ, New England Med Ctr, Dept Med, Div Hematol Oncol, Boston, MA 02111 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Foss, FM (reprint author), Lymphoma Serv, 750 Washington St,Box 245, Boston, MA 02111 USA. NR 30 TC 51 Z9 53 U1 0 U2 1 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD MAR PY 2003 VL 9 IS 3 BP 170 EP 176 DI 10.1053/bbmt.2003.50006 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 661ZK UT WOS:000181920400004 PM 12652467 ER PT J AU Li, Y Lin, XH AF Li, Y Lin, XH TI Testing the correlation for clustered categorical and censored discrete time-to-event data when covariates are measured without/with errors SO BIOMETRICS LA English DT Article DE clustered data; frailty models; grouped survival data; longitudinal data; polytomous responses; random effects; score test; SIMEX; variance components ID MODELS; SURVIVAL AB In the analysis of clustered categorical data, it is of common interest to test for the correlation within clusters, and the heterogeneity across different clusters. We address this problem by proposing a class of score tests for the null hypothesis that the variance components are zero in random effects models, for clustered nominal and ordinal categorical responses. We extend the results to accommodate clustered censored discrete time-to-event data. We next consider such tests in the situation where covariates are measured with errors. We propose using the SIMEX method to construct the score tests for the null hypothesis that the variance components are zero. Key advantages of the proposed score tests are that they can be easily implemented by fitting standard polytomous regression models and discrete failure time models, and that they are robust in the sense that no assumptions need to be made regarding the distributions of the random effects and the unobserved covariates. The asymptotic properties of the proposed tests are studied. We illustrate these tests by analyzing two data sets and evaluate their performance with simulations. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. RP Li, Y (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. NR 15 TC 2 Z9 2 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 2003 VL 59 IS 1 BP 25 EP 35 DI 10.1111/1541-0420.00004 PG 11 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 663GG UT WOS:000181997400004 PM 12762438 ER PT J AU Dudoit, S Gendeman, RC Quackenbush, J AF Dudoit, S Gendeman, RC Quackenbush, J TI Open source software for the analysis of microarray data SO BIOTECHNIQUES LA English DT Article ID GENE-EXPRESSION PATTERNS; MOLECULAR CLASSIFICATION; DNA MICROARRAY; CARCINOMAS; CANCER AB DNA microarray assays represent the first widely used application that attempts to build upon the information provided by genome projects in the study of biological questions. One of the greatest challenges with working with microarrays is collecting, managing, and analyzing data. Although several commercial and noncommercial solutions exist, there is a growing body of freely available, open source software that allows users to analyze data using a host of existing techniques and to develop their own and integrate them within the system. Here we review three of the most widely used and comprehensive systems, the statistical analysis tools written in R through the Bioconductor project (http://www.bioconductor.org), the Java(R)-based TM4 software system available from The Institute for Genomic Research (http://www.tigr.org/software), and BASE, the Web-based system developed at Lund University (http://base.thep.lu.se). C1 Inst Genom Res, Rockville, MD 20858 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. RP Quackenbush, J (reprint author), Inst Genom Res, 9712 Med Ctr Dr, Rockville, MD 20858 USA. FU NCI NIH HHS [U01-CA8552-01A1]; NHLBI NIH HHS [U01 HL66580-01, 1 R33 HL3712-01]; NLM NIH HHS [R01 LM007609-01] NR 40 TC 156 Z9 161 U1 1 U2 7 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD MAR PY 2003 SU S BP 45 EP 51 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 656EM UT WOS:000181595900007 PM 12664684 ER PT J AU Chan, C Hwang, D Stephanopoulos, GN Yarmush, ML Stephanopoulos, G AF Chan, C Hwang, D Stephanopoulos, GN Yarmush, ML Stephanopoulos, G TI Application of multivariate analysis to optimize function of cultured hepatocytes SO BIOTECHNOLOGY PROGRESS LA English DT Article ID BIOARTIFICIAL LIVER; GLYCOGEN-SYNTHESIS; HUMAN PLASMA; KREBS CYCLE; AMINO-ACID; RAT-LIVER; GLUCOSE; CLASSIFICATION; FAILURE; FLUXES AB Understanding the metabolic and regulatory pathways of hepatocytes is important for biotechnological applications involving liver cells, including the development of bioartificial liver (BAL) devices. To characterize intermediary metabolism in the hepatocytes, metabolic flux analysis (MFA) was applied to elucidate the changes in intracellular pathway fluxes of primary rat hepatocytes exposed to human plasma and to provide a comprehensive snapshot of the hepatic metabolic profile. In the current study, the combination of preconditioning and plasma supplementation produced distinct metabolic states. Combining the metabolic flux distribution obtained by MFA with methodologies such as Fisher discriminant analysis (FDA) and partial least squares or projection to latent structures (PLS) provided insights into the underlying structure and causal relationship within the data. With the aid of these analyses, patterns in the cellular response of the hepatocytes that contributed to the separation of the different hepatic states were identified. Of particular interest was the recognition of distal pathways that strongly correlated with a particular hepatic function. The hepatic functions investigated were intracellular triglyceride accumulation and urea production. This study illustrates a framework for optimizing hepatic function and a possibility of identifying potential targets for improving hepatic functions. C1 Michigan State Univ, Dept Chem Engn & Mat Sci, E Lansing, MI 48824 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Engn Med, Surg Serv, Boston, MA 02114 USA. Shriners Hosp Children, E Lansing, MI 48824 USA. RP Chan, C (reprint author), Michigan State Univ, Dept Chem Engn & Mat Sci, E Lansing, MI 48824 USA. NR 39 TC 36 Z9 39 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD MAR-APR PY 2003 VL 19 IS 2 BP 580 EP 598 DI 10.1021/bp025660h PG 19 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 665LH UT WOS:000182121800049 PM 12675604 ER PT J AU Rasmussen, SA Olney, RS Holmes, LB Lin, AE Keppler-Noreuil, KM Moore, CA AF Rasmussen, SA Olney, RS Holmes, LB Lin, AE Keppler-Noreuil, KM Moore, CA CA National Birth Defects Prevention TI Guidelines for case classification for the national birth defects prevention study SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article ID NEURAL-TUBE DEFECTS; CONOTRUNCAL HEART-DEFECTS; LIP AND/OR PALATE; ETIOLOGIC HETEROGENEITY; CONGENITAL-ANOMALIES; VASCULAR DISRUPTION; VACTERL-ASSOCIATION; CHARGE ASSOCIATION; MALFORMATIONS; EPIDEMIOLOGY AB BACKGROUND: Previous studies have suggested that etiologic heterogeneity may complicate epidemiologic analyses designed to identify risk factors for birth defects. Case classification uses knowledge of embryologic and pathogenetic mechanisms to make case groups more homogeneous and is important to the success of birth defects studies. METHODS: The goal of the National Birth Defects Prevention Study (NBDPS), an ongoing multi-site case-control study, is to identify environmental and genetic risk factors for birth defects. Information on environmental risk factors is collected through an hour-long maternal interview, and DNA is collected from the infant and both parents for evaluation of genetic risk factors. Clinical data on infants are reviewed by clinical geneticists to ensure they meet the detailed case definitions developed specifically for the study. To standardize the methods of case classification for the study, an algorithm has been developed to guide NBDPS clinical geneticists in this process. RESULTS: Methods for case classification into isolated, multiple, and syndrome categories are described. Defects considered minor for the purposes of case classification are defined. Differences in the approach to case classification for studies of specific defects and of specific exposures are noted. CONCLUSIONS: The case classification schema developed for the NBDPS may be of value to other clinicians working on epidemiologic studies of birth defects etiology. Consideration of these guidelines will lead to more comparable case groups, an important element of careful studies aimed at identifying risk factors for birth defects. (C) 2003 Wiley-Liss, Inc. C1 Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30341 USA. Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, Boston, MA 02114 USA. Univ Iowa Hosp & Clin, Dept Pediat, Div Med Genet, Iowa City, IA 52242 USA. RP Rasmussen, SA (reprint author), Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, 4770 Buford Highway,NE,MS F45, Atlanta, GA 30341 USA. RI Publications, NBDPS/B-7692-2013 NR 50 TC 310 Z9 312 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAR PY 2003 VL 67 IS 3 BP 193 EP 201 DI 10.1002/bdra.10012 PG 9 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 720XD UT WOS:000185286600008 PM 12797461 ER PT J AU Sacco, DE Daller, M Grocela, JA Babayan, RK Zietman, AL AF Sacco, DE Daller, M Grocela, JA Babayan, RK Zietman, AL TI Corticosteroid use after prostate brachytherapy reduces the risk of acute urinary retention SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; brachytherapy; urinary retention ID RADIOACTIVE SEED IMPLANTATION; CANCER; MORBIDITY; COMPLICATIONS; I-125 AB OBJECTIVES To evaluate the role of short-term steroids after prostate brachytherapy to reduce oedema and thus the risk of urinary retention associated with brachytherapy, as this can require surgical intervention and may even result in incontinence. PATIENTS AND METHODS A retrospective review was conducted on 400 consecutive patients with early-stage prostate cancer who underwent ultrasonography-guided transperineal brachytherapy. Androgen deprivation was given to 146 patients for 3 months before the implant and 280 received a 2-week course of dexamethasone (4 mg twice daily for 1 week then 2 mg twice daily). Forty-five patients developed acute urinary retention at a median of 12 days after implantation. Univariate and multivariate analyses were used to evaluate the potential risk factors for urinary retention. RESULTS Acute urinary retention developed in 11.1% of the patients and the risk was predicted by increasing prostate volume at the time of diagnosis. This risk was higher (18.8%) for men receiving no dexamethasone and lower (8.2%) for those who did. In the multivariate analysis the volume at diagnosis and the use of dexamethasone remained significant. The use of steroids counterbalanced the effect of increasing prostate volume on the incidence of retention. The risk of retention was higher in those men receiving androgen deprivation to shrink their prostates than in those whose prostates were of suitable size for implantation at the time of diagnosis. CONCLUSION Reducing prostate volume by androgen deprivation before brachytherapy may be less important in preventing brachytherapy-related urinary retention than the use of corticosteroids to reduce oedema afterward. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Boston Med Ctr, Dept Urol, Boston, MA USA. RP Zietman, AL (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 18 TC 15 Z9 17 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD MAR PY 2003 VL 91 IS 4 BP 345 EP 349 DI 10.1046/j.1464-4096.2003.04082.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 649VH UT WOS:000181228300016 PM 12603412 ER PT J AU Rossi, HA Becker, PS Emmons, RVB Westervelt, P Levy, W Liu, Q Clark, Y Ballen, K AF Rossi, HA Becker, PS Emmons, RVB Westervelt, P Levy, W Liu, Q Clark, Y Ballen, K TI High-dose cyclophosphamide, BCNU, and VP-16 (CBV) conditioning before allogeneic stem cell transplantation for patients with non-Hodgkin's lymphoma SO BONE MARROW TRANSPLANTATION LA English DT Article DE non-Hodgkin lymphoma; stem cell transplantation; allogeneic; conditioning therapy; carmustine ID BONE-MARROW TRANSPLANTATION; CHRONIC LYMPHOCYTIC-LEUKEMIA; TOTAL-BODY IRRADIATION; AUTOLOGOUS TRANSPLANTATION; PREPARATIVE REGIMEN; DISEASE; ETOPOSIDE; CARMUSTINE; CHEMOTHERAPY; THERAPY AB Allogeneic stem cell transplantation (SCT) has been shown to be a curative therapy for some patients with non-Hodgkin's lymphoma (NHL). Total-body irradiation and high-dose cyclophosphamide combinations are the most established conditioning regimens used in this setting. We examined the efficacy and toxicity of cyclophosphamide, BCNU, and VP-16 (CBV) as a suitable chemotherapy-only regimen for NHL patients. In total, 18 patients, median age 42 years, with NHL were treated with CBV followed by allotransplant. Patients had received a median of two prior chemotherapy regimens. Median times to neutrophil and platelet recovery were 19 and 15 days, respectively. Interstitial pneumonitis occurred in one patient. There have been four relapses after a median follow-up of 39 months. Overall, there were four deaths, one because of relapse. The 2-year estimates of relapse-free and overall survival are 56 and 76%, respectively. CBV is a safe and an effective alternative to TBI-containing regimens before allogeneic SCT for NHL. C1 Umass Med Healthcare, Div Hematol & Oncol, Worcester, MA 01655 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA USA. Univ Massachusetts, Sch Med, Ctr Canc, Worcester, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rossi, HA (reprint author), Umass Med Healthcare, Div Hematol & Oncol, 55 Lake Ave N, Worcester, MA 01655 USA. NR 43 TC 9 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2003 VL 31 IS 6 BP 441 EP 446 DI 10.1038/sj.bmt.1703874 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 666KV UT WOS:000182177200005 PM 12665838 ER PT J AU Hamer, HM Luders, HO Knake, S Fritsch, B Oertel, WH Rosenow, F AF Hamer, HM Luders, HO Knake, S Fritsch, B Oertel, WH Rosenow, F TI Electrophysiology of focal clonic seizures in humans: a study using subdural and depth electrodes SO BRAIN LA English DT Article DE clonic; tonic; seizure; subthalamic nucleus; human ID DEEP BRAIN-STIMULATION; SUBTHALAMIC NUCLEUS; BASAL GANGLIA; EPILEPTIC SEIZURES; MOTOR CORTEX; EEG AB Focal clonic seizures are a frequent epileptic phenomenon. However, there are few data about their pathogenesis. Eleven patients with focal epilepsy who experienced focal clonic seizures during prolonged video-EEG monitoring were included in this study. Nine patients had subdural electrodes on the precentral gyrus and one patient had additional bilateral subthalamic nucleus (STN) depth electrodes. In five patients, the EEG was co-registered with the EMG of muscles which were involved in the clonic seizures. The frequency, pattern and evolution of the ictal EEG were analysed and their relationship to STN and EMG activity was studied. Focal clonic seizures were always associated with a polyspike-wave pattern in the EEG of the primary motor area (frequency range 1.6-3.4 Hz), while neighbouring electrodes not overlying the precentral gyrus showed different EEG patterns. At seizure onset, the ictal EEG derived from the precentral gyrus consisted of repetitive spiking for 8-28 s (median 19.5 s), accompanied by a continuous increase in muscle tone. This evolved to a pattern of polyspike-wave complexes which were associated with clinical clonus and lasted for 14-202 s (median 30.5 s). The clonic muscle contractions consisted of bursts of compound muscle action potentials (CMAPs) which occurred synchronously in agonistic and antagonistic muscles and were separated by periods of complete muscle relaxation. Each series of CMAPs followed the polyspikes in the EEG with a latency of 17-50 ms. The periods of muscle relaxation occurred during the EEG slow waves. Only some of the cortical spikes were followed by ipsilateral STN spikes. CMAPs followed the cortical polyspikes independently of whether or not STN spikes were seen. The study suggests that focal clonic seizures are focal tonic-clonic seizures. The epileptic clonus consisted of simultaneous contractions of agonistic and antagonistic muscles at regular intervals and was generated by localized polyspike-wave activity in cortical primary motor areas. Activation of the STN did not appear to be an essential component of clonic seizures. C1 Univ Marburg, Dept Neurol, D-35033 Marburg, Germany. Cleveland Clin Fdn, Dept Neurol, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, NMR Ctr, Boston, MA 02114 USA. RP Hamer, HM (reprint author), Univ Marburg, Dept Neurol, Rudolf Bultmann Str 8, D-35033 Marburg, Germany. OI Fritsch, Brita/0000-0003-4884-9049 NR 19 TC 14 Z9 14 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAR PY 2003 VL 126 BP 547 EP 555 DI 10.1093/brain/awg051 PN 3 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 652XY UT WOS:000181407200004 PM 12566276 ER PT J AU McNamara, P Durso, R AF McNamara, P Durso, R TI Pragmatic communication skills in patients with Parkinson's disease SO BRAIN AND LANGUAGE LA English DT Article DE pragmatics; communication; Parkinson's disease; frontal lobes; unawareness ID MONITORING SKILLS; BRAIN-DAMAGE; LANGUAGE; IMPAIRMENTS; CLINICIAN; ABILITY; INJURY AB Background. Pragmatic communication abilities may depend on intact frontal lobe systems. Independent evidence suggests that some persons with Parkinson's disease (PD) are impaired on measures of frontal lobe function. Hypothesis. We therefore hypothesized in Study I that pragmatic communication skills would be impaired in some persons with PD and would be linked to frontal dysfunction in these patients. In Study 2 we hypothesized that PD patients would be unaware of their pragmatic communication deficits. Methods. In Study I we administered tests of pragmatic abilities and frontal lobe functioning to twenty-two persons with Parkinson's disease (PD) and 10 healthy controls. In Study 2 we obtained self-ratings of pragmatic abilities from 11 PD patients and then checked these self-ratings against ratings of these same abilities by the patient's spouses. Results. We found in Study I that patients with PD were: (a) significantly impaired on measures of pragmatic communication abilities, especially in the areas of conversational appropriateness, turn-taking, prosodics and proxemics, and that this impairment was significantly related to measures of frontal lobe function. In study 2 we found that PD patients overestimated their own abilities relative to spousal ratings of those abilities and thus were unaware of the extent of their problems with pragmatic social communication skills. Conclusion. We conclude that pragmatic social communication skills are impaired in PD and that this impairment may be related to frontal lobe dysfunction. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Boston VA Healthcare Syst, Boston, MA 02130 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. RP McNamara, P (reprint author), Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. EM mcnamar@bu.edu NR 34 TC 45 Z9 47 U1 1 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD MAR PY 2003 VL 84 IS 3 BP 414 EP 423 DI 10.1016/S0093-934X(02)00558-8 PG 10 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 665UX UT WOS:000182140600007 PM 12662979 ER PT J AU Kogai, T Kanamoto, Y Brent, GA AF Kogai, T Kanamoto, Y Brent, GA TI The modified firefly luciferase reporter gene (luc+) but not Renilla luciferase is induced by all-trans retinoic acid in MCF-7 breast cancer cells SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE all-trans retinoic acid; MCF-7 cells; modified firefly luciferase; Renilla luciferase; reporter assay ID THYROID-HORMONE RECEPTOR; DIMETHYL-SULFOXIDE; GROWTH-INHIBITION; EXPRESSION; PROMOTER; BETA; MODULATION; ELEMENT; METABOLISM; INDUCTION AB Luciferase genes are widely used as reporters to analyze promoter and regulatory elements. We found that a luciferase reporter gene vector with a modified firefly luciferase gene (luc+), but not Renilla luciferase (Rluc), was induced by all-trans retinoic acid (tRA) in the MCF-7 breast cancer cell line. tRA (5 x 10(-6) M) increased luciferase activity of the pGL3 promoter vector (containing luc+)up to similar to3.8-fold in MCF-7 cells, but not in LNCaP prostate cancer cells or JEG-3 choriocarcinoma cells. Chimeric plasmids were constructed and showed that tRA-induction required the luc+ gene, but not any specific promoter or vector sequence. Time course and dose-response studies of tRA-induction indicated that longer treatment (>24 h) and higher tRA dose (>10(-6) M) were required for luc+ induction compared with those for a positive retinoic acid response element (maximum induction at 6 h and 10(-8) M tRA). Studies with the translation inhibitor, cycloheximide, indicated the half-life of the luc+ protein was increased from 9.7 +/- 1.5 to 22.1 +/- 3.1 h with tRA treatment. Other retinoids, TTNPB, a retinoic acid receptor beta/gamma-specific ligand, and a retinoid X receptor ligand, did not significantly increase luc+ expression. Caution is needed in analysis of retinoid responsive gene regulation with the luciferase reporter system in MCF-7 cells, especially at high retinoid concentrations. C1 VA Greater Los Angeles Healthcare Syst, Mol Endocrinol Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Physiol, Los Angeles, CA 90024 USA. RP Brent, GA (reprint author), VA Greater Los Angeles Healthcare Syst, Mol Endocrinol Lab, 11301 Wilshire Blvd,Bldg 114,Room 230, Los Angeles, CA 90073 USA. FU NCI NIH HHS [CA8936401] NR 39 TC 13 Z9 14 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD MAR PY 2003 VL 78 IS 1 BP 119 EP 126 DI 10.1023/A:1022179717847 PG 8 WC Oncology SC Oncology GA 639WD UT WOS:000180651700014 PM 12611464 ER PT J AU Abe, S Yamamoto, Y Uno, S Andou, M Akasaka, T Mihm, MC AF Abe, S Yamamoto, Y Uno, S Andou, M Akasaka, T Mihm, MC TI Malignant melanoma arising in a sebaceous nevus of the scalp SO BRITISH JOURNAL OF PLASTIC SURGERY LA English DT Article DE malignant melanoma; sebaceous nevus; scalp; nine years follow-up ID JADASSOHN AB This is the first report of malignant melanoma arising from sebaceous nevus (SN) of the scalp, although it has been known that various benign and malignant neoplasms may develop in association with SN. After the excisional biopsy for SN with 5 mm free margin, pathological examination revealed the coexistence of nodular melanoma invading to the reticular dermis (IV level of Clark) for a maximal depth of 4 nun. After resection with another 20 mm free margin, there has been no evidence of local recurrence or distant metastasis for nine years. (C) 2003 The British Association of Plastic Surgeons. Published by Elsevier Science Ltd. All rights reserved. C1 Asahikawa Red Cross Hosp, Dept Plast & Reconstruct Surg, Asahikawa, Hokkaido 0708530, Japan. Iwate Med Univ, Dept Dermatol, Morioka, Iwate 020, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Asahikawa Red Cross Hosp, Dept Clin Pathol, Asahikawa, Hokkaido 0708530, Japan. RP Abe, S (reprint author), Asahikawa Red Cross Hosp, Dept Plast & Reconstruct Surg, 1-1 Akebono, Asahikawa, Hokkaido 0708530, Japan. NR 11 TC 11 Z9 12 U1 0 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-1226 J9 BRIT J PLAST SURG JI Br. J. Plast. Surg. PD MAR PY 2003 VL 56 IS 2 BP 171 EP 173 DI 10.1016/S0007-1226(03)00041-9 PG 3 WC Surgery SC Surgery GA 694DQ UT WOS:000183758900021 PM 12791367 ER PT J AU Shekelle, P AF Shekelle, P TI New contract for general practitioners - A bold initiative to improve quality of care, but implementation will be difficult SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material C1 Univ Calif Los Angeles, Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90073 USA. RP Shekelle, P (reprint author), Univ Calif Los Angeles, Greater Los Angeles Vet Affairs Healthcare Syst, 11731 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 2 TC 56 Z9 57 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD MAR 1 PY 2003 VL 326 IS 7387 BP 457 EP 458 DI 10.1136/bmj.326.7387.457 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 653EC UT WOS:000181421400001 PM 12609914 ER PT J AU Earle, CC Agboola, O Maroun, J Zuraw, L AF Earle, CC Agboola, O Maroun, J Zuraw, L CA Canc Care Ontario Practice Guide TI The treatment of locally advanced pancreatic cancer: A practice guideline SO CANADIAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE advanced pancreatic cancer; practice guideline; treatment ID ONCOLOGY-GROUP; 5-FLUOROURACIL; THERAPY; ADENOCARCINOMA; RADIOTHERAPY; SURVIVAL; TRIAL AB BACKGROUND: Pancreatic adenocarcinoma is the fourth most common cause of adult cancer death. About 50% of patients present with metastatic disease, 20% with resectable disease and the remaining 30% of patients are diagnosed with incurable, locally advanced unresectable but nonmetastatic pancreatic cancer. OBJECTIVES: To evaluate the current evidence regarding treatment of incurable, locally advanced, unresectable but nonmetastatic pancreatic cancer and produce an evidence-based practice guideline. METHODS: A systematic review of the literature was performed. The MEDLINE, CANCERLIT, and Cochrane Library databases were searched using the following medical subject heading search terms: 'pancreatic neoplasms', 'chemotherapy, adjuvant', 'radiotherapy', 'immunotherapy', combined with the text words: 'chemotherapy', 'radiotherapy', 'radiation', 'immunotherapy', combined with terms for the following study designs or publication types: practice guidelines, meta-analyses and randomized controlled trials. The Physician Data Query clinical trials database and the proceedings of the annual meetings of the American Society of Clinical Oncology (1996 to 2001) and the American Society for Therapeutic Radiology and Oncology (1999 to 2001) were searched for reports of new or ongoing trials. Relevant literature was selected and reviewed independently, and the reference lists from these sources were searched for additional trials. Interpretation of evidence was resolved by consensus. RESULTS: Eight randomized trials were obtained that met the inclusion criteria. CONCLUSIONS: Recommendations are to offer combined chemotherapy and radiotherapy to suitable patients. The preferred chemotherapeutic agent to combine with radiotherapy is bolus or infusional 5-fluorouracil, but the optimal mode and duration of 5-fluorouracil delivery is unclear. Chemotherapy alone with gemcitabine is an acceptable alternative. C1 Ottawa Reg Canc Ctr, Gen Div, Gastrointestinal Canc Dis Site Grp, Ottawa, ON K1H 8L6, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. RP Ottawa Reg Canc Ctr, Gen Div, Gastrointestinal Canc Dis Site Grp, 501 Smyth Rd, Ottawa, ON K1H 8L6, Canada. EM jean.maroun@cancercare.on.ca NR 20 TC 7 Z9 8 U1 0 U2 1 PU HINDAWI PUBLISHING CORP PI NEW YORK PA 315 MADISON AVE 3RD FLR, STE 3070, NEW YORK, NY 10017 USA SN 2291-2797 J9 CAN J GASTROENTEROL JI Can. J. Gastroenterol. Hepatol. PD MAR PY 2003 VL 17 IS 3 BP 161 EP 167 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 659RJ UT WOS:000181791000001 PM 12677264 ER PT J AU Trihia, H Murray, S Price, K Gelber, RD Golouh, R Goldhirsch, A Coates, AS Collins, J Castiglione-Gertsch, M Gusterson, BA AF Trihia, H Murray, S Price, K Gelber, RD Golouh, R Goldhirsch, A Coates, AS Collins, J Castiglione-Gertsch, M Gusterson, BA CA Int Breast Canc Study Grp TI Ki-67 expression in breast carcinoma - Its association with grading systems, clinical parameters, and other prognostic factors - A surrogate marker? SO CANCER LA English DT Article DE Ki-67; MIB-1; breast carcinoma; histologic grade; Nottingham grade; Bloom-Richardson grade ID LYMPH-NODE METASTASIS; MONOCLONAL-ANTIBODY KI-67; CELL-CYCLE ANALYSIS; TERM FOLLOW-UP; HISTOLOGIC GRADE; ADJUVANT THERAPY; FLOW-CYTOMETRY; PARAFFIN SECTIONS; GROWTH FRACTION; RECEPTOR STATUS AB BACKGROUND. The number of mitoses and, thus, the proliferative capacity of a tumor is one of the most crucial variables for tumor grading. The Ki-67 nuclear antigen may be considered as an alternative to mitotic counts in grading schemes and as a single parameter that can be used in fine-needle aspirates and small biopsies. METHODS. Immunohistochemistry using the anti-Ki-67 antibody MIB-1 was performed on 434 breast carcinoma specimens from the International Breast Cancer Study Group (formerly Ludwig) Trial V. Three groups based on Ki-67 percent were used to replace the mitotic counts component in the Nottingham grade (NHG) to produce the Nottingham/Ki-67 grade (NKG) and to assess Ki-67 as a single parameter. RESULTS. In both the lymph node positive subgroup and the lymph node negative subgroup, the NKG and Ki-67 group was correlated significantly with Bloom-Richardson grade (BRG), NHG, and Nottingham type. Tumor size in the lymph node negative cohort and estrogen receptor status, progesterone receptor status, and c-erbB-2 expression in the lymph node positive cohort also were correlated significantly with NKG. Ki-67 percentage was correlated significantly with c-erbB-2 expression in the lymph node positive cohort only. NKG was similar to BRG and NHG when it was evaluated for prognostic significance. Patients with higher categoric Ki-67 percentages had worse overall and disease free survival in all groups except for the untreated, lymph node negative group. CONCLUSIONS. Ki-67 detection represents a valuable tool and is a good objective substitute for mitotic counts when used in a grading system. When it is used alone, Ki-67 detection provides valuable information, although it is necessary to combine this with other parameters in the study of core biopsies and fine-needle aspirates. (C) 2003 American Cancer Society. C1 Univ Glasgow, Western Infirm, Dept Pathol, Pathol Ctr,Int Breast Canc Study Grp, Glasgow G11 6NT, Lanark, Scotland. Int Breast Canc Study Grp, Ctr Stat, Boston, MA USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Inst Oncol, Dept Pathol, Ljubljana, Slovenia. Ist Europeo Oncol, Milan, Italy. Oncol Inst So Switzerland, Lugano, Switzerland. Canc Council Australia, Sydney, NSW, Australia. Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia. Royal Melbourne Hosp, Dept Surg, Melbourne, Vic, Australia. Int Breast Canc Study Grp, Coordinating Ctr, Bern, Switzerland. Univ Glasgow, Dept Pathol, Glasgow G12 8QQ, Lanark, Scotland. RP Gusterson, BA (reprint author), Univ Glasgow, Western Infirm, Dept Pathol, Pathol Ctr,Int Breast Canc Study Grp, Glasgow G11 6NT, Lanark, Scotland. RI gusterson, barry/D-3752-2009 FU NCI NIH HHS [CA-75362] NR 68 TC 107 Z9 113 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 1 PY 2003 VL 97 IS 5 BP 1321 EP 1331 DI 10.1002/cncr.11188 PG 11 WC Oncology SC Oncology GA 649CU UT WOS:000181190000024 PM 12599241 ER PT J AU Li, Y Chen, W Ren, J Yu, WH Li, Q Yoshida, K Kufe, D AF Li, Y Chen, W Ren, J Yu, WH Li, Q Yoshida, K Kufe, D TI DF3/MUC1 signaling in multiple myeloma cells is regulated by intarleukin-7 SO CANCER BIOLOGY & THERAPY LA English DT Article DE MUC1; IL-7; multiple myeloma; Lyn; beta-catenin ID CARCINOMA-ASSOCIATED ANTIGEN; PROTEIN-TYROSINE KINASE; BETA-CATENIN; FUNCTIONAL INTERACTION; INTERLEUKIN-7; GENE; LYN; EXPRESSION; ACTIVATION; RECEPTOR AB The human DF3/MUC1 transmembrane protein is aberrantly expressed in multiple myeloma cells and other B cell malignancies. The regulation of MUC1 in B cells and its potential function as a signaling molecule ore unknown. The present results demonstrate that interleukin-7 (IL-7) stimulates MUC1 expression in multiple myeloma cells. The results also demonstrate the IL-7 induces binding of MUC1 to the Lyn tyrosine kinase. The MUC1 C-terminal subunit binds directly to Lyn through interactions with the Lyn SH3 and SH2 domains. Activation of Lyn in response to IL-7 stimulation results in increased tyrosine phosphorylation of the MUC1 C-terminal subunit. In vitro and in vivo studies show that Lyn phosphorylates MUC1, at least in large part, on a YEKV life in the MUC1 cytoplasmic tail. The functional significance of the MUC1-Lyn interaction is supported by the demonstration that Lyn-mediated phosphorylation of MUC1 on YEKV induces binding of MUC1 and the beta-catenin signaling protein. In concert with these results, IL-7 treatment is associated with binding of MUC1 to beta-catenin and targeting of the MUC1-beta-catenin complex to the nucleus. These findings indicate that IL-7 regulates MUC1 expression and function in multiple myeloma cells. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA097098, CA100707] NR 34 TC 57 Z9 60 U1 1 U2 1 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 MAR-APR PY 2003 VL 2 IS 2 BP 187 EP 193 PG 7 WC Oncology SC Oncology GA 688PU UT WOS:000183445200013 PM 12750561 ER PT J AU Dolma, S Lessnick, SL Hahn, WC Stockwell, BR AF Dolma, S Lessnick, SL Hahn, WC Stockwell, BR TI Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells SO CANCER CELL LA English DT Article ID DNA TOPOISOMERASE-I; PROTEIN PHOSPHATASE 2A; HUMAN CANCER; CLEAVABLE COMPLEXES; SUBUNIT INTERACTION; DRUG CAMPTOTHECIN; MAMMALIAN PROTEIN; REPLICATION FORKS; ANTICANCER DRUG; TYROSINE KINASE AB We used synthetic lethal high-throughput screening to interrogate 23,550 compounds for their ability to kill engineered tumorigenic cells but not their isogenic normal cell counterparts. We identified known and novel compounds with genotype-selective activity, including doxorubicin, daunorubicin, mitoxantrone, camptothecin, sangivamycin, echinomycin, bouvardin, NSC146109, and a novel compound that we named erastin. These compounds have increased activity in the presence of hTERT, the SV40 large and small T oncoproteins, the human papillomavirus type 16 (HPV) E6 and E7 oncoproteins, and oncogenic HRAS. We found that overexpressing hTERT and either E7 or LT increased expression of topoisomerase 2alpha and that overexpressing RAS(V12) and ST both increased expression of topoisomerase I and sensitized cells to a nonapoptotic cell death process initiated by erastin. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Stockwell, BR (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. FU NCI NIH HHS [K01 CA94223, 1K08CA96755-01, 1R01CA97061-01, K08 CA096755-01, R01 CA097061] NR 59 TC 162 Z9 166 U1 2 U2 17 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAR PY 2003 VL 3 IS 3 BP 285 EP 296 DI 10.1016/S1535-6108(03)00050-3 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 662MP UT WOS:000181951400011 PM 12676586 ER PT J AU Bauer, S Corless, CL Heinrich, MC Dirsch, O Antoch, G Kanja, J Seeber, S Schutte, J AF Bauer, S Corless, CL Heinrich, MC Dirsch, O Antoch, G Kanja, J Seeber, S Schutte, J TI Response to imatinib mesylate of a gastrointestinal stromal tumor with very low expression of KIT SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE gastrointestinal stromal tumor; GIST; imatinib; KIT immunonegativity ID MUTATIONS; EFFICACY; ST1571; SAFETY AB More than 90% of gastrointestinal stromal tumors (GISTs) express the receptor tyrosine kinase KIT, and activating mutations of the KIT gene are detectable in the vast majority of these tumors. Imatinib mesylate (formerly STI571) is a potent inhibitor of KIT kinase activity and has been proven to be highly active in patients with unresectable or metastatic GIST expressing immunohistochemically detectable KIT protein. Here we report a patient with metastatic GIST who responded well to imatinib mesylate treatment despite the near absence of KIT expression in two different samples of his tumor. The tumor was morphologically typical for a GIST, stained positively for CD34, and harbored an in-frame deletion (WK 557-558) in KIT exon 11 that is common in GISTs. Our experience with this patient suggests that even GISTs with very low levels of KIT expression may respond to imatinib mesylate therapy. C1 Univ Essen Gesamthsch, Sch Med, Dept Internal Med Canc Res, Essen, Germany. Oregon Hlth Sci Univ, Dept Pathol, OHSU Canc Inst, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Med, OHSU Canc Inst, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Univ Essen Gesamthsch, Sch Med, Dept Pathol, Essen, Germany. Univ Essen Gesamthsch, Sch Med, Dept Diagnost & Intervent Radiol, Essen, Germany. Univ Essen Gesamthsch, Sch Med, Dept Nucl Med, Essen, Germany. Univ Klinikum Essen, Westdeutsch Tumorzentrum, Innere Klin & Poliklin Tumorforsch, D-5545122 Essen, Germany. RP Bauer, S (reprint author), Univ Essen Gesamthsch, Sch Med, Dept Internal Med Canc Res, Essen, Germany. RI Bauer, Sebastian/D-8120-2012 OI Bauer, Sebastian/0000-0001-5949-8120 NR 12 TC 53 Z9 61 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAR PY 2003 VL 51 IS 3 BP 261 EP 265 DI 10.1007/s00280-002-0564-x PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 671TF UT WOS:000182479600012 PM 12655446 ER PT J AU Li, FP DiGianni, LM AF Li, FP DiGianni, LM TI Reducing the unequal burden of cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Li, FP (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM fli@partners.org NR 9 TC 2 Z9 2 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2003 VL 12 IS 3 BP 230S EP 231S PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 658AC UT WOS:000181698600010 PM 12646515 ER PT J AU Chabner, BA AF Chabner, BA TI Cancer therapy and survivorship SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Chabner, BA (reprint author), Massachusetts Gen Hosp, 100 Blossom St, Boston, MA 02114 USA. EM bchabner@partners.org NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2003 VL 12 IS 3 BP 269S EP 269S PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 658AC UT WOS:000181698600020 PM 12646525 ER PT J AU Gilligan, TD Carrington, MA Sellers, TP Casal, L Schnipper, LE Li, FP AF Gilligan, TD Carrington, MA Sellers, TP Casal, L Schnipper, LE Li, FP TI Cancer survivorship issues for minority and underserved populations SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Li, FP (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM frederick_li@dfci.harvard.edu NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2003 VL 12 IS 3 BP 284S EP 286S PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 658AC UT WOS:000181698600023 PM 12646528 ER PT J AU Ehrlich, M Hopkins, NE Jinag, GC Dome, JS Yu, MC Woods, CB Tomlinson, GE Chintagumpala, M Champagne, M Dillerg, L Parham, DM Sawyer, J AF Ehrlich, M Hopkins, NE Jinag, GC Dome, JS Yu, MC Woods, CB Tomlinson, GE Chintagumpala, M Champagne, M Dillerg, L Parham, DM Sawyer, J TI Satellite DNA hypomethylation in karyotyped Wilms tumors SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID ICF SYNDROME; PERICENTROMERIC HETEROCHROMATIN; 5-METHYLCYTOSINE CONTENT; MULTIPLE-MYELOMA; METHYLATION; GENE; ACETYLATION; BINDING; CELLS; ACTIVATION AB Previously, a high percentage of Wilms tumors was found to be hypomethylated in the unusually long region of pericentromeric satellite DNA on chromosome 1. We now show that these pediatric cancers are also frequently hypomethylated in centromeric satellite DNA throughout the genome and compare satellite DNA hypomethylation with chromosome rearrangements. Relative to normal somatic tissues, 83% of the tumors were hypomethylated in centromeric satellite alpha DNA. This was assessed by blot hybridization under low-stringency conditions after digestion with CpG methylation-sensitive restriction endonucleases. Similar results were obtained with different enzymes, indicating generalized hypomethylation of centromeric DNA. Hypomethylation of another heterochromatic sequence, juxtacentromeric satellite 2 DNA of chromosome 1, was observed in 51% of the tumors. By cytogenetic analysis, rearrangements in the centromeric or juxtacentromeric heterochromatin of chromosome I were the most frequent structural aberration and were seen in 14% of the tumors. Tumors with such rearrangements had hypomethylation of satellite DNA in the pericentromeric region. These results show a high degree of targeting of DNA hypomethylation to centromeric and juxtacentromeric satellite DNA sequences in cancer and are consistent with satellite DNA hypomethylation contributing to, but not sufficing for, karyotypic instability in cancer and possibly playing other roles in carcinogenesis. (C) 2003 Elsevier Science Inc. All rights reserved. C1 Tulane Med Sch, Tulane Canc Ctr, New Orleans, LA USA. Tulane Med Sch, Human Genet Program, New Orleans, LA USA. St Jude Childrens Res Hosp, Dept Hematol Oncol, Memphis, TN 38105 USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. Univ Texas, SW Med Ctr, Dept Pediat, Dallas, TX 75230 USA. Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. Hop St Justine, Serv Hematol Oncol, Montreal, PQ H3T 1C5, Canada. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Arkansas Childrens Hosp, Dept Pathol, Little Rock, AR 72202 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. RP Ehrlich, M (reprint author), Tulane Med Sch, Tulane Canc Ctr, New Orleans, LA USA. EM ehrlich@tulane.edu FU NCI NIH HHS [CA 81506] NR 38 TC 52 Z9 56 U1 1 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 MAR PY 2003 VL 141 IS 2 BP 97 EP 105 AR PII S0165-4608(02)00668-4 DI 10.1016/S0165-4608(02)00668-4 PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 651PF UT WOS:000181328100002 PM 12606126 ER PT J AU Benjamin, R Capparella, J Brown, A AF Benjamin, R Capparella, J Brown, A TI Classification of glioblastoma multiforme in adults by molecular genetics SO CANCER JOURNAL LA English DT Article DE glioblastoma multiforme; oncogenes; tumor suppressor genes; cell cycle; FISH; laser capture microdissection; DNA microarray; gene therapy ID EPIDERMAL GROWTH-FACTOR; LASER CAPTURE MICRODISSECTION; FACTOR RECEPTOR GENE; LONG-TERM SURVIVORS; HUMAN GLIOMAS; BRAIN-TUMORS; SECONDARY GLIOBLASTOMAS; ASTROCYTIC TUMORS; MALIGNANT GLIOMAS; P53 MUTATIONS AB Recent advances in cytogenetic and molecular methodologies have elucidated certain principal characteristics of oncogenesis in glioblastoma multiforme. The earliest clues implicate gene sequence alterations, such as gene amplification and numerical gain or loss of function in specific chromosomes. Genetic classification and expression patterns have thus been constructed, conferring the likelihood of two types of glioblastoma, primary (de novo) as opposed to secondary (evolving from a pre-existing low-grade glioma). The former group of tumors exhibits more frequent occurrences of EGFR gene amplification, whereas the latter group relies strongly on TP53gene inactivation. Many other tumor suppressor genes and oncogenes have been discovered. Most gene alterations induce cell cycle dysfunction on a complex molecular level. Further insight into tumor genesis by means of genomic assays may aid in predicting the clinical behavior of glioblastoma and in providing individualized potential targets for therapeutic agents. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. Carolina Neurosurg & Spine Associates, Charlotte, NC USA. RP Brown, A (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, 100 Blossom St Cox 315, Boston, MA 02114 USA. NR 75 TC 45 Z9 51 U1 0 U2 2 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD MAR-APR PY 2003 VL 9 IS 2 BP 82 EP 90 DI 10.1097/00130404-200303000-00003 PG 9 WC Oncology SC Oncology GA 678XR UT WOS:000182892400003 PM 12784873 ER PT J AU Pogue, BW O'Hara, JA Demidenko, E Wilmot, CM Goodwin, IA Chen, B Swartz, HM Hasan, T AF Pogue, BW O'Hara, JA Demidenko, E Wilmot, CM Goodwin, IA Chen, B Swartz, HM Hasan, T TI Photodynamic therapy with verteporfin in the radiation-induced fibrosarcoma-1 tumor causes enhanced radiation sensitivity SO CANCER RESEARCH LA English DT Article ID PARAMAGNETIC-RESONANCE OXIMETRY; ACID-INDUCED PROTOPORPHYRIN; IN-VIVO; IONIZING-RADIATION; MURINE TUMOR; FLUENCE RATE; OXYGEN-CONSUMPTION; INDUCED APOPTOSIS; HYPOXIC FRACTION; GAMMA-RADIATION AB Photodynamic therapy (PDT) with verteporfin (lipid form of benzoporphyrin derivative, benzoporphyrin derivative monoacid ring A) was used to treat radiation-induced fibrosarcoma tumors before X-ray treatment. When verteporfin was injected 3 h before light irradiation, the tumor partial pressure of oxygen (pO(2)) rose from a pretreatment value of 2.8 +/- 1 to 15.2 +/- 6.9 mm Hg immediately after light application was complete (P = 0.048). When the optical irradiation was given 15 min after verteporfin injection, the tumor pO(2) decreased slightly after treatment [i.e., 6.8 +/- 1.6 mm Hg (pretreatment) versus 4.1 +/- 0.3 mm Hg (posttreatment)], whereas control tumor pO(2) did not change significantly. In vitro study of the cellular oxygen consumption rate before and after PDT treatment indicated that the consumption rate decreased linearly with delivered optical dose and quantitatively matched the loss of cell viability as measured by a mitochondrial tetrazolium assay. Doppler measurements show that red cell flux is still patent immediately after treatment, indicating that oxygen should still be delivered to the tumor. Computational simulations of the oxygen supply from the vessels and the consumption from mitochondrial activity confirmed that if oxygen consumption is decreased in the presence of unhindered blood flow, the tumor oxygenation should rise, and the hypoxic fraction of the tumor should decrease. Combination treatments with PDT delivered (100 J/cm(2) optical dose, with 1 mg/kg benzoporphyrin derivative monoacid ring A injected 3 h before treatment) after radiation treatment (10 Gy from 300 keV source) were compared with PDT delivered simultaneously with radiation. Tumor regrowth assay showed that the delays to reach double the tumor volume for PDT alone and radiation alone were 2.7 +/- 1.6 and 3.2 +/- 1.7 days, respectively. When radiation was given before PDT, the delay was 5.4 +/- 1.4 days, and when PDT was given at the same time as radiation, the delay was 8.1 +/- 1.5 days. This observation indicates that the combined effect in the latter case was greater than additive (P = 0.049). C1 Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. Dartmouth Coll Sch Med, Dept Diagnost Radiol, Hanover, NH 03755 USA. Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. Harvard Univ, Sch Med, Wellman Labs Photomed, Massachusetts Gen Hosp,Dept Dermatol, Boston, MA 02114 USA. RP Pogue, BW (reprint author), Dartmouth Coll, Thayer Sch Engn, 8000 Cummings Hall, Hanover, NH 03755 USA. FU NCI NIH HHS [R01CA78734, P01CA84203]; NCRR NIH HHS [P41 RR11602] NR 71 TC 43 Z9 47 U1 3 U2 10 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2003 VL 63 IS 5 BP 1025 EP 1033 PG 9 WC Oncology SC Oncology GA 651PC UT WOS:000181327700020 PM 12615718 ER PT J AU Da Silva, MS Horton, JA Wijelath, JM Blystone, LW Fish, WR Wijelath, E Strand, K Blystone, SD Sobel, M AF Da Silva, MS Horton, JA Wijelath, JM Blystone, LW Fish, WR Wijelath, E Strand, K Blystone, SD Sobel, M TI Heparin modulates integrin-mediated cellular adhesion: Specificity of interactions with alpha and beta integrin subunits SO CELL COMMUNICATION AND ADHESION LA English DT Article DE cellular adhesion; glycosaminoglycans; heparins; integrins ID MOLECULAR-WEIGHT HEPARIN; BINDING DOMAIN; UNFRACTIONATED HEPARIN; HUMAN PLATELETS; INHIBITION; RECEPTOR; ALPHA(V)BETA(3); ALPHA(5)BETA(1); MIGRATION; PEPTIDE AB Heparin is known to influence the growth, proliferation, and migration of vascular cells, but the precise mechanisms are unknown. We previously demonstrated that unfractionated heparin (UH) binds to the platelet integrin alpha(IIb)beta(3) , and enhances ligand binding. To help define the specificity and site(s) of heparin-integrin interactions, we employed the erythroleukemic K562 cell line, transfected to express specific integrins (alpha(v)beta(3) , alpha(v)beta(5) , and alpha(IIb)beta(3)). By comparing K562 cells expressing a common alpha subunit (Kalpha (v)beta(3) , Kalpha(v)beta(5)) with cells expressing a common beta subunit (Kalpha (v)beta(3) , Kalpha(IIb)beta(3)), we observed that heparin differentially modulated integrin-mediated adhesion to vitronectin. UH at 0.5-7.5 mug/ml consistently enhanced the adhesion of beta(3) expressing cells (Kalpha(v)beta(3) ,Kalpha(IIb)beta(3)). In contrast, UH at 0.5-7.5 mug/ml inhibited Kalpha(v)beta(5) adhesion. Experiments using integrin-blocking antibodies, appropriate control ligands, and nontransfected native K562 cells revealed that heparin's actions were mediated by the specific integrins under study. Preincubation of heparin with Kalpha(v)beta(3) cells enhanced adhesion, while preincubation of heparin with the adhesive substrate (vitronectin) had minimal effect. There was a structural specificity to heparin's effect, in that a low molecular weight heparin and chondroitin sulfate showed significantly less enhancement of adhesion. These findings suggest that heparin's modulation of integrin-ligand interactions occurs through its action on the integrin. The inhibitory or stimulatory effects of heparin depend on the beta subunit type, and the potency is dictated by structural characteristics of the glycosaminoglycan. C1 VA Puget Sound HCS, Dept Surg, Div Vasc Surg, Seattle, WA 98108 USA. SUNY Upstate Med Univ, Dept Surg, Syracuse, NY USA. Vet Affairs Med Ctr, Syracuse, NY USA. Univ Washington, Sch Med, Seattle, WA USA. SUNY Upstate Med Univ, Dept Cell & Dev Biol, Syracuse, NY USA. RP Sobel, M (reprint author), VA Puget Sound HCS, Dept Surg, Div Vasc Surg, Mailstop 112,1660 S Columbian Way, Seattle, WA 98108 USA. FU NHLBI NIH HHS [F32 HL 0442, HL 39903]; NIAID NIH HHS [AI 40602] NR 31 TC 17 Z9 19 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1061-5385 J9 CELL COMMUN ADHES JI Cell Commun. Adhes. PD MAR-APR PY 2003 VL 10 IS 2 BP 59 EP 67 DI 10.1080/15419060390260905 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 755BF UT WOS:000187367400001 PM 14681057 ER PT J AU Littner, MR AF Littner, MR TI Continuous positive airway pressure - By nose or mouth? SO CHEST LA English DT Editorial Material ID OBSTRUCTIVE SLEEP-APNEA; CPAP THERAPY; MASK C1 Vet Affairs Greater Los Angeles Healthcare Syst, Pulm Crit Care & Sleep Med Div, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RP Littner, MR (reprint author), Dept Pulm, 16111 Plummer St 111P,Bldg 200,Room 3534, North Hills, CA 91343 USA. NR 7 TC 1 Z9 1 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 MAR PY 2003 VL 123 IS 3 BP 662 EP 664 DI 10.1378/chest.123.3.662 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 655DR UT WOS:000181536500003 PM 12628854 ER PT J AU Malave, HA Taylor, AA Nattama, J Deswal, A Mann, DL AF Malave, HA Taylor, AA Nattama, J Deswal, A Mann, DL TI Circulating levels of tumor necrosis factor correlate with indexes of depressed heart rate variability - A study in patients with mild-to-moderate heart failure SO CHEST LA English DT Article DE cytokine; heart failure; heart rate variability; norepinephrine; tumor necrosis factor ID LEFT-VENTRICULAR DYSFUNCTION; CORONARY-ARTERY DISEASE; FACTOR-ALPHA; DILATED CARDIOMYOPATHY; EJECTION FRACTION; CARDIAC MYOCYTES; SECONDARY; IMPAIRMENT; MECHANISM; SEVERITY AB Objectives: Patients with heart failure have increased circulating levels of tumor necrosis factor (TNF) and TNF receptors. It is not known whether TNF, which is known to blunt beta-adrenergic responsiveness in experimental models, contributes to the loss of heart rate variability in patients with heart failure. Therefore, we examined heart rate variability in relation to circulating levels of TNF, TNF receptors, and norepinephrine in patients with heart failure and in control subjects. Methods: Heart rate variability was obtained from 24-h ambulatory ECG recordings in age-matched control subjects (n=10)and patients with mild (n=15) to moderate (n=14) heart failure. Plasma levels of TNF and soluble type 1 and 2 TNF receptors were measured by enzyme-linked immunoassay; plasma norepinephrine levels were measured by high-performance liquid chromatography. Results: There was a significant inverse linear correlation between increased circulating levels of TNF, TNF receptors, and norepinephrine for time-domain and frequency-domain indexes of heart rate variability among patients with heart failure and control subjects. Multiple stepwise linear regression analysis showed that TNF was a stronger independent predictor of frequency-domain indexes of heart rate variability than norepinephrine. Conclusions: TNF is an independent predictor of depressed heart rate variability in patients with heart failure. insofar as TNF blunts beta-adrenergic signaling, this study suggests the possibility that overexpression of TNF and subsequent loss of beta-adrenergic responsiveness contributes to the decrease in heart rate variability observed in heart failure. C1 Winters Ctr Heart Failure Res, Houston, TX 77030 USA. Baylor Coll Med, Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. Ctr Expt Therapeut, Houston, TX USA. Houston Vet Affairs Med Ctr, Houston, TX USA. RP Mann, DL (reprint author), Winters Ctr Heart Failure Res, 6565 Fannin,MS 524, Houston, TX 77030 USA. OI Mann, Douglas /0000-0002-2516-0145 FU NHLBI NIH HHS [R01 HL58081-01, R01 HL61543-01, P50 HL-06H, HL-42250-10/10] NR 36 TC 50 Z9 51 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAR PY 2003 VL 123 IS 3 BP 716 EP 724 DI 10.1378/chest.123.3.716 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 655DR UT WOS:000181536500017 PM 12628868 ER PT J AU Kelley, A Garshick, E Gross, ER Lieberman, SL Tun, CG Brown, R AF Kelley, A Garshick, E Gross, ER Lieberman, SL Tun, CG Brown, R TI Spirometry testing standards in spinal cord injury SO CHEST LA English DT Article; Proceedings Paper CT International Conference of the American-Thoracic-Society CY APR 23-29, 1999 CL SAN DIEGO, CALIFORNIA SP Amer Thorac Soc DE reference standards; spinal cord injury; spirometry ID LUNG-FUNCTION; ASSOCIATION; POPULATION; CRITERIA; HEALTH AB Study objectives: Because muscle paralysis makes it uncertain whether subjects with spinal cord injury (SCI) can perform spirometry in accordance with American Thoracic Society (ATS) standards, determinants of test failure were examined. Design: Cross-sectional study. Setting: Veterans Affairs (VA) medical center. Participants: Veterans with SCI at VA Boston Healthcare System and nonveterans recruited by mail and advertisement. Measurements and results: Two hundred thirty of 278 subjects (83%) were able to produce three expiratory efforts lasting greater than or equal to6 s and without excessive back-extrapolated volume (EBEV). In 217 of 230 subjects (94%), FVC and FEV1 were each reproducible in accordance with 1994 ATS standards. in the remaining 48 subjects, efforts with smooth and continuous volume-time tracings and acceptable flow-volume loops were identified. These subjects had a lower percentage of predicted FVC, FEV1, and maximum expiratory and inspiratory pressures compared to the others, and a greater proportion had neurologically complete cervical injury (42% compared to 16%). In 19 subjects (40%), some expiratory efforts were not sustained maximally for greater than or equal to6 s but had at least a 0.5-s plateau at residual volume (short efforts). in eight subjects (17%), some efforts were not short but had EBEV. In the remaining 21 subjects (44%), some efforts were short, some had EBEV, and some had both. If these efforts were not rejected, 262 of 278 subjects (94%) would have produced three acceptable efforts, and in 257 subjects (92%), the efforts were reproducible. Conclusions: Subjects with SCI with the most impaired respiratory muscles and abnormal pulmonary function are able to perform spirometry reproducibly despite not meeting usual ATS acceptability standards. Exclusion of these subjects would lead to bias in studies of respiratory function in SCI. The modification of spirometry testing standards to include efforts with EBEV and with a 0.5-s plateau if < 6 s would reduce the potential for bias. C1 VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, Med Serv, W Roxbury, MA 02132 USA. VA Boston Healthcare Syst, Rehabil Med Serv, W Roxbury, MA 02132 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Garshick, E (reprint author), VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, Med Serv, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. FU NICHD NIH HHS [R01 HD042141] NR 17 TC 50 Z9 53 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 MAR PY 2003 VL 123 IS 3 BP 725 EP 730 DI 10.1378/chest.123.3.725 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 655DR UT WOS:000181536500018 PM 12628869 ER PT J AU Chen, M Li, W Fan, J Kasahara, N Woodley, D AF Chen, M Li, W Fan, J Kasahara, N Woodley, D TI An efficient gene transduction system for studying gene function in primary human dermal fibroblasts and epidermal keratinocytes SO CLINICAL AND EXPERIMENTAL DERMATOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NONDIVIDING CELLS; LENTIVIRAL VECTOR; EXPRESSION; TRANSFECTION; INTEGRATION; TRANSGENE; DELIVERY AB One of the critical challenges for cellular genetic studies in primary human skin cells is lack of a gene delivery system that provides efficient transduction and sustained expression of the transgenes. Due to the limited time of survival in culture, the processes of drug selection and clonal expansion for establishing gene stably expressing cell lines are not a realistic option for primary skin cells. We have examined various gene transduction techniques in primary dermal fibroblasts and epidermal keratinocytes of human skin. We report here that vectors based on the human immunodeficiency virus (HIV, lentivirus) offer more than 90% gene transduction efficiency and sustained expression of transgenes in both human skin cell types. In contrast, most of the commonly used techniques have at best 30% transduction efficiency in these cells. Using two previously reported migration control genes, protein kinase Cdelta and p38alpha-MAPK, as examples, we provide evidence that the unprecedented efficiency of the lentiviral system enables a clear detection of the genes' dominant negative effects, which are otherwise greatly compromised by ordinary transfection techniques. We believe that a wide application of this gene transduction system will greatly benefit studies of gene function in human skin cells. C1 Univ So Calif, Keck Sch Med, Dept Med, Div Dermatol, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, USC Norris Canc Ctr, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90033 USA. Greater Los Angles Vet Adm Hlth Syst, Los Angeles, CA USA. RP Chen, M (reprint author), Univ So Calif, Keck Sch Med, Dept Med, Div Dermatol, Los Angeles, CA 90033 USA. EM cherm@hsc.usc.edu FU NIAMS NIH HHS [AR46538, AR47981] NR 15 TC 26 Z9 27 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0307-6938 J9 CLIN EXP DERMATOL JI Clin. Exp. Dermatol. PD MAR PY 2003 VL 28 IS 2 BP 193 EP 199 DI 10.1046/j.1365-2230.2003.01191.x PG 7 WC Dermatology SC Dermatology GA 659QV UT WOS:000181789700019 PM 12653712 ER PT J AU Neva, MH Kotaniemi, A Kaarela, K Lehtinen, JT Belt, EA Kauppi, M AF Neva, MH Kotaniemi, A Kaarela, K Lehtinen, JT Belt, EA Kauppi, M TI Atlantoaxial disorders in rheumatoid arthritis associate with the destruction of peripheral and shoulder joints, and decreased bone mineral density SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article DE rheumatoid arthritis; cervical spine; bone mineral density; peripheral joints; shoulder joint; risk factors ID CERVICAL-SPINE; RADIOLOGICAL CHANGES; AXIAL SUBLUXATION; FOLLOW-UP; INVOLVEMENT; PROGRESSION; DISLOCATION; PREVALENCE; MYELOPATHY; PATHOLOGY AB Objective To evaluate whether cervical spine changes are associated with the destruction of shoulder or peripheral joints and with bone mineral density (BMD) in patients with long-term RA. Methods An inception cohort of 67 patients with seropositive and erosive RA were followed up for 20 years. Cervical spine, shoulder hand and foot radiographs, and the BMD of the lumbar spine and femoral neck were evaluated. Results A positive relationship was detected between the occurrence of atlantoaxial disorders and the destruction of both shoulder (p < 0.001) and peripheral (p = 0.001) joints. In addition, the severity of anterior atlantoaxial subluxation and atlantoaxial impaction positively correlated with the grade of destruction in the evaluated joints. Furthermore, patients with atlantoaxial disorders presented decreased BMD of the femoral neck (p = 0.019). The occurrences of subaxial subluxations (SAS) and subaxial disc space narrowings only associated with higher onset age of RA. Conclusions Patients with severe RA and osteoporosis have an increased risk for atlantoaxial disorders. The co-existence of shoulder destruction and cervical spine disorders makes the differential diagnosis of shoulder and neck pain challenging. C1 Tampere Univ Hosp, Div Orthopaed & Trauma Surg, Dept Surg, Tampere 33521, Finland. Rheumatism Fdn Hosp, Dept Rheumatol, SF-18120 Heinola, Finland. Rheumatism Fdn Hosp, Dept Orthopaed Surg, SF-18120 Heinola, Finland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Neva, MH (reprint author), Tampere Univ Hosp, Div Orthopaed & Trauma Surg, Dept Surg, PL 2000, Tampere 33521, Finland. NR 31 TC 15 Z9 15 U1 1 U2 2 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD MAR-APR PY 2003 VL 21 IS 2 BP 179 EP 184 PG 6 WC Rheumatology SC Rheumatology GA 668RT UT WOS:000182307500010 PM 12747271 ER PT J AU Freidlin, B Breathnach, OS Johnson, BE AF Freidlin, B Breathnach, OS Johnson, BE TI A model to select regimens for phase III trials for patients with advanced-stage non-small cell lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID SOUTHWEST-ONCOLOGY-GROUP; TYROSINE KINASE INHIBITOR; MITOMYCIN-C FAM; RANDOMIZED TRIAL; COMBINATION CHEMOTHERAPY; CISPLATIN; VINDESINE; ETOPOSIDE; ADENOCARCINOMA; VINORELBINE AB Purpose: Historical data from pilot, Phase II, and Phase III studies for patients with advanced-stage non-small cell lung cancer (NSCLC) were used to evaluate a statistical model developed to provide assistance in selecting regimens from pilot studies for subsequent use in larger Phase III randomized studies. Experimental Design: Information from 33 Phase III trials for patients with advanced-stage NSCLC performed from 1973 and 1994 in the United States and Canada was collected. The data from antecedent pilot or Phase II and subsequent Phase III trials were analyzed using a predictive statistical model. This model uses the number of patients in the pilot/Phase II study, the median survival of patients in the pilot, and the number of deaths observed, to estimate the statistical likelihood that the pilot regimen will be shown superior to standard therapy in a subsequent Phase III trial. Results: Ten pilot/Phase II studies were identified that preceded eleven subsequent Phase III studies. The three pilot regimens associated with Phase III trials, revealing statistically significant longer survival, had an expected power of 0.69, 0.85, and 0.94 respectively. The regimens from the seven other pilot studies for which the median power expected was 0.38 (range, 0.07-0.80) showed no difference when compared with standard treatment in a Phase III trial. Conclusion: The use of the expected power model provides an important enhancement to the screening of new therapies. Regimens with an expected power of >0.55 may be good candidates for testing in Phase III trials. C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. Univ Coll, Cork Univ Hosp, Dept Oncol, Cork, Ireland. Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol,Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Johnson, BE (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 44 Binney St, Boston, MA 02115 USA. NR 40 TC 14 Z9 14 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 2003 VL 9 IS 3 BP 917 EP 922 PG 6 WC Oncology SC Oncology GA 653JA UT WOS:000181430400001 PM 12631588 ER PT J AU Sharma, S Stolina, M Yang, SC Baratelli, F Lin, JF Atianzar, K Luo, J Zhu, L Lin, Y Huang, M Dohadwala, M Batra, RK Dubinett, SM AF Sharma, S Stolina, M Yang, SC Baratelli, F Lin, JF Atianzar, K Luo, J Zhu, L Lin, Y Huang, M Dohadwala, M Batra, RK Dubinett, SM TI Tumor cyclooxygenase 2-dependent suppression of dendritic cell function SO CLINICAL CANCER RESEARCH LA English DT Article ID MHC CLASS-I; ENDOTHELIAL GROWTH-FACTOR; ANTIGEN-PRESENTING CELLS; COLON-CANCER CELLS; LUNG-CANCER; PROSTAGLANDIN E-2; INTERLEUKIN-12 PRODUCTION; EXPRESSION; MATURATION; IL-10 AB Dendritic cells (DCs) serve as professional antigen-presenting cells and are pivotal in the host immune response to tumor antigens. To define the pathways limiting DC function in the tumor microenvironment, we assessed the impact of tumor cyclooxygenase (COX)-2 expression on DC activities. Bone marrow-derived DCs were cultured in either tumor supernatant (TSN) or TSN from COX-2-inhibited tumors. After culture, DCs were pulsed with tumor-specific peptides, and their ability to generate antitumor immune responses was assessed following injection into established murine lung cancer. In vitro, DC phenotype, alloreactivity, antigen processing and presentation, and interleukin (IL)-10 and IL-12 secretion were evaluated. DCs cultured in TSN failed to generate antitumor immune responses and caused immunosuppressive effects that correlated with enhanced tumor growth. However, genetic or pharmacological inhibition of tumor COX-2 expression restored DC function and effective antitumor immune responses. Functional analyses indicated that TSN causes a decrement in DC capacity to (a) process and present antigens, (b) induce alloreactivity, and (c) secrete IL-12. Whereas TSN DCs showed a significant reduction in cell surface expression of CD11c, DEC-205, MHC class I antigen, MHC class II antigen, CD80, and CD86 as well as a reduction in the transporter-associated proteins, transporter associated with antigen processing 1 and 2, the changes in phenotype and function were not evident when DCs were cultured in supernatant from COX2-inhibited tumors. We conclude that inhibition of tumor COX-2 expression or activity can prevent tumor-induced suppression of DC activities. C1 Univ Calif Los Angeles, Sch Med, Div Pulm & Crit Care Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Wadsworth Pulm Immunol Lab, Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Sch Med, Los Angeles, CA 90024 USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, Sch Med, Ctr Hlth Sci 37 131, Div Pulm & Crit Care Med, 10833 LeConte Ave, Los Angeles, CA 90095 USA. FU NCI NIH HHS [CA 71818, P50 CA 90388, R01 CA078654-02, R01 CA 78654] NR 41 TC 139 Z9 160 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 2003 VL 9 IS 3 BP 961 EP 968 PG 8 WC Oncology SC Oncology GA 653JA UT WOS:000181430400006 PM 12631593 ER PT J AU Braaten, KM Betensky, RA de Laval, L Okada, Y Hochberg, FH Louis, DN Harris, NL Batchelor, TT AF Braaten, KM Betensky, RA de Laval, L Okada, Y Hochberg, FH Louis, DN Harris, NL Batchelor, TT TI BCL-6 expression predicts improved survival in patients with primary central nervous system lymphoma SO CLINICAL CANCER RESEARCH LA English DT Article ID B-CELL LYMPHOMA; BRAIN LYMPHOMA; P16(INK4A); GENE; SUBCLASSIFICATION; INACTIVATION; DERIVATION; DELETIONS; SECTIONS; PROTEIN AB Purpose: The purpose of this study was to investigate the histogenetic origin of primary central nervous system lymphoma (PCNSL) with respect to stage of B-cell differentiation and to identify prognostic markers in a cohort of patients with PCNSL treated with i.v. high-dose methotrexate therapy. Experimental Design: This study included 33 patients with PCNSL treated with high-dose i.v. methotrexate at the Massachusetts General Hospital for whom archival tumor tissue was available. All 33 patients tested negative for HIV. The lymphomas were morphologically subclassified according to the Kiel system, as modified in the WHO classification. Immunohistochemistry for the following antigens was performed: BCL-6; BCL-2; MUM1; CD10; vs38c; CD138; CD44; p16; and p53. Fluorescence in situ hybridization and multiplex PCR for CDKN2A/p16 were also performed. Results: There were 17 women and 16 men enrolled, with a median age of 60 years. All tumors were diffuse large B-cell lymphomas. Of the 23 cases that could be subclassified, 22 were centroblastic, and 1 was immunoblastic. Twenty-six of 33 tumors were BCL-6+, 6 of 32 tumors were CD10+, 27 of 29 tumors were BCL-2+, 31 of 32 tumors were MUM1+,11 of 31 tumors were CD44+, 4 of 33 tumors were vs38c+, and 0 of 32 tumors were CD138+. There were 18 of 32 (56%) complete responses and 8 of 32 (25 %) partial responses to methotrexate, whereas 6 of 33 (18%) progressed during treatment. Ten patients died of disease. Expression of BCL-6 was significantly associated with longer overall survival (P = 0.002; median survival, 101 versus 14.7 months, with approximately 95% lower confidence limits of 41.7 and 8.8 months, respectively). Conclusions: In this group of 33 patients with PCNSL, expression of BCL-6 was significantly associated with longer overall survival. BCL-6 warrants further investigation as a potentially important prognostic marker in this disease. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02114 USA. RP Batchelor, TT (reprint author), Brain Tumor Ctr, Dept Neurol, Cox 315,100 Blossom St, Boston, MA 02114 USA. NR 39 TC 106 Z9 113 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 2003 VL 9 IS 3 BP 1063 EP 1069 PG 7 WC Oncology SC Oncology GA 653JA UT WOS:000181430400021 PM 12631608 ER PT J AU Morioka, H Weissbach, L Vogel, T Nielsen, GP Faircloth, GT Shao, L Hornicek, FJ AF Morioka, H Weissbach, L Vogel, T Nielsen, GP Faircloth, GT Shao, L Hornicek, FJ TI Antiangiogenesis treatment combined with chemotherapy produces chondrosarcoma necrosis SO CLINICAL CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; PLASMINOGEN-RELATED GENE; SOFT-TISSUE SARCOMAS; TUMOR-GROWTH; CANCER-CELLS; ANGIOGENESIS; THERAPY; AGENTS; ECTEINASCIDIN-743; ANGIOSTATIN AB A combination therapy protocol using a marine chemotherapeutic and an antiangiogenic molecule was tested in a mouse tumor xenograft model for the ability to curtail the growth of a human chondrosarcoma (CHSA). Ecteinascidin-743 (ET-743), a marine-derived chemotherapeutic, was effective at slowing the growth of a primary CHSA. Plasminogen-related protein B, which antagonizes various endothelial cell activities, also elicited a significant. inhibition of neoplastic growth, albeit with reduced effectiveness. The combination of the two agents resulted in only a modest further repression of tumor growth over that associated with ET-743 treatment alone, as measured by tumor volume (82% versus 76% inhibition, respectively). However, analysis of the extent of tumor necrosis and vascularization of the tumor revealed that the coadministration of the two compounds was clearly more effective, eliciting a 2.5-fold increase in tumor necrosis relative to single-agent treatment. The combination therapy also was most effective at antagonizing tumor-associated microvessel formation, as assessed by CD31 immunostaining, suggesting that combination therapy may hold promise for treating CHSA. Tumor necrosis produced by combination therapy of ET-743 and recombinant plasminogen-related protein B was also significantly greater than that produced by conventional doxorubicin treatment, further corroborating the efficacy of combination therapy. C1 Massachusetts Gen Hosp, Orthoped Res Labs, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Biotechnol Gen Ltd, Rehovot, Israel. PharmaMar USA, Cambridge, MA 02149 USA. RP Weissbach, L (reprint author), Massachusetts Gen Hosp, Orthoped Res Labs, GRJ 1124,55 Fruit St, Boston, MA 02114 USA. NR 34 TC 47 Z9 53 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 2003 VL 9 IS 3 BP 1211 EP 1217 PG 7 WC Oncology SC Oncology GA 653JA UT WOS:000181430400040 PM 12631627 ER PT J AU Zile, MR AF Zile, MR TI Peter C. Gazes: Physician, teacher, scholar SO CLINICAL CARDIOLOGY LA English DT Biographical-Item C1 Med Univ S Carolina, Div Cardiol, Gazes Cardiac Res Inst, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Zile, MR (reprint author), Med Univ S Carolina, Div Cardiol, Gazes Cardiac Res Inst, Dept Med, 96 Jonathan Lucas St,Suite 816,POB 250623, Charleston, SC 29425 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU CLINICAL CARDIOLOGY PUBL CO PI MAHWAH PA PO BOX 832, MAHWAH, NJ 07430-0832 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD MAR PY 2003 VL 26 IS 3 BP 158 EP 159 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 655AH UT WOS:000181528800012 PM 12685625 ER PT J AU Margolis, SA Vangel, M Duewer, DL AF Margolis, SA Vangel, M Duewer, DL TI Certification of standard reference material 970, ascorbic acid in serum, and analysis of associated interlaboratory bias in the measurement process SO CLINICAL CHEMISTRY LA English DT Article ID PLASMA VITAMIN-C; CANCER AB Background: The accurate and reproducible measurement of ascorbic acid is essential in delineating the role of ascorbic acid as a diagnostic tool for human disease and for the comparison of data acquired by different laboratories. A stabilized pair of standards of ascorbic acid in human serum, which is compatible with most analytical methods, have been prepared. Methods: The certification was based on the gravimetric addition of ascorbic acid to metaphosphoric acid-stabilized, ascorbic acid-depleted serum and NIST liquid chromatography-electrochemical measurements. The NIST results were analyzed statistically for homogeneity, and the expanded uncertainty of each SRM was calculated using all of the NIST data. An interlaboratory comparison exercise was also performed. Results: These materials, Standard Reference Material (SRM) 970 Ascorbic Acid in Serum, Level I and Level 11, are homogeneous and are certified to contain (10.07 +/- 0.21) and (30.57 +/- 0.28) mmol ascorbic acid/L of solution (expanded uncertainty), respectively. In the interlaboratory comparison (n = 17), the relative SDs for the two materials were 22% and 19%. Conclusions: Two lots of serum, each containing different amounts of ascorbic acid stabilized in metaphosphoric acid, have been prepared and characterized. Many laboratories provide inaccurate results. (C) 2003 American Association for Clinical Chemistry. C1 Natl Inst Stand & Technol, Div Analyt Chem, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA. Massachusetts Gen Hosp, MRI Imaging Dept, Charlestown, MA 02129 USA. RP Margolis, SA (reprint author), Natl Inst Stand & Technol, Div Analyt Chem, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA. RI Duewer, David/B-7410-2008 NR 19 TC 10 Z9 10 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAR PY 2003 VL 49 IS 3 BP 463 EP 469 DI 10.1373/49.3.463 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 649EL UT WOS:000181193900014 PM 12600959 ER PT J AU Holmes, CB Losina, E Walensky, RP Yazdanpanah, Y Freedberg, KA AF Holmes, CB Losina, E Walensky, RP Yazdanpanah, Y Freedberg, KA TI Review of human immunodeficiency virus type 1-related opportunistic infections in sub-Saharan Africa SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID PNEUMOCYSTIS-CARINII PNEUMONIA; BLOOD-STREAM INFECTIONS; TRIMETHOPRIM-SULFAMETHOXAZOLE PROPHYLAXIS; HIV-1-INFECTED UGANDAN ADULTS; RANDOMIZED CONTROLLED TRIAL; FEMALE SEX-WORKERS; DAR-ES-SALAAM; HIV-INFECTION; COTE-DIVOIRE; NATURAL-HISTORY AB Understanding the natural history of human immunodeficiency virus type 1 (HIV-1) and opportunistic infections in sub-Saharan Africa is necessary to optimize strategies for the prophylaxis and treatment of opportunistic infections and to understand the likely impact of antiretroviral therapy. We undertook a systematic review of the literature on HIV-1 infection in sub-Saharan Africa to assess data from recent cohorts and selected cross-sectional studies to delineate rates of opportunistic infections, associated CD4 cell counts, and associated mortality. We searched the MEDLINE database and the Cochrane Database of Systematic Reviews and Cochrane Clinical Trials Register for English-language literature published from 1990 through April 2002. Tuberculosis, bacterial infections, and malaria were identified as the leading causes of HIV-related morbidity across sub-Saharan Africa. Of the few studies that reported CD4 cell counts, the range of cell counts at the time of diagnosis of opportunistic infections was wide. Policies regarding the type and timing of opportunistic infection prophylaxis may be region specific and urgently require further study. C1 Harvard Univ, Sch Med, Div Infect Dis, Dept Med,Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Partners AIDS Res Ctr, Dept Med,Massachusetts Gen Hosp, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. Ctr Hosp Tourcoing, Serv Malad Infect & Voyageur, Tourcoing, France. Harvard Univ, Sch Med, Div Gen Med, Dept Med,Massachusetts Gen Hosp, Boston, MA USA. RP Holmes, CB (reprint author), Div Gen Med, 50 Staniford St, 9th Fl, Boston, MA 02114 USA. FU NIAID NIH HHS [K25 AI50436, 1P30AI42851, K23 AI001794, K23 AI01794, K25 AI050436, P30 AI042851, R01 AI042006, R01 AI42006]; ODCDC CDC HHS [CCU/U64 119525] NR 110 TC 99 Z9 105 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 1 PY 2003 VL 36 IS 5 BP 652 EP 662 DI 10.1086/367655 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 647CE UT WOS:000181073600017 PM 12594648 ER PT J AU Stojanovic, MP Zhou, Y Hord, D Vallejo, R Cohen, SP AF Stojanovic, MP Zhou, Y Hord, D Vallejo, R Cohen, SP TI Single needle approach for multiple medial branch blocks: A new technique SO CLINICAL JOURNAL OF PAIN LA English DT Article DE diagnostic block; facet joint; lumbar zygapophyseal joint; medial branch ID ZYGAPOPHYSIAL JOINT PAIN; LOW-BACK-PAIN; INJECTION AB Background and Objectives: Medial branch blocks are an important tool for the diagnosis of facet joint arthropathy. The most commonly used technique involves multiple needle placements, one for each nerve blocked. This multiple needle technique may require a large amount of local anesthetic for anesthetizing the skin, thereby increasing the rate of false-positive blocks. Technique: Diagnostic lumbar medial branch blocks are usually performed using multiple needles, one for each branch. The authors describe a different technique using a single needle for all levels. Initially, the needle is directed toward the medial branch located at the level of the affected facet joint in the antero-posterior view. After anesthetizing this nerve with local anesthetic, the same needle is withdrawn to the skin with the tip still in the subcutaneous tissue and repositioned to block the medial branch above, and thereafter below, while continuing to use only the antero-posterior view, thereby using only one entry site. Conclusions: When performed correctly, the single needle technique provides accuracy similar to the more conventional multiple needle approach during the performance of diagnostic facet joint nerve blocks. Because only one skin entry point is needed, however, this technique may afford several advantages over the multiple needle approach. These may include less patient discomfort, less time required and less radiation exposure since only one C-arm position is used, a smaller volume of local anesthetic, and possibly a lower incidence of false-positive blocks. C1 Massachusetts Gen Hosp, MGH Pain Ctr, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Intervent Pain Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Walter Reed Army Med Ctr, Uniformed Serv Univ Hlth Sci, Dept Anesthesia, Pain Management Ctr, Washington, DC 20307 USA. RP Hord, D (reprint author), Massachusetts Gen Hosp, MGH Pain Ctr, Dept Anesthesia & Crit Care, WACC-324,15 Parkman St, Boston, MA 02114 USA. NR 13 TC 9 Z9 9 U1 0 U2 0 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 MAR-APR PY 2003 VL 19 IS 2 BP 134 EP 137 DI 10.1097/00002508-200303000-00009 PG 4 WC Anesthesiology; Clinical Neurology SC Anesthesiology; Neurosciences & Neurology GA 653JD UT WOS:000181430700009 PM 12616184 ER PT J AU Alston, TA AF Alston, TA TI Sepsis and hypovolemia: Two bad SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE cocaine; endotoxin priming; malariotherapy; multiple organ failure; second attack; vasoconstrictor ID INFLAMMATORY RESPONSE SYNDROME; BACTERIAL LIPOPOLYSACCHARIDE; MALARIOTHERAPY; NEUTROPHILS; SURGERY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02115 USA. RP Alston, TA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02115 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAR PY 2003 VL 31 IS 3 BP 991 EP 992 DI 10.1097/01.CCM.0000050290.66035.3E PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 660RP UT WOS:000181846800062 PM 12627028 ER PT J AU Bigatello, LM George, E Hurford, WE AF Bigatello, LM George, E Hurford, WE TI Ethical considerations for research in critically ill patients SO CRITICAL CARE MEDICINE LA English DT Article DE informed consent; critical care; research ID INFORMED CONSENT; CARE RESEARCH C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02115 USA. RP Bigatello, LM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02115 USA. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 11 TC 21 Z9 21 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAR PY 2003 VL 31 IS 3 SU S BP S178 EP S181 DI 10.1097/01.CCM.0000064518.50241.fa PG 4 WC Critical Care Medicine SC General & Internal Medicine GA 661XL UT WOS:000181915100011 PM 12626965 ER PT J AU Koski, G AF Koski, G TI Research ethics and the intensive care unit: Getting behind the wheel SO CRITICAL CARE MEDICINE LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. US Dept HHS, Washington, DC 20201 USA. RP Koski, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAR PY 2003 VL 31 IS 3 SU S BP S119 EP S120 DI 10.1097/00003246-200303001-00001 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 661XL UT WOS:000181915100001 PM 12626955 ER PT J AU Rubin, LR Fitts, ML Becker, AE AF Rubin, LR Fitts, ML Becker, AE TI "Whatever feels good in my soul": Body ethics and aesthetics among African American and Latina women SO CULTURE MEDICINE AND PSYCHIATRY LA English DT Article DE aesthetics; body image; culture; ethnicity ID WHITE ADOLESCENT FEMALES; EATING DISORDERS; IMAGE; DISTURBANCES; ATTITUDES; BEHAVIORS; ETHNICITY; GENDER; GIRLS; MEDIA AB Ethnicity-specific differences in body aesthetic ideals and body satisfaction have been cited as a potential explanation for interethnic differences in the prevalence and presentation of eating disorders. It has been widely hypothesized that such ethnically based differences in aesthetic body ideals mitigate cultural pressures that contribute to body disparagement and disordered eating among white women. However, mechanisms by which a cultural milieu maybe protective against the development of disordered eating remain poorly understood. This study investigated relationships among ethnicity, self-representation, and body aesthetic ideals among 18 college-educated black and Latina women through analysis of focus group discussion data. Rather than confirming body aesthetic ideals different from those of white culture, study respondents reframed the discussion about body aesthetics to one of body ethics. That is, study subjects both contested ideologies defining thinness and whiteness as inherently beautiful and espoused a body ethic of self-acceptance and nurturance that rejects mainstream cultural pressures to reshape bodies to approximate aesthetic ideals promulgated in the media. We conclude that understanding body image concerns from the standpoint of body ethics, rather than body aesthetics, may be a more productive and inclusive approach to the study of ethnically diverse women's embodied experience. Ultimately it is anticipated that this will better illuminate the complex relationships among ethnicity, culture, and risk for body image and eating disorders. C1 Arizona State Univ, Dept Psychol, Tempe, AZ 85287 USA. Arizona State Univ, Sch Justice Studies, Tempe, AZ 85287 USA. Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Adult Eating & Weight Disorders Program, Boston, MA 02114 USA. RP Rubin, LR (reprint author), Arizona State Univ, Dept Psychol, Tempe, AZ 85287 USA. NR 62 TC 68 Z9 68 U1 3 U2 12 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0165-005X J9 CULT MED PSYCHIAT JI Cult. Med. Psychiatr. PD MAR PY 2003 VL 27 IS 1 BP 49 EP 75 DI 10.1023/A:1023679821086 PG 27 WC Anthropology; Psychiatry; Social Sciences, Biomedical SC Anthropology; Psychiatry; Biomedical Social Sciences GA 673YF UT WOS:000182608100003 PM 12825784 ER PT J AU Christiani, DC Wang, XR AF Christiani, DC Wang, XR TI Respiratory effects of long-term exposure to cotton dust SO CURRENT OPINION IN PULMONARY MEDICINE LA English DT Article ID ENDOTOXIN AB Traditionally, the concept of cotton dust-related disease focused on acute airway responses. A possible connection of long-term exposure to cotton dust with chronic obstructive airway disease was not addressed until the past two decades. This review summarizes the latest findings relevant to this topic that were observed from longitudinal cohort studies and discusses the relation between acute airway responses and chronic losses of lung function. (C) 2003 Lippincott Williams Wilkins. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit,Dept Med, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. RI Lin, Sihao/A-8412-2012 FU NIEHS NIH HHS [ES000002]; NIOSH CDC HHS [OH2421] NR 6 TC 13 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-5287 J9 CURR OPIN PULM MED JI Curr. Opin. Pulm. Med. PD MAR PY 2003 VL 9 IS 2 BP 151 EP 155 DI 10.1097/00063198-200303000-00010 PG 5 WC Respiratory System SC Respiratory System GA 643XR UT WOS:000180889100010 PM 12574696 ER PT J AU Goldgeier, M Fox, CA Zavislan, JM Harris, D Gonzalez, S AF Goldgeier, M Fox, CA Zavislan, JM Harris, D Gonzalez, S TI Noninvasive imaging, treatment and microscopic confirmation of clearance of basal cell carcinoma SO DERMATOLOGIC SURGERY LA English DT Article ID SCANNING LASER MICROSCOPY; IMMUNE-RESPONSE MODIFIER; IN-VIVO; HUMAN SKIN; HISTOLOGY AB Background. The diagnosis of basal cell carcinoma (BCC) is generally established by skin biopsy followed by tissue preparation and microscopic analysis. Treatment of BCC is often accomplished by surgical excision. Objective. To confirm the presence of BCC with a noninvasive imaging technique, to treat the patient with a topical immune response modifier, and to confirm the clearance of BCC noninvasively. Methods. Confocal microscopy (CM) is a noninvasive technique for real-time imaging of skin in vivo. Imiquimod, an immune response modifier, is applied topically by the patient to the skin lesion. Results. The presence of BCC was confirmed with CM. Posttreatment CM imaging confirmed the clearance of BCC from the entire treatment field. Both the pretreatment and the posttreatment CM findings were confirmed by invasive biopsy. Conclusion. The ability to use CM to image in real time without discomfort to the patient makes it a powerful tool to assist in the diagnosis of skin disease. C1 Lucid Inc, Med Advisory Board, Rochester, NY USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA USA. RP Goldgeier, M (reprint author), 125 Lattimore Rd, Rochester, NY 14620 USA. NR 14 TC 29 Z9 31 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD MAR PY 2003 VL 29 IS 3 BP 205 EP 210 DI 10.1046/j.1524-4725.2003.29050.x PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA 651QC UT WOS:000181330800001 PM 12614409 ER PT J AU Longo, MI Lazaro, P Bueno, C Carreras, JL Montz, R AF Longo, MI Lazaro, P Bueno, C Carreras, JL Montz, R TI Fluorodeoxyglucose-positron emission tomography imaging versus sentinel node biopsy in the primary staging of melanoma patients SO DERMATOLOGIC SURGERY LA English DT Article ID CUTANEOUS MALIGNANT-MELANOMA AB Background. Positron emission tomography (PET) imaging is superior to conventional techniques for the evaluation of patients with stage III and stage IV cutaneous-melanoma. Several studies have highlighted the advantages of this noninvasive technique for the assessment of lymph node involvement. Objective. To compare PET imaging with sentinel node biopsy for primary staging of cutaneous melanoma and to discuss the technical limitations of PET scanning. Methods. Twenty-five consecutive patients with a histologic diagnosis of melanoma with a Breslow thickness equal or greater to 1 mm underwent a preoperative PET to assess lymph node involvement. Results. Sentinel node biopsy and PET showed a sensitivity of 100% and 22%, respectively, in the identification of lymph node metastases. Conclusion. PET is not a sensitive technique for the primary staging of cutaneous melanoma. C1 Hosp Gen Gregorio Maranon, Serv Dermatol, Madrid, Spain. Inst PET Dr Carreras, Madrid, Spain. RP Longo, MI (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, 13th St,Bldg 149, Charlestown, MA 02129 USA. NR 8 TC 30 Z9 30 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD MAR PY 2003 VL 29 IS 3 BP 245 EP 248 DI 10.1046/j.1524-4725.2003.29058.x PG 4 WC Dermatology; Surgery SC Dermatology; Surgery GA 651QC UT WOS:000181330800009 PM 12614417 ER PT J AU Abiko, T Abiko, A Clermont, AC Shoelson, B Horio, N Takahashi, J Adamis, AP King, GL Bursell, SE AF Abiko, T Abiko, A Clermont, AC Shoelson, B Horio, N Takahashi, J Adamis, AP King, GL Bursell, SE TI Characterization of retinal leukostasis and hemodynamics in insulin resistance and diabetes - Role of oxidants and protein kinase-C activation SO DIABETES LA English DT Article ID SOLUBLE ADHESION MOLECULES; BLOOD-FLOW; IN-VIVO; NITRIC-OXIDE; VITAMIN-E; RATS; RETINOPATHY; INHIBITION; COMPLICATIONS; EXPRESSION AB Increases in leukostasis/monocyte adhesion to the capillary endothelium (leukostasis) and decreases in retinal blood flow may be causally associated and are implicated in the pathogenesis of diabetic retinopathy. In this study, we demonstrate that increases in leukostasis are observed in insulin-resistant states without diabetes, whereas decreases in retinal blood flow require diabetes and hyperglycemia. Microimpaction studies using beads mimicking retinal capillary obstruction by leukocytes did not affect retinal blood flow. In diabetic rats, treatment with the antioxidant alpha-lipoic acid normalized the amount of leukostasis but not retinal blood flow. In contrast, treatment with D-alpha-tocopherol and protein kinase-C beta-isoform inhibition (LY333531) prevented the increases in leukostasis and decreases in retinal blood flow in diabetic rats. Serum hydroxyperoxide, a marker of oxidative stress, was increased in diabetic rats, but normalized by treatment with antioxidants alpha-lipoic acid and D-alpha-tocopherol and, surprisingly, PKC beta-isoform inhibition. These findings suggest that leukostasis is associated with endothelial dysfunction, insulin resistance, and oxidative stress but is not related to retinal blood flow and is not sufficient to cause diabetic-like retinopathy. Moreover, treatment with PKC beta inhibition is effective to normalize diabetes or hyperglycemia-induced PKC beta-isoform activation and oxidative stress. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02215 USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. FU NEI NIH HHS [EY/RO 15110] NR 39 TC 104 Z9 108 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2003 VL 52 IS 3 BP 829 EP 837 DI 10.2337/diabetes.52.3.829 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652DF UT WOS:000181364000032 PM 12606527 ER PT J AU Yokota, T Ma, RC Park, JY Isshiki, K Sotiropoulos, KB Rauniyar, RK Bornfeldt, KE King, GL AF Yokota, T Ma, RC Park, JY Isshiki, K Sotiropoulos, KB Rauniyar, RK Bornfeldt, KE King, GL TI Role of protein kinase C on the expression of platelet-derived growth factor and endothelin-1 in the retina of diabetic rats and cultured retinal capillary pericytes SO DIABETES LA English DT Article ID MESSENGER-RNA EXPRESSION; IN-VIVO; GENE-EXPRESSION; PHOSPHOLIPASE-C; FACTOR-BETA; PDGF-B; ACTIVATION; TRANSCRIPTION; INSULIN; COMPLICATIONS AB Increased expression of endothelin-1 (ET-1) is associated with diabetic retinopathy and vasculopathy, although the molecular explanation has not been defined. The effects of high glucose and protein kinase C (PKC) activation on platelet-derived growth factor (PDGF)-BB and of ET-1 expression in the retina of streptozotocin (STZ)-induced diabetic rats and bovine retinal pericytes (BRPC) were examined. In 4-week diabetic rats, PDGF-B and prepro-ET-1 (ppET-1) mRNA levels increased significantly by 2.8- and 1.9-fold, respectively, as quantified by RT-PCR. Treatment with PKC-beta isoform-specific inhibitor (LY333531) or insulin normalized retinal ET-1 and PDGF-B expression. In BRPC, high glucose levels increased ppET-1 and PDGF-B mRNA expression by 1.7- and 1.9-fold, respectively. The addition of PDGF-BB but not PDGF-AA increased expression of ppET-1 and vascular endothelial growth factor mRNA by 1.6- and 2.1-fold, respectively, with both inhibited by AG1296, a selective PDGF receptor kinase inhibitor. A general PKC inhibitor, GF109203X, suppressed PDGF-BB's induction of ET-1 mRNA. Thus, increased ET-1 expression in diabetic retina could be due to increased expression of PDGF-BB, mediated via PDGF-beta receptors in part by PKC activation. The novel demonstration of elevated expression of PDGF-B and its induction by PKC activation identifies a potential new molecular step in the pathogenesis of diabetic retinopathy. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Vasc Cell Biol,Res Div, Boston, MA 02215 USA. Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Vasc Cell Biol,Res Div, 1 Joslin Pl, Boston, MA 02215 USA. RI Ma, Ronald/C-2788-2009 OI Ma, Ronald/0000-0002-1227-803X FU NEI NIH HHS [EY 5110, EY 9178] NR 40 TC 66 Z9 76 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2003 VL 52 IS 3 BP 838 EP 845 DI 10.2337/diabetes.52.3.838 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 652DF UT WOS:000181364000033 PM 12606528 ER PT J AU Hayashi, T Boyko, EJ Leonetti, DL McNeely, MJ Newell-Morris, L Kahn, SE Fujimoto, WY AF Hayashi, T Boyko, EJ Leonetti, DL McNeely, MJ Newell-Morris, L Kahn, SE Fujimoto, WY TI Visceral adiposity and the risk of impaired glucose tolerance - A prospective study among Japanese Americans SO DIABETES CARE LA English DT Article ID CORONARY-HEART-DISEASE; BODY-FAT DISTRIBUTION; INSULIN SENSITIVITY; INTRAABDOMINAL FAT; DIABETES-MELLITUS; ABDOMINAL FAT; MEN; NIDDM; RESISTANCE; OBESITY AB OBJECTIVE - Greater visceral adiposity, higher insulin resistance, and impaired insulin secretion increase the risk of type 2 diabetes. Whether visceral adiposity increases risk of impaired glucose tolerance (IGT) independent of other adipose depots, insulin resistance, and insulin secretion is not known. RESEARCH DESIGN AND METHODS - Study subjects included 128 Japanese Americans with normal glucose tolerance at entry. Baseline variables included plasma glucose and insulin measured after an overnight fast and during a 75-g oral glucose tolerance test, fat areas by computed tomography, insulin secretion (incremental insulin response [IIR] [30 min insulin fasting insulin]/30 min glucose), and insulin resistance index (homeostasis model assessment for insulin resistance [HOMA-IR]). RESULTS - During the 10- to 11-year follow-up period, we confirmed 57 cases of IGT. Significant predictors of IGT included intra-abdominal fat area (IAFA) (odds ratio [OR] for a I SD increase 3.82, 95% CI 1.63-8.94 at a fasting plasma glucose [FPG] level of 4.5 mmol/l), HOMA-IR (2.41, 1.15-5.04), IIR (0.30, 0.13-0.69 at an FPG level of 4.5 mmol/l), the interactions of IAFA by FPG (P = 0.003), and IIR by FPG (P = 0.030) after adjusting for age, sex, FPG, and BMI. The multiple-adjusted OR of IAFA increased and that of IIR decreased as FPG level decreased because of these interactions. Even after adjustment for total fat area, total subcutaneous fat area, or abdominal subcutaneous fat area, all of these associations remained a significant predictor of IGT incidence. CONCLUSIONS - Greater visceral adiposity increases the risk of IGT independent of insulin resistance, insulin secretion, and other adipose depots in Japanese Americans. C1 Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. RP Boyko, EJ (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, S-152E,1660 S Columbian Way, Seattle, WA 98108 USA. RI Hayashi, Tomoshige/N-8508-2015; OI Kahn, Steven/0000-0001-7307-9002 FU NCRR NIH HHS [RR-00037]; NHLBI NIH HHS [HL-49293]; NIDDK NIH HHS [DK-02654, DK-17047, DK-31170, DK-35816] NR 26 TC 103 Z9 111 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2003 VL 26 IS 3 BP 650 EP 655 DI 10.2337/diacare.26.3.650 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UM UT WOS:000185505100016 PM 12610016 ER PT J AU van der Ven, NCW Weinger, K Yi, J Pouwer, F Ader, H van der Ploeg, HM Snoek, FJ AF van der Ven, NCW Weinger, K Yi, J Pouwer, F Ader, H van der Ploeg, HM Snoek, FJ TI The confidence in diabetes self-care scale - Psychometric properties of a new measure of diabetes-specific self-efficacy in Dutch and US patients with type 1 diabetes SO DIABETES CARE LA English DT Article ID ADOLESCENTS; ADHERENCE; MELLITUS; BEHAVIORS; ADULTS; QUESTIONNAIRE; DEPRESSION; VARIABLES; DISTRESS; VALIDITY AB Objective-To examine psychometric properties of the Confidence in Diabetes Self-Care (CIDS) scale, a newly developed instrument assessing diabetes-specific self-efficacy in Dutch and U.S. patients with type 1 diabetes. Research Design and Methods-Reliability and validity of the CIDS scale were evaluated in Dutch (n=151) and U.S. (n=190) outpatients with type 1 diabetes. In addition to the CIDS scale, assessment included HbA(1c) emotional distress, fear of hypoglycemia self-esteem, anxiety, depression, and self-care behavior. The Dutch sample completed additional measures on perceived burden and importance of self-care. Test-retest reliability was established in a second Dutch sample (n=62). Results-internal consistency (Cronbach's alpha=0.86 for Dutch patients and 0.90 U.S. patients) and test-retest reliability (Spearman's r=0.85, P<0.0001) of the CIDS scale were high. Exploratory factor analysis showed one strong general factor. Spearman's correlations between the CIDS scale and other measures were moderate and in the expected directions, and high HbA(1c) levels were associated with low CIDS scores in the U.S. sample only. Low CIDS scores were positively associated with self-care but not with glycemic control in the original samples. CIDS scores in the U.S. and Dutch samples did not show any statistically significant differences. U.S. men had higher CIDS scores than U.S. women. Conclusions-The CIDS scale is a reliable and valid measure of diabetes-specific self-efficacy for use in patients with type 1 diabetes. High psychometric similarity allows for cross-cultural comparisons. C1 Vrije Univ Amsterdam, Med Ctr, Dept Psychol Med, NL-1081 BT Amsterdam, Netherlands. Vrije Univ Amsterdam, Res Inst Endocrinol Reprod & Metab, Med Ctr, Amsterdam, Netherlands. Joslin Diabet Ctr, Behav & Mental Hlth Res Sect, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Vrije Univ Amsterdam, Inst Res Extramural Med, Med Ctr, Amsterdam, Netherlands. RP van der Ven, NCW (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Psychol Med, Van Boechorststr 7, NL-1081 BT Amsterdam, Netherlands. FU NIDDK NIH HHS [DK-42315, R01 DK042315] NR 44 TC 65 Z9 66 U1 2 U2 15 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2003 VL 26 IS 3 BP 713 EP 718 DI 10.2337/diacare.26.3.713 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UM UT WOS:000185505100027 PM 12610027 ER PT J AU McNeely, MJ Boyko, EJ Leonetti, DL Kahn, SE Fujimoto, WY AF McNeely, MJ Boyko, EJ Leonetti, DL Kahn, SE Fujimoto, WY TI Comparison of a clinical model, the oral glucose tolerance test, and fasting glucose for prediction of type 2 diabetes risk in Japanese Americans SO DIABETES CARE LA English DT Article ID OPERATING CHARACTERISTIC CURVES; LIFE-STYLE; MELLITUS; PREVENTION; DIAGNOSIS; CRITERIA; POPULATION; OVERWEIGHT; HOORN; AREAS AB Objective-To test the validity of a published clinical model for predicting incident diabetes in Japanese Americans. Research Design and Methods-A total of 465 nondiabetic Japanese Americans (243 men, 222 women), aged 34-75 years, were studied at baseline and at 5-6 years. A total of 412 subjects were studied at 10 years. The clinical model included age, sex, ethnicity, BMI, systolic blood pressure, fasting plasma glucose (FPG), HDL cholesterol, and family history of diabetes at baseline. Diabetes status at 5-6 and 10 years was determined by 75-g oral glucose tolerance test. The clinical model, 2-h glucose, and FPG were compared using receiver-operating characteristic (RCC) curves. Results-The diabetes risk associated with BMI, sex, and HDL cholesterol differed by age (Pless than or equal to0.011). At 5-6 years, the clinical model ROC curve area (0.896) was higher than that for FPG (0.776, P=0.008), but not for 2-h glucose (0.851, P=0.341), for subjects aged less than or equal to55 years. For older subjects, the clinical model ROC curve area (0.599) was lower than that for 2-h glucose (0.792, Pless than or equal to0.001), but not for FPG (0.627, P=0.467). At 10 years, there were no significant differences between the clinical model, FPG, and 2-h glucose ROC curve areas in either age group. Conclusions-In Japanese Americans aged less than or equal to55 years, a clinical model was better than FPG for predicting diabetes after 5-6 years but not after 10 years. The model was not useful in older Japanese Americans, whereas 2-h glucose was useful for predicting diabetes risk regardless of age. C1 Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA 98196 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Vet Affairs Epidemiol Res & Informat Ctr, Seattle, WA USA. Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. RP McNeely, MJ (reprint author), Univ Washington, Dept Med, Div Gen Internal Med, Box 356429, Seattle, WA 98196 USA. OI Kahn, Steven/0000-0001-7307-9002 FU NCRR NIH HHS [RR-00037]; NHLBI NIH HHS [HL-49292]; NIDDK NIH HHS [DK-02654, DK-17047, DK-31170, DK-35816] NR 22 TC 74 Z9 75 U1 3 U2 8 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2003 VL 26 IS 3 BP 758 EP 763 DI 10.2337/diacare.26.3.758 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UM UT WOS:000185505100034 PM 12610034 ER PT J AU Jenkins, AJ Lyons, T Zheng, DY Otvos, JD Lackland, DT McGee, D Garvey, WT Klein, RL AF Jenkins, AJ Lyons, T Zheng, DY Otvos, JD Lackland, DT McGee, D Garvey, WT Klein, RL CA DCCT EDIC Res Grp TI Serum lipoproteins in the diabetes control and complications trial/epidemiology of diabetes intervention and complications cohort - Associations with gender and glycemia SO DIABETES CARE LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; CORONARY-ARTERY-DISEASE; GRADIENT GEL-ELECTROPHORESIS; ISCHEMIC-HEART-DISEASE; POSTMENOPAUSAL WOMEN; FOLLOW-UP; PROGRESSION; SUBCLASSES; TRIAL; ATHEROSCLEROSIS AB Objective-To relate the nuclear magnetic resonance (NMR)-determined lipoprotein profile, conventional lipid and apolipoprotein measures, and in vitro oxidizibility of LDL with gender and glycemia in type 1 diabetes. Research Design and Methods-in the 1997-1999 Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complications (DCCT/EDIC) cohort, serum from 428 women and 540 men were characterized by conventional lipids, NMR, apolipoprotein levels, and LDL susceptibility to in vitro oxidation. Simple and partial correlation coefficients were calculated for each lipoprotein-related parameter versus gender, with and without covariates (age, diabetes duration, concurrent HbA(1c), DCCT randomization, hypertension, BMI, waist-to-hip ratio, and albuminuria). For concurrent HbA(1c), data were analyzed as above, exchanging gender for HbA(1c). Associations were significant if P<0.05. Results-Although men and women had similar total and LDL cholesterol and triglycerides, men exhibited the following significant percent differences in NMR profiles versus women: small VLDL 41; IDL -30; medium LDL 39; small LDL 2 1; large HDL -32; small HDL 35; LDL particle concentration 4; VLDL and HDL diameters -8 and -4, respectively. Small VLDL, small HDL, medium LDL (women only), small LDL (men only), and LDL particle concentration were positively correlated, and HDL size was inversely correlated, with concurrent HbA(1c). NMR profile was unrelated to prior DCCT randomization. Susceptibility of LDL to oxidation was unrelated to gender and glycemia. Conclusions-Male gender and poor glycemia are associated with a potentially more. atherogenic NMR lipoprotein profile. Neither gender nor glycemia influence LDL oxidation in vitro. C1 Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Charleston, SC 29403 USA. Med Univ S Carolina, Dept Biometry, Charleston, SC 29425 USA. N Carolina State Univ, Dept Biochem, Raleigh, NC 27695 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. NDIC Epidemiol Diabet Intervent & Complicat, Bethesda, MD USA. RP Klein, RL (reprint author), Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, POB 250766,114 Doughty St, Charleston, SC 29403 USA. EM kleinrl@musc.edu FU NHLBI NIH HHS [P01 HL55782] NR 50 TC 71 Z9 74 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2003 VL 26 IS 3 BP 810 EP 818 DI 10.2337/diacare.26.3.810 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UM UT WOS:000185505100042 PM 12610042 ER PT J AU Wolf, M Sandler, L Hsu, K Vossen-Smirnakis, K Ecker, JL Thadhani, R AF Wolf, M Sandler, L Hsu, K Vossen-Smirnakis, K Ecker, JL Thadhani, R TI First-trimester C-roactive protein and subsequent gestational diabetes SO DIABETES CARE LA English DT Article ID APPARENTLY HEALTHY-MEN; INSULIN-RESISTANCE ATHEROSCLEROSIS; CARDIOVASCULAR RISK-FACTORS; REACTIVE PROTEIN; GLUCOSE-TOLERANCE; ADIPOSE-TISSUE; CIRCULATING INTERLEUKIN-6; SUBCLINICAL INFLAMMATION; METABOLIC SYNDROME; BLOOD-PRESSURE AB Objective-Systemic inflammation is associated with the development of type 2 diabetes. We tested the hypothesis that increased inflammation, measured early in pregnancy, is associated with the subsequent development of gestational diabetes mellitus (GDM), a precursor of type 2 diabetes. Research Design and Methods-We conducted a prospective nested case-control study in a pregnancy cohort. First-trimester C-reactive protein (CRP) levels were measured using a high-resolution assay in 43 women who subsequently developed GDM and in a random sample of 94 women who remained euglycemic throughout pregnancy. Median CRP levels were compared using Wilcoxon's rank-sum test. Logistic regression was used to compute unadjusted and multivariable-adjusted odds ratios for developing GDM among CRP tertiles. Results-First-trimester CRP levels were significantly increased among women who subsequently developed GDM compared with control subjects (3.1 vs. 2.1 mg/l, P<0.01). The risk of developing GDM among women in the highest CRP tertile compared with the lowest tertile was 3.2 (95% CI 1.2-8.8). After adjusting for age, race/ethnicity, smoking, parity, blood pressure, and gestational age at CRP sampling, the risk of developing GDM among women in the highest compared with the lowest tertile was 3.6 (95% CI 1.2-11.4). When BMI was included in the model, however, the association between increased CRP and GDM was attenuated (odds ratio for the highest compared with lowest tertile 1.5 [95% CI 0.4-5.5]). Conclusions-in women who develop GDM, there is evidence of increased inflammation during the first trimester. This association is mediated in part by increased BMI. Larger studies are needed to verify these results. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit,Dept Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Wolf, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit,Dept Med, Bulfinch 127,55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL04095, HL03804]; NICHD NIH HHS [HD39223] NR 43 TC 107 Z9 113 U1 1 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2003 VL 26 IS 3 BP 819 EP 824 DI 10.2337/diacare.26.3.819 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UM UT WOS:000185505100043 PM 12610043 ER PT J AU Meneilly, GS McIntosh, CHS Pederson, RA Habener, JF Ehlers, MRW Egan, JM Elahi, D AF Meneilly, GS McIntosh, CHS Pederson, RA Habener, JF Ehlers, MRW Egan, JM Elahi, D TI Effect of glucagon-like peptide 1 (7-36 amide) on insulin-mediated glucose uptake in patients with type 1 diabetes SO DIABETES CARE LA English DT Article ID GLYCOGEN-SYNTHASE; SKELETAL-MUSCLE; GLP-I; METABOLISM; MELLITUS; HUMANS; RATS; SENSITIVITY; HEPATOCYTES; INHIBITION AB OBJECTIVE - To examine the insulinomimetic insulin-independent effects of glucagon-like peptide (GLP)-1 on glucose uptake in type I diabetic patients. RESEARCH DESIGN AND METHODS - We used the hyperinsulinemic-euglycemic clamp (480 pmol . m(-2) . min(-1)) in paired randomized studies of six women and five men with type 1 diabetes. In the course of one of the paired studies, the subjects also received GLP-1 at a dose of 1.5 pmol . kg(-1) . min(-1). The patients were 41 +/- 3 years old with a BMI of 25 +/- 1 kg/m(2). The mean duration of diabetes was 23 - 3 years. RESULTS - Plasma glucose was allowed to fall from a fasting level of similar to11 mmol/l to 5.3 mmol/l in each study and thereafter was held stable at that level. Plasma insulin levels during both studies were similar to900 pmol/l. Plasma C-peptide levels did not change during the studies. In the GLP-1 study, plasma total GLP-1 levels were elevated from the fasting level of 31 +/- 3 to 150 +/- 17 pmol/l. Plasma glucagon levels fell from the fasting levels of similar to 14 pmol/l to 9 pmol/l during both paired studies. Hepatic glucose production was suppressed during the glucose clamps in all studies. Glucose uptake was not different between the two studies (similar to40 mumol . kg(-1) . min(-1)). CONCLUSIONS - GLP-1 does not augment insulin-mediated glucose uptake in lean type 1 diabetic patients. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Geriatr Res Lab, Boston, MA 02114 USA. Univ British Columbia, Dept Med, Vancouver, BC, Canada. Univ British Columbia, Dept Physiol, Vancouver, BC, Canada. Harvard Univ, Sch Med, Howard Hughes Med Inst, Mol Endocrinol Lab, Boston, MA 02115 USA. Restoragen Inc, Dept Drug Dev, Lincoln, NE USA. NIA, NIH, Baltimore, MD 21224 USA. RP Elahi, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Geriatr Res Lab, GRB SB 0015,55 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-98-02] NR 29 TC 24 Z9 28 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2003 VL 26 IS 3 BP 837 EP 842 DI 10.2337/diacare.26.3.837 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 724UM UT WOS:000185505100046 PM 12610046 ER PT J AU Davis, TM Baer, JS Saxon, AJ Kivlahan, DR AF Davis, TM Baer, JS Saxon, AJ Kivlahan, DR TI Brief motivational feedback improves post-incarceration treatment contact among veterans with substance use disorders SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE motivational interviewing; treatment; veterans; criminal justice; prisons ID INTERVENTION; DRINKERS; OUTPATIENTS; READINESS; PROGRAM AB Objectives: To test the efficacy of providing brief motivational feedback to increase post-incarceration substance use disorders (SUD) treatment contact. Design: Randomized clinical trial (feedback vs. control) with a 2-month post-incarceration follow-up. Participants: Veterans (N = 73) incarcerated in a county jail system who met SUD diagnostic criteria. Measures: Baseline assessment included the Addiction Severity Index, the Form-90 assessment of recent alcohol use, and a DSM-IV SUD criteria checklist. The primary outcome was Veterans Adminstration (VA) appointments. Secondary outcomes were the Addiction Severity Index-Followup and the Treatment Services Review. Intervention: All participants received baseline assessment. The feedback condition received personalized feedback and encouragement to explore ambivalence about change and treatment in a single interview. Results: Participants receiving feedback were more likely to schedule appointments at a VA addictions clinic within 60 days of their jail release dates (67 vs. 41%; P <0.03). Though differences were not statistically significant, more feedback participants attended addictions clinic appointments (47 vs. 32%; ns) and were retained in addictions treatment at 90 days (31 vs. 14%; P < 0.08). Treatment appointments were more likely when intervention occurred close to release. Loss of participants to post-release follow-up interviews was > 50%, limiting power to detect significant differences by self-report. Conclusion: Brief motivational feedback shows promise as a way to link incarcerated individuals to SUD treatment services. Published by Elsevier Science Ireland Ltd. C1 VA Puget Sound Hlth Care Syst, Seattle Div, Ctr Excellence Substance Abuse Treatment & Educ, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. RP Davis, TM (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div, Ctr Excellence Substance Abuse Treatment & Educ, S116ATC,1660 S Columbian Way, Seattle, WA 98108 USA. NR 32 TC 30 Z9 30 U1 0 U2 6 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAR 1 PY 2003 VL 69 IS 2 BP 197 EP 203 AR PII S0376-8716(02)00317-4 DI 10.1016/S0376-8716(02)00317-4 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 650PP UT WOS:000181272800010 PM 12609701 ER PT J AU Schlozman, SC AF Schlozman, SC TI Innovative models for school consultation SO EDUCATIONAL LEADERSHIP LA English DT Article C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Harvard Univ, Harvard Grad Sch Educ, Cambridge, MA 02138 USA. RP Schlozman, SC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC SUPERVISION CURRICULUM DEVELOPMENT PI ALEXANDRIA PA 1703 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0013-1784 J9 EDUC LEADERSHIP JI Educ. Leadership PD MAR PY 2003 VL 60 IS 6 BP 87 EP 89 PG 3 WC Education & Educational Research SC Education & Educational Research GA 653GY UT WOS:000181427900020 ER PT J AU Qian, J Colbert, MC Witte, D Kuan, CY Gruenstein, E Osinska, H Lanske, B Kronenberg, HM Clemens, TL AF Qian, J Colbert, MC Witte, D Kuan, CY Gruenstein, E Osinska, H Lanske, B Kronenberg, HM Clemens, TL TI Midgestational lethality in mice lacking the parathyroid hormone (PTH)/PTH-related peptide receptor is associated with abrupt cardiomyocyte death SO ENDOCRINOLOGY LA English DT Article ID VASCULAR SMOOTH-MUSCLE; OSTEOBLAST-LIKE CELLS; PTH/PTHRP RECEPTOR; TRANSGENIC MICE; PROTEIN PTHRP; TARGETED OVEREXPRESSION; BLOOD-PRESSURE; CA2+ CHANNELS; FREE CALCIUM; EXPRESSION AB PTHrP is a key developmental regulatory protein and a potent vasoactive agent. Previous studies have shown that mice lacking either the Pthrp or the PTH type 1 receptor (Pth1r) gene exhibit severe chondrodysplasia. In addition, in most genetic backgrounds, the receptor null mice die prenatally at mid-gestation, but the cause of death remains elusive. Here we show the loss of the Pth1r gene in C57BL6 mice leads to massive, abrupt cardiomyocyte death and embryonic lethality between embryonic days (E) E11.5 and E12.5. PTH1R mRNA was abundantly expressed in the developing wild-type mouse heart and cardiomyocytes from E11.5 embryos demonstrated acute increases in cAMP and increased Ca2+ oscillations in response to PTHrP-(1-34)NH2. Analyses of more than 300 embryos (E8-E14.5) from C57BL6/PTH1R +/- matings showed that PTH1R-/- mice survived until Ell with no obvious defects in any tissue. By E12, only 10% of the PTH1R-/- embryos survived and all PTH1R null mice were dead by E13. Ultrastructural and histological analysis revealed striking mitochondrial abnormalities at E11.5 and precipitous cardiomyocyte death between E12.0 and E12.5, followed by degenerative changes in the liver and massive necrosis of other tissues. No abnormalities were observed in the yolk sac or placenta implicating the heart degeneration as the primary cause of death. Taken together, these findings indicate that the PTH1R is required for the development of normal cardiomyocyte function. C1 Univ Cincinnati, Dept Med, Cincinnati, OH 45267 USA. Univ Cincinnati, Dept Mol Genet, Cincinnati, OH 45267 USA. Childrens Hosp, Med Ctr, Dept Pathol, Cincinnati, OH 45229 USA. Childrens Hosp, Med Ctr, Dept Mol Dev Biol, Cincinnati, OH 45229 USA. Forsythe Inst, Dept Oral Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Dent, Boston, MA 02115 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Clemens, TL (reprint author), Vontz Ctr Mol Studies, Div Endocrinol & Metab, 3125 Eden Ave, Cincinnati, OH 45267 USA. FU NHLBI NIH HHS [HL-36059, HL-47811]; NIDDK NIH HHS [DK-56246] NR 45 TC 29 Z9 29 U1 0 U2 3 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 2003 VL 144 IS 3 BP 1053 EP 1061 DI 10.1210/en.2002-220993 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 648WL UT WOS:000181173900034 PM 12586782 ER PT J AU Silverman, SL AF Silverman, SL TI Calcitonin SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article ID INTRANASAL SALMON-CALCITONIN; POSTMENOPAUSAL BONE LOSS; OSTEOPOROTIC VERTEBRAL FRACTURES; ESTABLISHED OSTEOPOROSIS; RANDOMIZED TRIAL; DOUBLE-BLIND; NASAL CALCITONIN; MINERAL DENSITY; DOSE-RESPONSE; PREVENTION AB Calcitonin is FDA approved for the treatment of postmenopausal osteoporosis but not for prevention. The preferred delivery system is nasal. Nasal calcitonin is safe and well tolerated. The vertebral fracture efficacy of calcitonin is less robust than the two approved bisphosphonates (alendronate and risedronate) but is similar to raloxifene in the treatment of established osteoporosis. Calcitonin has not been demonstrated to reduce hip fracture risk, although a post-hoc pooled analysis suggests potential effectiveness of nasal calcitonin. Calcitonin produces small increments in bone mass of the spine and modestly reduces bone turnover in women with osteoporosis. Calcitonin may have analgesic benefit in patients with acute painful vertebral fractures. Treatment with calcitonin should be considered for older women with osteoporosis with painful vertebral fractures and for women who fail to respond to or cannot tolerate bisphosphonates. Calcitonin may also be indicated for women who are unable to take bisphosphonates because of impaired renal function. C1 OMC Clin Res Ctr, Beverly Hills, CA 90211 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Greater Los Angeles VA Med Ctr, Los Angeles, CA 90073 USA. RP Silverman, SL (reprint author), OMC Clin Res Ctr, 8641 Wilshire Blvd,Suite 301, Beverly Hills, CA 90211 USA. NR 53 TC 25 Z9 30 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 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD MAR PY 2003 VL 32 IS 1 BP 273 EP + DI 10.1016/S0889-8529(02)00060-9 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 661UH UT WOS:000181907900016 PM 12699303 ER PT J AU Wu, MT Kelsey, K Schwartz, J Sparrow, D Weiss, S Hu, H AF Wu, MT Kelsey, K Schwartz, J Sparrow, D Weiss, S Hu, H TI A delta-aminolevulinic acid dehydratase (ALAD) polymorphism may modify the relationship of low-level lead exposure to uricemia and renal function: The Normative Aging Study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE delta-aminolevulinic; acid dehydratase; bone lead; serum creatinine; serum uric acid ID BLOOD LEAD; BONE LEAD; ELDERLY MEN; WORKERS; ASSOCIATIONS; TOXICITY; GENOTYPE; MARKER AB In this study we investigated whether a known delta-aminolevulinic acid dehydratase (ALAD) exon 4 polymorphism has a modifying effect on the association of blood or bone lead level with uricemia and indices of renal function among middle-aged and elderly men. We performed a cross-sectional study of subjects who participated between 1991 and 1995 in the Department of Veterans Affairs Normative Aging Study. Information on blood lead levels, bone lead levels (measured by K-shell X-ray fluorescence), serum uric acid, serum creatinine, estimated creatinine clearance, and ALAD polymorphism status was available in 709 subjects. Regression models were constructed to examine the relationships of serum uric acid, serum creatinine, and estimated creatinine clearance to blood or bone lead level, stratified by genotype. We also adjusted for age, body mass index, blood pressure, smoking, alcohol consumption, and ingestion of analgesic medications (n = 638). Of the 709 subjects, 7 (1%) and 107 (15%) were homozygous and heterozygous for the variant (ALAD-2) allele, respectively. The mean (range) serum uric acid and creatinine levels were 6.5 (2.9-10.6) and 1.2 (0.6-2.5) mg/dL. No significant differences were found in serum uric acid, serum creatinine, or estimated creatinine, clearance by ALAD genotype. However, after adjusting for other potential confounders, we found a significant linear relationship between serum uric acid and patella bone lead (p = 0.040) among the ALAD 1-2/2-2 genotype individuals above a threshold patellar lead level of 15 mug/g. In contrast, among the wild-type (ALAD 1-1) individuals, there was a suggestion of a significant linear relationship of serum uric acid with patella bone lead (p = 0.141), but only after a threshold of 101 mug/g. There was evidence of a significant (P = 0.025) interaction of tibia lead with genotype (ALAD 1-1 vs. ALAD 1-212-2) regarding serum creatinine as an outcome, but in the same linear regression model tibia lead alone was not a significant predictor of serum creatinine. Conversely, for estimated creatinine clearance, patella lead,,but not the interaction of patella lead with genotype, was a significantly independent predictor (p = 0.026). Our findings suggest that ALAD genotype may modify the effect of lead on the renal excretion of uric acid as well as overall renal function among middle-aged and elderly men who had community (nonoccupational) exposures to lead. Additional research is needed to ascertain whether this constitutes a true gene-environment interaction and, if so, its clinical impact. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Kaohsiung Med Univ Hosp, Grad Inst Occupat Safety & Hlth, Kaohsiung, Taiwan. Kaohsiung Med Univ Hosp, Dept Occupat Med, Kaohsiung, Taiwan. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. US Dept Vet Affairs, Normat Aging Study, Boston, MA USA. RP Hu, H (reprint author), Harvard Univ, Sch Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. RI Wu, Ming-Tsang/G-5637-2012 FU NCRR NIH HHS [M01RR02635]; NIEHS NIH HHS [P42-ES05947, ES 05257-06A1, 2 P30 ES00002, 2R44 ES03918-02] NR 33 TC 28 Z9 29 U1 0 U2 3 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2003 VL 111 IS 3 BP 335 EP 340 DI 10.1289/ehp.5504 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 655ZJ UT WOS:000181583200030 PM 12611663 ER PT J AU Maass, A Scholz, J Moser, A AF Maass, A Scholz, J Moser, A TI Modeled ligand-protein complexes elucidate the origin of substrate specificity and provide insight into catalytic mechanisms of phenylalanine hydroxylase and tyrosine hydroxylase SO EUROPEAN JOURNAL OF BIOCHEMISTRY LA English DT Article DE phenylalanine hydroxylase; tyrosine hydroxylase; substrate specificity; catecholamines; feedback inhibition ID AMINO-ACID HYDROXYLASES; CRYSTAL-STRUCTURE; ACTIVE-SITE; PHOSPHORYLATION; BINDING; DOCKING; DOMAIN; IDENTIFICATION; SPECTROSCOPY; MUTAGENESIS AB NMR spectroscopy and X-ray crystallography have provided important insight into structural features of phenylalanine hydroxylase (PAH) and tyrosine hydroxylase (TH). Nevertheless, significant problems such as the substrate specificity of PAH and the different susceptibility of TH to feedback inhibition by l-3,4-dihydroxyphenylalanine (l-DOPA) compared with dopamine (DA) remain unresolved. Based on the crystal structures 5pah for PAH and 2toh for TH (Protein Data Bank), we have used molecular docking to model the binding of 6(R )-l-erythro-5,6,7,8-tetrahydrobiopterin (BH4 ) and the substrates phenylalanine and tyrosine to the catalytic domains of PAH and TH. The amino acid substrates were placed in positions common to both enzymes. The productive position of tyrosine in TH.BH4 was stabilized by a hydrogen bond with BH4 . Despite favorable energy scores, tyrosine in a position trans to PAH residue His290 or TH residue His336 interferes with the access of the essential cofactor dioxygen to the catalytic center, thereby blocking the enzymatic reaction. DA and l-DOPA were directly coordinated to the active site iron via the hydroxyl residues of their catechol groups. Two alternative conformations, rotated 180degrees around an imaginary iron-catecholamine axis, were found for DA and l-DOPA in PAH and for DA in TH. Electrostatic forces play a key role in hindering the bidentate binding of the immediate reaction product l-DOPA to TH, thereby saving the enzyme from direct feedback inhibition. C1 Fraunhofer Inst Algorithms & Sci Comp SCAI, D-53754 St Augustin, Germany. Med Univ Lubeck, Dept Neurol, Neurochem Res Grp, D-23538 Lubeck, Germany. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Maass, A (reprint author), Fraunhofer Inst Algorithms & Sci Comp SCAI, Schloss Birlinghoven, D-53754 St Augustin, Germany. NR 42 TC 10 Z9 10 U1 1 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0014-2956 J9 EUR J BIOCHEM JI Eur. J. Biochem. PD MAR PY 2003 VL 270 IS 6 BP 1065 EP 1075 DI 10.1046/j.1432-1033.2003.03429.x PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 655JX UT WOS:000181549200006 PM 12631267 ER PT J AU Enzweiler, CNH Wiese, TH Petersein, J Lembcke, AE Borges, AC Dohmen, P Hoffmann, U Hamm, B AF Enzweiler, CNH Wiese, TH Petersein, J Lembcke, AE Borges, AC Dohmen, P Hoffmann, U Hamm, B TI Diameter changes of occluded venous coronary artery bypass grafts in electron beam tomography: preliminary findings SO EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY LA English DT Article DE coronary vessels, diseases; coronary vessels, stents and prostheses; coronary vessels, surgery; coronary vessels, computed tomography; computed tomography, electron beam; computed tomography, angiography ID COMPUTED-TOMOGRAPHY; SAPHENOUS-VEIN; FOLLOW-UP; THROMBOSIS; ANGIOGRAPHY; DIAGNOSIS; DISEASE; PATENCY; CT AB Objective: To differentiate acute from chronic graft occlusions through diameter measurements by means of electron beam tomography (EBT). Methods: Contrast enhanced EBT volume studies were carried out in 37 patients with one or more occluded venous coronary bypass grafts. Seventeen of 37 patients did not meet the inclusion criteria and were excluded from the assessment. The remaining 20 patients had a total of 39 bypasses (16 patent, 23 occluded) and were assigned to one of three groups: group A consisted of patent grafts only (patent grafts, 13 patients). Group B comprised 11 of 23 occluded grafts diagnosed within 10 days after bypass surgery (acutely occluded grafts, ten patients). Group C contained 12 of 23 bypass occlusions that were at least 6 months old as documented by coronary angiography (chronically occluded grafts, ten patients). The mean graft diameter was determined by repetitive measurements on a workstation through blinded readers. The Mann-Whitney-U-test for unpaired samples was used for statistical evaluation. Results: Mean graft diameter for groups A-C (patent, acutely, and chronically occluded bypasses, respectively) was 3.9 mm ( +/-0.6; n = 16), 5.4 mm ( +/-1.9; n = 11), and 0.3 mm (+/-.9; n = 12), respectively (P < 0.01 each). Sensitivity and specificity for the detection of acute and chronic occlusions were 87 and 92% (cut-off 4.5 mm), respectively, and 92 and 96% (cut-off 1 mm), respectively. Conclusions: EBT may allow for non-invasive differentiation between acute and chronic venous coronary bypass occlusions. This could help prevent unnecessary invasive recanalization procedures. Body veins may conserve their ability to increase in diameter in acute thrombosis when transplanted as coronary bypasses. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Humboldt Univ, Charite, Dept Radiol, Berlin, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. Humboldt Univ, Charite, Dept Cardiothorac Surg, Berlin, Germany. RP Enzweiler, CNH (reprint author), Humboldt Univ, Charite, Dept Radiol, Berlin, Germany. NR 21 TC 6 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1010-7940 J9 EUR J CARDIO-THORAC JI Eur. J. Cardio-Thorac. Surg. PD MAR PY 2003 VL 23 IS 3 BP 347 EP 353 DI 10.1016/S1010-7940(02)00802-3 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 656VR UT WOS:000181630800024 PM 12614805 ER PT J AU Schumacher, B Alpi, A Wittenburg, N Boulton, S Hofmann, K Saham, S Vidal, M Conradt, B Gartner, A AF Schumacher, B Alpi, A Wittenburg, N Boulton, S Hofmann, K Saham, S Vidal, M Conradt, B Gartner, A TI The roads to death, DNA damage induced apoptosis in the C. elegans germline SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Deutschen-Gesellschaft-fur-Zellbiologie/Gesellschaft-fur-Entwicklungsbio logie CY MAR 26-29, 2003 CL BONN, GERMANY SP Deutsch Gesell Zellbiol, Gesell Entwicklungsbiol C1 Max Planck Inst Biochem, Dept Cell Biol, D-82152 Martinsried, Germany. Max Planck Inst Neurobiol, Cell Death Regulat Grp, D-82152 Martinsried, Germany. Memorec Stoffel GmbH, D-50829 Cologne, Germany. Canc Res UK, Clare Hall Labs, S Mimms, Herts, England. Rockefeller Univ, New York, NY 10021 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Conradt, Barbara/K-2665-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD MAR PY 2003 VL 82 SU 53 BP 56 EP 56 PG 1 WC Cell Biology SC Cell Biology GA 663QL UT WOS:000182016200102 ER PT J AU Ogino, S Gao, SZ Leonard, DGB Paessler, M Wilson, RB AF Ogino, S Gao, SZ Leonard, DGB Paessler, M Wilson, RB TI Inverse correlation between SMN1 and SMN2 copy numbers: evidence for gene conversion from SMN2 to SMN1 SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE spinal muscular atrophy; SMN1; SMN2; copy number; gene conversion; SMN ID SPINAL MUSCULAR-ATROPHY; DE-NOVO; DOSAGE ANALYSIS; SURVIVAL; IDENTIFICATION; SMA; MECHANISMS; PHENOTYPE; COPIES; PCR AB Most carriers of autosomal recessive spinal muscular atrophy (SMA) have only one copy of SMN1 because of SMN1 gene deletions or gene conversions from SMN1 to SMN2, which has only one base difference in coding sequence from SMN1. Using SMN gene dosage analysis, we determined the copy numbers of SMN1 and SMN2 in the general population as well as in SMA patients and carriers. Increased SMN1 copy number is associated with decreased SMN2 copy number in the general population; that is, SMN2 copy number was decreased to one or zero copies in 11 of 13 individuals with three or four copies of SMN1, whereas only 71 of 16.4 individuals with two copies of SMN1 had one or zero copies of SMN2 (P<0.01). SMN2 copy number was increased to three or four in a subset of SMN1 deletion/conversion carriers, and in most SMA patients with a milder phenotype. In conclusion, our data provide evidence that gene conversion from SMN2 to SMN1 occurs, and that SMN1 converted from SMN2 is present in the general population. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. Univ Penn, Med Ctr, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Ogino, S (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St,Amory 3rd Floor, Boston, MA 02115 USA. NR 19 TC 19 Z9 21 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD MAR PY 2003 VL 11 IS 3 BP 275 EP 277 DI 10.1038/sj.ejhg.5200957 PG 3 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 666RG UT WOS:000182189800011 PM 12673282 ER PT J AU Klein, L Trautman, L Psarras, S Schnell, S Siermann, A Liblau, R von Boehmer, H Khazaie, K AF Klein, L Trautman, L Psarras, S Schnell, S Siermann, A Liblau, R von Boehmer, H Khazaie, K TI Visualizing the course of antigen-specific CD8 and CD4 T cell responses to a growing tumor SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE tumor; antigen; CD4/CD8; T cell; immune response; exhaustion ID IN-VIVO; IFN-GAMMA; CROSS-PRESENTATION; SELF-ANTIGENS; SOLID TUMORS; ACTIVATION; TOLERANCE; ERADICATION; DELETION; RECEPTOR AB Spontaneous tumors frequently express antigens that can be recognized by the immune system but nevertheless manage to evade immune surveillance. To better understand the mechanism of evasion, we followed CD8 and CD4 T cells reacting against a subcutaneously growing tumor, modified to express influenza hemagglutinin (HA) as surrogate tumor antigen. Adoptive transfer of 8,000 antigen-specific CD8 T cells was sufficient to protect against challenge with 1x10(6) tumor cells, while larger numbers of T cells rejected established tumors. HA-specific CD4 T cells could not reject tumors on their own but helped rejection by CD8 T cells. Rejection of the tumor coincided with prolonged survival of expanded antigen-specific CD8 and CD4 T cells, while a failing anti-tumor response was accompanied by transient expansion followed by rapid elimination of antigen-specific T cells. Thus, a highly immunogenic tumor can evade immune surveillance because of an insufficient number of tumor-specific T cells and antigen overload, resulting in exhaustion of the immune response. In this scenario, adoptive immunotherapy rather than vaccination promises successful treatment. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & Aids, Boston, MA 02115 USA. Univ Athens, Allergy Unit, Pediat Clin 2, Athens, Greece. Inst Biol, INSERM, Unite 463, Nantes, France. Hop La Pitie Salpetriere, Lab Immunol Cellulaire, Paris, France. RP Khazaie, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & Aids, 44 Binney St, Boston, MA 02115 USA. RI Klein, Ludger/G-8785-2011 NR 32 TC 40 Z9 41 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAR PY 2003 VL 33 IS 3 BP 806 EP 814 DI 10.1002/eji.200323800 PG 9 WC Immunology SC Immunology GA 655WT UT WOS:000181576200024 PM 12616501 ER PT J AU Hagopian, K Ramsey, JJ Weindruch, R AF Hagopian, K Ramsey, JJ Weindruch, R TI Influence of age and caloric restriction on liver glycolytic enzyme activities and metabolite concentrations in mice SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE caloric restriction; glucose; glycolysis; glycolytic metabolites; glycolytic enzymes ID GLUCOKINASE GENE-TRANSCRIPTION; RAT-LIVER; PYRUVATE-KINASE; MESSENGER-RNA; FRUCTOSE 2,6-BISPHOSPHATE; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; DIETARY RESTRICTION; RHESUS-MONKEYS; MAMMARY-GLAND; REDOX STATUS AB The influence of caloric restriction (CR) from 2 months of age on the activities of liver glycolytic enzymes and metabolite levels was studied in young and old mice. Livers were sampled 48 h after the last scheduled feeding time. Old mice on CR showed significant decreases in the activities of all the enzymes studied, except for aldolase, triosephosphate isomerase and phosphoglycerate mutase, which were unchanged. The metabolites glucose, glucose-6-phosphate, fructose-6-phosphate, pyruvate and lactate were lower while fructose-1,6-bisphosphate, glyceraldehyde-3-phosphate, dihydroxyacetone phosphate, 3-phosphoglycerate and phosphoenolpyruvate were increased in old CR. Young mice on CR also showed reduced enzyme activities, except for aldolase, triosephosphate isomerase and enolase which were unchanged when compared with young controls. The metabolites glucose, glucose-6-phosphate, fructose-6-phosphate and pyruvate were decreased when compared with young controls, while phosphoenolpyruvate was increased. Ketone bodies increased (65%) in old, but not young, CR mice while fructose-2,6-bisphosphate decreased in both young (22%) and old CR (28%) mice. The results indicate that decreased hepatic glucose levels in CR mice are associated with decreased enzyme activities but not a uniform decrease in metabolite levels. Increased ketone body levels indicate increased utilization of non-carbohydrate fuels while decreased fructose- 2,6-bisphosphate level suggests its importance in the control of glycolysis in CR. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Univ Calif Davis, Dept Mol Biosci, Sch Vet Med, Davis, CA 95616 USA. Univ Wisconsin, Sch Med, Dept Med, Madison, WI 53705 USA. William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53715 USA. RP Hagopian, K (reprint author), Univ Calif Davis, Dept Mol Biosci, Sch Vet Med, 1 Shield Ave, Davis, CA 95616 USA. EM khagopian@ucdavis.edu FU NIA NIH HHS [R01 AG17902, P01 AG11915] NR 59 TC 44 Z9 46 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD MAR PY 2003 VL 38 IS 3 BP 253 EP 266 AR PII S0531-5565(02)00203-6 DI 10.1016/S0531-5565(02)00203-6 PG 14 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 653HL UT WOS:000181429100006 PM 12581789 ER PT J AU Hagopian, K Ramsey, JJ Weindruch, R AF Hagopian, K Ramsey, JJ Weindruch, R TI Caloric restriction increases gluconeogenic and transaminase enzyme activities in mouse liver SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE caloric restriction; gluconeogenesis; phosphoenolpyruvate carboxykinase; pyruvate carboxylase; fructose-1,6-bisphosphatase; glucose-6-phosphatase; transaminase ID FOOD RESTRICTION; GENE-EXPRESSION; RAT-LIVER; ASPARTATE-AMINOTRANSFERASE; PYRUVATE-CARBOXYLASE; PROTEIN-TURNOVER; PHOSPHOENOLPYRUVATE CARBOXYKINASE; HEPATIC GLUCONEOGENESIS; DIETARY RESTRICTION; FISCHER-344 RAT AB Long-term caloric restriction (CR) has been shown to extend maximum life span in laboratory rodents. We investigated the activities of gluconeogenic and transaminase enzymes in the livers of old and young mice fed either control or calorie-restricted diets. Livers were sampled 48 h after the last scheduled feeding time. Old mice on CR showed significant increases in the activities of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase and glucose-6-phosphatase when compared with controls, indicating increased gluconeogenesis. Increased activities of tyrosine, tryptophan, histidine, phenylalanine, alanine and aspartate transaminases, as well as of malate and glutamate dehydrogenases were also observed, while branched-chain amino acid transaminase was unchanged. Young mice on CR showed a significant increase only in the phosphoenolpyruvate carboxykinase activity in the gluconeogenic pathway, while transaminases were increased significantly, except for tryptophan and branched-chain amino acid transaminases. Glutamate dehydrogenase also showed increased activity but malate dehydrogenase was unchanged. Increases in the level of acetyl-CoA and [Acetyl-CoA]/[CoA] ratio were observed only in the old CR mice. Our results demonstrate increased gluconeogenic activity in CR mice and are consistent with a state of increased hepatic gluconeogenesis and protein turnover during CR. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Univ Wisconsin, Sch Med, Dept Med, Madison, WI 53705 USA. William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. Univ Calif Davis, Dept Mol Biosci, Sch Vet Med, Davis, CA 95616 USA. Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53715 USA. RP Hagopian, K (reprint author), Univ Wisconsin, Sch Med, Dept Med, Madison, WI 53705 USA. EM khagopian@ucdavis.edu FU NIA NIH HHS [P01 AG11915, R01 AG17902] NR 63 TC 75 Z9 77 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD MAR PY 2003 VL 38 IS 3 BP 267 EP 278 AR PII S0531-5565(02)00202-4 DI 10.1016/S0531-5565(02)00202-4 PG 12 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 653HL UT WOS:000181429100007 PM 12581790 ER PT J AU Parmar, K Sauk-Schubert, C Burdick, D Handley, M Mauch, P AF Parmar, K Sauk-Schubert, C Burdick, D Handley, M Mauch, P TI Sca(+)CD34(-) murine side population cells are highly enriched for primitive stem cells SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; ACUTE MYELOID-LEUKEMIA; HEMATOPOIETIC STEM; BONE-MARROW; FETAL LIVER; IN-VITRO; COMPETITIVE REPOPULATION; PROGENITOR CELLS; CYTOTOXIC AGENTS; CD34 ANTIGEN AB Objective. The aim of this study was to characterize murine side population (SP) stem cells and SP cell subpopulations for primitive stem cell capacity. Materials and Methods. SP cells, characterized by a specific Hoechst dye efflux pattern, were isolated by flow cytometric analysis and sorting from murine adult whole bone marrow (WBM). Different subpopulations of SP cells were isolated by staining with anti-Sca and anti-CD34 antibodies. Primitive stem cell content of SP cells and SP subsets were determined by cobblestone area-forming cell (CAFC) frequencies. Results. Measurement of CAFC frequencies revealed that SP cells are greatly enriched for both primitive stem cells (day-28-35 CAFC) and somewhat more mature hematopoietic cells (day 14-21 CAFC) compared to WBM. The day-28 and day-35 CAFC enrichments in SP cells vs WBM cells were 1065 and 471, respectively. Analysis of the subpopulations of SP cells revealed that SP(+)Sca(-)CD34(+) cells contained almost exclusively day-7 CAFC and had little day-28-35 CAFC activity. SP(+)Sca(+) CD34(+) cells had high day-7-14 CAFC frequencies, but lower day-35 CAFC frequencies compared to SP(+)Sca(+)CD34(-) cells. SP(+)Sca(+)CD34(-) cells contained very low day-7 CAFC activity, but nearly 2200 times the day-28-35 CAFC activity as normal bone marrow. To evaluate the influence of Hoechst dye efflux capacity, we divided the SP tail into four groups of cells. The SP cells with lowest efflux of Hoechst dye contained the highest progenitor activity (day-7-14 CAFC). The highest day-35 CAFC frequencies, nearly 6000 times those of normal marrow, were seen in the SP cells with the greatest efflux of the Hoechst dye. Conclusions. Murine SP cells contain both progenitor and primitive populations of hematopoietic stem cells. The most primitive stem cells measured in the in vitro CAFC assay mark for Sca(+) and CD34(-) and have a high ability to efflux Hoechst dye. Isolation of these cells may provide the means to directly study mechanisms of primitive stem cell damage. (C) 2003 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA USA. Dana Farber Canc Inst, Cell Sorter Facil Res Adm, DFCI Core Flow Cytometry Facil, Boston, MA USA. RP Mauch, P (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. FU NCI NIH HHS [CA-10941-30] NR 42 TC 20 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD MAR PY 2003 VL 31 IS 3 BP 244 EP 250 DI 10.1016/S0301-472X(02)01074-3 PG 7 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 656LY UT WOS:000181610300009 PM 12644022 ER PT J AU Carlson, JA Slominski, A Linette, GP Mihm, MC Ross, JS AF Carlson, JA Slominski, A Linette, GP Mihm, MC Ross, JS TI Biomarkers in melanoma: predisposition, screening and diagnosis SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE biomarkers; cell proliferation; comparative genomic hybridization; diagnosis; genetic screening; melanoma; tumor progression ID CUTANEOUS MALIGNANT-MELANOMA; BENIGN MELANOCYTIC NEVI; PIGMENTED SKIN-LESIONS; TUMOR-SUPPRESSOR GENE; MULTIPLE PRIMARY MELANOMAS; MELANOCORTIN-1 RECEPTOR MC1R; CDKN2A GERMLINE MUTATIONS; CYCLIN-DEPENDENT KINASES; FIBROBLAST-GROWTH-FACTOR; CLINIC-BASED POPULATION AB Melanoma's incidence and mortality for certain groups has appeared to level off after a steady increase over the last half century. This trend is suspected to be due to better detection and removal of thin, biological early melanomas. However, to date, no prospective evidence exists to clearly demonstrate the efficacy of prevention and early detection in decreasing melanoma mortlity. Nonetheless, many studies suggest that both self-assessment of risk factors or clinician examination can identify a proportion of patients at highest risk for melanoma who may benefit from behavior modification (primary prevention) and routine screening (secondary prevention). Compromising these goals is the fact that neither the clinical or histologic diagnosis of melanoma is 100% accurate. Clinical diagnosis of melanoma, based on evaluation of a skin lesion's color and shape, correlates best with the experience of the clinician. Ancillary technologies have been developed to improve clinical accuracy of suspicious skin lesions but a subset of melanomas exist that do not fall in the spectrum of the 'ABCDE' guidelines commonly used for melanoma identification. Similarly, at the histologic level (the 'gold standard' of diagnosis), overlap exists between benign and malignant melanocytic proliferations leading to both over and underdiagnosis of melanoma. A better understanding of melanoma's pathogenesis has identified disease-related biomarkers that may more reliably differentiate a melanocytic nevus from melanoma. In this paper, we review current and novel, potentially more accurate, biomarkers; and supplementary technologies that can be used for the prevention, screening and diagnosis of melanoma. C1 Albany Med Coll, Div Dermatopathol, Albany, NY 12208 USA. Univ Tennessee, Sch Med, Dept Pathol, Memphis, TN USA. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Millennium Pharmaceut Inc, Div Mol Med, Cambridge, MA USA. Albany Med Coll, Dept Pathol & Lab Med, Albany, NY 12208 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Carlson, JA (reprint author), Albany Med Coll, Div Dermatopathol, MC-81, Albany, NY 12208 USA. EM carlsoa@mail.amc.edu OI Carlson, John Andrew/0000-0002-6866-6314 NR 264 TC 19 Z9 19 U1 0 U2 0 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEYY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD MAR PY 2003 VL 3 IS 2 BP 163 EP 184 DI 10.1586/14737159.3.2.163 PG 22 WC Pathology SC Pathology GA 767KA UT WOS:000188437700005 PM 12647994 ER PT J AU Armstrong, K Weiner, J Weber, B Asch, DA AF Armstrong, K Weiner, J Weber, B Asch, DA TI Early adoption of BRCA1/2 testing: Who and why SO GENETICS IN MEDICINE LA English DT Article DE BRCA1/2 genetic testing; utilization; diffusion ID OVARIAN-CANCER SUSCEPTIBILITY; HEREDITARY BREAST; HEALTH PROMOTION; DIFFUSION-THEORY; MUTATIONS; FAMILIES; RISK; POPULATION; PREVENTION; DECISIONS AB Purpose: Relatively little is known about the characteristics of women who chose to undergo BRCA1/2 testing soon after testing became available, including how they became aware of and chose to pursue testing. Diffusion of innovation theory states that acceptance of an innovation is a function of the potential adopter's value for innovation and perceptions of the compatibility, complexity, and relative advantage of the innovation. These factors may contribute to early uptake of BRCA1/2 testing. The purpose of this study was to describe the characteristics of women who were "early adopters" of clinical BRCA1/2 testing and to determine whether diffusion theory explains variation in uptake of testing after participation in genetic counseling for BRCA1/2 testing. Methods: A retrospective cohort study of participants in genetic counseling for BRCA1/2 testing was conducted at a clinical program in a large academic health system. Measures included components of diffusion of innovation theory (participant's value for innovation, i.e., "innovativeness," and perceptions of the compatibility, complexity, and relative advantage of BRCA1/2 testing), characteristics of how the participant became aware of and sought BRCA1/2 testing, and decisions about testing after counseling. Results: From the 229 respondents, 71 (31%) had undergone testing at the time of the survey. Fifty-seven women (25%) had sought BRCA1/2 testing because a family member had breast or ovarian cancer and 37 (16%) because they had breast or ovarian cancer. Only 15 women (7%) reported seeking testing because of a physician's recommendation. After multivariate adjustment, higher innovativeness and higher ratings of the compatibility of BRCA1/2 testing were associated with undergoing testing after counseling [relative risk (RR) 1.76, 95% confidence interval (CI) 1.2-2.6]. However, ratings of the complexity or relative advantage of testing were not associated with testing decisions. Higher innovativeness was associated with being the first in the family to undergo testing (RR 4.85, 95% Cl 1.6-14.9), becoming aware of BRCA1/2 testing through the media (RR 1.50, 95% CI 1.0-2.4), and being aware of BRCA1/2 testing prior to counseling (RR 1.25, 95% CI 1.1-1.4). Conclusions: The uptake of BRCA1/2 testing among women undergoing genetic counseling was associated with innovative characteristics of the participant and the perceived compatibility of the test with existing values and needs, but not with the complexity or relative advantage of the test. Most "early adopters" had heard of BRCA1/2 testing from a source other than their physician and had sought testing because of a personal or family member's cancer diagnosis. These findings can inform predictions surrounding the introduction of future genetic susceptibility tests and strategies for guiding the further diffusion of BRCA1/2 testing. C1 Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Ctr Canc, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Armstrong, K (reprint author), 1233 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. OI Weiner, Janet/0000-0001-5810-5807; Asch, David/0000-0002-7970-286X FU NCI NIH HHS [CA57601, CA82393] NR 34 TC 23 Z9 24 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD MAR-APR PY 2003 VL 5 IS 2 BP 92 EP 98 DI 10.1097/01.GIM.0000056829.76915.2A PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 709QM UT WOS:000184635900007 PM 12644778 ER PT J AU Schneider, A Pogue-Geile, K Barmada, MM Myers-Fong, E Thompson, BS Whitcomb, DC AF Schneider, A Pogue-Geile, K Barmada, MM Myers-Fong, E Thompson, BS Whitcomb, DC TI Hereditary, familial, and idiopathic chronic pancreatitis are not associated with polymorphisms in the tumor necrosis factor alpha (TNF-alpha) promoter region or the TNF receptor 1 (TNFR1) gene SO GENETICS IN MEDICINE LA English DT Article DE chronic pancreatitis; gene polymorphisms; hereditary pancreatitis; soluble tumor necrosis factor receptors; tumor necrosis factor alpha ID SERINE-PROTEASE INHIBITOR; CYSTIC-FIBROSIS GENE; INSULIN-RESISTANCE; SOLUBLE RECEPTORS; KAZAL TYPE-1; CELL-DEATH; MUTATIONS; IDENTIFICATION; EXPRESSION; CLONING AB Purpose: Genetic alterations that are associated with acute and chronic pancreatitis remain to be identified. Methods: The authors investigated two functionally active tumor necrosis factor (TNF) promoter region polymorphisms at positions -238 and -308 and the entire coding region of the corresponding TNF receptor 1 (TNFR1) gene in 54 patients with hereditary, familial, and idiopathic chronic pancreatitis who were previously tested negative for cationic trypsinogen mutations by direct DNA sequencing. Results: In three patients, we detected novel DNA variants in the TNFR1 gene that did not segregate with the disease. The genotype frequencies of the TNF promoter polymorphisms were similar between patients and controls. Conclusion: These polymorphisms are not associated with hereditary, familial, or idiopathic chronic pancreatitis. C1 Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, VA Pittsburgh Hlth Care Syst, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Ctr Genom Sci, Pittsburgh, PA 15213 USA. RP Schneider, A (reprint author), Univ Pittsburgh, Dept Med, 571 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15213 USA. OI Barmada, M Michael/0000-0002-3604-6460 FU NIDDK NIH HHS [DK54709] NR 43 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD MAR-APR PY 2003 VL 5 IS 2 BP 120 EP 125 DI 10.1097/01.GIM.0000055199.32817.CA PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 709QM UT WOS:000184635900011 PM 12644782 ER PT J AU Xu, YH Stange-Thomann, N Weber, G Bo, RH Dodge, S David, RG Foley, K Beheshti, J Harris, NL Birren, B Lander, ES Meyerson, M AF Xu, YH Stange-Thomann, N Weber, G Bo, RH Dodge, S David, RG Foley, K Beheshti, J Harris, NL Birren, B Lander, ES Meyerson, M TI Pathogen discovery from human tissue by sequence-based computational subtraction SO GENOMICS LA English DT Review DE genome; lymphoma; pathogen; subtraction; virus ID BACILLARY ANGIOMATOSIS; EPSTEIN-BARR; HUMAN GENOME; IDENTIFICATION AB We have recently reported a new pathogen discovery approach, "computational subtraction". With this approach, non-human transcripts are detected by sequencing cDNA libraries from infected tissue and eliminating those transcripts that match the human genome. We show now that this method is experimentally feasible. We generated a cDNA library from a tissue sample of post-transplant lymphoproliferative disorder (PTLD). 27,840 independent cDNA sequences were filtered by computational subtraction against the known human sequence to identify 32 nonmatching transcripts. Of these, 22 (0.1%) were found to be amplifiable from both infected and noninfected samples and were inferred to be human DNA not yet contained in the available human genome sequence. The remaining 10 sequences could be amplified only from Epstein-Barr virus (EBV)-infected tissues. All 10 corresponded to the known EBV sequence. This proof-of-principle experiment demonstrates that computational subtraction can detect pathogenic microbes in primary human-diseased tissue. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. MIT, Whitehead Inst Biomed Res, Ctr Genome Res, Cambridge, MA 02142 USA. Brigham & Womens Hosp, Decis Syst Grp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. MIT, Dept Biol, Cambridge, MA 02138 USA. RP Meyerson, M (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Room M430,44 Binney St, Boston, MA 02115 USA. EM matthew_meyerson@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012; OI Weber, Griffin/0000-0002-2597-881X NR 18 TC 32 Z9 33 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD MAR PY 2003 VL 81 IS 3 BP 329 EP 335 DI 10.1016/S0888-7543(02)00043-5 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 663JE UT WOS:000182001800009 PM 12659816 ER PT J AU Batorfi, J Ye, B Mok, SC Cseh, I Berkowitz, RS Fulop, V AF Batorfi, J Ye, B Mok, SC Cseh, I Berkowitz, RS Fulop, V TI Protein profiling of complete mole and normal placenta using ProteinChip analysis on laser capture microdissected cells SO GYNECOLOGIC ONCOLOGY LA English DT Article DE surface-enhanced laser desorption/ionization mass spectrometry (SELDI-MS); laser; capture microdissection (LCM); gestational trophoblastic disease (GTD); complete hydatidiform mole ID HYDATIDIFORM MOLE; HUMAN TROPHOBLAST; C-FMS; EXPRESSION; CHORIOCARCINOMA; MYC; DIFFERENTIATION; IDENTIFICATION; ONCOPROTEINS; PROTEOMICS AB Introduction. Surface-enhanced laser desorption/ionization mass spectrometry (SELDI-MS) is a novel method for biomarker discovery that can provide a rapid protein expression profile from a variety of biological samples. Since SELDI-MS requires a small amount of biological material, this technique is ideal for analyzing proteins isolated from microdissected tissue samples. The current study was undertaken to investigate potential differences in protein expression between normal and molar trophoblast procured by laser capture microdissection (LCM) utilizing SELDI ProteinChip array technology. Further knowledge of protein expression in complete mole may advance our understanding of the pathogenesis of gestational trophoblastic diseases. Materials and methods. Laser capture microdissected trophoblast cells from nine fresh complete moles were analyzed and compared to the trophoblast cells from 10 fresh normal placentas of comparable gestational age, using SELDI ProteinChip to identify potential differences in protein expression. Results. Three metal binding polypeptides were identified with the estimated molecular weights of 11.3, 13.8, and 14.0 kDa, which appeared in significantly lower levels in complete mole as compared to normal trophoblast cells (P < 0.001, P < 0.03, and P < 0.01). Discussion. While further characterization of these protein peaks is important and necessary, our current work clearly demonstrates that the combined technology of SELDI and LCM is effective in distinguishing protein expression between normal placenta and complete mole. Further knowledge of protein expression in complete mole may advance our understanding of molecular mechanisms and improve management in gestational trophoblastic diseases. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Harvard Univ, Sch Med,Brigham & Womens Hosp,Div Gynecol Oncol, Dana Farber Canc Inst,Dept Obstet & Gynecol, New England Trophoblast Dis Ctr,Lab Gynecol Oncol, Boston, MA 02115 USA. Natl Hlth Ctr, Dept Obstet & Gynecol, Budapest, Hungary. RP Berkowitz, RS (reprint author), Harvard Univ, Sch Med,Brigham & Womens Hosp,Div Gynecol Oncol, Dana Farber Canc Inst,Dept Obstet & Gynecol, New England Trophoblast Dis Ctr,Lab Gynecol Oncol, 75 Francis St, Boston, MA 02115 USA. EM rberkowitz@partners.org NR 23 TC 35 Z9 43 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2003 VL 88 IS 3 BP 424 EP 428 DI 10.1016/S0090-8258(02)00167-1 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 658NB UT WOS:000181726100026 PM 12648597 ER PT J AU del Carmen, MG Lovett, D Goodman, A AF del Carmen, MG Lovett, D Goodman, A TI A case of Mullerian adenosarcoma of the uterus treated with liposomal doxorubicin SO GYNECOLOGIC ONCOLOGY LA English DT Article DE uterine adenocarcinoma; recurrent; chemotherapy; liposomal doxorubicin ID CLINICOPATHOLOGICAL ANALYSIS; UTERINE SARCOMAS AB Objective. We report on a case of uterine a denosarcoma responsive to treatment with liposomal doxorubicin (Doxil). Methods. The clinical course, histopathology, and radiologic studies of the case were reviewed and are reported. Results. A 69-year-old woman presented to our institution with dehydration and failure to thrive, and recurrent uterine adenosarcoma, 9 months after initial diagnosis. She had undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy at the time of diagnosis, followed by two cycles of Ifosfamide and treatment with megestrol acetate. The patient presented to our institution for hospice care placement, severely dehydrated and with lethargy and with recurrent disease in the pelvis and vagina. She underwent treatment with six cycles of liposomal doxorubicin with a marked response. Given the development of Grade II hand-foot syndrome, liposomal doxorubicin was stopped and two cycles of carboplatin/paclitaxel chemotherapy were administered. Given the patient's disease progression on this regimen, surgical cytoreduction for localized recurrent disease was then performed. The patient developed disease recurrence after a 7-month disease-free interval and 2 years after initial diagnosis. Following another two cycles of liposomal doxorubicin, the patient underwent another cytoreductive procedure for recurrent disease. Two months later, the patient expired, 29 months after diagnosis and 20 months after initial treatment with liposomal doxorubicin chemotherapy. Conclusion. Liposomal doxorubicin appears to be active in the treatment of recurrent uterine adenosarcoma. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Gynecol Oncol Serv, Boston, MA 02114 USA. Cape Cod Hosp, Mugar Canc Ctr, Hyannis, MA 02601 USA. RP del Carmen, MG (reprint author), Kelly Gynecol Oncol Serv, 600 N Wolfe St Phipps 281, Baltimore, MD 21287 USA. EM mdelcar1@jhmi.edu NR 9 TC 6 Z9 6 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 0090-8258 EI 1095-6859 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAR PY 2003 VL 88 IS 3 BP 456 EP 458 DI 10.1016/S0090-8258(02)00093-8 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 658NB UT WOS:000181726100033 PM 12648604 ER PT J AU Iosifescu, DV Renshaw, PF AF Iosifescu, DV Renshaw, PF TI 31P-magnetic resonance spectroscopy and thyroid hormones in major depressive disorder: Toward a bioenergetic mechanism in depression? SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID TRICYCLIC ANTIDEPRESSANT RESPONSE; TREATMENT-RESISTANT DEPRESSION; P-31 NMR-SPECTROSCOPY; HIGH-DOSE THYROXINE; REFRACTORY DEPRESSION; SKELETAL-MUSCLE; IN-VIVO; TRIIODOTHYRONINE AUGMENTATION; HUMAN BRAIN; PHOSPHORUS-METABOLISM AB In this paper we review studies of brain cellular high-energy phosphate metabolism, as measured by phosphorus-31 magnetic resonance spectroscopy (31P-MRS), in subjects with major depressive disorder (MDD). We also review the literature on the role of thyroid hormones on the cellular high-energy phosphate metabolism in multiple organs. Finally, we review data on the efficacy of thyroid hormones as adjuvant treatment in MDD. The framework established by these findings enables us to hypothesize that dysfunction of brain cellular energy metabolism is a vulnerability factor for MDD, and that correcting cellular energy metabolism (e.g., with thyroid hormones) is a valid therapeutic strategy for improving the symptoms of MDD. We discuss our hypothesis in the context of other current theories on the mechanism of thyroid hormones in MDD. C1 Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, McLean Hosp, Brain Imaging Ctr, Boston, MA USA. RP Iosifescu, DV (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, 15 Parkman St,WACC 812, Boston, MA 02114 USA. NR 87 TC 21 Z9 22 U1 2 U2 7 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAR-APR PY 2003 VL 11 IS 2 BP 51 EP 63 DI 10.1080/10673220303959 PG 13 WC Psychiatry SC Psychiatry GA 664TG UT WOS:000182076700001 PM 12868506 ER PT J AU Joffe, H Hall, JE Cohen, LS Taylor, AE Baldessarini, RJ AF Joffe, H Hall, JE Cohen, LS Taylor, AE Baldessarini, RJ TI A putative relationship between valproic acid and polycystic ovarian syndrome: Implications for treatment of women with seizure and bipolar disorders SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID REPRODUCTIVE ENDOCRINE DISORDERS; IMPAIRED GLUCOSE-TOLERANCE; TERM FOLLOW-UP; INSULIN RESISTANCE; WEIGHT-GAIN; PUBERTAL MATURATION; PLASMA PROLACTIN; MENSTRUAL-CYCLE; EPILEPSY; PREVALENCE C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Joffe, H (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WACC 815, Boston, MA 02114 USA. FU NICHD NIH HHS [K24-HD-01290, U54-HD-29164]; NIMH NIH HHS [K05-MH-47370] NR 85 TC 13 Z9 13 U1 2 U2 3 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAR-APR PY 2003 VL 11 IS 2 BP 99 EP 108 DI 10.1080/10673220303957 PG 10 WC Psychiatry SC Psychiatry GA 664TG UT WOS:000182076700005 PM 12868510 ER PT J AU Robb, G Lewin, JS AF Robb, G Lewin, JS TI Speech and swallowing outcomes in reconstructions of the pharynx and cervical esophagus SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article C1 Univ Texas, MD Anderson Canc Ctr, Dept Plast Surg, Div Surg, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Head & Neck Surg, Sect Speech Pathol & Audiol, Houston, TX 77030 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA USA. Washington Univ, St Louis Sch Med, Dept Otolaryngol Head & Neck Surg, Div Head & Neck Surg Oncol, St Louis, MO USA. Princess Margaret Hosp, Wharton Head & Neck Ctr, Toronto, ON M4X 1K9, Canada. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Texas, MD Anderson Canc Ctr, Dept Head & Neck Surg, Sect Speech Pathol & Audiol, Houston, TX 77030 USA. RP Robb, G (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Plast Surg, Div Surg, MB 443,1515 Holcombe Blvd, Houston, TX 77030 USA. OI Langmore, Susan/0000-0003-0521-7375 NR 0 TC 24 Z9 25 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD MAR PY 2003 VL 25 IS 3 BP 232 EP 244 DI 10.1002/hed.10233 PG 13 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 648BW UT WOS:000181130800009 PM 12599291 ER PT J AU Fernandopulle, R Ferris, T Epstein, A McNeil, B Newhouse, J Pisano, G Blumenthal, D AF Fernandopulle, R Ferris, T Epstein, A McNeil, B Newhouse, J Pisano, G Blumenthal, D TI A research agenda for bridging the 'quality chasm' SO HEALTH AFFAIRS LA English DT Article ID CARE; PHYSICIANS; PERFORMANCE; IMPROVEMENT; INFORMATION; INCENTIVES; STRATEGIES; ADHERENCE; CONSUMERS; OUTCOMES AB Realizing the vision of the IOM's landmark report, Crossing the Quality Chasm, will require new knowledge to support new policy and management. This paper lays out a research agenda that must be pursued if the health care system is to bridge the quality chasm. Based on a consensus process involving leading health care researchers and authorities, the paper highlights knowledge gaps and research directions in five areas identified by the Quality Chasm report as critical to its goals of building organizational supports for change; applying evidence to health care delivery; developing information technology; aligning payment policies with quality improvement; and preparing the workforce. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 41 TC 34 Z9 34 U1 2 U2 3 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD MAR-APR PY 2003 VL 22 IS 2 BP 178 EP 190 DI 10.1377/hlthaff.22.2.178 PG 13 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 653RG UT WOS:000181450400027 PM 12674420 ER PT J AU Hadley, J Polsky, D Mandelblatt, JS Mitchell, JM Weeks, JC Wang, Q Hwang, YT AF Hadley, J Polsky, D Mandelblatt, JS Mitchell, JM Weeks, JC Wang, Q Hwang, YT CA OPTIONS Res Team TI An exploratory instrumental variable analysis of the outcomes of localized breast cancer treatments in a medicare population SO HEALTH ECONOMICS LA English DT Article DE instrumental variable analysis; observational data bias; outcomes of localized breast cancer; health outcomes research ID COMPARING TOTAL MASTECTOMY; GEOGRAPHIC-VARIATION; HEALTH; SURGERY; WEAK AB This study is motivated by the potential problem of using observational data to draw inferences about treatment outcomes when experimental data are not available. We compare two statistical approaches, ordinary least-squares (OLS) and instrumental variables (IV) regression analysis, to estimate the outcomes (three-year post-treatment survival) of three treatments for early stage breast cancer in elderly women: mastectomy (MST), breast conserving surgery with radiation therapy (BCSRT), and breast conserving surgery only (BCSO). The primary data source was Medicare claims for a national random sample of 2907 women (age 67 or older) with localized breast cancer who were treated between 1992 and 1994. Contrary to randomized clinical trial (RCT) results, analysis with the observational data found highly significant differences in survival among the three treatment alternatives: 79.2% survival for BCSO, 85.3% for MST, and 93.0% for BCSRT. Using OLS to control for the effects of observable characteristics narrowed the estimated survival rate differences, which remained statistically significant. In contrast, the IV analysis estimated survival rate differences that were not significantly different from 0. However, the IV-point estimates of the treatment effects were quantitatively larger than the OLS estimates, unstable, and not significantly different from the OLS results. In addition, both sets of estimates were in the same quantitative range as the RCT results. We conclude that unadjusted observational data on health outcomes of alternative treatments for localized breast cancer should not be used for cost-effectiveness studies. Our comparisons suggest that whether one places greater confidence in the OLS or the IV results depends on at least three factors: (1) the extent of observable health information that can be used as controls in OLS estimation, (2) the outcomes of statistical tests of the validity of the instrumental variable method, and (3) the similarity of the OLS and IV estimates. In this particular analysis, the OLS estimates appear to be preferable because of the instability of the IV estimates. Copyright (C) 2002 John Wiley Sons, Ltd. C1 Urban Inst, Washington, DC 20037 USA. Ctr Study Hlth Syst Change, Washington, DC USA. Univ Penn, Philadelphia, PA 19104 USA. Georgetown Univ, Sch Med, Vincent T Lombardi Canc Res Ctr, Dept Human Oncol & Med, Washington, DC USA. Georgetown Univ, Publ Policy Inst, Washington, DC USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Georgetown Univ, Inst Hlth Care Res & Policy, Washington, DC USA. Georgetown Univ, Sch Med, Vincent T Lombardi Canc Res Ctr, Dept Human Oncol, Washington, DC USA. RP Hadley, J (reprint author), Urban Inst, 2100 M St NW, Washington, DC 20037 USA. FU AHRQ HHS [HS08395] NR 24 TC 30 Z9 30 U1 3 U2 9 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1057-9230 J9 HEALTH ECON JI Health Econ. PD MAR PY 2003 VL 12 IS 3 BP 171 EP 186 DI 10.1002/hec.710 PG 16 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 654DH UT WOS:000181478300001 PM 12605463 ER PT J AU Baker, CW Little, TD Brownell, KD AF Baker, CW Little, TD Brownell, KD TI Predicting adolescent eating and activity behaviors: The role of social norms and personal agency SO HEALTH PSYCHOLOGY LA English DT Article DE adolescent; eating; activity; obesity; theory of planned behavior ID PLANNED BEHAVIOR; PHYSICAL-ACTIVITY; REASONED ACTION; EXERCISE BEHAVIOR; SELF-EFFICACY; BODY-WEIGHT; ALCOHOL-USE; ATTITUDES; CHILDREN; YOUNG AB Guided by the theory of planned behavior, this 2-week longitudinal study examined health behaviors in a sample of 279 adolescents. Social norms and perceived behavioral control (PBC) were tested as predictors of self-reported intentions and behaviors in 2 domains, eating and physical activity. Differentiating, as opposed to aggregating, parent and peer norms provided unique information. For PBC, the authors distinguished global causality beliefs from self-related agency beliefs and intraself (effort, ability) from extraself (parents, teachers) means. Intraself agency beliefs strongly predicted healthy intentions, whereas intraself causality beliefs had a negative influence. Patterns differed somewhat across behaviors and gender. Results highlight theoretical issues and provide potential targets for research on health promotion programs for youth. C1 Yale Univ, Dept Psychol, New Haven, CT 06520 USA. Yale Univ, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. RP Baker, CW (reprint author), Massachusetts Gen Hosp, Weight Ctr, 50 Staniford St,4th Floor, Boston, MA 02114 USA. RI Loureiro, Nuno/I-6400-2012 OI Loureiro, Nuno/0000-0002-1166-3219 NR 55 TC 84 Z9 85 U1 3 U2 34 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD MAR PY 2003 VL 22 IS 2 BP 189 EP 198 DI 10.1037/0278-6133.22.2.189 PG 10 WC Psychology, Clinical; Psychology SC Psychology GA 655VJ UT WOS:000181573100008 PM 12683739 ER PT J AU Bouma, BE Tearney, GJ Yabushita, H Shishkov, M Kauffman, CR Gauthier, DD MacNeill, BD Houser, SL Aretz, HT Halpern, EF Jang, IK AF Bouma, BE Tearney, GJ Yabushita, H Shishkov, M Kauffman, CR Gauthier, DD MacNeill, BD Houser, SL Aretz, HT Halpern, EF Jang, IK TI Evaluation of intracoronary stenting by intravascular optical coherence tomography SO HEART LA English DT Article ID CORONARY-ARTERY; ULTRASOUND OBSERVATIONS; EXPERIMENTAL RESTENOSIS; IN-VIVO; IMPLANTATION; GUIDANCE; VISUALIZATION; PATHOLOGY; INJURY AB Background: Conventional contrast cineangiography and intravascular ultrasound (IVUS) provide a limited definition of vessel microstructure and are unable to evaluate dissection, tissue prolapse, and stent apposition on a size scale less than 100 pm. Objective: To evaluate the use of intravascular optical coherence tomography (OCT) to assess the coronary arteries in patients undergoing coronary stenting. Methods: OCT was employed in patients having percutaneous coronary interventions. Images were obtained before initial balloon dilatation and following stent deployment, and were evaluated for vessel dissection, tissue prolapse, stent apposition, and stent asymmetry. IVUS images were obtained before OCT, using an automatic pull back device. Results: 42 stents were imaged in 39 patients without complications. Dissection, prolapse, and incomplete stent opposition were observed more often with OCT than with IVUS. Vessel dissection was identified in eight stents by OCT and two by IVUS. Tissue prolapse was identified in 29 stents by OCT and 12 by IVUS; the extent of the prolapse (mean (SD)) was 242 (156) pm by OCT and 400 (100) Pm by IVUS. Incomplete stent apposition was observed in seven stents by OCT and three by IVUS. Irregular strut separation was identified in 18 stents by both OCT and IVUS. Conclusions: Intracoronary OCT for monitoring stent deployment is feasible and provides superior contrast and resolution of arterial pathology than IVUS. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Bouma, BE (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, BAR 703, Boston, MA 02114 USA. NR 26 TC 184 Z9 200 U1 1 U2 8 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD MAR PY 2003 VL 89 IS 3 BP 317 EP 320 DI 10.1136/heart.89.3.317 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 650QZ UT WOS:000181276000028 PM 12591841 ER PT J AU Wertheimer, AM Miner, C Lewinsohn, DM Sasaki, AW Kaufman, E Rosen, HR AF Wertheimer, AM Miner, C Lewinsohn, DM Sasaki, AW Kaufman, E Rosen, HR TI Novel CD4(+) and CD8(+) T-cell determinants within the NS3 protein in subjects with spontaneously resolved HCV infection SO HEPATOLOGY LA English DT Article; Proceedings Paper CT 21st Annual AASLD Meeting CY 2001 CL DALLAS, TEXAS SP AASLD ID HEPATITIS-C VIRUS; DENDRITIC CELLS; NONSTRUCTURAL PROTEIN-3; LYMPHOCYTE-RESPONSES; EFFECTOR FUNCTION; PERIPHERAL-BLOOD; IMMUNE-RESPONSES; EPITOPE; RNA; SPECIFICITY AB Spontaneous resolution of hepatitis C virus (HCV) infection is a relatively infrequent event, and these individuals provide a unique opportunity to characterize correlates of protective immunity as an important first step in the development of vaccine candidates. The aim of this study was to directly and comprehensively enumerate I-ICY-nonstructural protein 3 (NS3) specific CD4(+) and CD8(+) T cells ex vivo from HLA diverse individuals who had been successful in spontaneously resolving HCV infection. We measured interferon gamma (IFN-gamma) production with an ELISPOT assay using magnetic bead-separated CD4(+) or CD8(+) T cells in response to autologous DCs that had been pulsed with 15mer per peptides overlapping by 11 amino acids and spanning all of the NS3 protein (150 total peptides). All subjects with spontaneously recovered HCV infection demonstrated vigorous and multispecific CD4(+) T-cell responses to NS3 peptides, and 6 of 10 subjects demonstrated CD8(+) T-cell responses. More importantly, we identified novel, previously unpredicted antigenic regions, which in most cases elicited high frequencies within a given individual. In conclusion, subjects who have spontaneously eradicated HCV infection up to 35 years earlier demonstrate persistent CD4(+) and CD8(+) T-cell responses specific to NS3. By providing a comprehensive screening of all potential T-cell epitopes contained in the NS3 region, our strategy defines the breadth of the T-cell response and identifies novel, unpredicted specificities. C1 Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol, Dept Med, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol & Liver Transplantat, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Res Serv, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Dept Mol Microbiol & Immunol, Portland, OR 97207 USA. Chiron Corp, Emeryville, CA 94608 USA. RP Rosen, HR (reprint author), Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol, Dept Med, 3710 SW US Vet Hosp Rd,P3-G1, Portland, OR 97207 USA. RI Yang, Chen/G-1379-2010; Lewinsohn, David/I-4936-2013 OI Lewinsohn, David/0000-0001-9906-9494 FU NIDDK NIH HHS [DK60590-01] NR 43 TC 103 Z9 109 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAR PY 2003 VL 37 IS 3 BP 577 EP 589 DI 10.1053/jhep.2003.50115 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 650RJ UT WOS:000181276800014 PM 12601356 ER PT J AU Achenbach, S AF Achenbach, S TI Clinical use of multi-slice CT coronary angiography SO HERZ LA German DT Article DE computed tomography; multi-slice computed tomography; coronary angiography; coronary artery disease ID BEAM COMPUTED-TOMOGRAPHY; ARTERY STENOSES; HEART-RATE; SPIRAL CT; NONINVASIVE DETECTION; IMAGE-RECONSTRUCTION; RESOLUTION; VISUALIZATION; OPTIMIZATION; QUALITY AB As compared to conventional CT scanners, multi-slice spiral CT (MSCT) has improved temporal and spatial resolution. Dedicated image reconstruction algorithms permit to create cross-sectional images with a temporal resolution of approximately 150-250 ms, and a slice thickness of 0.75-1.3 mm (see Figure 1). In addition, image reconstruction can be synchronized to the ECG. This permits to use MSCT for visualization of the coronary artery lumen and detection of stenosis (see Figures 2 and 3). Various post-processing techniques can be used to display the coronary arteries. A low heart rate has been identified as an important prerequisite to obtain a sufficiently high image quality, and most authors recommend routine use of beta blocker premedication. Comparisons Of 4-slice MSCT to invasive angiography concerning the detection of hemodynamically relevant coronary artery stenoses have resulted in sensitivities ranging from 72-93% and specificities ranging from 84-98%. However, up to 32% of all coronary segments had to be excluded from evaluation due to impaired image quality, in most cases due to severe calcification or insufficient suppression of motion artifacts. Initial results obtained with 16-slice MSCT scanners,which provide somewhat higher temporal and -through decreased slice thickness - improved spatial resolution, show promise that diagnostic accuracy may be increased while the number of coronary artery segments with nondiagnostic image quality may be reduced as compared to the prior generation of 4-slice scanners. Further studies are necessary to identify patient subgroups which might benefit from MSCT "noninvasive coronary angiography" in a clinical setting. C1 Massachusetts Gen Hosp, CIMIT Vulnerable Plaque Program, Boston, MA 02114 USA. RP Achenbach, S (reprint author), Massachusetts Gen Hosp, CIMIT Vulnerable Plaque Program, 100 Charles River Plaza,Suite 400, Boston, MA 02114 USA. NR 29 TC 14 Z9 14 U1 0 U2 0 PU URBAN & VOGEL PI MUNICH PA NEUMARKTER STRASSE 43, D-81673 MUNICH, GERMANY SN 0340-9937 J9 HERZ JI Herz PD MAR PY 2003 VL 28 IS 2 BP 119 EP 125 DI 10.1007/s00059-003-2442-7 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 666RX UT WOS:000182191200007 PM 12669225 ER PT J AU Madry, H Cucchiarini, M Terwilliger, EF Trippel, SB AF Madry, H Cucchiarini, M Terwilliger, EF Trippel, SB TI Recombinant adeno-associated virus vectors efficiently and persistently transduce chondrocytes in normal and osteoarthritic human articular cartilage SO HUMAN GENE THERAPY LA English DT Article ID MEDIATED GENE-TRANSFER; DELIVERY; TRANSPLANTATION; EXPRESSION; ARTHRITIS; THERAPY; REPAIR; INTEGRATION; SYNOVIUM; CULTURE AB Successful gene transfer into articular cartilage is a prerequisite for gene therapy of articular joint disorders. In the present study we tested the hypothesis that recombinant adeno-associated virus (rAAV) vectors are capable of effecting gene transfer in isolated articular chondrocytes in vitro, articular cartilage tissue in vitro, and sites of articular damage in vivo. Using an rAAV vector carrying the Escherichia coli beta-galactosidase gene (lacZ) under the control of the cytomegalovirus (CMV) immediate-early promoter/enhancer (rAAV-lacZ), transduction efficiency exceeded 70% for isolated normal human adult articular chondrocytes, and osteoarthritic human articular chondrocytes. These were comparable to the transduction efficiency obtained with neonatal bovine articular chondrocytes. Transduction of explant cultures of articular cartilage resulted in reporter gene expression within the tissue of all three cartilage types to a depth exceeding 450 mm, which remained present until 150 days. When rAAV-lacZ vectors were applied to femoral chondral defects and osteochondral defects in vivo in a rat knee model, reporter gene expression was achieved for at least 10 days after transduction. These data suggest that AAV-based vectors can efficiently transduce and stably express foreign genes in articular chondrocytes, including chondrocytes of normal and osteoarthritic human articular cartilage. The data further suggest that the same rAAV vectors are capable of transducing chondrocytes in situ within their native matrix to a depth sufficient to be of potential clinical significance. Finally, the data demonstrate that these rAAV vectors are capable of effectively delivering recombinant genes to chondral and osteochondral defects in vivo. C1 Massachusetts Gen Hosp, Dept Orthoped Surg, Orthoped Res Labs, Boston, MA 02115 USA. Harvard Univ, Inst Med, Div Expt Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Madry, H (reprint author), Univ Saarland, Med Ctr, Lab Expt Orthopaed, D-66421 Homburg, Germany. FU NIAMS NIH HHS [AR 31068, AR 48413, AR 45749] NR 39 TC 96 Z9 103 U1 0 U2 5 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAR PY 2003 VL 14 IS 4 BP 393 EP 402 DI 10.1089/104303403321208998 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 662CW UT WOS:000181929500007 PM 12659680 ER PT J AU Gines, S Seong, IS Fossale, E Ivanova, E Trettel, F Gusella, JF Wheeler, VC Persichetti, F MacDonald, ME AF Gines, S Seong, IS Fossale, E Ivanova, E Trettel, F Gusella, JF Wheeler, VC Persichetti, F MacDonald, ME TI Specific progressive cAMP reduction implicates energy deficit in presymptomatic Huntington's disease knock-in mice SO HUMAN MOLECULAR GENETICS LA English DT Article ID CREB-BINDING PROTEIN; NEURODEGENERATIVE DISEASE; EXPANDED POLYGLUTAMINE; MEDIATED TRANSCRIPTION; RECEPTOR ACTIVATION; GENE-EXPRESSION; STRIATAL CELLS; CYTOCHROME-C; NUCLEAR; MOUSE AB Defects in gene transcription and mitochondrial function have been implicated in the dominant disease process that leads to the loss of striatal neurons in Huntington's disease (HD). Here we have used precise genetic HD mouse and striatal cell models to investigate the hypothesis that decreased cAMP responsive element (CRE)-mediated gene transcription may reflect impaired energy metabolism. We found that reduced CRE-signaling in Hdh(Q111) striatum, monitored by brain derived neurotrophic factor and phospho-CRE binding protein (CREB), predated inclusion formation. Furthermore, cAMP levels in Hdh(Q111) striatum declined from an early age (10 weeks), and cAMP was significantly decreased in HD postmortem brain and lymphoblastoid cells, attesting to a chronic deficit in man. Reduced CRE-signaling in cultured STHdh(Q111) striatal cells was associated with cytosolic CREB binding protein that mirrored diminished cAMP synthesis. Moreover, mutant cells exhibited mitochondrial respiratory chain impairment, evidenced by decreased ATP and ATP/ADP ratio, impaired MTT conversion and heightened sensitivity to 3-nitropropionic acid. Thus, our findings strongly suggest that impaired ATP synthesis and diminished cAMP levels amplify the early HD disease cascade by decreasing CRE-regulated gene transcription and altering energy dependent processes essential to neuronal cell survival. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. RP MacDonald, ME (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. OI Gines Padros, Silvia/0000-0002-9479-8185; trettel, flavia/0000-0002-7983-2955 FU NINDS NIH HHS [NS32765, NS16367] NR 40 TC 155 Z9 159 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAR 1 PY 2003 VL 12 IS 5 BP 497 EP 508 DI 10.1093/hmg/ddg046 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 652LA UT WOS:000181379600005 PM 12588797 ER PT J AU Lopes, HF Martin, KL Nashar, K Morrow, JD Goodfriend, TL Egan, BM AF Lopes, HF Martin, KL Nashar, K Morrow, JD Goodfriend, TL Egan, BM TI DASH diet lowers blood pressure and lipid-induced oxidative stress in obesity SO HYPERTENSION LA English DT Article DE obesity; insulin resistance; fatty acids; F-2-isoprostanes; oxidative stress; antioxidants ID INSULIN-RESISTANCE; ASCORBIC-ACID; HYPERTENSION; PLASMA; POTASSIUM; HYPERINSULINEMIA; COMPLICATIONS; CHOLESTEROL; ACTIVATION; OXIDASE AB Evidence suggests that obesity may raise blood pressure (BP) through oxidative stress-sensitive mechanisms and that the Dietary Approaches to Stop Hypertension combination diet (DASH-CD) may decrease BP by enhancing antioxidant capacity. To address this question, 12 obese patients with high-normal-to-stage 1 hypertension (hypertensives) and 12 lean normotensives were studied on their usual diets and after following the DASH-CD and a low-antioxidant diet in random sequence for 4 weeks each. Acute oxidative stress was induced by a 4-hour infusion of intralipid and heparin. Ferric-reducing activity of plasma (FRAP) and plasma F-2-isoprostanes were measured as biomarkers of antioxidant capacity and oxidative stress, respectively. BP was lower in obese hypertensives on the DASH-CD than on the usual and low-antioxidant diets (-8.1+/-1.5/-7.4+/-1.6 mm Hg, P<0.05). BP did not change significantly in lean normotensives after 4 weeks on the DASH-CD but tended to rise on the low-antioxidant diet. FRAP on usual diets was higher in lean subjects than in obese subjects. FRAP increased in obese but not lean volunteers on the DASH-CD compared with usual diet, and the group difference disappeared. F-2-isoprostanes increased from baseline during intralipid and heparin in both groups on the low-antioxidant diet but not in obese hypertensives on the DASH-CD. Among free-living obese hypertensives, the DASH-CD raises antioxidant capacity, lowers BP, and reduces oxidative stress induced by acute hyperlipidemia. The findings are consistent with evidence that elevated BP in obese subjects may reflect an imbalance between antioxidant capacity and oxidative stress that is improved by the DASH-CD. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pharmacol, Charleston, SC 29425 USA. Med Univ S Carolina, Gen Clin Res Ctr, Charleston, SC 29425 USA. USP, HCFM, Unidade Hipertensao Heart Inst InCor, BR-09500900 Sao Paulo, Brazil. Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. Univ Wisconsin, Dept Pharmacol, Madison, WI 53706 USA. Univ Wisconsin, Dept Med, Madison, WI USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Egan, BM (reprint author), Med Univ S Carolina, Dept Med, 96 Jonathan Lucas St,CSB 826H, Charleston, SC 29425 USA. FU NCI NIH HHS [CA77839]; NCRR NIH HHS [RR-01070]; NHLBI NIH HHS [HL04290, HL55782, HL58794]; NIDDK NIH HHS [DK26657, DK48831]; NIGMS NIH HHS [GM42056] NR 41 TC 104 Z9 109 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD MAR PY 2003 VL 41 IS 3 BP 422 EP 430 DI 10.1161/01.HYP.0000053450.19998.11 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 653QD UT WOS:000181447500008 PM 12623938 ER PT J AU Wall, C Weinberg, MS AF Wall, C Weinberg, MS TI Balance prostheses for postural control SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Article C1 Massachusetts Eye & Ear Infirm, Jenks Vestibular Diagnost Lab, Boston, MA 02114 USA. RP Wall, C (reprint author), Massachusetts Eye & Ear Infirm, Jenks Vestibular Diagnost Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01 DC6201] NR 41 TC 36 Z9 38 U1 1 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD MAR-APR PY 2003 VL 22 IS 2 BP 84 EP 90 DI 10.1109/MEMB.2003.1195701 PG 7 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA 671YX UT WOS:000182494200017 PM 12733464 ER PT J AU Smith, DJ King, WF Barnes, LA Peacock, Z Taubman, MA AF Smith, DJ King, WF Barnes, LA Peacock, Z Taubman, MA TI Immunogenicity and protective immunity induced by synthetic peptides associated with putative immunodominant regions of Streptococcus mutans glucan-binding protein B SO INFECTION AND IMMUNITY LA English DT Article ID EXPERIMENTAL DENTAL-CARIES; SALIVARY IMMUNOGLOBULIN; SEQUENCE-ANALYSIS; GLUCOSYLTRANSFERASE; IMMUNIZATION; GENE; ANTIBODY; RATS; INFECTION; BIOLOGY AB Glucan-binding protein B (GbpB) from Streptococcus mutans has been shown to induce protective immunity to dental caries in experimental models. Having recently sequenced the gbpB gene, our objective in this study was to identify immunogenic regions within the GbpB sequence for use in subunit vaccines. Potential regions of immunogenicity were sought by use of a matrix-based algorithm (EpiMatrix) to estimate the binding characteristics of peptides derived from the GbpB sequence by using a database of known major histocompatibility complex class II binding alleles. Screening the entire sequence revealed several peptides with estimated high binding probabilities. Two N-terminal 20-mer peptides (SYI and QGQ) subtending two of these regions were synthesized. A preliminary experiment, in which these peptides were synthesized in the multiple antigenic peptide format and were used to subcutaneously immunize Sprague-Dawley rats twice at a 21-day interval, revealed that the SYI peptide induced a higher percentage of responses to the inciting peptide as well as to intact GbpB, as measured by enzyme-linked immunosorbent assay. The effect of immunization with the SYI Peptide construct on the cariogenicity of S. mutans was then investigated by immunizing weanling Sprague-Dawley rats twice at a 9-day interval with SYI or with phosphate-buffered saline. All rats were then orally infected with S. mutans strain SJ. After a 78-day infection period, the SYI-immunized groups had significant reductions in dental caries on both smooth and occlusal surfaces compared with the sham-immunized group. Thus, these experiments indicated that at least one linear sequence, derived from the N-terminal third of GbpB, was sufficiently immunogenic to induce a protective immune response in this experimental rat model for dental caries. C1 Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. RP Smith, DJ (reprint author), Forsyth Inst, Dept Immunol, 140 The Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-06153, R37 DE006153] NR 29 TC 29 Z9 31 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 2003 VL 71 IS 3 BP 1179 EP 1184 DI 10.1128/IAI.71.3.1179-1184.2003 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 650NU UT WOS:000181270900018 PM 12595430 ER PT J AU Brown, SM Lubimova, AV Khrustalyeva, NM Shulaeva, SV Tekhova, I Zueva, LP Goldmann, D O'Rourke, EJ AF Brown, SM Lubimova, AV Khrustalyeva, NM Shulaeva, SV Tekhova, I Zueva, LP Goldmann, D O'Rourke, EJ TI Use of alcohol-based hand rub and quality improvement interventions to improve hand hygiene in a Russian neonatal intensive care unit SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID INCREASING HANDWASHING COMPLIANCE; PATIENT-CARE; NOSOCOMIAL INFECTIONS; SKIN; HEALTH; MORTALITY; ANTISEPSIS; PREVENTION; MORBIDITY; PERSONNEL AB BACKGROUND: Hand hygiene (HH) is critical to infection control, but compliance is low. Alcohol-based antiseptics may improve HH. HH practices in Russia are not well described, and facilities are often inadequate. SETTING: Four 6-bed units in a neonatal intensive care unit in St. Petersburg, Russia. METHODS: Prospective surveillance of HH compliance, nosocomial colonization, and antibiotic administration was performed from January until June 2000. In February 2000, alcohol-based hand rub was provided for routine HH use. Eight weeks later, a quality improvement intervention was implemented, consisting of review of interim data, identification of opinion leaders, posting of colonization incidence rates, and regular feedback. Means of compliance, colonization, and antibiotic use were compared for periods before and after each intervention. RESULTS: A total of 1,027 events requiring HH were observed. Compliance was 44.2% before the first intervention, 42.3% between interventions, and 48% after the second intervention. Use of alcohol rose from 15.2% of HH indications to 25.2% between interventions and 41.5% after the second intervention. The incidence of nosocomial colonization (per 1,000 patient-days) with Klebsiella pneumoniae was initially 21.5, decreased to 4.7, and then was 3.2 in the final period. Rates of antibiotic and device use also decreased. CONCLUSIONS: HH may have increased slightly, but the largest effect was a switch from soap and water to alcohol, which may have been associated with decreased cross-transmission of Klebsiella, although this may have been confounded by lower device use. Alcohol-based antiseptic may be an improvement over current practices, but further research is required. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Davis Ctr Russian Studies, Boston, MA 02115 USA. Mechnikov State Med Acad, Infect Control Training Ctr, St Petersburg, Russia. Mechnikov State Med Acad, Dept Epidemiol, St Petersburg, Russia. First Childrens Hosp, St Petersburg, Russia. Childrens Hosp, Boston, MA 02115 USA. Harvard Med Int, Boston, MA USA. RP Brown, SM (reprint author), 527 Leverett Mail Ctr, Cambridge, MA 02138 USA. RI Brown, Samuel/E-6846-2015 OI Brown, Samuel/0000-0003-1206-6261 NR 57 TC 60 Z9 63 U1 0 U2 5 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD MAR PY 2003 VL 24 IS 3 BP 172 EP 179 DI 10.1086/502186 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 656LA UT WOS:000181608200004 PM 12683507 ER PT J AU Queiroz-Telles, F McGinnis, MR Salkin, I Graybill, JR AF Queiroz-Telles, F McGinnis, MR Salkin, I Graybill, JR TI Subcutaneous mycoses SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID SPOROTHRIX-SCHENCKII; FONSECAEA-PEDROSOI; SYSTEMIC SPOROTRICHOSIS; AMPHOTERICIN-B; CUTANEOUS SPOROTRICHOSIS; ANTIFUNGAL ACTIVITY; FILAMENTOUS FUNGI; AIDS PATIENT; CHROMOBLASTOMYCOSIS; ITRACONAZOLE AB Subcutaneous mycoses include a heterogeneous group of fungal infections that develop at the site of transcutaneous trauma. Infection slowly evolves as the etiologic agent survives and adapts to the adverse host tissue environment. Diagnosis rests on clinical presentation, histopathology, and culture of the etiologic agents. This article considers sporotrichosis, chromoblastomycosis, and mycetoma. C1 Univ Texas, Med Branch, Dept Pathol, Galveston, TX 77555 USA. Univ Fed Parana, Hosp Clin, BR-80060000 Curitiba, Parana, Brazil. Informat Sci, W Sand Lake, NY 12196 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. RP McGinnis, MR (reprint author), Univ Texas, Med Branch, Dept Pathol, 301 Univ Blvd, Galveston, TX 77555 USA. NR 94 TC 56 Z9 64 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD MAR PY 2003 VL 17 IS 1 BP 59 EP + DI 10.1016/S0891-5520(02)00066-1 PG 28 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 672BK UT WOS:000182500800005 PM 12751261 ER PT J AU Carey, K AF Carey, K TI Hospital cost efficiency and system membership SO INQUIRY-THE JOURNAL OF HEALTH CARE ORGANIZATION PROVISION AND FINANCING LA English DT Article ID HEALTH-CARE PROVIDERS; MULTIHOSPITAL SYSTEMS; FINANCIAL PERFORMANCE; STOCHASTIC FRONTIER; MERGERS; MARKETS; COMPETITION; NONPROFIT; CONSOLIDATION; OWNERSHIP AB Using a recently developed taxonomy of hospital organizations, this paper estimates a stochastic frontier cost function to test for inefficiency differences among system hospitals having common strategic and/or structural characteristics. System hospitals that centralized around physician arrangements and insurance products display the smallest deviations from the least cost locus. This suggests efficiency benefits from organization of physician and insurance activities at the system level, with discretion over the array of service offerings left to individual members. Policymakers should be mindful of potential efficiency gains from hospital consolidations and be aware that common ownership alone may be too general a rubric for evaluating those gains usefully. C1 US Dept Vet Affairs, VA Management Sci Grp, Bedford, MA 01730 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. RP Carey, K (reprint author), US Dept Vet Affairs, VA Management Sci Grp, Bldg 12,200 Springs Rd, Bedford, MA 01730 USA. NR 45 TC 35 Z9 36 U1 3 U2 11 PU BLUE CROSS BLUE SHIELD ASSOC PI ROCHESTER PA 150 EAST MAIN ST, ROCHESTER, NY 14647 USA SN 0046-9580 J9 INQUIRY-J HEALTH CAR JI Inquiry-J. Health Care Organ. Provis. Financ. PD SPR PY 2003 VL 40 IS 1 BP 25 EP 38 PG 14 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 691JH UT WOS:000183602500003 PM 12836906 ER PT J AU Davidson, SM Davidson, H Miracle-McMahill, H Oakes, JM Crawford, S Blumenthal, D Valentine, DP AF Davidson, SM Davidson, H Miracle-McMahill, H Oakes, JM Crawford, S Blumenthal, D Valentine, DP TI Utilization of services by chronically ill people in managed care and indemnity plans: Implications for quality SO INQUIRY-THE JOURNAL OF HEALTH CARE ORGANIZATION PROVISION AND FINANCING LA English DT Article ID HEALTH-INSURANCE; PERFORMANCE AB Because incentives for managed care organizations favor cost containment, concerns have been raised that quality of care has suffered, especially for chronically ill people. This study compares utilization rates of managed care and indemnity patients with three chronic conditions, using five years of claims records (1993-97) from private plans and Medicare in one market. Findings show that for all three conditions, managed care patients were more likely to see both primary care physicians and specialists within a year, but less likely to use a hospital emergency department or to be an inpatient. Assuming that patients with these illnesses should see a physician annually and that good primary care reduces the need for emergency and inpatient services, it appears that the patterns of care used by chronically ill managed care patients in this market do not reflect lower quality than that received by similar indemnity patients. C1 Boston Univ, Sch Management, Strategy & Policy Dept, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Minnesota, Sch Publ Hlth, Minneapolis, MN 55455 USA. Univ Massachusetts, Sch Med, Amherst, MA 01003 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Gillette Co, Boston, MA 02199 USA. RP Davidson, SM (reprint author), Boston Univ, Sch Management, Strategy & Policy Dept, 595 Commonwealth Ave, Boston, MA 02215 USA. RI Miracle, Maria /G-3482-2016 NR 17 TC 2 Z9 2 U1 0 U2 2 PU BLUE CROSS BLUE SHIELD ASSOC PI ROCHESTER PA 150 EAST MAIN ST, ROCHESTER, NY 14647 USA SN 0046-9580 J9 INQUIRY-J HEALTH CAR JI Inquiry-J. Health Care Organ. Provis. Financ. PD SPR PY 2003 VL 40 IS 1 BP 57 EP 70 PG 14 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 691JH UT WOS:000183602500005 PM 12836908 ER PT J AU Weissman, JS Gaskin, DJ Reuter, J AF Weissman, JS Gaskin, DJ Reuter, J TI Hospitals' care of uninsured patients during the 1990s: The relation of teaching status and managed care to changes in market share and market concentration SO INQUIRY-THE JOURNAL OF HEALTH CARE ORGANIZATION PROVISION AND FINANCING LA English DT Article ID UNCOMPENSATED CARE; PROVISION; CHARITY AB Competitive forces in health care make it difficult for hospitals to shift the costs of caring for poor and uninsured patients onto paying patients. The care of uninsured patients in teaching hospitals may have been especially affected by increased levels of managed care during the 1990s. We found that the market share of uninsured patients during the 1990s grew at academic health center hospitals relative to other hospitals in their service areas, and these increases occurred primarily in areas with high levels of managed care. More generally, in urban areas, the care of uninsured patients was twice as concentrated as that of all patients, and the ratio of concentration (uninsured patients vs. all patients) was greater in areas with high managed care levels than in areas with low managed care levels (p < .01). These results have implications for the design of payment policies for indigent care. C1 Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. RP Weissman, JS (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. NR 33 TC 11 Z9 11 U1 4 U2 4 PU BLUE CROSS BLUE SHIELD ASSOC PI ROCHESTER PA 150 EAST MAIN ST, ROCHESTER, NY 14647 USA SN 0046-9580 J9 INQUIRY-J HEALTH CAR JI Inquiry-J. Health Care Organ. Provis. Financ. PD SPR PY 2003 VL 40 IS 1 BP 84 EP 93 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 691JH UT WOS:000183602500007 PM 12836910 ER PT J AU Tibaldi, EV Reinherz, EL AF Tibaldi, EV Reinherz, EL TI CD2BP3, CIN85 and the structurally related adaptor protein CMS bind to the same CD2 cytoplasmic segment, but elicit divergent functional activities SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE c-Cbl; cytoskeletal polarization; intramolecular regulation; RNA splicing; T cell ID T-CELL ACTIVATION; CYTOSKELETAL-ASSOCIATED PROTEIN; PCH FAMILY PROTEINS; NERVE GROWTH-FACTOR; TYROSINE-PHOSPHATASE; SIGNAL-TRANSDUCTION; PTP-PEST; C-CBL; CD2-ASSOCIATED PROTEIN; NEGATIVE REGULATION AB Interaction trap cloning was used to identify a CD2 cytoplasmic tail-binding protein termed CD2BP3. CD2BP3 is the major RNA splice variant of the CIN85 locus in human T lymphocytes, lacking SH3A, the first of three SH3 domains found in CIN85, but retaining SH3B, SH3C, a proline-rich domain and C-terminal coiled coil. CD2BP3 has 35% amino acid identity to CMS, a structurally related protein binding to the same highly conserved segment of the CD2 tail and known to be involved in T cell polarization/cytoskeletal interactions. Unlike CMS, however, CD2BP3 does not co-localize with F-actin and binds p130(Cas) weakly, if at all. Moreover, CIN85/CD2BP3 proteins are readily degraded by TCR cross-linking, consistent with the presence of a PEST sequence C-terminal to SH3C. CIN85 SH3A and CIN85/CD2BP3 SH3B bind to proline-rich segments within CIN85/CD2BP3 themselves as evidenced by mAb accessibility analysis and protein interaction studies including c-Cbl binding. This form of intramolecular regulation is not manifest by CMS. CMS and CIN85 activities are antagonistic, while the functions of CIN85 and CD2BP3 are also distinct. Thus, CD2-mediated adhesion, signaling and cell motility are regulated in a highly complex manner. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Reinherz, EL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI 21226] NR 66 TC 35 Z9 38 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD MAR PY 2003 VL 15 IS 3 BP 313 EP 329 DI 10.1093/intimm/dxg032 PG 17 WC Immunology SC Immunology GA 655JB UT WOS:000181546600002 PM 12618476 ER PT J AU Lowe, NJ Gonzalez, J Bagel, J Caro, I Ellis, CN Menter, A AF Lowe, NJ Gonzalez, J Bagel, J Caro, I Ellis, CN Menter, A TI Repeat courses of intravenous alefacept in patients with chronic plaque psoriasis provide consistent safety and efficacy SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Article ID T-CELL RESPONSES; QUALITY-OF-LIFE; DISEASE; CD2; LYMPHOCYTES; THERAPIES; RISK; PUVA AB Background Psoriasis is a chronic, relapsing skin disease that may require multiple treatment courses. Alefacept targets the memory T cells implicated in psoriasis pathogenesis. This open-label study evaluated the safety and tolerability, efficacy, and pharmacodynamics of repeat courses of alefacept in men and women with chronic plaque psoriasis. This article reports the interim results of this ongoing study. Methods Patients (n = 174) who participated in previous phase II studies of alefacept were included in this retreatment study. Intravenous alefacept (7.5 mg) was administered once weekly for 12 weeks followed by 12 weeks of observation. Initial and subsequent retreatment courses were only given when, in the opinion of the investigators, disease had returned and necessitated treatment; CD4(+) T-cell counts had to be at or above the lower limit of normal. Results Adverse events were similar regardless of the retreatment course. No opportunistic infections, rebound of disease, or flares were reported. Low titers of anti-alefacept antibodies occurred in a few patients without related safety issues. Sixty-six per cent of patients achieved a greater than or equal to 50% reduction in the Psoriasis Area and Severity Index (PASI) at any time after the first dose of retreatment course 1. Patients who received two retreatment courses (n = 50) had consistent or improved responses after the second course; 64% and 68% of these patients achieved a greater than or equal to 50% PASI improvement at any time after the first dose of retreatment courses 1 and 2, respectively. Alefacept selectively reduced memory T cells without cumulative effects. Conclusions Repeat courses of alefacept were well tolerated, and subsequent retreatment courses were at least as effective as the initial course of therapy. C1 Clin Res Specialists, Santa Monica, CA USA. Sylvana Res, San Antonio, TX USA. Psoriasis Treatment Ctr Cent New Jersey, E Windsor, NJ USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. Baylor Univ, Med Ctr, Dallas, TX USA. RP Lowe, NJ (reprint author), 2001 Santa Monica Blvd,Suite 490W, Santa Monica, CA 90404 USA. EM nlowecrs@aol.com RI menter md, alan/A-8250-2009 NR 24 TC 26 Z9 28 U1 1 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD MAR PY 2003 VL 42 IS 3 BP 224 EP 230 DI 10.1046/j.1365-4362.2003.01793.x PG 7 WC Dermatology SC Dermatology GA 659QF UT WOS:000181787800014 PM 12653922 ER PT J AU Becker, AE Franko, DL Speck, A Herzog, DB AF Becker, AE Franko, DL Speck, A Herzog, DB TI Ethnicity and differential access to care for eating disorder symptoms SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article; Proceedings Paper CT International Conference on Eating Disorders CY APR 24-26, 1998 CL NEW YORK, NEW YORK DE ethnicity; eating disorder symptoms; clinician bias; National Eating Disorders Screening Program ID PERCEPTIONS; WOMEN; RACE AB Objective: The impact of ethnicity on access to health care for eating disorder symptoms among participants in the 1996 National Eating Disorders Screening Program (NEDSP) was examined in two studies. Method:,Self-report and clinician-assessed data were analyzed from 9,069 participants in an educational and two-stage screening program for eating disorders in Study I. In Study II, both cross-sectional and prospective data from a randomly selected sample of 289 participants from the same program were analyzed to investigate the impact of ethnic minority status on both help-seeking patterns and clinician referral patterns for eating disorder symptoms. Results: Even after controlling for severity of self-reported eating disorder symptoms, both Latino and Native American participants in the NEDSP were significantly less likely than Whites to receive a recommendation or referral for further evaluation or care. Ethnic minority subjects with self-acknowledged eating and weight concerns were also significantly less likely than non-minority participants to have been asked by a doctor about eating disorder symptoms. Only one marginally significant difference was found between ethnic minority and non-minority respondents with respect to their help-seeking behaviors, namely, ethnic minority subjects were less likely (at the level of a trend) to seek eating disorders treatment within 11/2-2 years following the NEDSP. Discussion: These data suggest that clinician bias may be an important barrier to access to care for eating disorder symptoms in ethnic minority populations. (C) 2003 by Wiley Periodicals, Inc. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA. Harvard Univ, Eating Disorders Ctr, Boston, MA USA. Northeastern Univ, Dept Counseling & Appl Educ Psychol, Boston, MA USA. RP Becker, AE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WAC 816C,15 Parkman St, Boston, MA 02114 USA. NR 18 TC 70 Z9 70 U1 1 U2 9 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD MAR PY 2003 VL 33 IS 2 BP 205 EP 212 DI 10.1002/eat.10129 PG 8 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 649QF UT WOS:000181218900011 PM 12616587 ER PT J AU Takahashi, T Yamamoto, H Ogawa, Y Yoshida, S Kataoka, S Majumdar, M Morris, E Tripple, SB AF Takahashi, T Yamamoto, H Ogawa, Y Yoshida, S Kataoka, S Majumdar, M Morris, E Tripple, SB TI Role of apoptosis inhibition in various chondrocyte culture systems SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Article DE chondrocytes; apoptosis; autologous serum; culture ID HUMAN ARTICULAR-CARTILAGE; NITRIC-OXIDE; PROLIFERATION; CULTIVATION; DISEASE; GELS; BONE AB Apoptosis may limit the utility of cell-based therapies for articular cartilage disorders. We tested the hypothesis that chondrocyte apoptosis can be reduced by optimizing the conditions employed to expand chondrocyte numbers in culture. Chondrocyte apoptosis was examined in monolayer and suspension culture, in the presence of fetal bovine serum (FBS) or autologous serum, and for culture periods of 2 or 4 days. The effect of these variables was assessed by measuring cell viability, Annexin V labeling and mitochondrial membrane potential. After 2 days of culture, the greatest increase in viable cell number (3.7-fold) occurred in monolayer cultures with autologous serum. After 4 days of culture, the greatest increase in cell number (9.0-fold) occurred in monolayer cultures supplemented with FBS. By Annexin V staining, the proportion of cells undergoing apoptosis after 2 days was not affected by the type of serum used or by culture in monolayer versus suspension. After 4 days of culture, the proportion of apoptotic cells was significantly reduced (35% to 13%, p<0.02) in suspension cultures with autologous serum. Apoptosis assessed by loss of mitochondrial membrane potential was decreased in the presence of autologous serum. These data suggest that suspension culture with autologous serum is useful in simultaneously maintaining cell proliferation and minimizing apoptosis in cultured human articular chondrocytes. C1 Kochi Med Sch, Dept Orthopaed Surg, Nanko Ku, Kochi 7838505, Japan. Kochi Med Sch, Dept Radiol, Kochi 7838505, Japan. Kochi Med Sch, Med Res Ctr, Kochi 7838505, Japan. Genet Inst Inc, Cambridge, MA 02140 USA. Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. RP Takahashi, T (reprint author), Kochi Med Sch, Dept Orthopaed Surg, Nanko Ku, Oko Cho, Kochi 7838505, Japan. NR 23 TC 7 Z9 8 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD MAR PY 2003 VL 11 IS 3 BP 299 EP 303 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 645NB UT WOS:000180983300004 PM 12579330 ER PT J AU Huerta, S Harris, DM Jazirehi, A Bonavida, B Elashoff, D Livingston, EH Heber, D AF Huerta, S Harris, DM Jazirehi, A Bonavida, B Elashoff, D Livingston, EH Heber, D TI Gene expression profile of metastatic colon cancer cells resistant to cisplatin-induced apoptosis SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE colon cancer; apoptosis; SW480; SW620; caspases; cisplatin; microarray ID OLIGONUCLEOTIDE ARRAYS; PHASE-II; LINES; MODEL; PROGRESSION; CARCINOMA AB The current chemotherapeutic modalities for advanced colorectal cancer are limited. DNA-platinating drugs such as cisplatin have poor efficacy against this malignancy. The aim of this study was to identify genes that render survival advantage after cisplatin treatment in metastatic colon cancer. Cell lines SW480 (primary colon cancer) and SW620 (metastatic lesion from the same patient) were obtained from ATCC. Apoptosis was measured by FACS analysis of cisplatin-treated (0.01-10 mug/ml) and untreated cells. Simultaneous analysis of similar to1200 cDNAs was performed by microarray technique on untreated and treated cells from lines. Microarray results were confirmed by RT-PCR. The SW620 cell line was more resistant to apoptosis induced by cisplatin. Western blot analysis revealed equal expression of pro-caspases 3, 8, and 9 in both cell lines. Microarray analysis identified 15 genes and 9 expressed sequence tags (ESTs) significantly altered both by cell type (metastatic vs. non-metastatic) and treatment vs. non-treatment. Several of these transcripts are well-characterized genes including MCT, GAD67, P19, GSTM3, Cyclin D1, ATM, and CO-029 that have been implicated in various malignancies. In the present study, we have identified a set of genes responsible for apoptosis resistance following treatment with cisplatin in the late stages of carcinogenesis. Targeting these genes may increase chemotherapy effectiveness in advanced colon cancer and reduce toxicity in normal tissue. C1 Univ Calif Los Angeles, Ctr Human Nutr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, VA Greater Los Angeles, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. RP Huerta, S (reprint author), Univ Calif Los Angeles, Ctr Human Nutr, 900 Vet Ave,12-217 Warren Hall, Los Angeles, CA 90095 USA. FU NCI NIH HHS [CA42710] NR 25 TC 50 Z9 55 U1 1 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAR PY 2003 VL 22 IS 3 BP 663 EP 670 PG 8 WC Oncology SC Oncology GA 645KP UT WOS:000180975000024 PM 12579322 ER PT J AU Trantolo, DJ Sonis, ST Thompson, BMJ Wise, DL Lewandrowski, KU Hile, DD AF Trantolo, DJ Sonis, ST Thompson, BMJ Wise, DL Lewandrowski, KU Hile, DD TI Evaluation of a porous, biodegradable biopolymer scaffold for mandibular reconstruction SO INTERNATIONAL JOURNAL OF ORAL & MAXILLOFACIAL IMPLANTS LA English DT Article DE autologous transplantation; biocompatibility; bioresorbable polymers; bone substitutes; mandible; polypropylenes ID BONE-CEMENT; POLY(PROPYLENE; FOAMS; IMPLANTS; GRAFT AB Purpose: Bioresorbable bone graft substitutes could eliminate disadvantages associated with the use of autografts, allografts, and other synthetic materials. The authors investigated the osteoinductive capacity of a bioresorbable bone graft substitute made from the, unsaturated polyester poly(propylene glycol-co-fumaric acid) (PPF) for mandibular reconstruction in a rat model. The eventual intention is to use this material either as a stand-alone bone graft substitute or as an extender to autograft harvested from mandibular reconstruction sites. Materials and Methods: The PPF bone graft was crosslinked in the presence of a hydroxyapatite filler and effervescent foaming agents to develop porosity in situ by generating carbon dioxide during the effervescent reaction of citric acid and sodium bicarbonate. The latter reagents are responsible for foam formation and expansion, resulting in a polymeric scaffold with pore sizes in the range of 100 to 500 mum. Twenty adult Sprague-Dawley rats had 3-mm-diameter cortical defects decorticated on the outer aspect of their left mandibular ramus using a Hall drill. Animals were divided into 2 groups of 10 animals each. Animals in group A were treated with implantation of the PPF-based bone graft substitute. Implants were applied buccally to defects on the left side. In group B animals with similar defects, the drill holes were left to heal unaided. The amount of new bone formation and the presence of an inflammatory infiltrate were evaluated at 7 weeks postoperatively. Results: Histologic analysis of the healing process revealed enhanced in vivo new bone formation with the PPF bone graft substitute. These findings were corroborated by the histomorphometric analysis of new bone formation. Discussion: Results of this study demonstrated biocompatibility of the porous PPF-based scaffold in a mandibular defect. Conclusions: These findings may have applicability to the further development of bone graft substitutes for oral/maxillofacial applications. C1 Cambridge Sci, Cambridge, MA 02138 USA. Harvard Univ, Sch Dent Med, Dept Oral med & Diagnost Sci, Boston, MA 02115 USA. Albany Med Coll, Albany, NY 12208 USA. Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. RP Trantolo, DJ (reprint author), Cambridge Sci, 180 Fawcett St, Cambridge, MA 02138 USA. FU NIDCR NIH HHS [1 R43 DE 14272] NR 19 TC 7 Z9 8 U1 1 U2 6 PU QUINTESSENCE PUBL CO INC PI CAROL STREAM PA 551 NORTH KIMBERLY DR, CAROL STREAM, IL 60188-1881 USA SN 0882-2786 J9 INT J ORAL MAX IMPL JI Int. J. Oral Maxillofac. Implants PD MAR-APR PY 2003 VL 18 IS 2 BP 182 EP 188 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 665WF UT WOS:000182143700003 PM 12705295 ER PT J AU Hanninen, ML Utriainen, M Happonen, I Dewhirst, FE AF Hanninen, ML Utriainen, M Happonen, I Dewhirst, FE TI Helicobacter sp flexispira 16S rDNA taxa 1, 4 and 5 and Finnish porcine Helicobacter isolates are members of the species Helicobacter trogontum (taxon 6) SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article ID CANINE GASTRIC HELICOBACTER; RNA GENE POLYMORPHISMS; SP-NOV; IDENTIFICATION SCHEME; BACTERIAL SYSTEMATICS; RAPPINI BACTEREMIA; LABORATORY MICE; CAMPYLOBACTER; GASTROENTERITIS; ABORTION AB The term 'flexispira' refers to micro-organisms with a particular morphology: fusiform-shaped with helical periplasmic fibrils and bipolar tufts of sheathed flagella. Two flexispira taxa. have been formally named, Helicobacter bilis and Helicobacter trogontum, a third named species is Helicobacter aurati and eight additional 16S rRNA sequence-based flexispira taxa have been described by Dewhirst et al. (Int J Syst Evol Microbiol 50, 1781-1787, 2000) and given the provisional designation Helicobacter sp. flexispira taxa 1-5, 7, 8 and 10. In the present study, seven gastric or intestinal flexispira isolates from seven Finnish pigs originating from different farms were characterized. Morphologically, all these porcine isolates had typical flexispira morphology. Analysis of the 16S rDNA sequences of five isolates showed that they were most closely related to the sequences of flexispira. taxa 4 and 5 and H. trogontum (taxon 6), but less closely related to taxa 1 -3 and 8, H. bilis and H. aurati. Phenotypic characterization, analysis of RFLPs of 16S and 23S rDNAs and SDS-PAGE profiles revealed that all of the porcine isolates, reference strains of flexispira taxa 1, 4 and 5 and the type strain of H. trogontum (ATCC 700114(T)) had highly related characteristics that differed from those of the reference strains of taxa 2, 3 and 8 and H. bilis. Furthermore, a high DNA-DNA binding rate was found, in dot-blot hybridization studies, between the Finnish porcine strains, taxa. 1, 4 and 5 reference strains and H. trogontum ATCC 700114(T). In conclusion, polyphasic characterization of novel porcine flexispira isolates and previously described taxa 1, 4 and 5 reference strains showed that they all belong to a validly described species, H. trogontum, and that the taxonomy of known flexispiras is less complicated than proposed on the basis of 16S rDNA sequence analysis. C1 Univ Helsinki, Fac Med Vet, Dept Food & Environm Hyg, Helsinki 00014, Finland. Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. RP Hanninen, ML (reprint author), Univ Helsinki, Fac Med Vet, Dept Food & Environm Hyg, POB 57, Helsinki 00014, Finland. FU NIDCR NIH HHS [DE-10374] NR 45 TC 20 Z9 20 U1 0 U2 4 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD MAR PY 2003 VL 53 BP 425 EP 433 DI 10.1099/ijs.0.02389-0 PN 2 PG 9 WC Microbiology SC Microbiology GA 661NY UT WOS:000181897700008 PM 12710608 ER PT J AU Zacks, DN Hanninen, V Pantcheva, M Ezra, E Grosskreutz, C Miller, JW AF Zacks, DN Hanninen, V Pantcheva, M Ezra, E Grosskreutz, C Miller, JW TI Caspase activation in an experimental model of retinal detachment SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID PHOTORECEPTOR CELL-DEATH; METHYL-N-NITROSOUREA; IN-VIVO; OXYGEN SUPPLEMENTATION; C-FOS; APOPTOSIS; DEGENERATION; EXPRESSION; ABSENCE; MOUSE AB PURPOSE. To test for apoptotic photoreceptor cell death and caspase activation as a function of time after induction of an experimental retinal detachment. METHODS. Retinal detachments were created in Brown Norway rats by injecting 10% hyaluronic acid into the subretinal space using a transvitreous approach. light microscopy and terminal dUTP-biotin nick end-labeling (TUNEL) was performed at 1, 3, 5, and 7 days after detachment to assess for the morphologic features associated with apoptosis. Western blot analysis of retinal protein extracts was performed using antibodies against caspase-3, -7, and -9 and poly-ADP ribose-polymerase (PARP) at 1, 3, and 5 days after detachment. RESULTS. Light microscopic analysis of detached retinas showed the presence of pyknotic nuclei in the outer nuclear layer and disruption of the normal organization of the photoreceptor outer segments. TUNEL-staining was positive in the outer nuclear layer only in the detached portions of the retina. Western blot analysis confirmed the time-dependent activation of caspase-3, -7, and -9 and PARP in the detached retinas. No morphologic stigmata of apoptosis or caspase activation was detected in attached retinas. CONCLUSIONS. The apoptotic photoreceptor cell death in experimental retinal detachments is associated with caspase activation. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Laser Lab, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Angiogenesis Lab, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Glaucoma Serv, Boston, MA 02115 USA. RP Zacks, DN (reprint author), Univ Michigan, Med Ctr, Kellogg Eye Ctr, Retina Serv, 1000 Wall St, Ann Arbor, MI 48105 USA. RI Zacks, David/I-4394-2013; OI Zacks, David/0000-0001-8592-5165 NR 32 TC 70 Z9 77 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2003 VL 44 IS 3 BP 1262 EP 1267 DI 10.1167/iovs.02-0492 PG 6 WC Ophthalmology SC Ophthalmology GA 649TD UT WOS:000181223300045 PM 12601057 ER PT J AU Zhang, DS Murakami, A Johnson, RP Sui, JH Cheng, JH Bai, JR Marasco, WA AF Zhang, DS Murakami, A Johnson, RP Sui, JH Cheng, JH Bai, JR Marasco, WA TI Optimization of ex vivo activation and expansion of macaque primary CD4-Enriched peripheral blood mononuclear cells for use in anti-HIV immunotherapy and gene therapy strategies SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE macaque CD4; T cells; proliferation; coreceptors; transduction ID CD4(+) T-CELLS; IMMUNODEFICIENCY-VIRUS; IN-VITRO; INTRABODIES; LYMPHOCYTES; EXPRESSION; INHIBITION; INFECTION; RECEPTOR; VECTORS AB The rhesus macaque model is a useful experimental system to evaluate effects of T-cell autotransfusion and gene therapies for HIV-1 infection and AIDS prior to a clinical trial. To obtain sufficient numbers of primary macaque CD4 T lymphocytes for this purpose, we examined the culture conditions that were needed to optimize ex vivo activation and expansion of macaque primary CD4-enriched peripheral blood mononuclear cells (PBMCs). In this report, we compared the effects of various stimulants on cell expansion, surface expression of CCR5 and CXCR4, and levels of transduction with a Moloney leukemia virus (MoLV) vector encoding the phenotypic selection marker truncated human nerve growth factor receptor (DeltaNGFR) alone or with the human anti-HIV-1 tat intrabody sFvhutat2. The use of feeder cells strikingly increased the proliferation rate of macaque CD4-enriched PBMCs in vitro. In the presence of an irradiated rhesus macaque B-lymphoblastoid cell line (BLCL), the highest cell expansion over 21 days was achieved with cells activated by Con A (9648-fold), in turn, from high to low, phytohemagglutinin (PHA) (4855-fold), and anti-CD3/CD28-coated beads (2367-fold). Further studies showed that BLCL feeder cells were more effective than human PBMCs (hPBMCs) in promoting proliferation of macaque CD4-enriched PBMCs activated with Con A and anti-CD3/CD28, respectively. The combined use of both BLCL and hPBMC feeder cells did not further increase cell expansion when compared with the use of BLCL cells alone. In addition, the addition of BLCL-conditioned medium (CM) and hPBMC-CM induced cell growth at a rate higher than did the culture medium alone but not as high as with feeder cells. Con A-activated macaque CD4-enriched PBMCs retained 88% of CXCR4 and 39% of CCR5 expression over 17 days compared with PHA-activated cells (50% for CXCR4, 16% for CCR5) and anti-CD3/CD28-activated cells (34% for CXCR4, 37% for CCR5). Finally, PHA, Con A, and CD3/CD28-coated beads supported comparable levels of MoLV transduction. The results should improve the utility of the rhesus macaque model for the testing of T-cell autotransfusion and gene therapies for HIV-1 infection/AIDS. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med,Dept Canc Immunol & AIDS, Boston, MA 02115 USA. New England Reg Primate Res Ctr, Dept Immunol, Southborough, MA 01772 USA. Harvard Univ, Sch Med, Southborough, MA 01772 USA. RP Marasco, WA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med,Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. FU NCRR NIH HHS [RR00168, 5R01 RR14447-03] NR 22 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAR PY 2003 VL 32 IS 3 BP 245 EP 254 DI 10.1097/00126334-200303010-00002 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 655NW UT WOS:000181559800002 PM 12626883 ER PT J AU Jackson, DJ Lang, JM Ecker, J Swartz, WH Heeren, T AF Jackson, DJ Lang, JM Ecker, J Swartz, WH Heeren, T TI Impact of collaborative management and early admission in labor on method of delivery SO JOGNN-JOURNAL OF OBSTETRIC GYNECOLOGIC AND NEONATAL NURSING LA English DT Article DE assisted delivery; certified nurse midwives; cesarean section; labor management; latent phase ID RANDOMIZED CONTROLLED TRIAL; CERTIFIED NURSE-MIDWIVES; CLINICAL-DATA; CARE; OBSTETRICIANS; LESSONS; RATES; WOMEN AB Objective: This study compared the effects of early admission in labor and perinatal care provider on delivery method. Higher spontaneous vaginal delivery rates for certified nurse midwives as compared with physicians have been reported in observational studies and randomized clinical trials. Certified nurse midwives, with their more expectant approach to labor management, would be expected to admit women later in labor than obstetricians. Methods: Prospective cohort study of 2,196 low-risk pregnancies, with singleton, vertex infants admitted in spontaneous labor. Independent and joint effects of perinatal care provider and cervical dilation at admission on delivery method were evaluated. Confounding was addressed using restriction and multiple regression. Results: Fewer (23.4%) women in collaborative care were admitted in early labor (< 4 cm cervical dilation) than women managed by obstetricians (95% CI = -27.6 to -19.2). Obstetrician care had 9% to 30% fewer spontaneous vaginal deliveries. Women admitted early in labor also had 6% to 34% fewer spontaneous vaginal deliveries. Evaluation of joint effects suggested that interaction between obstetrician provider and earlier admission increased the risk of operative delivery. Conclusion: Later admission in labor (at,4 cm or greater cervical dilation) and management of perinatal care by certified nurse midwives in collaboration with obstetricians increased the rate of spontaneous vaginal delivery in low-risk women. C1 Univ Western Cape, Sch Publ Hlth, ZA-8018 Cape Town, South Africa. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. RP Jackson, DJ (reprint author), Univ Western Cape, Sch Publ Hlth, POB 16239, ZA-8018 Cape Town, South Africa. OI Heeren, Timothy/0000-0001-5643-3559 FU AHRQ HHS [R01-HS07161] NR 24 TC 35 Z9 35 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0884-2175 J9 JOGNN JI JOGNN PD MAR-APR PY 2003 VL 32 IS 2 BP 147 EP 157 DI 10.1177/0884217503252045 PG 11 WC Nursing; Obstetrics & Gynecology SC Nursing; Obstetrics & Gynecology GA 654XU UT WOS:000181522900001 PM 12685666 ER PT J AU Halperin, AC Rigotti, NA AF Halperin, AC Rigotti, NA TI US public universities' compliance with recommended tobacco-control policies SO JOURNAL OF AMERICAN COLLEGE HEALTH LA English DT Article DE campus policy; college students; smoking; tobacco use ID COLLEGE-STUDENTS; YOUNG-ADULTS; CIGARETTE USE; SMOKING; PROGRAMS AB To address the rise in tobacco use among college students, several national health organizations, including the American College Health Association, recommend that colleges enact smoking bans in and around all campus buildings, including student housing, and prohibit the sale, advertisement, and promotion of tobacco products on campus. Key informants at 50 US public universities, one from each state, Were interviewed during the 2001/2002 academic year to assess the prevalence of these recommended policies. More than half (54%) of the colleges banned smoking in all campus buildings and student residences, 68% had no tobacco sales on campus, and 32% of the schools' newspapers did not accept tobacco advertising. Regional differences in adoption of these campus tobacco-control policies were present. Although this national sample of public universities had implemented some of the recommended policies, they must take further actions to comply fully with campus tobacco-control guidelines. C1 Univ Washington, Ctr Hlth Educ & Res, Dept Family Med, Seattle, WA 98195 USA. Univ Washington, Ctr Hlth Educ & Res, Dept Hlth Serv, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. RP Halperin, AC (reprint author), Univ Washington, Ctr Hlth Educ & Res, Dept Family Med, Seattle, WA 98195 USA. FU NHLBI NIH HHS [HL04440] NR 26 TC 30 Z9 32 U1 0 U2 4 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 0744-8481 J9 J AM COLL HEALTH JI J. Am. Coll. Health PD MAR PY 2003 VL 51 IS 5 BP 181 EP 188 PG 8 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 684TN UT WOS:000183222800001 PM 12822709 ER PT J AU Chen, ZY Toth, T Godfrey-Bailey, L Mercedat, N Schiff, I Hauser, R AF Chen, ZY Toth, T Godfrey-Bailey, L Mercedat, N Schiff, I Hauser, R TI Seasonal variation and age-related changes in human semen parameters SO JOURNAL OF ANDROLOGY LA English DT Article DE epidemiology; sperm concentration; motility; morphology ID FERTILE MEN; QUALITY; SPERMATOGENESIS; DETERIORATION; MORPHOLOGY; SUMMER AB Although semen quality has been discussed extensively with regard to age and season in the andrology literature, the results vary and firm conclusions are still outstanding. To investigate seasonal and age-related variations in human semen parameters, we analyzed data that were collected from an andrology clinic population. We performed a retrospective review of 551 semen analysis records collected from 1989 to 2000 from the Vincent Memorial Andrology Laboratory at Massachusetts General Hospital. Semen volume, sperm concentration, total sperm count, motility, total motile sperm, and morphology significantly decreased as age increased. In addition, as age increased, the percentage of sperm with tail defects increased. Sperm concentration was significantly higher in winter (mean 157.9 million/mL) than in fall (mean 119.1 million/mL) (P < .05). The mean percentage of sperm with normal morphology was significantly higher in winter (9.2%) than in summer and spring (7.0% and 7.5%, respectively; P < .05). The mean percentage of sperm with head defects was significantly higher in fall and summer (74.0% and 72.3%, respectively) than in winter (68.6%; P < .05). Seasonal variations were found in sperm concentration and morphology, with higher sperm concentrations in winter than in fall, and a greater percentage of sperm with normal morphology in winter than in spring and summer. Sperm concentration was lowest in the fall, whereas the percentage of sperm with normal morphology was lowest in summer. Semen volume, sperm concentration, total sperm count, motility, total motile sperm, and morphology decreased as age increased. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Androl Lab, Boston, MA USA. Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, In Vitro Fertilizat Unit, Boston, MA USA. RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Bldg 1,Room 1405,665 Huntington Ave, Boston, MA 02115 USA. FU NIEHS NIH HHS [ES09718, ES00002] NR 20 TC 58 Z9 64 U1 0 U2 3 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD MAR-APR PY 2003 VL 24 IS 2 BP 226 EP 231 PG 6 WC Andrology SC Endocrinology & Metabolism GA 658ZY UT WOS:000181752700014 PM 12634309 ER PT J AU Peretti, GM Zaporojan, V Spangenberg, KM Randolph, MA Fellers, J Bonassar, LJ AF Peretti, GM Zaporojan, V Spangenberg, KM Randolph, MA Fellers, J Bonassar, LJ TI Cell-based bonding of articular cartilage: An extended study SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the Society-for-Biomaterials CY APR 24-27, 2002 CL TAMPA, FLORIDA SP Soc Biomat DE cartilage repair; chondrocyte; cell adhesion; matrix bonding; tissue engineering; cartilage; biomechanics ID OSTEOCHONDRAL DEFECTS; EXPERIMENTAL-MODEL; PERIOSTEAL GRAFTS; IN-VITRO; REPAIR; CHONDROCYTES; RECONSTRUCTION; AUTOGRAFTS; STRENGTH; RABBIT AB This study evaluated the biomechanical characteristics of newly formed cartilaginous tissue synthesized from isolated chondrocytes and seeded onto devitalized cartilage in an extended study in vivo. Cartilage from porcine articular joints was cut into regular discs and devitalized by multiple freeze-thaw cycles. Articular chondrocytes were enzymatically isolated and incubated in suspension culture in the presence of devitalized cartilage discs for 21 days. This procedure allowed the isolated chondrocytes to adhere to the devitalized matrix surfaces. Chondrocyte-matrix constructs were assembled with fibrin glue and implanted in dorsal subcutaneous pockets in nude mice for up to 8 months. Histological evaluation and biomechanical testing were performed to quantify the integration of cartilage pieces and the mechanical properties of the constructs over time. Histological analysis indicated that chondrocytes grown on devitalized cartilage discs produced new matrix that bonded and integrated individual cartilage elements with mechanically functional tissue. Biomechanical testing demonstrated a time dependent increase in tensile strength, failure strain, failure energy, and tensile modulus to values 5-30% of normal articular cartilage by 8 months in vivo. The values recorded at 4 months were not statistically different from those collected at the latest time point, indicating that the limits of the biomechanical property values were reached after four months from implantation. (C) 2003 Wiley Periodicals, Inc. C1 Univ Massachusetts, Med Ctr, Ctr Tissue Engn, Worcester, MA 01605 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Plast Surg Res Labs, Boston, MA USA. Hosp San Raffaele, Dept Orthopaed, I-20132 Milan, Italy. RP Bonassar, LJ (reprint author), Univ Massachusetts, Med Ctr, Ctr Tissue Engn, Worcester, MA 01605 USA. RI Bonassar, Lawrence/C-2103-2016; OI Bonassar, Lawrence/0000-0003-1094-6433; Peretti, Giuseppe/0000-0001-9341-7187 NR 26 TC 39 Z9 41 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9304 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD MAR 1 PY 2003 VL 64A IS 3 BP 517 EP 524 DI 10.1002/jbm.a.10367 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 671EY UT WOS:000182453400014 PM 12579566 ER PT J AU King, A Strand, B Rokstad, AM Kulseng, B Andersson, A Skjak-Braek, G Sandler, S AF King, A Strand, B Rokstad, AM Kulseng, B Andersson, A Skjak-Braek, G Sandler, S TI Improvement of the biocompatibility of alginate/poly-L-lysine/alginate microcapsules by the use of epimerized alginate as a coating SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the Society-for-Biomaterials CY APR 24-27, 2002 CL TAMPA, FLORIDA SP Soc Biomat DE alginate; microencapsulation; epimerase; biocompatibility; transplantation ID POLYLYSINE MICROCAPSULES; POLYCATION MICROCAPSULES; AZOTOBACTER-VINELANDII; CAPSULE COMPOSITION; GENE-THERAPY; ISLETS; XENOTRANSPLANTATION; IMMUNOSUPPRESSION AB Alginate/poly-L-lysine(PLL)/alginate capsules are used widely for the microencapsulation of cells. Alginate consists of guluronic acid and mannuronic acid, the ratio and sequence of which affect the properties of the alginate. Using C5-epimerases, mannuronic acid can be converted to guluronic acid in the alginate polymer. Such an enzyme, AlgE4, was used to convert blocks of mannuronic acid (M-blocks) to blocks of alternating sequence (MG-blocks). The aims of this study were 1) to investigate whether the use of epimerized alginate as a coating could improve the biocompatibility of alginate/PLL/alginate capsules and 2) to study the biocompatibility of simple alginate beads prepared with epimerized alginate. Four different capsules, two of which contained epimerized alginate, were investigated after implantation in C57BL/6 mice for 1 week. The biocompatibility of alginate/PLL/alginate capsules, as measured by retrieval rates of the capsules and DNA contents and glucose oxidation rates of the cellular overgrowth, was improved when an epimerized coating alginate was used. There were, however, no statistically significant differences in the biocompatibility of simple alginate beads made from epimerized alginate when compared with non-epimerized alginate beads. In general, such beads produced without a PLL coating swelled to a higher extent than the conventional alginate/PLL/alginate capsules. In conclusion, the use of an epimerized coating on alginate-PLL-alginate can improve the biocompatibility of such capsules but still cannot completely eliminate the detrimental effects of PLL on the biocompatibility of the capsules. (C) 2003 Wiley Periodicals, Inc. C1 Univ Uppsala, Dept Med Cell Biol, Biomed Ctr, SE-75123 Uppsala, Sweden. Norwegian Univ Sci & Technol, Dept Biotechnol, Trondheim, Norway. Med Tech Ctr, Dept Canc Res & Mol Biol, Trondheim, Norway. RP King, A (reprint author), Joslin Diabet Ctr, Islet Transplantat & Cell Biol Sect, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. RI King, Aileen/I-5935-2013; Strand, Berit Lokensgard/O-3999-2015 OI King, Aileen/0000-0001-5759-7985; Strand, Berit Lokensgard/0000-0002-9951-0355 NR 25 TC 48 Z9 56 U1 0 U2 16 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9304 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD MAR 1 PY 2003 VL 64A IS 3 BP 533 EP 539 DI 10.1002/jbm.a.10276 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 671EY UT WOS:000182453400016 PM 12579568 ER PT J AU Lee, CR Grodzinsky, AJ Spector, A AF Lee, CR Grodzinsky, AJ Spector, A TI Biosynthetic response of passaged chondrocytes in a type II collagen scaffold to mechanical compression SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the Society-for-Biomaterials CY APR 24-27, 2002 CL TAMPA, FLORIDA SP Soc Biomat DE articular chondrocytes; compression; type II collagen; matrix synthesis ID ARTICULAR-CARTILAGE; EXTRACELLULAR-MATRIX; DYNAMIC COMPRESSION; STATIC COMPRESSION; AGAROSE GELS; TISSUE; EXPLANTS; CULTURE; PROLIFERATION; DEFORMATION AB To investigate the potential utility of mechanical loading in articular cartilage tissue engineering, porous type II collagen scaffolds seeded with adult canine passaged chondrocytes were subjected to static and dynamic compressions of varying magnitudes (0-50% static strain) and durations (1-24 h), and at different times during culture (2-30 days postseeding). The effects of mechanical compression on the biosynthetic activity of the chondrocytes were evaluated by measuring the amount of H-3-proline-labeled proteins and S-35-sulfate-labeled proteoglycans that accumulated in the cell-scaffold construct and was released to the medium during the loading period. Similar to published results on loading of articular cartilage explants, static compression decreased protein and proteoglycan biosynthesis in a time- and dose-dependent manner (each p < 0.005), and selected dynamic compression protocols were able to increase rates of biosynthesis (p < 0.05). The main difference between the results seen for this tissue engineering system and cartilage explants was in the amount of newly synthesized matrix molecules that accumulated within the construct under dynamic loading, with less accumulating in the type II collagen scaffold. In summary, the general biosynthetic response of passaged chondrocytes in the porous type II collagen scaffolds is similar to that seen for chondrocytes in their native environment. Future work needs to be directed to modifications of the cell-seeded construct to allow for the capture of the newly synthesized matrix molecules by the scaffold. (C) 2003 Wiley Periodicals, Inc. C1 MIT, Dept Mech Engn, Cambridge, MA 02139 USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. VA Boston Healthcare Syst, Rehabil Engn Res & Dev, W Roxbury, MA 02132 USA. RP Spector, A (reprint author), MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. FU NIAMS NIH HHS [AR 33236] NR 43 TC 84 Z9 91 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9304 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD MAR 1 PY 2003 VL 64A IS 3 BP 560 EP 569 DI 10.1002/jbm.a.10443 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 671EY UT WOS:000182453400019 PM 12579571 ER PT J AU Fujiwara, I Aravindan, R Horst, RL Drezner, MK AF Fujiwara, I Aravindan, R Horst, RL Drezner, MK TI Abnormal regulation of renal 25-hydroxyvitamin D-1 alpha-hydroxylase activity in X-linked hypophosphatemia: A translational or post-translational defect SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE rickets; phosphate; CYP27B1; parathyroid hormone; thyrocalcitonin ID VITAMIN-D METABOLISM; D-3 1-ALPHA-HYDROXYLASE GENE; PARATHYROID-HORMONE; HYP MICE; 25-HYDROXYVITAMIN-D-1-ALPHA-HYDROXYLASE ACTIVITY; D-3-1-ALPHA-HYDROXYLASE GENE; CALCITRIOL PRODUCTION; HUMAN KERATINOCYTES; GENERALIZED DEFECT; MAMMALIAN KIDNEY AB The hyp mouse exhibits abnormal metabolic/hormonal regulation of renal 25(OH)D-1alpha-hydroxylase activity. Whether this results from aberrant transcriptional regulation of the 1alpha-hydroxylase gene, CYP27B1, remains unknown. To investigate this possibility, we compared phosphate and parathyroid hormone effects on renal proximal convoluted tubule and thyrocalcitonin effects on proximal straight tubule enzyme activity and mRNA expression in normal and hyp mice. We assayed 25(OH)D-1alpha-hydroxylase activity by measuring 1,25(OH)(2)D production and mRNA by ribonuclease protection. Phosphate-depleted mice exhibited a 3-fold increment of 25(OH)D-1alpha-hydroxylase activity compared with normals, whereas hyp mice displayed no enhanced enzyme function. Phosphate-depleted mice concurrently displayed a 2-fold increase in mRNA transcripts; in contrast, despite failure to alter enzyme activity, hyp mice exhibited a similar increment in mRNA transcripts. Parathyroid hormone stimulation of normal mice increased 25(OH)D-1alpha-hydroxylase activity 10-fold,while eliciting only a 2-fold increment in hyp mouse enzyme function. This disparity occurred despite increments of mRNA transcripts to comparable levels (22.2 +/- 3.5- vs. 19.9 +/- 1.8-fold). The dissociation between phosphate- and parathyroid hormone-mediated transcriptional activity and protein function was not universal. Thus, thyrocalcitonin stimulation of normal and hyp mice resulted in comparable enhancement of mRNA transcripts and enzyme activity. These observations indicate that abnormal regulation of vitamin D metabolism in hyp mice occurs in the proximal convoluted tubule and results, not from aberrant transcriptional regulation, but from a defect in translational or post-translational activity. C1 Univ Wisconsin, Sch Med, Clin Sci Ctr H4 554, Dept Med, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, CRECC, Madison, WI USA. Tohoku Univ, Dept Pediat, Sendai, Miyagi 980, Japan. ARS, Natl Anim Dis Ctr, USDA, Ames, IA USA. RP Drezner, MK (reprint author), Univ Wisconsin, Sch Med, Clin Sci Ctr H4 554, Dept Med, 600 Highland Ave, Madison, WI 53792 USA. FU PHS HHS [R01-27032-22] NR 45 TC 17 Z9 17 U1 0 U2 2 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAR PY 2003 VL 18 IS 3 BP 434 EP 442 DI 10.1359/jbmr.2003.18.3.434 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 648YC UT WOS:000181178400007 PM 12619927 ER PT J AU Witcher, JW Long, A Smith, B Sauer, JM Heilgenstein, J Wilens, T Spencer, T Biederman, J AF Witcher, JW Long, A Smith, B Sauer, JM Heilgenstein, J Wilens, T Spencer, T Biederman, J TI Atomoxetine pharmacokinetics in children and adolescents with attention deficit hyperactivity disorder SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID RAT-BRAIN; DEXTROMETHORPHAN; TOMOXETINE AB Objective: Atomoxetine is indicated for the treatment of attention deficit hyperactivity disorder in children, adolescents, and adults. This study was conducted, in part, to evaluate the single-dose and steady-state pharmacokinetics of atomoxetine in pediatric patients. Methods: This was an open-label, dose-titration study in pediatric patients with attention deficit hyperactivity disorder. Eligible patients could elect to participate in a single-dose or steady-state discontinuation pharmacokinetic evaluation including serial plasma sample collection over 24 hours. Plasma concentrations of atomoxetine, 4-hydroxyatomoxetine, and N-desmethylatomoxetine were determined using an atmospheric pressure chemical ionization liquid chromatography/mass spectrometry/mass spectrometry assay. Pharmacokinetic parameters were calculated using noncompartmental analysis. Results: Twenty-one cytochrome P450 2D6 extensive metabolizer patients participated in these single-dose and steady-state pharmacokinetic evaluations. Atomoxetine was rapidly absorbed, with peak plasma concentrations occurring 1 to 2 hours after dosing. Half-life averaged 3.12 and 3.28 hours after a single dose and at steady state, respectively. Minimal accumulation occurred in plasma after multiple twice-daily dosing in extensive metabolizer pediatric patients, as expected based on single-dose pharmacokinetics. As the dose (in mg/kg) increased, proportional increases in area under the curve were observed. Conclusions: The pharmacokinetics of atomoxetine in extensive metabolizer patients were well characterized over a wide range of doses in this study. Atomoxetine pharmacokinetics in pediatric patients and adult subjects were similar after adjustment for body weight. C1 Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA USA. RP Witcher, JW (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. FU NIMH NIH HHS [R29 MH 57511] NR 17 TC 61 Z9 62 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD SPR PY 2003 VL 13 IS 1 BP 53 EP 63 DI 10.1089/104454603321666199 PG 11 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 679QT UT WOS:000182934000006 PM 12804126 ER PT J AU Grinspoon, S Miller, K Herzog, D Clemmons, D Klibanski, A AF Grinspoon, S Miller, K Herzog, D Clemmons, D Klibanski, A TI Effects of recombinant human insulin-like growth factor (IGF)-I and estrogen administration on IGF-I, IGF binding protein (IGFBP)-2, and IGFBP-3 in anorexia nervosa: A randomized-controlled study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BONE TURNOVER; HORMONE; WOMEN; OSTEOPOROSIS; PLASMA; REDUCTION; CULTURES; CHILDREN; WEIGHT AB Administration of recombinant human (rh) IGF-I has been shown to have positive effects on bone density in anorexia nervosa, but the effects of rhIGF-I and estrogen on IGF binding protein (IGFBP)-2 and IGFBP-3 in anorexia nervosa are not known. Sixty-five osteopenic women with anorexia nervosa were randomized to rhIGF-I (30 mug/kg sc twice daily) alone (n = 15), daily ethinyl estradiol (Ovcon 35) with rhIGF-I (n = 15), estradiol and placebo (n = 15), or placebo (n = 14) for 9 months. Subjects were 25.6 +/- 6.8 yr of age, low weight (body mass index 16.6 +/- 0.2 kg/m(2)) and osteopenic (T scores -2.06 +/- 0.09 for spine and -1.76 +/- 0.13 for hip). IGFBP-3 correlated with total hip bone density (r = 0.47, P = 0.0002) and was a significant predictor of hip bone density (P = 0.010) independent of IGF-I and body mass index in a multivariate regression model. During therapy, IGFBP-2 increased by 48 +/- 19 ng/ml in response to rhIGF-I and decreased by -38 +/- 22 ng/ml in response to placebo (P = 0.011). IGFBP-3 decreased (-895 +/- 120 ng/ml) in response to rhIGF-I but showed a minimal change (-53 +/- 99 ng/ml) in response to placebo (P < 0.0001). In contrast, no significant effect of estrogen was seen on IGF-I, IGFBP-2 or IGFBP-3. Among patients receiving rhIGF-I, the change in IGFBP-2 was inversely associated with the change in total hip bone density (R = -0.47, P = 0.013). In conclusion, our data suggest that chronic rhIGF-I administration increases IGF-I and IGFBP-2 and decreases IGFBP-3 in women with anorexia nervosa. IGFBP-2 and IGFBP-3 may be important determinants of bone density in this population. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Eating Disorders Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ N Carolina, Div Endocrine, Chapel Hill, NC USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NCRR NIH HHS [M01-RR-01066]; NIA NIH HHS [AG-02331]; NIDDK NIH HHS [DK-52625] NR 32 TC 19 Z9 19 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 MAR PY 2003 VL 88 IS 3 BP 1142 EP 1149 DI 10.1210/jc.2002-021402 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 655HR UT WOS:000181545700030 PM 12629097 ER PT J AU Joffe, S AF Joffe, S TI Public dialogue and the boundaries of moral community SO JOURNAL OF CLINICAL ETHICS LA English DT Article ID PATIENT; INFORMATION; PRIVACY; CONSENT; MODEL C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Joffe, S (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. OI Joffe, Steven/0000-0002-0667-7384 FU NCI NIH HHS [K01 CA96872] NR 32 TC 4 Z9 4 U1 0 U2 0 PU UNIV PUBLISHING GROUP PI HAGERSTOWN PA 17100 COLE RD #312, HAGERSTOWN, MD 21740-6901 USA SN 1046-7890 J9 J CLIN ETHIC JI J. Clin. Ethics PD SPR-SUM PY 2003 VL 14 IS 1-2 BP 101 EP 108 PG 8 WC Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Biomedical Social Sciences GA 706PH UT WOS:000184461700014 PM 12953358 ER PT J AU Soberman, RJ AF Soberman, RJ TI The expanding network of redox signaling: new observations, complexities, and perspectives SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PROTEIN-TYROSINE PHOSPHATASES; THIOL REDUCTASE GILT; REVERSIBLE INACTIVATION; PROSTANOID FORMATION; HYDROGEN-PEROXIDE; GROWTH-FACTOR; DNA-BINDING; FATTY-ACIDS; CELLS; HIF AB Over thirty years ago, the observations that eventually led to the discovery of the NADPH oxidase were made by Baehner, Karnovsky, and colleagues (1-3). These have served as a focal point of interest in placing reactive oxygen species (ROS) in the conceptual forefront of the biomedical community. Over the last decade, the examination of the roles of oxygen and redox tone in regulating cell function has turned inward to the intracellular environment. Because oxidative metabolism is central to the biology and health of all humans, how we respond to conditions of low and high oxygen stress has become a critical consideration in biology and medicine. Humans live in a world where we continually balance the use of oxygen as a source of energy, and as a source of cellular injury. The generation of oxygen radicals secondary to mitochondrial disruption, the activation of cellular NADPH oxidases, the metabolism of xenobiotics, or other forms of oxidative stress can lead to mutations in DNA, lipid peroxidation, and protein damage. We have therefore evolved a marvelously complex system of both defense mechanisms and sensing mechanisms for changes in cellular redox tone. These include the enzymes superoxide dismutase, catalase, and glutathione peroxidase that detoxify ROS. We have also developed signaling mechanisms that utilize ROS to initiate processes that allow cells to survive exposure to oxidative stress within certain tolerances, but also, when stress and damage become too great, to ensure cell death. How these pathways are initiated and controlled on a molecular basis by ROS and also molecular oxygen is at the heart of what is generally considered redox signaling and the response to oxidative stress. The molecular species that fall under the term ROS include superoxide, hydrogen peroxide (H2O2), hydroxyl radical, and singlet oxygen. Each of these can play a role in a variety of intracellular processes. Finally, we have adapted these molecular species, particularly H2O2 and NO, as signaling molecules in multiple biological processes. The organization of redox signaling and the use of oxygen to transmit information are proving to be much, more complex than one could have originally imagined. As this Perspective series evolved, discussions with the authors suggested that we should cast a wide net and include various mechanisms by which oxygen and reducing equivalents have been adapted to transmit information within cells, or to create cellular damage. Our discussions seemed to raise as many questions as they answered. In the resulting series, several broad areas emerge that may focus the thinking of readers in new directions. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. RP Soberman, RJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit, Bldg 149,Navy Yard,13th St, Charlestown, MA 02129 USA. FU NIGMS NIH HHS [R01GM-061823, R01 GM061823] NR 50 TC 52 Z9 54 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2003 VL 111 IS 5 BP 571 EP 574 DI 10.1172/JCI200318099 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 651XA UT WOS:000181346600002 PM 12618508 ER PT J AU Kim, YM Sachs, T Asavaroengchai, W Bronson, R Sykes, M AF Kim, YM Sachs, T Asavaroengchai, W Bronson, R Sykes, M TI Graft-versus-host disease can be separated from graft-versus-lymphoma effects by control of lymphocyte trafficking with FTY720 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; POSSESSING UNIQUE MECHANISMS; STEM-CELL TRANSPLANTATION; FULLY ALLOGENEIC CHIMERAS; SKIN ALLOGRAFT SURVIVAL; TOTAL-BODY IRRADIATION; HEMATOLOGIC MALIGNANCIES; IMMUNOSUPPRESSIVE AGENT; COMPARING METHOTREXATE; CYCLOSPORINE-A AB Graft-versus-host disease (GvHD) mediated by donor T cells recognizing host alloantigens is associated with beneficial graft-versus-tumor effects in recipients of allogeneic hematopoietic cell transplants. Since leukemias and lymphomas reside largely within the lymphohematopoietic system, we have proposed that the desired graft-versus-leukemia or graft-versus-lymphoma effect can be separated from the complication of GvHD by confinement of the graft-versus-host alloresponse to the lymphohematopoietic tissues. Since the new sphingosine-1-phosphate receptor agonist immunosuppressive drug FTY720 leads to trapping of T cells in secondary lymphoid tissues, we evaluated the possibility that this drug could diminish GvHD, a disease involving epithelial target tissues, while permitting a beneficial alloresponse to take place within the lymphohematopoietic system, leading to graft-versus-lymphoma. effects. We demonstrate here that FTY720 markedly reduces GvHD in a clinically relevant, haploidentical strain combination, while permitting antitumor effects against a T cell lymphoma of unshared host MHC haplotype to proceed unhindered. These results establish a potential new immunotherapeutic approach to separating graft-versus-leukemia effects from GvHD. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Tufts Univ, Sch Vet Med, Hosp Large Anim, Dept Sci Biol, North Grafton, MA USA. RP Sykes, M (reprint author), Harvard Univ, Sch Med, Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr, MGH E,13th St,Bldg 149-5102, Boston, MA 02129 USA. FU NCI NIH HHS [R01 CA079989, R01 CA79989] NR 70 TC 91 Z9 98 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2003 VL 111 IS 5 BP 659 EP 669 DI 10.1172/JCI200316950 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 651XA UT WOS:000181346600014 PM 12618520 ER PT J AU Safran, M Kaelin, WG AF Safran, M Kaelin, WG TI HIF hydroxylation and the mammalian oxygen-sensing pathway SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TUMOR-SUPPRESSOR GENE; HYPOXIA-INDUCIBLE FACTOR; HIPPEL-LINDAU-DISEASE; RENAL-CELL CARCINOMA; ENDOTHELIAL GROWTH-FACTOR; BIOLOGICALLY-ACTIVE PRODUCT; UBIQUITIN LIGASE COMPLEX; PROLYL HYDROXYLATION; TRANSCRIPTION FACTOR; SOMATIC MUTATIONS C1 Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Howard Hughes Med Inst, 44 Binney St,Mayer 457, Boston, MA 02115 USA. NR 75 TC 223 Z9 227 U1 0 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 MAR PY 2003 VL 111 IS 6 BP 779 EP 783 DI 10.1172/JCI200318181 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 656FN UT WOS:000181598300003 PM 12639980 ER PT J AU Recklitis, C O'Leary, T Diller, L AF Recklitis, C O'Leary, T Diller, L TI Utility of routine psychological screening in the childhood cancer survivor clinic SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LONG-TERM SURVIVORS; YOUNG-ADULT SURVIVORS; BEHAVIORAL-ADJUSTMENT; SUICIDE IDEATION; HODGKINS-DISEASE; DEPRESSION; LEUKEMIA; ADOLESCENT; SYMPTOMS; CHILDREN AB Purpose: This study examined the utility of routine psychologic screening in a childhood cancer survivor clinic by evaluating patient acceptance, comparing subjects' symptoms to normative data, examining the utility of specific tests, and identifying risk factors associated with psychological distress. Methods: During their annual clinic visit, 101 adult survivors of childhood cancer (median age, 25 years) completed the Symptom Checklist 90 Revised (SCL-90), as well as the Short Form 36 (SF-36), Beck Depression Inventory (RDI), and one additional suicide question. Psychological distress was operationally defined according to the published SCL-90 clinical case rule, classifying subjects with a consistent pattern of symptom elevations as clinical cases. Results: The majority of subjects (80%) completed the screening in less than 30 minutes and reported little (15%) or no (84%) distress. Sixty-four percent believed it would help "very much" or "moderately" in getting to know them, and 35% thought it would help "slightly." On the SCL-90, 32 subjects (31.7%) had a positive screen, indicating significant psychological distress. All subjects with clinically significant symptoms on the BDI and SF-36 Mental Health Scale were cases on the SCL-90 (case-positive). Suicidal symptoms were reported in 13.9% of the sample, all of whom were SCL-90 cases. In a logistic regression model, subjects' dissatisfaction with physical appearance, poor physical health, and treatment with cranial radiation were associated with psychological distress. Conclusion: Results demonstrate that routine psychological screening can be successfully integrated into the cancer survivor clinic and may be effective in identifying those survivors with significant distress who require further evaluation. C1 Dana Farber Canc Inst, David B Perini Jr Qual Life Clin, Boston, MA 02115 USA. RP Recklitis, C (reprint author), Dana Farber Canc Inst, David B Perini Jr Qual Life Clin, 44 Binney St, Boston, MA 02115 USA. FU AHRQ HHS [T32 HS00063] NR 52 TC 53 Z9 53 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2003 VL 21 IS 5 BP 787 EP 792 DI 10.1200/JCO.2003.05.158 PG 6 WC Oncology SC Oncology GA 652FK UT WOS:000181369000008 PM 12610175 ER PT J AU Fuchs, CS Moore, MR Harker, G Villa, L Rinaldi, D Hecht, JR AF Fuchs, CS Moore, MR Harker, G Villa, L Rinaldi, D Hecht, JR TI Phase III comparison of two irinotecan dosing regimens in second-line therapy of metastatic colorectal cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RANDOMIZED TRIAL; FLUOROURACIL FAILURE; CARCINOMA; CPT-11; MULTICENTER; LEUCOVORIN AB Purpose: Randomized trials in fluorouracil (FU)-refractory colorectal cancer demonstrate significant survival advantages for patients receiving irinotecan. We prospectively compared the efficacy and tolerability of two irinotecan regimens (once a week for 4 weeks followed by a 2-week rest period [weekly] v once every 3 weeks) in such patients. Patients and Methods: This multicenter, open-label, phase III study randomly assigned patients in a 1:2 ratio to irinotecan given either weekly (125 mg/m(2)) or once every 3 weeks (350 mg/m(2), or 300 mg/m(2) in patients who were : 70 years of age, who had Eastern Cooperative Oncology Group performance status equal to 2, or who had prior pelvic irradiation). Results: With median follow-up of 15.8 months, there was no significant difference in 1-year survival (46% v 41%, respectively; P = .42), median survival (9.9 v 9.9 months, respectively, P = .43), or median time to progression (4.0 v 3.0 months, respectively, P = .54) between the two regimens. Grade 3/4 diarrhea occurred in 36% of patients treated weekly and in 19% of those treated once every 3 weeks (P = .002). Grade 3/4 neutropenia occurred in 29% of patients treated weekly and 34% of those treated once every 3 weeks (P = .35). Treatment-related mortality occurred in five patients (5.3%) receiving irinotecan weekly and three patients (1.6%) given therapy once every 3 weeks (P = .12). Global quality of life was not statistically different between treatment groups. Conclusion: Irinotecan schedules of weekly and of once every 3 weeks demonstrated similar efficacy and quality of life in patients with FU-refractory, metastatic colorectal cancer. The regimen of once every 3 weeks was associated with a significantly lower incidence of severe diarrhea. (C) 2003 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Georgia Canc Res Ctr, Decatur, GA USA. Intermountain Hematol Oncol Associates PC, Salt Lake City, UT USA. Mercy Hosp, Oncol Radiat Associates, Miami, FL USA. Louisiana Oncol Associates, Lafayette, LA USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. RP Fuchs, CS (reprint author), Dana Farber Canc Inst, 44 Binney St,Off Dana 1232, Boston, MA 02115 USA. NR 17 TC 185 Z9 189 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2003 VL 21 IS 5 BP 807 EP 814 DI 10.1200/JCO.2003.08.058 PG 8 WC Oncology SC Oncology GA 652FK UT WOS:000181369000011 PM 12610178 ER PT J AU Johnston, PG Benson, AB Catalano, P Rao, MS O'Dwyer, PJ Allegra, CJ AF Johnston, PG Benson, AB Catalano, P Rao, MS O'Dwyer, PJ Allegra, CJ TI Thymidylate synthase protein expression in primary colorectal cancer: Lack of correlation with outcome and response to fluorouracil in metastatic disease sites SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ADVANCED COLON-CANCER; CELL-LINES; CLINICAL-RESPONSE; PRIMARY TUMOR; 5-FLUOROURACIL; LEUCOVORIN; RESISTANCE; P53; CHEMOTHERAPY; QUANTITATION AB Purpose: The aim of this study was to investigate the utility of quantitating thymidylate synthase (TS) in the primary tumor as a surrogate for metastatic disease sites to predict the likelihood of response and outcome to fluorouracil (FU) treatment in patients with metastatic colorectal cancer. Methods: TS protein expression was evaluated using the TS 106 antibody and the avidin biotin labeling immunahistochemical technique in primary tumor samples from 219 patients with metastatic colorectal cancer. The patients were a representative sample of those patients enrolled into the Eastern Cooperative Oncology Group E2290 protocol that evaluated five separate FU-containing regimens in patients with metastatic residual or recurrent colorectal carcinoma. Results: Our retrospective analysis found that the level and extent of TS protein expression in the primary tumor did not correlate with overall survival in patients with metastatic or recurrent colorectal cancer. A trend toward a direct correlation between the level of TS protein expression and response was noted in tumors that expressed high TS levels. This response advantage for patients expressing high TS levels in the primary tumor was apparent regardless of what FU-based treatment the patient received but was most apparent in the subgroup treated with leucovorin, in which the level of TS expression and response to FU and leucovorin reached statistical significance (P = .034). No significant interaction could be detected between the addition of leucovorin to FU and the level of TS expression in the primary tumor. Conclusion: This study demonstrated that measurement of TS protein levels in the primary tumor tissue does not aid in predicting outcome or response to FU in a metastatic disease site. These assays must be performed on biopsy tissue from the metastatic disease site that is used to radiologically assess response and outcome to treatment. (C) 2003 by American Society of Clinical Oncology. C1 Queens Univ Belfast, Belfast City Hosp, Dept Oncol, Canc Res Ctr, Belfast BT9 7AB, Antrim, North Ireland. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Clin Invest Program, Chicago, IL 60611 USA. Dana Farber Canc Inst, Dept Biostat Sci, Eastern Cooperat Oncol Grp, Ctr Stat, Boston, MA 02115 USA. Northwestern Mem Hosp, Chicago, IL USA. Univ Penn, Philadelphia, PA 19104 USA. NCI, Med Branch, Bethesda, MD 20892 USA. RP Johnston, PG (reprint author), Queens Univ Belfast, Belfast City Hosp, Dept Oncol, Canc Res Ctr, Univ Floor,97 Lisburn Rd, Belfast BT9 7AB, Antrim, North Ireland. NR 21 TC 64 Z9 69 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 MAR 1 PY 2003 VL 21 IS 5 BP 815 EP 819 DI 10.1200/JCO.2003.07.039 PG 5 WC Oncology SC Oncology GA 652FK UT WOS:000181369000012 PM 12610179 ER PT J AU Coyne, CA Xu, RH Raich, P Plomer, K Dignan, M Wenzel, LB Fairclough, D Habermann, T Schnell, L Quella, S Cella, D AF Coyne, CA Xu, RH Raich, P Plomer, K Dignan, M Wenzel, LB Fairclough, D Habermann, T Schnell, L Quella, S Cella, D TI Randomized, controlled trial of an easy-to-read informed consent statement for clinical trial participation: A study of the eastern cooperative oncology group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LONGITUDINAL DATA-ANALYSIS; READABILITY; FORMS; UNDERSTAND; HOSPITALS; LITERACY; MODELS AB Purpose: Studies have documented that the majority of consent documents for medical diagnosis and treatment are written at a reading level above that of the majority of the U.S. population. This study hypothesized that use of an easy-to-read consent statement, when compared with a standard consent statement, will result in higher patient comprehension of the clinical treatment protocol, lower patient anxiety, higher patient satisfaction, and higher patient accrual. Methods: A randomized controlled trial was conducted in 44 institutions that were members or affiliates of three cooperative oncology groups. Institutions were randomly assigned to administer either an easy-to-read consent statement or the standard consent statement to patients being recruited to participate in selected cancer treatment trials. Telephone interviews were conducted with a total of 207 patients to assess study outcomes. Results: Patients in the intervention arm demonstrated significantly lower consent anxiety and higher satisfaction compared with patients in the control arm. Patient comprehension and state anxiety were not affected by the intervention. Accrual rates into the parent studies also did not differ significantly between the two study groups. Conclusion: Clinical trial informed consent statements can be modified to be easier to read without omitting critical information. Patient anxiety and satisfaction can be affected by the consent document. The generalizability of these study results is limited by the characteristics of the patient sample. Ninety percent of the sample were white women, and the mean Rapid Estimate of Adult Literacy in Medicine score was approximately 64, indicating a literacy level at or above the ninth grade. (C) 2003 by American Society of Clinical Oncology. C1 W Virginia Univ, Sch Med, Dept Community Med, Morgantown, WV 26506 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Colorado, Hlth Sci Ctr, AMC Canc Res Ctr, Denver, CO 80202 USA. Univ Colorado, Hlth Sci Ctr, Colorado Hlth Outcomes Program, Denver, CO 80202 USA. Univ Kentucky, Prevent Res Ctr, Lexington, KY USA. Univ Calif Irvine, Div Epidemiol, Irvine, CA USA. Mayo Clin, Rochester, MN USA. Metro Minnesota CCOP, St Louis Pk, MN USA. Evanston Northwestern Healthcare, Evanston, IL USA. RP Coyne, CA (reprint author), W Virginia Univ, Sch Med, Dept Community Med, POB 9190, Morgantown, WV 26506 USA. FU NCI NIH HHS [CA13650, CA72592, CA23318, CA21115] NR 26 TC 112 Z9 115 U1 0 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2003 VL 21 IS 5 BP 836 EP 842 DI 10.1200/JCO.2003.07.022 PG 7 WC Oncology SC Oncology GA 652FK UT WOS:000181369000015 PM 12610182 ER PT J AU Mandelblatt, JS Edge, SB Meropol, NJ Senie, R Tsangaris, T Grey, L Peterson, BM Hwang, YT Kerner, J Weeks, J AF Mandelblatt, JS Edge, SB Meropol, NJ Senie, R Tsangaris, T Grey, L Peterson, BM Hwang, YT Kerner, J Weeks, J TI Predictors of long-term outcomes in older breast cancer survivors: Perceptions versus patterns of care SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LYMPH-NODE DISSECTION; BLACK-AND-WHITE; AXILLARY DISSECTION; CLINICAL-TRIAL; ELDERLY WOMEN; CARCINOMA; STAGE; COMORBIDITY; MORBIDITY; QUALITY AB Purpose: There are few data on sequelae, of breast cancer treatments in older women. We evaluated posttreatment quality of life and satisfaction in a national population. Patients and Methods: Telephone surveys were conducted with a random cross-sectional sample of 1,812 Medicare beneficiaries 67 years of age and older who were 3, 4, and 5 years posttreatment for stage I and II breast cancer. Regression models were used to estimate the adjusted risk of decrements in physical and mental health functioning by treatment. In a subset of women (n = 732), additional data were used to examine arm problems, impact of cancer, and satisfaction, controlling for baseline health, perceptions of ageism and racism, demographic and clinical factors, region, and surgery year. Results: Use of axillary dissection was the only surgical treatment that affected outcomes, increasing the risk of arm problems four-fold (95% confidence interval, 1.56 to 10.51), controlling for other factors. Having arm problems, in turn, exerted a consistently negative independent effect on all outcomes (P less than or equal to .001). Processes of care were also associated with quality of life and satisfaction. For example, women who perceived high levels of ageism or felt that they had no choice of treatment reported significantly more bodily pain, lower mental health scores, and less general satisfaction. These some factors, as well as high perceived racism, were significantly associated with diminished satisfaction with the medical care system. Conclusion: With the exception of axillary dissection, the processes of care, and not the therapy itself, are the most important determinants of long-term quality of life in older women. (C) 2003 by American Society of Clinical Oncology. C1 Lombardi Canc Ctr, Dept Oncol, Canc Control Program, Washington, DC 20007 USA. Georgetown Univ, Dept Surg, Sch Med, Washington, DC 20057 USA. Sibley Mem Hosp, Dept Surg, Washington, DC USA. Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY 10027 USA. Beth Israel Med Ctr, Dept Surg, New York, NY 10003 USA. SUNY Buffalo, Roswell Pk Canc Inst, Dept Surg, Buffalo, NY 14263 USA. Fox Chase Canc Ctr, Div Med Sci, Philadelphia, PA 19111 USA. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. NCI, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Mandelblatt, JS (reprint author), Lombardi Canc Ctr, Dept Oncol, Canc Control Program, 223 Wisconsin Ave,Suite 317, Washington, DC 20007 USA. OI Kerner, Jon/0000-0002-8792-3830 FU AHRQ HHS [R01 HS 08395] NR 59 TC 88 Z9 88 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 MAR 1 PY 2003 VL 21 IS 5 BP 855 EP 863 DI 10.1200/JCO.2003.05.007 PG 9 WC Oncology SC Oncology GA 652FK UT WOS:000181369000018 PM 12610185 ER PT J AU Sahani, D Saini, S D'Souza, RV O'Neill, MJ Prasad, SR Kalra, MK Halpern, EF Mueller, P AF Sahani, D Saini, S D'Souza, RV O'Neill, MJ Prasad, SR Kalra, MK Halpern, EF Mueller, P TI Comparison between low (3 : 1) and high (6 : 1) pitch for routine abdominal/pelvic imaging with multislice computed tomography SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE multislice computed tomography; pitch; image quality; abdominal imaging ID HELICAL CT; SPIRAL-CT AB Purpose: The purpose of this study was to compare the performance of low helical pitch acquisition (3:1) and high helical pitch acquisition (6:1) for routine abdominal/pelvic imaging with multislice computed tomography (CT). Method: Three hundred eighty-four patients referred for abdominal/pelvic CT were examined in a breath-hold on a multislice CT scanner (LightSpeed QX/I; General Electric Medical Systems, Milwaukee, WI). Patients were randomized and scanned with pitch of 3:1 or 6:1 using a constant 140 peak kV and 280-300 mA. Images were reconstructed at a 3.75-mm slice thickness. Direct comparison between the two pitches was possible in a subset of 40 patients who had a follow-up scan performed with the second pitch used in each patient. A comparison was also performed between standard dose CT using a pitch of 6:1 and 20% reduced radiation dose CT using a pitch of 3:1. Two readers performed a blind evaluation using a three-point scale for image quality, anatomic details, and motion artifacts. Statistical analysis was performed using a rank sum test and the Wilcoxon signed rank test. Results: Overall image quality mean scores were 2.5 and 2.3 for a pitch of 3:1 and a pitch of 6:1, respectively (P = 0.134). Likewise, mean anatomic detail and motion artifact scores were 2.5 and 2.6 for a 3:1 pitch and 2.3 and 2.5 for a 6:1 pitch, respectively (P > 0.05). In patients with a direct comparison of the two pitches (with the standard radiation dose as well as with a 20% reduction in milliamperes), no statistically significant difference in the performance of the two pitches was observed (P > 0.05). Conclusion: Image quality with a high pitch (6:1) is acceptable for routine abdominal/pelvic CT. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. Massachusetts Gen Hosp, Data Management Grp, Boston, MA 02114 USA. RP Sahani, D (reprint author), 234-E,55 Fruit St, Boston, MA 02114 USA. NR 9 TC 6 Z9 7 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAR-APR PY 2003 VL 27 IS 2 BP 105 EP 109 DI 10.1097/00004728-200303000-00001 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 678QZ UT WOS:000182879100001 PM 12702997 ER PT J AU Ptak, T Novelline, RA AF Ptak, T Novelline, RA TI Amiodarone administered for cardiac resuscitation does not alter the integrity of noncontrast cerebral computed tomography performed on neurologically symptomatic patients before therapeutic cardiac catheterization SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE contrast; cerebral computed tomography; cardiac arrhythmia ID APOPTOSIS AB Purpose: Recent revisions of the advanced cardiac life support guidelines support the use of amiodarone in treating acute cardiac arrhythmia. Chemically, amiodarone has two atoms of iodine per molecule (39.3% wt/wt). We propose that at antiarrhythmic doses as prescribed by advanced cardiac life support guidelines, enhancement resulting from the bound amiodarone iodine is not significantly different from routine noncontrasted screening cerebral computed tomography (CT) studies. Method: Six patients presenting to the our emergency department with successful resuscitation after cardiac arrhythmia were identified before obtaining a screening CT scan and subsequent transfer to the cardiac catheterization laboratory for intervention. The total dose of amiodarone (bolus + drip) was calculated up to the moment of the CT scan. Subjects were age and gender matched with two control subjects. Hematocrit value and CT density measurements in the pons, putamen, centrum semiovale, and cerebral venous blood pool were recorded. Paired t test and linear regression analyses were performed. Amiodarone dose and hematocrit were used as covariates in the regression model to correct for altered density as a result of relative anemia. Results: Mean density in the blood pool was increased in the amiodarone subjects in both the univariate and regression models. Although the mean density difference of 3 HU was statistically significant, it is not likely detectable by the eye. All other brain area measurements showed nonsignificant differences in mean density for both the univariate analysis and regression model. Conclusion: Amiodarone administered at doses recommended by the American Heart Association for treatment of cardiac arrhythmia does not interfere with interpretation of the precatheterization noncontrasted screening cerebral CT scan. C1 Massachusetts Gen Hosp, Dept Radiol, Div Emergency Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ptak, T (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Emergency Radiol, 55 Fruit St,FND-210, Boston, MA 02114 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAR-APR PY 2003 VL 27 IS 2 BP 226 EP 230 DI 10.1097/00004728-200303000-00020 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 678QZ UT WOS:000182879100020 PM 12703016 ER PT J AU Aquino, SL Hayman, LA Loomis, SL Taber, KH AF Aquino, SL Hayman, LA Loomis, SL Taber, KH TI Source and direction of thoracic lymphatics: Part I - Upper thorax SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE lymphatics, lung cancer; lung cancer, metastases; lung cancer, surgery; TNM classification; thorax, computed tomography ID POSITRON-EMISSION-TOMOGRAPHY; LUNG-CANCER; DRAINAGE; SEGMENTS; VESSELS AB The purpose of this set of two articles is to illustrate the source and direction of lymphatic drainage in the thorax on axial CT schematics. The first article describes the upper thorax. The second article will describe the lower thorax. The nodal groups are given conventional anatomic names and the corresponding terminology of the American Thoracic Society. Arrows indicate the direction of the flow. The region or organ drained is color-coded, and nodes that receive lymph from each area are assigned appropriately colored boxes. Major drainage patterns are also described. This information can be used to assess a suggestive lymph node by tracing it to the region of drainage and looking for pathological lesions. Alternatively, one may extrapolate the potential drainage routes of a tumor and scrutinize specific sites for nodal metastases. C1 Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. Baylor Coll Med, Herbert J Frensley Ctr Imaging Res, Houston, TX 77030 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Aquino, SL (reprint author), Baylor Coll Med, Dept Radiol, 1 Baylor Plaza, Houston, TX 77030 USA. NR 13 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAR-APR PY 2003 VL 27 IS 2 BP 292 EP 296 DI 10.1097/00004728-200303000-00033 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 678QZ UT WOS:000182879100033 PM 12703029 ER PT J AU Crowson, AN Mihm, MC Magro, CM AF Crowson, AN Mihm, MC Magro, CM TI Cutaneous vasculitis: a review SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Review ID HENOCH-SCHONLEIN PURPURA; SYSTEMIC-LUPUS-ERYTHEMATOSUS; HEPATITIS-C VIRUS; ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; ESSENTIAL MIXED CRYOGLOBULINEMIA; BOWEL-BYPASS SYNDROME; LEUKOCYTOCLASTIC VASCULITIS; ELEVATUM-DIUTINUM; WEGENERS GRANULOMATOSIS; RHEUMATOID VASCULITIS AB As the skin is commonly involved in systemic vasculitic disorders as well as those hypersensitivity states whose expression is largely skin-confined, cutaneous vasculitic lesions offer a window to diagnosis and a ready source of accessible tissue for biopsy. In this review, we discuss the pathologic manifestations of chronic vasculitic syndromes such as granuloma faciale and erythema elevatum diutinum; IgA-associated vasculitis including Henoch-Schonlein purpura; vasculitis seen in the setting of cryoglobulinemia and hypergammaglobulinemia of Waldenstrom, hereditary deficiencies of complement, and IgA deficiency; those leukocytoclastic vasculitides resulting from hypersensitivity reactions to drug, chemical and foodstuff ingestion; and those vasculitides seen in patients with systemic diseases such as polyarteritis nodosa, rheumatoid arthritis, mixed connective tissue disease, systemic lupus erythematosus, Sjogren's syndrome, relapsing polychondritis, Behcet's disease, Wegener's granulomatosis, and allergic granulomatosis of Churg and Strauss. C1 St Johns Hosp, Reg Med Lab, Tulsa, OK 74114 USA. Univ Oklahoma, Tulsa, OK USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. RP Crowson, AN (reprint author), St Johns Hosp, Reg Med Lab, 1923 S Utica, Tulsa, OK 74114 USA. NR 110 TC 78 Z9 83 U1 1 U2 8 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD MAR PY 2003 VL 30 IS 3 BP 161 EP 173 DI 10.1034/j.1600-0560.2003.00033.x PG 13 WC Dermatology; Pathology SC Dermatology; Pathology GA 656WE UT WOS:000181633400001 PM 12641775 ER PT J AU Kressin, NR Boehmer, U Nunn, ME Spiro, A AF Kressin, NR Boehmer, U Nunn, ME Spiro, A TI Increased preventive practices lead to greater tooth retention SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE preventive dentistry; self-care; health behavior; toothbrushing; tooth loss ID ORAL HEALTH-STATUS; DENTAL BEHAVIORS; HYGIENE AB Prior research has rarely examined the impact of ADA-recommended preventive practices on tooth retention. We hypothesized that better oral hygiene leads to increased tooth retention. We examined the association of cross-sectional and long-term assessments of preventive practices, as well as various combinations of hygiene practices, with tooth retention. Among 736 male participants in the VA Dental Longitudinal Study, we utilized cross-sectional and longitudinal self-reports of toothbrushing, dental floss. use, annual prophylaxis, and combinations of such behaviors, and examined their association with clinically assessed numbers of teeth. Baseline and long-term hygiene behaviors (except brushing) were associated with an increased baseline number of teeth and decreased subsequent tooth loss. Use of multiple hygiene behaviors was associated with greater tooth retention, cross-sectionally and longitudinally. Adherence to ADA recommendations for preventive care leads to better oral health, and consistently practicing preventive behaviors over the long term confers greater benefits than doing so over the short term. C1 VAMC, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. Boston Univ, Sch Publ Hlth, Dept Hlth Serv, Boston, MA USA. Boston Univ, Dept Hlth Policy & Hlth Serv Res, Goldman Sch Dent Med, Boston, MA USA. Boston VA Healthcare Syst, VA Normat Aging Study, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. RP Kressin, NR (reprint author), VAMC, Ctr Hlth Qual Outcomes & Econ Res, 200 Springs Rd,Bldg 70 152, Bedford, MA 01730 USA. FU NIDCR NIH HHS [DE11455] NR 13 TC 39 Z9 41 U1 2 U2 4 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAR PY 2003 VL 82 IS 3 BP 223 EP 227 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 648HR UT WOS:000181145500014 PM 12598553 ER PT J AU Marino, M Lisi, S Pinchera, A Chiovato, L McCluskey, RT AF Marino, M Lisi, S Pinchera, A Chiovato, L McCluskey, RT TI Targeting of thyroglobulin to transcytosis following megalin-mediated endocytosis: Evidence for a preferential pH-independent pathway SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Article DE thyroglobulin; megalin; transcytosis; thyroid; pH ID THYROID EPITHELIAL-CELLS; RECEPTOR GENE FAMILY; NONDIPLOID KARYOTYPE; HORMONE RELEASE; PROTEIN; GP330; BINDING AB TG internalized from the colloid by megalin, bypasses the lysosomal pathway and is transported across thyrocytes by transcytosis. Although most of the intracellular mechanisms responsible for targeting of ligands to transcytosis are unknown, for certain ligands a role of lysosomal pH has been established. Thus, ligands that undergo lysosomal degradation dissociate from their receptors due to the low pH of endosomes, whereas certain ligands that undergo transcytosis fail to dissociate because they bind to their receptors at acidic pH. Here we studied the role of pH in TG transcytosis. We first investigated the effect of pH on megalin binding to TG in solid phase assays and found that, although megalin bound to TG at various pH values (ranging from 4-8), optimal binding was seen at acidic pH (ranging from 4.5-6). We then studied the effect of chloroquine (CQ) and ammonium chloride (AC), which increase endosomal pH, on transcytosis of TG across Fisher rat thyroid (FRTL-5 cells). Transcytosis assays were performed using FRTL-5 cells cultured on filters in dual chambered devices, with megalin expression only on the up-per surface of the layers. TG was added to the upper chamber and transcytosed TG was measured in fluids collected from the lower chamber after incubation at 37 C. Treatment of FRTL-5 cells with CQ or AC did not affect binding and uptake of TG, but it did reduce T-3 release from exogenously added TG, used as a measure of TG degradation in the lysosomal pathway. Treatment with CQ or AC resulted in an increase of transcytosis of TG across FRTL-5 cells, but only to a minimal extent (115-20%). The effects of CQ or AC and those of a megalin competitor (the monoclonal antibody 1H2, which reduced transcytosis) were not additive, suggesting that CQ and AC act on the megalin-mediated pathway. In conclusion, because TG binding to megalin is greatest at acidic pH, it is possible that TG does not dissociate from megalin in the lysosomal pathway. However, the pH-dependence of TG binding to megalin does not account for much of transcytosis, which probably occurs largely because of other mechanisms of targeting. (C) 2003, Editrice Kurtis. C1 Univ Pisa, Dipartimento Endocrinol, I-56124 Pisa, Italy. Univ Pavia, Salvatore Maugeri Fdn, IRCSS, I-27100 Pavia, Italy. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Marino, M (reprint author), Univ Pisa, Dipartimento Endocrinol, Via Paradisa 2, I-56124 Pisa, Italy. NR 31 TC 7 Z9 7 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD MAR PY 2003 VL 26 IS 3 BP 222 EP 229 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 681DH UT WOS:000183021300008 PM 12809172 ER PT J AU Podolsky, DK AF Podolsky, DK TI The future of IBD treatment SO JOURNAL OF GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT 88th Annual Meeting of the Japanese-Society-of-Gastroenterology CY APR 24-26, 2002 CL ASAHIKAWA, JAPAN SP Japanese Soc Gastroenterol DE inflammatory bowel disease; mucosal immunology; microbial flora ID ACTIVE CROHNS-DISEASE; PLACEBO-CONTROLLED TRIAL; RECOMBINANT HUMAN INTERLEUKIN-10; INFLAMMATORY-BOWEL-DISEASE; NECROSIS-FACTOR-ALPHA; ULCERATIVE-COLITIS; DOUBLE-BLIND; MONOCLONAL-ANTIBODY; THERAPY; INFLIXIMAB AB Throughout most of the past 50 years, treatment of Crohn's disease and ulcerative colitis has been dominated by the use of agents whose efficacy was defined on an empiric basis. Many of these, including most especially 5-amino salicylic acid (5-ASA)-based agents and corticosteroids, remain mainstays of current treatment even as research is catching up with clinical experience to define the mechanistic basis of their efficacy. Other agents, also of established utility in at least a subset of patients, were developed on the basis of general inferences about disease pathogenesis. These agents are exemplified by antibiotics (metronidazole) and immunosuppressive agents (azathioprine/6-mercaptopurine, methotrexate, and cyclosporine); attention was directed on the assumption of the general likely importance of microbial species and immunoactivation, respectively. However, the rapid progress, even if still incomplete in understanding of pathophysiological mechanisms that play a role in IBD, has transformed the development of new therapeutic agents, enabling the development of several agents now available or currently in advanced clinical development. It is notable that each of the major overall thrusts in development of new therapeutic strategies parallels, and may be reasonably viewed as the partial outgrowth of, dominant areas of progress in understanding of disease mechanisms relevant to IBD. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. NR 31 TC 23 Z9 23 U1 0 U2 0 PU SPRINGER-VERLAG TOKYO PI TOKYO PA 3-3-13, HONGO, BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 0944-1174 J9 J GASTROENTEROL JI J. Gastroenterol. PD MAR PY 2003 VL 38 SU 15 BP 63 EP 66 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 662VF UT WOS:000181969000017 PM 12698875 ER PT J AU Sarr, MG Murr, M Smyrk, TC Yeo, CJ Fernandez-del-Castillo, C Hawes, RH Freeny, PC AF Sarr, MG Murr, M Smyrk, TC Yeo, CJ Fernandez-del-Castillo, C Hawes, RH Freeny, PC TI Primary cystic neoplasms of the pancreas: Neoplastic disorders of emerging importance - Current state-of-the-art and unanswered questions SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 19-22, 2002 CL SAN FRANCISCO, CALIFORNIA SP Soc Surg Alimentary Tract ID PAPILLARY MUCINOUS TUMORS; INTRADUCTAL PAPILLARY; DIFFERENTIAL-DIAGNOSIS; FLUID ANALYSIS; CLINICOPATHOLOGICAL FEATURES; HELICAL CT; CYSTADENOCARCINOMA; CYSTADENOMAS; MANAGEMENT; PANCREATOSCOPY C1 Mayo Clin & Mayo Fdn, Dept Surg, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Pathol, Rochester, MN 55905 USA. Univ S Florida, Dept Surg, Tampa, FL 33620 USA. Johns Hopkins Univ Hosp, Dept Surg, Baltimore, MD 21287 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Med Univ S Carolina, Dept Gastroenterol, Charleston, SC 29425 USA. Univ Washington, Dept Radiol, Seattle, WA 98195 USA. RP Sarr, MG (reprint author), Mayo Clin & Mayo Fdn, Dept Surg, 200 1st St SW AL 2-435, Rochester, MN 55905 USA. NR 46 TC 136 Z9 148 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAR-APR PY 2003 VL 7 IS 3 BP 417 EP 428 AR PII S1091-255X(02)00163-4 DI 10.1016/S1091-255X(02)00163-4 PG 12 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 661HY UT WOS:000181886200018 PM 12654569 ER PT J AU Glorioso, JC Krisky, D Wolfe, D Goins, W Goss, J Hao, SL Chattopadhyay, M Mata, M Fink, D AF Glorioso, JC Krisky, D Wolfe, D Goins, W Goss, J Hao, SL Chattopadhyay, M Mata, M Fink, D TI Treatment of sensory neuron disease using HSV gene vectors SO JOURNAL OF GENE MEDICINE LA English DT Meeting Abstract CT 2nd International Symposium on Molecular Diagnostics and Skin Gene therapy CY MAR 27-29, 2003 CL DUSSELDORF, GERMANY C1 Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 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 1099-498X J9 J GENE MED JI J. Gene. Med. PD MAR PY 2003 VL 5 IS 3 BP S15 EP S15 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 662WU UT WOS:000181972700050 ER PT J AU Connelly, MT Sullivan, AM Peters, AS Clark-Chiarelli, N Zotov, N Martin, N Simon, SR Singer, JD Block, SD AF Connelly, MT Sullivan, AM Peters, AS Clark-Chiarelli, N Zotov, N Martin, N Simon, SR Singer, JD Block, SD TI Variation in predictors of primary care career choice by year and stage of training - A national survey SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE medical education; primary care; career choice; role models ID MEDICAL-SCHOOL; SPECIALTY CHOICES; INTERNAL-MEDICINE; ROLE MODELS; GENERALIST PHYSICIANS; STUDENTS; PEDIATRICS; MASTERFILE; RESIDENCY; PROGRAMS AB CONTEXT: It is not known whether factors associated with primary care career choice affect trainees differently at different times or stages of medical education. OBJECTIVE: To examine how role models, encouragement, and personal characteristics affect career choice at different stages (medical school vs residency) and periods (1994 vs 1997) of training. DESIGN: A split-panel design with 2 cross-sectional telephone surveys and a panel survey in 1994 and 1997. PARTICIPANTS: A national probability sample of fourth-year students (307 in 1994, 219 in 1997), 645 second-year residents in 1994, and 494 third-year residents in 1997. Of the fourth-year students interviewed in 1994, 241 (78.5%) were re-interviewed as third-year residents in 1997. MAIN OUTCOME MEASURE: Primary care (general internal medicine, general pediatrics, or family medicine) career choice. RESULTS: Having a primary care role model was a stronger predictor of primary care career choice for residents (odds ratio [OR], 18.0; 95% confidence interval [95% CI], 11.2 to 28.8 in 1994; OR, 43.7; 95% CI, 24.4 to 78.3 in 1997) than for students (OR, 6.5; 95% CI, 4.3 to 10.2; no variation by year). Likewise, peer encouragement was more predictive for residents (OR, 5.4; 95% CI, 3.3 to 8.9 in 1994; OR, 16.6; 95% CI; 9 .7 to 28.4 in 1997) than for students (OR, 2.1; 95% CI, 1.3 to 3.2; no variation by year). Orientation to the emotional aspects of care was consistently associated with primary care career choice across stages and years of training. CONCLUSIONS: The effect of peer encouragement and role models on career choice differed for students and residents and, in the case of residents, by year of training, suggesting that interventions to increase the primary care workforce should be tailored to stage of training. C1 Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. Harvard Pilgrim Hlth Care, Boston, MA 02115 USA. Vanderbilt Univ, Dept Psychol & Human Dev, Nashville, TN USA. Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Div Psychiat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Connelly, MT (reprint author), Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, 133 Brookline Ave,6th Floor, Boston, MA 02215 USA. RI Singer, Judith/B-6846-2008; OI Singer, Judith/0000-0002-5828-4961 NR 48 TC 24 Z9 25 U1 0 U2 6 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2003 VL 18 IS 3 BP 159 EP 169 DI 10.1046/j.1525-1497.2003.01208.x PG 11 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 657EL UT WOS:000181652400001 PM 12648246 ER PT J AU Bean-Mayberry, BA Chang, CCH McNeil, MA Whittle, J Hayes, PM Scholle, SH AF Bean-Mayberry, BA Chang, CCH McNeil, MA Whittle, J Hayes, PM Scholle, SH TI Patient satisfaction in women's clinics versus traditional primary care clinics in the Veterans Administration SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT VA Health Services Resarch and Development Annual Meeting CY FEB, 2002 CL WASHINGTON, D.C. DE patient satisfaction; primary health care; quality of health care; veterans; women ID NATIONAL CENTERS; GENERAL-PRACTICE; HEALTH CENTERS; HOSPITAL-CARE; GENDER; EXCELLENCE; OUTCOMES; SETTINGS AB OBJECTIVE: To compare patient satisfaction in women's clinics (WCs) versus traditional primary care clinics (TCs). DESIGN: Anonymous, cross-sectional mailed survey. SETTING: Eight Department of Veterans Affairs (VA) medical centers in 3 states. PATIENTS: A random sample of women stratified by site and enrollment in WC versus TC (total response rate = 61%). MEASURES: Overall satisfaction and gender-specific satisfaction as measured by the Primary Care Satisfaction Survey for Women (PCSSW). ANALYSIS: We dichotomized the satisfaction scores (excellent versus all other), and compared excellent satisfaction in WCs versus TCs using logistic regression, controlling for demographics, health status, health care use, and location. RESULTS: Women enrolled in WCs were more likely than those in TCs to report excellent overall satisfaction (odds ratio, 1.42; 95% confidence interval, 1.00 to 2.02; P = .05). Multivariate models demonstrated that receipt of care in WCs was a significant positive predictor for all 5 satisfaction domains (i.e., getting care, privacy and comfort, communication, complete care, and follow-up care) with the gender-specific satisfaction instrument (PCSSW). CONCLUSIONS: This study is the first to consistently show higher satisfaction in WCs versus TCs despite age and race differences and comparable health status. Since these WCs show better quality in terms of satisfaction, other quality indicators should be evaluated. If WCs reduce fragmentation and improve health care delivery, the model will be applicable in VA and non-VA outpatient settings. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Ctr Res Hlth Care, Div Gen Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. Kansas City VA Hosp, Kansas City, MO USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. RP Bean-Mayberry, BA (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C 130-U, Pittsburgh, PA 15240 USA. NR 26 TC 34 Z9 34 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2003 VL 18 IS 3 BP 175 EP 181 DI 10.1046/j.1525-1497.2003.20512.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 657EL UT WOS:000181652400003 PM 12648248 ER PT J AU Wyrwich, KW Fihn, SD Tierney, WM Kroenke, K Babu, AN Wolinsky, FD AF Wyrwich, KW Fihn, SD Tierney, WM Kroenke, K Babu, AN Wolinsky, FD TI Clinically important changes in health-related quality of life for patients with chronic obstructive pulmonary disease - An expert consensus panel report SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Academy-of-Health-Services-Research-and-Health-Policy CY JUN, 2002 CL WASHINGTON, D.C. SP Acad Hlth Serv Res & Hlth Policy DE quality of life; COPD; important change; consensus panel; RAND method; Delphi process ID OF-LIFE; INTRAINDIVIDUAL CHANGES; IMPORTANT DIFFERENCE; FUNCTIONAL STATUS; LUNG-DISEASE; QUESTIONNAIRE; DYSPNEA; COPD; RELIABILITY; OUTCOMES AB OBJECTIVE: Without clinical input on what constitutes a significant change, health-related quality of life (HRQoL) measures are less likely to be adopted by clinicians for use in daily practice. Although standards can be determined empirically by within-person change studies based on patient self-reports, these anchor-based methods incorporate only the patients' perspectives of important HRQoL change, and do not reflect an informed clinical evaluation. The objective of this study was to establish clinically important difference standards from the physician's perspective for use of 2 HRQoL measures among patients with chronic obstructive pulmonary disease (COPD). DESIGN: We assembled a 9-person expert panel of North American physicians familiar with the use of the Chronic Respiratory Questionnaire (CRQ), a disease-specific HRQoL measure, or the generic Medical Outcomes Study Short-Form 36-Item Health Survey (SF-36, Version 2.0) among patients with COPD. RESULTS: Using 2 rounds of the Delphi process, 1 in-person meeting, and an iterative improvement process for circulating and correcting the final report, the expert panel established small, moderate, and large clinically important change levels for the CRQ and SF-36. CONCLUSIONS: For this expert physician panel, levels for detecting clinically important differences on the CRQ were equal to or slightly higher than previous studies based on patient-reported differences. Clinically important differences on the SF-36, Version 2.0, were noticeably larger than previous estimates based on cross-sectional differences between clinically defined patient groups. C1 St Louis Univ, Dept Res Methodol, Sch Publ Hlth, St Louis, MO 63103 USA. St Louis Univ, Sch Med, St Louis, MO USA. Vet Adm Med Ctr, St Louis, MO 63125 USA. Univ Washington, Med Ctr, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Indiana Univ, Sch Med, Regrenstrief Inst Hlth Care, Indianapolis, IN 46202 USA. Richard L Roudebush Vet Adm Med Ctr, Indianapolis, IN 46202 USA. RP Wyrwich, KW (reprint author), 221 N Grand Ave, St Louis, MO 63103 USA. RI Wolinsky, Fredric/F-9231-2011; OI Wolinsky, Fredric/0000-0002-0916-4955 FU AHRQ HHS [HS10234, K02 HS011635, K02 HS11635, R01 HS010234] NR 42 TC 71 Z9 71 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2003 VL 18 IS 3 BP 196 EP U6 DI 10.1046/j.1525-1497.2003.20203.x PG 13 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 657EL UT WOS:000181652400006 PM 12648251 ER PT J AU Bonner, LT Tsuang, DW Cherrier, MM Eugenio, CJ Du, JQ Steinbart, EJ Limprasert, P La Spada, AR Seltzer, B Bird, TD Leverenz, JB AF Bonner, LT Tsuang, DW Cherrier, MM Eugenio, CJ Du, JQ Steinbart, EJ Limprasert, P La Spada, AR Seltzer, B Bird, TD Leverenz, JB TI Familial dementia with Lewy bodies with an atypical clinical presentation SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE Lewy bodies; familial dementia; Alzheimer's disease ID ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; BODY-DISEASE; FEATURES; MUTATION; CONSORTIUM; CONSENSUS; PATHOLOGY; DLB AB The authors report a case of a 64-year-old male with Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) pathology at autopsy who did not manifest the core symptoms of DLB until very late in his clinical course. His initial presentation of early executive and language dysfunction suggested a cortical dementia similar to frontotemporal lobar degeneration (FTLD). Core symptoms of DLB including dementia, hallucination, and parkinsonian symptoms were not apparent until late in the course of his illness. Autopsy revealed both brainstem and cortical Lewy bodies and AD pathology. Family history revealed 7 relatives with a history of dementia including 4 with possible or probable DLB. This case is unique because of the FTLD-like presentation, positive family history of dementia, and autopsy confirmation of DLB. C1 Univ Washington, Parkinsons Dis Res Educ & Clin Ctr, Seattle, WA 98195 USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Tulane Univ, Sch Med, Dept Psychiat & Neurol, New Orleans, LA 70112 USA. Dept Vet Affairs S Cent MIRECC, New Orleans, LA USA. RP Leverenz, JB (reprint author), VA Puget Sound Hlth Care Syst, MIRECC, 116 MIRECC,1660 S Columbian Way, Seattle, WA 98108 USA. EM leverenz@u.washington.edu RI Tsuang, Debby/L-7234-2016; OI Tsuang, Debby/0000-0002-4716-1894; Limprasert, Pornprot/0000-0001-5022-5361 FU NIA NIH HHS [P50 AG005136, P50 AG05136, R01 AG018644, R01-AG18644]; NINDS NIH HHS [R01 NS048595] NR 34 TC 12 Z9 12 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD MAR PY 2003 VL 16 IS 1 BP 59 EP 64 DI 10.1177/0891988702250585 PG 6 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 847GH UT WOS:000223380200011 PM 12641375 ER PT J AU Niswender, KD Gallis, B Blevins, JE Corson, MA Schwartz, MW Baskin, DG AF Niswender, KD Gallis, B Blevins, JE Corson, MA Schwartz, MW Baskin, DG TI Immunocytochemical detection of phosphatidylinositol 3-kinase activation by insulin and leptin SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE phosphatidylinositol 3-kinase; PIP3; insulin; leptin; endothelium; hepatocyte ID NITRIC-OXIDE SYNTHASE; SIGNAL-TRANSDUCTION; RECEPTOR SUBSTRATE-2; HYPOTHALAMIC NEURONS; ENDOTHELIAL-CELLS; GLUCOSE-TRANSPORT; KINASE; MUSCLE; PHOSPHORYLATION; ASSOCIATION AB Intracellular signaling mediated by phosphatidylinositol 3-kinase (PI3K) is important for a number of cellular processes and is stimulated by a variety of hormones, including insulin and leptin. A histochemical method for assessment of PI3K signaling would be an important advance in identifying specific cells in histologically complex organs that are regulated by growth factors and peptide hormones. However, current methods for detecting PI3K activity require either homogenization of the tissue or cells or the ability to transfect probes that bind to phosphatidylinositol 3,4,5 trisphosphate (PIP3), the reaction product of PI3K catalysis. Here we report the validation of an immunocytochemical method to detect changes in PI3K activity, using a recently developed monoclonal antibody to PIP3, in paraformaldehyde-fixed bovine aortic endothelial cells (BAECs) in culture and in hepatocytes of intact rat liver. Treatment with either insulin or leptin increased BAEC PIP3 immunoreactivity, and these effects were blocked by pretreatment with PI3K inhibitors. Furthermore, infusion of insulin into the hepatic portal vein of fasted rats caused an increase of PIP3 immunostaining in hepatocytes that was associated with increased serine phosphorylation of the downstream signaling molecule protein kinase B/Akt (PKB/Akt). We conclude that immunocytochemical PIP3 staining can detect changes in PI3K activation induced by insulin and leptin in cell culture and intact liver. C1 Univ Washington, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. Univ Washington, Div Cardiol, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Div Endocrinol & Metab, Seattle, WA USA. RP Niswender, KD (reprint author), Harborview Med Ctr, Box 359757,300 9th Ave, Seattle, WA 98104 USA. RI Schwartz, Michael/H-9950-2012 FU NIDDK NIH HHS [DK12829, DK52989, T32 DK07247, DK17047]; NINDS NIH HHS [NS32273] NR 35 TC 81 Z9 84 U1 0 U2 4 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD MAR PY 2003 VL 51 IS 3 BP 275 EP 283 PG 9 WC Cell Biology SC Cell Biology GA 648YX UT WOS:000181180400002 PM 12588955 ER PT J AU Chestukhin, A DeCaprio, JA AF Chestukhin, A DeCaprio, JA TI Western blot screening for monoclonal antibodies against human separase SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE maltose-binding protein; glutathione S-transferase; slot blot; mitosis; miniblotter ID SISTER-CHROMATID SEPARATION; ANAPHASE; MECHANISM; METAPHASE; SECURIN; YEAST AB Separase is a cysteine protease that participates in separation of sister chromatids during mitosis. Human separase is a 230-kDa enzyme that is inhibited by binding to its protein inhibitor securin, specific phosphorylation, and subcellular localization. To further characterize human separase, we raised monoclonal antibodies specific against a C-terminal fragment of the protein. A critical step in monoclonal antibody production procedure is the primary screening of hybridoma supernatants. Here we report primary screening protocol utilizing Western blot analysis. The described screening protocol is carried out using fusion of a human separase fragment with two different purification tags, maltose-binding protein (MBP) and glutathione S-transferase (GST). Immunization by MBP-fusion was followed by primary screening with both MBP- and GST-separase fusions combined in the same preparation separated in SDS-PAGE. This highly sensitive screening approach reduced the number of positive signals by eliminating antibodies specific for the purification tag used in the immunization procedure. The described separase-specific antibodies were suitable for detection of endogenous separase in crude extracts, immunoprecipitation, and immuno fluorescent cell staining experiments. The presented procedure is fast, reproducible and could be adopted as a primary screening scheme for a variety of protein antigens. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP DeCaprio, JA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Mayer 457,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [P01-CA50661, 1F32 CA84752] NR 15 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD MAR 1 PY 2003 VL 274 IS 1-2 BP 105 EP 113 DI 10.1016/S0022-1759(02)00508-2 PG 9 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 654KN UT WOS:000181496200010 PM 12609537 ER PT J AU Jones, N Agrawal, D Elrefaei, M Hanson, A Novitsky, V Wong, JT Cao, HY AF Jones, N Agrawal, D Elrefaei, M Hanson, A Novitsky, V Wong, JT Cao, HY TI Evaluation of antigen-specific responses using in vitro enriched T cells SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE T cell; CMI; bispecific monoclonal antibody ID EX-VIVO EXPANSION; MONOCLONAL-ANTIBODIES; LYMPHOCYTES; IDENTIFICATION; EPITOPES; BINDING; ASSAY AB Antigen-specific lymphocytes are important in the immune response to viral infection. Peripheral blood mononuclear cells (PBMC) are traditionally used as a source of effector cells in most immunological studies. We described here the use of the bispecific monoclonal antibodies (BSMAB) anti CD3:CD8 (CD3,8) and anti CD3:CD4 (CD3,413) to expand and selectively enrich CD4+ and CD8+ T cell populations, respectively. The expanded cells demonstrated >90% CD3+ CD4+ or CD3+ CD8+ by 14 days. We measured HIV- and CMV-specific responses of these subset-enriched T cell and found that sensitivity and specificity is similar or higher when compared to PBMC in various cellular immunology assays (CMI). Vbeta analysis of BSMAB-enriched cells demonstrated comparable repertoir to the parent PBMC. Although both CD45RA(hi) and CD45RO(hi) cell populations were expanded with the BSMAB, selective subset depletion demonstrated that the antigen-specific T cell responses were restricted to the initial CD45RO(hi) memory effector subgroup. In conclusion, BSMAB in vitro enrichment of T cells allows significant expansion of the cell population without loss of specificity. This technique of cell expansion permits studies of T cell subset function in situations where the initial cell source is scarce, and presents an alternative for viable and functional T cells in immunological assays. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Calif Dept Hlth Serv, VRDL, Richmond, CA 94804 USA. Partners AIDS Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Cao, HY (reprint author), Calif Dept Hlth Serv, VRDL, 850 Marina Bay Pkwy, Richmond, CA 94804 USA. NR 15 TC 26 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD MAR 1 PY 2003 VL 274 IS 1-2 BP 139 EP 147 AR PII S0022-1759(02)00510-0 DI 10.1016/S0022-1759(02)00510-0 PG 9 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 654KN UT WOS:000181496200013 PM 12609540 ER PT J AU Tonomura, N McLaughlin, K Grimm, L Goldsby, RA Osborne, BA AF Tonomura, N McLaughlin, K Grimm, L Goldsby, RA Osborne, BA TI Glucocorticoid-induced apoptosis of thymocytes: Requirement of proteasome-dependent mitochondrial activity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DEXAMETHASONE-INDUCED APOPTOSIS; CYTOCHROME-C; BCL-2 FAMILY; OXIDATIVE STRESS; CELL-DEATH; PROTEINS; MEMBRANE; COMPLEX; RELEASE; OXYGEN AB Thymocytes undergo negative and positive selection during development in the thymus. During this selection process, the majority of thymocytes are eliminated by apoptosis through signaling via TCR or die by neglect, possibly mediated through glucocorticoids. In this study, we report that thymocytes require molecular oxygen to undergo apoptosis induced by dexamethasone (DEX), a synthetic glucocorticoid, and treatment with N-acetyl-L-cysteine (NAC), a thiol antioxidant, inhibits thymocyte apoptosis in vivo as well as ex vivo. We detected elevated intracellular levels of hydrogen peroxide (H2O2) during DEX-induced apoptosis, which is reduced by NAC treatment, indicating that the elevated levels of intracellular H2O2 are proapoptotic. We also show that loss of mitochondrial membrane potential, cytochrome c release, as well as caspase-3 activation induced by DEX are attenuated by NAC treatment. We identified the production site for H2O2 as the ubiquinone cycle at complex III of mitochondria by using various inhibitors of the mitochondrial electron transport chain, and we show that the cell death events mediated by mitochondria are also significantly reduced when the inhibitors were used. Through inhibition of the proteasome, we also show that the production of H2O2 and the cell death events mediated by mitochondria are regulated by proteosomal activities in DEX-induced thymocyte apoptosis. We conclude that in DEX-treated thymocytes, the increased production of H2O2 originates from mitochondria and is proapoptotic for cell death mediated by mitochondria. We also conclude that all the apoptotic events mediated by mitochondria are regulated by proteasomes. C1 Univ Massachusetts, Dept Vet & Anim Sci, Amherst, MA 01003 USA. Univ Massachusetts, Program Mol & Cellular Biol, Amherst, MA 01003 USA. Tufts Univ, Dept Biol, Medford, MA 02155 USA. Amherst Coll, Dept Biol, Amherst, MA 01002 USA. Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. RP Osborne, BA (reprint author), Univ Massachusetts, Dept Vet & Anim Sci, Amherst, MA 01003 USA. FU NIA NIH HHS [R01 AG47922] NR 36 TC 65 Z9 69 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2003 VL 170 IS 5 BP 2469 EP 2478 PG 10 WC Immunology SC Immunology GA 648JD UT WOS:000181146800029 PM 12594272 ER PT J AU George, RT Sykes, M Spitzer, TR AF George, RT Sykes, M Spitzer, TR TI Risk factors for acute graft versus host disease following allogeneic non-myeloablative bone marrow transplantation. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Clinical Research 2003 Meeting CY MAR 13-16, 2003 CL BALTIMORE, MARYLAND C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Bone Marrow Transplantat Program, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Surg, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2003 VL 51 SU 2 BP S374 EP S375 PG 2 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 652QW UT WOS:000181390700109 ER PT J AU Grenon, SM Sheynberg, N Hurwitz, S Xiao, X Ehrman, M Cohen, RJ Williams, GH AF Grenon, SM Sheynberg, N Hurwitz, S Xiao, X Ehrman, M Cohen, RJ Williams, GH TI The effect of a constant high salt diet on the renal, cardio-endocrine and cardiovascular responses to simulated microgravity. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Clinical Research 2003 Meeting CY MAR 13-16, 2003 CL BALTIMORE, MARYLAND C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Med, Div Endocrinol, Boston, MA USA. McGill Univ, Div Cardiothorac Surg, Montreal, PQ, Canada. MIT, NASA, Ctr Quantat Cardiovasc Physiol Modeling & Data An, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2003 VL 51 SU 2 BP S377 EP S377 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 652QW UT WOS:000181390700125 ER PT J AU Perlstein, TS Litonjua, AA Raby, BA Gaziano, JM Weiss, ST Williams, GH AF Perlstein, TS Litonjua, AA Raby, BA Gaziano, JM Weiss, ST Williams, GH TI Polymorphisms of angiotensinogen and endothelial nitric oxide synthase genes and the risk of hypertension: The normative aging study. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Clinical Research 2003 Meeting CY MAR 13-16, 2003 CL BALTIMORE, MARYLAND C1 Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA USA. Harvard Univ, Sch Med, Channing Lab, Boston VA Healthcare Syst, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2003 VL 51 SU 2 BP S373 EP S373 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 652QW UT WOS:000181390700102 ER PT J AU Stevanovic, RD Price, DA Lansang, CM Laffel, L Fisher, ND Hollenberg, NK AF Stevanovic, RD Price, DA Lansang, CM Laffel, L Fisher, ND Hollenberg, NK TI Renin release in response to renin system blockade: Further evidence for activation of the intrarenal renin system in type-1 diabetes mellitus. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Clinical Research 2003 Meeting CY MAR 13-16, 2003 CL BALTIMORE, MARYLAND C1 Brigham & Womens Hosp, Dept Endocrinol & Hypertens, Boston, MA 02115 USA. Joslin Clin, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2003 VL 51 SU 2 BP S377 EP S377 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 652QW UT WOS:000181390700124 ER PT J AU Wolf, MS Shah, A Sandler, L Sauk, J Jimenez-Kimble, R Thadhani, R AF Wolf, MS Shah, A Sandler, L Sauk, J Jimenez-Kimble, R Thadhani, R TI Differential risk of hypertensive disorders of pregnancy among Hispanic women SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Clinical Research 2003 Meeting CY MAR 13-16, 2003 CL BALTIMORE, MARYLAND C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Renal Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2003 VL 51 SU 2 BP S372 EP S372 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 652QW UT WOS:000181390700095 ER PT J AU Zacks, ES Patton, K Chang, JY Melo, K MacRae, C Ruskin, J Ellinor, P AF Zacks, ES Patton, K Chang, JY Melo, K MacRae, C Ruskin, J Ellinor, P TI Morbidity of lone atrial fibrillation SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Clinical Research 2003 Meeting CY MAR 13-16, 2003 CL BALTIMORE, MARYLAND C1 Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. RI Patton, Kristen/A-5626-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2003 VL 51 SU 2 BP S358 EP S358 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 652QW UT WOS:000181390700015 ER PT J AU Virella, G Thorpe, SR Alderson, NL Stephan, EM Atchley, D Wagner, F Lopes-Virella, MF AF Virella, G Thorpe, SR Alderson, NL Stephan, EM Atchley, D Wagner, F Lopes-Virella, MF CA DCCT EDIC Res Grp TI Autoimmune response to advanced glycosylation end-products of human LDL SO JOURNAL OF LIPID RESEARCH LA English DT Article DE modified lipoproteins; diabetes; immunogenicity of advanced glycosylation end-products-LDL; advanced glycosylation end-products-LDL antibodies ID LOW-DENSITY-LIPOPROTEIN; CONTAINING IMMUNE-COMPLEXES; ADVANCED GLYCATION ENDPRODUCTS; MONOCYTE-DERIVED MACROPHAGES; CORONARY-ARTERY DISEASE; ATHEROSCLEROTIC LESIONS; DIABETES-MELLITUS; OXIDIZED LDL; OXIDATIVE STRESS; HEALTHY CONTROLS AB Advanced glycosylation end-products (AGES) are believed to play a significant role in the development of vascular complications in diabetic patients. One such product, AGE-L LDL,has been shown to be immunogenic. In this report, we describe the isolation and characterization of human AGE-LDL antibodies from the sera of seven patients with Type 1 diabetes by affinity chomatography using an immobilized AGE-LDL preparation that contained primarily the AGE NE(carboxymethyl)lysine (CML, 14.6 mmol/mol lysine), and smaller amounts of N-epsilon (carboxyethyl)lysine (CEL, 2.7 mmol/mol lysine). The isolated antibodies were predominantly IgG of subclasses 1 and 3, and considered proinflammatory because of their ability to promote FcgammaR-mediated phagocytosis and to activate complement. We determined dissociation constants (K-d) for the purified antibodies. The average K-d values (4.76 +/- 2.52 x 10(-9) mol/l) indicated that AGE-LDL antibodies are of higher avidity than oxidized LDL antibodies measured previously (K-d = 1.53 07 x 10(-8) ml/l), but of lower avidity than rabbit polyclonal LDL antibodies (K-d = 9.34 x 10(-11)). Analysis of the apolipoprotein B-rich lipoproteins isolated with polyethylene glycol-precipitated antigen-antibody complexes from the same patients showed the presence of both CML and CEL, thus confirming that these two modifications are recognized by human autoantibodies.jlr A comparative study of the reactivity of purified AGE-LDL antibodies with CML-LDL and CML-serum albumin showed no cross-reactivity. C1 Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. Univ S Carolina, Dept Chem & Biochem, Columbia, SC 29208 USA. Med Univ S Carolina, Div Endocrinol Metab Nutr, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson VAMC, Charleston, SC 29425 USA. RP Virella, G (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. FU NHLBI NIH HHS [P01-HL55782]; NIDDK NIH HHS [DK19971] NR 50 TC 50 Z9 53 U1 0 U2 2 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAR PY 2003 VL 44 IS 3 BP 487 EP 493 DI 10.1194/jlr.M200370-JLR200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 653XF UT WOS:000181461800007 PM 12562876 ER PT J AU Vergnes, L Phan, J Stolz, A Reue, K AF Vergnes, L Phan, J Stolz, A Reue, K TI A cluster of eight hydroxysteroid dehydrogenase genes belonging to the aldo-keto reductase supergene family on mouse chromosome 13 SO JOURNAL OF LIPID RESEARCH LA English DT Article DE gene identification; gene expression; alternative splicing ID HEPATIC 3-ALPHA-HYDROXYSTEROID DEHYDROGENASE; BILE-ACID BINDERS; IN-SITU HYBRIDIZATION; RADIATION HYBRID MAP; RAT-LIVER CYTOSOL; DIHYDRODIOL DEHYDROGENASE; 20-ALPHA-HYDROXYSTEROID DEHYDROGENASE; TYPE-5 17-BETA-HYDROXYSTEROID-DEHYDROGENASE; GENOMIC ORGANIZATION; TISSUE DISTRIBUTION AB A subclass of hydroxysteroid dehydrogenases (HSD) are NADP(H)-dependent oxidoreductases that belong to the aldo-keto reductase (AKR) superfamily. They are involved in prereceptor or intracrine steroid modulation, and also act as bile acid-binding proteins. The HSD family members characterized thus far in human and rat have a high degree of protein sequence similarity but exhibit distinct substrate specificity. Here we report the identification of nine murine AKR genes in a cluster on chromosome 13 by a combination of molecular cloning and in silico analysis of this region. These include four previously isolated mouse HSD genes (Akr1c18, Akr1c6, Akr1c12, Akr1c13), the more distantly related Akr1e1, and four novel HSD genes. These genes exhibit highly conserved exon/intron organization and protein sequence predictions indicate 75% amino acid similarity. The previously identified AKR protein active site residues are invariant among all nine proteins, but differences are observed in regions that have been implicated in determining substrate specificity. Differences also occur in tissue expression patterns, with expression of some genes restricted to specific tissues and others expressed at high levels in multiple tissues.jlr Our findings dramatically expand the repertoire of AKR genes and identify unrecognized family members with potential roles in the regulation of steroid metabolism. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet & Med, Los Angeles, CA 90095 USA. Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90033 USA. RP Reue, K (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet & Med, Los Angeles, CA 90095 USA. FU NHLBI NIH HHS [HL-58267, HL-28481]; NIDDK NIH HHS [5P30DK048522, DK-41014]; NIGMS NIH HHS [GM08042] NR 46 TC 40 Z9 43 U1 1 U2 3 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAR PY 2003 VL 44 IS 3 BP 503 EP 511 DI 10.1194/jlr.M200399-JLR200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 653XF UT WOS:000181461800009 PM 12562828 ER PT J AU Best, CA Cluette-Brown, JE Teruya, M Teruya, A Laposata, M AF Best, CA Cluette-Brown, JE Teruya, M Teruya, A Laposata, M TI Red blood cell fatty acid ethyl esters: a significant component of fatty acid ethyl esters in the blood SO JOURNAL OF LIPID RESEARCH LA English DT Article DE ethanol; red blood cell membranes; alcohol monitoring; alcoholism; alcohol; addiction ID ERYTHROCYTE-MEMBRANE; ETHANOL INTAKE; ALCOHOLICS; CONSUMPTION; TOLERANCE; PLATELETS; MARKERS; PROTEIN; DAMAGE; PLASMA AB Although alcohol abuse is known to cause an array of ethanol-induced red blood cell (RBC) abnormalities, the underlying molecular mechanisms remain poorly understood. Fatty acid ethyl esters (FAEEs) are toxic, nonoxidative ethanol metabolites that have been found in blood, plasma, and tissues. Because FAEEs have been shown to be incorporated into phospholipid bilayers, we conducted a controlled ethanol intake study to test the hypothesis that FAEEs accumulate and persist within RBCs following ethanol ingestion. We demonstrated that RBC FAEEs account for approximately 5% to 20% of total whole-blood FAEEs, and that the fatty acid composition of FAEEs in RBCs and plasma are different and vary differently over time. These data indicate that a significant percentage of FAEEs in the blood is associated with RBCs and that the metabolism of RBC FAEEs and that of plasma FAEEs (bound to albumin or lipoproteins) are largely independent. C1 Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. NR 41 TC 23 Z9 23 U1 0 U2 1 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAR PY 2003 VL 44 IS 3 BP 612 EP 620 DI 10.1194/jlr.M200398-JLR200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 653XF UT WOS:000181461800023 PM 12562827 ER PT J AU Bohning, DE Shastri, A Lomarev, MP Lorberbaum, JP Nahas, Z George, MS AF Bohning, DE Shastri, A Lomarev, MP Lorberbaum, JP Nahas, Z George, MS TI BOLD-fMRI response vs. transcranial magnetic stimulation (TMS) pulse-train length: Testing for linearity SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article; Proceedings Paper CT 8th Annual Meeting of the International-Society-for-Magnetic-Resonance-in-Medicine CY APR 01-07, 2000 CL DENVER, COLORADO SP Int Soc Magnet Resonance Med DE transcranial magnetic stimulation (TMS); fMRI; train-length; BOLD response linearity; motor cortex ID CEREBRAL BLOOD-FLOW; FUNCTIONAL MRI; MOTOR CORTEX; CORTICAL ACTIVATION; SENSORY STIMULATION; BRAIN ACTIVATION; AUDITORY-CORTEX; SIGNAL; CONNECTIVITY; MOVEMENT AB Purpose: To measure motor and auditory cortex blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) response to impulse-like transcranial magnetic stimulation (TMS) pulses as a function of train length. Materials and Methods: Interleaved with fMRI at 1.5 T, TMS pulses 0.3-msec long were applied at 1 Hz to the motor cortex area for thumb. Six subjects were studied in a TR = 1 second session administering trains of 1, 2, 4, 8, and 16 pulses, and a TR = 3 seconds session administering trains of 1, 2, 4, 8, 16, and 24 pulses. A simple hemodynamic model with finite recovery and saturation was used to quantitatively characterize the BOLD-fMRI response as a function of train length. Results: In both the activations directly induced in motor cortex by TMS and the indirect activation sin auditory cortex caused by the sound of the TMS coil firing, the BOLD-fMRI responses to multiple pulses were well described by a summation of single-pulse impulse functions. Conclusion: Up to 24 discrete pulses, BOLD-fMRI response to 1 Hz TMS in both motor cortex and auditory cortex were consistent with a linear increase in amplitude and length with train length, possibly suggesting that stimuli of 1 to 2 seconds may be too long to represent impulses. C1 Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Inst Human Brain, St Petersburg, Russia. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Ralph H Johnson Vet Hosp, Charleston, SC USA. RP Bohning, DE (reprint author), Med Univ S Carolina, Dept Radiol, 169 Ashley Ave, Charleston, SC 29425 USA. FU PHS HHS [R21] NR 40 TC 19 Z9 19 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 MAR PY 2003 VL 17 IS 3 BP 279 EP 290 DI 10.1002/jmri.10271 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 670JF UT WOS:000182403600001 PM 12594717 ER PT J AU Stewart, JA Wei, CC Brower, GL Rynders, PE Hankes, GH Dillon, AR Lucchesi, PA Janicki, JS Dell'Italia, LJ AF Stewart, JA Wei, CC Brower, GL Rynders, PE Hankes, GH Dillon, AR Lucchesi, PA Janicki, JS Dell'Italia, LJ TI Cardiac mast cell- and chymase-mediated matrix metalloproteinase activity and left ventricular remodeling in mitral regurgitation in the dog SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE matrix metalloproteinase; angiotensin-converting enzyme; myocardial remodeling; volume overload; heart failure ID CONGESTIVE-HEART-FAILURE; ANGIOTENSIN-II; DILATED CARDIOMYOPATHY; MYOCARDIAL-INFARCTION; COLLAGEN LATTICES; IN-VIVO; ACTIVATION; INHIBITION; FIBROSIS; RAT AB The present study tested the hypothesis that cardiac mast cells and chymase are associated with matrix metalloproteinase (MMP) activation and extracellular matrix (ECM) degradation in the evolution of left ventricular (LV) chamber remodeling secondary to experimental mitral regurgitation (MR) in dogs. LV mast cell density, chymase activity, and angiotensin II (ANG II) levels were significantly increased 2 and 4 weeks post-MR, while an increase in angiotensin-converting enzyme (ACE) activity was not seen prior to the chronic 24 week stage. As early as 2 and 4 weeks, there was a significant decrease in interstitial myocardial collagen content that was associated with an increase in LV end-diastolic diameter (LVEDD) but a normal LVEDD/wall thickness ratio. While mast cell density decreased to normal at 24 weeks, both chymase and MMP-2 activity remained increased throughout the entire 24-week period post-MR. By 24 weeks a transition to an adverse pattern of LV remodeling characterized by a 2-fold increase in the LVEDD/wall thickness ratio had occurred. Thus, this study supports the hypothesis that mast cells and chymase are important modulators of MMP activity and ECM degradation, contributing to adverse LV remodeling in chronic volume overload secondary to MR. (C) 2003 Elsevier Science Ltd. All fights reserved. C1 Auburn Univ, Dept Anat Physiol & Pharmacol, Auburn, AL 36849 USA. Univ Alabama, Birmingham Vet Affairs Med Ctr, Dept Med,Div Cardiovasc Dis, Vasc Biol & Hypertens Program, Birmingham, AL 35294 USA. Dept Clin Sci, Auburn, AL 36849 USA. Univ Stn, Dept Physiol & Biophys, Birmingham, AL 35924 USA. RP Janicki, JS (reprint author), Auburn Univ, Dept Anat Physiol & Pharmacol, 106 Greene Hall, Auburn, AL 36849 USA. EM janjanicjs@auburwn.edu RI Lucchesi, Pamela/E-3558-2011 FU NHLBI NIH HHS [R01-HL54816, R01-HL59981, R01-HL62228] NR 52 TC 88 Z9 91 U1 1 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD MAR PY 2003 VL 35 IS 3 BP 311 EP 319 DI 10.1016/S0022-2828(03)00013-0 PG 9 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 667CE UT WOS:000182212600010 PM 12676546 ER PT J AU Roy-Byrne, P Berliner, L Russo, J Zatzick, D Pitman, RK AF Roy-Byrne, P Berliner, L Russo, J Zatzick, D Pitman, RK TI Treatment preferences and determinants in victims of sexual and physical assault SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID NATIONAL COMORBIDITY SURVEY; PRIMARY-CARE PATIENTS; MAJOR DEPRESSION; STRESS-DISORDER; MEDICATION AB To determine the treatment preferences (i.e., medication, counseling, or both) for victims of recent trauma at risk for posttraumatic stress disorder and the determinants of those choices, preferences were elicited from 466 consecutive victims of physical or sexual assault at an urban emergency department as part of the routine clinical evaluation by emergency department social workers. Demographics, assault characteristics, and clinical history were used to predict preference. More than 80% of victims expressed an interest in treatment, with more interested in counseling (76%) than medication (62%). Female gender and assaults of a sexual nature were most highly predictive of preference for medication, whereas female gender, sexual assault, a history of psychiatric treatment, and perceived life threat from the trauma were most predictive of preference for counseling and preference for any treatment. Because treatment preferences were easily obtained from assault victims seeking emergency care, the elicitation of these treatment preferences and the consideration of them in the treatment planning process could facilitate engagement in treatment and overcome the avoidance of treatment by some victims. C1 Univ Washington, Harborview Med Ctr, Dept Psychiat & Behav Sci, Seattle, WA 98104 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Roy-Byrne, P (reprint author), Univ Washington, Harborview Med Ctr, Dept Psychiat & Behav Sci, 325 9Th Ave,Box 355911, Seattle, WA 98104 USA. NR 22 TC 28 Z9 28 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD MAR PY 2003 VL 191 IS 3 BP 161 EP 165 DI 10.1097/00005053-200303000-00004 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 655LD UT WOS:000181553000004 PM 12637842 ER PT J AU Romeo, HE Tio, DL Taylor, AN AF Romeo, HE Tio, DL Taylor, AN TI Effects of glossopharyngeal nerve transection on central and peripheral cytokines and serum corticosterone induced by localized inflammation SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE glossopharyngeal nerve transection; lipopolysaccharide; interleukin-1 beta; interleukin-1ra; corticosterone; soft palate; rat ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; TO-BRAIN COMMUNICATION; FETAL ALCOHOL EXPOSURE; INTRAPERITONEAL LIPOPOLYSACCHARIDE; CIRCULATING PYROGENS; FEBRILE RESPONSE; INDUCED FEVER; VAGUS NERVE; IMMUNE; VAGOTOMY AB Bilateral transection of the glossopharyngeal nerves (GLOx) disrupts the immune-to-brain communication from the posterior oral cavity. The current report tested whether this effect is due to the afferent (sensory) or efferent (parasympathetic motor) components of the nerve. Injection of lipopolysaccharide (LPS) into the soft palate (ISP) of GLOx or sham-operated (SHAM) rats increased the circulating levels of interleukin-1beta (IL-1beta), interleukin-1 receptor antagonist (IL-1ra) and corticosterone (CORT), as well the hypothalamic content of IL-1beta; no difference in circulating levels and hypothalamic content was found between GLOx and SHAM at 2 and 4.5 h after LPS injection. These results indicate that glossopharyngeal neural efferents do not mediate the effects of GLOx on the immune-to-brain communication. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Univ Calif Los Angeles, Dept Neurobiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Brain Res Inst, David Geffen Sch Med, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, West Los Angeles Healthcare Ctr, Los Angeles, CA 90073 USA. RP Romeo, HE (reprint author), Univ Calif Los Angeles, Dept Neurobiol, 10833 Le Conte Ave, Los Angeles, CA 90095 USA. FU NIAAA NIH HHS [AA09850] NR 42 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD MAR PY 2003 VL 136 IS 1-2 BP 104 EP 111 DI 10.1016/S0165-5728(0300033-X PG 8 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 660PC UT WOS:000181840700012 PM 12620648 ER PT J AU O'Connor, KC Chitnis, T Griffin, DE Piyasirisilp, S Bar-Or, A Khoury, S Wucherpfennig, KW Hafler, DA AF O'Connor, KC Chitnis, T Griffin, DE Piyasirisilp, S Bar-Or, A Khoury, S Wucherpfennig, KW Hafler, DA TI Myelin basic protein-reactive autoantibodies in the serum and cerebrospinal fluid of multiple sclerosis patients are characterized by low-affinity interactions SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE antibodies; autoimmunity; diabetes; EAE/MS; human; myelin basic protein ID OLIGODENDROCYTE GLYCOPROTEIN; B-CELL; RADIOLIGAND ASSAY; CELIAC-DISEASE; ANTIBODIES; IDENTIFICATION; EPITOPES; PEPTIDE; CSF; MS AB The presence of autoantibodies to the immunodominant antigen, myelin basic protein (MBP), in the serum and cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) has been poorly characterized. Many studies report detectable levels of autoantibodies to myelin basic protein though other studies, using similar techniques, report their absence. We compared a solution-phase assay that has detected clinically relevant autoantibodies in diabetes and other autoimmune diseases to solid phase assays similar to those used in previous reports. The solution-phase assay consistently measured autoantibodies to MBP in serum from human subjects with Semple rabies vaccine (SRV)-induced demyelinating disease and from MBP-immunized animals. A solid phase assay detected MBP autoantibodies in the serum of a fraction of patients with MS. Autoantibodies capable of binding to MBP in the solution-phase were not detected in the CSF or serum of patients with MS. Additional solution-phase measurements revealed that anti-MBP antibodies from individuals with SRV-induced demyelinating disease demonstrated a binding affinity profile consistent with that of polyclonal antibodies with a range of affinities from low to high. In contrast, antibodies to MBP in the serum of MS patients detected by ELISA did not bind soluble MBP in the same assay. These results indicate that the Immoral response in patients with MS does not include moderate- or high-affinity autoantibodies to MBP. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Harvard Inst Med, Ctr Neurol Dis,Lab Mol Immunol, Boston, MA 02115 USA. Johns Hopkins Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. McGill Univ, Montreal Neurol Inst, Dept Neurol & Neurosurg, Montreal, PQ H3A 2B4, Canada. McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3A 2B4, Canada. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Hafler, DA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Harvard Inst Med, Ctr Neurol Dis,Lab Mol Immunol, Rm 780,77 Ave Louis Pasteur, Boston, MA 02115 USA. RI Bar-Or, Amit/C-4213-2011; OI khoury, samia/0000-0003-3198-6063 FU NIAID NIH HHS [N01AI95380, P01 AI39671, P01 AI45757, R01 AI44447, U01 AI46130]; NIDDK NIH HHS [R01 DK52127]; NINDS NIH HHS [P01 NS38037, R01 NS24247] NR 45 TC 64 Z9 65 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 MAR PY 2003 VL 136 IS 1-2 BP 140 EP 148 DI 10.1016/S0165-5728(03)00002-X PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 660PC UT WOS:000181840700017 PM 12620653 ER PT J AU Taber, KH Rauch, SL Lanius, RA Hurley, RA AF Taber, KH Rauch, SL Lanius, RA Hurley, RA TI Functional magnetic resonance imaging: Application to posttraumatic stress disorder SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID HUMAN BRAIN; SIGNAL; FMRI; MRI C1 Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. Baylor Coll Med, Dept Behav Sci, Houston, TX 77030 USA. Baylor Coll Med, Herbert J Frensley Ctr Imaging Res, Houston, TX 77030 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. Univ Western Ontario, Dept Psychiat, London Hlth Sci Ctr, London, ON N6A 3K7, Canada. Houston Vet Affairs Med Ctr, Psychiat Serv, Houston, TX USA. RP Taber, KH (reprint author), Baylor Coll Med, Dept Radiol, 1 Baylor Plaza, Houston, TX 77030 USA. NR 20 TC 8 Z9 8 U1 1 U2 2 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SPR PY 2003 VL 15 IS 2 BP 125 EP 129 DI 10.1176/appi.neuropsych.15.2.125 PG 5 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 672VQ UT WOS:000182544000001 PM 12724452 ER PT J AU Clark, DG Mendez, ME Farag, E Vinters, HV AF Clark, DG Mendez, ME Farag, E Vinters, HV TI Clinicopathologic case report: Progressive aphasia in a 77-year-old man SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID ALZHEIMERS-DISEASE; PICKS DISEASE; LANGUAGE; DEMENTIA; PATHOLOGY; FEATURES; ATROPHY C1 Univ Calif Los Angeles, Dept Neurol, Med Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Med Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Pathol & Lab Med Neuropathol, Med Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Brain Res Inst & Neuropsychiat Inst, Med Ctr, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Mendez, ME (reprint author), VA Greater Los Angeles Healthcare Syst, Neurobehav Unit 116AF, Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIA NIH HHS [P50-AG-16570]; PHS HHS [T32-N507356] NR 26 TC 7 Z9 7 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SPR PY 2003 VL 15 IS 2 BP 231 EP 238 DI 10.1176/appi.neuropsych.15.2.231 PG 8 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 672VQ UT WOS:000182544000016 PM 12724467 ER PT J AU Long, Y Zou, LL Liu, H Lu, H Yuan, XQ Robertson, CS Yang, KY AF Long, Y Zou, LL Liu, H Lu, H Yuan, XQ Robertson, CS Yang, KY TI Altered expression of randomly selected genes in mouse hippocampus after traumatic brain injury SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE microarray; hippocampus; gene expression; brain; trauma ID CORTICAL IMPACT INJURY; SERINE-PROTEASE INHIBITORS; PLATELET-ACTIVATING-FACTOR; CENTRAL-NERVOUS-SYSTEM; MESSENGER-RNA; CELL-DEATH; RAT-BRAIN; MICROARRAY ANALYSIS; KINASE-C; UTEROGLOBIN AB Using a cDNA microarray method, we analyzed gene expression profiles in mouse hippocampus after traumatic brain injury (TBI). Of 6,400 randomly selected arrayed genes and expressed sequence tags from a mouse cDNA library, 253 were found to be differentially expressed (106 increased and 147 decreased). Genes involved in cell homeostasis and calcium signaling were primarily up-regulated while those encoding mitochondrial enzymes, metabolic molecules, and structural proteins were predominantly down-regulated. Equal numbers of genes related to inflammatory reactions showed increased or decreased expression. Importantly, a large proportion of the dysregulated genes we identified have not been reported as differentially expressed in TBI models. Semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR) analyses of representative genes confirmed the validity of the corresponding microarray findings. Thus, our microarray-based evaluation of gene expression in traumatically injured hippocampus identified both known and novel genes that respond to TBI. Further investigation of these candidate molecules may suggest new ways to attenuate the traumatic effects of brain injury. (C) 2002 Wiley-Liss, Inc. C1 Baylor Coll Med, Dept Neurosurg, Houston, TX 77030 USA. Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. PADRECC, Neurol Care Line, VA Med Ctr, Houston, TX USA. RP Yang, KY (reprint author), Baylor Coll Med, Dept Neurosurg, 1 Baylor Plaza, Houston, TX 77030 USA. FU NINDS NIH HHS [P01-NS38660, R01-NS35502-04] NR 48 TC 51 Z9 56 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAR 1 PY 2003 VL 71 IS 5 BP 710 EP 720 DI 10.1002/jnr.10524 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 650CK UT WOS:000181244700010 PM 12584729 ER PT J AU Wiseman, GA Kornmehl, E Leigh, B Erwin, WD Podoloff, DA Spies, S Sparks, RB Stabin, MG Witzig, T White, CA AF Wiseman, GA Kornmehl, E Leigh, B Erwin, WD Podoloff, DA Spies, S Sparks, RB Stabin, MG Witzig, T White, CA TI Radiation dosimetry results and safety correlations from Y-90-ibritumomab tiuxetan radioimmunotherapy for relapsed or refractory non-Hodgkin's lymphoma: Combined data from 4 clinical trials SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE dosimetry; radioimmunotherapy; Y-90-ibritumomab tiuxetan; rituximab ID BONE-MARROW DOSIMETRY; IDEC-Y2B8 RADIOIMMUNOTHERAPY; IBRITUMOMAB TIUXETAN; ANTIBODIES AB Ibritumomab tiuxetan is an ant-CD20 murine IgG1 K monoclonal antibody (ibritumomab) conjugated to the linker-chelator tiuxetan, which securely chelates In-111 for imaging or dosimetry and Y-90 for radioimmunotherapy (RIT). Dosimetry and pharmacokinetic data from 4 clinical trials of Y-90-ibritumomab tiuxetan RIT for relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL) were combined and assessed for correlations with toxicity data. Methods: Data from 17 patients were available for analysis. Common eligibility criteria included <25% bone marrow involvement by NHL, no prior myeloablative therapy, and no prior RIT. The baseline platelet count was required to be greater than or equal to100,000 cells/mm(3) for the reduced Y-90-ibritumomab tiuxetan administered dose (7.4-11 MBq/kg [0.2-0.3 mCi/kg]) or greater than or equal to150,000 cells/mm3 for the standard Y-90-ibritumomab tiuxetan administered dose (15 MBq/kg [0.4 mCi/kg]). Patients were given a tracer administered dose of 185 MBq (5 mCi) In-111-ibritumomab tiuxetan on day 0, evaluated with dosimetry, and then a therapeutic administered dos of 7.4-15 MBq/kg (0.20.4 mCi/kg) Y-90-ibritumomab tiuxetan on day 7. Both ibritumomab tiuxetan administered doses were preceded by an infusion of 250 mg/m(2) rituximab to clear peripheral B-cells and improve ibritumomab tiuxetan biodistribution. Residence times for Y-90 in blood and major organs were estimated from In-111 biodistribution, and the MIRDOSE3 computer software program was used, with modifications to account for patient-specific organ masses, to calculate radiation absorbed doses to organs and red marrow. Results: Median radiation absorbed doses for Y-90 were 7.42 Gy to spleen, 4.50 Gy to liver, 2.11 Gy to lung, 0.23 Gy to kidney, 0.62 Gy (blood-derived method) and 0.97 Gy (sacral image-derived method) to red marrow, and 0.57 Gy to total body. The median effective blood half-life was 27 h, and the area under the curve (AUC) was 25 h. No patient failed to meet protocol-defined dosimetry safety criteria and all patients were eligible for treatment. Observed toxicity was primarily hematologic, transient, and reversible. Hematologic toxicity did not correlate with estimates of red marrow radiation absorbed dose, total-body radiation absorbed dose, blood-effective half-life, or blood AUC. Conclusion: Relapsed or refractory NHL in patients with adequate bone marrow reserve and <25% bone marrow involvement by NHL can be treated safely with Y-90-ibritumomab tiuxetan RIT on the basis of a fixed, weight-adjusted dosing schedule. Dosimetry and pharmacokinetic results do not correlate with toxicity. C1 Mayo Clin & Mayo Fdn, Dept Internal Med, Div Hematol, Rochester, MN 55905 USA. Vanderbilt Univ, Nashville, TN USA. Oak Ridge Associated Univ, Knoxville, TN USA. MD Anderson Canc Ctr, Dept Nucl Med, Houston, TX USA. Northwestern Univ, Dept Nucl Med, Chicago, IL 60611 USA. IDEC Pharmaceut Corp, San Diego, CA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Radiat Oncol, Boston, MA 02115 USA. Mayo Clin & Mayo Fdn, Dept Radiol, Rochester, MN 55905 USA. RP Wiseman, GA (reprint author), Mayo Clin, Dept Diagnost Radiol, 200 1st St SW, Rochester, MN 55905 USA. NR 21 TC 144 Z9 148 U1 1 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD MAR PY 2003 VL 44 IS 3 BP 465 EP 474 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 653QF UT WOS:000181447700028 PM 12621016 ER PT J AU Murray, MM Rice, K Wright, RJ Spector, M AF Murray, MM Rice, K Wright, RJ Spector, M TI The effect of selected growth factors on human anterior cruciate ligament cell interactions with a three-dimensional collagen-GAG scaffold SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article ID MEDIAL COLLATERAL LIGAMENT; FIBROBLAST-GROWTH; TGF-BETA; IN-VITRO; INTRINSIC-PROPERTIES; GENE-EXPRESSION; FACTOR ISOFORMS; PDGF; MYOFIBROBLAST; MIGRATION AB Our work focuses on development of a collagen-glycosamimoglycan (CG) scaffold to facilitate ligament healing in the gap between the ruptured ends of the human anterior cruciate ligament (ACL). In the present investigation, we evaluated the effects of selected growth factors on human ACL cell responses important in tissue regeneration, namely cell migration, proliferation, collagen production, and expression of alpha-smooth muscle actin (SMA). Methods: Explants from six human ACLs were cultured on top of a CG scaffold. Culture conditions were with either 2% FBS (control), or 2% FBS supplemented with TGF-beta1, PDGF-AB, EGF, or FGF-2. Histologic cell distribution, total DNA content, proliferation rate, rate of collagen synthesis, scaffold diameter and percentage of SMA positive cells were determined at two, three and four weeks. Results: The addition of TGF-beta1 to the culture medium resulted in increased cell number, increased collagen production and increased expression of SMA within the scaffold. Supplementation with PDGF-AB resulted in increased cell proliferation rates within the scaffold and increased collagen production. The addition of FGF-2 resulted in increased cell proliferation rates and slowed rates of scaffold shrinkage when compared with the control group. Discussion: This work suggests that certain growth factors can alter the biologic functions of human ACL cells in a CG scaffold implanted as a bridge at the site of an ACL rupture. Based on these findings, the addition of selected growth factors to an implantable CG scaffold may facilitate ligament healing in the gap between the ruptured ends of the human ACL. (C) 2002 Published by Elsevier Science Ltd. on behalf of Orthopaedic Research Society. C1 Childrens Hosp Boston, Div Sports Med, Dept Orthopaed Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. VA Boston Healthcare Syst, Boston, MA 02130 USA. RP Murray, MM (reprint author), Childrens Hosp Boston, Div Sports Med, Dept Orthopaed Surg, 300 Longwood Ave, Boston, MA 02115 USA. NR 45 TC 49 Z9 51 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD MAR PY 2003 VL 21 IS 2 BP 238 EP 244 AR PII S0736-0266(02)00142-0 DI 10.1016/S0736-0266(02)00142-0 PG 7 WC Orthopedics SC Orthopedics GA 650FG UT WOS:000181251900007 ER PT J AU Lee, CR Grodzinsky, AJ Hsu, HP Spector, M AF Lee, CR Grodzinsky, AJ Hsu, HP Spector, M TI Effects of a cultured autologous chondrocyte-seeded type II collagen scaffold on the healing of a chondral defect in a canine model SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article ID ARTICULAR-CARTILAGE DEFECTS; IN-VITRO; TISSUE REGENERATION; MATRIX; REPAIR; BEHAVIOR; CONTRACTION; DELIVERY; INVITRO; CELLS AB Using a previously established canine model for repair of articular cartilage defects, this study evaluated the 15-week healing of chondral defects (i.e., to the tidemark) implanted with an autologous articular chondrocyte-seeded type 11 collagen scaffold that had been cultured in vitro for four weeks prior to implantation. The amount and composition of the reparative tissue were compared to results from our prior studies using the same animal model in which the following groups were analyzed: defects implanted with autologous chondrocyte-seeded collagen scaffolds that had been cultured in vitro for approximately 12 h prior to implantation, defects implanted with autologous chondrocytes alone, and untreated defects. Chondrocytes, isolated from articular cartilage harvested from the left knee joint of six adult canines, were expanded in number in monolayer for three weeks, seeded into porous type 11 collagen scaffolds, cultured for an additional four weeks in vitro and then implanted into chondral defects in the trochlear groove of the right knee joints. The percentages of specific tissue types filling the defects were evaluated histomorphometrically and certain mechanical properties of the repair tissue were determined. The reparative tissue filled 88 +/- 6% (mean +/- SEM; range 70-100%) of the cross-sectional area of the original defect, with hyaline cartilage accounting for 42 +/- 10% (range 7-67%) of defect area. These values were greater than those reported previously for untreated defects and defects implanted with a type 11 collagen scaffold seeded with autologous chondrocytes within 12 h prior to implantation. Most striking, was the decreased amount of fibrous tissue filling the defects in the current study, 5 +/- 5% (range 0-26%) as compared to previous treatments. Despite this improvement, indentation testing of the repair tissue formed in this study revealed that the compressive stiffness of the repair tissue was well below (20-fold lower stiffness) that of native articular cartilage. (C) 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. MIT, Dept Engn Mech, Cambridge, MA 02139 USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Biol Engn Div, Cambridge, MA 02139 USA. VA Boston Healthcare Syst, Boston, MA 02130 USA. RP Spector, M (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Orthopaed Surg, 75 Francis St,MRB 106, Boston, MA 02115 USA. NR 34 TC 131 Z9 142 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD MAR PY 2003 VL 21 IS 2 BP 272 EP 281 AR PII S0736-0266(02)00153-5 DI 10.1016/S0736-0266(02)00153-5 PG 10 WC Orthopedics SC Orthopedics GA 650FG UT WOS:000181251900012 PM 12568959 ER PT J AU Morales, TI Hunziker, EB AF Morales, TI Hunziker, EB TI Localization of insulin-like growth factor binding protein-2 in chondrocytes of bovine articular cartilage SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article ID FACTOR-I; OSTEOARTHRITIC CARTILAGE; INCREASED EXPRESSION; IGF-I; BINDING-PROTEIN-3; DIFFERENTIATION; PROTEOGLYCANS; POTENTIATION; CELLS AB Purpose: Previous work indicated that transforming growth factor (TGF-beta) treatment of bovine articular cartilage resulted in an accumulation of insulin-like growth factor binding protein-2 (IGF-BP-2). The purpose of the work presented in this paper was to define the localization of the IGF-BP-2 in freshly excised articular cartilage and in slices cultured in the presence and absence of TGF-beta. Method: Newborn calf articular cartilage was dissected and immediately fixed or maintained in organ culture for five days under basal conditions (media without added serum or growth factors) or with basal media containing 15 ng/ml of TGF-beta1. Frozen or paraffin embedded sections were prepared, and immunohistochemistry using anti-IGF-BP-2 performed. Results: The paraffin sections provided the best preservation of morphology and consistency of immunohistochemical staining patterns. In fresh cartilage slices, IGF-BP-2 was associated with most of the chondrocytes. The basal cultured cartilage showed positive immunostaining in some areas, but not others: the most consistently stained area was the upper radial zone. In all cases where a positive reaction was observed, it was associated mostly with chondrocytes. On the other hand, all the TGF-beta treated samples that were examined in this study were evenly stained, and most chondrocytes were positive in all areas from superficial to deep zones, thus closely resembling the pattern of fresh tissue. Conclusions: It is concluded that IGF-BP-2 is closely cell associated in bovine articular cartilage. Following culture of cartilage slices, TGF-beta increases the number of cells with positive immunostaining. These data help to support the postulate that TGF-beta exerts at least some of its actions in articular cartilage via cross-talk mechanisms involving the IGF-BP-2 system. (C) 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Bern, ITI Res Inst, CH-3010 Bern, Switzerland. RP Morales, TI (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Jackson 1223,55 Fruit St, Boston, MA 02114 USA. NR 27 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD MAR PY 2003 VL 21 IS 2 BP 290 EP 295 AR PII S0736-0266(02)00154-7 DI 10.1016/S0736-0266(02)00154-7 PG 6 WC Orthopedics SC Orthopedics GA 650FG UT WOS:000181251900014 PM 12568961 ER PT J AU Schnitzer, J AF Schnitzer, J TI Separate and cooperate, cooperate and separate: The disengagement of the Palestine health care system from Israel and its emergence as an independent system SO JOURNAL OF PALESTINE STUDIES LA English DT Book Review C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Schnitzer, J (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 2 U2 2 PU UNIV CALIF PRESS PI BERKELEY PA C/O JOURNALS DIVISION, 2000 CENTER ST, STE 303, BERKELEY, CA 94704-1223 USA SN 0377-919X J9 J PALESTINE STUD JI J. Palest. Stud. PD SPR PY 2003 VL 32 IS 3 BP 108 EP 110 PG 3 WC Area Studies SC Area Studies GA 679UH UT WOS:000182940000011 ER PT J AU Hussein, MR Haemel, AK Wood, GS AF Hussein, MR Haemel, AK Wood, GS TI Apoptosis and melanoma: molecular mechanisms SO JOURNAL OF PATHOLOGY LA English DT Review DE pro-apoptotic molecules; anti-apoptotic molecules; CMM; cutaneous malignant melanoma; programmed cell death ID NF-KAPPA-B; TRAIL-INDUCED APOPTOSIS; ANTISENSE OLIGODEOXYNUCLEOTIDES ENHANCE; CUTANEOUS MALIGNANT-MELANOMA; LIGAND-INDUCED APOPTOSIS; CYTOCHROME-C RELEASE; UV-INDUCED APOPTOSIS; HAMSTER OVARY CELLS; P53 GENE MUTATION; DOWN-REGULATION AB Melanoma cells can undergo self-destruction via programmed cell death, i.e. apoptosis. In these tumours, the molecular components of apoptosis include positive (apoptotic) and negative (anti-apoptotic) regulators. The former include p53, Bid, Noxa, PUMA, Bax, TNF, TRAIL, Fas/FasL, PITSLRE, interferons, and c-KIT/SCF. The latter include Bcl-2, Bcl-X-L, Mcl-1, NF-B-K, survivin, livin, and ML-IAP. Alternatively, some molecules such as TRAF-2, c-Myc, endothelins, and integrins may have either pro- or anti-apoptotic effects. Some of these molecules are of potential therapeutic use, such as: (1) p53, which influences resistance to chemotherapy; (2) Mcl-1 and Bcl-X-L, which can override apoptosis; (3) TRAIL, which has selective fatal effects on tumour cells; (4) NF-B-K, which when downregulated sensitizes cells to TRAIL and TNF; (5) the PITSLRE kinases, whose alteration appears to result in Fas resistance; (6) interferons, which sensitize cells to other factors; and (7) survivin and other IAPs that inhibit apoptosis. This review summarizes the state of current knowledge about the key molecular components and mechanisms of apoptosis in melanoma, discusses potential therapeutic ramifications, and provides directions for future research. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Univ Wisconsin, Dept Dermatol, Madison, WI 53715 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Wood, GS (reprint author), Univ Wisconsin, Dept Dermatol, 1 S Pk,7th Floor, Madison, WI 53715 USA. FU NIAMS NIH HHS [AR02136] NR 121 TC 144 Z9 157 U1 0 U2 6 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD MAR PY 2003 VL 199 IS 3 BP 275 EP 288 DI 10.1002/path.1300 PG 14 WC Oncology; Pathology SC Oncology; Pathology GA 651YA UT WOS:000181350100001 PM 12579529 ER PT J AU Patenaude, AF AF Patenaude, AF TI Pediatric psychology training and genetics: What will twenty-first-century pediatric psychologists need to know? SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Article DE genetic testing; hereditary cancer syndromes; psychiatric genetics ID FRAGILE-X-SYNDROME; FOLLOW-UP; CANCER SUSCEPTIBILITY; CYSTIC-FIBROSIS; BRCA1 MUTATION; CHILDREN; IMPACT; PREDISPOSITION; ADOLESCENTS; DEPRESSION AB Objective To demonstrate the importance of genetic knowledge in coming decades and to outline necessary areas of genetic education. Method This article reviews research involving genetic testing of children for cancer syndromes, development disabilities, psychiatric problems, and other conditions. Results The developmental, clinical, research, and consultation skills of well-trained pediatric psychologists will make them valuable collaborators with genetics professionals. Pediatric psychologists study the genetic etiology of psychiatric conditions and outcomes of genetic testing for physical disease. Conclusions Pediatric psychologists will need training in the concepts and methods of the New Genetics. They should understand the implications of risk notification and genetic test disclosure and should be aware of related ethical concerns. C1 Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Patenaude, AF (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 55 TC 8 Z9 8 U1 2 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD MAR PY 2003 VL 28 IS 2 BP 135 EP 145 DI 10.1093/jpepsy/28.2.135 PG 11 WC Psychology, Developmental SC Psychology GA 650QY UT WOS:000181275900008 PM 12556513 ER PT J AU Stephen, AE Segev, DL Ryan, DP Mullins, ME Kim, SH Schnitzer, JJ Doody, DP AF Stephen, AE Segev, DL Ryan, DP Mullins, ME Kim, SH Schnitzer, JJ Doody, DP TI The diagnosis of acute appendicitis in a pediatric population: To CT or not to CT SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the American-Pediatric-Surgical-Association CY MAY 19-23, 2002 CL PHOENIX, ARIZONA SP American Pediatric Surg Assoc DE appendicitis; computed tomography; x-ray; surgery; diagnostic techniques and procedures; emergency treatment ID HELICAL CT; COMPUTED-TOMOGRAPHY; CHILDREN; ULTRASONOGRAPHY; US AB Purpose: The aim of this study was to determine if focused appendiceal computed tomography with colon contrast (FACT-CC) increases the accuracy of the preoperative diagnosis of acute appendicitis in children. Methods: A 5-year retrospective review was conducted of a university hospital database of 283 patients (age 0.8 to 19.3 years; mean, 11.3 years) treated with appendectomy for presumed acute appendicitis. Results: Of the 283 patients in whom appendectomies were performed, 268 were confirmed by pathologic analysis of the specimen to have acute appendicitis for a diagnostic accuracy in our institution of 94.7%. Ninety-six patients (34%) underwent FACT-CC scans as part of their preoperative evaluation. The sensitivity of the computed tomography (CT) scan was 94.6%, and the positive predictive value was 95.6%. In girls older than 10 years, CT imaging was not significantly more accurate in predicting appendicitis than examination alone (93.9% v. 87.5%; P = .46). Conclusions: Preoperative FACT-CC did not increase the accuracy in diagnosing appendicitis when compared with patients diagnosed by history, physical examination and laboratory studies. If there was a strong suspicion of appendicitis, a negative CT scan did not exclude the diagnosis of appendicitis. However, focused appendiceal CT scan is a sensitive test with a high positive predictive value and may be useful in a patient with an atypical history or examination. Copyright 2003, Elsevier Science (USA). All rights reserved. C1 Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. RP Doody, DP (reprint author), Massachusetts Gen Hosp, Dept Pediat Surg, 55 Fruit St, Boston, MA 02114 USA. NR 18 TC 47 Z9 51 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 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD MAR PY 2003 VL 38 IS 3 BP 367 EP 370 DI 10.1053/jpsu.2003.50110 PG 4 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 650YU UT WOS:000181293000032 PM 12632351 ER PT J AU Picker, JD Puga, AC Levy, LL Marsden, D Shih, VE DeGirolami, U Ligon, KL Cederbaum, SD Kern, RM Cox, GF AF Picker, JD Puga, AC Levy, LL Marsden, D Shih, VE DeGirolami, U Ligon, KL Cederbaum, SD Kern, RM Cox, GF TI Arginase deficiency with lethal neonatal expression: Evidence for the glutamine hypothesis of cerebral edema SO JOURNAL OF PEDIATRICS LA English DT Article ID HYPERARGININEMIA; ENCEPHALOPATHY AB We describe a rare and lethal case of arginase deficiency in a 2-day-old female infant with encephalopathy and cerebral edema. The levels of glutamine and arginine but not ammonia were markedly elevated, lending support to the "glutamine hypothesis" as the mechanism of cerebral edema in urea cycle defects. C1 Childrens Hosp, Div Genet, Metab Program, Boston, MA 02115 USA. Childrens Hosp, Div Neuropathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Genzyme Corp, Clin Res, Cambridge, MA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Mental Retardat Res Ctr, Los Angeles, CA USA. RP Picker, JD (reprint author), Childrens Hosp, Div Genet, Metab Program, IC Smith Bldg,300 Longwood Ave, Boston, MA 02115 USA. EM jonathan.picker@tch.harvard.edu FU NICHD NIH HHS [HD-06576, HD-36415] NR 17 TC 29 Z9 29 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAR PY 2003 VL 142 IS 3 BP 349 EP 352 DI 10.1067/mpd.2003.97 PG 4 WC Pediatrics SC Pediatrics GA 658YL UT WOS:000181748600030 PM 12640389 ER PT J AU Mukhin, YV Garnovsky, EA Ullian, ME Garnovskaya, MN AF Mukhin, YV Garnovsky, EA Ullian, ME Garnovskaya, MN TI Bradykinin B2 receptor activates extracellular signal-regulated protein kinase in mIMCD-3 cells via epidermal growth factor receptor transactivation SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SMOOTH-MUSCLE CELLS; EGF RECEPTOR; COUPLED RECEPTORS; ANGIOTENSIN-II; MESANGIAL CELLS; LYSOPHOSPHATIDIC ACID; COLLECTING DUCT; PATHWAY; MAPK; PYK2 AB Bradykinin (BK) has been implicated in the regulation of renal function. Activation of extracellular signal-regulated protein kinase (ERK1/2) has been demonstrated in several models of toxic or proliferative renal injury. We studied activation of ERK1/2 by BK in a cell model of the most distal part of the nephron, inner medullary collecting duct (mIMCD-3) cells. Exposure of mIMCD-3 cells to BK (10(-10)-10(-5) M) resulted in a concentration-dependent increase in tyrosine phosphorylation of ERK1/2, with maximal effect at 10(-8) M BK. ERK1/2 activation by BK was observed as early as 1 min, peaked at 5 min, and was sustained at least for 1 h. The effect of BK was mediated by the B-2 receptor and was pertussis toxin-independent. Inhibition of phospholipase C, protein kinase C, or phosphatidylinositol 3-kinase did not alter ERK1/2 activation by BK. BK-induced ERK1/2 activation was Ca2+-calmodulin-independent but was sensitive to genistein, an inhibitor of tyrosine kinase(s). AG1478, a specific inhibitor of epidermal growth factor receptor (EGFR) kinase, completely blocked the effect of BK, suggesting an essential role of EGFR in ERK1/2 activation by BK. Immunoprecipitation/ Western blot studies revealed that BK stimulated tyrosine phosphorylation of EGFR, its association with an adapter molecule Grb2, and complex formation between Grb2 and the adapter protein Shc. Activation studies of monomeric G protein Ras showed that BK-induced stimulation of Ras was dependent on EGFR tyrosine kinase activity. These studies demonstrate that BK stimulates Ras-dependent activation of ERK1/2 in mIMCD-3 cells via transactivation of EGFR through a novel mechanism. C1 Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Med Serv, Charleston, SC USA. Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC USA. RP Garnovskaya, MN (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, Room 829 CSB,171 Ashley Ave, Charleston, SC 29425 USA. FU NIDDK NIH HHS [K01-DK02694] NR 40 TC 25 Z9 26 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAR PY 2003 VL 304 IS 3 BP 968 EP 977 DI 10.1124/jpet.102.043943 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 648XP UT WOS:000181176900009 PM 12604671 ER PT J AU Rasmussen, DD Marck, BT Boldt, BM Yellon, SM Matsumoto, AM AF Rasmussen, DD Marck, BT Boldt, BM Yellon, SM Matsumoto, AM TI Suppression of hypothalamic pro-opiomelanocortin (POMC) gene expression by daily melatonin supplementation in aging rats SO JOURNAL OF PINEAL RESEARCH LA English DT Article DE aging; gene expression; hypothalamus; melatonin; POMC; proopiomelanocortin; mRNA ID PROOPIOMELANOCORTIN MESSENGER-RNA; AGE-RELATED-CHANGES; ARCUATE NUCLEUS; OVARIECTOMIZED RATS; RIBONUCLEIC-ACID; DIURNAL RHYTHM; PLASMA LEPTIN; PINEAL-GLAND; LONG-TERM; LIGHT AB Both plasma melatonin levels and hypothalamic arcuate nucleus pro-opiomelanocortin (POMC) (biosynthetic precursor to the endogenous opioid ss-endorphin and other opiomelanocortins) mRNA content decrease with aging. To test whether the decline in melatonin is responsible for the decline in POMC mRNA, we investigated the effects of daily melatonin treatment on hypothalamic POMC mRNA content in middle-aged and older Sprague-Dawley rats. Daily nocturnal melatonin treatment (50 mug kg bw(-1) night(-1) , in the night-time drinking water) for 7 months, starting at 13 months of age, did not significantly alter female arcuate nucleus POMC mRNA content determined at the end of the light period (i.e., before nightly melatonin administration), but suppressed (24%, P < 0.05) POMC mRNA content at the end of the dark period (i.e., following melatonin administration). Likewise, nocturnal administration of 50 or 500 mug melatonin kg bw(-1) night(-1) to male rats for 7 months suppressed (31 or 28%, respectively; P < 0.05) POMC mRNA content at the middle of the dark period at 20 months of age. Finally, 10 wk administration of 30 mug melatonin kg bw(-1) day(-1) suppressed (31%, P < 0.01) POMC mRNA content in middle-aged male rats killed at the end of the dark period. Melatonin treatments did not significantly alter estradiol or testosterone levels. Thus, moderate-dosage nocturnal melatonin supplementation suppressed nocturnal hypothalamic POMC gene expression in both middle-aged males and females, suggesting that melatonin supplementation during aging decreases, rather than increases, forebrain opiomelanocortinergic activity. These POMC responses were apparently not dependent on gonadal steroid responses and did not become refractory to melatonin treatment maintained until old age. C1 VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. Univ Washington, Ctr Geriatr Res Educ & Clin, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA USA. Loma Linda Univ, Dept Physiol, Loma Linda, CA 92350 USA. RP Rasmussen, DD (reprint author), VA Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, 116 MIRECC,1660 S Columbian Way, Seattle, WA 98108 USA. FU NIAAA NIH HHS [AA10567] NR 34 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0742-3098 J9 J PINEAL RES JI J. Pineal Res. PD MAR PY 2003 VL 34 IS 2 BP 127 EP 133 DI 10.1034/j.1600-079X.2003.00019.x PG 7 WC Endocrinology & Metabolism; Neurosciences; Physiology SC Endocrinology & Metabolism; Neurosciences & Neurology; Physiology GA 641JM UT WOS:000180741700007 PM 12562504 ER PT J AU Goldman, RJ Reinbold, KA Iglarsh, A Neustadter, LM Oatis, CA Schumacher, HR AF Goldman, RJ Reinbold, KA Iglarsh, A Neustadter, LM Oatis, CA Schumacher, HR TI Phase I design and evaluation of an isometric muscle reeducation device for knee osteoarthritis rehabilitation SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE biofeedback device; isometric exercise; muscle reeducation; osteoarthritis of the knee; patient compliance ID RANDOMIZED CONTROLLED TRIAL; EXERCISE THERAPY; OSTEO-ARTHRITIS; CLINICAL-TRIAL; PRESSURE; STRENGTH; HIP; AGE; PROGRAM; TORQUE AB Our long-term goal is to improve adherence to a home-based isometric program for rehabilitation of knee osteoarthritis (OA) using a force-biofeedback device (Isopad(TM)). Our goal for Phase I was to design and evaluate an Isopad-based program in a supervised clinical setting. Our subjects were five patients with knee OA of Kellgren stage II or greater. A capacitive force sensor was tested for accuracy, repeatability, and durability. An Arthritis Foundation home-based isometric program inspired the Isopad design. The Isopad provided visual and auditory feedback instantaneously and continuously about force generated between the ankles. The five subjects completed a supervised 8-week progressive isometric program using the Isopad. Absolute isolated quadriceps and hamstring torques were quantified with a dynamometer, and patients completed a self-assessment of symptoms (Western Ontario and McMaster Universities Osteoarthritis Index). The capacitive sensor accuracy error averaged 10% and repeatability 4%. Cognitively intact subjects used the Isopad successfully for isometric progressive resistance training. Quadriceps and hamstrings absolute torques increased an average of 30%. Patients reported decreased functional complaints (Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index). All changes were trends. The Isopad helped subjects with knee OA adhere to a supervised isometric program and meet progressive strength targets. The next-generation Isopad will be employed in a home-based program. C1 SensorPad Syst Inc, Norristown, PA USA. Univ Sci Philadelphia, Philadelphia, PA USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Arcadia Univ, Glenside, PA USA. RP Goldman, RJ (reprint author), SensorPad Syst Inc, 527 W Sedgwick St, Philadelphia, PA USA. FU NIAMS NIH HHS [1 R43 AR45153-01] NR 47 TC 1 Z9 1 U1 0 U2 2 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAR-APR PY 2003 VL 40 IS 2 BP 95 EP 107 DI 10.1682/JRRD.2003.03.0095 PG 13 WC Rehabilitation SC Rehabilitation GA 674DU UT WOS:000182622400002 PM 15077636 ER PT J AU Hsu, FC Starkebaum, G Boyko, EJ Dominitz, JA AF Hsu, FC Starkebaum, G Boyko, EJ Dominitz, JA TI Prevalence of rheumatoid arthritis and hepatitis C in those age 60 and older in a US population based study SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE hepatitis C virus; rheumatoid arthritis; rheumatoid factor ID VIRUS-INFECTION; UNITED-STATES; AUTOIMMUNITY; DISEASE AB Objective. A positive association between rheumatoid arthritis (RA) and hepatitis C virus (HCV) infection has been reported in clinic based cross sectional studies. We investigated if RA and HCV are associated in a population based survey. Methods. Using data from the National Health and Nutrition Examination Survey III, hepatitis C and RA status were determined for subjects greater than or equal to 60 years of age. RA was defined to be present when 3 of 6 American College of Rheumatology (ACR) criteria were met. Results. Of 6596 subjects, 1827 (27.7%) were excluded due to missing data. Of the remaining 4769, 196 subjects (4.1%) met our modified ACR criteria for probable RA: 63 tested positive for anti-HCV antibodies (1.3%) while 35 were HCV RNA positive (0.7%). Two subjects had both HCV antibodies and RA, while one subject was both HCV RNA positive and had RA. HCV antibody positivity was not associated with RA (OR 0.44, 95% Cl 0.07-2.80). Similarly, HCV positivity by polymerase chain reaction was not associated with RA (OR 0.77, 95% Cl 0.10-6.19). Conclusion. These results argue against a potential role for HCV in the etiology of RA in the US population aged 60 years and over. C1 VA Puget Sound Hlth Care Syst, Arthrit Sect, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Gastroenterol Sect, Seattle, WA 98108 USA. Univ Washington, Sch Med,VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Dept Med,Div Gen Internal Med, Seattle, WA USA. Univ Washington, Sch Med, Div Rheumatol, Dept Med, Seattle, WA 98195 USA. RP Dominitz, JA (reprint author), VA Puget Sound Hlth Care Syst, Arthrit Sect, 111 Gastro,1660 S Columbian Way, Seattle, WA 98108 USA. OI Dominitz, Jason/0000-0002-8070-7086 NR 18 TC 13 Z9 14 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 MAR PY 2003 VL 30 IS 3 BP 455 EP 458 PG 4 WC Rheumatology SC Rheumatology GA 652GU UT WOS:000181372100007 PM 12610800 ER PT J AU O'Malley, KJ Suarez-Almazor, M Aniol, J Richardson, P Kuykendall, DH Moseley, JB Wray, NP AF O'Malley, KJ Suarez-Almazor, M Aniol, J Richardson, P Kuykendall, DH Moseley, JB Wray, NP TI Joint-specific multidimensional assessment of pain (J-MAP): Factor structure, reliability, validity, and responsiveness in patients with knee osteoarthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE joint pain; outcome measure; osteoarthritis; validity; equal interval scaling ID QUALITY-OF-LIFE; HEALTH-STATUS; INTRAINDIVIDUAL CHANGES; RHEUMATOID-ARTHRITIS; IMPORTANT DIFFERENCE; WESTERN ONTARIO; WOMAC; QUESTIONNAIRE; SCALE; INDEX AB Objective. To develop a reliable and valid instrument for measuring and monitoring joint-specific pain. Methods. Developed using patient interviews, reviews of pain literature, and expert input from orthopedic surgeons, the final Joint-Specific Multidimensional Assessment of Pain (J-MAP) includes the 6-item Pain Sensory and the 4-item Pain Affect subscales. Scores on the J-MAP Pain Sensory and Affect subscales range from 0 to 100, with higher scores indicating more pain intensity and worse pain distastefulness; respectively. Following the assessment of the factor structure, patients' scores (n = 180) on the J-MAP subscales were converted to equal interval scores using Rasch analyses. A psychometric evaluation of the items and Rasch-calibrated scores was conducted and included an assessment of reliability, validity, and responsiveness for use with patients with radiographic knee osteoarthritis. Results. Evidence from the factor analyses showed that the J-MAP Pain Sensory and Affect items made up 2 distinct factors. Internal consistency estimates for the J-MAP subscales exceeded 0.85. The J-MAP subscales showed evidence for validity and were shown to be internally and externally responsive, demonstrating greater responsiveness than the Arthritis Impact Measurement Scale or the Medical Outcome Study Short Form-36 pain subscales. Finally, evidence was found supporting the J-MAP subscales' ability to distinguish target joint pain from pain emanating from other musculoskeletal conditions. Conclusion. The J-MAP is a reliable, valid, and responsive measure for assessing joint-specific pain at a single time point, or changes over time for one or a group of patients with knee osteoarthritis. With this initial evidence of its psychometric rigor, further testing of the measurement properties of the J-MAP in other joints and in other populations should be undertaken. C1 Baylor Coll Med, VAMC 152, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Houston VAMC, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Int Survey Res, London, England. Baylor Coll Med, Dept Orthoped Surg, Houston, TX 77030 USA. RP O'Malley, KJ (reprint author), Baylor Coll Med, VAMC 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 67 TC 11 Z9 11 U1 11 U2 12 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 MAR PY 2003 VL 30 IS 3 BP 534 EP 543 PG 10 WC Rheumatology SC Rheumatology GA 652GU UT WOS:000181372100021 PM 12610814 ER PT J AU Guihan, M Simmons, B Nelson, A Bosshart, HT Burns, SP AF Guihan, M Simmons, B Nelson, A Bosshart, HT Burns, SP TI Spinal cord injury providers' perceptions of barriers to implementing selected clinical practice guideline recommendations SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article; Proceedings Paper CT Annual Conference of the American-Paraplegia-Society CY SEP, 2002 CL LAS VEGAS, NEVADA SP Amer Paraplegia Soc DE clinical practice guideline; spinal cord injuries; rehabilitation; thromboembolism; neurogenic bowel; quality enhancement research initiative; health services research; health care outcomes; focus groups AB Background/Objective: Twelve focus groups were conducted at 6 Department of Veterans Affairs (DVA) Spinal Cord Injury (SCI) Centers. The purpose of these focus groups was to identify provider-perceived barriers to implementing selected recommendations of two clinical practice guidelines (CPGs)-Prevention of Thromboembolism in Spinal Cord Injury and Management of Neurogenic Bowel in Adults With Spinal Cord Injury-at their sites. Methods: A total of 75 SCI direct-care staff (including physicians, nurses, dieticians, rehabilitation therapists, psychologists, and social workers) participated in the focus groups, which were conducted by trained focus group facilitators. Woolf's framework was used to classify perceived barriers into I of 4 categories: (a) lack of knowledge, (b) lack of agreement, (c) lack of ability, or (d) lack of systematic reminders for implementation. The "lack of ability" category was further expanded to reflect which specific aspect of the environment was seen as the obstacle: (a) patient, (b) provider, (c) SCI unit, (d) hospital or medical center, or (e) non-Veterans Affairs (VA) hospital setting. Results: Providers disagreed with the recommendation to reinstitute prophylaxis in patients with nonacute SCI to prevent deep vein thrombosis and identified a number of system-level problems with providing appropriate prophylaxis. Providers identified patient reluctance to changing their bowel programs and difficulties in documenting changes in the patients' bowel program as obstacles to implementing the neurogenic bowel CPG. Conclusion: Based on this feedback, interventions were developed to address provider-perceived barriers. These interventions were implemented at 6 Veterans Affairs SCI Centers. C1 Edward Hines Jr Vet Adm Hosp, Midwest Ctr Hlth Serv & Policy Res, Hines, IL 60141 USA. Edward Hines Jr Vet Adm Hosp, Spinal Cord Injury Qual Enhancement Res Initiat R, Hines, IL USA. Northwestern Univ, Inst Hlth Serv Res & Policy Studies, Evanston, IL USA. Tampa Vet Affairs Med Ctr, Tampa, FL USA. Vet Hlth Adm, Patient Safety Ctr Inquiry, Tampa, FL USA. Tampa Vet Affairs Med Ctr, Tampa, FL USA. Univ S Florida, Coll Nursing, Tampa, FL USA. Augusta Vet Affairs Med Ctr, Augusta, GA USA. Vet Affairs Puget Sound Hlth Care Syst, Spinal Cord Injury Serv, Seattle, WA USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Guihan, M (reprint author), Edward Hines Jr Vet Adm Hosp, Midwest Ctr Hlth Serv & Policy Res, 151H,5th Ave & Roosevelt Rd, Hines, IL 60141 USA. NR 28 TC 5 Z9 5 U1 0 U2 0 PU AMER PARAPLEGIA SOC PI JACKSON HWIGHTS PA 75-20 ASTORIA BLVD, JACKSON HWIGHTS, NY 11370-1177 USA SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD SPR PY 2003 VL 26 IS 1 BP 48 EP 58 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 739PG UT WOS:000186355200011 PM 12830970 ER PT J AU Komar, JC James, JJ Little, JW AF Komar, JC James, JJ Little, JW TI Scheuermann's kyphosis following cervical spinal cord injury SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE Scheuermann's kyphosis; spinal cord injuries; rehabilitation; neurologic complications; tetraplegia ID COMPRESSION AB Background: Scheuermann's kyphosis is an uncommon autosomal dominant disease that manifests as a progressive thoracic skeletal deformity. It can lead to severe restrictive lung disease or predispose to spinal cord injury (SCI). Neurologic sequelae are rarely reported in the literature. Method: Case Presentation Summary: A 47-year-old man sustained a cervical SCI requiring surgical anterior fusion and reoperation for fracture of the affected vertebra. One year after SCI, he presented with further kyphotic progression and cervical spine instability. Clinical presentation and family history led to a diagnosis of Scheuermann's kyphosis. To prevent further progression, he underwent extensive multilevel anterior and posterior surgical stabilization. Conclusion: This case illustrates the importance of early diagnosis and treatment of progressive spinal deformities. With proper surgical correction, this patient made substantial gains in mobility, self-care, and respiratory status. C1 Univ Washington, Dept Rehabil Med, VA Puget Sound Hlth Care Syst, Spinal Cord Injury Unit, Seattle, WA 98195 USA. RP Komar, JC (reprint author), Univ Washington, Dept Rehabil Med, VA Puget Sound Hlth Care Syst, Spinal Cord Injury Unit, 1959 NE Pacific St,Box 356490, Seattle, WA 98195 USA. NR 7 TC 1 Z9 2 U1 0 U2 0 PU AMER PARAPLEGIA SOC PI JACKSON HWIGHTS PA 75-20 ASTORIA BLVD, JACKSON HWIGHTS, NY 11370-1177 USA SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD SPR PY 2003 VL 26 IS 1 BP 92 EP 94 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 739PG UT WOS:000186355200017 PM 12830976 ER PT J AU Bates-Jensen, BM Alessi, CA Al-Samarrai, NR Schnelle, JF AF Bates-Jensen, BM Alessi, CA Al-Samarrai, NR Schnelle, JF TI The effects of an exercise and incontinence intervention on skin health outcomes in nursing home residents SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE pressure ulcer prevention; exercise; incontinence ID PRESSURE ULCER DEVELOPMENT; RISK-FACTORS; PREVENTIVE INTERVENTIONS; NIGHTTIME INCONTINENCE; HOSPITALIZED-PATIENTS; SORES; CARE AB OBJECTIVES: To examine skin health outcomes of an exercise and incontinence intervention. DESIGN: Randomized controlled trial with blinded assessments of outcomes at three points over 8 months. SETTING: Four nursing homes (NHs). PARTICIPANTS: One hundred ninety incontinent NH residents. INTERVENTION: In the intervention group, research staff provided exercise and incontinence care every 2 hours from 8:00 a.m. to 4:30 p.m. (total of four daily care episodes) 5 days a week for 32 weeks. The control group received usual care from NH staff. MEASUREMENTS: Perineal skin wetness and skin health outcomes (primarily blanchable erythema and pressure ulcers) as measured by direct assessments by research staff, urinary and fecal incontinence frequency, and percentage of behavioral observations with resident engaged in standing or walking. RESULTS: Intervention subjects were significantly better in urinary and fecal incontinence, physical activity, and skin wetness outcome measures than the control group. However, despite these improvements, differences in skin health measures were limited to the back distal perineal area, which included the sacral and trochanter regions. There was no difference between groups in the incidence rate of pressure ulcers as measured by research staff, even though those residents who improved the most on fecal incontinence showed improvement in pressure ulcers in one area. CONCLUSION: A multifaceted intervention improved four risk factors related to skin health but did not translate into significant improvements in most measures of skin health. Even if they had adequate staffing resources, NHs might not be able to improve skin health quality indicators significantly if they attempt to implement preventive interventions on all residents who are judged at risk because of their incontinence status. C1 Univ Calif Los Angeles, Jewish Home Borun Ctr, Sch Med, Div Geriatr, Reseda, CA 91335 USA. Univ Calif Los Angeles, Jewish Home Aging Borun Ctr Gerontol Res, Reseda, CA 91335 USA. Univ Calif Los Angeles, Multicampus Program Geriatr Med & Gerontol, Sepulveda, CA USA. Sepulveda Geriatr Res Educ & Clin Ctr, Vet Adm Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. RP Bates-Jensen, BM (reprint author), Univ Calif Los Angeles, Jewish Home Borun Ctr, Sch Med, Div Geriatr, 7150 Tampa Ave, Reseda, CA 91335 USA. FU NIA NIH HHS [AG 10415, AG 13013] NR 40 TC 35 Z9 35 U1 3 U2 7 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2003 VL 51 IS 3 BP 348 EP 355 DI 10.1046/j.1532-5415.2003.51108.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 646GW UT WOS:000181028100008 PM 12588578 ER PT J AU Satre, DD Knight, BG Dickson-Fuhrmann, E Jarvik, LF AF Satre, DD Knight, BG Dickson-Fuhrmann, E Jarvik, LF TI Predictors of alcohol-treatment seeking in a sample of older veterans in the GET SMART program SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE alcohol; substance abuse treatment; structural equation modeling ID CAGE QUESTIONNAIRE; ABUSE; DIAGNOSIS; CARE AB OBJECTIVES: To examine the predictive value of demographic characteristics and substance abuse indicators to explain treatment seeking for substance abuse problems by older male medical patients. DESIGN: Longitudinal analysis of screening data and treatment-seeking behavior. SETTING: Inpatient medical and outpatient substance abuse treatment center. PARTICIPANTS: Participants in the study were 855 medically ill male veterans aged 55 and older, who were screened for alcohol problems during inpatient medical treatment after clinician referral. MEASUREMENTS: The CAGE alcohol screen (Cut down on your drinking, Annoyed by criticism of your drinking, Guilty about your drinking, Eye-opener), drug use, and demographic measures administered at time of screening. Predictors of treatment seeking in the sample were examined using structural equation modeling. RESULTS: Expressed interest in treatment and later attendance at a pretreatment evaluation were associated with younger age and a higher CAGE alcohol screening score. Being unmarried and using drugs in addition to alcohol were associated with treatment interest but not with evaluation attendance. In the path model tested, the effect of higher CAGE score partially explained the effect of younger age on treatment seeking. CONCLUSION: The model examined shows utility in predicting alcohol-treatment seeking in this sample. Age-related factors may deter treatment seeking by older male medical inpatients. C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ So Calif, Andrus Gerontol Ctr, Los Angeles, CA USA. Va Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Satre, DD (reprint author), Univ Calif San Francisco, 401 Parnassus Ave,Box 0984-OVS, San Francisco, CA 94143 USA. FU NIA NIH HHS [2T32 AG 00037] NR 29 TC 13 Z9 13 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAR PY 2003 VL 51 IS 3 BP 380 EP 386 DI 10.1046/j.1532-5415.2003.51112.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 646GW UT WOS:000181028100012 PM 12588582 ER PT J AU Jacobson, AF Williams, JE AF Jacobson, AF Williams, JE TI Bone scintigraphic findings in patients with foot ulcers and normal plain film radiographs SO JOURNAL OF THE AMERICAN PODIATRIC MEDICAL ASSOCIATION LA English DT Article ID DIABETIC-PATIENTS; PEDAL OSTEOMYELITIS; LEUKOCYTE SCINTIGRAPHY; TC-99M MDP; DIAGNOSIS; IN-111; MR; INFECTION; ABNORMALITIES; THERAPY AB A prospective study was performed to examine the performance of bone scintigraphy in the earliest stage of soft-tissue foot ulceration with potential risk for progression to osteomyelitis. Twenty-three podiatry clinic patients with new or recurrent foot ulcers but negative plain film radiographs of the foot underwent 24 (one patient was studied twice) multiphase bone scans (flow, blood pool, and 3- and 24-hour delayed images) that were visually scored for severity of increased uptake on a scale of 0 to 3+, with 0 indicating normal and 3+ indicating severe. Twenty-one scans (88%) showed abnormal uptake on at least one phase, with 17 (71%) having increased bone uptake on late images. Ulcer healing without complications occurred in 20 cases (83%), whereas 4 cases had adverse outcomes, 3 requiring surgical resection for failure to heal and 1 having radiographic progression to frank osteomyelitis. All three patients whose bone scans showed severe abnormal uptake had an adverse clinical outcome. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA USA. RP Jacobson, AF (reprint author), Amersham Hlth, 101 Carnegie Ctr, Princeton, NJ 08540 USA. NR 25 TC 1 Z9 1 U1 0 U2 1 PU AMER PODIATRIC MED ASSN PI BETHESDA PA 9312 OLD GEORGETOWN ROAD, BETHESDA, MD 20814-1621 USA SN 8750-7315 J9 J AM PODIAT MED ASSN JI J. Am. Podiatr. Med. Assoc. PD MAR-APR PY 2003 VL 93 IS 2 BP 91 EP 96 PG 6 WC Orthopedics SC Orthopedics GA 722DC UT WOS:000185359300001 PM 12644514 ER PT J AU Shrager, JB Wain, JC Wright, CD Donahue, DM Vlahakes, GJ Moncure, AC Grillo, HC Mathisen, DJ AF Shrager, JB Wain, JC Wright, CD Donahue, DM Vlahakes, GJ Moncure, AC Grillo, HC Mathisen, DJ TI Omentum is highly effective in the management of complex cardiothoracic surgical problems SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 12th World Congress of the World-Society-of-Cardio-Thoracic-Surgeons CY MAR 03-06, 2002 CL LUZERN, SWITZERLAND SP World Soc Cardio Thoracic Surgeons ID POSTPNEUMONECTOMY EMPYEMA; BRONCHIAL OMENTOPEXY; MUSCLE TRANSPOSITION; CONSECUTIVE PATIENTS; ANGIOGENIC FACTOR; ACCOUNT; FLAPS AB Objectives: Vascularized, pedicled tissue flaps are often used for cardiothoracic surgical problems complicated by factors that adversely affect healing, such as previous irradiation, established infection, or steroid use. We reviewed our experience with use of the omentum in these situations to provide a yardstick against which results with other vascularized flaps (specifically muscle flaps) could be compared. Methods: A retrospective review was undertaken of 85 consecutive patients in whom omentum was used in the chest. In 47 patients (group 1), use of omentum was prophylactic to aid in the healing of closures or anastomoses considered to be at high risk for failure. In 32 patients (group 11), omentum was used in the treatment of problems complicated by established infection. In 6 patients (group 111), omentum was used for coverage of prosthetic chest wall replacements after extensive chest wall resection. Results: Overall, omental transposition was successful in its prophylactic or therapeutic purpose in 88% of these difficult cases (75/85). Success with omentum was achieved for 89% of patients (42/47) in group I, 91% of patients (29/32) in group II, and 67% of patients (4/6) in group III. Three patients (3.5%) had complications 4 of omental mobilization. Four patients (4.7%) died after the operation as a result of failure of the omentum to manage the problem for which it was used. Conclusions: Results with omental transposition compare favorably with published series of similarly challenging cases managed with muscle transposition. Complications of omental mobilization are rare. We believe that its unique properties render the omentum an excellent choice of vascularized pedicle in the management of the most complex cardiothoracic surgical problems. C1 Massachusetts Gen Hosp, Thorac Surg Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac Surg Unit, Boston, MA 02114 USA. RP Shrager, JB (reprint author), Univ Penn, Sch Med, Sect Gen Thorac Surg, Philadelphia, PA 19104 USA. NR 14 TC 57 Z9 58 U1 1 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAR PY 2003 VL 125 IS 3 BP 526 EP 532 DI 10.1067/mtc.2003.12 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 662MB UT WOS:000181949800015 PM 12658194 ER PT J AU Takahashi, TA Merrill, JO Boyko, EJ Bradley, KA AF Takahashi, TA Merrill, JO Boyko, EJ Bradley, KA TI Type and location of injection drug use-related soft tissue infections predict hospitalization SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article DE abscess; cellulitis; health care utilization; injection drug use; soft tissue infection ID NECROTIZING FASCIITIS; MEDICAL-CARE; EMERGENCY; ABUSE; COSTS; ACCIDENT; CHARGES AB The prevalence of soft tissue infections (abscesses, cellulitides, infected ulcers) among injection drug users (IDUs) is estimated to be between 21% and 32%. Little is known regarding the health care utilization associated with these infections. This study describes IDUs seeking emergency department (ED) care for soft tissue infections, their inpatient health care utilization, including operating room procedures, and the types and locations of infections associated with increased inpatient health care utilization. This study used a medical record case series of all ID Us seeking initial care for soft tissue infections at an urban, public emergency department from November 1999 through April 2000. Initial care for IDU-related soft tissue infections was sought by 242 patients. Most were male (63.6%), Caucasian (69.4%) and without health insurance (S2.0%), and most bad abscesses (72.3%). All patients with only cellulitis bad arm or leg infections, while most abscesses were arm, deltoid, or buttock infections (81.1%). Forty percent of the patients were hospitalized, and 44.3 % of the hospitalizations were for 3 or more days. Patients with only cellulitis were more likely to be hospitalized compared to those with abscesses. Among those with abscesses, deltoid abscesses were 5.2 times more likely to receive an operating room procedure compared to other abscess locations. IDUs with cellulitis and deltoid abscesses commonly required inpatient care and operating room procedures. The morbidity associated with such infections and the intensive use of hospital services needed to treat these infections provide strong rationale for the development of preventive interventions and improved care for this neglected clinical problem. C1 VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Takahashi, TA (reprint author), VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, 1660 S Columbian Way.S-111-GIMC, Seattle, WA 98108 USA. FU NIAAA NIH HHS [K23AA00313] NR 24 TC 21 Z9 21 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1099-3460 J9 J URBAN HEALTH JI J. Urban Health PD MAR PY 2003 VL 80 IS 1 BP 127 EP 136 DI 10.1093/jurban/jtg127 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 655KK UT WOS:000181550800014 PM 12612102 ER PT J AU Freedland, SJ Kane, CJ Presti, JC Terris, MK Amling, CL Dorey, F Aronson, WJ AF Freedland, SJ Kane, CJ Presti, JC Terris, MK Amling, CL Dorey, F Aronson, WJ TI Comparison of preoperative prostate specific antigen density and prostate specific antigen for predicting recurrence after radical prostatectomy: Results from the search data base SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; prostatectomy; prostate-specific antigen; tumor markers, biological ID SEXTANT BIOPSIES; EXTRACAPSULAR EXTENSION; CANCER; PERCENTAGE; PSA AB Purpose: Prostate specific antigen (PSA) density based on the surgical weight of the radical prostatectomy specimen has previously been shown to be an independent predictor of biochemical recurrence after radical prostatectomy. We determined whether preoperative PSA density calculated using transrectal ultrasound prostate volume was a better predictor of advanced pathological findings or biochemical recurrence after radical prostatectomy relative to PSA. Materials and Methods: We examined 552 men from the newly established Shared Equal Access Regional Cancer Hospital data base of men treated with radical prostatectomy at equal access medical centers to determine whether preoperative PSA density was a significant predictor of an adverse pathological condition or PSA recurrence after radical prostatectomy. Models using PSA density were compared with models using PSA to determine whether PSA density improved risk stratification relative to PSA. PSA density was examined as a continuous and a categorical variable using cutoffs to separate patients into groups at different risks for PSA failure. Results: PSA density and PSA were significant predictors of adverse pathological findings on univariate analysis. Using PSA density in the multivariate model resulted in slightly better but statistically insignificant improvement in prediction of positive surgical margins (p = 0.134) and extracapsular extension (p = 0.771) relative to using PSA in the model. Neither PSA nor PSA density were significant independent predictors of seminal vesicle invasion. Area under the ROC curves for predicting biochemical recurrence for PSA and PSA density were not significantly different (0.589 and 0.58, respectively, p = 0.691). On separate multivariate analyses PSA density and PSA were significant independent predictors of biochemical failure. The multivariate model using PSA density provided only slight improvement in risk assessment relative to the model using PSA (index C = 0.589 and 0.581, respectively). To determine whether using PSA density as a categorical variable would result in improved prognostication we evaluated PSA density to determine the cutoff points that would provide the greatest risk stratification. PSA density cutoffs of less than 0.4, 0.4 to 1 and greater than 1 ng./ml./cc separated patients into 3 distinct groups at increasing risk for biochemical failure (p < 0.001). While these cutoffs provided better risk stratification than when PSA density was examined as a continuous variable (index C = 0.684 versus 0.58), they provided only marginal improvement relative to the standard PSA cutoffs of less than 10, 10 to 20 and greater than 20 ng./ml. (index C = 0.676). Conclusions: The use of preoperative PSA density relative to PSA provided only slight improvement for predicting adverse pathological findings and biochemical recurrence after radical prostatectomy. The minimal and statistically insignificant improvement in preoperative risk assessment provided by PSA density does not justify the time and effort necessary to calculate this value. C1 Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Biostat, Los Angeles, CA USA. Vet Adm Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. Univ Calif San Francisco, Dept Urol, Sch Med, San Francisco, CA 94143 USA. Stanford Univ, Sch Med, Dept Urol, Stanford, CA 94305 USA. San Diego Naval Hosp, Dept Urol, San Diego, CA USA. Med Coll Georgia, Div Urol, Augusta, GA 30912 USA. RP Kane, CJ (reprint author), Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA 90024 USA. OI Terris, Martha/0000-0002-3843-7270 NR 16 TC 27 Z9 27 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAR PY 2003 VL 169 IS 3 BP 969 EP 973 DI 10.1097/01.ju.0000051400.85694.bb PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 644KM UT WOS:000180916500039 PM 12576824 ER PT J AU Barry, MJ AF Barry, MJ TI Indwelling ureteral stents: Evaluation of symptoms, quality of life and utility - Editorial comment SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Med Pract Evaluat Ctr, Boston, MA 02114 USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Med Pract Evaluat Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAR PY 2003 VL 169 IS 3 BP 1069 EP 1069 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 644KM UT WOS:000180916500064 ER PT J AU Harris, JR Fan, CM Geller, SC Brewster, DC Greenfield, AJ Santilli, JG Waltman, AC AF Harris, JR Fan, CM Geller, SC Brewster, DC Greenfield, AJ Santilli, JG Waltman, AC TI Renal perfusion defects after endovascular repair of abdominal aortic aneurysms SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article DE aneurysm, abdominal; aneurysm, therapy; kidney, blood supply ID SURGERY AB PURPOSE: To determine the prevalence of new renal perfusion defects and the association of these events with aneurysm neck atheroma during endovascular stent-graft repair of abdominal aortic aneurysm (AAA). MATERIALS AND METHODS: A retrospective review was performed of 50 patients who underwent AAA repair with bifurcated endovascular stent-grafts without suprarenal components between June 1998 and May 1999. Pre- and postprocedural computed tomographic (CT) angiograms were reviewed to determine the prevalence of new renal perfusion defects. The percent volume of atheroma of the aneurysm neck was determined by three-dimensional volumetric reformation and correlated with prevalence of new postprocedural renal perfusion defects. Follow-up CT angiography was performed between 6 months and 2 years after the procedure and used to evaluate the presence of residual defects and interval changes. RESULTS: Of 50 subjects, 18% (n = 9) had new perfusion defects presumed to be embolic in origin. Follow-up was available for four patients: scarring and cortical thinning consistent with infarction developed in two, whereas the defects resolved in the other two. Analysis of aneurysm neck revealed an average percentage of atheroma of 32% and a range of 0%-73%. In subjects with greater than or equal to40% neck atheroma, the prevalence of new renal perfusion defects was 45.4% (five of 11), compared to 10.3% (four of 39) in subjects with <40% neck atheroma. This difference was significant (P = .0170). CONCLUSIONS: In this series, the frequency of renal embolic events associated with AAA endovascular repair was 18%. Prevalence of renal embolic perfusion defects was shown to correlate with volume of aneurysm neck atheroma. C1 Massachusetts Gen Hosp, Dept Vasc Radiol, Boston, MA 02114 USA. RP Harris, JR (reprint author), 314 Amory St 3, Jamaica Plain, MA 02130 USA. NR 11 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD MAR PY 2003 VL 14 IS 3 BP 329 EP 333 DI 10.1097/01.RVI.0000058421.01661.c5 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 656GZ UT WOS:000181601400007 PM 12631637 ER PT J AU Zhu, WH Han, JH Nicosia, RF AF Zhu, WH Han, JH Nicosia, RF TI Requisite role of p38 MAPK in mural cell recruitment during angiogenesis in the rat aorta model SO JOURNAL OF VASCULAR RESEARCH LA English DT Article DE angiogenesis; p38 MAPK; mural cells; pericytes; angiopoietin-1 ID ACTIVATED PROTEIN-KINASE; SMOOTH-MUSCLE CELLS; GROWTH-FACTOR; TIE2 RECEPTOR; PDGF-B; ANGIOPOIETIN-1; PERICYTE; DIFFERENTIATION; PROLIFERATION; INHIBITION AB During the early stage of angiogenesis, neovascular sprouts are composed primarily of endothelial cells. As they mature, microvessels acquire a coating of mural cells, which are critical for the development and maintenance of a functional vasculature. Though growth factor regulation of mural cell recruitment has been extensively investigated, the intracellular signaling events involved in this process remain poorly understood. Among the intracellular kinases implicated in angiogenesis, the p38 MAPK has been shown to transduce signals critical for vascular remodeling and maturation. The rat aorta model of angiogenesis was used to further investigate the role of this signaling pathway in the recruitment of mural cells during angiogenesis. The p38 MAPK inhibitor SB203580 selectively blocked mural cell recruitment, resulting in the formation of naked endothelial tubes without mural cells. SB203580 inhibited angiopoietin-1-induced mural cell recruitment without influencing angiopoietin-1-stimulated endothelial sprouting. Adenoviral vector-mediated expression of a dominant negative form of p38 MAPK significantly reduced mural cell recruitment, whereas overexpression of a constitutively activated form of MKK6, an upstream activator of p38 MAPK, increased mural cell number. These results indicate that the p38 MAPK signaling pathway plays a critical role in mural cell recruitment during neovascularization and may represent a therapeutic target in angiogenesis-related disorders. Copyright (C) 2003 S. Karger AG, Basel. C1 VA Puget Sound Hlth Care Syst, Div Pathol & Lab Med, Lab S113, Seattle, WA 98108 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA USA. RP Nicosia, RF (reprint author), VA Puget Sound Hlth Care Syst, Div Pathol & Lab Med, Lab S113, 1660 S Columbian Way, Seattle, WA 98108 USA. RI Han, J/G-4671-2010 FU NHLBI NIH HHS [HL52585] NR 29 TC 26 Z9 26 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-1172 J9 J VASC RES JI J. Vasc. Res. PD MAR-APR PY 2003 VL 40 IS 2 BP 140 EP 148 DI 10.1159/000070711 PG 9 WC Physiology; Peripheral Vascular Disease SC Physiology; Cardiovascular System & Cardiology GA 694ZD UT WOS:000183804800007 PM 12808350 ER PT J AU Pan, JH Lindholt, JS Sukhova, GK Baugh, JA Henneberg, EW Bucala, R Donnelly, SC Libby, P Metz, C Shi, GP AF Pan, JH Lindholt, JS Sukhova, GK Baugh, JA Henneberg, EW Bucala, R Donnelly, SC Libby, P Metz, C Shi, GP TI Macrophage migration inhibitory factor is associated with aneurysmal expansion SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID ABDOMINAL AORTIC-ANEURYSMS; NECROSIS-FACTOR-ALPHA; SMOOTH-MUSCLE CELLS; FACTOR MIF; RHEUMATOID-ARTHRITIS; REGULATORY ROLE; EXPRESSION; LIPOPROTEIN; ACTIVATION; GROWTH AB Background. Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine released mainly from macrophages and activated lymphocytes. Both atherosclerosis and abdominal aortic aneurysm.(AAA) are inflammatory diseases tightly linked to the function of these cells. The correlation and contribution of MIF to these human diseases remain unknown, although a recent rabbit study showed expression of this cytokine in atherosclerotic lesions. Material and Methods. MIF inummohistochemistry was performed on tissue sections from five normal aortas, seven atherosclerotic carotids, and six AAAs. A group of 112 men with small AAAs (defined as 3 to 5 cm) was recruited at the time of diagnosis, had serum samples taken, and was followed annually for 1 to 5 years (mean, 2.9 years) and referred for surgery if the AAA exceeded 5 cm in diameter. Of this study group, 98 had serum MIF measured with an enzyme-linked immunosorbent assay and 61 had detectable levels. Results. In human atherosclerotic and aneurysmal lesions, MIF protein colocalized in macrophages, endothelial cells, and smooth muscle cells, but normal arteries had negligible MIF expression. Furthermore, serum-MIF levels correlated significantly with annual expansion rate (r = 0.28; P = .005), persisting after adjustment for initial AAA size, smoking habits, diastolic blood pressure, ankle blood pressure index, and age. After exclusion of 38 cases with MIF levels below the detection limit, initial AAA size was also significantly correlated with the MIF levels (r = 0.42; P = .001), persisting after adjustment for similar confounders, and the correlation coefficient with expansion rate increased to 0.42 (P = .001). Conclusion: Highly expressed MIF in macrophages, endothelial cells, and smooth muscle cells in lesions from atherosclerosis and AAA and significant association between serum MIF level and AAA initial size and AAA expansion rate in a group of patients with AAA suggest a potential involvement of this proinflammatory cytokine in the pathogenesis of these cardiovascular diseases. C1 Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Rigshosp, Dept Vasc Surg, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Leducq Ctr Cardiovasc Res, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02138 USA. Picower Inst Med Res, Manhasset, NY USA. Hosp Viborg, Dept Vasc Surg, Copenhagen, Denmark. RP Shi, GP (reprint author), Div Pulm & Crit Care Med, Surge 203,Med Ctr Way, San Francisco, CA 94143 USA. OI Lindholt, Jes/0000-0001-9536-4488; Christine, Metz/0000-0002-1013-1691; Donnelly, Seamas/0000-0001-7145-1843 FU NHLBI NIH HHS [HL 60942, HL 34636] NR 40 TC 40 Z9 42 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAR PY 2003 VL 37 IS 3 BP 628 EP 635 DI 10.1067/mva.2003.74 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 652DJ UT WOS:000181364400024 PM 12618703 ER PT J AU von Lindern, JJ Rojo, D Grovit-Ferbas, K Yeramian, C Deng, C Herbein, G Ferguson, MR Pappas, TC Decker, JM Singh, A Collman, RG O'Brien, WA AF von Lindern, JJ Rojo, D Grovit-Ferbas, K Yeramian, C Deng, C Herbein, G Ferguson, MR Pappas, TC Decker, JM Singh, A Collman, RG O'Brien, WA TI Potential role for CD63 in CCR5-mediated human immunodeficiency virus type 1 infection of macrophages SO JOURNAL OF VIROLOGY LA English DT Article ID CD4(+) T-CELLS; MONONUCLEAR PHAGOCYTES; CHEMOKINE RECEPTORS; MEMBRANE CHOLESTEROL; SYNCYTIUM FORMATION; HIV-1 ENTRY; LIPID RAFTS; IN-VIVO; HLA-DR; FUSION AB Macrophages and CD4(+) lymphocytes are the principal target cells for human immunodeficiency virus type 1 (HIV-1) infection, but the molecular details of infection may differ between these cell types. During studies to identify cellular molecules that could be involved in macrophage infection, we observed inhibition of HIV-1 infection of macrophages by monoclonal antibody (MAb) to the tetraspan transmembrane glycoprotein CD63. Pretreatment of primary macrophages with anti-CD63 MAb, but not MAbs to other macrophage cell surface tetraspanins (CD9, CD81, and CD82), was shown to inhibit infection by several R5 and dualtropic strains, but not by X4 isolates. The block to productive infection was postfusion, as assessed by macrophage cell-cell fusion assays, but was prior to reverse transcription, as determined by quantitative PCR assay for new viral DNA formation. The inhibitory effects of anti-CD63 in primary macrophages could not be explained by changes in the levels of CD4, CCR5, or beta-chemokines. Infections of peripheral blood lymphocytes and certain cell lines were unaffected by treatment with anti-CD63, suggesting that the role of CD63 in HIV-1 infection may be specific for macrophages. C1 Univ Texas, Med Branch, Div Infect Dis, Dept Microbiol & Immunol, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Internal Med, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Pathol, Galveston, TX 77555 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, AIDS Inst, Los Angeles, CA 90095 USA. Univ Alabama, Howard Hughes Med Inst, Birmingham, AL 35294 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. RP O'Brien, WA (reprint author), Univ Texas, Med Branch, Div Infect Dis, Dept Microbiol & Immunol, 301 Univ Blvd, Galveston, TX 77555 USA. FU NHLBI NIH HHS [R01 HL088999, R01 HL088999-05]; NIAID NIH HHS [T32 AI007388, AI35502, AI46250, AI52041, R01 AI035502, R01 AI052041, R56 AI052041, T32/AI07388]; NINDS NIH HHS [NS27405, P01 NS027405] NR 61 TC 50 Z9 52 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2003 VL 77 IS 6 BP 3624 EP 3633 DI 10.1128/JVI.77.6.3624-3633.2003 PG 10 WC Virology SC Virology GA 652FZ UT WOS:000181370300029 PM 12610138 ER PT J AU Miller, KK AF Miller, KK TI Mechanisms by which nutritional disorders cause reduced bone mass in adults SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Article; Proceedings Paper CT Symposium on Nutrition and Womens Health CY JUN 14-15, 2002 CL BOSTON, MASSACHUSETTS SP Harvard Med Sch, Div Nutrit ID INFLAMMATORY BOWEL-DISEASE; GLUTEN-FREE DIET; ANOREXIA-NERVOSA; MINERAL DENSITY; SECONDARY AMENORRHEA; DISTANCE RUNNERS; CELIAC-DISEASE; WOMEN; OSTEOPOROSIS; OSTEOPENIA AB Nutritional disorders that cause bone loss in adults include disordered eating behaviors (female athlete triad and anorexia nervosa), gastrointestinal diseases (celiac sprue, inflammatory bowel disease, and other malabsorption syndromes), alcoholism, and hypervitaminosis A. These disorders exert their effects on bone through a number of mechanisms, including estrogen deficiency. Deficiencies of anabolic hormones may also be important, including insulin-like growth factor I (IGF-I), a nutritionally regulated bone trophic factor. In addition, low weight itself is a risk factor for bone loss and decreased bone formation. Reduced calcium and vitamin D availability, with resultant secondary hyperparathyroidism, is another important mechanism of bone loss in nutritional disorders. This review discusses nutritional causes of reduced bone mass in adults and how nutritional disorders exert deleterious effects on the skeleton. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. RP Miller, KK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR01066-25S1, M01-RR01066]; NIDDK NIH HHS [R01-DK52625] NR 36 TC 12 Z9 13 U1 3 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PD MAR PY 2003 VL 12 IS 2 BP 145 EP 150 DI 10.1089/154099903321576538 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 670MR UT WOS:000182413000007 PM 12737712 ER PT J AU Intano, GW Cho, EJ McMahan, CA Walter, CA AF Intano, GW Cho, EJ McMahan, CA Walter, CA TI Age-related base excision repair activity in mouse brain and liver nuclear extracts SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID DNA-POLYMERASE-BETA; OLD MICE; GENE; EXPRESSION; CELLS; MUTATION; PROTEIN; DAMAGE; SITES; RECONSTITUTION AB To assess DNA repair activity relative to age, in vitro base excision repair assays were performed using brain and liver nuclear extracts prepared from mice of various ages. An 85% decline in repair activity was observed in brain nuclear extracts and a 50% decrease in liver nuclear extracts prepared from old mice compared with 6-day-old mice. Brain nuclear extracts prepared from old mice showed a decreased abundance of DNA polymerase-beta, but the addition of purified protein did not restore base excision repair activity. Abundances of other tested base excision repair proteins did not change relative to age. The conclusion is that, during aging, a decline in DNA repair could contribute to increased levels of DNA damage and mutagenesis. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. Audie L Murphy Hosp, S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Walter, CA (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, Mail Code 7762,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NIA NIH HHS [AG19360, AG00205, AG13560, AG14674]; NIEHS NIH HHS [ESO9136] NR 44 TC 53 Z9 53 U1 0 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAR PY 2003 VL 58 IS 3 BP 205 EP 211 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 653QA UT WOS:000181447200002 PM 12634285 ER PT J AU Schnelle, JF AF Schnelle, JF TI Guest editorial - Improving nursing home quality assessment: Capturing the voice of cognitively impaired elders SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material ID RESIDENTS; SATISFACTION; CARE C1 Univ Calif Los Angeles, Dept Med, Div Geriatr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Reseda, CA USA. Jewish Home Aging, Borun Ctr Gerontol Res, Reseda, CA USA. Vet Adm Greater Los Angeles Healthcare Syst, Sepulveda Geriatr Res Educ & Clin Ctr, Sepulveda, CA USA. RP Schnelle, JF (reprint author), Univ Calif Los Angeles, Dept Med, Div Geriatr, Los Angeles, CA 90024 USA. NR 11 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAR PY 2003 VL 58 IS 3 BP 238 EP 239 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 653QA UT WOS:000181447200007 PM 12634290 ER PT J AU Han, WK Choi, HK Roth, RM Mccluskey, RT Niles, JL AF Han, WK Choi, HK Roth, RM Mccluskey, RT Niles, JL TI Serial ANCA titers: Useful tool for prevention of relapses in ANCA-associated vasculitis SO KIDNEY INTERNATIONAL LA English DT Article DE ANCA-associated vasculitis; ANCA titers; relapses; MPO-ANCA; PRE-ANCA; Birmingham Vasculitis Activity Score ID ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; WEGENERS-GRANULOMATOSIS; SYSTEMIC VASCULITIS; DISEASE-ACTIVITY; CRESCENTIC GLOMERULONEPHRITIS; FOLLOW-UP; AUTOANTIBODIES; DIAGNOSIS; MYELOPEROXIDASE; METAANALYSIS AB Background. The value of measuring serial antineutrophil cytoplasmic autoantibody (ANCA) titers in guiding therapy among patients with ANCA-associated vasculitis is controversial. Methods. We measured serial titers of proteinase 3 (PR3)- and myeloperoxidase (MPO)-ANCA by antigen-specific enzyme-linked immunosorbent assays (ELISAs) in 48 patients with ANCA-associated vasculitis who were followed up during remission at the Massachusetts General Hospital from 1990 through 2000 (mean follow-up, 46.2 months). We retrospectively assessed disease activity by Birmingham Vasculitis Activity Score (BVAS). Results. We found 21 episodes of fourfold or greater ANCA titer rises in 17 patients who were in complete remission (BVAS = 0). Among eight patients who had 10 such titer rises and were not given increased immunosuppression, (group I), all suffered relapses after each episode (mean interval, 5.8 months), whereas among 11 patients, each with one titer rise, who received preemptive increased immunosuppression, (group II), only two relapses occurred, at 3 and 6 months. The difference in the cumulative incidence of relapses in a 1-year period between the two groups was 82% (P = 0.0002). Changes in ANCA titers were also used to help guide therapy in the other 31 patients in the study; patients with slight titer rises often received incremental increases in immunosuppression, whereas those with falling titers received incremental decreases. The overall outcome in the entire group was favorable; 46 patients were alive at the end of the study; two died of unrelated diseases. Conclusion. Serial measurements of PR3- and MPO-ANCA titers in patients with ANCA-associated vasculitis during remission can help predict relapses, and preemptive increases in immunosuppression following fourfold titer rises reduces the risk of relapses. Moreover, adjustment of immunosuppression based on lesser titer changes appears to result in a favorable outcome. C1 Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Niles, JL (reprint author), 100 Charles River,Plaza Suite 701, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK10036-01] NR 35 TC 77 Z9 86 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAR PY 2003 VL 63 IS 3 BP 1079 EP 1085 DI 10.1046/j.1523-1755.2003.00821.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 643FX UT WOS:000180852200031 PM 12631091 ER PT J AU Kondo, S Stevens, J AF Kondo, S Stevens, J TI IACUC should "get tough" SO LAB ANIMAL LA English DT Editorial Material C1 Univ Hawaii, Lab Anim Serv, Honolulu, HI 96822 USA. Univ Colorado, Sch Med, Denver, CO USA. Denver VAMC, Denver, CO USA. RP Kondo, S (reprint author), Univ Hawaii, Lab Anim Serv, Honolulu, HI 96822 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD MAR PY 2003 VL 32 IS 3 BP 21 EP 21 DI 10.1038/laban0303-21 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 651EX UT WOS:000181308500004 ER PT J AU Van Cott, EM Laposata, M AF Van Cott, EM Laposata, M TI Algorithms for hypercoagulation testing SO LABORATORY MEDICINE LA English DT Editorial Material ID ACTIVATED PROTEIN-C; DEEP-VEIN THROMBOSIS; POOR ANTICOAGULANT RESPONSE; COAGULATION-FACTOR-V; VENOUS THROMBOSIS; INHERITED THROMBOPHILIA; LEIDEN THROMBOPHILIA; HEALTHY POPULATION; RISK FACTOR; DEFICIENCY C1 Massachusetts Gen Hosp, Dept Pathol, Clin Labs, Boston, MA 02114 USA. RP Van Cott, EM (reprint author), Massachusetts Gen Hosp, Dept Pathol, Clin Labs, Boston, MA 02114 USA. NR 33 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0007-5027 J9 LAB MED JI Lab. Med. PD MAR PY 2003 VL 34 IS 3 BP 216 EP + DI 10.1309/VPRJ9KYAC8X5P3FG PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 649QZ UT WOS:000181220600018 ER PT J AU Carr, A Emery, S Law I Puls, R Lundgren, JD Powderly, WG Carr, B Cooper, DA Grinspoon, S Ioannidis, J Lewis, R Law, M Lichtenstein, K Murray, J Pizzuti, D Rozenbaum, W Schambelan, M Moore, A Miller, J AF Carr, A Emery, S Law, I Puls, R Lundgren, JD Powderly, WG Carr, B Cooper, DA Grinspoon, S Ioannidis, J Lewis, R Law, M Lichtenstein, K Murray, J Pizzuti, D Rozenbaum, W Schambelan, M Moore, A Miller, J CA HIV Lipodystrophy Case Definition TI An objective case definition of lipodystrophy in HIV-infected adults: a case-control study SO LANCET LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; REVERSE-TRANSCRIPTASE INHIBITORS; PROTEASE INHIBITORS; PREADIPOCYTE DIFFERENTIATION; METABOLIC ABNORMALITIES; INSULIN-RESISTANCE; COHORT; RISK AB Background Lipodystrophy (peripheral lipoatrophy, central fat accumulation, and lipomatosis) is a common and disfiguring problem in adult patients with HIV-1 infection on antiretrovirals. However, an objective, validated definition of the disorder does not exist. We aimed to develop an objective, sensitive, specific, and broadly applicable case definition of HIV lipodystrophy. Methods In a case-control study, 1081 consecutive, HIV-infected, adult outpatients (261 [15%] women) without active AIDS were recruited from 32 sites worldwide. We classed patients with at least one moderate or severe subjective lipodystrophic feature, identified by lipodystrophy-specific physical examination and patient questionnaire, and apparent to both doctor and patient as cases (n=417). We classed patients with no such feature as controls (n=371), and patients without a clear diagnosis as non-assigned. We used objective clinical, metabolic, and body composition measurements to construct a logistic regression model with a subset of randomly selected cases and controls. The model was validated in the remaining patients. Findings A model including age, sex, duration of HIV infection, HIV disease stage, waist to hip ratio, anion gap, serum HDL cholesterol concentration, trunk to peripheral fat ratio, percentage leg fat, and intra-abdominal to extra-abdominal fat ratio had 79% (95% CI 70-85) sensitivity and 80% (95% Cl 71-87) specificity for diagnosis of lipodystrophy. Models that incorporated only clinical, or only clinical and metabolic variables had lower sensitivity and specificity than the inclusive model. Models for lipoatrophy, fat accumulation, and lipomatosis could not be developed since pure phenotypes occurred in fewer than 10% of patients with clinical diagnoses of these disorders. Interpretation Our objective case definition of HIV-associated lipodystrophy should improve assessment of lipodystrophy prevalence, risk factors, and pathogenesis; prevention and treatment approaches; and assist in diagnosis. C1 St Vincents Hosp, HIV Immunol & Infect Dis Clin Serv Unit, Sydney, NSW 2010, Australia. Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. Hvidovre Univ Hosp, Copenhagen, Denmark. Washington Univ, Sch Med, St Louis, MO USA. Forum Collaborat HIV Res, Baltimore, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Ioannina, GR-45110 Ioannina, Greece. Agouron Pharmaceut, San Diego, CA USA. HIV Outpatient Study Ctr Dis Control & Prevent, Denver, CO USA. US FDA, US Dept HHS, Washington, DC 20204 USA. Bristol Myers Squibb Co, Princeton, NJ USA. Hop Rothschild, F-75571 Paris, France. Agence Natl Res SIDA, Paris, France. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Carr, A (reprint author), St Vincents Hosp, HIV Immunol & Infect Dis Clin Serv Unit, Sydney, NSW 2010, Australia. EM acarr@stvincents.com.au RI Ioannidis, John/G-9836-2011; Puls, Rebekah/A-3992-2013; OI Lundgren, Jens/0000-0001-8901-7850; Rozenbaum, Willy/0000-0003-1975-3566 NR 32 TC 307 Z9 316 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD MAR 1 PY 2003 VL 361 IS 9359 BP 726 EP 735 DI 10.1016/S0140-6736(03)12656-6 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 649WY UT WOS:000181232000007 PM 12620736 ER PT J AU Stone, RM AF Stone, RM TI Induction and postremission therapy: new agents SO LEUKEMIA LA English DT Article; Proceedings Paper CT Acute Leukemia Forum CY APR 19, 2002 CL SAN FRANCISCO, CALIFORNIA ID ACUTE MYELOID-LEUKEMIA; TYROSINE KINASE INHIBITOR; COLONY-STIMULATING FACTOR; PHASE-I TRIAL; MYELODYSPLASTIC SYNDROME; MULTIDRUG-RESISTANCE; BCL-2 ANTISENSE; FARNESYLTRANSFERASE INHIBITOR; MYELOPROLIFERATIVE DISEASE; CELLS C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Adult Leukemia Program, Boston, MA 02115 USA. RP Stone, RM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Adult Leukemia Program, 44 Binney St,Room D-840, Boston, MA 02115 USA. NR 45 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAR PY 2003 VL 17 IS 3 BP 496 EP 498 DI 10.1038/sj.leu.2402864 PG 3 WC Oncology; Hematology SC Oncology; Hematology GA 660GK UT WOS:000181825300004 PM 12646937 ER PT J AU Stone, ME AF Stone, ME TI No more periods?: The risks of menstrual suppression and other cutting-edge issues in women's reproductive health. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp 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 MAR 1 PY 2003 VL 128 IS 4 BP 110 EP 110 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 673WN UT WOS:000182603400127 ER PT J AU Refaai, MA Nguyen, PN Cluette-Brown, JE Laposata, M AF Refaai, MA Nguyen, PN Cluette-Brown, JE Laposata, M TI Ethyl arachidonate is the predominant fatty acid ethyl ester in the brains of alcohol-intoxicated subjects at autopsy SO LIPIDS LA English DT Article ID ETHANOL INTAKE; POSTMORTEM MARKERS; LINOLENIC ACID; ADIPOSE-TISSUE; LIVER; IDENTIFICATION; METABOLITES; LIPIDS; ORGANS; ABUSE AB The role of fatty acid ethyl esters (FAEF), the nonoxidative ethanol metabolites, as mediators of alcohol-induced organ damage is increasingly being recognized. FAEE are detectable in the blood and in liver and adipose tissue after ethanol ingestion, and on that basis, FAEE can be used as markers of ethanol intake. In this study, 10 samples of human brain were collected at autopsy at the Massachusetts Medical Examiner's Office and analyzed for FAEE. FAFE were isolated and quantified as mass per gram of wet weight. The blood ethanol level was also obtained in each case along with the other drugs detected in routine postmortem toxicology screening tests. Ethyl arachidonate was the predominant FAEE species in the brain, representing up to 77.4% of total FAEE in the brain. The percent age of ethyl arachidonate of the total FAEE in the brain was significantly higher than what has been found in all other organs and tissues previously analyzed. Linoleate, the precursor of arachidonate, was a poor substrate for FAEE synthesis, as the percentage of ethyl linoleate of the total FAEE content was extremely low. Thus, this reflects preferred incorporation of arachidonate into newly synthesized FAEE in the brain. Since arachidonate is derived from linoleate, which is depleted in FAFE while arachidonate is enriched, the synthesis of FAFE may be linked to the desaturation and elongation of linoleate to arachidonate. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02115 USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Clin Labs, Room 235,Gray Bldg, Boston, MA 02114 USA. NR 22 TC 6 Z9 6 U1 2 U2 2 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0024-4201 J9 LIPIDS JI Lipids PD MAR PY 2003 VL 38 IS 3 BP 269 EP 273 DI 10.1007/s11745-003-1060-6 PG 5 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 680CZ UT WOS:000182959900010 PM 12784867 ER PT J AU Berner, ES Baker, CS Funkhouser, E Heudebert, GR Allison, JJ Fargason, CA Li, Q Person, SD Kiefe, CI AF Berner, ES Baker, CS Funkhouser, E Heudebert, GR Allison, JJ Fargason, CA Li, Q Person, SD Kiefe, CI TI Do local opinion leaders augment hospital quality improvement efforts? A randomized trial to promote adherence to unstable angina guidelines SO MEDICAL CARE LA English DT Article DE qpinion leaders; unstable angina; practice guidelines ID CLINICAL-PRACTICE; CARE; PHYSICIANS; INFORMATION; FEEDBACK; MANAGEMENT; DISEASE; IMPACT AB BACKGROUND. The influence of an opinion leader intervention on adherence to Unstable Angina (UA) guidelines compared with a traditional quality improvement model was investigated. RESEARCH DESIGN. A group-randomized controlled trial with 2210 patients from 21 hospitals was designed. There were three intervention arms: (1) no intervention (NI); (2) a traditional Health Care Quality Improvement Program (HCQIP); and (3) a physician opinion leader in addition to the HCQIP model (OL). Quality indicators included: electrocardiogram within 20 minutes, antiplatelet therapy within 24 hours and at discharge, and heparin and beta-blockers during hospitalization. Hospitals could determine the specific indicators they wished to target. Potential cases of UA were identified from Medicare claims data. UA confirmation was determined by a clinical algorithm based on data abstracted from medical records. Data analyses included both hospital level analysis (analysis of variance) and patient level analysis (generalized, linear models). RESULTS. The only statistically significant postintervention difference in percentage compliant was greater improvement for the OL group in the use of antiplatelet therapy at 24 hours in both hospital level (P = 0.01) and patient level analyses (P <0.05) compared with the HCQIP and NI groups. When analyses were confined to hospitals that targeted specific indicators, compared with the HCQIP hospitals, the OL hospitals showed significantly greater change in percentage compliant postintervention in both antiplatelet therapy during the first 24 hours (20.2% vs. -3.9%, P = 0.02) and heparin (31.0% vs.9.1%, P = 0.05). CONCLUSIONS. The influence of physician opinion leaders was unequivocally positive for only one of five quality indicators. To maximize adherence to best practices through physician opinion leaders, more research on how these physicians influence health care delivery in their organizations will be required. C1 Univ Alabama, Sch Hlth Related Profess, Hlth Serv Adm Dept, Birmingham, AL 35294 USA. Univ Alabama, Ctr Outcomes & Effectiveness Res & Educ, Birmingham, AL 35294 USA. Univ Alabama, Div Gen Internal Med, Birmingham, AL 35294 USA. Univ Alabama, Div Prevent Med, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Sch Med, Dept Pediat, Birmingham, AL 35294 USA. Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. Univ Alabama, Sch Publ Hlth, Dept Hlth Care Org & Policy, Birmingham, AL 35294 USA. Univ Alabama, Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. RP Berner, ES (reprint author), Univ Alabama, Sch Hlth Related Profess, Hlth Serv Adm Dept, 1530 3rd Ave S,WEBB 544, Birmingham, AL 35294 USA. OI Allison, Jeroan/0000-0003-4472-2112; Berner, Eta/0000-0003-4319-2949 NR 38 TC 45 Z9 45 U1 5 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD MAR PY 2003 VL 41 IS 3 BP 420 EP 431 DI 10.1097/00005650-200303000-00010 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 653EQ UT WOS:000181422600010 PM 12618645 ER PT J AU Dec, GW AF Dec, GW TI Digoxin remains useful in the management of chronic heart failure SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID CONVERTING ENZYME-INHIBITORS; SINUS RHYTHM; INTRAVENOUS DIGOXIN; COMBINED THERAPY; SODIUM-PUMP; DIGITALIS; WITHDRAWAL; CAPTOPRIL; DYSFUNCTION; COMBINATION AB Digoxin remains an important therapeutic option for the outpatient management of patients with chronic symptomatic heart failure caused by systolic dysfunction. Randomized control trials have convincingly confirmed its efficacy in improving ejection fraction, improving submaximal exercise capacity, and decreasing heart failure hospitalizations. The Digitalis Investigation Group trial confirmed its safety during long-term use. Repeat assessment of drug levels is unnecessary in most patients. Current consensus guidelines re;commend its use for patients in whom NYHA class II-IV symptoms persist despite conventional therapy with diuretics, angiotensin-converting enzyme inhibitors, and a beta-adrenergic blocker. C1 Massachusetts Gen Hosp, Heart Failure & Transplantat Unit, Boston, MA 02114 USA. RP Dec, GW (reprint author), Massachusetts Gen Hosp, Heart Failure & Transplantat Unit, 55 Fruit St, Boston, MA 02114 USA. NR 64 TC 23 Z9 25 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAR PY 2003 VL 87 IS 2 BP 317 EP + DI 10.1016/S0025-7125(02)00172-4 PG 23 WC Medicine, General & Internal SC General & Internal Medicine GA 662JB UT WOS:000181942600003 PM 12693728 ER PT J AU Hajjar, RJ Huq, F Matsui, T Rosenzweig, A AF Hajjar, RJ Huq, F Matsui, T Rosenzweig, A TI Genetic editing of dysfunctional myocardium SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID RECOMBINANT ADENOASSOCIATED VIRUS; STAGE HEART-FAILURE; GROWTH-FACTOR-I; SARCOPLASMIC-RETICULUM CA2+-ATPASE; RABBIT VENTRICULAR MYOCYTES; DILATED CARDIOMYOPATHY; NA+-CA2+ EXCHANGER; CARDIAC MYOCYTES; TRANSGENIC MICE; CELL-DEATH AB Improvements in vector technology, cardiac gene delivery, and, most importantly, our understanding of the pathogenesis of heart failure, prompt consideration of the possibility of gene therapy for heart failure at this time. We will review recent advances in gene transfer and examine several potential targets for therapeutic intervention in heart failure. Gene transfer provides not only a potential therapeutic modality but also an approach to identifying and validating molecular targets. Bridging the gap between basic investigative studies and clinical gene therapy remains a daunting challenge. Technologic advances and emerging insights into the pathogenesis of heart failure, however, prompt cautious optimism for the future. C1 Massachusetts Gen Hosp East, Cardiovasc Res Ctr, Program Cardiovasc Gene Therapy, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rosenzweig, A (reprint author), Massachusetts Gen Hosp East, Cardiovasc Res Ctr, Program Cardiovasc Gene Therapy, 114 16th St,Room 2600, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL04250, HL59521, HL61557, HL50361, HL57623] NR 89 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 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAR PY 2003 VL 87 IS 2 BP 553 EP + DI 10.1016/S0025-7125(02)00175-X PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 662JB UT WOS:000181942600014 PM 12693739 ER PT J AU Wu, T Stewart, A Stanton, M McCauley, T Phillips, W Kopans, DB Moore, RH Eberhard, JW Opsahl-Ong, B Niklason, L Williams, MB AF Wu, T Stewart, A Stanton, M McCauley, T Phillips, W Kopans, DB Moore, RH Eberhard, JW Opsahl-Ong, B Niklason, L Williams, MB TI Tomographic mammography using a limited number of low-dose cone-beam projection images SO MEDICAL PHYSICS LA English DT Article DE digital mammography; computed tomography; low-dose imaging; tomosynthesis; cone-beam ID DIGITAL MAMMOGRAPHY; RECONSTRUCTION TECHNIQUES; TRANSMISSION TOMOGRAPHY; COMPUTED-TOMOGRAPHY; ORDERED SUBSETS; ALGORITHM; DETECTOR; LIKELIHOOD; CT AB A method is described for using a limited number (typically 10-50) of low-dose radiographs to reconstruct the three-dimensional (3D) distribution of x-ray attenuation in the breast. The method uses x-ray cone-beam imaging, an electronic digital detector, and constrained nonlinear iterative computational techniques. Images are reconstructed with high resolution in two dimensions and lower resolution in the third dimension. The 3D distribution of attenuation that is projected into one image in conventional mammography can be separated into many layers (typically 30-80 1-mm-thick layers, depending on breast thickness), increasing the conspicuity of features that are often obscured by overlapping structure in a single-projection view. Schemes that record breast images at nonuniform angular increments, nonuniform image exposure, and nonuniform detector resolution are investigated in order to reduce the total x-ray exposure necessary to obtain diagnostically useful 3D reconstructions, and to improve the quality of the reconstructed images for a given exposure. The total patient radiation dose can be comparable to that used for a standard two-view mammogram. The method is illustrated with images from mastectomy specimens, a phantom, and human volunteers. The results show how image quality is affected by various data-collection protocols. (C) 2003 American Association of Physicists in Medicine. C1 Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02454 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Gen Elect Global Res, Niskayuna, NY 12309 USA. Univ Virginia, Charlottesville, VA 22908 USA. RP Wu, T (reprint author), Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02454 USA. FU NCI NIH HHS [CA69452, CA66232] NR 37 TC 232 Z9 236 U1 2 U2 20 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAR PY 2003 VL 30 IS 3 BP 365 EP 380 DI 10.1118/1.1543934 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 656AX UT WOS:000181587500012 PM 12674237 ER PT J AU Greendale, GA Huang, MH Wang, Y Finkelstein, JS Danielson, ME Sternfeld, B AF Greendale, GA Huang, MH Wang, Y Finkelstein, JS Danielson, ME Sternfeld, B TI Sport and home physical activity are independently associated with bone density SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE bone density; physical activity; women; menopause; ethnicity ID MINERAL DENSITY; WOMEN; MASS; OSTEOPOROSIS; QUESTIONNAIRE; DETERMINANTS; FRACTURE AB Purpose: To study the relations between four domains of physical activity-sport, home, work, and active living-and bone mineral density (BMD). Methods: Baseline data from African-American (N = 544), Caucasian (N = 1044), Chinese (N = 230), and Japanese (N = 239) participants, aged 42-52 yr, from the study of Women's Health Across the Nation were analyzed. BMD was measured with Hologic 2000 or 4500A densitometers. Physical activity was assessed with the Kaiser Physical Activity Scale, which rates each domain of activity between 1 (low) and 5 (high). Multiply adjusted linear regression models were used to estimate the relations between each activity domain and BMD. Results: The mean and median values of sport, home, work, and active living each approximated the midpoint of the scale and did not differ substantially among ethnic groups. Scores for each domain of activity were not highly correlated, with r values ranging between -0.03 and 0.33. Independent of age, body mass index, ethnic group, alcohol use, dietary calcium, smoking, menopause status, SWAN site, and other domains of physical activity, higher sport activity was statistically significantly associated with greater BMD at the lumbar spine (P = 0.008), femoral neck (P = 0.0002), and total hip (P < 0.0001). More home physical activity was associated with higher BMD at the spine (P = 0.049) and femoral neck (P = 0.008). Neither work physical activity nor active living was related to BMD at any bone site. Conclusions: These results highlight the need to consider domain-specific physical activity in relation to health outcomes in women. C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, Los Angeles, CA 90095 USA. Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Sch Med, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Hlth Equ Res & Promot, Sch Med, Pittsburgh, PA USA. Kaiser Permanente, Div Res, Dept Epidemiol & Biostat, Oakland, CA USA. RP Greendale, GA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Geriatr, 10945 Le Conte Ave,Suite 2339, Los Angeles, CA 90095 USA. FU NIA NIH HHS [U01 AG12495, U01 AG12505, U01 AG12531, U01 AG12535, U01 AG12539, U01 AG12546, U01 AG12553, U01 AG12554]; NIDDK NIH HHS [K24 DK02759]; NINR NIH HHS [U01 NR04061]; PHS HHS [U01 A12539] NR 36 TC 15 Z9 18 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAR PY 2003 VL 35 IS 3 BP 506 EP 512 DI 10.1249/01.MSS.0000056725.64347.C9 PG 7 WC Sport Sciences SC Sport Sciences GA 652NZ UT WOS:000181386400019 PM 12618583 ER PT J AU Lei, EP Stern, CA Fahrenkrog, B Krebber, H Moy, TI Aebi, U Silver, PA AF Lei, EP Stern, CA Fahrenkrog, B Krebber, H Moy, TI Aebi, U Silver, PA TI Sac3 is an mRNA export factor that localizes to cytoplasmic fibrils of nuclear pore complex SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID MESSENGER-RNA EXPORT; ATTACHED INTRANUCLEAR FILAMENTS; HNRNP-LIKE PROTEINS; SACCHAROMYCES-CEREVISIAE; POLY(A)(+) RNA; RIBOSOMAL-SUBUNIT; BINDING PROTEIN; IN-VIVO; FUNCTIONAL-CHARACTERIZATION; MOLECULAR ARCHITECTURE AB In eukaryotes, mRNAs are transcribed in the nucleus and exported to the cytoplasm for translation to occur. Messenger RNAs complexed with proteins referred to as ribonucleoparticles are recognized for nuclear export in part by association with Mex67, a key Saccharomyces cerevisiae mRNA export factor and homolog of human TAP/NXF1. Mex67, along with its cofactor Mtr2, is thought to promote ribonucleoparticle translocation by interacting directly with components of the nuclear pore complex (NPC). Herein, we show that the nuclear pore-associated protein Sac3 functions in mRNA export. Using a mutant allele of MTR2 as a starting point, we have identified a mutation in SAC3 in a screen for synthetic lethal interactors. Loss of function of SAC3 causes a strong nuclear accumulation of mRNA and synthetic lethality with a number of mRNA export mutants. Furthermore, Sac3 can be coimmunoprecipitated with Mex67, Mtr2, and other factors involved in mRNA export. Immunoelectron microscopy analysis shows that Sac3 localizes exclusively to cytoplasmic fibrils of the NPC. Finally, Mex67 accumulates at the nuclear rim when SAC3 is mutated, suggesting that Sac3 functions in Mex67 translocation through the NPC. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Basel, ME Muller Inst Struct Biol, Biozentrum, CH-4056 Basel, Switzerland. RP Silver, PA (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RI Fahrenkrog, Birthe/D-5840-2011; OI Fahrenkrog, Birthe/0000-0003-4080-9413 NR 68 TC 46 Z9 46 U1 2 U2 3 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAR PY 2003 VL 14 IS 3 BP 836 EP 847 DI 10.1091/mbc.E02-08-0520 PG 12 WC Cell Biology SC Cell Biology GA 655XV UT WOS:000181578700002 PM 12631707 ER PT J AU Porter, D Lahti-Domenici, J Keshaviah, A Bae, YK Argani, P Marks, J Richardson, A Cooper, A Strausberg, R Riggins, GJ Schnitt, S Gabrielson, E Gelman, R Polyak, K AF Porter, D Lahti-Domenici, J Keshaviah, A Bae, YK Argani, P Marks, J Richardson, A Cooper, A Strausberg, R Riggins, GJ Schnitt, S Gabrielson, E Gelman, R Polyak, K TI Molecular markers in ductal carcinoma in situ of the breast SO MOLECULAR CANCER RESEARCH LA English DT Article ID MAMMARY EPITHELIAL-CELLS; GENE-EXPRESSION; SERIAL ANALYSIS; CLUSTER-ANALYSIS; HUMAN EPIDERMIS; PROTEIN; PSORIASIN; CLONING; CANCER; PROGRESSION AB Gene expression patterns in ductal carcinoma in situ (DCIS), and in invasive, and metastatic breast tumors were determined using serial analysis of gene expression (SAGE). We used mRNA in situ hybridization to examine gene expression at the cellular level and immunohistochemistry on tissue microarrays to determine association between gene expression patterns and histopathologic characteristics of the tumors. We found that that the most dramatic transcriptome change occurs at the normal to DCIS transition, while there is no clear universal "in situ" or "invasive" tumor molecular signature. From the 16,430 transcripts analyzed, we identified only 5 and 11 that were preferentially up-regulated in DCIS and invasive tumors, respectively. The majority of invasive cancer specific SAGE tags correspond to novel genes. The genes we identified may define biologically and clinically meaningful subgroups of DCIS with a high risk of progression to invasive disease. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Faulkner & Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02215 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. NCI, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,D740C, Boston, MA 02115 USA. EM Kornelia_Polyak@dfci.harvard.edu FU NCI NIH HHS [CA89393, CA88843] NR 31 TC 183 Z9 190 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD MAR PY 2003 VL 1 IS 5 BP 362 EP 375 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 660QR UT WOS:000181844300004 PM 12651909 ER PT J AU Ogawa, Y Lee, JT AF Ogawa, Y Lee, JT TI Xite, X-inactivation Intergenic transcription elements that regulate the probability of choice SO MOLECULAR CELL LA English DT Article ID BETA-GLOBIN LOCUS; CHROMOSOME INACTIVATION; GENE-EXPRESSION; XIST GENE; REGION; TSIX; MOUSE; METHYLATION; ACCUMULATION; REPLICATION AB Allelic expression differences contribute to phenotypic variation. In X chromosome inactivation (XCI), unfavorable XCI ratios promote X-linked disease penetrance in females. During XCI, one X is randomly silenced by Xist. X chromosome choice is determined by asymmetric expression of Tsix whose antisense action represses Xist. Here, we discover a cis element in the mouse X-inactivation center that regulates Tsix. Xite harbors intergenic transcription start sites and DNasel hypersensitive sites with allelic differences. At the onset of XCI, deleting Xite downregulates Tsix in cis and skews XCI ratios, suggesting that Xite promotes Tsix persistence on the active X. Truncating Xite RNA is inconsequential, indicating that Xite action does not require intact transcripts. We propose that allele-specific Xite action promotes Tsix asymmetry and generates X chromosome inequality. Therefore, Xite is a candidate for the Xce, the classical modifier of XCI ratios. C1 Harvard Univ, Sch Med, Dept Genet, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Lee, JT (reprint author), Harvard Univ, Sch Med, Dept Genet, Howard Hughes Med Inst, Boston, MA 02114 USA. FU NIGMS NIH HHS [GM58839] NR 49 TC 157 Z9 161 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAR PY 2003 VL 11 IS 3 BP 731 EP 743 DI 10.1016/S1097-2765(03)00063-7 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 664EX UT WOS:000182049700018 PM 12667455 ER PT J AU Jurisicova, A Antenos, M Varmuza, S Tilly, JL Casper, RF AF Jurisicova, A Antenos, M Varmuza, S Tilly, JL Casper, RF TI Expression of apoptosis-related genes during human preimplantation embryo development: potential roles for the Harakiri gene product and Caspase-3 in blastomere fragmentation SO MOLECULAR HUMAN REPRODUCTION LA English DT Article DE apoptosis; Caspase-3; cell death; embryo; Hrk ID PROGRAMMED CELL-DEATH; IN-VITRO; HUMAN BLASTOCYST; FAMILY MEMBERS; MESSENGER-RNA; MOUSE EMBRYOS; RT-PCR; BCL-X; PROTEIN; BAX AB In order to resolve the mechanisms and reasons of cellular fragmentation it is crucial to understand what genes may be responsible for regulation of this process. We report herein that human oocytes and preimplantation embryos possess abundant levels of transcripts encoding cell death suppressors, Mcl-1, Bcl-x and Bag-1, and the cell death inducer genes, Bax and Caspase-2. Lower but detectable levels of mRNA expression for the Bfl-1/a1, Bcl-w, Harakiii (Hrk) and Caspase-3 genes were also detected during all developmental stages. We also performed analysis of gene expression in single human embryos exhibiting various degrees of fragmentation at the 2-, 4-. and 8-cell stages. At the 4-cell stage, embryos displaying 30-50% fragmentation showed a significant increase in Hrk mRNA levels (P = 0.016). Immunostaining with anti-Hrk antibody confirmed increased staining in some, but not all, fragmented embryos. While Caspase-3 transcripts were elevated in both 4- and 8-cell embryos exhibiting a severe degree of fragmentation, this difference did not reach statistical significance. However, accumulation of Caspase-3 mRNA in fragmented embryos was paralleled by an induction of Caspase-3-like activity. These findings suggest that cellular fragmentation in a subset of human preimplantation embryos could be regulated by certain components of a genetic programme of cell death. C1 Univ Toronto, Dept Obstet & Gynecol, Div Reprod Sci, Toronto, ON, Canada. Univ Toronto, Dept Zool, Toronto, ON, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Vincent Ctr Reprod Biol, Boston, MA 02114 USA. RP Jurisicova, A (reprint author), Mt Sinai Hosp, Samuel Lunenfeld Res Inst, 600 Univ Ave, Toronto, ON M5G 1X5, Canada. RI Jurisicova, Andrea/E-4580-2013; Casper, Robert/E-3775-2013 OI Casper, Robert/0000-0002-6249-462X NR 58 TC 68 Z9 78 U1 2 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1360-9947 J9 MOL HUM REPROD JI Mol. Hum. Reprod. PD MAR PY 2003 VL 9 IS 3 BP 133 EP 141 DI 10.1093/molehr/gag016 PG 9 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 667NB UT WOS:000182237300003 PM 12606589 ER PT J AU Gonzalez, RR Leary, K Petrozza, JC Leavis, PC AF Gonzalez, RR Leary, K Petrozza, JC Leavis, PC TI Leptin regulation of the interleukin-1 system in human endometrial cells SO MOLECULAR HUMAN REPRODUCTION LA English DT Article DE human endometrial cells; implantation; interleukin-1; leptin; leptin receptor ID RECEPTOR ANTAGONIST EXPRESSION; NECROSIS-FACTOR-ALPHA; GROWTH-FACTOR-BETA; MENSTRUAL-CYCLE; IL-1 RECEPTOR; EMBRYONIC IMPLANTATION; SOLUBLE RECEPTOR; GENE-EXPRESSION; MESSENGER-RNA; STROMAL CELLS AB We have previously shown that (i) leptin and leptin receptor (Ob-R) are expressed in the human endometrium, and (ii) leptin secretion is regulated in blastocyst and endometrial epithelial cell (EEC) co-cultures. Interleukin-1beta (IL-1beta) up-regulates leptin and Ob-R, and both cytokines up-regulate beta3 integrin expression in EEC. In the present investigation we examined the effect of leptin on the expression of the IL-1 system in EEC and endometrial stromal cells (ESC) cultured in a medium containing insulin, leptin or IL-1beta (0-3 nmol/l). Leptin stimulated IL-1 antagonist (IL-1Ra), IL-1beta secretion and expression of IL-1 receptor type I (IL-1R tI) in both cell types. IL-1beta and IL-1Ra secretion were down-regulated by IL-1R tI blockade using specific antibodies. Interestingly, leptin partially neutralized this effect. The blockade of Ob-R neutralized the effects of both leptin and IL-1beta on expression of the IL-1beta system and beta3 integrin and on phosphorylation of signal transducer and activator of transcription 3 (Stat3). These results suggest that leptin regulates the IL-1 system and that the blockade of functional Ob-R impairs leptin and IL-1beta functions at the endometrial level. Leptin could be an important molecule for implantation and a molecular mediator for actions of the IL-1 system. The fact that leptin, in the absence of IL-1, can trigger the expression of markers of endometrial receptivity and of the invasive trophoblast phenotype (as does IL-1), suggest that leptin could substitute for these IL-1 functions during the implantation process. C1 Boston Biomed Res Inst, Watertown, MA 02472 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Tufts Univ, Sch Med, Dept Physiol, Boston, MA 02111 USA. Analyt Biotechnol Inc, Watertown, MA 02472 USA. RP Gonzalez, RR (reprint author), Boston Biomed Res Inst, 64 Grove St, Watertown, MA 02472 USA. NR 50 TC 26 Z9 29 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1360-9947 J9 MOL HUM REPROD JI Mol. Hum. Reprod. PD MAR PY 2003 VL 9 IS 3 BP 151 EP 158 DI 10.1093/molehr/gag022 PG 8 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 667NB UT WOS:000182237300005 PM 12606591 ER PT J AU Weisbart, RH Yang, FS Chan, G Wakelin, R Ferreri, K Zack, DJ Harrison, B Leinwand, LA Cole, GM AF Weisbart, RH Yang, FS Chan, G Wakelin, R Ferreri, K Zack, DJ Harrison, B Leinwand, LA Cole, GM TI Cell type specific targeted intracellular delivery into muscle of a monoclonal antibody that binds myosin IIb SO MOLECULAR IMMUNOLOGY LA English DT Article DE antibodies; cell trafficking; molecular biology ID DNA ANTIBODIES; MURINE; AUTOANTIBODY; CHAINS AB Methods for cell type specific targeted intracellular delivery of proteins in vivo remain limited. A murine monoclonal anti-dsDNA antibody, rnAb 3E10, was selectively transported into skeletal muscle cells in vivo. The antibody bound a 200 kDa protein only found in lysates of skeletal muscle by Western blotting. The 200 kDa protein was purified from muscle lysate by antibody affinity chromatography and identified as the skeletal muscle specific heavy chain of myosin IIb by electrospray mass spectrometry. Antibody binding specificity for myosin Ilb was demonstrated in Western blots by binding myosin in skeletal muscle lysates from mice null for myosin lid but not in mice null for myosin IIb. Myosin IIb is implicated in the specific targeting of mAb 3E10 to skeletal muscle. Published by Elsevier Science Ltd. C1 Vet Affairs Greater Los Angeles Hlth Care Syst, Dept Med, Div Rheumatol, Sepulveda, CA 91343 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Dept Geriatr, Sepulveda, CA 91343 USA. City Hope Natl Med Ctr, Dept Endocrinol, Duarte, CA 91010 USA. Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA. RP Weisbart, RH (reprint author), Vet Affairs Greater Los Angeles Hlth Care Syst, Dept Med, Div Rheumatol, Sepulveda, CA 91343 USA. OI LEINWAND, LESLIE/0000-0003-1470-4810; Ferreri, Kevin/0000-0003-0379-0389 NR 15 TC 8 Z9 8 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD MAR PY 2003 VL 39 IS 13 BP 783 EP 789 DI 10.1016/S0161-5890(03)00003-8 PG 7 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 657FJ UT WOS:000181654700003 PM 12617993 ER PT J AU Resendiz, JC Feng, SJ Ji, GL Francis, KA Berndt, MC Kroll, MH AF Resendiz, JC Feng, SJ Ji, GL Francis, KA Berndt, MC Kroll, MH TI Purinergic P2Y(12) receptor blockade inhibits shear-induced platelet phosphatidylinositol 3-kinase activation SO MOLECULAR PHARMACOLOGY LA English DT Article ID BETA-GAMMA-SUBUNITS; PHOSPHOINOSITIDE 3-KINASE; ADENOSINE-DIPHOSPHATE; INTEGRIN ALPHA(IIB)BETA(3); THROMBUS FORMATION; FLOW CONDITIONS; COATED SURFACE; AGGREGATION; STRESS; IB AB Pathologically elevated shear stress triggers aspirin-insensitive platelet thrombosis. Signaling mechanisms involved in shear-induced platelet thrombosis are not well understood. To investigate these, we examined the hypothesis that functionally important platelet phosphatidylinositol 3-kinase (PI3-K) activity is stimulated by an in vitro shear stress of 120 dynes/cm(2) (shear rate of 6000 sec(-1)). Phosphatidylinositol 3,4,5-trisphosphate (PIP3) production was examined in washed human platelets subjected to pathological shear stress in a cone-plate viscometer. PIP3 production peaks 30 s after shear begins and is initiated by von Willebrand factor (VWF) binding to the glycoprotein (Gp) Ib-IX-V complex. Inhibiting PI3-K with wortmannin or 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) results in the inhibition of shear-induced platelet aggregation. In resting platelets, class IA PI3-K associates with the tyrosine kinase Syk. Within 30 s of beginning shear, PI3-K-associated Syk becomes tyrosine phosphorylated. Inhibiting Syk activation with piceatannol results in the inhibition of PIP3 production and aggregation. Selective blockade of the P2Y(12) receptor results in the inhibition of Syk phosphorylation, PIP3 production, and aggregation. These results indicate that shear-induced VWF binding to platelet GpIb-IX-V stimulates functionally important PI3-K activity. PI3-K activation is signaled by rapid feedback amplification that involves P2Y(12) receptor-mediated activation of Syk. C1 Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA. Rice Univ, Houston, TX 77251 USA. Wihuri Res Inst, SF-00140 Helsinki, Finland. Monash Univ, Clayton, Vic 3168, Australia. RP Kroll, MH (reprint author), Baylor Coll Med, VA Med Ctr, 2002 Holcombe Blvd, Houston, TX 77030 USA. RI Berndt, Michael/D-5580-2012 FU NHLBI NIH HHS [HL65967, HL18454] NR 42 TC 42 Z9 42 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD MAR PY 2003 VL 63 IS 3 BP 639 EP 645 DI 10.1124/mol.63.3.639 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 649HL UT WOS:000181201400022 PM 12606772 ER PT J AU Atlas, SJ Nardin, RA AF Atlas, SJ Nardin, RA TI Evaluation and treatment of low back pain: An evidence-based approach to clinical care SO MUSCLE & NERVE LA English DT Review DE evaluation; low back pain; management; review; treatment ID LUMBAR SPINAL STENOSIS; RANDOMIZED CONTROLLED TRIAL; HERNIATED NUCLEUS PULPOSUS; EQUINA SYNDROME SECONDARY; NERVE ROOT COMPRESSION; MAGNETIC-RESONANCE; PHYSICAL-EXAMINATION; FOLLOW-UP; BED REST; GENERAL-PRACTICE AB Low back pain is a common reason for patient visits to a health care provider. For most patients, low back symptoms are nonspecific, meaning that the pain is localized to the back or buttocks and is due to a presumed musculoligamentous process. For patients with radicular leg symptoms, a precise etiology is more commonly identified. The history and physical examination usually provide clues to the uncommon but potentially serious causes of low back pain, as well as to those patients at risk for prolonged recovery. Diagnostic testing should not be a routine part of the initial evaluation, but used selectively based upon the history, examination, and initial treatment response. For patients without significant neurological impairment, initial treatments should include activity modification, nonnarcotic analgesics, and education. For patients whose symptoms are not improving over 2 to 4 weeks, referral for physical treatments is appropriate. A variety of therapeutic options of limited or unproven benefit are available for patients with radicular leg symptoms or chronic low back pain. Patients with radicular pain and little or no neurological findings should receive conservative treatment, but elective surgery is appropriate for those with nerve root compression who are unresponsive to conservative therapy. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Med Serv, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Med Serv, Clin Epidemiol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA. RP Atlas, SJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Med Serv, Div Gen Med, 503 Staniford St, Boston, MA 02114 USA. FU AHRQ HHS [HS-09804, HS-06344, HS-08194] NR 171 TC 39 Z9 41 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD MAR PY 2003 VL 27 IS 3 BP 265 EP 284 DI 10.1002/mus.10311 PG 20 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 651YP UT WOS:000181351800001 PM 12635113 ER PT J AU Nicolas, M Wolfer, A Raj, K Kummer, JA Mill, P van Noort, M Hui, CC Clevers, H Dotto, GP Radtke, F AF Nicolas, M Wolfer, A Raj, K Kummer, JA Mill, P van Noort, M Hui, CC Clevers, H Dotto, GP Radtke, F TI Notch1 functions as a tumor suppressor in mouse skin SO NATURE GENETICS LA English DT Article ID POSTIMPLANTATION DEVELOPMENT; NEOPLASTIC TRANSFORMATION; KERATINOCYTE GROWTH; BETA-CATENIN; DIFFERENTIATION; MICE; GENE; CARCINOGENESIS; DETERMINANT; EXPRESSION AB Notch proteins are important in binary cell-fate decisions and inhibiting differentiation in many developmental systems(1), and aberrant Notch signaling is associated with tumorigenesis(2-5). The role of Notch signaling in mammalian skin is less well characterized and is mainly based on in vitro studies, which suggest that Notch signaling induces differentiation in mammalian skin(6,7). Conventional gene targeting is not applicable to establishing the role of Notch receptors or ligands in the skin because Notch1(-/-) embryos die during gestation(8-12). Therefore, we used a tissue-specific inducible gene-targeting approach to study the physiological role of the Notch1 receptor in the mouse epidermis and the corneal epithelium of adult mice. Unexpectedly, ablation of Notch1 results in epidermal and corneal hyperplasia followed by the development of skin tumors and facilitated chemical-induced skin carcinogenesis. Notch1 deficiency in skin and in primary keratinocytes results in increased and sustained expression of Gli2, causing the development of basal-cell carcinoma-like tumors. Furthermore, Notch1 inactivation in the epidermis results in derepressed beta-catenin signaling in cells that should normally undergo differentiation. Enhanced beta-catenin signaling can be reversed by re-introduction of a dominant active form of the Notch1 receptor. This leads to a reduction in the signaling-competent pool of beta-catenin, indicating that Notch1 can inhibit beta-catenin-mediated signaling. Our results indicate that Notch1 functions as a tumor-suppressor gene in mammalian skin. C1 Univ Lausanne, Ludwig Inst Canc Res, Lausanne Branch, CH-1066 Epalinges, Switzerland. Swiss Inst Expt Canc Res, CH-1066 Epalinges, Switzerland. VU Univ Med Ctr, Dept Pathol, Amsterdam, Netherlands. Univ Toronto, Hosp Sick Children, Program Dev Biol, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Mol & Med Genet, Toronto, ON, Canada. Erasmus Univ, Dept Immunol, NL-3000 DR Rotterdam, Netherlands. Univ Med Ctr Utrecht, Dept Immunol, NL-3584 CX Utrecht, Netherlands. Univ Med Ctr Utrecht, Dept Cell Biol, NL-3584 CX Utrecht, Netherlands. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Harvard Med Sch, Charlestown, MA USA. RP Radtke, F (reprint author), Univ Lausanne, Ludwig Inst Canc Res, Lausanne Branch, CH-1066 Epalinges, Switzerland. OI Mill, Pleasantine/0000-0001-5218-134X NR 30 TC 608 Z9 658 U1 2 U2 30 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAR PY 2003 VL 33 IS 3 BP 416 EP 421 DI 10.1038/ng1099 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 651GT UT WOS:000181312700022 PM 12590261 ER PT J AU Wherry, EJ Teichgraber, V Becker, TC Masopust, D Kaech, SM Antia, R von Andrian, UH Ahmed, R AF Wherry, EJ Teichgraber, V Becker, TC Masopust, D Kaech, SM Antia, R von Andrian, UH Ahmed, R TI Lineage relationship and protective immunity of memory CD8 T cell subsets SO NATURE IMMUNOLOGY LA English DT Article ID IN-VIVO; EFFECTOR FUNCTION; CUTTING EDGE; HOMEOSTATIC PROLIFERATION; DENDRITIC CELLS; DEFICIENT MICE; LYMPH-NODES; L-SELECTIN; ANTIGEN; NAIVE AB Memory CD8 T cells can be divided into two subsets, central (T-CM) and effector (T-EM), but their lineage relationships and their ability to persist and confer protective immunity are not well understood. Our results show that T-CM have a greater capacity than T-EM to persist in vivo and are more efficient in mediating protective immunity because of their increased proliferative potential. We also demonstrate that, following antigen clearance, T-EM convert to T-CM and that the duration of this differentiation is programmed within the first week after immunization. We propose that T-CM and T-EM do not necessarily represent distinct subsets, but are part of a continuum in a linear naive effector --> T-EM --> T-CM differentiation pathway. C1 Emory Univ, Dept Biol, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Ahmed, R (reprint author), Emory Univ, Dept Biol, Atlanta, GA 30322 USA. RI masopust, david/B-5027-2008; von Andrian, Ulrich/A-5775-2008 FU NIAID NIH HHS [AI30048, AI44644] NR 56 TC 1135 Z9 1169 U1 10 U2 53 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAR PY 2003 VL 4 IS 3 BP 225 EP 234 DI 10.1038/ni889 PG 10 WC Immunology SC Immunology GA 649HH UT WOS:000181201000010 PM 12563257 ER PT J AU Song, EW Lee, SK Wang, J Ince, N Ouyang, N Min, J Chen, JS Shankar, P Lieberman, J AF Song, EW Lee, SK Wang, J Ince, N Ouyang, N Min, J Chen, JS Shankar, P Lieberman, J TI RNA interference targeting Fas protects mice from fulminant hepatitis SO NATURE MEDICINE LA English DT Article ID GENE-EXPRESSION; CONCANAVALIN-A; LIGAND; APOPTOSIS; FIBROSIS; DISEASE; INJURY; INVOLVEMENT; INHIBITION; FAILURE AB RNA interference (RNAi) is a powerful tool to silence gene expression post-transcriptionally(1). However, its potential to treat or prevent disease remains unproven. Fas-mediated apoptosis is implicated in a broad spectrum of liver diseases, where inhibiting hepatocyte death is life-saving(2). We investigated the in vivo silencing effect of small interfering RNA (siRNA) duplexes targeting the gene Fas (also known as Tnfrsf6), encoding the Fas receptor, to protect mice from liver failure and fibrosis in two models of autoimmune hepatitis. Intravenous injection of Fas siRNA specifically reduced Fas mRNA levels and expression of Fas protein in mouse hepatocytes, and the effects persisted without diminution for 10 days. Hepatocytes isolated from mice treated with Fas siRNA were resistant to apoptosis when exposed to Fas-specific antibody or co-cultured with concanavalin A (ConA)-stimulated hepatic mononuclear cells. Treatment with Fas siRNA 2 days before ConA challenge abrogated hepatocyte necrosis and inflammatory infiltration and markedly reduced serum concentrations of transaminases. Administering Fas siRNA beginning one week after initiating weekly ConA injections protected mice from liver fibrosis. In a more fulminant hepatitis induced by injecting agonistic Fas-specific antibody, 82% of mice treated with siRNA that effectively silenced Fas survived for 10 days of observation, whereas all control mice died within 3 days. Silencing Fas expression with RNAi holds therapeutic promise to prevent liver injury by protecting hepatocytes from cytotoxicity. C1 Harvard Med Sch, Ctr Blood Res, Boston, MA 02115 USA. Harvard Med Sch, Dept Pediat, Boston, MA USA. Sun Yat Sen Mem Hosp, Dept Hepatobiliary Surg, Guangzhou, Peoples R China. Guangzhou Med Inst, Dept Cell Pathol, Guangzhou, Peoples R China. RP Lieberman, J (reprint author), Harvard Med Sch, Ctr Blood Res, Boston, MA 02115 USA. RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [AI45306, AI45406, AI42510, AI49792] NR 30 TC 790 Z9 928 U1 16 U2 124 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 2003 VL 9 IS 3 BP 347 EP 351 DI 10.1038/nm828 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 651GN UT WOS:000181312300037 PM 12579197 ER PT J AU Gomez-Isla, T Irizarry, MC Mariash, A Cheung, B Soto, O Schrump, S Sondel, J Kotilinek, L Day, J Schwarzschild, MA Cha, JHJ Newell, K Miller, DW Ueda, K Young, AB Hyman, BT Ashe, KH AF Gomez-Isla, T Irizarry, MC Mariash, A Cheung, B Soto, O Schrump, S Sondel, J Kotilinek, L Day, J Schwarzschild, MA Cha, JHJ Newell, K Miller, DW Ueda, K Young, AB Hyman, BT Ashe, KH TI Motor dysfunction and gliosis with preserved dopaminergic markers in human alpha-synuclein A30P transgenic mice SO NEUROBIOLOGY OF AGING LA English DT Article DE synuclein; transgenic mice; Parkinson's disease; Lewy body; tyrosine hydroxylase; substantia nigra; dopamine ID LEWY BODY DISEASE; MULTIPLE SYSTEM ATROPHY; CENTRAL-NERVOUS-SYSTEM; A-BETA COMPONENT; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; IN-VITRO; PRESYNAPTIC PROTEIN; MESSENGER-RNA AB alpha-Synuclein is a major component of Lewy bodies (LBs) in the substantia nigra and cortex in Parkinson's disease (PD) and dementia with Lewy bodies (DLB), and in glial inclusions in multiple systems atrophy (MSA). Mutations in alpha-synuclein have been associated with autosomal dominant forms of PD. We investigated the clinical and neuropathological effects of overexpression of human alpha-synuclein, alpha-synuclein A30P, and alpha-synuclein A53T under the control of the hamster prion protein (PrP) promoter; 5-15 x endogenous levels of protein expression were achieved with widespread neuronal, including nigral, transgene expression. High expression of alpha-synuclein A30P in the Tg5093 line was associated with a progressive motor disorder with rigidity, dystonia, gait impairment, and tremor. Histological analysis of this line showed aberrant expression of the protein in cell soma and progressive CNS gliosis, but no discrete Lewy body-like alpha-synuclein inclusions could be identified. Biochemical analysis demonstrated alpha-synuclein fragmentation. Despite strong expression of the transgene in the nigra, there was no specific deterioration of the nigrostriatal dopaminergic system as assessed by quantitation of nigral tyrosine hydroxylase (TH) containing neurons, striatal TH immunoreactivity, dopamine levels, or dopamine receptor number and function. Lower expressing lines had no specific behavioral or histopathological phenotype. Thus, high expression of mutant human alpha-synuclein resulted in a progressive motor and widespread CNS gliotic phenotype independent of dopaminergic dysfunction in the Tg5093 line. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Tokyo Inst Psychiat, Dept Neural Plast, Tokyo 1568585, Japan. RP Ashe, KH (reprint author), Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA. NR 51 TC 108 Z9 109 U1 1 U2 4 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 MAR-APR PY 2003 VL 24 IS 2 BP 245 EP 258 AR PII S0197-4580(02)00091-X DI 10.1016/S0197-4580(02)00091-X PG 14 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 639FC UT WOS:000180616100005 PM 12498958 ER PT J AU Rutten, BR Wirths, O Van de Berg, WDJ Lichtenthaler, SF Vehoff, J Steinbusch, HWM Korr, H Beyreuther, K Multhaup, G Bayer, TA Schmitz, C AF Rutten, BR Wirths, O Van de Berg, WDJ Lichtenthaler, SF Vehoff, J Steinbusch, HWM Korr, H Beyreuther, K Multhaup, G Bayer, TA Schmitz, C TI No alterations of hippocampal neuronal number and synaptic bouton number in a transgenic mouse model expressing the beta-cleaved C-terminal APP fragment SO NEUROBIOLOGY OF DISEASE LA English DT Article DE immunohistochemistry; intraneuronal A beta; neurodegeneration; SPA4CT; stereology; synaptophysin; transgenic; western blot ID AMYLOID PRECURSOR PROTEIN; FAMILIAL ALZHEIMERS-DISEASE; PLAQUE-FORMATION; GAMMA-SECRETASE; MISSENSE MUTATIONS; MICE; PRESENILIN-1; GENE; NEUROTOXICITY; BRAIN AB Previous studies in the literature have resulted in conflicting reports on the potential neurotoxicity of the beta-cleaved Alzheimer's disease C-terminal fragment (beta-CTF) of beta-amyloid precursor protein in vivo. To readdress this question by rigorous quantitative methods, we analyzed transgenic mice expressing human beta-CTF with the I45F mutation (SPA4CT) under control of the prion protein promoter by stereological techniques. The transgene was expressed in hippocampus and cortex in large pyramidal neurons and in dentate gyrus granule cells. Proteolytic processing of beta-CTF released Abeta. However, most of it remained uncleaved. Neurodegeneration was evaluated by investigating the numbers of hippocampal pyramidal and granule neurons, as well as the number of synaptophysin-immunopositive presynaptic boutons in the hippocampus of 15-month-old SPA4CT mice with design-based stereological techniques. The analyses showed that a fourfold higher expression of the transgene compared to murine APP levels had no effect on the numbers of both neurons and synaptophysin-immunopositive presynaptic boutons. These data implicate that expression of beta-CTF per se is not neurotoxic, and that other mechanisms are responsible for the neurotoxic events in Alzheimer's disease brain. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Univ Maastricht, Dept Psychiat & Neuropsychol, Maastricht, Netherlands. Univ Aachen, Rhein Westfal TH Aachen, Dept Anat & Cell Biol, D-52057 Aachen, Germany. European Grad Sch Neurosci, EURON, Bonn, Germany. Univ Bonn, Med Ctr, Dept Psychiat, D-5300 Bonn, Germany. Univ Maastricht, Dept Pediat, GROW, Maastricht, Netherlands. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. Univ Heidelberg, Ctr Mol Biol, ZMBH, D-6900 Heidelberg, Germany. RP Schmitz, C (reprint author), Univ Maastricht, Dept Psychiat & Neuropsychol, Maastricht, Netherlands. RI Lichtenthaler, Stefan/B-6587-2016; OI Lichtenthaler, Stefan/0000-0003-2211-2575; Wirths, Oliver/0000-0002-4115-0334 NR 50 TC 28 Z9 29 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD MAR PY 2003 VL 12 IS 2 BP 110 EP 120 DI 10.1016/S0969-9961(02)00015-3 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 664GK UT WOS:000182053200002 PM 12667466 ER PT J AU Chimowitz, M Howlett-Smith, H Calcaterra, A Lessard, N Stern, B Lynn, M Hertzberg, V Cotsonis, G Swanson, S Tutu-Gxashe, T Griffin, P Kosinski, A Chester, C Asbury, W Rogers, S Chimowitz, M Stern, B Frankel, M Howlett-Smith, H Hertzberg, V Lynn, M Levine, S Chaturvedi, S Benesch, C Woolfenden, A Sila, C Zweifler, R Lyden, P Barnett, H Easton, D Fox, A Furlan, A Gorelick, P Hart, R Meldrum, H Sherman, D Cloft, H Hudgins, P Tong, F Caplan, L Anderson, D Miller, V Sperling, L Weintraub, W Marshall, J Manoukian, S Chimowitz, M Stern, B Frankel, M Samuels, O Howlett-Smith, H Lessard, N Lane, B Braimah, J Sailor-Smith, S Asbury, B Chester, C Chaturvedi, S Levine, S Wiseman, D Andersen, J Sampson-Haggood, A Kasner, S Liebeskind, D Cucchiara, B Chalela, J McGarvey, M Luciano, J Shaw, S Corrozi, M Rockwell, K Benesch, C Zentner, J Bean, S Cole, D Sila, C Katzan, I Rudd, N Horvat, M Bragg, L Begany, K Mazzoli, G Woolfenden, A Teal, P Johnston, C Synnot, D Busser, J Lyden, P Jackson, C Werner, J Kelly, N McClean, T Gonzales, J Adams, C Romano, J Forteza, A Hidalgo, A Concha, M Koch, S Ferreira, A Wityk, R Aldrich, E Lane, K Rice, S White, L Traill, T Hemphill, C Smith, W Hewlett, L Reed, C Fields, S Nehira, J Wechsler, L Gebel, J Goldstein, S Jovin, T DeCesare, S Harbison, B Bernstein, R Zweifler, R Mendizabal, J Alday, D Yunker, R Umana, E Neal, T Cruz-Flores, S Selhorst, J Leira, E Holzemer, E Armbruster, J Walden, H Olsen, T Chan, R Pullicino, P Harrington, S Hopkins, L Crone, K Seyse, S Hanna, J Winkelman, M Liskay, A Schella, M Lewayne, N Gullion, L Thakore, N Tong, D Garcia, M Kemp, S Shen, H Tuholski, M LaFranchise, E Reel, S Maddox, R Rice, D Mitsias, P Papamitsakis, N Reuther, J Marchese, P Kaatz, S McCord, J Bruno, A Sears, A Pettigrew, T Unwin, D Johnson, M Graybeal, D Redhead, A Stanford, J Croft, C Lee, R Culebras, A Vertino, M Dean, M Ayers, J Zaleski, J Silliman, S Ray, W Ballew, K Darracott, D Robinson, K Malcolm, K Johnston, K Haley, E Nathan, B Maupin, K Grandinetti, C Adams, A Libman, R Benson, R Bhatnagar, R Gonzaga-Camfield, R Grant, Y Kwiatkowski, T Alagappan, K Saver, J Kidwell, C Liebeskind, D Leary, M Ferguson, K Llanes, J Melamed, F Cohen, S Krauss, T Jolly, T Date, L Abedi, G Song, A Wells, M Dandapani, B Waddill, A Parker, L Vicari, R Howard, M Tuhrim, S Wright, P Augustine, S Ali, J Halperin, J Rothlauf, E Kelley, R Pajeau, A Jinkins, P Wang, Y Booth, A Middlebrook, M Grotta, J Campbell, M Shaw, S Boudreaux, R Hickey, J Munson, R Homer, D McGinn, T Small, B Feinberg, A Shim, B Nichols, F Sahm, M Kutlar, A Belden, J Diconzo-Fanning, D Carr, A Allan, W Spiro, R Thaler, D Scandura, T Douglass, L Libenson, M Kase, C Licata-Gehr, E Ansell, J McDonough, M Babikian, V Allen, N Brophy, M Reilly, C Slivka, A Notestine, P Marcy, L Anderson, L Labadie, E Bruck, D Rensuold, D Devine, J Kistler, S Gaines, K Abbott, F Leedom, K Beyer, S Lutsep, H Clark, W Vaishnav, A Gaul, M Doherty, A Pasco, S Brown, J Hollander, J Honch, G Weber, C Sass, A Porter, B Lynch, J Chaves, C Linfante, I Horkan, C Barron, L Ryan, P Tarsey, D Karanjia, P St Louis, E Stephani, L Matit, C Bachhuber, M Thorne, W Schneck, M Whited, K Frame, D Ruderman, G Johnson, C Kaminski, M Hill, L Pitts, D Naftilan, A Dandapani, B Salanga, V Patino-Pauo, R Piccarillo, M Grove, M Rosenthal, R Sloan, M Shuler, L Vaughan, S Chacko, B Tietjen, G Korsnack, A Scotton, S Alberts, M Goldstein, L Edwards, G Thames, B Mohammad, Y Roach, C Martin, T King, J Hurst, D Tindall, M Beasley, K Sleeper, R Gaines, K Johnson, C Kirshner, I Sweeney, B Haden, K Abbatte, M Gateley, K Azhar, S Latwis-Viellette, E Cameron, A Nazarian, S Metzer, W Epperson, E Sanders, P Powell, B Verro, P Rudisill, N Kelly-Messineo, A Branch, J Ramos, L Kalafut, M Kampelman, J Perlman, M Lewis, M Wozniak, M Kittner, S Zappala, N Haines, S Seitzman-Siegel, A Felberg, R Soldani, J Deitelzweig, S Frisard, C Hickenbottom, S Maddox, K Ahmed, A Tamer, H Tilley, B Ansell, J Smith, K Khan, J Radziszewska, B Marler, J Powers, W Thompson, J Simon, R Brass, L Furie, K AF Chimowitz, M Howlett-Smith, H Calcaterra, A Lessard, N Stern, B Lynn, M Hertzberg, V Cotsonis, G Swanson, S Tutu-Gxashe, T Griffin, P Kosinski, A Chester, C Asbury, W Rogers, S Chimowitz, M Stern, B Frankel, M Howlett-Smith, H Hertzberg, V Lynn, M Levine, S Chaturvedi, S Benesch, C Woolfenden, A Sila, C Zweifler, R Lyden, P Barnett, H Easton, D Fox, A Furlan, A Gorelick, P Hart, R Meldrum, H Sherman, D Cloft, H Hudgins, P Tong, F Caplan, L Anderson, D Miller, V Sperling, L Weintraub, W Marshall, J Manoukian, S Chimowitz, M Stern, B Frankel, M Samuels, O Howlett-Smith, H Lessard, N Lane, B Braimah, J Sailor-Smith, S Asbury, B Chester, C Chaturvedi, S Levine, S Wiseman, D Andersen, J Sampson-Haggood, A Kasner, S Liebeskind, D Cucchiara, B Chalela, J McGarvey, M Luciano, J Shaw, S Corrozi, M Rockwell, K Benesch, C Zentner, J Bean, S Cole, D Sila, C Katzan, I Rudd, N Horvat, M Bragg, L Begany, K Mazzoli, G Woolfenden, A Teal, P Johnston, C Synnot, D Busser, J Lyden, P Jackson, C Werner, J Kelly, N McClean, T Gonzales, J Adams, C Romano, J Forteza, A Hidalgo, A Concha, M Koch, S Ferreira, A Wityk, R Aldrich, E Lane, K Rice, S White, L Traill, T Hemphill, C Smith, W Hewlett, L Reed, C Fields, S Nehira, J Wechsler, L Gebel, J Goldstein, S Jovin, T DeCesare, S Harbison, B Bernstein, R Zweifler, R Mendizabal, J Alday, D Yunker, R Umana, E Neal, T Cruz-Flores, S Selhorst, J Leira, E Holzemer, E Armbruster, J Walden, H Olsen, T Chan, R Pullicino, P Harrington, S Hopkins, L Crone, K Seyse, S Hanna, J Winkelman, M Liskay, A Schella, M Lewayne, N Gullion, L Thakore, N Tong, D Garcia, M Kemp, S Shen, H Tuholski, M LaFranchise, E Reel, S Maddox, R Rice, D Mitsias, P Papamitsakis, N Reuther, J Marchese, P Kaatz, S McCord, J Bruno, A Sears, A Pettigrew, T Unwin, D Johnson, M Graybeal, D Redhead, A Stanford, J Croft, C Lee, R Culebras, A Vertino, M Dean, M Ayers, J Zaleski, J Silliman, S Ray, W Ballew, K Darracott, D Robinson, K Malcolm, K Johnston, K Haley, E Nathan, B Maupin, K Grandinetti, C Adams, A Libman, R Benson, R Bhatnagar, R Gonzaga-Camfield, R Grant, Y Kwiatkowski, T Alagappan, K Saver, J Kidwell, C Liebeskind, D Leary, M Ferguson, K Llanes, J Melamed, F Cohen, S Krauss, T Jolly, T Date, L Abedi, G Song, A Wells, M Dandapani, B Waddill, A Parker, L Vicari, R Howard, M Tuhrim, S Wright, P Augustine, S Ali, J Halperin, J Rothlauf, E Kelley, R Pajeau, A Jinkins, P Wang, Y Booth, A Middlebrook, M Grotta, J Campbell, M Shaw, S Boudreaux, R Hickey, J Munson, R Homer, D McGinn, T Small, B Feinberg, A Shim, B Nichols, F Sahm, M Kutlar, A Belden, J Diconzo-Fanning, D Carr, A Allan, W Spiro, R Thaler, D Scandura, T Douglass, L Libenson, M Kase, C Licata-Gehr, E Ansell, J McDonough, M Babikian, V Allen, N Brophy, M Reilly, C Slivka, A Notestine, P Marcy, L Anderson, L Labadie, E Bruck, D Rensuold, D Devine, J Kistler, S Gaines, K Abbott, F Leedom, K Beyer, S Lutsep, H Clark, W Vaishnav, A Gaul, M Doherty, A Pasco, S Brown, J Hollander, J Honch, G Weber, C Sass, A Porter, B Lynch, J Chaves, C Linfante, I Horkan, C Barron, L Ryan, P Tarsey, D Karanjia, P St Louis, E Stephani, L Matit, C Bachhuber, M Thorne, W Schneck, M Whited, K Frame, D Ruderman, G Johnson, C Kaminski, M Hill, L Pitts, D Naftilan, A Dandapani, B Salanga, V Patino-Pauo, R Piccarillo, M Grove, M Rosenthal, R Sloan, M Shuler, L Vaughan, S Chacko, B Tietjen, G Korsnack, A Scotton, S Alberts, M Goldstein, L Edwards, G Thames, B Mohammad, Y Roach, C Martin, T King, J Hurst, D Tindall, M Beasley, K Sleeper, R Gaines, K Johnson, C Kirshner, I Sweeney, B Haden, K Abbatte, M Gateley, K Azhar, S Latwis-Viellette, E Cameron, A Nazarian, S Metzer, W Epperson, E Sanders, P Powell, B Verro, P Rudisill, N Kelly-Messineo, A Branch, J Ramos, L Kalafut, M Kampelman, J Perlman, M Lewis, M Wozniak, M Kittner, S Zappala, N Haines, S Seitzman-Siegel, A Felberg, R Soldani, J Deitelzweig, S Frisard, C Hickenbottom, S Maddox, K Ahmed, A Tamer, H Tilley, B Ansell, J Smith, K Khan, J Radziszewska, B Marler, J Powers, W Thompson, J Simon, R Brass, L Furie, K CA Warfarin-Aspirin Symptomat Intracran TI Design, progress and challenges of a double-blind trial of warfarin versus aspirin for symptomatic intracranial arterial stenosis SO NEUROEPIDEMIOLOGY LA English DT Article DE intracranial atherosclerosis; stroke; warfarin; aspirin; clinical trial; cerebral angiography ID TRANSIENT ISCHEMIC ATTACKS; MIDDLE CEREBRAL-ARTERY; ATRIAL-FIBRILLATION; STROKE PREVENTION; FOLLOW-UP; OCCLUSIVE DISEASE; ANGIOGRAPHY; ANTICOAGULANTS; HYPOTHESES; INFARCTION AB Background and Relevance: Atherosclerotic stenosis of the major intracranial arteries is an important cause of transient ischemic attack (TIA) or stroke. Of the 900,000 patients who suffer a TIA or stroke each year in the USA, intracranial stenosis is responsible for approximately 10%, i.e. 90,000 patients. There have been no prospective trials evaluating antithrombotic therapies for preventing recurrent vascular events in these patients. The main objective of this trial is to compare warfarin [international Normalized Ratio (INR) 2-3] with aspirin (1,300 mg/day) for preventing stroke (ischemic and hemorrhagic) and vascular death in patients presenting with TIA or stroke caused by stenosis of a major intracranial artery. Study Design: Prospective, randomized, double-blind, multicenter trial. The sample size required will be 403 patients per group, based on stroke and vascular death rates of 33% per 3 years in the aspirin group vs. 22% per 3 years in the warfarin group, a p value of 0.05, power of 80%, a 24% rate of 'withdrawal of therapy', and a 1% rate of 'lost to follow-up'. Conduct of Trial. Patients with TIA or nondisabling stroke caused by greater than or equal to50% stenosis of a major intracranial artery documented by catheter angiography are randomized to warfarin or aspirin. Patients are contacted monthly by phone and examined every 4 months until a common termination date. Mean follow-up in the study is expected to be 3 years. Conclusion: This study will determine whether warfarin or aspirin is superior for patients with symptomatic intracranial arterial stenosis. Furthermore, it will identify patients whose rate of ischemic stroke in the territory of the stenotic intracranial artery on best medical therapy is sufficiently high to justify a subsequent trial comparing intracranial angioplasty/stenting with best medical therapy in this subset of patients. Copyright (C) 2003 S. Karger AG, Basel. C1 Emory Clin, Dept Neurol, Atlanta, GA 30322 USA. Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. Emory Univ Hosp, Atlanta, GA 30322 USA. Wayne State Univ, Detroit, MI 48202 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Rochester, Rochester, NY 14627 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Vancouver Gen Hosp, Vancouver, BC, Canada. Univ Calif San Diego, San Diego VA Med Ctr, San Diego, CA 92103 USA. Univ Miami, Coral Gables, FL 33124 USA. Johns Hopkins Med Ctr, Baltimore, MD USA. Univ Calif San Francisco, San Francisco Gen Hosp, San Francisco, CA USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ S Alabama, Mobile, AL 36688 USA. St Louis Univ, St Louis, MO 63103 USA. Buffalo Gen Hosp, Buffalo, NY 14203 USA. Metrohlth Med Ctr, Cleveland, OH USA. Stanford Stroke Ctr, Stanford, CA USA. Neurol Inst Savannah, Savannah, GA USA. Henry Ford Hosp, Detroit, MI 48202 USA. Indiana Univ, Bloomington, IN 47405 USA. SW Texas State Univ, San Marcos, TX 78666 USA. Syracuse VA Med Ctr, Syracuse, NY USA. Univ Florida, Jacksonville, FL USA. Univ Virginia, Charlottesville, VA 22903 USA. Long Isl Jewish Med Ctr, New Hyde Pk, NY 11042 USA. Univ Calif Los Angeles, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Melbourne Internal Med Associates, Melbourne, FL USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Louisiana State Univ, Baton Rouge, LA 70803 USA. Univ Texas, Houston, TX USA. Evanston Hosp Corp, Evanston, IL 60201 USA. Med Coll Georgia, Augusta, GA 30912 USA. Maine Med Ctr, Portland, ME 04102 USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Boston Univ, Boston, MA 02215 USA. Boston VA Med Ctr, Boston, MA USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Arizona, Tucson, AZ 85721 USA. Field Neurosci Inst, Saginaw, MI USA. Rochester Gen Hosp, Rochester, NY 14621 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Cleveland Clin Florida, Weston, FL 33331 USA. Harbin Clin, Rome, GA USA. Med Coll Ohio, Toledo, OH 43699 USA. Duke Univ, Durham, NC 27706 USA. Univ Mississippi, University, MS 38677 USA. Texas Tech, Lubbock, TX USA. Williamson Med Ctr, Franklin, TN USA. St Lukes Roosevelt Hosp, New York, NY USA. Cent Arkansas VA, Little Rock, AR USA. Univ Calif Davis, Davis, CA 95616 USA. Scripps Clin, La Jolla, CA USA. Univ Maryland, College Pk, MD 20742 USA. Ochsner Fdn Clin & Hosp, New Orleans, LA USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Chimowitz, M (reprint author), Emory Clin, Dept Neurol, 4th Floor,Clin A Bldg,1365 Clifton Rd, Atlanta, GA 30322 USA. EM mchimow@emory.edu RI Kasner, Scott/C-6109-2011; Gaines, Kenneth/D-4730-2011; Zweifler, Richard/K-1314-2015 NR 50 TC 58 Z9 58 U1 0 U2 13 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PD MAR-APR PY 2003 VL 22 IS 2 BP 106 EP 117 DI 10.1159/000068744 PG 12 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 657ZC UT WOS:000181695400003 ER PT J AU Inskip, PD Tarone, RE Hatch, EE Wilcosky, TC Selker, RG Fine, HA Black, PM Loeffler, JS Shapiro, WR Linet, MS AF Inskip, PD Tarone, RE Hatch, EE Wilcosky, TC Selker, RG Fine, HA Black, PM Loeffler, JS Shapiro, WR Linet, MS TI Laterality of brain tumors SO NEUROEPIDEMIOLOGY LA English DT Article DE brain cancer; brain tumors; laterality; glioma; meningioma; acoustic neuroma; epidemiology ID CELLULAR-TELEPHONE USE; WHITE-MATTER; CANCER; RISK; HISTOPATHOLOGY; CLASSIFICATION; PERFORMANCE; HEMISPHERE; DIAGNOSIS; GLIOMAS AB Tumor laterality was evaluated with respect to presenting symptoms and demographic factors among 489 adults with histologically confirmed glioma (354 high-grade, 135 low-grade), 197 with meningioma, and 96 with acoustic neuroma. The ratio of left-sided to right-sided tumors did not differ significantly from 1.00 for any of the major tumor types. Low-grade glioma and meningioma occurred nonsignificantly more often on the left side, whereas high-grade glioma and acoustic neuroma occurred nonsignificantly more often on the right side. Aphasia or mental status changes were significantly more common among glioma patients with tumors on the left side than among those with tumors on the right side. Associations between tumor laterality and symptoms may influence the probability or timing of diagnosis, possibly differentially by marital status. Copyright (C) 2003 S. Karger AG, Basel. C1 NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Res Triangle Inst, Epidemiol & Med Studies Program, Res Triangle Pk, NC 27709 USA. Western Penn Hosp, Div Neurosurg, Pittsburgh, PA 15224 USA. NCI, Neurooncol Branch, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Radiat Oncol Branch, Boston, MA 02114 USA. St Josephs Hosp, Barrow Neurol Inst, Dept Neurol, Phoenix, AZ USA. RP Inskip, PD (reprint author), Execut Plaza S,Room 7052, Bethesda, MD 20892 USA. EM inskippe@mail.nih.gov OI Hatch, Elizabeth/0000-0001-7901-3928 FU NCI NIH HHS [N01-CP-15679-01] NR 39 TC 6 Z9 6 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PD MAR-APR PY 2003 VL 22 IS 2 BP 130 EP 138 DI 10.1159/000068747 PG 9 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 657ZC UT WOS:000181695400006 PM 12629279 ER PT J AU Dumoulin, SO Hoge, RD Baker, CL Hess, RF Achtman, RL Evans, AC AF Dumoulin, SO Hoge, RD Baker, CL Hess, RF Achtman, RL Evans, AC TI Automatic volumetric segmentation of human visual retinotopic cortex SO NEUROIMAGE LA English DT Article DE fMRI; retinotopy; visual areas; vision; human cortex; brain mapping ID HUMAN CEREBRAL-CORTEX; POSITRON-EMISSION TOMOGRAPHY; COORDINATE SYSTEM; CORTICAL SURFACE; INTERSUBJECT VARIABILITY; INTENSITY NONUNIFORMITY; FUNCTIONAL-ANALYSIS; OCCIPITAL CORTEX; CALCARINE SULCUS; HUMAN BRAIN AB Previous identification of early visual cortical areas in humans with phase-encoded retinotopic mapping techniques have relied on an accurate cortical surface reconstruction. Here a 3D phase-encoded retinotopic mapping technique that does not require a reconstruction of the cortical surface is demonstrated. The visual field sign identification is completely automatic and the method directly supplies volumes for a region-of-interest analysis, facilitating the application of cortical mapping to a wider population. A validation of the method is provided by simulations and comparison to cortical surface-based methodology. (C) 2003 Elsevier Science (USA). All rights reserved. C1 McGill Univ, McGill Vis Res Unit, Dept Ophthalmol, Montreal, PQ H3A 1A1, Canada. McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ, Canada. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA USA. RP Dumoulin, SO (reprint author), McGill Univ, McGill Vis Res Unit, Dept Ophthalmol, 687 Pine Ave W,H4-14, Montreal, PQ H3A 1A1, Canada. RI Hess, Robert/A-5624-2008; Baker, Curtis/A-8794-2011; Dumoulin, Serge/A-3603-2012 OI Dumoulin, Serge/0000-0001-7474-7711 NR 61 TC 44 Z9 46 U1 3 U2 6 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 MAR PY 2003 VL 18 IS 3 BP 576 EP 587 DI 10.1016/S1053-8119(02)00058-7 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 664HY UT WOS:000182056700002 PM 12667835 ER PT J AU Wright, CI Martis, B Schwartz, CE Shin, LM Fischer, H McMullin, K Rauch, SL AF Wright, CI Martis, B Schwartz, CE Shin, LM Fischer, H McMullin, K Rauch, SL TI Novelty responses and differential effects of order in the amygdala, substantia innominata, and inferior temporal cortex SO NEUROIMAGE LA English DT Article ID FACIAL EMOTION DISCRIMINATION; SURFACE-BASED ANALYSIS; CORTICAL SURFACE; FUNCTIONAL MRI; BEHAVIORAL FINDINGS; COORDINATE SYSTEM; PREFRONTAL CORTEX; FACE PERCEPTION; HUMAN BRAIN; FEAR AB Recent studies of amygdala function have focused on examining responses to emotionally valenced versus neutral stimuli. However, electrophysiologic and neuroimaging studies also suggest that novel neutral faces activate the amygdala, though few investigations have examined the effects of novelty and its relation to changes in stimulus condition. To further investigate how the human amygdala and related structures react to novel neutral faces and to stimulus condition changes, we evaluated human brain responses to blocks containing multiple novel and single repeated face stimuli, presented in two different orders, using functional magnetic resonance imaging (fMRI). Significantly increased signal was present in the amygdala, substantia innominata (SI), and inferior temporal cortex (ITC) to the contrast of multiple novel versus single faces. However, these regions differed in their responses based on whether a stimulus condition was presented 1st or 2nd, with the amygdala and SI having significantly different response profiles than the ITC. Specifically, greater responses to stimuli presented 2nd (i.e., after a condition change) were found in the amygdala and SI, but not in the ITC. Furthermore, the response difference to the Multiple versus Single contrast was greatest in the amygdala and SI, when single faces were presented 1st, and multiple faces presented 2nd, but this pattern was the reverse in the ITC. We speculate that the signal changes to neutral faces in the amygdala and SI with respect to condition (multiple or single faces) and stimulus order may relate to the involvement of these structures in novelty detection and the orienting response. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat Neuroimaging Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dev Psychopathol Grp, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Dept Neurol, Behav Neurol Grp, Boston, MA 02115 USA. Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Karolinska Inst, ARC Aging Res Ctr, Stockholm, Sweden. Stockholm Univ, S-10691 Stockholm, Sweden. RP Wright, CI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat Neuroimaging Res Grp, 13th St,Bldg 149,CNY-9, Charlestown, MA 02129 USA. FU NIMH NIH HHS [MH64806, MH60219] NR 59 TC 95 Z9 95 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAR PY 2003 VL 18 IS 3 BP 660 EP 669 DI 10.1016/S1053-8119(02)00037-X PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 664HY UT WOS:000182056700010 PM 12667843 ER PT J AU Gordon, LK AF Gordon, LK TI Diagnostic dilemmas in orbital inflammatory disease SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Review DE inflammation; orbit; myositis; pseudotumor ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; TOLOSA-HUNT-SYNDROME; FINE-NEEDLE ASPIRATION; IDIOPATHIC SCLEROSING INFLAMMATION; THYROID-ASSOCIATED ORBITOPATHY; POSTERIOR SCLERITIS; OPTIC PERINEURITIS; WEGENERS GRANULOMATOSIS; RADIATION-THERAPY; PSEUDOTUMOR AB Orbital inflammatory disease (OID) broadly describes a variety of pathologic processes and clinical presentations. OID may be idiopathic or may be secondary to a systemic inflammatory disease, retained foreign body, or infectious disease. OID includes the spectrum of bacterial or fungal infections, diffuse inflammation of multiple tissues (e.g., sclerosing orbititis or diffuse anterior OID), and preferential involvement of specific orbital structures (e.g., orbital myositis or optic perineuritis). Mimics of OID include congenital orbital mass lesions or orbital neoplastic disease such as lymphoma or rhabdomyosarcoma. The ultimate diagnosis and treatment plan relies on a careful history and detailed clinical examination followed by the judicious use of ancillary diagnostic testing and a comprehensive treatment plan. The purpose of this review is to provide an overview of the spectrum of diseases known as OID, with emphasis on specific diagnostic challenges in the evaluation and management of patients with idiopathic OID. C1 Univ Calif Los Angeles, Jules Stein Eye Inst, Ctr Hlth Sci, Los Angeles, CA 90095 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. RP Gordon, LK (reprint author), Univ Calif Los Angeles, Jules Stein Eye Inst, Ctr Hlth Sci, 100 Stein Plaza, Los Angeles, CA 90095 USA. NR 91 TC 24 Z9 26 U1 0 U2 1 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD MAR PY 2003 VL 11 IS 1 BP 3 EP 15 DI 10.1076/ocii.11.1.3.15577 PG 13 WC Ophthalmology SC Ophthalmology GA 706UD UT WOS:000184472700001 PM 12854023 ER PT J AU Fay, A Lee, LC Pasquale, LR AF Fay, A Lee, LC Pasquale, LR TI Dermatochalasis causing apparent bitemporal hemianopsia SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID GLAUCOMATOUS VISUAL-FIELD AB We describe a previously unreported cause of apparent bitemporal hemianopsia. Three patients with bilateral dermatochalasis underwent Humphrey visual field (HVF) testing in anticipation of corrective blepharoplasty. Unexpectedly, the HVF showed bitemporal hernianopsia in each case, prompting magnetic resonance imaging of the brain in one case. The scan was negative. The HVF tests were repeated with the upper eyelids taped in elevation, and were normal. We conclude that the bitemporal hemianopic defects in our patients resulted from the testing strategy employed by the HVF analyzer software to measure the visual field. Reasons for these artifactual results are discussed. Clinicians should be aware of this uncommon cause of bitemporal hernianopic visual field defects. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Fay, A (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 5 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHALMIC PLAST REC JI Ophthalmic Plast. Reconstr. Surg. PD MAR PY 2003 VL 19 IS 2 BP 151 EP 153 DI 10.1097/01.IOP.0000055827.78632.CA PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 660FY UT WOS:000181824200013 PM 12644764 ER PT J AU Fynn-Thompson, N McKiernan, JM Fay, A AF Fynn-Thompson, N McKiernan, JM Fay, A TI Transitional cell carcinoma of the urinary bladder metastatic to the orbit SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article AB We report a rare case of transitional cell carcinoma of the urinary bladder metastatic to the orbit, review the histopathology, and highlight characteristics of the few previously reported cases. A 68-year-old man with a remote history of transitional cell carcinoma of the urinary bladder presented with decreased visual acuity, afferent pupillary defect, and limited extraocular motility OS. Computed tomography scan of the orbits showed a diffuse infiltrate surrounding the left globe and optic nerve. Biopsy revealed metastatic transitional cell carcinoma. The patient expired one month later. With only seven cases previously reported, we conclude that transitional cell carcinoma of the urinary bladder rarely metastasizes to the orbit. When present, orbital metastases signify aggressive disease and a poor prognosis. Mean survival following orbital diagnosis is 2.2 months in the cases reported. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med,Dept Ophthalmol, Oculoplast Orbital & Cosmet Surg Serv, Boston, MA 02114 USA. Columbia Univ, Coll Phys & Surg, Dept Urol, Boston, MA USA. RP Fay, A (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med,Dept Ophthalmol, Oculoplast Orbital & Cosmet Surg Serv, 243 Charles St, Boston, MA 02114 USA. NR 12 TC 4 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0740-9303 J9 OPHTHALMIC PLAST REC JI Ophthalmic Plast. Reconstr. Surg. PD MAR PY 2003 VL 19 IS 2 BP 165 EP 167 DI 10.1097/01.IOP.0000056026.84209.1B PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 660FY UT WOS:000181824200020 PM 12644771 ER PT J AU Watkins, LM Pasternack, MS Banks, M Kousoubris, P Rubin, PAD AF Watkins, LM Pasternack, MS Banks, M Kousoubris, P Rubin, PAD TI Bilateral cavernous sinus thromboses and intraorbital abscesses secondary to Streptococcus milleri SO OPHTHALMOLOGY LA English DT Article ID ORBITAL CELLULITIS; SUBPERIOSTEAL ABSCESS; VISUAL-LOSS; COMPLICATIONS; DIAGNOSIS AB Purpose: To report the first case of bilateral cavernous sinus thromboses and bilateral intraorbital abscesses secondary to Streptococcus milleri. Study Design: Single interventional case report. Intervention and Testing: The findings of the ophthalmic evaluation, radiographic imaging, medical and surgical intervention, specimen cultures, and clinical course were analyzed. Results: A 17-year-old female had bilateral proptosis, decreased vision in the left eye, and altered mental status at presentation. An orbital compartment syndrome developed in the left eye and purulent material was present after lateral canthotomy, suggestive of an intraorbital abscess. Magnetic resonance imaging (MRI) scans revealed bilateral cavernous sinus thromboses, and subsequent computed tomographic (CT) scans revealed bilateral intraorbital abscesses in the setting of acute ethmoid and sphenoid sinusitis. Antibiotic treatment and surgical drainage of the orbital abscess and sinuses was performed, and specimen cultures revealed S. milleri. After surgery, the patient experienced hearing loss and a right internal capsule infarct, in addition to complete vision loss in the left eye. A second intraorbital abscess developed in the right eye and was drained surgically. The vision remained 20/20. Conclusions: Streptococcus milleri is a virulent organism with a propensity to form abscesses in multiple areas of the body and should be considered as a possible etiologic agent in abscess formation of the orbit and cavernous sinus thrombosis. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Emergency Ophthalmol Serv,Dept Neuroradiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ophthalm Plast Orbit Reconstruct & Cosmet Surg Se, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Infect Dis Unit, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroophthalmol Unit, Boston, MA 02115 USA. RP Watkins, LM (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Emergency Ophthalmol Serv,Dept Neuroradiol, Boston, MA 02114 USA. OI Kousoubris, Philip/0000-0003-2292-2850 NR 42 TC 15 Z9 18 U1 1 U2 3 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 MAR PY 2003 VL 110 IS 3 BP 569 EP 574 DI 10.1016/S0161-6420(02)01765-7 PG 6 WC Ophthalmology SC Ophthalmology GA 649XK UT WOS:000181233100030 PM 12623823 ER PT J AU Nguyen, QD Van Do, D Feke, GT Demirjian, ZN Lashkari, K AF Nguyen, QD Van Do, D Feke, GT Demirjian, ZN Lashkari, K TI Heparin-induced antiheparin-platelet antibody associated with retinal venous thrombosis SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT 60th Clinical Meeting of the Wilmer-Ophthalmological-Institute CY APR, 2001 CL BALTIMORE, MARYLAND SP Wilmer Ophthalmol Inst ID PROTEIN-S DEFICIENCY; INDUCED THROMBOCYTOPENIA; ARTERY-OCCLUSION; ANTICOAGULATION; LEPIRUDIN AB Objective: To report a case of a 33-year-old white woman in whom retinal venous thromboses developed secondary to heparin-induced antiheparin-platelet antibodies. Design: Interventional case report. Methods: The patient underwent complete ophthalmic and medical examinations. Laser Doppler measurement of retinal blood circulation also was performed. Intervention: Prolonged anticoagulation with thrombin inhibitors and warfarin. Main Outcome Measures: Visual symptoms, retinal appearance on clinical examination, and measurement of retinal blood flow by laser Doppler technique. Results: The patient experienced a scotoma in the visual field of the left eye, left retinal venous thrombosis, decreased venous blood flow in the left eye, and heparin-induced antiheparin-platelet antibodies in serum. After intervention, the visual symptoms and retinal appearance improved, and retinal blood flow normalized. Conclusions: Heparin-induced antiheparin-platelet antibody can lead to thrombosis of the ocular circulation. This index case, which is the first one ever reported in association with antiheparin-platelet antibodies, further illustrates the potential side effects of heparin and widens the spectrum of complications of heparin-induced thrombocytopenia (HIT) and HIT thrombosis syndrome (HITTS). C1 Johns Hopkins Univ, Johns Hopkins Hosp, Sch Med, Vitreoretinal Serv,Wilmer Ophthalmol Inst, Baltimore, MD 21287 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Schepens Retina Assoc Fdn, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Div Hematol Oncol, Boston, MA USA. RP Nguyen, QD (reprint author), Johns Hopkins Univ, Johns Hopkins Hosp, Sch Med, Vitreoretinal Serv,Wilmer Ophthalmol Inst, 600 N Wolfe St,Maumenee 721, Baltimore, MD 21287 USA. NR 15 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 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAR PY 2003 VL 110 IS 3 BP 600 EP 603 DI 10.1016/S0161-6420(02)01766-9 PG 4 WC Ophthalmology SC Ophthalmology GA 649XK UT WOS:000181233100036 PM 12623829 ER PT J AU Adelman, RA Brauner, SC Afshari, NA Grosskreutz, CL AF Adelman, RA Brauner, SC Afshari, NA Grosskreutz, CL TI Cataract formation after initial trabeculectomy in young patients SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology (ARVO) CY MAY 09-14, 1999 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol, Natl Hlth Publ Serv Award, Childrens Hosp, Res Fdn ID MITOMYCIN-C; SURGERY; GLAUCOMA; EYE AB Objective: To evaluate the risk of cataract formation in young patients after initial trabeculectomy. Design: Retrospective, noncomparative case series. Participants: Thirty-four eyes from 27 patients undergoing initial trabeculectomy at the Glaucoma Consultation Service, Massachusetts Eye and Ear Infirmary (mean age, 43.7 years; range, 12-54 years). Intervention: Follow-up averaged 42.6 months (range, 11-90 months). Methods: Lens status was observed before surgery and at 3 months; 6 months; and 1, 2, 3, 4, 5, and 6 years after initial trabeculectomy. Main Outcome Measure: The main outcome measure was defined as cataract extraction for visually significant lenticular opacifications that developed after trabeculectomy. Results: The rate of cataract extraction after initial trabeculectomy was 24% (n = 8). The average time from trabeculectomy to cataract extraction was 26 months (range, 5-58 months). Progression of lenticular opacities occurred throughout the follow-up period. There was no increased rate of cataract formation in subjects with uveitic and steroid-induced glaucoma when compared with all other types of glaucoma. In the patients with both eyes in the study, the first eye was a predictor of cataract progression in the fellow eye. Conclusions: Cataract is a common complication after trabeculectomy in young patients. The 24% rate of cataract extraction after trabeculectomy reported in this study is a significant risk of which young patients contemplating surgery should be aware. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Glaucoma Consultat Serv, Boston, MA 02114 USA. Yale Univ, Ctr Eye, New Haven, CT USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Duke Univ, Ctr Eye, Durham, NC USA. RP Grosskreutz, CL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Glaucoma Consultat Serv, 243 Charles St, Boston, MA 02114 USA. NR 18 TC 14 Z9 15 U1 0 U2 0 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 MAR PY 2003 VL 110 IS 3 BP 625 EP 629 DI 10.1016/S0161-6420(02)01769-4 PG 5 WC Ophthalmology SC Ophthalmology GA 649XK UT WOS:000181233100040 PM 12623833 ER PT J AU Sowers, MR Greendale, GA Bondarenko, I Finkelstein, JS Cauley, JA Neer, RM Ettinger, B AF Sowers, MR Greendale, GA Bondarenko, I Finkelstein, JS Cauley, JA Neer, RM Ettinger, B TI Endogenous hormones and bone turnover markers in pre- and perimenopausal women: SWAN SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE estrogen; follicle stimulating hormone; N-telopeptides; osteocalcin; perimenopause ID PYRIDINIUM CROSS-LINKS; MINERAL DENSITY; BIOCHEMICAL MARKERS; DIABETES-MELLITUS; HEALTH SURVEY; RISK-FACTORS; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; URINARY-EXCRETION; SERUM OSTEOCALCIN AB We tested the hypothesis that higher serum osteocalcin and urinary N-telopeptide of type I collagen (NTx) concentrations would be found in women with increasing cycle irregularity or increased follicle stimulating hormone concentrations. We studied 2,375 pre- and early perimenopausal women from the Study of Women's Health Across the Nation (SWAN), aged 42-52 years, who self-identified their race/ethnic origin as African-American (28.3%), Caucasian (49.4%), Japanese (10.5%) or Chinese (11.8%). Outcome measures were serum osteocalcin, a measure of bone formation, and NTx, a measure of bone resorption. The explanatory variables were menopausal status, based on self-reported regularity of menstrual bleeding, and circulating endogenous hormone concentrations including estradiol (E-2), testosterone (T), sex hormone binding globulin (SHBG) and follicle stimulating hormone (FSH) concentrations. Additionally, we evaluated the association of the bone turnover markers with the Free Androgen Index (FAI) and the Free Estradiol Index (FEI), ratios of total testosterone and estradiol concentrations to SHBG, respectively. Higher FSH concentrations were associated with higher NTx concentrations (beta=0.003, partial r(2)=2.1%, p<0.0001), both before and after adjusting for other covariates (total explained variability of 9%). Higher FSH concentrations were also associated with higher osteocalcin concentrations (beta=-0.216, partial r(2)=4.1%, p<0.0001, total explained variability of 15.4%). There were no significant associations of the bone turnover markers with other endogenous hormones, following adjustment for covariates. Mean osteocalcin and NTx values were not significantly different in premenopausal women compared to early perimenopausal women. In these pre- and early perimenopausal women, higher FSH concentrations, but not other serum reproductive hormone concentrations, are positively associated with greater bone turnover prior to the last menstrual period. C1 Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. Univ Calif Los Angeles, Sch Med, Div Geriatr, Los Angeles, CA 90095 USA. Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA. RP Sowers, MR (reprint author), Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Rm 2624,SPH-1,109 Observ St, Ann Arbor, MI 48109 USA. RI Perez , Claudio Alejandro/F-8310-2010; Cauley, Jane/N-4836-2015 OI Perez , Claudio Alejandro/0000-0001-9688-184X; Cauley, Jane/0000-0003-0752-4408 FU NIA NIH HHS [U01 AG12531, U01 AG12495, U01 AG12539, U01 AG12546, U01 AG12553, U01 AG12554]; NINR NIH HHS [U01 NR04061] NR 39 TC 56 Z9 60 U1 2 U2 4 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD MAR PY 2003 VL 14 IS 3 BP 191 EP 197 DI 10.1007/s00198-002-1329-4 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 740KB UT WOS:000186400600002 PM 12730778 ER PT J AU Rosowski, JJ Mehta, RP Merchant, SN AF Rosowski, JJ Mehta, RP Merchant, SN TI Diagnostic utility of laser-Doppler vibrometry in conductive hearing loss with normal tympanic membrane SO OTOLOGY & NEUROTOLOGY LA English DT Article DE laser-Doppler vibrometry; conductive hearing loss; middle ear function; audiometry ID HUMAN MIDDLE-EAR; MONGOLIAN GERBIL; TRANSMISSION; CAT; RECONSTRUCTION; IMPEDANCE; VIBRATION; ADULTS; MASS; TOOL AB Hypothesis: It was hypothesized that laser-Doppler vibrometry measurements of umbo velocity in aerated middle ears with conductive loss can differentiate ossicular interruptions, stapes fixations, and mallear fixations. More generally, we hypothesize that laser-Doppler vibrometry measurements of umbo velocity can give information about how differences in the impedance that the ossicles work against affect middle-ear function. Background: Laser-Doppler vibrometry is a well-established research tool for exploring middle-ear function. The authors wished to investigate its potential as a clinical tool for differential diagnosis of the cause of conductive hearing loss. Methods: Laser-Doppler vibrometry was used to investigate the relationship between the sound-induced velocity of the tympanic membrane at the umbo and the cause of conductive hearing loss when the tympanic membrane was normal and the middle ear was aerated. The results of measurements in 17 adult ears before exploratory tympanotomy were compared with the surgically determined cause of the hearing loss. The authors also measured the motion of the umbo in 10 patients who had undergone successful small-fenestra stapedectomy procedures. In all the studied ears, pure-tone audiograms were measured at the time of laser-Doppler vibrometry testing. Results: There were clear statistical differences between the umbo velocity in normal ears and in ears with different ossicular pathologic conditions. There was also a clear separation of the results between ears with ossicular interruptions and ossicular fixation. The pattern of laser-Doppler vibrometry measurements in poststapedectomy ears approximated the pattern in ears with ossicular interruptions. Conclusion: Comparison of laser-Doppler vibrometry results and audiometry may be a sensitive and selective indicator of ossicular pathologic conditions as well as a useful tool for investigating middle ear function. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Wallace Middle Ear Res Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. RP Rosowski, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Wallace Middle Ear Res Unit, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01 DC000194, R01 DC000194-22] NR 33 TC 51 Z9 54 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD MAR PY 2003 VL 24 IS 2 BP 165 EP 175 DI 10.1097/00129492-200303000-00008 PG 11 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 655ZE UT WOS:000181582800007 PM 12621328 ER PT J AU Mehta, RP Ravicz, ME Rosowski, JJ Merchant, SN AF Mehta, RP Ravicz, ME Rosowski, JJ Merchant, SN TI Middle-ear mechanics of Type III tympanoplasty (stapes columella): I. Experimental studies SO OTOLOGY & NEUROTOLOGY LA English DT Article; Proceedings Paper CT 135th Annual Scientific Meeting of the American-Otological-Society CY MAY 10-11, 2002 CL BOCA RATON, FLORIDA SP Amer Otol Soc DE Type III tympanoplasty; stapes columella tympanoplasty; middle ear; hearing ID RECONSTRUCTION; WINDOWS AB Objective: To investigate the mechanics of Type III tympanoplasty by developing a cadaveric temporal bone model. Background: Type Ill stapes columella tympanoplasty involves the placement of a tympanic membrane graft, usually made of temporalis fascia, directly onto the stapes head. The procedure is usually done in conjunction with a canal wall down mastoidectomy. Postoperative hearing results vary widely, with air-bone gaps of 10 to 60 dB. The structural features responsible for the wide range in hearing results have not been systematically investigated. Methods: Canal wall down Type Ill procedures were performed in eight cadaveric temporal bones. Acoustic stimuli were presented in the ear canal, and round window velocity V-RW (used as an index of hearing) was measured, while systematically varying stapes mobility, mechanical properties of tympanic membrane graft, and tightness of connection between tympanic membrane graft and stapes. The effect of interposing a thin cartilage disc between the tympanic membrane graft and stapes head was also assessed. Results: When the middle ear was aerated and the stapes was mobile, VRW was 15 to 30 dB lower than in an intact, normal ear. Stapes fixation led to a significant reduction in V-RW; reduction was greatest at low frequencies. There was little effect of varying the tightness of connection between the tympanic membrane graft and stapes head. Sound energy was transmitted from the graft to the stapes as long as the graft was in physical contact with the stapes head. Different tympanic membrane graft materials with a range of mechanical properties (stiffness and mass) resulted in little variation in V-RW. Interposing a thin cartilage disc between the tympanic membrane graft and stapes improved V-RW in the lower frequencies by 5 to 10 dB. The authors hypothesize that the disc acted to increase the effective vibrating area of the graft. Conclusions: The feasibility of using a cadaveric temporal bone model to study the mechanics of Type Ill tympanoplasty was demonstrated. A mobile stapes and aerated middle ear were essential for a successful Type Ill tympanoplasty. There was little effect of varying the mechanical properties of the tympanic membrane graft or changing the tightness of connection between the graft and stapes head. Improved results were achieved by interposing a thin cartilage disc between the graft and stapes head to increase the effective vibrating area of the graft. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01 DC004798, R01 DC04798] NR 23 TC 17 Z9 18 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD MAR PY 2003 VL 24 IS 2 BP 176 EP 185 DI 10.1097/00129492-200303000-00009 PG 10 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 655ZE UT WOS:000181582800008 PM 12621329 ER PT J AU Merchant, SN McKenna, MJ Mehta, RP Ravicz, ME Rosowski, JJ AF Merchant, SN McKenna, MJ Mehta, RP Ravicz, ME Rosowski, JJ TI Middle ear mechanics of Type III tympanoplasty (stapes columella): II. Clinical studies SO OTOLOGY & NEUROTOLOGY LA English DT Article; Proceedings Paper CT 135th Annual Scientific Meeting of the American-Otological-Society CY MAY 10-11, 2002 CL BOCA RATON, FLORIDA SP Amer Otol Soc DE Type III tympanoplasty; stapes columella tympanoplasty; middle ear; hearing ID RECONSTRUCTION; MASTOIDECTOMY AB Objectives: To determine the structural features that are responsible for the large variation in postoperative hearing results after Type III stapes columella tympanoplasty, to compare the clinical results after Type III tympanoplasty with predictions based on experimental investigations using a temporal bone model, and to investigate the effectiveness of a modification in surgical technique for Type III reconstruction. Study Design: Retrospective case review. Setting: Tertiary referral center. Inclusion Criteria: The ear was healed with an intact tympanic membrane graft; the status of the stapes was known, whether mobile or fixed; and the postoperative status of aeration of the middle ear was known, whether aerated or not. Main Outcome Measure: Air-bone gap at frequencies 250, 500, 1,000, 2,000 and 4,000 Hz. Results: In ears with temporalis fascia graft onto stapes head: mobile stapes and aerated middle ear (n = 34), mean air-bone gaps at audiometric frequencies were 15 to 30 dB, consistent with predictions of the experimental model; mobile stapes and nonaerated middle ear (n = 16), large air-bone gaps of 35 to 55 dB; fixed stapes and aerated middle ear (n = 4), large air-bone gaps of 30 to 50 dB; fixed stapes and nonaerated middle ear (n = 2), large air-bone gaps of 30 to 70 dB. In ears with a fascia-cartilage graft onto stapes head, where a thin disc of meatal cartilage, 0.3 to 0.5 mm thick and 4 to 6 mm in diameter was interposed between the fascia graft and the stapes head: mobile stapes and aerated middle ear (n = 9), mean air-bone gaps at audiometric frequencies were 10 to 25 dB, about 5 dB better at 250, 500, and 2,000 Hz than in ears with only a fascia graft (p <0.05), improvement consistent with that observed experimentally when a thin cartilage disc was used in the temporal bone model, hypothesis that the cartilage increased the effective vibrating area of the graft; mobile stapes and nonaerated middle ear (n = 2), air-bone gaps were 40 to 50 dB. Conclusions: Large air-bone gaps of 30 to 70 dB occurred as a result of stapes fixation, nonaeration of the middle car, or both. When the stapes was mobile and the middle ear was aerated, a fascia graft resulted in air-bone gaps of 15 to 30 dB. Interposing a thin disc of cartilage between the fascia graft and stapes head to improve the effective vibrating graft area gave better hearing, with air-bone gaps of 10 to 25 dB. The clinical Type Ill results were consistent with predictions based on experimental investigations of mechanics of the Type Ill procedure in a temporal bone model. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01 DC004798, R01 DC04798] NR 26 TC 14 Z9 17 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD MAR PY 2003 VL 24 IS 2 BP 186 EP 194 DI 10.1097/00129492-200303000-00010 PG 9 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 655ZE UT WOS:000181582800009 PM 12621330 ER PT J AU Kulich, RJ Driscoll, J Prescott, JC Pelletier, NJ Driscoll, S Cooke, W Correa, L Mehta, NR AF Kulich, RJ Driscoll, J Prescott, JC Pelletier, NJ Driscoll, S Cooke, W Correa, L Mehta, NR TI The Daubert standard, a primer for pain specialists SO PAIN MEDICINE LA English DT Article ID ADMISSIBILITY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Tufts Univ, Sch Dent Med, Craniofacial Pain Ctr, Boston, MA 02111 USA. Suffolk Univ, Sch Law, Boston, MA 02114 USA. Prescott & Pelletier, Boston, MA USA. RP Kulich, RJ (reprint author), 30 Union St, Charlestown, MA 02120 USA. NR 32 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD MAR PY 2003 VL 4 IS 1 BP 75 EP 80 DI 10.1046/j.1526-4637.2003.03007.x PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 654PP UT WOS:000181505500009 PM 12873280 ER PT J AU Billings, JA AF Billings, JA TI From the USA SO PALLIATIVE MEDICINE LA English DT Editorial Material ID PHYSICIAN-ASSISTED SUICIDE; TERMINAL SEDATION; DECISION-MAKING; OREGON DEATH; DIGNITY ACT; CARE; EXPERIENCES; EUTHANASIA; RULE C1 Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Ctr Palliat Care, Cambridge, MA 02138 USA. RP Billings, JA (reprint author), Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0269-2163 J9 PALLIATIVE MED JI Palliat. Med. PD MAR PY 2003 VL 17 IS 2 BP 104 EP 105 DI 10.1191/0269216303pm704op PG 2 WC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medicine, General & Internal SC Health Care Sciences & Services; Public, Environmental & Occupational Health; General & Internal Medicine GA 666YP UT WOS:000182204300006 ER PT J AU Osorio, Y Melby, PC Pirmez, C Chandrasekar, B Guarin, N Travi, BL AF Osorio, Y Melby, PC Pirmez, C Chandrasekar, B Guarin, N Travi, BL TI The site of cutaneous infection influences the immunological response and clinical outcome of hamsters infected with Leishmania panamensis SO PARASITE IMMUNOLOGY LA English DT Article DE cutaneous leishmaniasis; cytokines; immunity; Leishmania panamensis ID TRANSFORMING-GROWTH-FACTOR; EXPERIMENTAL VISCERAL LEISHMANIASIS; IMMUNE-RESPONSE; INTERFERON-GAMMA; FACTOR-BETA; NITRIC-OXIDE; BALB/C MICE; KALA-AZAR; IFN-GAMMA; MURINE LEISHMANIASIS AB We determined that the site of inoculation (foot or snout) influences the clinical evolution and immune responses of hamsters infected with Leishmania (Viannia) panamensis. Hamsters infected in the snout showed (i) a more rapid and severe lesion evolution at multiple time points ( P < 0.05), (ii) a more extensive inflammatory infiltrate and tissue necrosis, (iii) a higher tissue parasite burden, (iv) a higher antibody titre ( P < 0.01), but lower antigen-specific spleen cell proliferative response ( P = 0.02), and (v) a slower response to anti-leishmanial drug treatment ( P < 0.002). In both inoculation groups there was co-expression of type 1 (IFN-gamma and IL-12) and some type 2 (IL-10 and TGF-beta, but not IL-4) cytokines in the cutaneous lesions and spleen. Early in the course of infection, hamsters infected in the snout showed higher expression of splenic IL-10 ( P = 0.04) and intra-lesional IFN-gamma ( P = 0.02) than foot infections. No expression of IL-12p40 or IL-4 was detected. During the chronic phase, snout lesions expressed more IFN-gamma ( P = 0.001), IL-12p40 ( P = 0.01), IL-10 ( P = 0.009) and TGF-beta ( P = 0.001), and the level of expression of each of these cytokines correlated with lesion size ( P less than or equal to 0.01). These results suggest that the site of infection influences the clinical outcome in experimental cutaneous leishmaniasis, and that the expression of macrophage-deactivating type 2 cytokines and/or an exaggerated type 1 proinflammatory cytokine response may contribute to lesion severity. C1 CIDEIM, Cali, Colombia. S Texas Vet Hlth Care Syst, Dept Vet Affairs Med Ctr, Med Serv, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Inst Oswaldo Cruz, FIOCRUZ, Dept Bioquim & Biol Mol, BR-20001 Rio De Janeiro, Brazil. RP Osorio, Y (reprint author), CIDEIM, AA5390, Cali, Colombia. RI Pirmez, Claude/K-8579-2012 OI Pirmez, Claude/0000-0002-7443-0455 NR 58 TC 17 Z9 20 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0141-9838 J9 PARASITE IMMUNOL JI Parasite Immunol. PD MAR PY 2003 VL 25 IS 3 BP 139 EP 148 DI 10.1046/j.1365-3024.2003.00615.x PG 10 WC Immunology; Parasitology SC Immunology; Parasitology GA 711HD UT WOS:000184732800005 PM 12911522 ER PT J AU David, JK Anupindi, SA Deshpande, V Jaramillo, D AF David, JK Anupindi, SA Deshpande, V Jaramillo, D TI Intramuscular juvenile xanthogranuloma: sonographic and MR findings SO PEDIATRIC RADIOLOGY LA English DT Article DE juvenile xanthogranuloma; intramuscular mass; radiology AB Background: Juvenile xanthogranuloma is a rare benign lesion, most often cutaneous or subcutaneous, and found in infants. Objective: To review the imaging approach to an intramuscular mass in an infant. Methods: A case is reported of a 2-month-old boy who presented with a solitary left arm mass which was evaluated with ultrasound and MRI and then biopsied. Results: Imaging demonstrated a well-defined homogeneous solid mass located in the triceps muscle. The mass was resected and pathology revealed intramuscular juvenile xanthogranuloma. Conclusion: Intramuscular juvenile xanthogranuloma, although extremely rare, has imaging features similar to those of more common malignant tumors of infancy. The imaging findings are nonspecific, but this diagnosis should be considered in the differential of a solid intramuscular mass in an infant. C1 Massachusetts Gen Hosp, Dept Radiol, Div Pediat Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Anupindi, SA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Pediat Radiol, 34 Fruit St,White 246, Boston, MA 02114 USA. NR 11 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0301-0449 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD MAR PY 2003 VL 33 IS 3 BP 203 EP 206 DI 10.1007/s00247-002-0813-5 PG 4 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 657CK UT WOS:000181647700011 PM 12612822 ER PT J AU Sannicandro, T Means, RT Aquino, LZ Cagle, SW Collier, SL Cooper, SL Gray, AL Magill, MF Powell, BA Smith, KI Styk, DL AF Sannicandro, T Means, RT Aquino, LZ Cagle, SW Collier, SL Cooper, SL Gray, AL Magill, MF Powell, BA Smith, KI Styk, DL TI Improving patient safety in the antineoplastic medication-use system at a VA medical center with the development of a multidisciplinary clinical team. SO PHARMACOTHERAPY LA English DT Meeting Abstract CT Spring Practice and Research Forum of the American-College-of-Clinical-Pharmacy CY APR 27-30, 2003 CL PALM SPRINGS, CALIFORNIA SP American Coll Clin Pharmacy C1 Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RI Means, Robert/A-4454-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD MAR PY 2003 VL 23 IS 3 MA 184 BP 419 EP 419 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 650JL UT WOS:000181259900156 ER PT J AU Taub, PJ Rudkin, GH Clearihue, WJ Miller, TA AF Taub, PJ Rudkin, GH Clearihue, WJ Miller, TA TI Prefabricated alloplastic implants for cranial defects SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Editorial Material ID RECONSTRUCTION; HYDROXYAPATITE; CRANIOPLASTY; PROSTHESES C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Taub, PJ (reprint author), 11761 Sunset Blvd, Los Angeles, CA 90049 USA. NR 12 TC 13 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAR PY 2003 VL 111 IS 3 BP 1233 EP 1240 DI 10.1097/01.PRS.0000046048.77472.23 PG 8 WC Surgery SC Surgery GA 651MM UT WOS:000181323800039 PM 12621197 ER PT J AU Basile, JN AF Basile, JN TI Heart failure - A three-article symposium SO POSTGRADUATE MEDICINE LA English DT Editorial Material C1 Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. RP Basile, JN (reprint author), Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 USA SN 0032-5481 J9 POSTGRAD MED JI Postgrad. Med. PD MAR PY 2003 VL 113 IS 3 BP 29 EP 30 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 835TX UT WOS:000222509500004 ER PT J AU Basile, JN AF Basile, JN TI Titration of beta-blockers in heart failure - How to maximize benefit while minimizing adverse events SO POSTGRADUATE MEDICINE LA English DT Article ID RANDOMIZED INTERVENTION TRIAL; LEFT-VENTRICULAR FUNCTION; MERIT-HF; DILATED CARDIOMYOPATHY; ADRENERGIC-BLOCKADE; METOPROLOL CR/XL; CARVEDILOL; THERAPY; MORTALITY; DISEASE AB Despite extensive data supporting the use of beta-blockers in patients with chronic heart failure, fewer than one third of eligible patients receive these agents. Furthermore, some patients who do receive beta-blocker therapy are given suboptimal doses. In this article, Dr Basile discusses the careful adjustment of beta-blocker dose during initiation of therapy to successfully manage chronic heart failure and minimize adverse events. C1 Med Univ S Carolina, Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Basile, JN (reprint author), Med Univ S Carolina, Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA. EM jan.basile@med.va.gov NR 27 TC 4 Z9 4 U1 0 U2 1 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 USA SN 0032-5481 J9 POSTGRAD MED JI Postgrad. Med. PD MAR PY 2003 VL 113 IS 3 BP 63 EP 70 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 835TX UT WOS:000222509500007 PM 12647475 ER PT J AU Alterman, AI McDermott, PA Mulvaney, FD Cacciola, JS Rutherford, MJ Searles, JS Lynch, K Cnaan, A AF Alterman, AI McDermott, PA Mulvaney, FD Cacciola, JS Rutherford, MJ Searles, JS Lynch, K Cnaan, A TI Comparison of embedded and isolated administrations of the California Psychological Inventory's socialization subscale SO PSYCHOLOGICAL ASSESSMENT LA English DT Article ID SCALE DEVELOPMENT; YOUNG MEN; PERSONALITY; QUESTIONNAIRE; ALCOHOLICS; VALIDITY; ANTISOCIALITY; RISK AB Alternate administration methods were tested for the Socialization (So) subscale of the California Psychological Inventory (CPI; H. G. Gough, 1994; H. G. Gough & P. Bradley, 1996) in 437 young adult men. One method administered the 46 CPI-So items in isolation from the CPI, whereas the 2nd method administered the 46 items embedded in the CPI. External validity measures of antisociality were also administered over the 2 sessions. Isolated administration produced somewhat higher internal consistency and significantly better concurrent validity and demonstrated construct validity as a measure of antisociality. Additional factor analytic studies of the CPI-So and CPI revealed that the 2 CPI-So versions had different factorial structures and that the embedded CPI-So subscale did not retain factorial integrity or an appreciable amount of reliable and uniquely interpretable variance. C1 Univ Penn, Sch Med, Ctr Treatment & Evaluat, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Grad Sch Educ, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Washington, Alcohol & Drug Inst, Seattle, WA 98195 USA. Univ Vermont, Dept Psychiat, Burlington, VT 05405 USA. Childrens Hosp Philadelphia, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. RP Alterman, AI (reprint author), Univ Penn, Sch Med, Ctr Treatment & Evaluat, Dept Psychiat, 3440 Market St,Suite 370, Philadelphia, PA 19104 USA. FU NIAAA NIH HHS [AA 07361] NR 38 TC 6 Z9 6 U1 1 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD MAR PY 2003 VL 15 IS 1 BP 64 EP 70 DI 10.1037/1040-3590.15.1.64 PG 7 WC Psychology, Clinical SC Psychology GA 656BV UT WOS:000181589700006 PM 12674725 ER PT J AU Waters, G Caplan, D Yampolsky, S AF Waters, G Caplan, D Yampolsky, S TI On-line syntactic processing under concurrent memory load SO PSYCHONOMIC BULLETIN & REVIEW LA English DT Article ID WORKING-MEMORY; SENTENCE COMPREHENSION; INDIVIDUAL-DIFFERENCES; COMPLEXITY; CAPACITY AB Thirty-six university students were tested in a plausibility judgment task using a self-paced listening paradigm under no-interference and two-digit load conditions. listening times were longer at syntactically more complex portions of syntactically more complex sentences, and greater loads led to increased listening times. However, listening times at syntactically more complex positions in syntactically more complex sentences did not increase more than listening times at comparable positions in syntactically simple sentences under digit load conditions. The results indicate that a concurrent memory load does not reduce the availability of working memory resources used for on-line syntactic processing and, thus, provide evidence that the working memory system used for assigning syntactic structure is separate from that measured by standard working memory tasks. C1 Boston Univ, Dept Hlth Sci, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Waters, G (reprint author), Boston Univ, Dept Hlth Sci, 635 Commonwealth Ave, Boston, MA 02215 USA. NR 19 TC 14 Z9 14 U1 0 U2 2 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 USA SN 1069-9384 J9 PSYCHON B REV JI Psychon. Bull. Rev. PD MAR PY 2003 VL 10 IS 1 BP 88 EP 95 DI 10.3758/BF03196471 PG 8 WC Psychology, Mathematical; Psychology, Experimental SC Psychology GA 669BN UT WOS:000182332200007 PM 12747494 ER PT J AU Alpert, JE Petersen, T Roffi, PA Papakostas, GI Freed, R Smith, MM Spector, AR Nierenberg, AA Rosenbaum, JF Fava, M AF Alpert, JE Petersen, T Roffi, PA Papakostas, GI Freed, R Smith, MM Spector, AR Nierenberg, AA Rosenbaum, JF Fava, M TI Behavioral and emotional disturbances in the offspring of depressed parents with anger attacks SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE anger attacks; depression; offspring; parents ID PANIC DISORDER; HIGH-RISK; CHILDREN; PSYCHOPATHOLOGY; PATTERNS; ONSET AB Background. To examine the emotional and behavioral characteristics of the offspring of depressed parents with and without anger attacks. Methods: Forty-three parents who met criteria for major depressive disorder (MDD) completed the Achenbach Child Behavior Checklist Parent Report Version (CBCL) for each of their birth children (n = 58, age range 6-17 years). Unpaired ttests were used to evaluate the CBCL scale score differences between children of parents with and children of parents without anger attacks. Baseline demographics and clinical differences between the two groups of parents were also evaluated. Results: Parents with anger attacks had a significantly younger age of onset of IVIDD. Offspring of depressed parents with anger attacks were found to have significantly lower social and school competency scale scores and higher scores for delinquency, attention problems, and aggressive behavior. In addition, this group was found to have a significantly higher total T score (a global measure of psychopathology). Conclusions: There are some important differences between offspring of depressed parents with and without anger attacks. This finding may be important in identifying and formulating intervention strategies for childhood problems in the offspring of depressed parents. Copyright (C) 2003 S. Karger AG, Basel. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Petersen, T (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 15 Parkman St,WAC 812, Boston, MA 02114 USA. RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X NR 21 TC 14 Z9 14 U1 0 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PD MAR-APR PY 2003 VL 72 IS 2 BP 102 EP 106 DI 10.1159/000068682 PG 5 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 654GU UT WOS:000181487500007 PM 12601228 ER PT J AU Hamberg, LM Rhea, JT Hunter, GJ Thrall, JH AF Hamberg, LM Rhea, JT Hunter, GJ Thrall, JH TI Multi-detector row CT: Radiation dose characteristics SO RADIOLOGY LA English DT Article DE computed tomography (CT), multi-detector row; computed tomography (CT), radiation exposure; radiations, exposure to patients and personnel AB PURPOSE: To determine the dose characteristics of multi-detector row computed tomography (CT) and to provide tabulated dose values and rules of thumb that assist in minimizing the radiation dose at multi-detector row CT. MATERIALS AND METHODS: Weighted CT dose index, (CTDI100w) values were obtained from three multi-detector row CT scanners (LightSpeed; GE Medical Systems, Milwaukee, Wis) for both head and body CT modes by using standard CT-dose phantoms. The CTDI100w was determined as a function of x-ray tube voltage (80, 100, 120,140 kVp), tube current (range, 50-380 mA), tube rotation time (0.5-4.0 seconds), radiation profile width (RPW) (5, 10, 15, 20 mm), and acquisition mode.(helical high-quality and high-speed modes and axial one-, two-, and four-section modes). Statistical regression was performed to characterize the relationships between CTDI100w and various technique factors. RESULTS: The CTDI100w (milligray) increased linearly with tube current: in head mode, CTDI100w = (0.391 mGy/mA +/- 0.004) X tube current (milliampere) (r(2) = 0.999); in body mode, CTDI100w = (0.162 mGy/mA +/- 0.002) X tube current (millampere) (r(2) = 0.999). The CTDI100w increased linearly with rotation time: in head mode, CTDI100w = (34.7 mGy/sec +/- 0.2) X rotation time (seconds) (r(2) = 1.0); in body mode, CTDI100w = (13.957 mGy/sec 0.005) X rotation time (seconds) (r(2) = 1.0). The relationship of normalized CTDI100w (milligrays per 100 mAs) with tube voltage followed a power law: in head mode, CTDI100w = (0.00016 mGy/100 mAs (.) kVp +/-0.00007) X (tube voltage)((2.5+/-0.1)) (r(2) = 0.997); in body mode, CTD(100)w = (0.000012 mGy/100 mAs (.) kVp +/- 0.000007) X (tube voltage)((2.8+/-0.1)) (r(2) = 0.996). in all scanning modes, CTDI100w decreased when RPW increased. CTDI100w was 10% higher in head mode and 13% lower in body mode compared with the value suggested by the manufacturer, which is displayed at the scanner console. When deposited power exceeded 24 kW, CTDI100w increased by 10% as a result of use of the large focal spot. CONCLUSION: The authors provide a set of tables of radiation dose as a function of imaging protocol to facilitate implementation of radiation dose-efficient studies. ((C)) RSNA, 2003. C1 Massachusetts Gen Hosp, Dept Radiol, Perfus & Physiol Anal Lab, Boston, MA 02114 USA. RP Hamberg, LM (reprint author), Massachusetts Gen Hosp, Dept Radiol, Perfus & Physiol Anal Lab, 55 Fruit St,Gray Bldg,Rm B238, Boston, MA 02114 USA. NR 3 TC 94 Z9 99 U1 1 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAR PY 2003 VL 226 IS 3 BP 762 EP 772 DI 10.1148/radiol.2263020205 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 649QV UT WOS:000181220200020 PM 12616020 ER PT J AU Tombach, B Benner, T Reimer, P Schuierer, G Fallenberg, EM Geens, V Wels, T Sorensen, AG AF Tombach, B Benner, T Reimer, P Schuierer, G Fallenberg, EM Geens, V Wels, T Sorensen, AG TI Do highly concentrated gadolinium chelates improve MR brain perfusion imaging? Intraindividually controlled randomized crossover concentration comparison study of 0.5 versus 1.0 mol/L gadobutrol SO RADIOLOGY LA English DT Article DE brain, MR; contrast media, comparative studies gadolinium magnetic resonance (MR), contrast media ID CEREBRAL BLOOD-FLOW; HIGH-RESOLUTION MEASUREMENT; TRACER BOLUS PASSAGES; CONTRAST AGENTS; MAGNETIC-SUSCEPTIBILITY; VOLUME MAPS; INJECTION AB PURPOSE: To assess the potential advantages of using a 1.0 mol/L versus 0.5 mol/L 1 gadobutrol formulation for magnetic resonance (MR) brain perfusion imaging. MATERIALS AND METHODS: Forty-three healthy volunteers were enrolled in an intraindividually controlled, randomized crossover comparison study. Two gadobutrol formulations-0.5 and 1.0 mol/L- were randomly injected during two separate treatment periods. For intraindividual comparison of effectiveness parameters, single-section gradient-echo brain perfusion MR imaging was performed under identical conditions for both investigations. Quantitative and qualitative evaluations were performed. Differences between the two gadobutrol formulations were evaluated at analysis of covariance and tested for statistical significance (P < .05) with,, a t test. RESULTS: Use of 1.0 mol/L gadobutrol resulted in a significantly smaller bolus width at half maximum signal intensity decrease, a smaller mean peak time, a higher contrast and contrast-to-noise ratio between gray and white matter, and significant increases in both maximum change in transverse relaxation rate (DeltaR2(max)) and,, I differences in peak enhancement in gray matter among all volunteers (P < .001). In white matter, increases in AR2(max). (P = .262) and in differences in peak enhancement (P = .262) were smaller and not significant (P = .292). Parameter map analysis revealed improved quality and superior contrast in relative regional cerebral blood flow (P = .034) and mean transit time (P < .001). The lack of difference regarding relative regional cerebral blood volume maps was consistent with the use of the same dose of each gadobutrol formulation. CONCLUSION: Brain perfusion images obtained with 1.0 mol/L gadobutrol were superior to those obtained with 0.5 mol/L gadobutrol in healthy volunteers examined with the described MR imaging protoeol. (C) RSNA, 2003. C1 Univ Munster, Dept Clin Radiol, D-48129 Munster, Germany. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Dept Radiol, Boston, MA 02114 USA. Acad Teaching Hosp, Dept Radiol, Freiburg, Germany. Bezirksklinikum Regensburg, Inst Neuroradiol, Dept Radiol, Regensburg, Germany. Schering Plough SpA, Berlin, Germany. RP Tombach, B (reprint author), Univ Munster, Dept Clin Radiol, Albert Schweitzer Str 33, D-48129 Munster, Germany. FU NINDS NIH HHS [R01NS38477] NR 32 TC 42 Z9 48 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 MAR PY 2003 VL 226 IS 3 BP 880 EP 888 DI 10.1148/radiol.2263011970 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 649QV UT WOS:000181220200034 PM 12601217 ER PT J AU Zalis, ME Perumpillichira, J Del Frate, C Hahn, PF AF Zalis, ME Perumpillichira, J Del Frate, C Hahn, PF TI CT colonography: Digital subtraction bowel cleansing with mucosal reconstruction - Initial observations SO RADIOLOGY LA English DT Article; Proceedings Paper CT 89th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America (RSNA) CY NOV 30-DEC 05, 2003 CL CHICAGO, ILLINOIS SP Radiol Soc North America DE colon, CT; computed tomography (CT), image processing; computed tomography (CT), image display and recording ID COLORECTAL-CANCER; POLYPS; COLONOSCOPY AB The authors evaluated a computed tomography (CT) colonographic technique with a combination of preex-amination orally ingested positive contrast material and postacquisition image processing to subtract out the ingested opacified bowel contents. With this technique, rigorous physical purging of the bowel was not necessary before structural examination of the colon. With images obtained in 20 patients, two readers were able to correctly identify the majority of polyps confirmed at colonoscopy. Their performance for detection of lesions larger than 1 cm was similar to that with conventional CT colonography. (C) RSNA, 2003. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Zalis, ME (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. NR 19 TC 83 Z9 85 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 MAR PY 2003 VL 226 IS 3 BP 911 EP 917 DI 10.1148/radiol.2263012059 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 649QV UT WOS:000181220200038 PM 12601218 ER PT J AU Cohen, SP Abdi, S AF Cohen, SP Abdi, S TI Lateral branch blocks as a treatment for sacroiliac joint pain: A pilot study SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Article; Proceedings Paper CT 1st Joint World Congress of Regional Anaesthesia and Pain Therapy CY MAY 29-JUN 01, 2002 CL BARCELONA, SPAIN DE injection; low back pain; radiofrequency; sacroiliac joint ID LOW-BACK-PAIN; LUMBAR FACET DENERVATION; RADIOFREQUENCY NEUROTOMY; EFFICACY; INJECTIONS AB Background and objectives: Pain arising from the sacroiliac (SI) joint is a common cause of low back pain for which there is no universally accepted, long-term treatment. Previous studies have shown radiofrequency (RF) procedures to be an effective treatment for other types of spinal pain. The purpose of this study was to determine the efficacy of reducing SI joint pain by percutaneous RF lesioning of the nerves innervating the SI joint. Methods: Eighteen patients with confirmed SI joint pain underwent nerve blocks of the L4- 5 primary dorsal rami and S1-3 lateral branches innervating the affected joint. Those who obtained 50% or greater pain relief from these blocks proceeded to undergo RF denervation of the nerves. Results: Thirteen of 18 patients who underwent L4-5 dorsal rami and S1-3 lateral branch blocks (LBB) obtained significant pain relief, with 2 patients reporting prolonged benefit. At their next visit, 9 patients who experienced >50% pain relief underwent RF lesioning of the nerves. Eight of 9 patients (89%) obtained greater than or equal to50% pain relief from this procedure that persisted at their 9-month follow-up. Conclusions: In patients with SI joint pain who respond to L4-5 dorsal rami and S1-3 LBB, RF denervation of these nerves appears to be an effective treatment. Randomized, controlled trials are needed to further evaluate this procedure. Reg Anesth Pain Med 2003,-28:113-119. C1 NYU, Pain Management Ctr, Sch Med, New York, NY 10016 USA. Walter Reed Army Med Ctr, Dept Anesthesiol, Pain Management Ctr, Washington, DC 20307 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pain Ctr,Dept Anesthesia & Crit Care, Boston, MA USA. RP Cohen, SP (reprint author), NYU, Pain Management Ctr, Sch Med, 317 E 34th St,9th Fl, New York, NY 10016 USA. NR 26 TC 68 Z9 69 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 1098-7339 J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD MAR-APR PY 2003 VL 28 IS 2 BP 113 EP 119 DI 10.1053/rapm.2003.50029 PG 7 WC Anesthesiology SC Anesthesiology GA 664GF UT WOS:000182052800008 PM 12677621 ER PT J AU Kemp, DM Thomas, MK Habener, JE AF Kemp, DM Thomas, MK Habener, JE TI Developmental aspects of the endocrine pancreas SO REVIEWS IN ENDOCRINE & METABOLIC DISORDERS LA English DT Article DE pancreas development; islets of Langerhans insulin; diabetes; transcription factors; beta cells; neogenesis ID GLUCAGON-LIKE PEPTIDE-1; HELIX TRANSCRIPTION FACTOR; NUCLEAR FACTOR 3-BETA; BETA-CELL GROWTH; HOMEODOMAIN PROTEIN IDX-1; INSULIN-SECRETING CELLS; II DIABETES-MELLITUS; SONIC HEDGEHOG; IN-VITRO; EXOCRINE PANCREAS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Lab Mol Endocrinol, Boston, MA 02114 USA. RP Habener, JE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Lab Mol Endocrinol, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK55365, DK02476] NR 100 TC 21 Z9 22 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-9155 J9 REV ENDOCR METAB DIS JI Rev. Endocr. Metab. Disord. PD MAR PY 2003 VL 4 IS 1 BP 5 EP 17 DI 10.1023/A:1021809917576 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 717BZ UT WOS:000185066900001 PM 12618555 ER PT J AU Stehle, T Dermody, TS AF Stehle, T Dermody, TS TI Structural evidence for common functions and ancestry of the reovirus and adenovirus attachment proteins SO REVIEWS IN MEDICAL VIROLOGY LA English DT Review ID JUNCTIONAL ADHESION MOLECULE; TYPE-5 FIBER PROTEIN; CRYSTAL-STRUCTURE; ANGSTROM RESOLUTION; SIALIC-ACID; 1.7-ANGSTROM RESOLUTION; ENVELOPE GLYCOPROTEIN; CELLULAR RECEPTOR; INDUCED APOPTOSIS; SEROTYPE-2 FIBER AB The crystal structure of the reovirus attachment protein, sigma1, reveals a fibre-like structure that is remarkably similar to that of the adenovirus attachment protein, fibre. Both proteins are trimers with head-and-tail morphology. They share unique domain structures and functional properties including defined regions of flexibility within the tail and an unusual symmetry mismatch with the pentameric viral capsid protein into which they are inserted. Moreover, the receptors for reoviruses and adenoviruses, junctional adhesion molecule 1 and coxsackievirus and adenovirus receptor, respectively, also share key structural and functional properties. Although reoviruses and adenoviruses belong to different virus families and have few properties in common, the observed similarities between sigma1 and fibre point to a conserved mechanism of attachment and an ancient evolutionary relationship. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Dev Immunol & Renal Unit, Boston, MA 02114 USA. Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Microbiol, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Immunol, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Elizabeth B Lamb Ctr Pediat Res, Nashville, TN 37232 USA. RP Stehle, T (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Dev Immunol & Renal Unit, Boston, MA 02114 USA. FU NIAID NIH HHS [AI45716, AI38296] NR 66 TC 20 Z9 21 U1 1 U2 5 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1052-9276 J9 REV MED VIROL JI Rev. Med. Virol. PD MAR-APR PY 2003 VL 13 IS 2 BP 123 EP 132 DI 10.1002/rmv.379 PG 10 WC Virology SC Virology GA 656CW UT WOS:000181592100007 PM 12627395 ER PT J AU Ambros, V Bartel, B Bartel, DP Burge, CB Carrington, JC Chen, XM Dreyfuss, G Eddy, SR Griffiths-Jones, S Marshall, M Matzke, M Ruvkun, G Tuschl, T AF Ambros, V Bartel, B Bartel, DP Burge, CB Carrington, JC Chen, XM Dreyfuss, G Eddy, SR Griffiths-Jones, S Marshall, M Matzke, M Ruvkun, G Tuschl, T TI A uniform system for microRNA annotation SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE microRNA; noncoding RNA; Rfam; Dicer; genome annotation ID SMALL RNAS; CAENORHABDITIS-ELEGANS/; TARGETS; PREDICTION; PROTEIN; LIN-14; PLANTS AB MicroRNAs (miRNAs) are small noncoding RNA gene products about 22 nt long that are processed by Dicer from precursors with a characteristic hairpin secondary structure. Guidelines are presented for the identification and annotation of new miRNAs from diverse organisms, particularly so that miRNAs can be reliably distinguished from other RNAs such as small interfering RNAs. We describe specific criteria for the experimental verification of miRNAs, and conventions for naming miRNAs and miRNA genes. Finally, an online clearinghouse for miRNA gene name assignments is provided by the Rfam database of RNA families. C1 Dartmouth Coll Sch Med, Dept Genet, Hanover, NH 03755 USA. Rice Univ, Dept Biochem & Cell Biol, Houston, TX 77005 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Whitehead Inst Biomed Res, Cambridge, MA 02139 USA. Rutgers State Univ, Waksman Inst, Piscataway, NJ 08854 USA. Univ Penn, Sch Med, Howard Hughes Med Inst, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. Washington Univ, Howard Hughes Med Inst, Dept Genet, St Louis, MO 63110 USA. Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. Austrian Acad Sci, Inst Mol Biol, A-5020 Salzburg, Austria. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Max Planck Inst Biophys Chem, Dept Cellular Biochem, Gottingen, Germany. MIT, Dept Biol, Cambridge, MA 02142 USA. RP Ambros, V (reprint author), Dartmouth Coll Sch Med, Dept Genet, 7400 Remsen, Hanover, NH 03755 USA. RI Bartel, Bonnie/D-3550-2011; Griffiths-Jones, Sam/H-2998-2014; Carrington, James/A-4656-2012; OI Bartel, Bonnie/0000-0002-6367-346X; Griffiths-Jones, Sam/0000-0001-6043-807X; Carrington, James/0000-0003-3572-129X; Eddy, Sean/0000-0001-6676-4706 NR 18 TC 942 Z9 1039 U1 9 U2 104 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD MAR PY 2003 VL 9 IS 3 BP 277 EP 279 DI 10.1261/rna.2183803 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 706HD UT WOS:000184447500002 PM 12592000 ER PT J AU Balch, CM Sober, AJ Soong, SJ Gershenwald, JE AF Balch, CM Sober, AJ Soong, SJ Gershenwald, JE CA AJCC Melanoma Staging Comm TI The new melanoma staging system SO SEMINARS IN CUTANEOUS MEDICINE AND SURGERY LA English DT Article ID AMERICAN JOINT COMMITTEE; LYMPH-NODE BIOPSY; DESMOPLASTIC NEUROTROPIC MELANOMA; CUTANEOUS MALIGNANT-MELANOMA; PROGNOSTIC FACTORS ANALYSIS; SENTINEL LYMPHADENECTOMY; MULTIFACTORIAL ANALYSIS; TUMOR THICKNESS; REGIONAL NODES; NECK MELANOMA AB The new melanoma staging system from The American Joint Committee on Cancer (AJCC) is described. This major revision includes new criteria for staging the primary tumor (T), metastatic nodes (N) and distant metastases (M) as well as stage groupings. These criteria more accurately reflect those prognostic features of the primary and metastatic melanoma that correlate with survival outcome. Physicians managing melanoma should use this staging system in their clinical practice and in the conduct of melanoma clinical trials. (C) 2003 Elsevier Inc. All rights reserved. C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Alabama, Birmingham, AL USA. RP Balch, CM (reprint author), Johns Hopkins Univ, 600 Wolfe St,Carnegie 681, Baltimore, MD 21287 USA. NR 63 TC 16 Z9 16 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 1085-5629 J9 SEMIN CUTAN MED SURG JI Semin. Cutan. Med. Surg. PD MAR PY 2003 VL 22 IS 1 BP 42 EP 54 DI 10.1053/sder.2003.50004 PG 13 WC Dermatology; Surgery SC Dermatology; Surgery GA 675MK UT WOS:000182699000006 PM 12773013 ER PT J AU Worrall, BB Azhar, S Nyquist, PA Ackerman, RH Hamm, TL DeGraba, TJ AF Worrall, BB Azhar, S Nyquist, PA Ackerman, RH Hamm, TL DeGraba, TJ TI Interleukin-1 receptor antagonist gene Polymorphisms in carotid atherosclerosis SO STROKE LA English DT Article; Proceedings Paper CT 25th International Stroke Conference CY FEB 10, 2000 CL NEW ORLEANS, LOUISIANA SP Amer Heart Assoc DE atherosclerosis; carotid artery diseases; cytokines; interleukin-1 receptor antagonist; polymorphism ID DISEASE; ASSOCIATION; INFLAMMATION; VARIANTS; IL-1RA AB Background and Purpose-Inflammation plays an important role in the development of atherosclerosis. The gene for the counterinflammatory cytokine interleukin-1 receptor antagonist (IL-1ra) is polymorphic, and high frequencies of allele 2 have been found to be associated with other inflammatory diseases. This study examined the association of allele and carrier frequencies of the IL-1ra gene with the presence of carotid atherosclerosis and plaque symptomaticity. Methods-A total of 328 subjects identified as having carotid atherosclerosis or no atherosclerosis (controls) participated. Blood was obtained for DNA determination. Results-Frequency of allele 2 was significantly greater in patients with atherosclerosis compared with nonatherosclerotic subjects. No difference was seen between symptomatic and asymptomatic atherosclerosis patients. Noncarriage of allele 2 was associated with reduced likelihood of atherosclerosis (odds ratio [OR], 0.44; 95% CI, 0.27 to 0.71). The homozygous carrier state for allele 2 was associated with greater likelihood of atherosclerosis (unadjusted OR, 7.30; 95% CI, 2.31 to 22.94; adjusted OR, 13.78; 95% CI, 1.94 to 97.9). A gene-dose effect was detected. Conclusions-These data suggest that allele 2 of the IL-1ra gene represents a susceptibility factor in the development of carotid atherosclerosis. Further investigation appears warranted. C1 Natl Naval Med Res Inst, Clin Stroke Res Unit, Dept Neurol, Bethesda, MD 20889 USA. Univ Virginia, Dept Neurol, Charlottesville, VA USA. Univ Virginia, Dept Hlth Evaluat Sci, Charlottesville, VA USA. NINDS, Stroke Branch, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. RP DeGraba, TJ (reprint author), Natl Naval Med Res Inst, Clin Stroke Res Unit, Dept Neurol, Bldg 9,2nd Deck,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM TJDeGraba@bethesda.med.navy.mil NR 15 TC 37 Z9 42 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAR PY 2003 VL 34 IS 3 BP 790 EP 793 DI 10.1161/01.STR.0000057815.79289.EC PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 653ZJ UT WOS:000181466700044 PM 12624309 ER PT J AU Freytes, CO AF Freytes, CO TI Progress in central venous access? SO SUPPORTIVE CARE IN CANCER LA English DT Editorial Material ID ULTRASOUND GUIDANCE; SUCCESS RATE C1 Univ Texas, Hlth Sci Ctr, Adult Bone Marrow Transplant Program, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Freytes, CO (reprint author), Univ Texas, Hlth Sci Ctr, Adult Bone Marrow Transplant Program, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD MAR PY 2003 VL 11 IS 3 BP 135 EP 136 DI 10.1007/s00520-002-0430-8 PG 2 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 657JT UT WOS:000181663300002 PM 12618921 ER PT J AU Stephen, AE Berger, DL AF Stephen, AE Berger, DL TI Shortened length of stay and hospital cost reduction with implementation of an accelerated clinical care pathway after elective colon resection SO SURGERY LA English DT Article ID LAPAROSCOPIC SURGERY; COLORECTAL SURGERY; SIGMOID COLECTOMY; OUTCOMES; QUALITY; DIVERTICULITIS; DECOMPRESSION; RECOVERY; CANCER; TRIAL AB Background. Patient care pathways have been developed for operative procedures with documented improvements in length of stay and cost without compromising outcome. The average hospital stay after colonic resection is 5 to 10 days. This study describes a clinical pathway,for colon resections and examines patient outcome before and after institution of the pathway. Methods. One hundred thirty-eight patients underwent elective colon resections at our institution by a single surgeon before (n = 52) and after (n = 86) introduction of a clinical pathway. Length of stay, postoperative complications, readmissions, and cost per patient were compared between the 2 groups. Results. Mean total length of stay ( standard deviation [SD]) was less in the postclinical pathway patients (3.7 +/- 1.5 days) compared to preclinical pathway patients (6.6 +/- 3.3 days) (P <. 001). Men adjusted for age, sex, diagnosis, and type of operation, the difference in length of stay remains statistically significant (P < .001). There was 1 readmission in the prepathway group and 8 readmissions in the postpathway group. Men the readmissions were added to the original admissions, the mean length of stay in the postpathway patients was 4.2 +/- 2.8 days and in the prepathway patients was 6.9 +/- 4.1 days (P <. 001). The average cost per patient ( standard error of the mean), with readmission costs added, was $9310 +/- $5170 in the prepathway group and $7070 +/- $3670 in the postpathway group (P = .002). Conclusions. The institution of a clinical pathway for elective, open colon resections can be done safely with improvements in cost and length of stay. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Berger, DL (reprint author), Massachusetts Gen Hosp, Dept Surg, ACC 465,15 Parkman St, Boston, MA 02114 USA. NR 26 TC 116 Z9 122 U1 1 U2 9 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAR PY 2003 VL 133 IS 3 BP 277 EP 282 DI 10.1067/msy.2003.19 PG 6 WC Surgery SC Surgery GA 661LY UT WOS:000181893100008 PM 12660639 ER PT J AU Hunt, DP Haidet, P Coverdale, JH Richards, B AF Hunt, DP Haidet, P Coverdale, JH Richards, B TI The effect of using team learning in an evidence-based medicine course for medical students SO TEACHING AND LEARNING IN MEDICINE LA English DT Article ID EDUCATION AB Background: We implemented team learning, an instructional method that fosters small-group learning, in an evidence-based medicine (EBM) course. Our goal was to align instructional methods with EBM practices. Description: Team learning provides an alternative to lectures in large-group settings. It involves out-of-class preparation followed by in-class readiness assurance tests and group application activities. We used the method to teach a 7-week course in EBM for 2nd-year students. We evaluated the course using student performance, external observation, and student focus groups. Evaluation: Students performed well on all written assignments, indicating attainment of learning objectives. Observation data revealed a high level of student engagement in the classroom. Focus group data indicated that desired learning behaviors tended to occur but that many students devalued the method. Conclusion: Team learning served as a useful framework, enabling a large enrollment course to have small-group experiences without large numbers of faculty. The method fostered individual accountability and promoted teamwork-behaviors consistent with effective EBM practice. Students' lack of enthusiasm for the method may stem from their comfort with didactic lectures. C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Houston, TX USA. Baylor Coll Med, Dept Psychiat & Behav Sci, Houston, TX 77030 USA. Baylor Coll Med, Off Curriculum, Houston, TX 77030 USA. RP Hunt, DP (reprint author), Baylor Coll Med, Dept Med Gen Med, 1 Baylor Plaza,Mail Code BTGH, Houston, TX 77030 USA. NR 19 TC 69 Z9 70 U1 2 U2 6 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 1040-1334 J9 TEACH LEARN MED JI Teach. Learn. Med. PD SPR PY 2003 VL 15 IS 2 BP 131 EP 139 DI 10.1207/S15328015TLM1502_11 PG 9 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 666UF UT WOS:000182194300011 PM 12708072 ER PT J AU Kyriakis, J Chadee, DN AF Kyriakis, J Chadee, DN TI Functions of apoptosis signal-regulating kinase-1 revealed by RNA interference. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Massachusetts Gen Hosp, Diabet Res Lab, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 563 BP 116 EP 116 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518500566 ER PT J AU Handley, HM Stegeman, JJ Fishman, MC AF Handley, HM Stegeman, JJ Fishman, MC TI Characterization of TCDD-responsive genes identified by cDNA microarray analysis. SO TOXICOLOGICAL SCIENCES LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 2003 CL SALT LAKE CITY, UTAH SP Soc Toxicol C1 Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Novartis Inst Biomed Res Inc, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2003 VL 72 SU S MA 1284 BP 264 EP 264 PG 1 WC Toxicology SC Toxicology GA 654WB UT WOS:000181518501289 ER PT J AU Leon, P Sheen, J AF Leon, P Sheen, J TI Sugar and hormone connections SO TRENDS IN PLANT SCIENCE LA English DT Editorial Material ID ABSCISIC-ACID BIOSYNTHESIS; RESPONSIVE GENE-EXPRESSION; PROTEIN PHOSPHATASE 2C; SIGNAL-TRANSDUCTION; ARABIDOPSIS-THALIANA; 9-CIS-EPOXYCAROTENOID DIOXYGENASE; VEGETATIVE DEVELOPMENT; TRANSCRIPTION FACTOR; INSENSITIVE MUTANTS; HIGHER-PLANTS AB Sugars modulate many vital processes that are also controlled by hormones during plant growth and development. Characterization of sugar-signalling mutants in Arabidopsis has unravelled a complex signalling network that links sugar responses to two plant stress hormones - abscisic acid and ethylene - in opposite ways. Recent molecular analyses have revealed direct, extensive glucose control of abscisic acid biosynthesis and signalling genes that partially antagonizes ethylene signalling during seedling development under light. Glucose and abscisic acid promote growth at low concentrations but act synergistically to inhibit growth at high concentrations. The effects of sugar and osmotic stress on morphogenesis and gene expression are distinct. The plasticity of plant growth and development are exemplified by the complex interplay of sugar and hormone signalling. C1 Univ Nacl Autonoma Mexico, Inst Biotecnol, Dept Biol Mol Plantas, Cuernavaca 62271, Morelos, Mexico. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. RP Sheen, J (reprint author), Univ Nacl Autonoma Mexico, Inst Biotecnol, Dept Biol Mol Plantas, Cuernavaca 62271, Morelos, Mexico. NR 58 TC 324 Z9 349 U1 5 U2 59 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1360-1385 J9 TRENDS PLANT SCI JI Trends Plant Sci. PD MAR PY 2003 VL 8 IS 3 BP 110 EP 116 DI 10.1016/S1360-1385(03)00011-6 PG 7 WC Plant Sciences SC Plant Sciences GA 666UN UT WOS:000182195000005 PM 12663220 ER PT J AU Lee, AK Doytchinova, T Chen, MH Renshaw, AA Weinstein, M Richie, JP D'Amico, AV AF Lee, AK Doytchinova, T Chen, MH Renshaw, AA Weinstein, M Richie, JP D'Amico, AV TI Can the core length involved with prostate cancer identify clinically insignificant disease in low risk patients diagnosed on the basis of a single positive core? SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE prostate cancer; percent positive biopsies; clinically insignificant; prostate-specific antigen; outcome ID BEAM RADIATION-THERAPY; RADICAL PROSTATECTOMY; TUMOR VOLUME; BIOPSIES; ANTIGEN; PREDICT; UTILITY; MEN AB Clinically insignificant prostate cancer, defined as at most microscopic foci of Gleason grade less than or equal to 3 disease in the radical prostatectomy specimen, has been recognized in some low risk (PSA <10, biopsy Gleason score less than or equal to6, clinical T1c, 2a) patients with minimal biopsy cancer volume. The purpose of this study is to determine if the fraction of cancer in a single positive core biopsy could identify a subset of low risk prostate cancer patients with clinically insignificant disease. Of 1100 patients with T1c,2 prostate cancer that consecutively underwent radical prostatectomy at Brigham and Women's Hospital between 1989 to 2000, 130 low risk patients whose diagnoses were made on the basis of a single positive core comprised the study cohort. The pathologic findings at radical prostatectomy were enumerated for men with less than or equal to5% of a single core involved with prostate cancer in order to determine the rate of clinically insignificant prostate cancer in this population. Estimates of PSA survival were calculated using the actuarial method of Kaplan and Meier. Pairwise comparisons were made using the log rank test. For patients with less than or equal to5% (n = 14) and > 5% (n = 116) involvement of a single positive core, the 4 year PSA failure free survivals were 100% vs. 89% (P = 0.048), respectively. Within the subset of patients with less than or equal to5% of a single core involved, 7% (1/14) met the criteria for clinically insignificant disease. However, of the remaining 93%, 3, 8, and 2 patients had pathologic stage T2a, T2b, and T3a, respectively. Eleven patients had prostatectomy Gleason scores less than or equal to 3 + 3, two patients had pathologic Gleason scores of 3 + 4, and one patient had a positive surgical margin. Given that only 7% of low risk patients in this cohort with less than or equal to5% involvement of a single positive core had clinically insignificant disease, the involved core length alone cannot be used to identify patients with clinically insignificant disease. Further studies are needed in order to delineate which patients may not benefit from treatment. (C) 2003 Elsevier Science Inc. All rights reserved. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Worcester Polytech Inst, Dept Math, Worcester, MA 01609 USA. Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA USA. RP Lee, AK (reprint author), Joint Ctr Radiat Therapy, 1515 Holcombe Blvd,Box 97, Houston, TX 77030 USA. NR 17 TC 12 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 J9 UROL ONCOL-SEMIN O I JI Urol. Oncol.-Semin. Orig. Investig. PD MAR-APR PY 2003 VL 21 IS 2 BP 123 EP 127 AR PII S1078-1439(02)00240-5 DI 10.1016/S1078-1439(02)00240-5 PG 5 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 694CA UT WOS:000183755200005 PM 12856640 ER PT J AU Wessells, H Roy, J Bannow, J Grayhack, J Matsumoto, AM Tenover, L Herlihy, R Fitch, W Labasky, R Auerbach, S Parra, R Rajfer, J Culbertson, J Lee, M Bach, MA Waldstreicher, J AF Wessells, H Roy, J Bannow, J Grayhack, J Matsumoto, AM Tenover, L Herlihy, R Fitch, W Labasky, R Auerbach, S Parra, R Rajfer, J Culbertson, J Lee, M Bach, MA Waldstreicher, J CA PLESS study Grp TI Incidence and severity of sexual adverse experiences in finasteride and placebo-treated men with benign prostatic hyperplasia SO UROLOGY LA English DT Article ID OBSTRUCTION SYMPTOMATIC BPH; URINARY-TRACT SYMPTOMS; MALE PSEUDOHERMAPHRODITISM; CONTROLLED TRIAL; TERAZOSIN; TAMSULOSIN; MULTICENTER; ANTAGONIST; COMMUNITY; EFFICACY AB Objectives. To evaluate the incidence and resolution of sexual adverse experiences (AEs) in men with benign prostatic hyperplasia treated with finasteride 5 mg compared with placebo. Methods. The Proscar Long-term Efficacy and Safety Study (PLESS) was a 4-year, randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of finasteride 5 mg in 3040 men, aged 45 to 78 years, with symptomatic benign prostatic hyperplasia, enlarged prostates, and no evidence of prostate cancer. Patients completed a questionnaire at screening regarding their history of sexual dysfunction. During treatment, spontaneously self-reported sexual AEs were recorded. Results. At screening, 46% of patients in each treatment group reported some history of sexual dysfunction. During year 1 of the study, 15% of finasteride-treated patients and 7% of placebo-treated patients had sexual AEs that were considered drug related by the investigator (P < 0.001). During years 2 to 4, no between-group difference was noted in the incidence of new sexual AEs (7% in each group). The drug-related sexual AE profile for finasteride was similar for men with or without a history of sexual dysfunction. Sexual AEs resolved while continuing therapy in 12% of finasteride patients and 19% of placebo patients. Only 4% of finasteride and 2% of placebo patients discontinued the study because of sexual AEs. In men who discontinued with a sexual AE, 50% and 41% experienced resolution of their sexual AE after discontinuing finasteride or placebo therapy, respectively. Conclusions. Compared with placebo, men treated with finasteride experienced new drug-related sexual AEs with an increased incidence only during the first year of therapy. (C) 2003, Elsevier Science Inc. C1 Merck Res Labs, Rahway, NJ 07065 USA. Edmond, Oklahoma City, OK USA. Cedarwood Med Ctr, St Joseph, MI USA. NW Univ, Chicago, IL USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Wesley Woods Hlth Ctr, Atlanta, GA USA. Oklahoma City Clin, Oklahoma City, OK USA. St Louis Univ Hosp, St Louis, MO USA. Univ Calif Los Angeles, Ctr Med, Los Angeles, CA USA. RP Waldstreicher, J (reprint author), Merck Res Labs, 126 E Lincoln Ave,RY34-212, Rahway, NJ 07065 USA. NR 24 TC 51 Z9 56 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD MAR PY 2003 VL 61 IS 3 BP 579 EP 584 DI 10.1016/S0090-4295(02)02401-9 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 662CJ UT WOS:000181928200022 PM 12639651 ER PT J AU Mazzucco, D Spector, M AF Mazzucco, D Spector, M TI Effects of contact area and stress on the volumetric wear of ultrahigh molecular weight polyethylene SO WEAR LA English DT Article DE polyethylene; prosthetic joint; contact area; pin-on-flat tester; nominal contact stress ID TOTAL HIP-REPLACEMENT; MULTIDIRECTIONAL MOTION; FEMORAL HEADS; UHMWPE; SIMULATION; LUBRICANT; SOCKETS; JOINTS; INVIVO; KNEE AB The effects of contact area and contact stress on the wear of ultrahigh molecular weight polyethylene (PE) articulating with a polished surface of cobalt-chromium alloy were evaluated using a pin-on-disk apparatus implementing bi-directional movement. Within a relevant range of contact stresses, volumetric wear rate increased with increasing contact area. Volumetric wear was found to be independent of normal load within this range. Mechanistic issues related to these findings are discussed. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Francis Sch 75, Dept Orthopaed Surg, Boston, MA 02115 USA. MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Spector, M (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Francis Sch 75, Dept Orthopaed Surg, Boston, MA 02115 USA. NR 23 TC 34 Z9 35 U1 0 U2 2 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0043-1648 J9 WEAR JI Wear PD MAR PY 2003 VL 254 IS 5-6 BP 514 EP 522 DI 10.1016/S0043-1648(03)00135-2 PG 9 WC Engineering, Mechanical; Materials Science, Multidisciplinary SC Engineering; Materials Science GA 688UD UT WOS:000183454000014 ER PT J AU Washington, DL Caffrey, C Goldzweig, C Simon, B Yano, EM AF Washington, DL Caffrey, C Goldzweig, C Simon, B Yano, EM TI Availability of comprehensive women's health care through Department of Veterans Affairs medical center SO WOMENS HEALTH ISSUES LA English DT Article DE women's health services; health services accessibility; hospitals, veterans; ambulatory care/utilization AB Despite increased numbers of women veterans, little is known about health services delivery to women across the Department of Veterans Affairs (VA). To assess VA availability of women's health services, we surveyed the senior clinician at each VA site serving 400 or more women veterans. We found that virtually all sites have developed arrangements, either directly or through off-site contracts, to ensure availability of comprehensive women's health care. On-site care, however, is routinely available only for basic services. Future work should evaluate cost and quality trade-offs between using non-VA sites to increase specialized service availability and using VA sites to enhance continuity of care. C1 VA Greater Los Angeles Healthcare Syst, R&D Ctr Excellence, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Kaiser Permanente, Lancaster, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Washington, DL (reprint author), VA Greater Los Angeles Healthcare Syst, R&D Ctr Excellence, 11301 Wilshire Blvd,111G, Los Angeles, CA 90073 USA. NR 14 TC 37 Z9 37 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD MAR-APR PY 2003 VL 13 IS 2 BP 50 EP 54 AR PII S1049-3867(02)00195-0 DI 10.1016/S1049-3867(02)00195-0 PG 5 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 674EF UT WOS:000182623700003 PM 12732440 ER PT J AU Baumgarten, M Margolis, D Berlin, JA Strom, BL Garino, J Kagan, SH Kavesh, W Carson, JL AF Baumgarten, M Margolis, D Berlin, JA Strom, BL Garino, J Kagan, SH Kavesh, W Carson, JL TI Risk factors for pressure ulcers among elderly hip fracture patients SO WOUND REPAIR AND REGENERATION LA English DT Article ID DECUBITUS ULCERS; CLINICAL-TRIAL; NURSING-HOMES; FEMORAL-NECK; SORES; PREVENTION; EPIDEMIOLOGY; PREVALENCE; MANAGEMENT; OPERATIONS AB The purpose of this study was to estimate the incidence of hospital-acquired pressure ulcers among elderly patients hospitalized for hip fracture surgery and to identify extrinsic factors that are associated with increased risk. We conducted a secondary analysis of data abstracted from medical records at 20 hospitals in Pennsylvania, Texas, New Jersey, and Virginia. Participants were patients aged 60 years and older admitted with hip fracture to the study hospitals between 1983 and 1993. The incidence of hospital-acquired pressure ulcers was 8.8% (95% confidence interval 8.2%-9.4%). After adjusting for confounding variables, longer wait before surgery, intensive care unit stay, longer surgical procedure, and general anesthesia were significantly associated with higher pressure ulcer risk. Extrinsic factors may be important markers for high pressure ulcer risk in hospitalized hip fracture patients. Although it is not possible to eliminate factors such as requiring an intensive care unit stay or having a long surgical procedure, it may be possible to develop interventions that minimize pressure ulcer risk in patients who experience these factors. C1 Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA. RP Baumgarten, M (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, 660 W Redwood St,Suite 200, Baltimore, MD 21201 USA. FU AHRQ HHS [1-R01-HS07322] NR 67 TC 48 Z9 51 U1 1 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD MAR-APR PY 2003 VL 11 IS 2 BP 96 EP 103 DI 10.1046/j.1524-475X.2003.11204.x PG 8 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 654GJ UT WOS:000181485600002 PM 12631296 ER PT J AU Koulmanda, M Qipo, AD Smith, RN Auchincloss, H AF Koulmanda, M Qipo, AD Smith, RN Auchincloss, H TI Pig islet xenografts are resistant to autoimmune destruction by non-obese diabetic recipients after anti-CD4 treatment SO XENOTRANSPLANTATION LA English DT Article DE autoimmunity; isograft; non-obese diabetic mice; streptozotocin; xenotransplantation ID MICE; TRANSPLANTATION; ALLOGRAFTS; REJECTION; ISOGRAFTS AB In addition to providing a large source of donor tissue, xenogeneic islet transplantation might avoid recurrent autoimmunity in patients with type 1 diabetes. To examine this possibility further, xenogeneic pig islets were transplanted into recipient mice in the presence or absence of autoimmunity. Spontaneously, non-obese diabetic (NOD) recipients rejected isografts rapidly whether or not the recipients were depleted of CD4+ T-cells. Young NOD mice made diabetic with streptozotocin accepted islet isografts without immunosuppression, indicating that destructive autoimmunity did not develop in these recipients. Pig xenografts were rejected equally quickly in the two types of NOD recipients in the absence of immunosuppression and survived for up to 9 weeks in both types of NOD recipients after CD4 depletion. BALB/c mice often accepted pig xenografts indefinitely after anti-CD4 antibody treatment. These results suggest that pig islets are resistant to recurrent autoimmunity when CD4+ T-cells are depleted. The difficulty in obtaining indefinite islet xenograft survival in NOD recipients occurs independently from the development of destructive autoimmunity. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Islet Transplantat Lab,Sch Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Koulmanda, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Islet Transplantat Lab,Sch Med, WH 536,55 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [P01 DK53087] NR 16 TC 15 Z9 17 U1 1 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD MAR PY 2003 VL 10 IS 2 BP 178 EP 184 DI 10.1034/j.1399-3089.2003.02040.x PG 7 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 646HT UT WOS:000181030100009 PM 12588650 ER PT J AU Cindhuchao, N Quinn, DA Garg, HG Hales, CA AF Cindhuchao, N Quinn, DA Garg, HG Hales, CA TI Heparin inhibits SMC growth in the presence of human and fetal bovine serum SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE heparin; pulmonary artery smooth muscle cell; fetal bovine serum; human serum ID SMOOTH-MUSCLE CELLS; HYPOXIC PULMONARY-HYPERTENSION; STRUCTURAL DETERMINANTS; PROLIFERATION AB Heparin (HP) has antiproliferative as well as anticoagulant properties, but not all HP preparations are equally antiproliferative. A recent report found that HP lost its total antiproliferative activity when fetal bovine serum (FBS) was replaced with human serum (HS) in culture media. This observation led to the investigation of our most potent antiproliferative Upjohn HP preparation effects on bovine pulmonary artery smooth muscle cells (PASMC) and systemic SMC growth stimulated in the presence of either FBS or HS. Bovine PASNIC, human PASMC, and bovine aortic SMC were treated with 10 mug/ml Upjohn HP in either 15% FBS or 15% HS and the cell number was determined by a Coulter counter. We found that Upjohn HP significantly inhibited bovine PASMC and systemic SMC proliferation in both HS and FBS. The antiproliferative activity of the above HP preparation in HS may lead to an effective treatment of pulmonary vascular and systemic remodeling. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Massachusetts Gen Hosp, Dept Med, Pulm Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Garg, HG (reprint author), Massachusetts Gen Hosp, Dept Med, Pulm Crit Care Unit, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL03920, HL39150] NR 22 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 28 PY 2003 VL 302 IS 1 BP 84 EP 88 DI 10.1016/S0006-291X(03)00068-8 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 654KW UT WOS:000181496900014 PM 12593851 ER PT J AU Grziwa, B Grimm, MOW Masters, CL Beyreuther, K Hartmann, T Lichtenthaler, SF AF Grziwa, B Grimm, MOW Masters, CL Beyreuther, K Hartmann, T Lichtenthaler, SF TI The transmembrane domain of the amyloid precursor protein in microsomal membranes is on both sides shorter than predicted SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GAMMA-SECRETASE ACTIVITY; STAPHYLOCOCCAL ALPHA-HEMOLYSIN; ALZHEIMERS-DISEASE; BETA-PROTEIN; INTRAMEMBRANE CLEAVAGE; INTRACELLULAR DOMAIN; SCANNING MUTAGENESIS; GOLGI-APPARATUS; KEY RESIDUES; NOTCH AB The amyloid precursor protein is cleaved within its ectodomain by beta-amyloid-converting enzyme (BACE) yielding C99, which is further cleaved by gamma-secretase within its putative transmembrane domain (TMD). Because it is difficult to envisage how a protease may cleave within the membrane, alternative mechanisms have been proposed for gamma-cleavage in which the TMD is shorter than predicted or positioned such that the gamma-cleavage site is accessible to cytosolic proteases. Here, we have biochemically determined the length of the TMD of C99 in microsomal membranes. Using a single cysteine mutagenesis scan of C99 combined with cysteine modification with a membrane-impermeable labeling reagent, we identified which residues are accessible to modification and thus located outside of the membrane. We find that in endoplasmic reticulum-derived microsomes the TMD of C99 consists of 12 residues that span from residues 37 to 48, which is N- and C-terminally shorter than predicted. Thus, the gamma-cleavage sites are positioned around the middle of the lipid bilayer and are unlikely to be accessible to cytosolic proteases. Moreover, the center of the TMD is positioned at the gamma-cleavage site at residue 42. Our data are consistent with a model in which gamma-secretase is a membrane protein that cleaves at the center of the membrane. C1 Univ Heidelberg, Ctr Mol Biol, D-69120 Heidelberg, Germany. Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Grziwa, B (reprint author), Univ Heidelberg, Ctr Mol Biol, INF 282, D-69120 Heidelberg, Germany. RI Grimm, Marcus/F-8134-2011; Lichtenthaler, Stefan/B-6587-2016; OI Grimm, Marcus/0000-0002-4160-6506; Lichtenthaler, Stefan/0000-0003-2211-2575; Hartmann, Tobias/0000-0001-7481-6430 NR 47 TC 32 Z9 32 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 28 PY 2003 VL 278 IS 9 BP 6803 EP 6808 DI 10.1074/jbc.M210047200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 649EZ UT WOS:000181195100023 PM 12454010 ER PT J AU Minami, T Abid, MR Zhang, J King, G Kodama, T Aird, WC AF Minami, T Abid, MR Zhang, J King, G Kodama, T Aird, WC TI Thrombin stimulation of vascular adhesion molecule-1 in endothelial cells is mediated by protein kinase C (PKC)-delta-NF-kappa B and PKC-zeta-GATA signaling pathways SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SMOOTH-MUSCLE CELLS; NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR; COUPLED RECEPTOR; GENE-EXPRESSION; FACTOR-ALPHA; PHOSPHOINOSITIDE 3-KINASE; ACTIVATION; PHOSPHORYLATION AB We recently demonstrated that thrombin induces the expression of vascular adhesion molecule-1 (VCAM-1) in endothelial cells by an NF-kappaB- and GATA-dependent mechanism. In the present study, we describe the signaling pathways that mediate this response. Thrombin stimulation of the VCAM-1 gene and promoter in human umbilical vein endothelial cells was inhibited by preincubation with the phosphatidylinositol 3-kinase inhibitor, LY294002, the protein kinase C (PKC)-delta inhibitor, rottlerin, a PKC-xi peptide inhibitor, or by overexpression of dominant negative (DN)-PKC-xi. In electrophoretic mobility shift assays, thrombin-mediated induction of NF-kappaB p65 binding to two NF-kappaB motifs in the upstream promoter region of VCAM-1 was blocked by LY294002 and rottlerin, whereas the inducible binding of GATA-2 to a tandem GATA motif was inhibited by LY294002 and the PKC-xi peptide inhibitor. In co-transfection assays, thrombin stimulation of a minimal promoter containing multimerized VCAM-1 NF-kappaB sites was inhibited by DN-PKC-delta but not DN-PKC-xi. In contrast, thrombin-mediated transactivation of a minimal promoter containing tandem VCAM-1 GATA motifs was inhibited by DN-PKC-xi but not DN-PKC-delta. Finally, thrombin failed to induce VCAM-1 expression in vascular smooth muscle cells. Taken together, these data suggest that the endothelial cell-specific effect of thrombin on VCAM-1 expression involves the coordinate activity of PKC-delta-NF-kappaB and PKC-xi-GATA signaling pathways. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Mol Med, Boston, MA 02215 USA. Univ Tokyo, Lab Syst Biol & Med Res, Ctr Adv Sci & Technol, Tokyo 1538904, Japan. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Aird, WC (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Mol Med, RW-663, Boston, MA 02215 USA. FU NHLBI NIH HHS [HL 65216-03, HL 63609-02, HL 60585-02] NR 64 TC 83 Z9 94 U1 0 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 FEB 28 PY 2003 VL 278 IS 9 BP 6976 EP 6984 DI 10.1074/jbc.M208974200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 649EZ UT WOS:000181195100046 PM 12493764 ER PT J AU Moody, AM North, SJ Reinhold, B Van Dyken, SJ Rogers, ME Panico, M Dell, A Morris, HR Marth, JD Reinherz, EL AF Moody, AM North, SJ Reinhold, B Van Dyken, SJ Rogers, ME Panico, M Dell, A Morris, HR Marth, JD Reinherz, EL TI Sialic acid capping of CD8 beta core 1-O-glycans controls thymocyte major histocompatibility complex class I interaction SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CD8 CORECEPTOR FUNCTION; T-CELL ACTIVATION; PEANUT AGGLUTININ; POSITIVE SELECTION; MASS-SPECTROMETRY; MHC CLASS; GLYCOSYLATION; EXPRESSION; BINDING; DIFFERENTIATION AB Bidentate interaction of a T-cell receptor and CD8alphabeta heterodimer with a peptide-MHCI complex is required for the generation of cytotoxic T-lymphocytes. During thymic development, the modification of CD8beta glycans influences major histocompatibility complex class I binding to T-cell precursors called thymocytes. ES mass spectrometry (MS) and tandem MS/MS analysis were used to identify the changes occurring in the CD8beta-glycopeptides during T-cell development. Several threonine residues proximal to the CD8beta Ig headpiece are glycosylated with core-type 1 O-glycans. Non-sialylated glycoforms are present in immature thymocytes ut are virtually absent in mature thymocytes. These results suggest how sialylation in a discrete segment of the CD8beta stalk by ST3Gal-1 sialyltransferase creates a molecular developmental switch that affects ligan binding. C1 Dana Farber Canc Inst, Immunobiol Lab, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Med, Boston, MA 02115 USA. Univ London Imperial Coll Sci Technol & Med, Dept Sci Biol, London SW7 2AY, England. MSCAN Res & Training Ctr, Ascot SL5 7PZ, Berks, England. MSCAN Inc, W Chester, PA 19380 USA. Univ Calif San Diego, Howard Hughes Med Inst, Dept Cellular & Mol Med, San Diego, CA 92093 USA. RP Reinherz, EL (reprint author), Dana Farber Canc Inst, Immunobiol Lab, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI45022] NR 34 TC 58 Z9 58 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 28 PY 2003 VL 278 IS 9 BP 7240 EP 7246 DI 10.1074/jbc.M210468200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 649EZ UT WOS:000181195100079 PM 12459555 ER PT J AU Gupta, RA Sarraf, P Brockman, JA Shappell, SB Raftery, LA Willson, TM DuBois, RN AF Gupta, RA Sarraf, P Brockman, JA Shappell, SB Raftery, LA Willson, TM DuBois, RN TI Peroxisome proliferator-activated receptor gamma and transforming growth factor-beta pathways inhibit intestinal epithelial cell growth by regulating levels of TSC-22 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PPAR-GAMMA; TGF-BETA; STIMULATED CLONE-22; COLORECTAL-CANCER; HUMAN-COLON; IN-VIVO; DIFFERENTIATION; GENE; EXPRESSION; MOUSE AB Peroxisome proliferator-activated receptor gamma(PPARgamma) and transforming growth factor-beta (TGF-beta) are key regulators of epithelial cell biology. However, the molecular mechanisms by which either pathway induces growth inhibition and differentiation are incompletely understood. We have identified transforming growth factor-simulated clone-22 (TSC-22) as a target gene of both pathways in intestinal epithelial cells. TSC-22 is member of a family of leucine zipper containing transcription factors with repressor activity. Although little is known regarding its function in mammals, the Drosophila homolog of TSC-22, bunched, plays an essential role in fly development. The ability of PPARgamma to induce TSC-22 was not dependent on an intact TGF-beta1 signaling pathway and was specific for the gamma isoform. Localization studies revealed that TSC-22 mRNA is enriched in the postmitotic epithelial compartment of the normal human colon. Cells transfected with wild-type TSC-22 exhibited reduced growth rates and increased levels of p21 compared with vector-transfected cells. Furthermore, transfection with a dominant negative TSC-22 in which both repressor domains were deleted was able to reverse the p21 induction and growth inhibition caused by activation of either the PPARgamma or TGF-beta pathways. These results place TSC-22 as an important downstream component of PPARgamma and TGF-beta signaling during intestinal epithelial cell differentiation. C1 Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Cellular & Dev Biol, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Psychiat Genom Inc, Gaithersburg, MD 20878 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. GlaxoSmithKline, Nucl Receptor Discovery Res, Res Triangle Pk, NC 27709 USA. RP DuBois, RN (reprint author), Vanderbilt Univ, Med Ctr, Dept Med GI, MCN C-2104,1161 21st Ave S, Nashville, TN 37232 USA. RI Raftery, Laurel/H-1406-2012 OI Raftery, Laurel/0000-0003-4797-4163 FU NCI NIH HHS [P01CA-77839]; NIDDK NIH HHS [R01DK 47279]; NIEHS NIH HHS [P030 ES-00267-29] NR 49 TC 54 Z9 56 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 28 PY 2003 VL 278 IS 9 BP 7431 EP 7438 DI 10.1074/jbc.M208076200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 649EZ UT WOS:000181195100103 PM 12468551 ER PT J AU Bush, AI AF Bush, AI TI Losing my mind - An intimate look at life with Alzheimer's SO SCIENCE LA English DT Book Review C1 Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA 02129 USA. Mental Hlth Res Inst Victoria, Parkville, Vic 3052, Australia. RP Bush, AI (reprint author), Massachusetts Gen Hosp, Genet & Aging Res Unit, Bldg 114,16th St, Charlestown, MA 02129 USA. RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD FEB 28 PY 2003 VL 299 IS 5611 BP 1318 EP 1319 DI 10.1126/science.1079480 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 649DU UT WOS:000181192300027 ER PT J AU Hasty, P Campisi, J Hoeijmakers, J van Steeg, H Vijg, J AF Hasty, P Campisi, J Hoeijmakers, J van Steeg, H Vijg, J TI Aging and genome maintenance: Lessons from the mouse? SO SCIENCE LA English DT Review ID WERNER-SYNDROME HELICASE; EXCISION-REPAIR GENE; MICE LACKING; STRESS-RESPONSE; DEFICIENT MICE; CANCER; SENESCENCE; PROTEIN; P53; KU AB Recent progress in the science of aging is driven largely by the use of model systems, ranging from yeast and nematodes to mice. These models have revealed conservation in genetic pathways that balance energy production and its damaging by-products with pathways that preserve somatic maintenance. Maintaining genome integrity has emerged as a major factor in longevity and cell viability. Here we discuss the use of mouse models with defects in genome maintenance for understanding the molecular basis of aging in humans. C1 Univ Texas, Hlth Sci Ctr, Dept Mol Med, San Antonio, TX 78245 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78245 USA. Univ Texas, Hlth Sci Ctr, Barshop Ctr Longev & Aging Studies, San Antonio, TX 78245 USA. Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA. Buck Inst Age Res, Novato, CA USA. Erasmus Univ, Dept Cell Biol & Genet, CBG, NL-3000 DR Rotterdam, Netherlands. Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. RP Hasty, P (reprint author), Univ Texas, Hlth Sci Ctr, Dept Mol Med, San Antonio, TX 78245 USA. FU NIA NIH HHS [AG17242] NR 55 TC 374 Z9 382 U1 3 U2 22 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD FEB 28 PY 2003 VL 299 IS 5611 BP 1355 EP 1359 DI 10.1126/science.1079161 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 649DU UT WOS:000181192300041 PM 12610296 ER PT J AU Dyson, N AF Dyson, N TI Developmental biology - A twist in a mouse tale SO NATURE LA English DT Editorial Material ID CHIMERIC MICE; MUTATION; APOPTOSIS; EMBRYOS; GENE C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Dyson, N (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 10 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 27 PY 2003 VL 421 IS 6926 BP 903 EP 904 DI 10.1038/421903a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 649BK UT WOS:000181186900027 PM 12606983 ER PT J AU Rubin, RH King, ME Mark, EJ Calderon, HA Abramson, S Gewirtz, H Greene, RE AF Rubin, RH King, ME Mark, EJ Calderon, HA Abramson, S Gewirtz, H Greene, RE TI Case 7-2003: A 43-year-old man with fever, rapid loss of vision in the left eye, and cardiac findings - Pneumococcal pneumonia with endocarditis and endophthalmitis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID AORTIC-VALVE DISEASE; INFECTIVE ENDOCARDITIS; DIAGNOSIS; ABSCESS; NECROPSY; CRITERIA; ADULTS C1 Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Harvard MIT Div Hlth Sci & Technol, Ctr Expt Pharmacol & therapeut, Cambridge, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Rubin, RH (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St, Boston, MA 02115 USA. NR 23 TC 6 Z9 7 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 27 PY 2003 VL 348 IS 9 BP 834 EP 843 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 648WE UT WOS:000181173300011 PM 12606739 ER PT J AU Volpp, KGM Grande, D AF Volpp, KGM Grande, D TI Patient safety - Residents' suggestions for reducing errors in teaching hospitals SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID OF-MEDICINE REPORT; ADVERSE EVENTS; HOUSE OFFICERS; PERFORMANCE; CARE; INTERVENTION; DEPRIVATION; SYSTEMS; STAFF; SLEEP C1 Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Dept Hlth Care Syst, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. RP Volpp, KGM (reprint author), Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. NR 35 TC 161 Z9 168 U1 1 U2 6 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 27 PY 2003 VL 348 IS 9 BP 851 EP 855 DI 10.1056/NEJMsb021667 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 648WE UT WOS:000181173300014 PM 12606742 ER PT J AU Rosendale, JD Kauffman, HM McBride, MA Chabalewski, FL Zaroff, JG Garrity, ER Delmonico, FL Rosengard, BR AF Rosendale, JD Kauffman, HM McBride, MA Chabalewski, FL Zaroff, JG Garrity, ER Delmonico, FL Rosengard, BR TI Aggressive pharmacologic donor management results in more transplanted organs SO TRANSPLANTATION LA English DT Article ID BRAIN-DEATH; THERAPY; VASOPRESSIN; REVERSAL AB Background. Brain death results in adverse pathophysiologic effects in many cadaveric donors, resulting in cardiovascular instability and poor organ perfusion. Hormonal resuscitation (HR) has been reported to stabilize and improve cardiac function in brain-dead donors. The goal of this study was to examine the effect of HR on the brain-dead donor on the number of organs transplanted per donor. Methods. A retrospective analysis of all brain-dead donors recovered in the United States from January 1, 2000, to September 30, 2001, was conducted. HR consisted of a methylprednisolone bolus and infusions of vasopressin and either triiodothyronine or L-thyroxine. Univariate analyses and multivariate logistic regression analyses were used to detect differences between the HR group and those donors who did not receive HR. Results. Of 10,292 consecutive brain-dead donors analyzed, 701 received three-drug HR. Univariate analysis showed the mean number of organs from HR donors (3.8) was 22.5% greater than that from nonhormonal resuscitation donors (3.1) (P<0.001). Multivariate analyses showed that HR was associated with the following statistically significant increased probabilities of an organ being transplanted from a donor: kidney 7.3%, heart 4.7%, liver 4.9%, lung 2.8% and pancreas 6.0%. Extrapolation of these probabilities to the 5,921 brain-dead donors recovered in 2001 was calculated to yield a total increase of 2,053 organs. Conclusion. HR stabilizes certain brain-dead donors and is associated with significant increases in organs transplanted per donor. C1 UNOS, Profess Serv Dept, Richmond, VA 23218 USA. Univ Calif San Francisco, Dept Cardiol, San Francisco, CA 94143 USA. Loyola Univ, Dept Med, Chicago, IL 60611 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Rosengard, BR (reprint author), UNOS, Profess Serv Dept, 700 N 4th St,POB 2484, Richmond, VA 23218 USA. FU PHS HHS [231-00-0115] NR 18 TC 139 Z9 144 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD FEB 27 PY 2003 VL 75 IS 4 BP 482 EP 487 DI 10.1097/01.TP.0000045683.85282.93 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 650BG UT WOS:000181242000012 PM 12605114 ER PT J AU Bryson, CL Ioannou, G Rulyak, S Critchlow, C AF Bryson, CL Ioannou, G Rulyak, S Critchlow, C TI The association between gestational diabetes and pregnancy-induced hypertension SO CIRCULATION LA English DT Meeting Abstract CT 43rd Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 05-08, 2003 CL MIAMI, FLORIDA SP Amer Heart Assoc C1 VA Puget Sound Healthcare Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 25 PY 2003 VL 107 IS 7 MA P111 BP E7032 EP E7032 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 653GX UT WOS:000181427800192 ER PT J AU Bryson, CL Mozaffarian, D Spertus, J McDonell, MB Fihn, SD AF Bryson, CL Mozaffarian, D Spertus, J McDonell, MB Fihn, SD TI Anginal symptoms predict total mortality among outpatients with coronary disease irrespective of age, race, education, or comorbidities SO CIRCULATION LA English DT Meeting Abstract CT 43rd Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 05-08, 2003 CL MIAMI, FLORIDA SP Amer Heart Assoc C1 VA Puget Sound Healthcare Syst, Seattle, WA USA. St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. RI Mozaffarian, Dariush/B-2276-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 25 PY 2003 VL 107 IS 7 MA P103 BP E7030 EP E7030 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 653GX UT WOS:000181427800184 ER PT J AU Bryson, CL Smith, NL Kuller, L Manolio, T Paulo, C Lewis, W Boyko, E Furberg, C Psaty, BM AF Bryson, CL Smith, NL Kuller, L Manolio, T Paulo, C Lewis, W Boyko, E Furberg, C Psaty, BM TI Relative risk of heart failure in an elderly population treated with peripheral alpha-1 antagonists SO CIRCULATION LA English DT Meeting Abstract CT 43rd Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 05-08, 2003 CL MIAMI, FLORIDA SP Amer Heart Assoc C1 VA Puget Sound Healthcare Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Univ Pittsburgh, Pittsburgh, PA USA. NHLBI, Bethesda, MD 20892 USA. Johns Hopkins, Baltimore, MD USA. Univ Calif Davis, Sacramento, CA 95817 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 25 PY 2003 VL 107 IS 7 MA P52 BP E7020 EP E7020 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 653GX UT WOS:000181427800133 ER PT J AU Derby, CA Crawford, SL Pasternak, RC Sowers, M Sternfeld, B Matthews, KA AF Derby, CA Crawford, SL Pasternak, RC Sowers, M Sternfeld, B Matthews, KA TI Is early Perimenopause associated with adverse changes in lipids? The study of women's health across the nation (SWAN) SO CIRCULATION LA English DT Meeting Abstract CT 43rd Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 05-08, 2003 CL MIAMI, FLORIDA SP Amer Heart Assoc C1 Albert Einstein Coll Med, Bronx, NY 10467 USA. Univ Massachusetts, Sch Med, Worcester, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Calif Davis, Davis, CA 95616 USA. Kaiser Permanente, Oakland, CA USA. Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 25 PY 2003 VL 107 IS 7 MA P51 BP E7020 EP E7020 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 653GX UT WOS:000181427800132 ER PT J AU Derby, CA Fitzgerald, G Lasser, NL Pasternak, RC AF Derby, CA Fitzgerald, G Lasser, NL Pasternak, RC TI Application of Adult Treatment Panel III (ATPIII) guidelines to a multi-ethnic cohort of perimenropausal women: Inclusion of age > 55 will produce an important shift in the proportions requiring intervention SO CIRCULATION LA English DT Meeting Abstract CT 43rd Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 05-08, 2003 CL MIAMI, FLORIDA SP Amer Heart Assoc C1 New England Res Inst, Watertown, MA 02172 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 25 PY 2003 VL 107 IS 7 MA 30 BP E7007 EP E7007 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 653GX UT WOS:000181427800070 ER PT J AU Rexrode, KM Manson, JE Lee, IM Ridker, PM Sluss, PM Cook, NR Buring, JE AF Rexrode, KM Manson, JE Lee, IM Ridker, PM Sluss, PM Cook, NR Buring, JE TI Sex steroid hormone levels and risk of cardiovascular disease in postmenopausal women SO CIRCULATION LA English DT Meeting Abstract CT 43rd Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 05-08, 2003 CL MIAMI, FLORIDA SP Amer Heart Assoc C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 25 PY 2003 VL 107 IS 7 MA 25 BP E7006 EP E7006 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 653GX UT WOS:000181427800065 ER PT J AU Figlewicz, DP Evans, SB Murphy, J Hoen, M Baskin, DG AF Figlewicz, DP Evans, SB Murphy, J Hoen, M Baskin, DG TI Expression of receptors for insulin and leptin in the ventral tegmental area/substantia nigra (VTA/SN) of the rat SO BRAIN RESEARCH LA English DT Article DE dopamine; fluorescence immunocytochemistry; reward; ingestive behavior ID SENSITIVE POTASSIUM CHANNELS; CONDITIONED PLACE PREFERENCE; SUBSTANTIA-NIGRA; MESSENGER-RNA; FOOD-DEPRIVATION; DOPAMINE TRANSPORTER; HYPOTHALAMIC NEURONS; PARKINSONS-DISEASE; ADIPOSITY SIGNALS; K+ CHANNELS AB Recent studies have demonstrated that the metabolic hormones insulin and leptin can modulate behavioral performance in reward-related paradigms. However, specific anatomical substrate(s) within the CNS for these effects remain to be identified. We hypothesize that midbrain dopamine neurons, which have been implicated to be critical in the mediation of motivational and reward aspects of stimuli, contribute to these behavioral effects of insulin and leptin. As one approach to evaluate this hypothesis, we used double-labeling fluorescence immunohistochemistry to determine whether the raidbrain dopamine neurons express insulin receptors or leptin receptors. Extensive co-expression of tyrosine hydroxylase (a marker for dopamine neurons) with both the insulin receptor and the leptin receptor was observed in the ventral tegmentum and substantia nigra. These findings suggest that midbrain dopamine neurons are direct targets of insulin and leptin, and that they participate in mediating the effects of these hormones on reward-seeking behavior. (C) 2002 Elsevier Science B.V. All rights reserved. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Biol Struct, Seattle, WA 98195 USA. RP Figlewicz, DP (reprint author), VA Puget Sound Hlth Care Syst, 1660 So Columbian Way, Seattle, WA 98108 USA. EM latte@u.washington.edu FU NIDDK NIH HHS [DK-17047, R01DK-40963] NR 46 TC 250 Z9 252 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD FEB 21 PY 2003 VL 964 IS 1 BP 107 EP 115 DI 10.1016/S0006-8993(02)04087-8 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 647TZ UT WOS:000181111300012 PM 12573518 ER PT J AU Rose, ME Huerbin, MB Melick, J Marion, DW Palmer, AM Schiding, JK Kochanek, PM Graham, SH AF Rose, ME Huerbin, MB Melick, J Marion, DW Palmer, AM Schiding, JK Kochanek, PM Graham, SH TI Regulation of interstitial excitatory amino acid concentrations after cortical contusion injury (vol 943, pg 15, 2002) SO BRAIN RESEARCH LA English DT Correction C1 Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Anesthesiol & Crit Care Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Neurosurg, Pittsburgh, PA USA. Univ Pittsburgh, Safar Ctr Resuscitat Res, Pittsburgh, PA USA. Univ Pittsburgh, Brain Trauma Res Ctr, Pittsburgh, PA USA. Vernalis Ltd, Wokingham, England. Vet Affairs Pittsburgh Hlth Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Graham, SH (reprint author), Univ Pittsburgh, Dept Neurol, 526 S BST, Pittsburgh, PA 15213 USA. RI Kochanek, Patrick/D-2371-2015 OI Kochanek, Patrick/0000-0002-2627-913X NR 1 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD FEB 21 PY 2003 VL 964 IS 1 BP 168 EP 168 DI 10.1016/S0006-8993(02)04214-2 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 647TZ UT WOS:000181111300021 ER PT J AU Manfredi, G Kwong, JQ Oca-Cossio, JA Woischnik, M Gajewski, CD Martushova, K D'Aurelio, M Friedlich, AL Moraes, CT AF Manfredi, G Kwong, JQ Oca-Cossio, JA Woischnik, M Gajewski, CD Martushova, K D'Aurelio, M Friedlich, AL Moraes, CT TI BCL-2 improves oxidative phosphorylation and modulates adenine nucleotide translocation in mitochondria of cells harboring mutant mtDNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BCL-X(L) PREVENTS; ATP; APOPTOSIS; DECREASE; PROTEIN; GENE; INHIBITORS; MUTATION; SURVIVAL; CALCIUM AB Members of the BCL-2-related antiapoptotic family of proteins have been shown previously to regulate ATP/ ADP exchange across the mitochondrial membranes and to prevent the loss of coupled mitochondrial respiration during apoptosis. We have found that BCL-2/ BCL-x(L) can also improve mitochondrial oxidative phosphorylation in cells harboring pathogenic mutations in mitochondrial tRNA genes. The effect of BCL-2 overexpression in mutated cells was independent from apoptosis and was presumably associated with a modulation of adenine nucleotide exchange between mitochondria and cytosol. These results suggest that BCL-2 can regulate respiratory functions in response to mitochondrial distress by regulating the levels of adenine nucleotides. C1 Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. Univ Miami, Sch Med, Dept Neurol, Miami, FL 33136 USA. Massachusetts Gen Hosp, Lab Oxidat Biol Genet, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Aging Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Psychiat, Charlestown, MA USA. RP Manfredi, G (reprint author), Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, 525 E 68th St,A-505, New York, NY 10021 USA. FU NCI NIH HHS [CA085700]; NINDS NIH HHS [NS02179] NR 26 TC 27 Z9 29 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 FEB 21 PY 2003 VL 278 IS 8 BP 5639 EP 5645 DI 10.1074/jbc.M203080200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 648BF UT WOS:000181129400021 PM 12431997 ER PT J AU Podar, K Tai, YT Cole, CE Hideshima, T Sattler, M Hamblin, A Mitsiades, N Schlossman, RL Davies, FE Morgan, GJ Munshi, NC Chauhan, D Anderson, KC AF Podar, K Tai, YT Cole, CE Hideshima, T Sattler, M Hamblin, A Mitsiades, N Schlossman, RL Davies, FE Morgan, GJ Munshi, NC Chauhan, D Anderson, KC TI Essential role of caveolae in interleukin-6-and insulin-like growth factor I-triggered Akt-1-mediated survival of multiple myeloma cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PLASMA-MEMBRANE DOMAINS; TYROSINE PHOSPHORYLATION; SIGNAL-TRANSDUCTION; PHOSPHATIDYLINOSITOL 3'-KINASE; RECEPTOR SUBSTRATE-1; PROTEIN-COMPONENT; PROSTATE-CANCER; EXPRESSION; CHOLESTEROL; KINASE AB Caveolae, specialized flask-shaped lipid rafts on the cell surface, are composed of cholesterol, sphingolipids, and structural proteins termed caveolins; functionally, these plasma membrane microdomains have been implicated in signal transduction and transmembrane transport. In the present study, we examined the role of caveolin-1 in multiple myeloma cells. We show for the first time that caveolin-1, which is usually absent in blood cells, is expressed in multiple myeloma cells. Analysis of myeloma cell-derived plasma membrane fractions shows that caveolin-1 is co-localized with interleukin-6 receptor signal transducing chain gp130 and with insulin-like growth factor-I receptor. Cholesterol depletion by beta-cyclodextrin results in the loss of caveola structure in myeloma cells, as shown by transmission electron microscopy, and loss of caveolin-1 function. Interleukin-6 and insulin-like growth factor-I, growth and survival factors in multiple myeloma, induce caveolin-1 phosphorylation, which is abrogated by pre-treatment with beta-cyclodextrin. Importantly, inhibition of caveolin-1 phosphorylation blocks both interleukin-6-induced protein complex formation with caveolin-1 and downstream activation of the phosphatidylinositol 3-kinase/ Akt-1 pathway. beta-Cyclodextrin also blocks insulin-like growth factor-I-induced tyrosine phosphorylation of insulin-responsive substrate-1 and downstream activation of the phosphatidylinositol 3-kinase/Akt-1 pathway. Therefore, cholesterol depletion by beta-cyclodextrin abrogates both interleukin-6- and insulin-like growth factor-I-triggered multiple myeloma cell survival via negative regulation of caveolin-1. Taken together, this study identifies caveolin-1 and other structural membrane components as potential new therapeutic targets in multiple myeloma. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Univ Michigan, Ctr Med, Dept Internal Med, Ann Arbor, MI 48109 USA. Leeds Gen Infirm, Leeds 3EX LSI, W Yorkshire, England. Vet Affairs Hlth Care Ctr, Brockton, MA 02401 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. FU PHS HHS [P0-1 78378] NR 69 TC 100 Z9 101 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 21 PY 2003 VL 278 IS 8 BP 5794 EP 5801 DI 10.1074/jbc.M208636200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 648BF UT WOS:000181129400040 PM 12482878 ER PT J AU Walker, AK Blackwell, TK AF Walker, AK Blackwell, TK TI A broad but restricted requirement for TAF-5 (Human TAF(II)100) for embryonic transcription in Caenorhabditis elegans SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA-POLYMERASE-II; C-ELEGANS; IN-VIVO; ACETYLASE COMPLEX; SAGA COMPLEXES; YEAST; DROSOPHILA; DISTINCT; SUBUNIT; TBP AB As conserved components of the transcription factor (TF) IID- and TFTC/SAGA-related complexes, TATA-binding protein-associated factors (TAF(II)s) are important for eukaryotic mRNA transcription. In yeast, genetic analyses suggest that, although some individual TAF(II)s are required for transcription of most genes, others have highly specialized functions. Much less is known about the functions of TAF(II)s in metazoans, which have more complex genomes that include many tissue-specific genes. TAF-5 (human (h) TAF(II)100) is of particular interest because it is predicted to have an important structural role. Here we describe the first genetics-based analysis of TAF-5 in a metazoan. By performing RNA interference in Caenorhabditis elegans embryos, which can survive for several cell generations without transcription, we found that taf-5 is important for a significant fraction of transcription. However, TAF-5 is apparently not essential for the expression of multiple developmental and other metazoan-specific genes. This phenotype remarkably resembles the previously described effects of similarly depleting two C. elegans histone fold TAF(II)s, TAF-9 (hTAF(II)31/32) and TAF-10 (hTAF(II)130), but is distinct from the widespread transcription block caused by TAF-4 (hTAF(II)130) depletion. Our findings suggest that TAF-5, TAF-9, and TAF-10 are part of a functional module of TFIID- and TFTC/SAGA-related complexes that can be bypassed in many metazoan-specific genes. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Blackwell, TK (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. FU NIGMS NIH HHS [R01 GM062891, GM62891] NR 51 TC 6 Z9 20 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 FEB 21 PY 2003 VL 278 IS 8 BP 6181 EP 6186 DI 10.1074/jbc.M211056200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 648BF UT WOS:000181129400087 PM 12458202 ER PT J AU Hahnfeldt, P Folkman, J Hlatky, L AF Hahnfeldt, P Folkman, J Hlatky, L TI Minimizing long-term tumor burden: The logic for metronomic chemotherapeutic dosing and its antiangiogenic basis SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article ID METASTATIC BREAST-CANCER; HIGH-DOSE CHEMOTHERAPY; ADVANCED COLORECTAL-CANCER; STEM-CELL TRANSPLANTATION; THERAPY; ANGIOGENESIS; MODEL; DRUGS; RESENSITIZATION; FLUOROURACIL AB The general utility of the maximum tolerated dose (MTD) paradigm, a strategy aimed at optimizing the chance of total tumor cell eradication, is here questioned. Evidence to date suggests that for many tumors the potential for eradication is in fact remote, with patients consistently demonstrating tumor cell presence subsequent to MTD treatments having eradicative intent. The failure to eradicate is attributed largely to the heterogeneous nature of the tumor. Heterogeneous cell populations demonstrate short-term refractoriness to up-front dose delivery, but "resensitize" as part of dose recovery, showing increased overall susceptibility to a given series of doses when delivered more evenly spaced. It is demonstrated: (1) that the minimization of total tumor burden, rather than complete eradication, may often be the more practical objective; and (2) that regularly spaced, "metronomic" dosing is the best way to achieve it. As a corollary, it is found that the more efficient ability of the tumor endothelial cells to resensitize following dosing predicts a targeting bias towards the endothelial compartment of a tumor when metronomic dosing is employed. This lends theoretical support to recent empirical studies showing that regularly spaced dosing schedules with no extended rest periods act more antiangiogenically, thereby delaying or avoiding the onset of acquired resistance. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Surg, Surg Res Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Hahnfeldt, P (reprint author), Dana Farber Canc Inst, JFB-523,44 Binney St, Boston, MA 02115 USA. EM philip_hahnfeldt@dfci.harvard.edu FU NCI NIH HHS [CA 64481, CA78496, CA86302] NR 43 TC 91 Z9 95 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD FEB 21 PY 2003 VL 220 IS 4 BP 545 EP 554 DI 10.1006/jtbi.2003.3162 PG 14 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 657ZT UT WOS:000181697700007 PM 12623285 ER PT J AU Bates, SH Stearns, WH Dundon, TA Schubert, M Tso, AWK Wang, YP Banks, AS Lavery, HJ Haq, AK Maratos-Flier, E Neel, BG Schwartz, MW Myers, MG AF Bates, SH Stearns, WH Dundon, TA Schubert, M Tso, AWK Wang, YP Banks, AS Lavery, HJ Haq, AK Maratos-Flier, E Neel, BG Schwartz, MW Myers, MG TI STAT3 signalling is required for leptin regulation of energy balance but not reproduction SO NATURE LA English DT Article ID HYPOTHALAMIC NEURONS; CYTOKINE RECEPTORS; NEUROPEPTIDE-Y; POMC NEURONS; FEMALE MICE; EARLY-ONSET; OB-R; ACTIVATION; OBESITY; MOUSE AB Secretion of leptin from adipocytes communicates body energy status to the brain by activating the leptin receptor long form (LRb). LRb regulates energy homeostasis and neuroendocrine function; the absence of LRb in db/db mice results in obesity, impaired growth, infertility and diabetes(1-4). Tyr 1138 of LRb mediates activation of the transcription factor STAT3 during leptin action(5-8). To investigate the contribution of STAT3 signalling to leptin action in vivo, we replaced the gene encoding the leptin receptor (lepr) in mice with an allele coding for a replacement of Tyr 1138 in LRb with a serine residue (lepr(S1138)) that specifically disrupts the LRb-STAT3 signal. Here we show that, like db/db mice, lepr(S1138) homozygotes (s/s) are hyperphagic and obese. However, whereas db/db mice are infertile, short and diabetic, s/s mice are fertile, long and less hyperglycaemic. Furthermore, hypothalamic expression of neuropeptide Y (NPY) is elevated in db/db mice but not s/s mice, whereas the hypothalamic melanocortin system is suppressed in both db/db and s/s mice. LRb-STAT3 signalling thus mediates the effects of leptin on melanocortin production and body energy homeostasis, whereas distinct LRb signals regulate NPY and the control of fertility, growth and glucose homeostasis. C1 Beth Israel Deaconess Med Ctr, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98122 USA. RP Myers, MG (reprint author), Beth Israel Deaconess Med Ctr, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. RI Schubert, Markus/F-5150-2010; Banks, Alexander/B-4832-2012; Schwartz, Michael/H-9950-2012 OI Banks, Alexander/0000-0003-1787-6925; NR 25 TC 577 Z9 604 U1 2 U2 28 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 20 PY 2003 VL 421 IS 6925 BP 856 EP 859 DI 10.1038/nature01388 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 646QA UT WOS:000181044700051 PM 12594516 ER PT J AU Tyler, KL AF Tyler, KL TI Creutzfeldt-Jakob disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Tyler, KL (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. OI Tyler, Kenneth/0000-0003-3294-5888 NR 0 TC 10 Z9 10 U1 1 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 20 PY 2003 VL 348 IS 8 BP 681 EP 682 DI 10.1056/NEJMp020187 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 646BF UT WOS:000181014400002 PM 12594311 ER PT J AU Grier, HE Krailo, MD Tarbell, NJ Link, MP Fryer, CJH Pritchard, DJ Gebhardt, MC Dickman, PS Perlman, EJ Meyers, PA Donaldson, SS Moore, S Rausen, AR Vietti, TJ Miser, JS AF Grier, HE Krailo, MD Tarbell, NJ Link, MP Fryer, CJH Pritchard, DJ Gebhardt, MC Dickman, PS Perlman, EJ Meyers, PA Donaldson, SS Moore, S Rausen, AR Vietti, TJ Miser, JS TI Addition of ifosfamide and etoposide to standard chemotherapy for Ewing's sarcoma and primitive neuroectodermal tumor of bone SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID YOUNG-ADULTS; PEDIATRIC ONCOLOGY; NO BENEFIT; CHILDREN; CYCLOPHOSPHAMIDE; VINCRISTINE; DOXORUBICIN; COMBINATION; EXPERIENCE; CHILDHOOD AB BACKGROUND: Ewing's sarcoma and primitive neuroectodermal tumor of bone are closely related, highly malignant tumors of children, adolescents, and young adults. A new drug combination, ifosfamide and etoposide, was highly effective in patients with Ewing's sarcoma or primitive neuroectodermal tumor of bone who had a relapse after standard therapy. We designed a study to test whether the addition of these drugs to a standard regimen would improve the survival of patients with newly diagnosed disease. METHODS: Patients 30 years old or younger with Ewing's sarcoma, primitive neuroectodermal tumor of bone, or primitive sarcoma of bone were eligible. The patients were randomly assigned to receive 49 weeks of standard chemotherapy with doxorubicin, vincristine, cyclophosphamide, and dactinomycin or experimental therapy with these four drugs alternating with courses of ifosfamide and etoposide. RESULTS: A total of 518 patients met the eligibility requirements. Of 120 patients with metastatic disease, 62 were randomly assigned to the standard-therapy group and 58 to the experimental-therapy group. There was no significant difference in five-year event-free survival between the treatment groups (P=0.81). Among the 398 patients with nonmetastatic disease, the mean (+/-SE) five-year event-free survival among the 198 patients in the experimental-therapy group was 69+/-3 percent, as compared with 54+/-4 percent among the 200 patients in the standard-therapy group (P=0.005). Overall survival was also significantly better among patients in the experimental-therapy group (72+/-3.4 percent vs. 61+/-3.6 percent in the standard-therapy group, P=0.01). CONCLUSIONS: The addition of ifosfamide and etoposide to a standard regimen does not affect the outcome for patients with metastatic disease, but it significantly improves the outcome for patients with nonmetastatic Ewing's sarcoma, primitive neuroectodermal tumor of bone, or primitive sarcoma of bone. C1 Dana Farber Canc Inst, Dept Pediat Hematol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Orthoped Surg, Boston, MA 02115 USA. Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Radiat Oncol, Stanford, CA 94305 USA. King Khalid Natl Hosp, Dept Pediat, Jeddah, Saudi Arabia. Mayo Clin, Rochester, MN USA. Childrens Hosp Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA. Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Childrens Hosp, Dept Radiol, Los Angeles, CA 90027 USA. NYU Med Ctr, Dept Pediat, New York, NY 10016 USA. Washington Univ, Med Ctr, Div Pediat Hematol & Oncol, St Louis, MO USA. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. City Hope Natl Med Ctr, Dept Pediat, Duarte, CA 91010 USA. RP Grier, HE (reprint author), Dana Farber Canc Inst, Dept Pediat Hematol, 44 Binney St, Boston, MA 02115 USA. NR 26 TC 523 Z9 563 U1 2 U2 25 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 20 PY 2003 VL 348 IS 8 BP 694 EP 701 DI 10.1056/NEJMoa020890 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 646BF UT WOS:000181014400004 PM 12594313 ER PT J AU Sander, HW Hedley-Whyte, ET AF Sander, HW Hedley-Whyte, ET TI Case 6-2003: A nine-year-old girl with progressive weakness and areflexia - Chronic inflammatory demyelinating polyradiculoneuropathy. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID RANDOMIZED CONTROLLED TRIAL; INTRAVENOUS IMMUNOGLOBULIN; CLINICAL-FEATURES; PLASMA-EXCHANGE; DOUBLE-BLIND; CROSS-OVER; POLYNEUROPATHY; CHILDHOOD; THERAPY C1 Weill Cornell Med Coll, Peripheral Neuropathy Ctr, New York, NY 10021 USA. Weill Cornell Med Coll, Dept Neurol, New York, NY USA. NYU, Sch Med, Dept Neurol, New York, NY USA. New York Med Coll, Dept Neurol, Valhalla, NY 10595 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Sander, HW (reprint author), Weill Cornell Med Coll, Peripheral Neuropathy Ctr, New York, NY 10021 USA. NR 32 TC 10 Z9 10 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 20 PY 2003 VL 348 IS 8 BP 735 EP 743 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 646BF UT WOS:000181014400010 PM 12594319 ER PT J AU Plymate, SR Haugk, KH Sprenger, CC Nelson, PS Tennant, MK Zhang, YP Oberley, LW Zhong, WX Drivdahl, R Oberley, TD AF Plymate, SR Haugk, KH Sprenger, CC Nelson, PS Tennant, MK Zhang, YP Oberley, LW Zhong, WX Drivdahl, R Oberley, TD TI Increased manganese superoxide dismutase (SOD-2) is part of the mechanism for prostate tumor suppression by Mac25/insulin-like growth factor binding-protein-related protein-1 SO ONCOGENE LA English DT Article DE SOD-2; Mac25; prostate; cancer; IGFBP-rP1 ID CANCER CELL-LINE; EPITHELIAL-CELLS; T-ANTIGEN; HYDROGEN-PEROXIDE; EXPRESSION; APOPTOSIS; FIBROBLASTS; P53; OVEREXPRESSION; ACTIVATION AB Increased expression of mac25/insulin-like growth factor binding-protein related protein-1 (IGFBP-rP1) in human breast and prostate epithelial cell lines results in the suppression of tumor growth. CDNA expression array analysis revealed increased manganese superoxide dismutase (SOD-2) expression in the mac25/IGFBP-rP1-transfected M12 human prostate cancer cell line compared to M12 control cells. SOD-2 has been postulated to be a tumor suppressor. SOD-2 was also increased in LNCaP cells stably transfected with mac25/IGFBP-rP1, but not in mac25/IGFBP-rP1-transfected PC-3 cells. Mac25 LNCaP cells had a marked decrease in tumor growth in nude mice compared to controls, but there was no difference in tumor growth in mac25 PC-3 cells compared to control. Phosphorylated Erk and Akt were increased in the M12 and LNCaP transfected mac25/ IGFBP-rP1 cells but not PC-3 mac25. Inhibition of PI-3 kinase results in a marked decrease in viability of the M12-mac25 cells compared to M12 controls. Cells treated with H2O2 result, in an increase in phospho-ERK. Transfection of SOD-2 in M12 cells markedly decreased tumor growth, apoptosis, G1 delay in the cell cycle, and expression of senescence associated beta-galactosidase. These results suggest that one of the downstream mediators of the senescence-associated tumor suppression effect of mac25/IGFBP-rP1 is SOD-2. C1 Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98105 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98105 USA. Univ Washington, Sch Med, Dept Mol, Seattle, WA 98105 USA. Univ Washington, Sch Med, Cell Biol Program, Seattle, WA 98105 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98107 USA. Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA. Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53705 USA. William S Middleton Mem Vet Adm Med Ctr, Pathol Serv, Madison, WI 53705 USA. RP Plymate, SR (reprint author), Univ Washington, Harborview Med Ctr, 325 9Th Ave,Box 359755, Seattle, WA 98104 USA. FU NCI NIH HHS [P01-CA 85859]; NIDDK NIH HHS [DK52683] NR 34 TC 41 Z9 43 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 20 PY 2003 VL 22 IS 7 BP 1024 EP 1034 DI 10.1038/sj.onc.1206210 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 644PB UT WOS:000180926100008 PM 12592389 ER PT J AU Lincoff, AM Bittl, JA Harrington, RA Feit, F Kleiman, NS Jackman, JD Sarembock, IJ Cohen, DJ Spriggs, D Ebrahimi, R Keren, G Carr, J Cohen, EA Betriu, A Desmet, W Kereiakes, DJ Rutsch, W Wilcox, RG de Feyter, PJ Vahanian, A Topol, EJ AF Lincoff, AM Bittl, JA Harrington, RA Feit, F Kleiman, NS Jackman, JD Sarembock, IJ Cohen, DJ Spriggs, D Ebrahimi, R Keren, G Carr, J Cohen, EA Betriu, A Desmet, W Kereiakes, DJ Rutsch, W Wilcox, RG de Feyter, PJ Vahanian, A Topol, EJ CA REPLACE 2 Investigators TI Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention - REPLACE-2 Randomized Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACTIVE-CONTROL TRIALS; POSTINFARCTION ANGINA; ISCHEMIC EVENTS; ABCIXIMAB; INHIBITORS; THROMBIN; REVASCULARIZATION; THROMBOCYTOPENIA; ANGIOPLASTY; PLACEBO AB Context The direct thrombin inhibitor bivalirudin has been associated with better efficacy and less bleeding than heparin during coronary balloon angioplasty but has not been widely tested during contemporary percutaneous coronary intervention (PCI). Objective To determine the efficacy of bivalirudin, with glycoprotein Ilb/IIIa (Gp IIb/IIia) inhibition on a provisional basis for complications during PCI, compared with heparin plus planned Gp IIb/IIIa blockade with regard to protection from periprocedural ischemic and hemorrhagic complications. Design Setting, and Participants The Randomized Evaluation in PCI Linking Angiomax Reduced Clinical Events (REPLACE)72 trial, a randomized, double-blind, active-controlled trial conducted among 6010 patients undergoing urgent or elective PCI at 233 community or referral hospitals in 9 countries from October 2001 through August 2002. Interventions Patients were randomly assigned to receive intravenous bivalirudin (0.75-mg/kg bolus plus 1.75 mg/kg per hour for the duration of PCI), with provisional Gp IIb/IIIa inhibition (n=2999), or heparin (65-U/kg bolus) with planned Gp IIb/IIIa inhibition (abciximab or eptifibatide) (n=3011). Both groups received daily aspirin and a thienopyridine for at least 30 days after PCI. Main Outcome Measures The primary composite end point was 30-day incidence of death, myocardial infarction, urgent repeat revascularization, or in-hospital major bleeding; the secondary composite end point was 30-day incidence of death, myocardial infarction, or urgent repeat revascularization. Results Provisional Gp IIb/IIIa blockade was administered to 7.2%of patients in the bivalirudin group. By 30 days, the primary composite end point had occurred among 9.2% of patients in the bivalirudin group vs 10.0% of patients in the Neparin-plus-Gp IIb/IIIa group (odds ratio, 0.92; 95% confidence interval, 0.77-1.09; P=32). The secondary composite end point occurred in 7.6% of patients in the bivalirudin vs 7.1% of patients in the heparin-plus-Gp IIb/IIIa groups (odds ratio, 1.09; 95% confidence interval 0.90-1.32; P=.40). Prespecified statistical criteria for noninferiority to heparin plus Gp IIb/IIIa were satisfied for both end points. In-hospital major bleeding rates were significantly reduced by bivalirudin (2.4% vs 4.1%; P<.001). Conclusions Bivalirudin with provisional Gp IIb/IIIa blockade is statistically not inferior to heparin plus planned Go IIb/IIIa blockade during contemporary PCI with regard to suppression of acute ischemic end points and is associated with less bleeding. C1 Cleveland Clin Fdn, Dept Cardiovasc Med, Cleveland, OH 44195 USA. Munroe Reg Med Ctr, Ocala Heart Inst, Ocala, FL USA. Duke Clin Res Inst, Durham, NC USA. NYU, Sch Med, New York, NY USA. Baylor Coll Med, Houston, TX 77030 USA. Methodist Hosp, Houston, TX 77030 USA. Trinity Mother Frances Hosp, Tyler Cardiovasc Consultants, Tyler, TX USA. Univ Virginia Hlth Syst, Charlottesville, VA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Clearwater Cardiovasc Consultants, Clearwater, FL USA. W Los Angeles VA, Los Angeles, CA USA. Tel Aviv Sourasky Med Ctr, Tel Aviv, Israel. E Texas Med Ctr, Tyler, TX USA. Sunnybrook & Womens Coll Hlth Sci Ctr, Toronto, ON, Canada. Univ Barcelona, Hosp Clin, Barcelona, Spain. Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. Ohio Heart Hlth Ctr, Lindner Ctr, Cincinnati, OH USA. Univ Clin Charite Berlin, Berlin, Germany. Univ Nottingham Hosp, Nottingham NG7 2UH, England. Univ Hosp Dijkzigt, NL-3015 GD Rotterdam, Netherlands. Hop Bichat, F-75877 Paris, France. RP Lincoff, AM (reprint author), Cleveland Clin Fdn, Dept Cardiovasc Med, Desk F25,9500 Euclid Ave, Cleveland, OH 44195 USA. OI Topol, Eric/0000-0002-1478-4729 NR 37 TC 770 Z9 801 U1 1 U2 16 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 19 PY 2003 VL 289 IS 7 BP 853 EP 863 DI 10.1001/jama.289.7.853 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 647BW UT WOS:000181072200029 PM 12588269 ER PT J AU Cannon, CP AF Cannon, CP TI Small molecule glycoprotein IIb/IIIa receptor inhibitors as upstream therapy in acute coronary syndromes - Insights from the TACTICS TIMI-18 trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID WAVE MYOCARDIAL-INFARCTION; REFRACTORY UNSTABLE ANGINA; CONSERVATIVE MANAGEMENT STRATEGY; TROPONIN-T; RANDOMIZED TRIAL; BENEFIT; ELEVATION; TIROFIBAN; ABCIXIMAB; THROMBOLYSIS AB Glycoprotein (GP) IIb/IIIa inhibitors are beneficial in unstable angina/non-ST-segment elevation myocardial infarction (UA/NSTEMT). In large trials, the GP IIb/IIIa inhibitors tirofiban and eptifibatide were each found to reduce the risk of death or myocardial infarction (MI) in these patients at 30 days. These agents appear to be of greatest benefit in patients with a positive troponin at baseline, diabetes or ST-segment depression, recurrent angina, prior aspirin use, or a Thrombolysis In Myocardial Infarction (TIMI) risk score greater than or equal to 4. The Treat angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy (TACTICS) TIMI-18 trial was designed to compare the benefits of an early invasive versus a conservative strategy in high-risk UA/NSTEMI patients treated with GP IIb/IIIa inhibition. Patients were treated with tirofiban (for 48 h) plus aspirin and heparin and randomized to either invasive therapy (coronary angiography and revascularization when feasible) or conservative treatment (angiography only for patients with recurrent ischemia at rest or a positive stress test). A significant reduction in death or MI was demonstrated at 30 days (p = 0.02) and at 6 months (p = 0.0498). Death, MI, or rehospitalization for an acute coronary syndrome was also reduced with the invasive therapy at six months (p = 0.025). These results provide evidence to physicians that early GP IIb/IIIa inhibition in combination with a prompt invasive approach should be used more widely in UA/NSTEMI patients, particularly those at high risk. (C) 2003 by the American College of Cardiology Foundation. C1 Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. RP Cannon, CP (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. NR 45 TC 6 Z9 6 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 19 PY 2003 VL 41 IS 4 SU S BP 43S EP 48S DI 10.1016/S0735-1097(02)03018-8 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 647EX UT WOS:000181080800007 PM 12644340 ER PT J AU Sabatine, MS Antman, EM AF Sabatine, MS Antman, EM TI The thrombolysis in myocardial infarction risk score in unstable angina/non-ST-segment elevation myocardial infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ACUTE CORONARY SYNDROMES; CARDIAC ISCHEMIC EVENTS; ARTERY DISEASE; CONSERVATIVE STRATEGIES; ASPIRIN RESISTANCE; TRIAL; ELECTROCARDIOGRAM; CLASSIFICATION; STRATIFICATION; PATHOGENESIS AB Risk stratification in unstable angina (UA)/non-ST-segment elevation myocardial infarction (NSTEMI) can provide an estimate of a patient's prognosis and optimize clinical choices. The Thrombolysis In Myocardial Infarction (TIMI) risk score for UA/NSTEMI is an integrated approach that uses baseline variables that are part of the routine medical evaluation to identify patients at high risk for death and other major cardiac ischemic events. Using multivariable logistic regression, seven independent predictor variables were identified: age greater than or equal to 65 years, greater than or equal to 3 risk factors for coronary artery disease (CAD), known CAD (stenosis greater than or equal to 50%), severe anginal symptoms ( greater than or equal to 2 anginal events in preceding 24 h), use of aspirin in the last seven days, ST-segment deviation greater than or equal to 0.05 mV, and elevated serum cardiac markers of necrosis. Each predictor carried similar prognostic weight; therefore, a risk score was constructed as the simple arithmetic sum of the number of predictors. The rate of death, MI, or urgent revascularization significantly increased as the TIMI risk score increased, ranging from < 5% for patients with a risk score of 0 or 1 to > 40% for patients with a risk score of 6 or 7. The risk score has been validated in several other trials of UAJNSTEMI. In addition, using the risk score to categorize patients also effectively defines a gradient for benefit with specific treatments such as low-molecular-weight heparins, glycoprotein IIb/IIIa inhibitors, and an early invasive strategy. (C) 2003 by the American College of Cardiology Foundation. C1 Brigham & Womens Hosp, Div Cardiovasc, Dept Med, TIMI Study Grp, Boston, MA 02115 USA. RP Sabatine, MS (reprint author), Brigham & Womens Hosp, Div Cardiovasc, Dept Med, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [F32 HL68455-01] NR 35 TC 36 Z9 38 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 19 PY 2003 VL 41 IS 4 SU S BP 89S EP 95S DI 10.1016/S0735-1097(02)03019-X PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 647EX UT WOS:000181080800013 PM 12644346 ER PT J AU Kerwin, W Hooker, A Spilker, M Vicini, P Ferguson, M Hatsukami, T Yuan, C AF Kerwin, W Hooker, A Spilker, M Vicini, P Ferguson, M Hatsukami, T Yuan, C TI Quantitative magnetic resonance imaging analysis of neovasculature volume in carotid atherosclerotic plaque SO CIRCULATION LA English DT Article DE magnetic resonance imaging; contrast media; carotid arteries; atherosclerosis ID ENHANCED MRI; NEOVASCULARIZATION; ANGIOGENESIS; PERMEABILITY; ANGIOGRAPHY; ASSOCIATION; ARTERIES; RUPTURE; AGENT; WALL AB Background-Neovasculature within atherosclerotic plaques is believed to be associated with infiltration of inflammatory cells and plaque destabilization. The aim of the present investigation was to determine whether the amount of neovasculature present in advanced carotid plaques can be noninvasively measured by dynamic, contrast-enhanced MRI. Methods and Results-A total of 20 consecutive patients scheduled for carotid endarterectomy were recruited to participate in an MRI study. Images were obtained at 15-second intervals, and a gadolinium contrast agent was injected coincident with the second of 10 images in the sequence. The resulting image intensity within the plaque was tracked over time, and a kinetic model was used to estimate the fractional blood volume. For validation, matched sections from subsequent endarterectomy were stained with ULEX and CD-31 antibody to highlight microvessels. Finally, all microvessels within the matched sections were identified, and their total area was computed as a fraction of the plaque area. Results were obtained from 16 participants, which showed fractional blood volumes ranging from 2% to 41%. These levels were significantly higher than the histological measurements of fractional vascular area. Nevertheless, the 2 measurements were highly correlated, with a correlation coefficient of 0.80 (P<0.001). Conclusions-Dynamic contrast-enhanced MRI provides an indication of the extent of neovasculature within carotid atherosclerotic plaque. MRI therefore provides a means for prospectively studying the link between neovasculature and plaque vulnerability. C1 Univ Washington, Dept Radiol, Seattle, WA 98195 USA. Univ Washington, Dept Surg, Seattle, WA 98195 USA. Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Dept Surg & Perioperat Care, Seattle, WA USA. RP Kerwin, W (reprint author), Univ Washington, Dept Radiol, Box 357115,1959 NE Pacific Ave, Seattle, WA 98195 USA. RI Hooker, Andrew/A-7794-2015; OI Hooker, Andrew/0000-0002-2676-5912 FU NCRR NIH HHS [RR-12609]; NHLBI NIH HHS [R01 HL56874] NR 20 TC 209 Z9 239 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 18 PY 2003 VL 107 IS 6 BP 851 EP 856 DI 10.1161/01.CIR.0000048145.52309.31 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 651AV UT WOS:000181298600014 PM 12591755 ER PT J AU Rivolta, C Ayyagari, R Sieving, P Berson, E Dryja, T AF Rivolta, C Ayyagari, R Sieving, P Berson, E Dryja, T TI Evaluation of the ELOVL4 gene in patients with autosomal recessive retinitis pigmentosa and Leber congenital amaurosis SO MOLECULAR VISION LA English DT Article ID MACULAR DYSTROPHY; CHROMOSOME 6Q; CRB1 GENE; MUTATIONS; LOCUS; PROTEIN; FAMILY AB Purpose: To determine whether pathogenic mutations exist in the ELOVL4 gene in patients with inherited retinal degenerations other than Stargardt-like macular dystrophy or other hereditary macular degenerations. Methods: All six exons comprising the open reading frame of the ELOVL4 gene were evaluated by single-strand conformation analysis, direct nucleotide sequencing, or both methods. Results: No pathogenic mutations were found among 84 patients with autosomal recessive retinitis pigmentosa or among 51 patients with Leber congenital amaurosis (congenital retinal blindness). Conclusions: These data support the conclusion that recessive retinitis pigmentosa and Leber congenital amaurosis are rarely if ever associated with changes in the ELOVL4 gene. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. NEI, Bethesda, MD 20892 USA. Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA. RP Dryja, T (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY13198, EY00169, EY08683] NR 20 TC 8 Z9 11 U1 0 U2 0 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD FEB 18 PY 2003 VL 9 IS 7-8 BP 49 EP 51 PG 3 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 647FN UT WOS:000181082300002 PM 12592226 ER PT J AU Ng, HH Ciccone, DN Morshead, KB Oettinger, MA Struhl, K AF Ng, HH Ciccone, DN Morshead, KB Oettinger, MA Struhl, K TI Lysine-79 of histone H3 is hypomethylated at silenced loci in yeast and mammalian cells: A potential mechanism for position-effect variegation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SACCHAROMYCES-CEREVISIAE; PROTEIN SIR2; TELOMERIC HETEROCHROMATIN; FISSION YEAST; ACETYLATION; H4; TRANSCRIPTION; RECOMBINATION; DEACETYLATION; INHERITANCE AB Methylation of lysine-79 (K79) within the globular domain of histone H3 by Dot1 methylase is important for transcriptional silencing and for association of the Sir silencing proteins in yeast. Here, we show that the level of H3-K79 methylation is low at all Sir-dependent silenced loci but not at other transcriptionally repressed regions. Hypomethylation of H3-K79 at the telomeric and silent mating-type loci, but not the ribosomal DNA, requires the Sir proteins. Overexpression of Sir3 concomitantly extends the domain of Sir protein association and H3-K79 hypornethylation at telomeres. In mammalian cells, H3-K79 methylation is found at loci that are active for V(D)J recombination, but not at recombinationally inactive loci that are heterochromatic. These results suggest that H3-K79 methylation is an evolutionarily conserved marker of active chromatin regions, and that silencing proteins block the ability of Dot1 to methylate histone H3. Further, they suggest that Sir proteins preferentially bind chromatin with hypomethylated H3-K79 and then block H3-K79 methylation. This positive feedback loop, and the reverse loop in which H3-K79 methylation weakens Sir protein association and leads to further methylation, suggests a model for position-effect variegation. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Struhl, K (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RI Ng, Huck Hui/A-1135-2009; OI NG, HUCK HUI/0000-0001-6352-8417 FU NIGMS NIH HHS [GM 48026, GM 53720, R01 GM048026, R01 GM053720] NR 45 TC 199 Z9 207 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 18 PY 2003 VL 100 IS 4 BP 1820 EP 1825 DI 10.1073/pnas.0437846100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 647CA UT WOS:000181073000069 PM 12574507 ER PT J AU Vorup-Jensen, T Ostermeier, C Shimaoka, M Hommel, U Springer, TA AF Vorup-Jensen, T Ostermeier, C Shimaoka, M Hommel, U Springer, TA TI Structure and allosteric regulation of the alpha X beta 2 integrin I domain SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LEUKOCYTE ADHESION GLYCOPROTEIN; CRYSTAL-STRUCTURE; A-DOMAIN; HYDRODYNAMIC PROPERTIES; RECOGNITION SITE; HIGH-AFFINITY; P150,95; PROTEIN; ACTIVATION; BINDING AB The integrin alphaXbeta2 (CD11c/CD18, p150,95) binds ligands through the I domain of the alphaX subunit. Ligands include the complement factor fragment iC3b, a key component in the innate immune defense, which, together with the expression of alphaXbeta2 on dendritic cells and on other leukocytes, suggests a role in the immune response. We now report the structure of the alphaX I domain resolved at 1.65 Angstrom by x-ray crystallography. To analyze structural requirements for ligand binding we made a mutation in the alphaX I domain C-terminal helix, which increased the affinity for iC3b approximate to200-fold to 2.4 muM compared with the wild-type domain affinity of approximate to400 muM. Gel permeation chromatography supported a conformational change between the wild-type and mutated domains. Conservation of allosteric regulation in the alphaX I domain points to the functional importance of this phenomenon. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Novartis Pharma AG, Prot Struct Unit, CH-4002 Basel, Switzerland. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. OI Vorup-Jensen, Thomas/0000-0002-4140-6563 FU NCI NIH HHS [CA31799, R01 CA031799] NR 44 TC 60 Z9 62 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 18 PY 2003 VL 100 IS 4 BP 1873 EP 1878 DI 10.1073/pnas.0237387100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 647CA UT WOS:000181073000078 PM 12554829 ER PT J AU Welte, T Zhang, SSM Wang, T Zhang, ZY Hesslein, DGT Yin, ZN Kano, A Iwamoto, Y Li, E Craft, JE Bothwell, ALM Fikrig, E Koni, PA Flavell, RA Fu, XY AF Welte, T Zhang, SSM Wang, T Zhang, ZY Hesslein, DGT Yin, ZN Kano, A Iwamoto, Y Li, E Craft, JE Bothwell, ALM Fikrig, E Koni, PA Flavell, RA Fu, XY TI STAT3 deletion during hematopoiesis causes Crohn's disease-like pathogenesis and lethality: A critical role of STAT3 in innate immunity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; T-CELL PROLIFERATION; TRANSCRIPTION FACTOR; TYROSINE PHOSPHORYLATION; FAMILY MEMBER; GROWTH-FACTOR; ACTIVATION; MICE; NOD2; GENE AB Signal transducer and activator of transcription 3 (STAT3) is a key transcriptional mediator for many cytokines and is essential for normal embryonic development. We have generated a unique strain of mice with tissue-specific disruption of STAT3 in bone marrow cells during hematopoiesis. This specific STAT3 deletion causes death of these mice within 4-6 weeks after birth with Crohn's disease-like pathogenesis in both the small and large intestine, including segmental inflammatory cell infiltration, ulceration, bowel wall thickening, and granuloma formation. Deletion of STAT3 causes significantly increased cell autonomous proliferation of cells of the myeloid lineage, both in vivo and in vitro. Most importantly, Stat3 deletion during hematopoiesis causes overly pseudoactivated innate immune responses. Although inflammatory cytokines, including tumor necrosis factor alpha and IFN-gamma, are overly produced in these mice, the NAPDH oxidase activity, which is involved in antimicrobial and innate immune responses, is inhibited. The signaling responses to lipopolysaccharide are changed in the absence of STAT3, leading to enhanced NF-kappaB activation. Our results suggest a model in which STAT3 has critical roles in the development and regulation of innate immunity, and deletion of STAT3 during hematopoiesis results in abnormalities in myeloid cells and causes Crohn's disease-like pathogenesis. C1 Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA. Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06520 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06520 USA. Yale Univ, Sch Med, Rheumatol Sect, Dept Med, New Haven, CT 06520 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Fu, XY (reprint author), Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA. RI Koni, Pandelakis/A-3349-2008 FU NIAID NIH HHS [AI34522, R01 AI034522]; NIAMS NIH HHS [AR44906] NR 41 TC 251 Z9 259 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 18 PY 2003 VL 100 IS 4 BP 1879 EP 1884 DI 10.1073/PNAS.0237137100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 647CA UT WOS:000181073000079 PM 12571365 ER PT J AU Davachi, L Mitchell, JP Wagner, AD AF Davachi, L Mitchell, JP Wagner, AD TI Multiple routes to memory: Distinct medial temporal lobe processes build item and source memories SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMPAIRED RECOGNITION MEMORY; INFERIOR PREFRONTAL CORTEX; EVENT-RELATED FMRI; HIPPOCAMPAL-FORMATION; PERIRHINAL CORTEX; PARAHIPPOCAMPAL CORTICES; VISUAL RECOGNITION; ENTORHINAL CORTEX; RHINAL CORTEX; SEMANTIC MEMORY AB A central function of memory is to permit an organism to distinguish between stimuli that have been previously encountered and those that are novel. Although the medial temporal lobe (which includes the hippocampus and surrounding perirhinal, parahippocampal, and entorhinal cortices) is known to be crucial for recognition memory, controversy remains regarding how the specific subregions within the medial temporal lobe contribute to recognition. We used event-related functional MRI to examine the relation between activation in distinct medial temporal lobe subregions during memory formation and the ability (i) to later recognize an item as previously encountered (item recognition) and (it) to later recollect specific contextual details about the prior encounter (source recollection). Encoding activation in hippocampus and in posterior parahippocampal cortex predicted later source recollection, but was uncorrelated with item recognition. In contrast, encoding activation in perirhinal cortex predicted later item recognition, but not subsequent source recollection. These outcomes suggest that the subregions within the medial temporal lobe subserve distinct, but complementary, learning mechanisms. C1 MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, Picower Ctr Learning & Memory, Cambridge, MA 02139 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Davachi, L (reprint author), MIT, Dept Brain & Cognit Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. FU NIMH NIH HHS [F32 MH012793, MH12793, MH60941, R01 MH060941] NR 72 TC 517 Z9 524 U1 11 U2 35 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 18 PY 2003 VL 100 IS 4 BP 2157 EP 2162 DI 10.1073/pnas.0337195100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 647CA UT WOS:000181073000127 PM 12578977 ER PT J AU Schuyler, SC Liu, JY Pellman, D AF Schuyler, SC Liu, JY Pellman, D TI The molecular function of Ase1p: evidence for a MAP-dependent midzone-specific spindle matrix SO JOURNAL OF CELL BIOLOGY LA English DT Article DE mitosis; microtubule-associated protein; spindle midzone; anaphase; budding yeast ID MICROTUBULE-ASSOCIATED PROTEINS; ANAPHASE-PROMOTING COMPLEX; SACCHAROMYCES-CEREVISIAE; MITOTIC SPINDLE; BUDDING YEAST; CHROMOSOME SEGREGATION; CYTOPLASMIC MATRIX; LASER MICROBEAM; BIPOLAR KINESIN; MITOSIS AB The midzone is the domain of the mitotic spindle that maintains spindle bipolarity during anaphase and generates forces required for spindle elongation (anaphase B). Although there is a clear role for microtubule (MT) motor proteins at the spindle midzone, less is known about how microtubule-associated proteins (MAPs) contribute to midzone organization and function. Here, we report that budding yeast Ase1p is a member of a conserved family of midzone-specific MAPs. By size exclusion chromatography and velocity sedimentation, both Ase1p in extracts and purified Ase1p behaved as a homodimer. Ase1p bound and bundled MTs in vitro. By live cell microscopy, loss of Ase1p resulted in a specific defect: premature spindle disassembly in mid-anaphase. Furthermore, when overexpressed, Ase1p was sufficient to trigger spindle elongation in S phase-arrested cells. FRAP revealed that Ase1p has both a very slow rate of turnover within the midzone and limited lateral diffusion along spindle MTs. We propose that Ase1p functions as an MT cross-bridge that imparts matrix-like characteristics to the midzone. MT-dependent networks of spindle midzone MAPs may be one molecular basis for the postulated spindle matrix. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. RP Pellman, D (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St,Mayer 621A, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM55772] NR 74 TC 136 Z9 144 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD FEB 17 PY 2003 VL 160 IS 4 BP 517 EP 528 DI 10.1083/jcb.200210021 PG 12 WC Cell Biology SC Cell Biology GA 647JT UT WOS:000181090200006 PM 12591913 ER PT J AU Kim, DK Zhu, JL Kozyak, BW Burkman, JM Rubinstein, NA Lankford, EB Stedman, HH Nguyen, T Levine, S Shrager, JB AF Kim, DK Zhu, JL Kozyak, BW Burkman, JM Rubinstein, NA Lankford, EB Stedman, HH Nguyen, T Levine, S Shrager, JB TI Myosin heavy chain and physiological adaptation of the rat diaphragm in elastase-induced emphysema SO RESPIRATORY RESEARCH LA English DT Article DE Ca2+-transporting ATPase; muscle fatigue; myosin; respiratory muscles ID SKELETAL-MUSCLE; CELLULAR ADAPTATIONS; MESSENGER-RNA; RESPIRATORY MUSCLES; VENTILATORY MUSCLES; HAMSTER DIAPHRAGM; LUNG-FUNCTION; SINGLE-FIBER; ISOFORMS; EXPRESSION AB Background: Several physiological adaptations occur in the respiratory muscles in rodent models of elastase-induced emphysema. Although the contractile properties of the diaphragm are altered in a way that suggests expression of slower isoforms of myosin heavy chain (MHC), it has been difficult to demonstrate a shift in MHCs in an animal model that corresponds to the shift toward slower MHCs seen in human emphysema. Methods: We sought to identify MHC and corresponding physiological changes in the diaphragms of rats with elastase-induced emphysema. Nine rats with emphysema and 11 control rats were studied 10 months after instillation with elastase. MHC isoform composition was determined by both reverse transcriptase polymerase chain reaction (RT-PCR) and immunocytochemistry by using specific probes able to identify all known adult isoforms. Physiological adaptation was studied on diaphragm strips stimulated in vitro. Results: In addition to confirming that emphysematous diaphragm has a decreased fatigability, we identified a significantly longer time-to-peak-tension (63.9 +/- 2.7 ms versus 53.9 +/- 2.4 ms). At both the RNA (RT-PCR) and protein (immunocytochemistry) levels, we found a significant decrease in the fastest, MHC isoform (IIb) in emphysema. Conclusion: This is the first demonstration of MHC shifts and corresponding physiological changes in the diaphragm in an animal model of emphysema. It is established that rodent emphysema, like human emphysema, does result in a physiologically significant shift toward slower diaphragmatic MHC isoforms. In the rat, this occurs at the faster end of the MHC spectrum than in humans. C1 Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Penn Muscle Inst, Philadelphia, PA 19104 USA. Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. Philadelphia Vet Affairs Med Ctr, Dept Surg, Philadelphia, PA USA. Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA. RP Shrager, JB (reprint author), Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA. NR 51 TC 23 Z9 23 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-993X J9 RESPIR RES JI Respir. Res. PD FEB 17 PY 2003 VL 4 IS 1 AR 1 DI 10.1186/rr196 PG 10 WC Respiratory System SC Respiratory System GA 648JB UT WOS:000181146600001 PM 12617755 ER PT J AU Lau, J Long, A AF Lau, J Long, A TI Chronic rhinitis: Allergic or nonallergic? SO AMERICAN FAMILY PHYSICIAN LA English DT Editorial Material ID ASTHMA C1 Tufts Univ, New England Med Ctr, Div Clin Care Res, Boston, MA 02111 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. New England Cochrane Ctr, Boston, MA USA. Harvard Med Sch, Boston, MA USA. RP Lau, J (reprint author), Tufts Univ, New England Med Ctr, Div Clin Care Res, 750 Washington St,Box 63, Boston, MA 02111 USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD FEB 15 PY 2003 VL 67 IS 4 BP 705 EP 706 PG 2 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 648EG UT WOS:000181136400006 PM 12613726 ER PT J AU Januzzi, JL Sabatine, MS Wan, Y Servoss, SJ DiBattiste, PM Jang, IK Theroux, P AF Januzzi, JL Sabatine, MS Wan, Y Servoss, SJ DiBattiste, PM Jang, IK Theroux, P TI Interactions between age, outcome of acute coronary syndromes, and Tirofiban therapy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; ST-SEGMENT-ELEVATION; ELDERLY PATIENTS; ANTITHROMBOTIC THERAPY; RISK STRATIFICATION; PREDICTORS; DISEASE; ANTAGONISTS; REPERFUSION; REGISTRY AB In the Platelet Receptor Inhibition for Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) study, advancing age was associated with an increased risk for complications after a non-ST-segment elevation acute coronary syndrome (NSTE ACS) at all time points examined. Tirofiban therapy was well tolerated and effective for decreasing the considerable age-related risk in patients. with a NSTE ACS. C1 Montreal Heart Inst, Res Ctr, Div Cardiol, Montreal, PQ H1T 1C8, Canada. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Merck Res Labs, W Point, PA USA. RP Theroux, P (reprint author), Montreal Heart Inst, Res Ctr, Div Cardiol, 5000 E Belanger St, Montreal, PQ H1T 1C8, Canada. NR 20 TC 12 Z9 12 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 FEB 15 PY 2003 VL 91 IS 4 BP 457 EP + DI 10.1016/S0002-9149(02)03247-2 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 648LK UT WOS:000181152700018 PM 12586266 ER PT J AU Hoffmann, U Derfler, K Haas, M Stadler, A Brady, TJ Kostner, K AF Hoffmann, U Derfler, K Haas, M Stadler, A Brady, TJ Kostner, K TI Effects of combined low-density lipoprotein apheresis and aggressive statin therapy on coronary calcified plaque as measured by computed tomography SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID HUMAN ATHEROSCLEROTIC LESIONS; ARTERY CALCIUM; LDL-APHERESIS; FAMILIAL HYPERCHOLESTEROLEMIA; CALCIFICATION; QUANTIFICATION; CHOLESTEROL; DISEASE; MICE; PREVENTION AB Eight patients with heterozygous familial hypercholesterolemia who received combined long-term low-density lipoprotein apheresis and high-dose statin therapy showed a significant decrease in volume of coronary calcium over a period of 29 months as measured by, computed tomography. This suggests that the effects of aggressive lipid-lowering therapy can be assessed non-invasively and may be used as surrogate end points when testing new therapies. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Univ & Gen Hosp Vienna, Dept Diagnost Radiol, Vienna, Austria. Univ & Gen Hosp Vienna, Dept Nephrol, Vienna, Austria. Univ & Gen Hosp Vienna, Dept Cardiol, Vienna, Austria. Harvard Univ, Sch Med, Boston, MA USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Dept Radiol, 100 Charles River Plaza,Suite 400, Boston, MA 02114 USA. RI Kostner, Karam/F-5167-2010 NR 20 TC 27 Z9 27 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 FEB 15 PY 2003 VL 91 IS 4 BP 461 EP + DI 10.1016/S0002-9149(02)03248-4 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 648LK UT WOS:000181152700019 PM 12586267 ER PT J AU Wang, V Saab, S AF Wang, V Saab, S TI Ammonia levels and the severity of hepatic encephalopathy SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID PATHOGENESIS C1 Univ Calif Los Angeles, Med Ctr, Div Digest Dis, Dept Med,Liver Transplant Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Liver transplant Ctr, Dept Surg, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90095 USA. RP Saab, S (reprint author), Univ Calif Los Angeles, Med Ctr, Div Digest Dis, Dept Med,Liver Transplant Ctr, 44-138 CHS MC 168417,10833 Le Conte Ave, Los Angeles, CA 90095 USA. NR 11 TC 9 Z9 9 U1 0 U2 0 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 FEB 15 PY 2003 VL 114 IS 3 BP 237 EP 238 DI 10.1016/S0002-9343(02)01571-1 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 653YZ UT WOS:000181465800013 PM 12637141 ER PT J AU Pelosi, P Bottino, N Chiumello, D Caironi, P Panigada, M Gamberoni, C Colombo, G Bigatello, LM Gattinoni, L AF Pelosi, P Bottino, N Chiumello, D Caironi, P Panigada, M Gamberoni, C Colombo, G Bigatello, LM Gattinoni, L TI Sigh in supine and prone position during acute respiratory distress syndrome SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE acute lung injury; acute respiratory distress syndrome; mechanical ventilation; recruitment; end-expiratory lung volume ID ACUTE LUNG INJURY; FUNCTIONAL RESIDUAL CAPACITY; END-EXPIRATORY PRESSURE; GAS-EXCHANGE; RECRUITMENT MANEUVER; ALVEOLAR RECRUITMENT; TIDAL VOLUME; FAILURE; OXYGENATION; MECHANICS AB Interventions aimed at recruiting the lung of patients with acute respiratory distress syndrome (ARDS) are not uniformly effective. Because the prone position increases homogeneity of inflation of the lung, we reasoned that it might enhance its potential for recruitment. We ventilated 10 patients with early ARDS (Pa-O2/Fl(O2), 121 +/- 46 mm Hg; positive end-expiratory pressure, 14 +/- 3 cm H2O) in supine and prone, with and without the addition of three consecutive "sighs" per minute to recruit the lung. Inspired oxygen fraction, positive end-expiratory pressure, and minute ventilation were kept constant. Sighs increased Pa-O2 in both supine and prone (p < 0.01). The highest values of Pa-O2 (192 +/- 41 mm Hg) and end-expiratory lung volume (1,840 +/- 790 ml) occurred with the addition of sighs in prone and remained significantly elevated I hour after discontinuation of the sighs. The increase in Pa-O2 associated with the sighs, both in supine and prone, correlated linearly with the respective increase of end-expiratory lung volume (r = 0.82, p < 0.001). We conclude that adding a recruitment maneuver such as cyclical sighs during ventilation in the prone position may provide optimal lung recruitment in the early stage of ARDS. C1 Univ Milan, Ist Anestesia & Rianimaz, Osped Maggiore, IRCCS, I-20122 Milan, Italy. Inst Insubria, Dipartimento Sci Clin & Biol, Osped Circolo, Fdn Macchi, Varese, Italy. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA USA. RP Gattinoni, L (reprint author), Univ Milan, Ist Anestesia & Rianimaz, Osped Maggiore, IRCCS, Via Francesco Sforza 35, I-20122 Milan, Italy. RI Panigada, Mauro/K-4650-2014; OI Panigada, Mauro/0000-0003-4841-9794; CHIUMELLO, DAVIDE ALBERTO/0000-0001-9260-3930 NR 31 TC 60 Z9 83 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD FEB 15 PY 2003 VL 167 IS 4 BP 521 EP 527 DI 10.1164/rccm.200203-198OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 647MX UT WOS:000181097900006 PM 12493644 ER PT J AU Camargo, CA Smithline, HA Malice, MP Green, SA Reiss, TF AF Camargo, CA Smithline, HA Malice, MP Green, SA Reiss, TF TI A randomized controlled trial of intravenous montelukast in acute asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT 97th International Conference of the American-Thoracic-Society CY MAY 18-23, 2001 CL SAN FRANCISCO, CALIFORNIA SP Amer Thorac Soc DE leukotriene antagonists; injections; intravenous; exacerbation ID LEUKOTRIENE-RECEPTOR ANTAGONIST; IPRATROPIUM BROMIDE; EMERGENCY MANAGEMENT; DOUBLE-BLIND; ALBUTEROL; METAANALYSIS; EXACERBATION AB Many patients with acute asthma do not respond adequately to currently accepted therapy, including oxygen, beta-agonists, and corticosteroids. Leukotriene receptor antagonists such as montelukast have demonstrated efficacy in chronic asthma, but their efficacy in acute asthma is unknown. In this randomized, double-blind, parallel-group pilot study, adults with moderate to severe acute asthma received standard therapy plus either intravenous montelukast (7 or 14 mg) or matching placebo. A total of 201 patients were randomized, and 194 had complete data available for analysis. There was no difference in FEV1 response between the 7- and 14-mg montelukast groups. Montelukast improved FEV1, over the first 20 minutes after intravenous administration (mean percentage change from prerandomization baseline, 14.8% versus 3.6% for the pooled montelukast and placebo treatment groups, respectively; p = 0.007). This benefit was observed at 10 minutes and over 2 hours after intravenous therapy. Patients treated with montelukast tended to receive less beta-agonists and have fewer treatment failures than patients receiving placebo. The tolerability profile for montelukast was similar to that observed for placebo, and no unexpected adverse experiences were observed. We conclude that intravenous montelukast in addition to standard therapy causes rapid benefit and is well tolerated in adults with acute asthma. C1 Merck & Co Inc, Merck Sharp & Dohme Res Labs, Resp & Allergy, Rahway, NJ 07065 USA. Merck & Co Inc, Merck Sharp & Dohme Res Labs, Resp & Allergy, Rahway, NJ 07065 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA USA. Baystate Med Ctr, Dept Emergency Med, Springfield, MA USA. RP Green, SA (reprint author), Merck & Co Inc, Merck Sharp & Dohme Res Labs, Resp & Allergy, 126 E Lincoln Ave,RY 34B-340, Rahway, NJ 07065 USA. NR 32 TC 110 Z9 113 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD FEB 15 PY 2003 VL 167 IS 4 BP 528 EP 533 DI 10.1164/rccm.200208-802OC PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 647MX UT WOS:000181097900007 PM 12456380 ER PT J AU Stam, RW den Boer, ML Meijerink, JPP Ebus, MEG Peters, GJ Noordhuis, P Janka-Schaub, GE Armstrong, SA Korsmeyer, SJ Pieters, R AF Stam, RW den Boer, ML Meijerink, JPP Ebus, MEG Peters, GJ Noordhuis, P Janka-Schaub, GE Armstrong, SA Korsmeyer, SJ Pieters, R TI Differential mRNA expression of Ara-C-metabolizing enzymes explains Ara-C sensitivity in MLL gene-rearranged infant acute lymphoblastic leukemia SO BLOOD LA English DT Article ID PEDIATRIC-ONCOLOGY-GROUP; CYTIDINE DEAMINASE GENE; CHILDRENS CANCER GROUP; CYTOSINE-ARABINOSIDE; DEOXYCYTIDINE KINASE; IN-VITRO; CONFERS RESISTANCE; DRUG-RESISTANCE; POOR-PROGNOSIS; MTT ASSAY AB infant acute lymphoblastic leukemia (ALL) is characterized by a high incidence of mixed lineage leukemia (MLL) gene rearrangements, a poor outcome, and resistance to chemotherapeutic drugs. One exception is cytosine arabinoside (AraC), to which infant ALL cells are highly sensitive. To investigate the mechanism underlying Ara-C sensitivity in infants with ALL, mRNA levels of Ara-C-metabolizing enzymes were measured in infants (n = 18) and older children (noninfants) with ALL (n = 24). In the present study, infant ALL cells were 3.3-fold more sensitive to Ara-C (P = .007) and accumulated 2.3-fold more Ara-CTP (P = .011) upon exposure to Ara-C, compared with older children with ALL. Real-time quantitative reverse trancriptase-polymerase chain reaction (RT-PCR) (TaqMan) revealed that infants express 2-fold less of the Ara-C phosphorylating enzyme deoxycytidine kinase (dCK) mRNA (P = .026) but 2.5-fold more mRNA of the equilibrative nucleoside transporter 1 (hENT1), responsible for Ara-C membrane transport (P = .001). The mRNA expression of pyrimidine nucleotidase I (PN-I), cytidine deaminase (CDA), and deoxycytidylate deaminase (dCMPD) did not differ significantly between both groups. hENT1 mRNA expression inversely correlated with in vitro resistance to Ara-C (r(s) = -0.58, P = .006). The same differences concerning dCK and hENT1 mRNA expression were observed between MLL gene-rearranged (n = 14) and germ line MLL cases (n = 25). An oligonucleotide microarray screen (Affymetrix) comparing patients with MLL gene-rearranged ALL with those with nonrearranged ALL also showed a 1.9-fold lower dCK(P = .001) and a 2.7-fold higher hENT1 (P = .046) mRNA expression in patients with MLL gene-rearranged ALL. We conclude that an elevated expression of hENT1, which transports Ara-C across the cell membrane, contributes to Ara-C sensitivity in MLL gene-rearranged infant ALL. (C) 2003 by The American Society of Hematology. C1 Univ Rotterdam Hosp, Sophia Childrens Hosp, Erasmus MC,Dept Pediat Oncol Hematol, Lab Pediat,Div Oncol Hematol, NL-3015 GE Rotterdam, Netherlands. Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, Amsterdam, Netherlands. COALL Study Grp, Hamburg, Germany. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Stam, RW (reprint author), Univ Rotterdam Hosp, Sophia Childrens Hosp, Erasmus MC,Dept Pediat Oncol Hematol, Lab Pediat,Div Oncol Hematol, Rm Ee 15-14,Dr Molewaterpl 50, NL-3015 GE Rotterdam, Netherlands. RI Meijerink, Jules/D-4393-2017 OI Meijerink, Jules/0000-0002-6860-798X NR 35 TC 134 Z9 143 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 FEB 15 PY 2003 VL 101 IS 4 BP 1270 EP 1276 DI 10.1182/blood-2002-05-1600 PG 7 WC Hematology SC Hematology GA 643DM UT WOS:000180846700013 PM 12406912 ER PT J AU Hideshima, T Mitsiades, C Akiyama, M Hayashi, T Chauhan, D Richardson, P Schlossman, R Podar, K Munshi, NC Mitsiades, N Anderson, KC AF Hideshima, T Mitsiades, C Akiyama, M Hayashi, T Chauhan, D Richardson, P Schlossman, R Podar, K Munshi, NC Mitsiades, N Anderson, KC TI Molecular mechanisms mediating antimyeloma activity of proteasome inhibitor PS-341 SO BLOOD LA English DT Article ID DAMAGE-INDUCED PHOSPHORYLATION; OVERCOMES DRUG-RESISTANCE; MULTIPLE-MYELOMA CELLS; N-TERMINAL KINASE; PROTEIN-KINASE; APOPTOSIS; P53; STRESS; ATR; ACCUMULATION AB We have recently shown that proteasome inhibitor PS-341 induces apoptosis in drug-resistant multiple myelloma (MM) cells, inhibits binding of MM cells in the bone marrow microenvironment, and inhibits cytokines mediating MM cell growth, survival, drug resistance, and I migration in vitro. PS-341 also inhibits human MM cell growth and prolongs survival in a SCID mouse model. Importantly, PS-341 has achieved remarkable clinical res. ponses in patients with refractory relapsed MM. We here demonstrate molecular mechanisms whereby PS-341 mediates anti-MM activity by inducing p53 and MDM2 protein expression; inducing the phosphorylation (Ser15) of p53 protein; activating c-Jun NH2-terminal kinase (JNK), caspase-8, and caspase-3; and cleaving the DNA protein kinase catalytic subunit, ATM, and MDM2. Inhibition of JNK activity a abrogates PS-341-induced MM cell death. These studies identify molecular targets of PS-341 and provide the rationale for the development of second-generation, more targeted therapies. (C) 2003 by The American Society of Hematology. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, M557,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [R0-1 CA50947]; PHS HHS [P0-1 78378] NR 35 TC 397 Z9 419 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 FEB 15 PY 2003 VL 101 IS 4 BP 1530 EP 1534 DI 10.1182/blood-2002-08-2543 PG 5 WC Hematology SC Hematology GA 643DM UT WOS:000180846700048 PM 12393500 ER PT J AU Pastore, YD Jelinek, J Ang, S Guan, YL Liu, EL Jedlickova, K Krishnamurti, L Prchal, JT AF Pastore, YD Jelinek, J Ang, S Guan, YL Liu, EL Jedlickova, K Krishnamurti, L Prchal, JT TI Mutations in the VHL gene in sporadic apparently congenital polycythemia SO BLOOD LA English DT Article ID DOMINANT PRIMARY POLYCYTHEMIA; HIPPEL-LINDAU-DISEASE; PROLYL HYDROXYLATION; HIF-ALPHA; ERYTHROPOIETIN; FAMILY; HEMANGIOBLASTOMA; ERYTHROCYTOSIS; PHENOTYPE AB The congenital polycythemic disorders with elevated erythropoietin (Epo) have been until recently an enigma, and abnormality in the hypoxia-sensing pathway has been hypothesized as a possible mechanism. The tumor suppressor von Hippel-Lindau (VHL) participates in the hypoxia-sensing pathway, as it binds to the proline-hydroxylated form of the hypoxia-inducible factor 1alpha (HIF-1alpha) and mediates its ubiquitination and proteosomal degradation. The loss of VHL function may result in the accumulation of HIF-1alpha and overproduction of HIF-1 downstream target genes including Epo. VHL syndrome is an autosomal dominant disorder predisposing to the development of tumors, due to inherited mutations in the VHL gene. Some rare patients with VHL syndrome have polycythemia, which has been attributed to Epo production by a tumor. It was recently found that homozygosity for the VHL Arg200Trp mutation is the cause of Chuvash polycythemia, an autosomal recessive polycythemic disorder characterized by elevated serum Epo and hypersensitivity of erythroid cells to Epo. We evaluated the role of VHL in 8 children with a history of polycythemia and an elevated serum Epo level and found 3 different germline VHL mutations in 4 of them. One child was homozygous for the Arg200Trp VHL mutation, and another compound heterozygous for the Arg200Trp and the Val130Leu mutations. Two children (siblings) were heterozygous for an Asp126Tyr mutation, one of them fulfilling some criteria of VHL syndrome. We propose that mutations of the VHL gene represent an important cause of pediatric sporadic polycythemias with an inappropriately high serum Epo concentration. (C) 2003 by The American Society of Hematology. C1 Baylor Coll Med, Houston, TX 77030 USA. Texas Childrens Canc Ctr, Houston, TX USA. Hematol Serv, Houston, TX USA. Vet Adm Hosp, Houston, TX USA. Univ Minnesota, Minneapolis, MN USA. RP Prchal, JT (reprint author), Baylor Coll Med, 1 Baylor Plaza,Suite 802E, Houston, TX 77030 USA. RI Jelinek, Jaroslav/A-8476-2008; Jelinek, Jaroslav/D-2282-2012 OI Jelinek, Jaroslav/0000-0002-2533-0220 FU NHLBI NIH HHS [R01HL5007-08, R01HL66333-01] NR 30 TC 101 Z9 107 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 FEB 15 PY 2003 VL 101 IS 4 BP 1591 EP 1595 DI 10.1182/blood-2002-06-1843 PG 5 WC Hematology SC Hematology GA 643DM UT WOS:000180846700057 PM 12393546 ER PT J AU Ditaranto-Desimone, K Saito, M Tekirian, TL Saito, M Berg, M Dubowchik, G Soreghan, B Thomas, S Marks, N Yang, AJ AF Ditaranto-Desimone, K Saito, M Tekirian, TL Saito, M Berg, M Dubowchik, G Soreghan, B Thomas, S Marks, N Yang, AJ TI Neuronal endosomal/lysosomal membrane destabilization activates caspases and induces abnormal accumulation of the lipid secondary messenger ceramide SO BRAIN RESEARCH BULLETIN LA English DT Article ID DETERGENT N-DODECYLIMIDAZOLE; ALZHEIMERS-DISEASE PATHOGENESIS; PROGRAMMED CELL-DEATH; INDUCED APOPTOSIS; CATHEPSIN-D; LYSOSOMOTROPIC DETERGENTS; LYSOSOMAL SYSTEM; PC12 CELLS; ACIDIC SPHINGOMYELINASE; SERUM DEPRIVATION AB Impairment of endosomal/lysosomal functions are reported as some of the earliest changes in several age-related neurological disorders such as Alzheimer's disease. Dysregulation of the lysosomal system is also accompanied by the accumulation of age-associated pigments and several recent reports have indicated that this age-related lipofuscin accumulation can sensitize cells to oxidative stress and apoptotic cell death. In this study, we have established and evaluated an in vitro age-related pathology paradigm that models lipofuscin accumulation. Our model consists of the treatment of cultured primary mouse neurons with lysosomotropic detergents. We have observed that one of the earliest biochemical changes associated with lysosomotropic detergent-induced membrane instability is a loss of the endosomal/lysosomal proton gradient integrity, followed by an activation of sphingomyelin hydrolysis and ceramide accumulation within enlarged endosomal/lysosomal vesicles. In addition, we demonstrate that ceramide accumulation correlates with the activation of proximal procaspases-8 and -9 as well as distal caspase-3, prior to the appearance of cell death. Taken together, we propose that disturbances of the endosomal/lysosomal system, in addition to the activation of the sphingomyelinase hydrolysis cycle, play essential roles in the course of post-mitotic neuronal aging. The abnormal accumulation of undigested lipids and proteins within dysfunctional endosomal/lysosomal vesicle populations during the process of pathological aging may serve as triggers of the cell death programs that are associated with downstream neurodegeneration. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Univ So Calif, Sch Pharm, Dept Pharmaceut Sci, Los Angeles, CA 90033 USA. Nathan S Kline Inst Psychiat Res, Dementia Res Program, Orangeburg, NY 10962 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Bristol Myers Squibb Co, Pharmaceut Res Inst, Wallingford, CT 06492 USA. RP Yang, AJ (reprint author), Univ So Calif, Sch Pharm, Dept Pharmaceut Sci, Los Angeles, CA 90033 USA. FU NIA NIH HHS [R01 AG025323]; NIMH NIH HHS [MH59786-01, R01 MH059786] NR 52 TC 22 Z9 22 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD FEB 15 PY 2003 VL 59 IS 6 BP 523 EP 531 AR PII S0361-9230(02)00948-6 DI 10.1016/S0361-9230(02)00948-6 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 648DA UT WOS:000181133500015 PM 12576150 ER PT J AU Gibson, SL Dai, CY Lee, HW DePinho, RA Gee, MS Lee, WMF Furth, EE Brensinger, C Enders, GH AF Gibson, SL Dai, CY Lee, HW DePinho, RA Gee, MS Lee, WMF Furth, EE Brensinger, C Enders, GH TI Inhibition of colon tumor progression and angiogenesis by the Ink4a/Arf locus SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR EXPRESSION; COLORECTAL-CANCER; P16(INK4A); TUMORIGENESIS; MOUSE; METHYLATION; NEOPLASIA; CARCINOMA; P14(ARF); GENE AB The Ink4alArf locus is frequently methylated in colon carcinoma and other common human cancers, suggesting that the locus may play a broad, as yet poorly defined, role inhibiting tumor progression. We examined the influence of the locus in mice with multiple intestinal neoplasia (Min). Colon tumors in 3-month-old Min mice that were null for the Ink4alArf locus (-/-) were moderately larger than in Ink4a/Arf-wild-type(+/+) animals (P = 0.032). More strikingly, one-half of the -/- colon tumors were grossly red in color, whereas most of the +/+ tumors were white (P = 0.0025). This color difference remained statistically significant after normalizing for tumor area (P = 0.016). On histological analysis, -/- colon tumors displayed more RBCs near the tumor surface, twice the number of functional vessels, and features of carcinoma in situ not found in +/+ tumors. Biochemical analyses showed that red tumors had higher hemoglobin and vascular endothelial growth factor (VEGF) content than white tumors. Surprisingly, the small intestinal tumor burden was actually lower in -/- animals, and none of these tumors were red, underscoring the importance of tissue context in the function of the locus. These results provide direct evidence that the Ink4alArf locus inhibits colon tumor progression. The enhanced vascularity of the -/- tumors is particularly significant in light of the clinical importance of this property in the detection, recurrence, and therapy of colon tumors. C1 Univ Penn, GI Div, Dept Med, Dept Genet, Philadelphia, PA 19104 USA. Univ Penn, Abramson Canc Ctr, Dept Med, Div Hematol Oncol, Philadelphia, PA 19104 USA. Univ Penn, Abramson Canc Ctr, Dept Pathol, Philadelphia, PA 19104 USA. Univ Penn, Abramson Canc Ctr, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Sungkyunkwan Univ, Suwon, South Korea. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Enders, GH (reprint author), Univ Penn, GI Div, Dept Med, Dept Genet, 600 CRB,415 Curie Blvd, Philadelphia, PA 19104 USA. EM endersgh@mail.med.upenn.edu FU NIDDK NIH HHS [R01 DK064758-01, P30 DK50306] NR 33 TC 33 Z9 48 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 15 PY 2003 VL 63 IS 4 BP 742 EP 746 PG 5 WC Oncology SC Oncology GA 645XV UT WOS:000181006500002 PM 12591718 ER PT J AU Izumi, Y di Tomaso, E Hooper, A Huang, P Huber, J Hicklin, DJ Fukumura, D Jain, RK Suit, HD AF Izumi, Y di Tomaso, E Hooper, A Huang, P Huber, J Hicklin, DJ Fukumura, D Jain, RK Suit, HD TI Responses to antiangiogenesis treatment of spontaneous autochthonous tumors and their isografts SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; MONOCLONAL-ANTIBODY; FACTOR RECEPTOR-2; UP-REGULATION; IN-VIVO; ANGIOGENESIS; CARCINOMA; CELLS; MOUSE AB Preclinical studies typically use human tumor xenografts or murine tumor isografts. Tumor growth may be accelerated by in vivo passage, thus making these tumors more sensitive to some therapies than the original tumors. In the present study, by comparing the effects of DC101, an antimurine vascular endothelial growth factor receptor 2 (VEGFR2) monoclonal antibody, on spontaneous autochthonous tumors and their early generation transplants, we show that this growth acceleration is diminished by DC101 treatment. Spontaneous autochthonous tumors in aged C3H mice consisted of s.c. sarcomas and adenocarcinomas, and their growth rate was accelerated by in vivo passages. Anti-VEGFR2 treatment decreased vessel density, increased apoptosis, and reduced tumor growth in large (500 mm(3)) spontaneous autochthonous tumors. Anti-VEGFR2 treatment significantly delayed tumor growth and extended animal survival. Tumor growth acceleration by in vivo passage was diminished by DC101 treatment. To our knowledge, this is the first evaluation of antiangiogenic therapy in a spontaneous autochthonous tumor model, which may more closely resemble human tumors. Additionally, this is the first study to compare treatment response between the parental tumor and its isografts. Although passaged tumors behave differently, it is encouraging that the tumor growth rates under DC101 treatment are comparable among different passage generations. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. ImClone Syst Inc, New York, NY 10014 USA. RP Jain, RK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,COX 734, Boston, MA 02114 USA. FU NCI NIH HHS [P01-CA-80124] NR 22 TC 22 Z9 22 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 15 PY 2003 VL 63 IS 4 BP 747 EP 751 PG 5 WC Oncology SC Oncology GA 645XV UT WOS:000181006500003 PM 12591719 ER PT J AU Heuze-Vourc'h, N Zhu, L Krysan, K Batra, RK Sharma, S Dubinett, SM AF Heuze-Vourc'h, N Zhu, L Krysan, K Batra, RK Sharma, S Dubinett, SM TI Abnormal interleukin 10R alpha expression contributes to the maintenance of elevated cyclooxygenase-2 in non-small cell lung cancer cells SO CANCER RESEARCH LA English DT Article ID EPITHELIAL-CELLS; IL-10; RECEPTOR; BALANCE AB Non-small cell lung cancer (NSCLC) cells are known to constitutively overexpress cyclooxygenase (COX)-2. Tumor COX-2-dependent production of PGE(2) triggers the synthesis of lymphocyte and macrophage interleukin (IL)-10 that, in turn, is known to potently suppress COX-2 in normal cells. Thus, we investigated the capacity of IL-10 to down-regulate COX-2 expression in NSCLC cells. Western blotting and ELISA analyses revealed that IL-10 did not affect COX-2 expression and subsequent PGE(2) production in NSCLC cells. Although normal human bronchial epithelial cells expressed both intracellular and membrane IL-10Ralpha, NSCLC cells only expressed intracellular but not cell surface membrane IL-10R. Unresponsiveness of COX-2 to IL-10 is due to the deficiency of IL-10Ralpha on the surface of NSCLC cells. Our findings highlight a novel mechanism contributing to maintenance of elevated COX-2 and PGE(2) in the lung tumor environment. C1 Univ Calif Los Angeles, David Geffen Sch Med, Lung Canc Res Program, Div Pulm & Crit Care Med,Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Lung Canc Res Program, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Lung Canc Res Program, Div Pulm & Crit Care Med,Dept Med, 10833 Conte Ave,37-131 CHS, Los Angeles, CA 90095 USA. RI HEUZE-VOURC'H, Nathalie/P-8081-2016 FU NCI NIH HHS [1P50 CA90388, CA-16042, R01 CA71818, R01 CA85686]; NIAID NIH HHS [AI-28697] NR 28 TC 24 Z9 25 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD FEB 15 PY 2003 VL 63 IS 4 BP 766 EP 770 PG 5 WC Oncology SC Oncology GA 645XV UT WOS:000181006500007 PM 12591723 ER PT J AU Huang, JS Wilkie, SJ Dolan, S Gallafent, JH Aliabadi, N Sullivan, MP Grinspoon, S AF Huang, JS Wilkie, SJ Dolan, S Gallafent, JH Aliabadi, N Sullivan, MP Grinspoon, S TI Reduced testosterone levels in human immunodeficiency virus-infected women with weight loss and low weight SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID BODY-COMPOSITION; EUGONADAL MEN; MOOD; PARAMETERS; ENDOCRINE; EXERCISE; VALIDITY AB Risk factors for hypoandrogenemia among low-weight, human immunodeficiency virus (HIV)-infected patients are not known. Testosterone levels of 69 HIV-infected women with low weight and weight loss were compared with levels for 25 healthy, age- and body mass index-matched control subjects. HIV-infected subjects were of low weight, with a mean (+/- standard deviation) weight loss of -17.6% +/- 9.7% from preillness maximum, and 42% of HIV-infected subjects had a body mass index of <20 kg/m(2). Forty-nine percent of the HIV-infected population versus 8% of the control population exhibited low free testosterone levels (P<.001). Among HIV-infected women, when we controlled for chronic hepatitis status, age, and time of blood sampling, weight loss of >10% of maximum weight was a significant predictor of low free testosterone levels. Free testosterone levels did not differ by drug class or antiretroviral regimen. In conclusion, decreased androgen levels are common among HIV-infected women reporting significant weight loss, independent of exposure to antiretroviral medications. C1 Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St,LON,Ste 207, Boston, MA 02114 USA. FU NCRR NIH HHS [RR-01066]; NIAID NIH HHS [AI-51947, K23 AI051947, K23 AI051947-02]; NIDDK NIH HHS [DK-54167] NR 21 TC 11 Z9 11 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 15 PY 2003 VL 36 IS 4 BP 499 EP 506 DI 10.1086/367642 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 642AE UT WOS:000180778700018 PM 12567309 ER PT J AU Guzman, Y Stone, EA Fung, HB Brau, N AF Guzman, Y Stone, EA Fung, HB Brau, N TI Clostridium difficile colitis after forced anal-receptive intercourse SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HOMOSEXUAL MEN; CHEMOTHERAPY; DIARRHEA; PACLITAXEL AB Colitis caused by Clostridium difficile toxin has been reported in homosexual men. We report a case of C. difficile colitis that occurred in an immunocompetent heterosexual man after forced anal-receptive intercourse. C1 Bronx Vet Affairs Med Ctr, Pharm Program, Bronx, NY 10468 USA. Bronx Vet Affairs Med Ctr, Crit Care Sect, Bronx, NY 10468 USA. Bronx Vet Affairs Med Ctr, Infect Dis Sect, Program Med, Bronx, NY 10468 USA. Mt Sinai Sch Med, New York, NY USA. RP Brau, N (reprint author), Bronx Vet Adm Med Ctr, Infect Dis Sect 111F, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 15 PY 2003 VL 36 IS 4 BP E61 EP E62 DI 10.1086/367652 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 642AE UT WOS:000180778700031 PM 12567322 ER PT J AU Sledge, GW Neuberg, D Bernardo, P Ingle, JN Martino, S Rowinsky, EK Wood, WC AF Sledge, GW Neuberg, D Bernardo, P Ingle, JN Martino, S Rowinsky, EK Wood, WC TI Phase III trial of doxorubicin, paclitaxel, and the combination of doxorubicin and paclitaxel as front-line chemotherapy for metastatic breast cancer: An intergroup trial (E1193) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID INITIAL CHEMOTHERAPY; RANDOMIZED TRIAL; DRUG-THERAPY; ADRIAMYCIN; CARCINOMA; SURVIVAL; TAXOL AB Purpose : Between February 1993 and September 1995, 739 patients with metastatic breast cancer were entered on an Intergroup trial (E 1193) comparing doxorubicin (60 mg/ m(2)), paclitaxel (175 mg/m(2)/24 h), and the combination of doxrubicin and paclitaxel (AT, 50 mg/m(2) and 150 mg/ m(2)/24 h, plus granulocyte colony-stimulating factor 5 mg/ kg) as first-line therapy. Patients receiving single-agent doxorubicin or paclitaxel were crossed over to the other agent at time of progression. Patients and Methods: Patients were well balanced for on-study characteristics. Results: Responses (complete response and partial response) were seen in 36% of doxrubicin, 34% of paclitaxel, and 479% of AT patients (P =.84 for doxorubicin v paclitaxel, P =.007 for vAT, P =.004 for paclitaxel vAT). Median time to treatment failure (TTF) is 5.8, 6.0, and 8.0 months for doxorubicin, paclitaxel, and AT, respectively (P =.68 for doxorubicin v paclitaxel, P =.003 for doxorubicin v AT, P =.009 for paclitaxel v AT). Median survivals are 18.9 months for patients taking doxorubicin, 22.2 months for patients taking paclitaxel, and 22.0 months for patients taking AT (P = not significant). Responses were seen in 20% of patients crossing from doxrubicin --> paclitaxel and 22% of patients crossing from paclitaxel --> doxorubicin (P = not significant). Changes in global quality-of-life measurements from on-study to week 16 were similar in all three groups. Conclusion: (1) doxorubicin and paclitaxel, in the doses used here, have equivalent activity, (2) the combination of AT results in superior overall response rates and time to TTF; and (3) despite these results, combination therapy with AT did not improve either survival or quality of life compared to sequential single-agent therapy. C1 Indiana Univ, Med Ctr, Indianapolis, IN 46202 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. Westlake Comprehens Canc Ctr, Westlake Village, CA USA. Johns Hopkins Oncol Ctr, Baltimore, MD USA. Emory Univ, Atlanta, GA 30322 USA. RP Sledge, GW (reprint author), Indiana Univ, Med Ctr, Canc Pavill,535 Barnhill Dr,Room RT473, Indianapolis, IN 46202 USA. FU NCI NIH HHS [CA 49883, CA 13650, CA 16116, CA 21115, CA 23318, CA 32102, CA 66636] NR 21 TC 386 Z9 398 U1 3 U2 13 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 15 PY 2003 VL 21 IS 4 BP 588 EP 592 DI 10.1200/JCO.2003.08.013 PG 5 WC Oncology SC Oncology GA 645WE UT WOS:000181002500005 PM 12586793 ER PT J AU Partridge, AH Wang, PS Winer, EP Avorn, J AF Partridge, AH Wang, PS Winer, EP Avorn, J TI Nonadherence to adjuvant tamoxifen therapy in women with primary breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RECEPTOR-POSITIVE TUMORS; AGE-RELATED DIFFERENCES; ANTIHYPERTENSIVE THERAPY; PHARMACY RECORDS; CONTROLLED TRIAL; HEALTHY WOMEN; MEDICAID DATA; PILL COUNTS; ADHERENCE; VALIDATION AB Purpose : Although clinical trials have clearly demonstrated the benefits of tamoxifen in women with primary breast cancer, little is known about how this drug is actually used in the general population. We sought to estimate adherence and predictors of nonadherence in women starting tamoxifen as adjuvant breast cancer therapy. Patients and Methods: Subjects were age IS years or older initiating tamoxifen for primary breast cancer and enrolled in New Jersey's Medicaid or Pharmaceutical Assistance to the Aged and Disabled programs during the study period, from 1990 to 1996 (N = 2,378). Main outcome measures were number of days covered by filled prescriptions for tamoxifen in the first year of therapy with the 4 years after tamoxifen initiation for a subset, predictors of good versus poor adherence. Results: Twenty-three percent of patients missed taking tamoxifen on more than one fifth of days studied, although on average, patients filled prescriptions for tamoxifen for 87% of their first year of treatment. The youngest, oldest, nonwhite, and mastectomy patients had significantly lower rates of adherence; patients who had seen an oncologist before taking tamoxifen had significantly higher rates of adherence. Overall adherence decreased to 50% by year 4 of therapy. Conclusion: The mean level of adherence to tamoxifen is high compared with other chronic medications. However, nearly one fourth of patients may be at risk for inadequate clinical response because of poor adherence. Because of the efficacy of tamoxifen therapy in preventing recurrence and death in women with early-stage breast cancer, further efforts are necessary to identify and. prevent suboptimal adherence. C1 Dana Farber Canc Inst, Dept Med Oncol, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Partridge, AH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Div Pharmacoepidemiol & Pharmacoecon, 44 Binney St,D1210, Boston, MA 02115 USA. EM ahpartridge@partners.org FU NIA NIH HHS [R03 AG 18395] NR 47 TC 329 Z9 333 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 15 PY 2003 VL 21 IS 4 BP 602 EP 606 DI 10.1200/JCO.2003.07.071 PG 5 WC Oncology SC Oncology GA 645WE UT WOS:000181002500007 PM 12586795 ER PT J AU Duggan, DB Petroni, GR Johnson, JL Glick, JH Fisher, RI Connors, JM Canellos, GP Peterson, BA AF Duggan, DB Petroni, GR Johnson, JL Glick, JH Fisher, RI Connors, JM Canellos, GP Peterson, BA TI Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin's disease: Report of an intergroup trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID IMPROVES FAILURE-FREE; CLINICAL-TRIALS; 2ND NEOPLASMS; CHEMOTHERAPY; LEUKEMIA; RADIOTHERAPY; SURVIVAL AB Purpose : In a series of trials, doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and mechlorethamine, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, and vinblastine (MOPP/ABV) have been identified as effective treatments for Hodgkin's disease. We compared these regimens as initial chemotherapy for Hodgkin's disease. Patients and Methods: Adult patients (N = 856) with advanced Hodgkin's disease were randomly assigned to treatment with ABVD or MOPP/ABV. The major end points were failure-free and overall survival, life-threatening acute toxicities, and serious long-term toxicities, including cardiomyopathy, pulmonary toxicity, myelodysplastic syndromes (MDS), and secondary malignancies. Results: The rates of complete remission (76% v 80%, P=.16), failure-free survival at 5 years (63% v 66%, P=.42), and overall survival at 5 years (82% v 81%, P=.82) were similar for ABVD and MOPP/ABV, respectively. Clinically significant acute pulmonary and hematologic toxicity were more common with MOPP/ABV (P=.060 and .001, respectively). There was no difference in cardiac toxicity. There were 24 deaths attributed to initial treatment: nine with ABVD and 15 with MOPP/ABV (P=.057). There have been 18 second malignancies associated with ABVD and 28 associated with MOPP/ABV (P=.13). Thirteen patients have developed MDS or acute leukemia: 11 were initially treated with MOPP/ABV, and two were initially treated with ABVD but subsequently received MOPP-containing regimens and radiotherapy before developing leukemia (P=.011). Conclusion: ABVD and the MOPP/ABV hybrid are effective therapies for Hodgkin's disease. MOPP/ABV is associated with a greater incidence of acute toxicity, MDS, and leukemia. ABVD should be considered the standard regimen for treatment of advanced Hodgkin's disease. C1 SUNY Upstate Med Univ, Dept Med, Syracuse, NY 13210 USA. Univ Rochester, Sch Med, James P Wilmot Canc Ctr, Rochester, NY 14627 USA. Duke Univ, Ctr Stat, Canc & Leukemia Grp B, Durham, NC 27706 USA. Univ Minnesota, Sch Med, Div Oncol, Minneapolis, MN 55455 USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. British Columbia Canc Agcy, Vancouver Canc Ctr, Vancouver, BC V5Z 4E6, Canada. RP Duggan, DB (reprint author), SUNY Upstate Med Univ, Dept Med, 750 E Adams St, Syracuse, NY 13210 USA. FU NCI NIH HHS [CA 31946] NR 24 TC 273 Z9 292 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 FEB 15 PY 2003 VL 21 IS 4 BP 607 EP 614 DI 10.1200/JCO.2003.12.086 PG 8 WC Oncology SC Oncology GA 645WE UT WOS:000181002500008 PM 12586796 ER PT J AU Salgia, R Lynch, T Skarin, A Lucca, J Lynch, C Jung, K Hodi, FS Jaklitsck, M Mentzer, S Swanson, S Lukanich, J Buena, R Wain, J Mathisen, D Wright, C Fidias, P Donahue, D Clift, S Hardy, S Neuberg, D Mulligan, R Webb, I Sugarbaker, D Mihm, M Dranoff, G AF Salgia, R Lynch, T Skarin, A Lucca, J Lynch, C Jung, K Hodi, FS Jaklitsck, M Mentzer, S Swanson, S Lukanich, J Buena, R Wain, J Mathisen, D Wright, C Fidias, P Donahue, D Clift, S Hardy, S Neuberg, D Mulligan, R Webb, I Sugarbaker, D Mihm, M Dranoff, G TI Vaccination with irradiated autologous tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor augments antitumor immunity in some patients with metastatic non-small-cell lung carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; CANCER ANTIGENS; GENE-TRANSFER; PHASE-I; IDENTIFICATION; MELANOMA; EPITOPES; VACCINES; VIVO; IMMUNOTHERAPY AB Puspose : We demonstrated that vaccination with irradiated tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates potent, specific, and long-lasting antitumor immunity in multiple murine models and patients with metastatic melanoma. To test whether this vaccination strategy enhances antitumor immunity in patients with metastatic non-small-cell lung cancer (NSCLC), we conducted a phase I clinical trial. Patients and Methods: Resected metastases were processed to single-cell suspension, infected with a replication-defective adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines consisted of 1 x 10(6), 4 x 10(6), or 1 x 10(7) cells, depending on overall yield, and were administered intradermally and subcutaneously at weekly and biweekly intervals. Results: Vaccines were successfully manufactured for 34 (97%) of 35 patients. The average GM-CSF secretion was 513 ng/ 10(6) cells/24 h. Toxicities were restricted to grade 1 to 2 local skin reactions. Nine patients were withdrawn early because of rapid disease progression. Vaccination elicited dendritic cell, macrophage, granulocyte, and lymphocyte infiltrates in 18 of 25 assessable patients. Immunization stimulated the development of delayed-type hypersensitivity reactions to irradiated, dissociated, autologous, nontransfected tumor cells in 18 of 22 patients. Metastatic lesions resected after vaccination showed T lymphocyte and plasma cell infiltrates with tumor necrosis in three of six patients. Two patients surgically rendered as having no evidence of disease at enrollment remain free of disease at 43 and 42 months. Five patients showed stable disease durations of 33, 19, 12, 10, and 3 months. One mixed response was observed. Conclusion: Vaccination with irradiated autologous NSCLC cells engineered to secrete GM-CSF enhances antitumor immunity in some patients with metastatic NSCLC. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Hematol Oncol, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Hematol Oncol, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Hematol Oncol, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Hematol Oncol, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Hematol Oncol, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Hematol Oncol, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Dept Pathol, Boston, MA 02114 USA. Cell Genesys, Foster City, CA USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Dana 510E,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 74886] NR 37 TC 170 Z9 179 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 FEB 15 PY 2003 VL 21 IS 4 BP 624 EP 630 DI 10.1200/JCO.2003.03.091 PG 7 WC Oncology SC Oncology GA 645WE UT WOS:000181002500010 PM 12586798 ER PT J AU Flores-Villanueva, PO Hendel, H Caillat-Zucman, S Rappaport, J Burgos-Tiburcio, A Bertin-Maghit, S Ruiz-Morales, JA Teran, ME Rodriguez-Tafur, J Zagury, JF AF Flores-Villanueva, PO Hendel, H Caillat-Zucman, S Rappaport, J Burgos-Tiburcio, A Bertin-Maghit, S Ruiz-Morales, JA Teran, ME Rodriguez-Tafur, J Zagury, JF TI Associations of MHC ancestral haplotypes,with resistance/susceptibility to AIDS disease development SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I MOLECULES; HLA-E; NK CELLS; HIV-1 INFECTION; PROGRESSION; GENES; CD94/NKG2A; SUSCEPTIBILITY; POLYMORPHISM AB We tested the association of MHC ancestral haplotypes with rapid or slow progression to AIDS by comparing their frequencies in the French genetics of resistance/susceptibility to immunodeficiency virus cohort with that reported in a control French population. Seven ancestral haplotypes were identified in the genetics of resistance/susceptibility to immunodeficiency virus cohort with a frequency > 1%. The 8.1 (odds ratio (OR) = 3, p = 0.006), 35.1 (OR = 5.7, p = 0.001), and 44.2 (OR 3.4, p = 0.007) ancestral haplotypes were associated with rapid progression, whereas the 35.2 (OR = 3.6, p = 0.001), 44.1 (OR 5.4, p < 10(-4)), and 57.1 (OR = 5.8, p < 10(-4)) ancestral haplotypes were associated with slow progression to AIDS. Although the frequency of each ancestral haplotype is low in the population, the OR were quite higher than those previously obtained for single HLA allele associations, with some p values as low as 10(-4). The analysis of the recombinant fragments of these haplotypes allowed the identification of the MHC regions in the 35.1, 35.2, and 44.2 haplotypes associated with rapid progression to AIDS and the MHC regions of the 44.1 and 57.1 haplotypes associated with slow progression to AIDS. Previous studies have identified single HLA alleles associated with disease progression. Our results on recombinant fragments confirm the direct role of HLA-B35 in rapid progression. Associations with HLA-A29 and -B57 might be due to linkage disequilibrium with other causative genes within the MHC region. C1 Univ Paris 06, Ctr Rech Cordeliers, F-75006 Paris, France. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Hop Necker Enfants Malad, Immunol Lab, Paris, France. Temple Univ, Ctr Neurovirol & Canc, Philadelphia, PA 19122 USA. Univ Nacl Mayor San Marcos, Escuela Med San Fernando, Lima, Peru. RP Flores-Villanueva, PO (reprint author), Univ Paris 06, Ctr Rech Cordeliers, 15 Rue Ecole Med, F-75006 Paris, France. EM pedro_flores_villanueva@dfci.harvard.edu; jfz@ccr.jussieu.fr FU NHLBI NIH HHS [HL 29583, K30 HL 04095-04, R21 HL 72177-01] NR 32 TC 65 Z9 68 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 15 PY 2003 VL 170 IS 4 BP 1925 EP 1929 PG 5 WC Immunology SC Immunology GA 642ZC UT WOS:000180836400041 PM 12574360 ER PT J AU Xia, JC Tanaka, Y Koido, S Liu, CL Mukherjee, P Gendler, SJ Gong, JL AF Xia, JC Tanaka, Y Koido, S Liu, CL Mukherjee, P Gendler, SJ Gong, JL TI Prevention of spontaneous breast carcinoma by prophylactic vaccination with dendritic/tumor fusion cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; TRANSGENIC MICE; MAMMARY TUMORIGENESIS; IN-VIVO; ERADICATE TUMORS; CORE PROTEIN; HUMAN-MILK; C-MYC; ANTIGEN; IMMUNITY AB Genetically modified mice with spontaneous development of mammary carcinoma provide a powerful tool to study the efficacy of tumor vaccines, since they mimic breast cancer development in humans. We used a transgenic murine model expressing polyomavirus middle T oncogene and mucin I tumor-associated Ag to determine the preventive effect of a dendritic/tumor fusion cell vaccine. The MMT (a transgenic murine model) mice developed mammary carcinoma between the ages of 65-108 days with 100% penetrance. No spontaneous CTL were detected. However, prophylactic vaccination of MMT mice with dendritic/tumor fusion cells induced polyclonal CTL activity against spontaneous mammary carcinoma cells and rendered 57-61% of the mice free of the disease at the end of experiment (180 days). Furthermore, the level of CTL activity was maintained with multiple vaccinations. The antitumor immunity induced by vaccination with dendritic/tumor fusion cells reacted differently to injected tumor cells and autochthonous tumor. Whereas the injected tumor cells were rejected, the autochthonous tumor evaded the attack and was allowed to grow. Collectively these results indicate that prophylactic vaccination with dendritic/tumor fusion cells confers sufficient antitumor immunity to counter the tumorigenesis of potent oncogenic products. The findings in the present study are highly relevant to cancers in humans. C1 Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Med Ctr, Boston, MA 02115 USA. Mayo Clin Scottsdale, Scottsdale, AZ USA. RP Gong, JL (reprint author), Boston Univ, Sch Med, Dept Med, 88 E Newton St, Boston, MA 02118 USA. FU NCI NIH HHS [R01 CA 87057] NR 41 TC 65 Z9 71 U1 3 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 15 PY 2003 VL 170 IS 4 BP 1980 EP 1986 PG 7 WC Immunology SC Immunology GA 642ZC UT WOS:000180836400048 PM 12574367 ER PT J AU Davis, L Roullet, JB Thornburg, KL Shokry, M Hohimer, AR Giraud, GD AF Davis, L Roullet, JB Thornburg, KL Shokry, M Hohimer, AR Giraud, GD TI Augmentation of coronary conductance in adult sheep made anaemic during fetal life SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID LEFT-VENTRICULAR HYPERTROPHY; MYOCARDIAL BLOOD-FLOW; RESISTANCE VESSELS; RESERVE; HEART; GROWTH; YOUNG; RATS; AGE AB Maximal coronary conductance with adenosine in anaemic fetal sheep is twice that of non-anaemic fetuses. To investigate whether this increase in conductance persists into adulthood we studied twin sheep as fetuses and again as adults. Nine anaemic fetuses (118 days gestation) underwent isovolaemic haemorrhage for 18.0 +/- 4.6 days (means +/- S.D.) during which time the haematocrit was reduced from 39.9 +/- 5.2 % to 16.3 +/- 3.4 % and oxygen content from 8.6 +/- 1.3 to 2.3 +/- 0.2 ml dl(-1). At 138 days the anaemic fetuses were transfused; at delivery the haematocrit was 29.3 +/- 6.8 % compared to nine control fetuses in which the haematocrit was 38.5 +/- 4.3 %. The weight at delivery was 3.5 +/- 0.36 kg in the anaemic fetuses vs. 4.2 +/- 0.83 kg in controls. Twenty-eight weeks later, we placed an occluder on the descending thoracic aorta and inferior vena cava, a flow probe around the proximal left circumflex coronary artery, and catheters in the left atrial appendage, jugular and carotid vessels. Maximal coronary conductance was determined in the adults by recording coronary blood flow as driving pressure was altered by inflating the occluders while adenosine was infused into the left atrium. Right atrial, left atrial, systolic and mean arterial pressures, systemic vascular resistance and haematocrit were not different between 'in utero anaemic' and control adults. The adults that were anaemic in utero weighed less than the controls 39.4 +/- 4.6 kg vs. 45.0 +/- 5.6 kg. Maximal conductance was greater in the adults that were anaemic in utero: 11.2 +/- 4.0 ml min(-1) (100 g)(-1) mmHg(-1) as compared to 6.1 +/- 1.8 ml min(-1) (100 g)(-1) mmHg(-1) in the controls. Vascular reactivity of the mesenteric arteries was not different. These data suggest that coronary conductance can be modified in utero by anaemia (high flow and hypoxaemia) and that the remodelled coronary tree persists to adulthood. C1 Oregon Hlth Sci Univ, Dept Obstet, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Internal Med, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Heart Res Ctr, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 USA. RP Davis, L (reprint author), Oregon Hlth Sci Univ, Dept Obstet, Portland, OR 97239 USA. FU NHLBI NIH HHS [HL45043, R01 HL045043]; NICHD NIH HHS [P01 HD034430, P01HD34430] NR 19 TC 26 Z9 26 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD FEB 15 PY 2003 VL 547 IS 1 BP 53 EP 59 DI 10.1113/jphysiol.2002.023283 PG 7 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 690VD UT WOS:000183570400009 PM 12562949 ER PT J AU Stone, ME AF Stone, ME TI Women in medicine. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp Lib, Boston, MA USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp Lib, Boston, MA 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 FEB 15 PY 2003 VL 128 IS 3 BP 130 EP 130 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 673WM UT WOS:000182603300043 ER PT J AU Seibler, J Zevnik, B Kuter-Luks, B Andreas, S Kern, H Hennek, T Rode, A Heimann, C Faust, N Kauselmann, G Schoor, M Jaenisch, R Rajewsky, K Kuhn, R Schwenk, F AF Seibler, J Zevnik, B Kuter-Luks, B Andreas, S Kern, H Hennek, T Rode, A Heimann, C Faust, N Kauselmann, G Schoor, M Jaenisch, R Rajewsky, K Kuhn, R Schwenk, F TI Rapid generation of inducible mouse mutants SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RECOMBINASE ACTIVITY; SOMATIC MUTAGENESIS; LOXP RECOMBINATION; REPORTER STRAIN; CRE; MICE; CELLS; TRANSGENES; EXPRESSION; TAMOXIFEN AB We have generated an optimized inducible recombination system for conditional gene targeting based on a Cre recombinase-steroid receptor fusion. This configuration allows efficient Cre-mediated recombination in most organs of the mouse upon induction, without detectable background activity. An ES cell line, was established that carries the inducible recombinase and a loxP-flanked lacZ reporter gene. Out of this line, completely ES cell-derived mice were efficiently produced through tetraploid blastocyst complementation, without the requirement of mouse breeding. Our findings provide a new concept allowing the generation of inducible mouse mutants within 6 months, as compared to 14 months using the current protocol. C1 ARTEMIS Pharmaceut GmbH, D-51063 Cologne, Germany. MIT, Whitehead Inst Biomed Res, Cambridge, MA USA. MIT, Dept Biol, Cambridge, MA USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Schwenk, F (reprint author), ARTEMIS Pharmaceut GmbH, Neurather Ring 1, D-51063 Cologne, Germany. NR 27 TC 141 Z9 146 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 15 PY 2003 VL 31 IS 4 AR e12 DI 10.1093/nar/gng012 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 647VQ UT WOS:000181115100001 PM 12582257 ER PT J AU Jung, K Krell, HW Ortel, B Hasan, T Romer, A Schnorr, D Loening, SA Lein, M AF Jung, K Krell, HW Ortel, B Hasan, T Romer, A Schnorr, D Loening, SA Lein, M TI Plasma matrix metalloproteinase 9 as biomarker of prostate cancer progression in Dunning (Copenhagen) rats SO PROSTATE LA English DT Article DE matrix metalloproteinases; MatLyLu; MMP inhibitor; prostate cancer ID IN-SITU HYBRIDIZATION; IV COLLAGENASE; TISSUE INHIBITORS; CELL-LINES; NUDE-MICE; EXPRESSION; QUANTIFICATION; SECRETION; BENIGN; ADENOCARCINOMA AB BACKGROUND. Matrix metalloproteinases (MMPs) play an important role in invasion and metastatic spread of cancer cells. The objective of this study was to assess MMPs in plasma of Dunning tumor rats as indicators of the progression of prostate cancer and follow-up parameters after treatment. METHODS. Prostate cancer was induced in male Copenhagen rats by either subcutaneous or orthotopic implantation of R3327-MatLyLu cells. During the development of the tumor, plasma MMP-2, and MMP-9 were measured by gelatin-substrate zymography and Western blot technique with densitometry in untreated animals, rats treated with laser-induced hyperthermia, or with the new synthetic MMP inhibitor RO 28-2653. RESULTS. Normal prostatic tissue of the Copenhagen rats predominantly expressed proMMP-2 but not proMMP-9 whereas MMP-9 was only found in cancerous tissue. Elevated plasma MMP-9 values were demonstrated in rats with subcutaneous or orthotopic tumors. Animals with tumors and treated with the MMP inhibitor RO 28-2653 had both a lower tumor volume and a lower plasma MMP-9 concentration compared with controls. CONCLUSIONS. The determination of plasma MMP-9 in Dunning tumor rats is a useful tool to monitor the progression of prostate cancer and to assess the efficacy of drugs like MMP inhibitors or other treatment protocols. (C) 2002 Wiley-Liss, Inc. C1 Humboldt Univ, Hosp Charite, Dept Urol, D-10098 Berlin, Germany. Roche Diagnost GmbH, Pharma Res, Penzberg, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. RP Jung, K (reprint author), Humboldt Univ, Hosp Charite, Dept Urol, Schumann Str 20-21, D-10098 Berlin, Germany. NR 26 TC 15 Z9 17 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0270-4137 J9 PROSTATE JI Prostate PD FEB 15 PY 2003 VL 54 IS 3 BP 206 EP 211 DI 10.1002/pros.10183 PG 6 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 637YX UT WOS:000180542300005 PM 12518325 ER PT J AU Wu, A Yamada, K Neville, DM Awwad, M Wain, JC Shimizu, A Gojo, S Kitamura, H Colvin, RB Cooper, DKC Sykes, M Sachs, DH AF Wu, A Yamada, K Neville, DM Awwad, M Wain, JC Shimizu, A Gojo, S Kitamura, H Colvin, RB Cooper, DKC Sykes, M Sachs, DH TI Xenogeneic thymus transplantation in a pig-to-baboon model SO TRANSPLANTATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; SKIN-GRAFT TOLERANCE; THYMECTOMIZED MICE; INDUCTION; CELLS; BARRIER; MHC; ALLOGRAFTS; CHILDREN; SWINE AB Background We have tested whether fetal porcine thymic tissue transplantation can lead to tolerance across a discordant (pig-to-baboon) xenogeneic barrier. Methods. Six baboons underwent a conditioning regimen with thymectomy, splenectomy, and anti-monkey CD3 antibody conjugated to a diphtheria toxin binding site mutant (FN18-CRM9). Porcine fetal or neonatal thymic tissue was transplanted into three baboons. Three control baboons received either no transplanted pig tissue (n=1) or adult pig lymph node (n=2). Cellular responses and skin xenografts were used to test for tolerance. Results. Experimental baboons: After T-cell depletion and thymic transplantation, recovery of thymus-dependent naive-type CD4 cells (CD4/CD45RA(high)) and in vitro xenogeneic hyporesponsiveness were observed. No sensitization of alpha-galactosyl antibody responses was observed. The thymic grafts survived up to 48 days. Porcine skin xenografts were performed in two of these animals with survival of 22 and 24 days. Control baboons: Only two of these animals were completely T-cell depleted, and both failed to recover thymus-dependent T cells (CD4/CD45RA(high)). In one animal, general in vitro hyporesponsiveness was observed, with subsequent death from infection. The second animal demonstrated delayed recovery of T cells and prolonged general hyporesponsiveness in vitro. Neither animal demonstrated prolongation of porcine skin grafts compared with allografts (both rejected by day 13). Conclusions. Porcine thymic tissue is able to induce xenogeneic hyporesponsiveness. More efficient thymic engraftment may allow this approach to induce xenograft tolerance. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02115 USA. NIH, Bethesda, MD 20892 USA. Immerge Bio Therapeut, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. RP Sachs, DH (reprint author), Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. NR 21 TC 16 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD FEB 15 PY 2003 VL 75 IS 3 BP 282 EP 291 DI 10.1097/01.TP.0000044137.97841.99 PG 10 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 646UH UT WOS:000181053100008 PM 12589146 ER PT J AU Tse, WT Pendleton, JD Beyer, WM Egalka, MC Guinan, EC AF Tse, WT Pendleton, JD Beyer, WM Egalka, MC Guinan, EC TI Suppression of allogeneic T-cell proliferation by human marrow stromal cells: Implications in transplantation SO TRANSPLANTATION LA English DT Article ID MESENCHYMAL STEM-CELLS; BONE-MARROW; MICROENVIRONMENT; ALLOANTIGEN; INDUCTION; EXPANSION; RESPONSES; REJECTION; INFUSION; BIOLOGY AB Background. Marrow stromal cells (MSC) can differentiate into multiple mesenchymal tissues. To assess the feasibility of human MSC transplantation, we evaluated the in vitro immunogenicity of MSC and their ability to function as alloantigen presenting cells (APC). Methods. Human MSC were derived and used in mixed cell cultures with allogeneic peripheral blood mononuclear cells (PBMC). Expression of immunoregulatory molecules on MSC was analyzed by flow cytometry. An MSC-associated suppressive activity was analyzed using cell-proliferation assays and enzyme-linked immunoassays. Results. MSC failed to elicit a proliferative response when cocultured with allogeneic PBMC, despite provision of a costimulatory signal delivered by an anti-CD28 antibody and pretreatment of MSC with gamma-interferon. MSC express major histocompatibility complex (MHC) class I and lymphocyte function-associated antigen (LFA)-3 antigens constitutively and MHC class II and intercellular adhesion molecule (ICAM)-1 antigens upon gamma-interferon treatment but do not express CD80, CD86, or CD40 costimulatory molecules. MSC actively suppressed proliferation of responder PBMC stimulated by third-party allogeneic PBMC as well as T cells stimulated by anti-CD3 and anti-CD28 antibodies. Separation of MSC and PBMC by a semipermeable membrane did not abrogate the suppression. The suppressive activity could not be accounted for by MSC production of interleukin-10, transforming growth factor-beta1, or prostaglandin E2, nor by tryptophan depletion of the culture medium. Conclusions. Human MSC fail to stimulate allogeneic PBMC or T-cell proliferation in mixed cell cultures. Unlike other nonprofessional APC, this failure of function is not reversed by provision of CD28-mediated costimulation nor gamma-interferon pretreatment. Rather, MSC actively inhibit T-cell proliferation, suggesting that allogeneic MSC transplantation might be accomplished without the need for significant host immunosuppression. C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Tse, WT (reprint author), Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. NR 30 TC 852 Z9 1014 U1 2 U2 29 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD FEB 15 PY 2003 VL 75 IS 3 BP 389 EP 397 DI 10.1097/01.TP.0000045055.63901.A9 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 646UH UT WOS:000181053100026 PM 12589164 ER PT J AU Severino, ME Sarkis, PTN Walker, BD Yang, OO AF Severino, ME Sarkis, PTN Walker, BD Yang, OO TI Chimeric immune receptor T cells bypass class I requirements and recognize multiple cell types relevant in HIV-1 infection SO VIROLOGY LA English DT Article DE HIV-1; chimeric immune receptors; CTL; cellular immunity; immunotherapy; gene therapy; immune escape ID HUMAN-IMMUNODEFICIENCY-VIRUS; DENDRITIC CELLS; VIRAL REPLICATION; CD8(+) CELLS; LYMPHOCYTES; PATHOGENESIS; INHIBITION; ANTIGENS; TARGETS; ESCAPE AB Transduction of T cells with a chimeric immune T cell receptor (CIR) has been proposed as a strategy to generate cellular immunity against viral pathogens such as HIV-1. In the case of the CD4-CD3-zeta chain (CD4-zeta) CIR, specificity for HIV-1 is conferred by binding of the CD4 moiety to gp120 on the surface of infected cells. However, it is unclear whether CD4-zeta-T cells may differ from naturally derived CD8(+) cytotoxic T cells (CTL) in their susceptibility to viral escape mechanisms or ability to recognize different cell types that support viral replication. We demonstrate that CIR-T cells can mediate antiviral activity against HIV-1 in cells that are resistant to class I-restricted CTL-mediated activity. Furthermore, CIR-T cells can suppress virus in multiple cell types, including monocytes, dendritic cells, and lymphocyte-dendritic cell clusters. These results provide evidence that T cells can be redirected against novel targets, and that independence from the class I pathway may have distinct advantages. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Univ Calif Los Angeles, Med Ctr, Div Infect Dis, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Med Ctr, AIDS Inst, Los Angeles, CA 90095 USA. Massachusetts Gen Hosp, Ctr AIDS Res, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. RP Yang, OO (reprint author), Univ Calif Los Angeles, Med Ctr, Div Infect Dis, 37-121 CHS,10833 LeConte Ave, Los Angeles, CA 90095 USA. EM oyang@mednet.ucla.edu FU NIAID NIH HHS [AI043202, AI30914] NR 32 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD FEB 15 PY 2003 VL 306 IS 2 BP 371 EP 375 AR PII S0042-6822(02)00055-7 DI 10.1016/S0042-6822(02)00055-7 PG 5 WC Virology SC Virology GA 658TV UT WOS:000181737300018 PM 12642109 ER PT J AU Ferrantelli, F Hofmann-Lehmann, R Rasmussen, RA Wang, T Xu, WD Li, PL Montefiori, DC Cavacini, LA Katinger, H Stiegler, G Anderson, DC McClure, HM Ruprecht, RM AF Ferrantelli, F Hofmann-Lehmann, R Rasmussen, RA Wang, T Xu, WD Li, PL Montefiori, DC Cavacini, LA Katinger, H Stiegler, G Anderson, DC McClure, HM Ruprecht, RM TI Post-exposure prophylaxis with human monoclonal antibodies prevented SHIV89.6P infection or disease in neonatal macaques SO AIDS LA English DT Article DE post-exposure prophylaxis; passive immunization; neutralizing monoclonal antibodies; pathogenic simian-human immunodeficiency virus; (SHIV); rhesus macaques; maternal HIV transmission; oral infection ID HUMAN-IMMUNODEFICIENCY-VIRUS; DEPENDENT CELLULAR CYTOTOXICITY; HIV-1/SIV CHIMERIC VIRUS; NEUTRALIZING ANTIBODIES; PHASE-I; ENVELOPE GLYCOPROTEIN; IMMUNE GLOBULIN; RHESUS MACAQUES; LYMPHOID-TISSUE; TYPE-1 AB Background: The majority of infants infected through maternal transmission acquire the virus during birth or postpartum through breastfeeding: mucosal exposure is considered to be a major route of infection. Objectives: To develop passive immunization with human neutralizing monoclonal antibodies (mAbs) against mother-to-child transmission of HIV during delivery and through breastfeeding. Design: An oral challenge model in newborn rhesus macaques mimicked peri- and postpartum virus transmission. Methods: Neonatal rhesus macaques were challenged orally with the highly pathogenic, chimeric simian-human immunodeficiency virus SHIV89.6P and given post-exposure prophylaxis with a quadruple combination of neutralizing human mAbs, IgG1b12, 2G12, 2F5, and 4E10, directed against conserved epitopes of HIV envelope glycoproteins. Control animals were virus challenged but left untreated. All infants were followed prospectively for signs of viremia and immunodeficiency. Results: Two out of four macaque infants treated with neutralizing mAbs showed no evidence of infection; the other two maintained normal CD4 T cell counts. In contrast, all control animals became highly viremic and had profound CD4 T cell losses; three out of four died from AIDS within 1.5-6 weeks of the challenge. Conclusions: Passive immunization with this quadruple neutralizing mAbs combination may represent a promising approach to prevent peri- and postnatal HIV transmission. Furthermore, the epitopes recognized by the four neutralizing mAbs are key determinants to achieve complete protection and represent important targets against which to develop active, anti body-response-based AIDS vaccines. (C) 2003 Lippincott Williams Wilkins. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Univ Durham, Ctr Med, Dept Surg, Durham, NC USA. Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30322 USA. Agr Univ Vienna, Inst Appl Microbiol, A-1180 Vienna, Austria. Polymun Sci Immunobiol Forsch GmbH, Vienna, Austria. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. RI Hofmann-Lehmann, Regina/C-6528-2009; Ferrantelli, Flavia/J-7794-2016 OI Ferrantelli, Flavia/0000-0002-0768-1078 FU NCRR NIH HHS [RR 00165]; NIAID NIH HHS [R01 AI 34266, R01 AI 48280]; NIDCR NIH HHS [R01 DE 12937]; PHS HHS [1P30 28691] NR 48 TC 87 Z9 90 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD FEB 14 PY 2003 VL 17 IS 3 BP 301 EP 309 DI 10.1097/01.aids.0000050803.28043.96 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 653KR UT WOS:000181434800003 PM 12556683 ER PT J AU Xie, Y Zhong, R Chen, CM Calderwood, SK AF Xie, Y Zhong, R Chen, CM Calderwood, SK TI Heat shock factor 1 contains two functional domains that mediate transcriptional repression of the c-fos and c-fms genes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROINTERLEUKIN 1-BETA GENE; DNA-BINDING ABILITY; NF-KAPPA-B; C/EBP-BETA; FACTOR-I; ACTIVATION; PROTEIN; STRESS; EXPRESSION; PHOSPHORYLATION AB Heat shock factor I (HSF1), in addition to its pivotal role as a regulator of the heat shock response, functions as a versatile gene repressor. We have investigated the structural domains involved in gene repression using mutational analysis of the hsf1 gene. Our studies indicate that HSF1 contains two adjacent sequences located within the N-terminal half of the protein that mediate the repression of c-fos and c-fins. One region (NF) appears to be involved in quenching transcriptional activation factors on target promoters and binds to the basic zipper transcription factor NF-IL6 required for activation of c-fins and IL-1beta. The NF domain encompasses the leucine zipper 1 and 2 sequences as well as the linker domain between the DNA binding and leucine zipper regions. The function of this domain in gene repression is highly specific for HSF1, and the homologous region from conserved family member HSF2 does not restore repressive function in HSF2/HSF1 chimeras. In addition, HSF2 is not capable of binding to NF-IL6. The NF domain, although necessary for repression, is not sufficient, and a second region (REP) occupying a portion of the regulatory domain is required for repression. Neither domain functions independently, and both are required for repression. Furthermore, we constructed dominant inhibitors of c-fos repression by HSF1, which also blocked the repression of c-fins and IL-1beta, suggesting a shared mechanism for repression of these genes by HSF1. Our studies suggest a complex mechanism for gene repression by HSF1 involving the binding to and quenching of activating factors on target promoters. Mapping the structural domains involved in this process should permit further characterization of molecular mechanisms that mediate repression. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Mol & Cellular Biol Lab, Boston, MA 02115 USA. RP Calderwood, SK (reprint author), Boston Univ, Sch Med, Ctr Mol Stress Response, 88 E Newton St, Boston, MA 02118 USA. FU NCI NIH HHS [CA50642, CA31303, CA47407] NR 52 TC 30 Z9 40 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 14 PY 2003 VL 278 IS 7 BP 4687 EP 4698 DI 10.1074/jbc.M210189200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 645GY UT WOS:000180968900044 PM 12468538 ER PT J AU Hallmann, D Trumper, K Trusheim, H Ueki, K Kahn, R Cantley, LC Fruman, DA Horsch, D AF Hallmann, D Trumper, K Trusheim, H Ueki, K Kahn, R Cantley, LC Fruman, DA Horsch, D TI Altered signaling and cell cycle regulation in embryonal stem cells with a disruption of the gene for phosphoinositide 3-kinase regulatory subunit p85 alpha SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INSULIN-RECEPTOR SUBSTRATE-1; PHOSPHATIDYLINOSITOL 3-KINASE; ADIPOCYTE DIFFERENTIATION; MUSCLE; MICE; PHOSPHORYLATION; PROLIFERATION; EXPRESSION; ACTIVATION; ISOFORMS AB The p85alpha regulatory subunit of class I(A) phosphoinositide 3-kinases (PI3K) is derived from the Pik3r1 gene, which also yields alternatively spliced variants p50alpha and p55alpha. It has been proposed that excess monomeric p85 competes with functional PI3K p85-p110 heterodimers. We examined embryonic stem (ES) cells with heterozygous and homozygous disruptions in the Pik3r gene and found that wild type ES cells express virtually no monomeric p85alpha. Although, IGF-1-stimulated PI3K activity associated with insulin receptor substrates was unaltered in all cell lines, p85alpha-null ES cells showed diminished protein kinase B activation despite increased PI3K activity associated with the p85beta subunit. Furthermore, p85alpha-null cells demonstrated growth retardation, increased frequency of apoptosis, and altered cell cycle regulation with a G(0)/G(1) cell cycle arrest and up-regulation of p27(KIP), whereas signaling through CREB and MAPK was enhanced. These phenotypes were reversed by re-expression of p85alpha via adenoviral gene transfer. Surprisingly, all ES cell lines could be differentiated into adipocytes. In these differentiated ES cells, however, compensatory p85beta signaling was lost in p85alpha-null cells while increased signaling by CREB and MAPK was still observed. Thus, loss of p85alpha in ES cells induced alterations in IGF-1 signaling and regulation of apoptosis and cell cycle but no defects in differentiation. However, differentiated ES cells partially lost their ability for compensatory signaling at the level of PI3K, which may explain some of the defects observed in mice with homozygous deletion of the Pik3r1 gene. C1 Univ Marburg, Div Gastroenterol & Metab, Dept Internal Med, D-35033 Marburg, Germany. Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Signal Transduct, Boston, MA 02215 USA. Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA. RP Horsch, D (reprint author), Univ Marburg, Div Gastroenterol & Metab, Dept Internal Med, Baldingerstr, D-35033 Marburg, Germany. EM hoerschd@post.med.uni-marburg.de RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIDDK NIH HHS [R01 DK033201, P30 DK036836, R01 DK055545]; NIGMS NIH HHS [GM41890, R01 GM041890, R37 GM041890] NR 36 TC 32 Z9 36 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 14 PY 2003 VL 278 IS 7 BP 5099 EP 5108 DI 10.1074/jbc.M208451200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 645GY UT WOS:000180968900096 PM 12435753 ER PT J AU Moseley, AE Lieske, SP Wetzel, RK James, PF He, SW Shelly, DA Paul, RJ Boivin, GP Witte, DP Ramirez, JM Sweadner, KJ Lingrel, JB AF Moseley, AE Lieske, SP Wetzel, RK James, PF He, SW Shelly, DA Paul, RJ Boivin, GP Witte, DP Ramirez, JM Sweadner, KJ Lingrel, JB TI The Na,K-ATPase alpha 2 isoform is expressed in neurons, and its absence disrupts neuronal activity in newborn mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NA+-K+-ATPASE; CENTRAL-NERVOUS-SYSTEM; GENE-EXPRESSION; INVITRO DEVELOPMENT; SUBUNIT ISOFORMS; MESSENGER-RNAS; BETA-SUBUNITS; CELLS; BRAIN; ISOZYMES AB Na,K-ATPase is an ion transporter that impacts neural and glial physiology by direct electrogenic activity and the modulation of ion gradients. Its three isoforms in brain have cell-type and development-specific expression patterns. Interestingly, our studies demonstrate that in late gestation, the alpha2 isoform is widely expressed in neurons, unlike in the adult brain, in which alpha2 has been shown to be expressed primarily in astrocytes. This unexpected distribution of alpha2 isoform expression in neurons is interesting in light of our examination of mice lacking the alpha2 isoform which fail to survive after birth. These animals showed no movement; however, defects in gross brain development, muscle contractility, neuromuscular transmission, and lung development were ruled out. Akinesia suggests a primary neuronal defect and electrophysiological recordings in the pre-Botzinger complex, the brainstem breathing center, showed reduction of respiratory rhythm activity, with less regular and smaller population bursts. These data demonstrate that the Na,K-ATPase alpha2 isoform could be important in the modulation of neuronal activity in the neonate. C1 Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. Univ Cincinnati, Coll Med, Dept Pharmacol & Cell Biophys, Cincinnati, OH 45267 USA. Univ Cincinnati, Coll Med, Dept Mol & Cellular Physiol, Cincinnati, OH 45267 USA. Univ Cincinnati, Coll Med, Dept Pathol & Lab Med, Cincinnati, OH 45267 USA. Massachusetts Gen Hosp, Ctr Neurosci, Lab Membrane Biol, Charlestown, MA 02129 USA. Miami Univ, Dept Zool, Oxford, OH 45056 USA. Univ Chicago, Comm Neurobiol, Chicago, IL 60637 USA. Univ Chicago, Dept Organismal Biol & Anat, Chicago, IL 60637 USA. Childrens Hosp, Med Ctr, Dept Pathol, Cincinnati, OH 45229 USA. RP Lingrel, JB (reprint author), Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, 231 Albert Sabin Way,MSB Bldg,ML 0524, Cincinnati, OH 45267 USA. FU NHLBI NIH HHS [HL66062, HL28573, HL 60120]; NINDS NIH HHS [NS27653] NR 48 TC 92 Z9 94 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 14 PY 2003 VL 278 IS 7 BP 5317 EP 5324 DI 10.1074/jbc.M211315200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 645GY UT WOS:000180968900123 PM 12458206 ER PT J AU Rosenzweig, A AF Rosenzweig, A TI Endothelial progenitor cells SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Program Cardiovasc Gene Therapy, Charlestown, MA 02129 USA. RP Rosenzweig, A (reprint author), Massachusetts Gen Hosp, Program Cardiovasc Gene Therapy, Charlestown, MA 02129 USA. NR 0 TC 50 Z9 57 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 13 PY 2003 VL 348 IS 7 BP 581 EP 582 DI 10.1056/NEJMp020175 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 644HY UT WOS:000180912900002 PM 12584365 ER PT J AU Caro, I Zembowicz, A AF Caro, I Zembowicz, A TI A 16-year-old girl with a rash and chest pain - Cutaneous eruption of acute systemic lupus erythematosus. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MANIFESTATIONS; DIAGNOSIS C1 Massachusetts Gen Hosp, Dept Dermatol, Dermatol Clin Invest Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Dermatopathol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Caro, I (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Dermatol Clin Invest Unit, Boston, MA 02114 USA. NR 21 TC 2 Z9 2 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 13 PY 2003 VL 348 IS 7 BP 630 EP 637 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 644HY UT WOS:000180912900009 PM 12584372 ER PT J AU Steinman, MA Landefeld, CS Gonzales, R AF Steinman, MA Landefeld, CS Gonzales, R TI Predictors of broad-spectrum antibiotic prescribing for acute respiratory tract infections in adult primary care SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE BRONCHITIS; PATIENTS EXPECTATIONS; EDUCATIONAL OUTREACH; PHYSICIANS BEHAVIOR; CLINICAL-PRACTICE; CONTROLLED TRIAL; DRUG COMPANIES; PERCEPTIONS; PRESCRIPTION; PRINCIPLES AB Context Broad-spectrum antibiotics are commonly prescribed, but little is known about the physicians who prescribe and the patients who take these agents. Objective To identify factors associated with prescribing of broad-spectrum antibiotics by physicians caring for patients with nonpneumonic acute respiratory tract infections (ARTIs). Design, Setting, and Patients Cross-sectional study using data from the National Ambulatory Medical Care Survey between 1997 and 1999. Information was collected on a national sample of 1981 adults seen by physicians for the common cold and nonspecific upper respiratory tract infections (URTIs) (24%), acute sinusitis (24%), acute bronchitis (23%), otitis media (5%), pharyngitis, laryngitis, and tracheitis (11%), or more than 1 of the above diagnoses (13%). Main Outcome Measure Prescription of broad-spectrum antibiotics, defined for this study as quinolones; amoxicillin/clavulanate, second- and third-generation cephalosporins, and azithromycin and clarithromycin. Results, Antibiotics were prescribed to 63% of patients with an ARTI, ranging from 46% of patients with,the common cold or nonspecific URTIs to 69% of patients with acute sinusitis. Broad-spectrum agents were chosen in 54% of patients prescribed an antibiotic, including 51% of patients with the common cold and nonspecific URTIs, 53% with acute sinusitis, 62% with acute bronchitis, and 65% with otitis media. Multivariable analysis identified several clinical and nonclinical factors associated with choice of a broad-spectrum agent. After adjusting for diagnosis and chronic comorbid illnesses, the strongest independent predictors of broad-spectrum antibiotic prescribing were physician specialty (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.6-3.5 for internal medicine physicians compared with general and family physicians) and geographic region (OR, 2.6; 95% CI, 1.4-4.8 for Northeast and OR, 2.4; 95% CI, 1.4-4.2 for South [both compared with West]). Other independent predictors of choosing a broad-spectrum agent included black race, lack of health insurance, and health maintenance organization membership, each of which was associated with lower rates of broad-spectrum prescribing. Patient age, sex, and urban vs rural location were not significantly associated with prescribing choice. Conclusions Broad-spectrum antibiotics are commonly prescribed for the treatment of ARTIs, especially by internists and physicians in the Northeast and South. These high rates of prescribing, wide variations in practice patterns, and the strong association of nonclinical factors with antibiotic choice suggest opportunities to improve prescribing patterns. C1 San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, VA Natl Qual Scholars Program, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Steinman, MA (reprint author), San Francisco VA Med Ctr, Div Geriatr, 4150 Clement St,Box 181-G, San Francisco, CA 94121 USA. NR 58 TC 161 Z9 165 U1 2 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 12 PY 2003 VL 289 IS 6 BP 719 EP 725 DI 10.1001/jama.289.6.719 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 643WP UT WOS:000180886000026 PM 12585950 ER PT J AU Ropers, D Baum, U Pohle, K Anders, K Ulzheimer, S Ohnesorge, B Schlundt, C Bautz, W Daniel, WG Achenbach, S AF Ropers, D Baum, U Pohle, K Anders, K Ulzheimer, S Ohnesorge, B Schlundt, C Bautz, W Daniel, WG Achenbach, S TI Detection of coronary artery stenoses with thin-slice multi-detector row spiral computed tomography and multiplanar reconstruction SO CIRCULATION LA English DT Article DE imaging; coronary disease; tomography ID HEART-RATE; ANGIOGRAPHY; CT; VISUALIZATION AB Background-We analyzed the accuracy of multi-detector row spiral computed tomography (MDCT) using a 16-slice CT scanner with improved spatial and temporal resolution, as well as routine premedication with beta-blockers for detection of coronary stenoses. Methods and Results-Seventy-seven patients with suspected coronary disease were studied by MDCT (12x0.75-mm cross-sections, 420 ms rotation, 100 mL contrast agent IV at 5 mL/s). Patients with a heart rate above 60/min received 50 mg atenolol before the scan. In axial MDCT images and multiplanar reconstructions, all coronary arteries and side branches with a diameter of 1.5 mm or more were assessed for the presence of stenoses exceeding 50% diameter reduction. In comparison to invasive coronary angiography, MDCT correctly classified 35 of 41 patients (85%) as having at least 1 coronary stenosis and correctly detected 57 of 78 coronary lesions (73%). After excluding 38 of 308 coronary arteries (left main, left anterior descending, left circumflex, and right coronary artery in 77 patients) classified as unevaluable by MDCT (12%), 57 of 62 lesions were detected, and absence of stenosis was correctly identified in 194 of 208 arteries (sensitivity: 92%; specificity: 93%; accuracy: 93%; positive and negative predictive values: 79% and 97%). Conclusions-MDCT coronary angiography with improved spatial resolution and premedication with oral beta-blockade permits detection of coronary artery stenoses with high accuracy and a low rate of unevaluable arteries. C1 Massachusetts Gen Hosp, Dept Radiol, CIMIT, Boston, MA 02114 USA. Univ Erlangen Nurnberg, Dept Cardiol, D-8520 Erlangen, Germany. Univ Erlangen Nurnberg, Inst Diagnost Radiol, D-8520 Erlangen, Germany. Univ Erlangen Nurnberg, Inst Med Phys, D-8520 Erlangen, Germany. Siemens Med Solut, Forchheim, Germany. RP Achenbach, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, CIMIT, 100 Charles River Plaza 400, Boston, MA 02114 USA. NR 12 TC 651 Z9 702 U1 1 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 11 PY 2003 VL 107 IS 5 BP 664 EP 666 DI 10.1161/01.CIR.0000055738.31551.A9 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 648LY UT WOS:000181153900004 PM 12578863 ER PT J AU Arribas, M Valverde, AM Burks, D Klein, J Farese, RV White, MF Benito, M AF Arribas, M Valverde, AM Burks, D Klein, J Farese, RV White, MF Benito, M TI Essential role of protein kinase C zeta in the impairment of insulin-induced glucose transport in IRS-2-deficient brown adipocytes SO FEBS LETTERS LA English DT Article DE protein kinase C; insulin receptor substrate-2; glucose transport ID GROWTH-FACTOR-I; GLUT4 GENE-EXPRESSION; RECEPTOR SUBSTRATE-2; PHOSPHATIDYLINOSITOL 3-KINASE; POTENTIAL ROLE; TRANSLOCATION; STIMULATION; IRS-1; ACTIVATION; RESISTANCE AB Insulin receptor substrate-2-deficient (IRS-2(-/-)) mice develop type 2 diabetes. We have investigated the molecular mechanisms by which IRS-2(-/-) immortalized brown adipocytes showed an impaired response to insulin in inducing GLUT4 translocation and glucose uptake. IRS-2-associated phosphatidylinositol 3-kinase (PI 3-kinase) activity was blunted in IRS-2(-/-) cells, total PI 3-kinase activity being reduced by 30%. Downstream, activation of protein kinase C (PKC) zeta was abolished in IRS-2(-/-) cells. Reconstitution with retroviral IRS-2 restores IRS-2/PI 3-kinase/PKCzeta signalling, as well as glucose uptake. Wild-type cells expressing a kinase-inactive mutant of PKCzeta lack GLUT4 translocation and glucose uptake. Our results support the essential role played by PKCzeta in the insulin resistance and impaired glucose uptake observed in IRS-2-deficient brown adipocytes. (C) 2003 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies. C1 Univ Complutense, Fac Farm, CSIC, Ctr Mixto,Inst Bioquim,Dept Bioquim & Biol Mol, E-28040 Madrid, Spain. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Univ S Florida, Coll Med, Dept Internal Med, Tampa, FL 33612 USA. Med Univ Lubeck, Dept Internal Med 1, D-23538 Lubeck, Germany. Fac Med, Dept Anat, Salamanca 37007, Spain. RP Benito, M (reprint author), Univ Complutense, Fac Farm, CSIC, Ctr Mixto,Inst Bioquim,Dept Bioquim & Biol Mol, E-28040 Madrid, Spain. RI Farese, Robert/B-3605-2015; Benito, Manuel/J-5637-2014 OI Benito, Manuel/0000-0002-7218-406X NR 29 TC 18 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD FEB 11 PY 2003 VL 536 IS 1-3 BP 161 EP 166 DI 10.1016/S0014-5793(03)00049-8 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 645YY UT WOS:000181009100031 PM 12586357 ER PT J AU Tung, CH Weissleder, R AF Tung, CH Weissleder, R TI Arginine containing peptides as delivery vectors SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE membrane penetration; translocation; Tat; antennapedia; peptide; arginine ID HIV-1 TAT PROTEIN; EFFICIENT INTRACELLULAR DELIVERY; NUCLEAR-LOCALIZATION SEQUENCE; HUMAN-IMMUNODEFICIENCY-VIRUS; MAMMALIAN-CELLS; IN-VIVO; MEMBRANE TRANSLOCATION; CELLULAR DELIVERY; FUSION PROTEINS; GENE-THERAPY AB Recently several membrane translocalizational signals (MTS) have been identified and applied to various applications. These peptide signals, ranging between nine and 30 amino acid residues in length, have the capability of crossing plasma membrane, in addition to delivering other biological molecules into cells. To date, small molecules, peptides, proteins, oligonucleotides, plasmids and even nanometer-sized particles have been delivered. These MTS sequences vary from hydrophobic to purely hydrophilic, and, surprisingly, all of them are able to penetrate cellular membrane in an energy-independent pathway. Potentially, MTS could be used as delivery vectors for a number of therapeutic agents. In this review, we specifically focus on arginine-containing MTS, and their properties, characteristics, in vitro and in vivo applications are discussed in detail. (C) 2002 Elsevier Science B.V. All rights reserved. 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, 149 13th St,Rm 5406, Charlestown, MA 02129 USA. EM tung@helix.mgh.harvard.edu OI Tung, Ching-Hsuan/0000-0001-6648-6195 NR 90 TC 121 Z9 122 U1 3 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD FEB 10 PY 2003 VL 55 IS 2 BP 281 EP 294 AR PII S0169-409X(02)00183-7 DI 10.1016/S0169-409X(02)00183-7 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 652KK UT WOS:000181378200007 PM 12564981 ER PT J AU Heinrich, B Hartmann, C Stemmer-Rachamimov, AO Louis, DN MacCollin, M AF Heinrich, B Hartmann, C Stemmer-Rachamimov, AO Louis, DN MacCollin, M TI Multiple meningiomas: Investigating the molecular basis of sporadic and familial forms SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE meningioma; genetic analysis; neurofibromatosis 2; DAL-1; chromosome 22; chromosome 18 ID NF2 GENE; TUMOR-SUPPRESSOR; NEUROFIBROMATOSIS; SCHWANNOMAS; MUTATIONS; EXPRESSION; MERLIN; DAL-1 AB Meningiomas are common tumors of the coverings of the central nervous system (CNS), comprising 20% of intracranial neoplasms. The only genes known to be associated with sporadic meningiomas are NF2 on chromosome 22 and the related cytoskeleton element DAL-1 on chromosome 18. Between 1 and 8% of patients with meningiomas develop multiple meningiomas, a trait transmitted occasionally in an autosomal dominant fashion. We investigated the DAL-I and NF2 loci in 7 unrelated multiple meningioma patients without clinical evidence of NF2 by mutational and pathological analysis. Five novel intragenic microsatellite polymorphisms were developed for specific detection of loss of heterozygosity (LOH) at the DAL-I locus. Three of 7 patients had affected relatives and all affected individuals were female. No tumors from familial patients were of a fibroblastic subtype. Truncating NF2 mutations were detected in 3 tumor specimens, but were not present in the corresponding blood samples. Two tumors showed LOH at the NF2 locus. All tumors showing mutations at the NF2 locus originated from patients without affected relatives and were of the fibroblastic subtype. Five non-truncating alterations in the DAL-1 gene were found, however, LOH of chromosome 18 markers was not seen in any tumor. In contrast to the NF2 results, all DAL-1 alterations were found in paired blood specimens. Our findings provide further evidence that the molecular basis of sporadic and familial multiple meningiomas is fundamentally different and extend this dichotomy to pathologic subtypes. DAL-1 does not function as a true tumor suppressor in these patients. (C) 2002 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. Massachusetts Gen Hosp, Mol Neurooncol & Pathol Labs, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP MacCollin, M (reprint author), MGH E Bldg,149 13th St, Charlestown, MA 02129 USA. RI Hartmann, Christian/D-1882-2010 NR 24 TC 37 Z9 37 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD FEB 10 PY 2003 VL 103 IS 4 BP 483 EP 488 DI 10.1008/ijc.10840 PG 6 WC Oncology SC Oncology GA 630JZ UT WOS:000180104900007 PM 12478663 ER PT J AU Banfi, B Clark, RA Steger, K Krause, KH AF Banfi, B Clark, RA Steger, K Krause, KH TI Two novel proteins activate superoxide generation by the NADPH oxidase NOX1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NAD(P)H OXIDASE; DOMAIN; PHOSPHORYLATION; SUBUNIT; CELLS; IDENTIFICATION; EXPRESSION; P67(PHOX); P47(PHOX); HOMOLOG AB NOX1, an NADPH oxidase expressed predominantly in colon epithelium, shows a high degree of similarity to the phagocyte NADPH oxidase. However, superoxide generation by NOX1 has been difficult to demonstrate. Here we show that NOX1 generates superoxide when co-expressed with the p47(phox) and p67(phox) subunits of the phagocyte NADPH oxidase but not when expressed by itself. Since p47(phox) and p67(phox) are restricted mainly to myeloid cells, we searched for their homologues and identified two novel cDNAs. The mRNAs of both homologues were found predominantly in colon epithelium. Differences between the homologues and the phagocyte NADPH oxidase subunits included the lack of the auto-inhibitory domain and the protein kinase C phosphorylation sites in the p47(phox) homologue as well as the absence of the first Src homology 3 domain and the presence of a hydrophobic stretch in the p67(phox) homologue. Co-expression of NOX1 with the two novel proteins led to stimulus-independent high level superoxide generation. Stimulus dependence of NOX1 was restored when p47(phox) was used to replace its homologue. In conclusion, NOX1 is a superoxide-generating enzyme that is activated by two novel proteins, which we propose to name NOXO1 (NOX organizer 1) and NOXA1 (NOX activator 1). C1 Univ Hosp Geneva, Dept Geriatr, Biol Ageing Lab, CH-1225 Geneva, Switzerland. Inst Vet Anat, D-35392 Giessen, Germany. S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. RP Banfi, B (reprint author), Univ Hosp Geneva, Dept Geriatr, Biol Ageing Lab, 2 Ch Petit Bel Air, CH-1225 Geneva, Switzerland. RI Krause, Karl-Heinz/E-8030-2011 FU NIA NIH HHS [AG19519, R01 AG019519]; NIAID NIH HHS [AI20866, R01 AI020866, R37 AI020866] NR 27 TC 322 Z9 333 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 7 PY 2003 VL 278 IS 6 BP 3510 EP 3513 DI 10.1074/jbc.C200613200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 643PM UT WOS:000180869700002 PM 12473664 ER PT J AU Langenau, DM Traver, D Ferrando, AA Kutok, JL Aster, JC Kanki, JP Lin, S Prochownik, E Trede, NS Zon, LI Look, AT AF Langenau, DM Traver, D Ferrando, AA Kutok, JL Aster, JC Kanki, JP Lin, S Prochownik, E Trede, NS Zon, LI Look, AT TI Myc-induced T cell leukemia in transgenic zebrafish SO SCIENCE LA English DT Article ID DANIO-RERIO; NEOPLASIA; MODELS AB The zebrafish is an attractive model organism for studying cancer development because of its genetic accessibility. Here we describe the induction of clonally derived T cell acute lymphoblastic leukemia in transgenic zebrafish expressing mouse c-myc under control of the zebrafish Rag2 promoter. Visualization of leukemic cells expressing a chimeric transgene encoding Myc fused to green fluorescent protein (GFP) revealed that leukemias arose in the thymus, spread locally into gill arches and retro-orbital soft tissue, and then disseminated into skeletal muscle and abdominal organs. Leukemic cells homed back to the thymus in irradiated fish transplanted with GFP-labeled leukemic lymphoblasts. This transgenic model provides a platform for drug screens and for genetic screens aimed at identifying mutations that suppress or enhance c-myc-induced carcinogenesis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp Pittsburgh, Div Hematol Oncol, Pittsburgh, PA 15213 USA. Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp Boston, Div Hematol Oncol, Boston, MA 02115 USA. RP Look, AT (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 FU NCI NIH HHS [CA-06516, CA-68484] NR 24 TC 273 Z9 294 U1 2 U2 32 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD FEB 7 PY 2003 VL 299 IS 5608 BP 887 EP 890 DI 10.1126/science.1080280 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 642XN UT WOS:000180830900051 PM 12574629 ER PT J AU Wong, KK Maser, RS Bachoo, RM Menon, J Carrasco, DR Gu, YS Alt, FW DePinho, RA AF Wong, KK Maser, RS Bachoo, RM Menon, J Carrasco, DR Gu, YS Alt, FW DePinho, RA TI Telomere dysfunction and Atm deficiency compromises organ homeostasis and accelerates ageing SO NATURE LA English DT Article ID ATAXIA-TELANGIECTASIA; STEM-CELL; MICE; DNA; CANCER; MOUSE; STABILITY; DEFECTS; LEADS AB Ataxia-telangiectasia (A-T) results from the loss of ataxia-telangiectasia mutated (Atm) function and is characterized by accelerated telomere loss, genomic instability, progressive neurological degeneration, premature ageing and increased neoplasia incidence(1). Here we evaluate the functional interaction of Atm and telomeres in vivo. We examined the impact of Atm deficiency as a function of progressive telomere attrition at both the cellular and whole-organism level in mice doubly null for Atm and the telomerase RNA component (Terc)(2-4). These compound mutants showed increased telomere erosion and genomic instability, yet they experienced a substantial elimination of T-cell lymphomas associated with Atm deficiency. A generalized proliferation defect was evident in all cell types and tissues examined, and this defect extended to tissue stem/progenitor cell compartments, thereby providing a basis for progressive multi-organ system compromise, accelerated ageing and premature death. We show that Atm deficiency and telomere dysfunction act together to impair cellular and whole-organism viability, thus supporting the view that aspects of A-T pathophysiology are linked to the functional state of telomeres and its adverse effects on stem/progenitor cell reserves. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet & Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 92507 USA. Univ Washington, Sch Med, Dept Radiat Oncol & Immunol, Seattle, WA 98195 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Maser, Richard/B-2970-2012; OI wong, kwok kin/0000-0001-6323-235X NR 30 TC 263 Z9 274 U1 2 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD FEB 6 PY 2003 VL 421 IS 6923 BP 643 EP 648 DI 10.1038/nature01385 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 642KH UT WOS:000180803200045 PM 12540856 ER PT J AU Brainard, DM Ryan, ET AF Brainard, DM Ryan, ET TI Thoracic echinococcosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Brainard, DM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 6 PY 2003 VL 348 IS 6 BP 528 EP 528 DI 10.1056/NEJMicm020330 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 642JY UT WOS:000180801400006 PM 12571260 ER PT J AU Funakoshi, T Tachibana, I Hoshida, Y Kimura, H Takeda, Y Kijima, T Nishino, K Goto, H Yoneda, T Kumagai, T Osaki, T Hayashi, S Aozasa, K Kawase, I AF Funakoshi, T Tachibana, I Hoshida, Y Kimura, H Takeda, Y Kijima, T Nishino, K Goto, H Yoneda, T Kumagai, T Osaki, T Hayashi, S Aozasa, K Kawase, I TI Expression of tetraspanins in human lung cancer cells: frequent downregulation of CD9 and its contribution to cell motility in small cell lung cancer SO ONCOGENE LA English DT Article DE small cell lung cancer (SCLC); tetraspanin; CD9; motility ID KAI1/CD82 GENE-EXPRESSION; TRANSMEMBRANE-4 SUPERFAMILY; BREAST-CANCER; MONOCLONAL-ANTIBODY; TM4SF PROTEINS; TYROSINE PHOSPHORYLATION; INTEGRIN ALPHA-3-BETA-1; MOLECULAR-CLONING; PANCREATIC-CANCER; TUMOR PROGRESSION AB Small cell lung cancer (SCLC) invades locally and metastasizes distantly extremely early when compared with nonsmall cell lung cancer (NSCLC). The underlying molecular mechanisms, however, have not been elucidated. Accumulating evidence suggests that downregulation of several members of tetraspanins is associated with progression of solid tumors, thus indicating poor prognosis. Here we screened 30 lung cancer cell lines for expression of tetraspanins, CD9, CD63, CD81, CD82, CD151, and NAG-2. Flow cytometry revealed that, among these proteins, CD9 is broadly expressed in NSCLC lines, but is absent or highly reduced in most SCLC lines (P < 0.0001). Using the Boyden chamber and videomicroscopic cell motility assays, we showed that stable transfection of CD9 into an SCLC line, OS3-R5, reduced cell motility on fibronectin. Furthermore, by transient transfection of green fluorescent protein (GFP)-tagged CD9 into three other SCLC lines, we observed that SCLC cells expressing GFP-CD9 were uniformly less motile than untransfected cells. CD9 or GFP-CD9 was associated with beta1 integrins and distributed at the tumor cell periphery and cell-cell contacts, suggesting that CD9 modifies beta1 integrin function to reduce motility. These findings suggest that low expression of CD9 may contribute to the highly invasive and metastatic phenotype of SCLC. C1 Osaka Univ, Grad Sch Med, Dept Mol Med, Suita, Osaka 5650871, Japan. Osaka Univ, Grad Sch Med, Dept Pathol, Suita, Osaka 5650871, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Thorac & Adult Oncol, Boston, MA 02115 USA. RP Tachibana, I (reprint author), Osaka Univ, Grad Sch Med, Dept Mol Med, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan. NR 59 TC 57 Z9 69 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB 6 PY 2003 VL 22 IS 5 BP 674 EP 687 DI 10.1038/sj.onc.1206106 PG 14 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 639RB UT WOS:000180642100005 PM 12569360 ER PT J AU Levine, RA Schwammenthal, E AF Levine, RA Schwammenthal, E TI Stenosis is in the eye of the observer: Impact of pressure recovery on assessing aortic valve area SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID VALVULAR-HEART-DISEASE; ARTERY BYPASS-SURGERY; DOPPLER ULTRASOUND; CONTINUITY EQUATION; CATHETER GRADIENTS; FLOW EXPERIMENTS; FLUID-MECHANICS; ORIFICE AREA; ENERGY-LOSS; ECHOCARDIOGRAPHY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiac Ultrasound Lab, Boston, MA 02114 USA. Tel Aviv Univ, Sackler Sch Med, Inst Heart, Chaim Sheba Med Ctr, Tel Hashomer, Israel. RP Levine, RA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiac Ultrasound Lab, VBK 508,55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [K24 HL 67434] NR 30 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 5 PY 2003 VL 41 IS 3 BP 443 EP 445 DI 10.1016/S0735-1097(02)02765-1 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 641RN UT WOS:000180759800014 PM 12575973 ER PT J AU Charest, A Kheifets, V Park, J Lane, K McMahon, K Nutt, CL Housman, D AF Charest, A Kheifets, V Park, J Lane, K McMahon, K Nutt, CL Housman, D TI Oncogenic targeting of an activated tyrosine kinase to the Golgi apparatus in a glioblastoma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CHRONIC MYELOMONOCYTIC LEUKEMIA; BETA-R FUSION; C-ROS; MYELOPROLIFERATIVE DISORDER; MET ONCOPROTEIN; SH2 DOMAINS; CELL-LINES; PROTEIN; RECEPTOR; EXPRESSION AB Activating oncogenic mutations of receptor tyrosine kinases (RTKs) have been reported in several types of cancers. In many cases, genomic rearrangements lead to the fusion of unrelated genes to the DNA coding for the kinase domain of RTKs. All RTK-derived fusion proteins reported so far display oligomerization sequences within the 5' fusion partners that are responsible for oncogenic activation. Here, we report a mechanism by which an altered RTK gains oncogenic potential in a glioblastoma cell line. A microdeletion on 6q21 results in the fusion of FIG, a gene coding for a Golgi apparatus-associated protein, to the kinase domain of the protooncogene c-ROS. The fused protein product FIG-ROS is a potent oncogene, and its transforming potential resides in its ability to interact with and become localized to the Golgi apparatus. Thus we have found a RTK fusion protein whose subcellular location leads to constitutive kinase activation and results in oncogenic transformation. C1 MIT, Ctr Canc Res, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Mol Neurooncol Lab, Charlestown, MA 02129 USA. RP Charest, A (reprint author), MITCCR E17-536,77 Massachusetts Ave, Cambridge, MA 02139 USA. RI Nutt, Catherine/K-8794-2012 FU NCI NIH HHS [2-P01-CA42063-16, P01 CA042063] NR 42 TC 42 Z9 46 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 4 PY 2003 VL 100 IS 3 BP 916 EP 921 DI 10.1073/pnas.242741799 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 642ZU UT WOS:000180838100029 PM 12538861 ER PT J AU Akamatsu, Y Monroe, R Dudley, DD Elkin, SK Gartner, F Talukder, SR Takahama, Y Alt, FW Bassing, CH Oettinger, MA AF Akamatsu, Y Monroe, R Dudley, DD Elkin, SK Gartner, F Talukder, SR Takahama, Y Alt, FW Bassing, CH Oettinger, MA TI Deletion of the RAG2 C terminus leads to impaired lymphoid development in mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID B-CELL DEVELOPMENT; V(D)J RECOMBINATION; PHD FINGER; CORE REGION; TRANSCRIPTION; PROTEINS; GENE; REARRANGEMENT; LOCUS AB The recombination-activating gene (RAG)l and RAG2 proteins comprise the lymphocyte-specific components of the V(D)J recombinase and are required for the assembly of antigen-receptor variable-region genes. A mutant truncated RAG2 protein ("core" RAG2) lacking the C-terminal 144 amino acids, together with core RAG1, is able to mediate the basic biochemical steps required for V(D)J recombination in vitro and in transfected cell lines. Here we examine the effect of replacing the endogenous RAG2 locus in mice with core RAG2. These mice generate substantial numbers of B and T cells, demonstrating that the core RAG2 protein retains significant in vivo function. However, core RAG2 mice display a reduction in the total number of B and T cells, reflecting impaired lymphocyte development at the progenitor stage associated with reduced chromosomal V(D)J recombination. We discuss potential roles of the RAG2 C terminus in mediating rearrangement of endogenous antigen-receptor loci. C1 Harvard Univ, Sch Med, Ctr Blood Res, Childrens Hosp,Howard Hughes Med Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Univ Tokushima, Inst Genome Res, Tokushima 7708503, Japan. RIKEN, Res Ctr Allergy & Immunol, Tokushima 7708503, Japan. RP Bassing, CH (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Childrens Hosp,Howard Hughes Med Inst, Enders Bldg,Room 870,300 Longwood Ave, Boston, MA 02115 USA. RI Takahama, Yousuke/A-5863-2010 FU NIAID NIH HHS [AI20047, P01 AI035714, R37 AI020047, AI35714, R01 AI020047]; NIGMS NIH HHS [GM48026, R01 GM048026] NR 36 TC 66 Z9 67 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 4 PY 2003 VL 100 IS 3 BP 1209 EP 1214 DI 10.1073/pnas.0237043100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 642ZU UT WOS:000180838100080 PM 12531919 ER PT J AU Kannan, K Sharpless, NE Xu, J O'Hagan, RC Bosenberg, M Chin, L AF Kannan, K Sharpless, NE Xu, J O'Hagan, RC Bosenberg, M Chin, L TI Components of the Rb pathway are critical targets of UV mutagenesis in a murine melanoma model SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE P-16INK4a; p19(ARF); UVB; cdk6 ID ULTRAVIOLET-RADIATION; MALIGNANT-MELANOMA; DNA-DAMAGE; HUMAN SKIN; P16(INK4A); MUTATIONS; CDKN2A; MICE; EXPRESSION; P14(ARF) AB Epidemiological studies support a link between melanoma risk and UV exposure early in life, yet the molecular targets of UV's mutagenic actions are not known. By using well characterized murine models of melanoma, we provide genetic and molecular evidence that identifies components of the Rb pathway as the principal targets of UV mutagenesis in murine melanoma development. In a melanoma model driven by H-RAS activation and loss of p19(ARF) function, UV exposure resulted in a marked acceleration in melanoma genesis, with nearly half of these tumors harboring amplification of cyclin-dependent kinase (cdk) 6, whereas none of the melanomas arising in the absence of UV treatment possessed cdk6 amplification. Moreover, UV-induced melanomas showed a strict reciprocal relationship between cdk6 amplification and p16(INK4a) loss, which is consistent with the actions of UV along the Rb pathway. Most significantly, UV exposure had no impact on the kinetics of melanoma driven by H-RAS activation and p16(INK4a) deficiency. Together, these molecular and genetic data identify components of the Rb pathway as critical biological targets of UV-induced multagenesis in the development of murine melanoma in vivo. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. RP Chin, L (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St,M413, Boston, MA 02115 USA. NR 41 TC 82 Z9 86 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 4 PY 2003 VL 100 IS 3 BP 1221 EP 1225 DI 10.1073/pnas.0336397100 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 642ZU UT WOS:000180838100082 PM 12538879 ER PT J AU Yoshii, A Sheng, MH Constantine-Paton, M AF Yoshii, A Sheng, MH Constantine-Paton, M TI Eye opening induces a rapid dendritic localization of PSD-95 in central visual neurons SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POSTSYNAPTIC DENSITY PROTEIN; NMDA RECEPTORS; HIPPOCAMPAL-NEURONS; EXCITATORY SYNAPSES; SUPERIOR COLLICULUS; CEREBRAL-CORTEX; IN-VIVO; EXPRESSION; INTERACTS; DOMAIN AB The membrane-associated guanylate kinase PSD-95 scaffolds N-methyl-(D)-aspartate receptors to cytoplasmic signaling molecules, and associates with other glutamate receptors at central synapses. However, regulation of PSD-95 in vivo is poorly understood. We provide evidence of an activity-dependent redistribution of PSD-95 to dendrites in central visual neurons that is tied to eye opening. Six hours after eye opening, increased dendritic PSD-95 coimmunoprecipitates with the same proportions of stargazin, increased proportions of the N-methyl-(D)-aspartate receptor subunit NR2A, and decreased proportions of NR2B. Sustained high levels of PSD-95 in dendrites are dependent on continued pattern vision in juvenile but not mature animals, suggesting that the stabilization of PSD-95 at synapses may be involved in the control of developmental plasticity. C1 MIT, Dept Biol, Cambridge, MA 02139 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, Ctr Learning & Memory, Cambridge, MA 02139 USA. MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Constantine-Paton, M (reprint author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. FU NEI NIH HHS [R01EY06039, R01 EY006039]; NINDS NIH HHS [R01NS32290] NR 34 TC 64 Z9 69 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 4 PY 2003 VL 100 IS 3 BP 1334 EP 1339 DI 10.1073/pnas.0335785100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 642ZU UT WOS:000180838100101 PM 12552131 ER PT J AU Townsend, M Yoshii, A Mishina, M Constantine-Paton, M AF Townsend, M Yoshii, A Mishina, M Constantine-Paton, M TI Developmental loss of miniature N-methyl-D-aspartate receptor currents in NR2A knockout mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LATERAL GENICULATE-NUCLEUS; SYNAPTIC NMDA RECEPTORS; RAT VISUAL-CORTEX; RETINAL ACTIVITY; SUBUNIT; EXPRESSION; EXPERIENCE; PSD-95; ANTAGONIST; IFENPRODIL AB The N-methyl-(D)-aspartate (NMDA) glutamate receptor (NMDAR), long implicated in developmental plasticity, shows decay time kinetics that shorten postnatally as NR2A subunits are added to the receptor. Neither the mechanism nor immediate effect of this change is known. We studied developing NMDAR currents by using visual neurons in slices from NR2A knockout (NR2AKO) and WT mice. Both strains show increased dendritic levels of synaptic density scaffolding protein PSD-95 with age. Dendritic levels of NR2A increased at the same time in WT and immunoprecipitated with PSD-95. PSD-95/NMDAR binding was significantly decreased in the NR2AKO. Moreover, NMDAR miniature currents (minis) were lost and rise times of NMDAR evoked currents increased in mutant mice. Age-matched WT cells showed NR2A-rich receptors predominating in minis, yet slow NR2B mediated currents persisted in evoked currents. Disrupting photoreceptor activation of retinal ganglion cells eliminated increases in PSD-95 and NR2A in superior collicular dendrites of WT mice and slowed the loss of miniature NMDAR currents in NR2AKOs. These data demonstrate that NMDARs that respond to single quantal events mature faster during development by expressing the NR2A subunit earlier than NMDARs that respond to evoked release. We hypothesize that NR2A-rich NMDARs may be localized to the center of developing synapses by an activity-dependent process that involves the targeting of PSD-95 to the postsynaptic density. Neonatal receptors become restricted to perisynpatic or extrasynaptic sites, where they participate primarily in evoked currents. C1 MIT, Dept Biol, Cambridge, MA 02139 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. Yale Univ, Interdepartmental Neurosci Program, New Haven, CT 06520 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Tokyo, Sch Med, Dept Mol Neurobiol & Pharmacol, Bunkyo Ku, Tokyo 1130033, Japan. RP Constantine-Paton, M (reprint author), MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA. FU NEI NIH HHS [T32 EY007115, 5T32EY07115]; NIDA NIH HHS [T32 DA007290, 5T32DA07290]; NINDS NIH HHS [NS32290] NR 46 TC 73 Z9 78 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 4 PY 2003 VL 100 IS 3 BP 1340 EP 1345 DI 10.1073/pnas.0335786100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 642ZU UT WOS:000180838100102 PM 12552130 ER PT J AU Redwine, JM Kosofsky, B Jacobs, RE Games, D Reilly, JF Morrison, JH Young, WG Bloom, FE AF Redwine, JM Kosofsky, B Jacobs, RE Games, D Reilly, JF Morrison, JH Young, WG Bloom, FE TI Dentate gyrus volume is reduced before onset of plaque formation in PDAPP mice: A magnetic resonance microscopy and stereologic analysis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID AMYLOID-PRECURSOR PROTEIN; FAMILIAL ALZHEIMERS-DISEASE; CORPUS-CALLOSUM ATROPHY; LONG-TERM POTENTIATION; TRANSGENIC MICE; HIPPOCAMPAL-NEURONS; BETA-PROTEIN; SYNAPTIC TRANSMISSION; IN-VIVO; ENTORHINAL CORTEX AB High-resolution magnetic resonance microscopy (MRM) was used to determine regional brain volumetric changes in a mouse model of Alzheimer's disease. These transgenic (Tg) mice overexpress human mutant amyloid precursor protein (APP) V717F under control of platelet-derived growth factor promoter (PDAPP mice), and cortical and hippocampal beta-amyloid (Abeta) deposits accumulate in heterozygotes after 8-10 mos. We used MRM to obtain 3D volumetric data on mouse brains imaged in their skulls to define genotype- and age-related changes. Hippocampal, cerebellar, and brain volumes and corpus callosum length were quantified in 40-, 100-, 365-, and 630-day-old mice. Measurements taken at age 100 days, before Abeta deposition, revealed a 12.3% reduction of hippocampus volume in Tg mice compared with WT controls. This reduction persisted without progression to age 21 mos. A significant 18% increase in hippocampal volume occurred between 40 and 630days in WT mice, and no corresponding significant increase occurred in Tg mice. Cavalieri volume estimates of hippocampal subfields from 100-day-old Tg mice further localized a 28% volume deficit in the dentate gyrus. In addition, corpus callosum length was reduced by approximate to25% in Tg mice at all ages analyzed. In summary, reduced hippocampal volume and corpus callosum length can be detected by MIRM before Abeta deposition. We conclude that overexpression of APP and amyloid may initiate pathologic changes before the appearance of plaques, suggesting novel targets for the treatment of Alzheimer's disease and further reinforcing the need for early diagnosis and treatment. C1 Neurome Inc, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02129 USA. CALTECH, Beckman Inst, Pasadena, CA 91125 USA. Elan Pharmaceut, San Francisco, CA 94080 USA. Mt Sinai Sch Med, Kastor Neurobiol Aging Labs, New York, NY 10029 USA. Mt Sinai Sch Med, Fishberg Res Ctr Neurobiol, New York, NY 10029 USA. Scripps Res Inst, Dept Neuropharmacol, La Jolla, CA 92037 USA. RP Bloom, FE (reprint author), Neurome Inc, La Jolla, CA 92037 USA. RI Morrison, John/F-9229-2012 NR 66 TC 132 Z9 136 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD FEB 4 PY 2003 VL 100 IS 3 BP 1381 EP 1386 DI 10.1073/pnas.242746599 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 642ZU UT WOS:000180838100109 PM 12552120 ER PT J AU Migliaccio, AR Rana, RA Sanchez, M Lorenzini, R Centurione, L Bianchi, L Vannucchi, AM Migliaccio, G Orkin, SH AF Migliaccio, AR Rana, RA Sanchez, M Lorenzini, R Centurione, L Bianchi, L Vannucchi, AM Migliaccio, G Orkin, SH TI GATA-1 as a regulator of mast cell differentiation revealed by the phenotype of the GATA-1(low) mouse mutant SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE mast cells; GATA-1; differentiation; commitment; progenitor cells ID TRANSCRIPTION FACTOR GATA-1; CONNECTIVE-TISSUE-TYPE; HEMATOPOIETIC-CELLS; COMMON PRECURSOR; GENE-TRANSFER; GROWTH-FACTOR; EXPRESSION; MICE; RECEPTOR; LINEAGES AB Here it is shown that the phenotype of adult mice lacking the first enhancer (DNA hypersensitive site I) and the distal promoter of the GATA-1 gene (neoDeltaHS or GATA-1(low) mutants) reveals defects in mast cell development. These include the presence of morphologically abnormal alcian blue(+) mast cells and apoptotic metachromatic(-) mast cell precursors in connective tissues and peritoneal lavage and numerous (60-70% of all the progenitors) "unique" trilineage cells committed to erythroid, megakaryocytic, and mast pathways in the bone marrow and spleen. These abnormalities, which were mirrored by impaired mast differentiation in vitro, were reversed by retroviral-mediated expression of GATA-1 cDNA. These data indicate an essential role for GATA-1 in mast cell differentiation. C1 Ist Super Sanita, Lab Clin Biochem, I-00161 Rome, Italy. Ist Super Sanita, Cell Biol Lab, I-00161 Rome, Italy. Ist Super Sanita, Lab Serv Qual Sicurezza Anim, I-00161 Rome, Italy. Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp,Dept Pediat Oncol, Boston, MA 02115 USA. Univ Florence, Dept Hematol, I-50139 Florence, Italy. Univ G DAnnunzio, Dept Biomorphol, I-66100 Chieti, Italy. RP Migliaccio, AR (reprint author), Ist Super Sanita, Lab Clin Biochem, Viale Regina Elena 299, I-00161 Rome, Italy. NR 57 TC 152 Z9 154 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD FEB 3 PY 2003 VL 197 IS 3 BP 281 EP 296 DI 10.1084/jem.20021149 PG 16 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 644XE UT WOS:000180945200002 PM 12566412 ER PT J AU Newgard, CD Kim, S Camargo, CA AF Newgard, CD Kim, S Camargo, CA TI Emergency medicine leadership in industry-sponsored clinical trials SO ACADEMIC EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT SAEM Annual Meeting CY MAY, 2000 CL SAN DIEGO, CALIFORNIA SP SAEM DE emergency medicine; industry-sponsored trials; clinical trials; leadership AB Objective: To identify and characterize emergency medicine (EM) researchers who, since 1990, have served on a steering committee (SC) or as overall principal investigator (PI) of an industry-sponsored, multicenter clinical trial involving a pharmaceutical or device. Methods: North American EM research directors (RDs) and other prominent EM investigators (for those hospitals without a RD) were identified from eight sources, including the Society for Academic Emergency Medicine RD Interest Group and the Multicenter Airway Research Collaboration (MARC) database. The identified investigators were sent a screening survey requesting information regarding industry-sponsored clinical research at their site. The individual EM investigators identified by this screening survey were then interviewed by telephone (validation survey) to further explore their leadership experience in industry-sponsored clinical trials. Results: Of 153 identified RDs and prominent EM researchers, 138 responded to the screening survey (90% response rate). Eighty-five EM investigators reportedly had served on a SC or as overall PI for an industry-sponsored clinical trial. Of these 85 North American EM investigators, 77 were available for a structured telephone interview (91% response rate). Although 41 (53%) of the investigators confirmed their leadership role, 36 (47%) had riot served in either role. Among the 41 confirmed investigators, 19 (25%) had served as a SC member, 10 (13%) had served as overall PI, and 12 (16%) had experience in both roles. Individual responses provided suggestions for pursuing such leadership positions. Conclusions: These data suggest the opportunity to expand EM leadership in industry-sponsored clinical trials and demonstrate the need for validation of reports obtained by a departmental research contact. The suggestions from EM researchers who have attained these leadership roles may provide strategies for investigators interested in pursuing these positions. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA USA. Harbor UCLA Med Ctr, Res & Educ Inst, Dept Emergency Med, Torrance, CA 90509 USA. Oregon Hlth Sci Univ, Dept Emergency Med, Portland, OR 97201 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med,Coordinating Ctr, Boston, MA 02114 USA. RP Camargo, CA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med,Coordinating Ctr, 55 Fruit St,Clin Bldg 397, Boston, MA 02114 USA. NR 12 TC 1 Z9 1 U1 0 U2 0 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 FEB PY 2003 VL 10 IS 2 BP 169 EP 174 PG 6 WC Emergency Medicine SC Emergency Medicine GA 643BX UT WOS:000180843000011 PM 12574016 ER PT J AU Danforth, W Bigger, JT Davidoff, F Delaney, MJ Dentzer, S Ehringhaus, SH Graham, G Hellmann, S Kahn, J Kalb, M Kaufman, RE Kelch, RP Laret, MR Leonard, JS Levy, R Lieber, CE Martin, JB Miller, ED Murray, TH O'Brien, CP Porter, JE Porter, R Ramsey, PG Robinson, DK Smith, H Visco, FM Woo, S Wood, AJJ Turman, RJ Korn, D Kulynych, J AF Danforth, W Bigger, JT Davidoff, F Delaney, MJ Dentzer, S Ehringhaus, SH Graham, G Hellmann, S Kahn, J Kalb, M Kaufman, RE Kelch, RP Laret, MR Leonard, JS Levy, R Lieber, CE Martin, JB Miller, ED Murray, TH O'Brien, CP Porter, JE Porter, R Ramsey, PG Robinson, DK Smith, H Visco, FM Woo, S Wood, AJJ Turman, RJ Korn, D Kulynych, J CA AAMC Task Force Financial Conflict TI Protecting subjects, preserving trust, promoting progress I: Policy and guidelines for the oversight of individual financial interests in human subjects research SO ACADEMIC MEDICINE LA English DT Article AB In December 2001, the AAMC Task Force on Financial Conflicts of Interest in Clinical Research released this report, the first of two (both published in this issue of Academic Medicine). This report focuses on gaps in existing federal financial disclosure regulations of individual conflicts of interests, finding that additional scrutiny is recommended in two areas: human subjects research and privately sponsored research. The task force suggests that when potential conflicts exist, a conflicts of interest committee should apply a rebuttable presumption against engaging in human subjects research. The task force recommends that the circumstances giving rise to the presumption against the proposed activity be balanced against compelling circumstances in favor of the conduct of the research. The AAMC task force delineates core principles to guide institutional policy development. First, an institution should regard all significant financial interests in human subjects research as requiring close scrutiny. Second, in the event of compelling circumstances, an individual holding a significant financial interest may be permitted to conduct the research. Whether circumstances are deemed compelling will depend in each case upon the nature of the science, the nature of the interest, how closely the interest is related to the research, and the degree to which the interest may be affected by the research. Four other core principles for development of institutional policies are identified in the report, pertaining to reporting, monitoring, management of conflicts, and accountability. C1 Assoc Amer Med Coll, DBHSR, Washington, DC 20037 USA. Washington Univ, Board Trustees, St Louis, MO 63130 USA. Columbia Univ, New York, NY 10027 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Guidant Corp, Indianapolis, IN 46244 USA. Genentech Inc, San Francisco, CA 94080 USA. Univ Minnesota, Minneapolis, MN 55455 USA. John F Kennedy Sch Govt, Joan Shorenstein Ctr Press Polit & Publ Policy, Washington, DC USA. Duke Univ, Sch Med, Durham, NC 27706 USA. Univ Iowa, Coll Med, Iowa City, IA 52242 USA. Univ Calif San Francisco, Med Ctr, San Francisco, CA 94143 USA. Howard Hughes Med Inst, Coconut Grove, FL 33133 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Fac Med, Cambridge, MA 02138 USA. Hastings Ctr, Garrison, NY USA. Univ Penn, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Hogan & Hartson LLP, Washington, DC 20004 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Yale Univ, New Haven, CT 06520 USA. Mt Sinai Sch Med, Inst Gene Therapy, New York, NY 10029 USA. Vanderbilt Univ, Sch Med, Nashville, TN 37240 USA. Assoc Amer Univ, New York, NY 10012 USA. Assoc Amer Med Coll, Div Biomed & Hlth Sci Res, Washington, DC 20037 USA. RP Korn, D (reprint author), Assoc Amer Med Coll, DBHSR, 2450 N St NW, Washington, DC 20037 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD FEB PY 2003 VL 78 IS 2 BP 226 EP 236 PG 11 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 647CG UT WOS:000181073900018 ER PT J AU Danforth, W Bigger, JT Davidoff, F Delaney, M Dentzer, S Ehringhaus, SH Graham, G Hellmann, S Kahn, J Kalb, M Kaufman, RE Kelch, RP Laret, MR Leonard, JS Levy, R Lieber, CE Martin, JB Miller, ED Murray, TH O'Brien, CP Porter, JE Porter, R Ramsey, PG Robinson, DK Visco, FM Woo, S Wood, AJJ Turman, RJ Korn, D Kulynych, J AF Danforth, W Bigger, JT Davidoff, F Delaney, M Dentzer, S Ehringhaus, SH Graham, G Hellmann, S Kahn, J Kalb, M Kaufman, RE Kelch, RP Laret, MR Leonard, JS Levy, R Lieber, CE Martin, JB Miller, ED Murray, TH O'Brien, CP Porter, JE Porter, R Ramsey, PG Robinson, DK Visco, FM Woo, S Wood, AJJ Turman, RJ Korn, D Kulynych, J CA AAMC Task Force Financial Conflict TI Protecting subjects, preserving trust, promoting progress II: Principles and recommendations for oversight of an institution's financial interests in human subjects research SO ACADEMIC MEDICINE LA English DT Article AB The AAMC Task Force on Financial Conflicts of Interest in Clinical Research issued this report, the second of two, in October 2002. (The first report is also published in this issue of Academic Medicine.) This report offers a unique perspective on the new phenomenon of "institutional" conflicts of interest. The task force acknowledges the diverse obligations of academic institutions that conduct research and also invest in-and accept the philanthropy of-commercial research sponsors. The task force emphasizes the importance of disclosing institutional financial interests as an integral part of the research process, critical to allaying public concerns, and to strengthening the trust relationship between research subjects, the public and the scientific community. The task force found that the safety and welfare of research subjects and the objectivity of the research could be-or could appear to be-compromised whenever an institution holds a significant financial interest that may be affected by the outcome of the research. Thus, the task force recommends separating the functional and administrative responsibilities related to human subjects research from those related to investment managing and technology licensing, and encourages the establishment of institutional conflicts-of-interest committees. As in the first report, the task force recommends that institutions should develop policies establishing a rebuttable presumption against the conduct of research at or under the auspices of an institution where potential conflicts in human subjects research are identified. This presumption against engaging in the research is to be balanced against compelling circumstances in favor of the conduct of the proposed research activity. C1 Assoc Amer Med Coll, DBHSR, Washington, DC 20037 USA. Washington Univ, Board Trustees, St Louis, MO USA. Columbia Univ, New York, NY 10027 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Guidant Corp, Indianapolis, IN 46244 USA. Genentech Inc, San Francisco, CA 94080 USA. Univ Minnesota, Ctr Bioeth, Minneapolis, MN 55455 USA. John F Kennedy Sch Govt, Joan Shorenstein Ctr Press Polit & Publ Policy, Washington, DC USA. Duke Univ, Sch Med, Durham, NC 27706 USA. Univ Iowa, Coll Med, Iowa City, IA 52242 USA. Univ Calif San Francisco, Med Ctr, San Francisco, CA 94143 USA. Howard Hughes Med Inst, Coconut Grove, FL 33133 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Fac Med, Cambridge, MA 02138 USA. Hastings Ctr, Garrison, NY USA. Univ Penn, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Hogan & Hartson LLP, Washington, DC 20004 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Yale Univ, New Haven, CT 06520 USA. Mt Sinai Sch Med, Inst Gene Therapy, New York, NY 10029 USA. Assoc Amer Univ, Washington, DC 20005 USA. Assoc Amer Med Coll, Div Biomed & Hlth Sci Res, Washington, DC 20037 USA. RP Korn, D (reprint author), Assoc Amer Med Coll, DBHSR, 2450 N St NW, Washington, DC 20037 USA. NR 3 TC 21 Z9 22 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD FEB PY 2003 VL 78 IS 2 BP 237 EP 245 PG 9 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 647CG UT WOS:000181073900019 ER PT J AU Durfee, SM Jain, S Shaffer, K AF Durfee, SM Jain, S Shaffer, K TI Incorporating electronic media into medical student education: A survey of AMSER members on computer and Web use in radiology courses SO ACADEMIC RADIOLOGY LA English DT Article DE computers; educational aid; education; Internet ID INFORMATION TECHNOLOGY AB Rationale and Objectives. The purpose of this study was to define the current use of information technology in radiology tutorials for medical students. Materials and Methods. The authors conducted a Web-based survey of directors of medical school courses in radiology. The survey dealt with the details of the courses and the use of computers and the Web during the courses. Results. There were 48 responses. Most radiology courses were elective (73%) and were offered monthly. Most institutions (79%) had picture archiving and communication systems (PACS) available or were completely filmless. The teaching case presentations, however, often included film images displayed on a view box or by an overhead projector. Computers dedicated to student use were uncommon (28%). The Web was used infrequently as a teaching resource, and a Web site was not available in most courses. Computer technical support was variable and usually provided by the course director. Course directors at institutions with PACS were more likely to use digital technology for case presentations and more likely to use the Web for teaching purposes. Conclusion. Despite the widespread use of digital technology and PACS in the field of radiology, digital technology is underused in radiology courses. However, departments with PACS tend to use digital technology more frequently in education than do departments without PACS. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. RP Durfee, SM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. NR 9 TC 16 Z9 17 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD FEB PY 2003 VL 10 IS 2 BP 205 EP 210 DI 10.1016/S1076-6332(03)80046-6 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 640QB UT WOS:000180698500012 PM 12583573 ER PT J AU McLoud, TC AF McLoud, TC TI Organized radiology SO ACADEMIC RADIOLOGY LA English DT Article C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP McLoud, TC (reprint author), Massachusetts Gen Hosp, Dept Radiol, Founders 216, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD FEB PY 2003 VL 10 SU 1 BP S87 EP S91 DI 10.1016/S1076-6332(03)80157-5 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 641ZB UT WOS:000180776000018 PM 12585451 ER PT J AU Roeber, D Achari, A Manavalan, P Edmunds, T Scott, DL AF Roeber, D Achari, A Manavalan, P Edmunds, T Scott, DL TI Crystallization and preliminary X-ray analysis of recombinant human acid beta-glucocerebrosidase, a treatment for Gaucher's disease SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID REPLACEMENT THERAPY AB Acid beta-glucocerebrosidase (N-acylsphingosyl-1-O-beta-D-glucoside: glucohydrolase) is a lysosomal glycoprotein that catalyzes the hydrolysis of the glycolipid glucocerebroside to glucose and ceramide. Inadequate levels of this enzyme underly the pathophysiology of Gaucher's disease. Cerezyme (Genzyme Corporation, Cambridge, MA, USA) is a partially deglycosylated form of recombinant human acid beta-glucocerebrosidase that is used in the treatment of Gaucher patients. Although acid beta-glucocerebrosidase belongs to a large family of glycosidases, relatively little is known regarding its structural biology. Here, the crystallization and the initial diffraction analysis of Cerezyme are reported. The crystals are C-centered orthorhombic, with unit-cell parameters a = 285.0, b = 110.2, c = 91.7 Angstrom. A 99.9% complete data set has been collected to 2.75 Angstrom with an R-sym of 8.8%. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med & Orthopaed Surg, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Struct Biol Unit, Charlestown, MA 02129 USA. Genzyme Corp, Framingham, MA 01701 USA. NASA, George C Marshall Space Flight Ctr, Struct Biol Lab, Huntsville, AL 35812 USA. RP Scott, DL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med & Orthopaed Surg, 149 13th St, Charlestown, MA 02129 USA. NR 18 TC 4 Z9 4 U1 0 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD FEB PY 2003 VL 59 BP 343 EP 344 DI 10.1107/S0907444902020498 PN 2 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 639QZ UT WOS:000180641900017 PM 12554947 ER PT J AU Kitabwalla, M Ferrantelli, F Wang, T Chalmers, A Katinger, H Stiegler, G Cavacini, LA Chou, TC Ruprecht, RM AF Kitabwalla, M Ferrantelli, F Wang, T Chalmers, A Katinger, H Stiegler, G Cavacini, LA Chou, TC Ruprecht, RM TI Primary African HIV clade A and D isolates: Effective cross-clade neutralization with a quadruple combination of human monoclonal antibodies raised against clade B SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4 BINDING-SITE; SYNERGISTIC NEUTRALIZATION; PASSIVE-IMMUNIZATION; CD4-BINDING SITE; RHESUS-MONKEYS; V3 LOOP; TYPE-1; INFECTION; MACAQUES AB We investigated the ability of several human neutralizing monoclonal antibodies (nmAbs), originally raised against human immunodeficiency virus (HIV) clade B isolates, to neutralize primary clade A and D isolates as single agents and in combinations. All four primary HIV clade A isolates and five primary HIV clade D isolates tested were neutralized >99% by the quadruple combination of nmAbs IgG1b12, 2G12, 2F5, and 4E10. These mAbs recognize conserved epitopes on HIV-1 envelope (Env), resulting in strong cross-clade neutralization. Previously, we showed synergistic neutralization of primary HIV-1 clade C isolates in vitro by the same nMAb combination. We and others also showed neutralization of primary HIV clade B strains. Together, our data show that the quadruple combination of mAbs effectively neutralized primary HIV clade A, B, C, and D isolates. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Inst Appl Microbiol, A-1190 Vienna, Austria. Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Preclin Pharmacol Core Lab, Mol Pharmacol & Chem Program, New York, NY 10021 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. RI Chou, Ting-Chao/B-4111-2009; Ferrantelli, Flavia/J-7794-2016 OI Chou, Ting-Chao/0000-0002-3340-1594; Ferrantelli, Flavia/0000-0002-0768-1078 FU NIAID NIH HHS [P01 AI48280, R01AI34266] NR 50 TC 22 Z9 22 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD FEB PY 2003 VL 19 IS 2 BP 125 EP 131 DI 10.1089/088922203762688630 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 646RL UT WOS:000181048000006 PM 12639248 ER PT J AU Caetano, R Schafer, J Fals-Stewart, W O'Farrell, T Miller, B AF Caetano, R Schafer, J Fals-Stewart, W O'Farrell, T Miller, B TI Intimate partner violence and drinking: New research on methodological issues, stability and change, and treatment SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article ID UNITED-STATES; PHYSICAL AGGRESSION; HISPANIC COUPLES; SPOUSAL VIOLENCE; MARITAL VIOLENCE; AGREEMENT; RELIABILITY; ALCOHOL; WHITE; BLACK AB This article represents the proceedings of a symposium at the 2002 RSA meeting in San Francisco, California. The presentations were (1) Assessing couples' agreement about alcohol involvement in intimate partner violence, by John Schafer; (2) The occurrence of partner physical aggression on days of alcohol consumption: a longitudinal diary study, by Williams Fals-Stewart; (3) The 5-year stability of intimate partner violence and drinking among White, Black, and Hispanic couples, by Raul Caetano; (4) Partner violence before and after individually-based alcoholism treatment for male alcoholic patients, by Timothy O'Farrell. The discussant was Brenda Miller. C1 Univ Texas, Sch Publ Hlth, Dallas, TX 75390 USA. Univ Cincinnati, Community Hlth Adm & Psychiat Nursing Dept, Coll Nursing, Cincinnati, OH USA. SUNY Buffalo, Res Inst Addict, Buffalo, NY 14260 USA. Harvard Univ, Sch Med, Dept Psychiat, VA Boston Healthcare Syst, Boston, MA 02115 USA. Prevent Res Ctr, Berkeley, CA USA. RP Caetano, R (reprint author), Univ Texas, Sch Publ Hlth, 5323 Harry Hines Blvd,Room V8-112,Dallas Reg Camp, Dallas, TX 75390 USA. FU NIAAA NIH HHS [K02AA000319, K02AA00234, AA10356]; NIDA NIH HHS [R29DA909650, R01DA14402] NR 39 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD FEB PY 2003 VL 27 IS 2 BP 292 EP 300 DI 10.1097/01.ALC.0000057124.36127.45 PG 9 WC Substance Abuse SC Substance Abuse GA 648VW UT WOS:000181172400016 PM 12605079 ER PT J AU Massie, BM Ansari, MN AF Massie, BM Ansari, MN TI Specialty care for heart failure: Does it improve outcomes? SO AMERICAN HEART JOURNAL LA English DT Editorial Material ID ACUTE MYOCARDIAL-INFARCTION; CONVERTING ENZYME-INHIBITORS; PHYSICIAN SPECIALTY; PRACTICE GUIDELINES; FAMILY PHYSICIANS; CARDIOLOGISTS; GENERALIST; MANAGEMENT; KNOWLEDGE; PATTERNS C1 San Francisco VA Med Ctr, Div Cardiol, San Francisco, CA 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 VA Med Ctr, Div Cardiol, San Francisco, CA USA. NR 22 TC 6 Z9 6 U1 1 U2 1 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 FEB PY 2003 VL 145 IS 2 BP 209 EP 213 DI 10.1067/mhj.2003.55 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 647MU UT WOS:000181097500008 PM 12595835 ER PT J AU Gheorghiade, M Adams, KF Gattis, WA Teerlink, JR Orlandi, C O'Connor, CM AF Gheorghiade, M Adams, KF Gattis, WA Teerlink, JR Orlandi, C O'Connor, CM TI Surrogate end points in heart failure trials SO AMERICAN HEART JOURNAL LA English DT Article; Proceedings Paper CT Meeting on the Management of Decompensated Heart Failure Resulting in Hospitalization CY APR 20-22, 2001 CL SPRINGFIELD, VIRGINIA ID MORTALITY; FLOSEQUINAN; ENALAPRIL; SURVIVAL; THERAPY C1 Northwestern Univ, Feinberg Sch Med, Div Cardiol, Chicago, IL 60611 USA. Univ N Carolina, Chapel Hill, NC USA. Duke Clin Res Inst, Durham, NC USA. Univ Calif San Francisco, Sch Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Otsuka Maryland Res Inst, Rockville, MD USA. RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch Med, Div Cardiol, Galter 10-240,201 E Huron St, Chicago, IL 60611 USA. RI Teerlink, John/D-2986-2012; Stough, Wendy/R-4287-2016 OI Stough, Wendy/0000-0001-8290-1205 NR 22 TC 12 Z9 12 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 FEB PY 2003 VL 145 IS 2 SU S BP S67 EP S70 DI 10.1067/mhj.2003.159 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 648TE UT WOS:000181166000012 PM 12594457 ER PT J AU Jain, P Massie, BM Gattis, WA Klein, L Gheorghiade, M AF Jain, P Massie, BM Gattis, WA Klein, L Gheorghiade, M TI Current medical treatment for the exacerbation of chronic heart failure resulting in hospitalization SO AMERICAN HEART JOURNAL LA English DT Article; Proceedings Paper CT Meeting on the Management of Decompensated Heart Failure Resulting in Hospitalization CY APR 20-22, 2001 CL SPRINGFIELD, VIRGINIA ID LEFT-VENTRICULAR DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED CONTROLLED TRIAL; HIGH-DOSE FUROSEMIDE; INTRAVENOUS NESIRITIDE; INOTROPIC STIMULATION; PULMONARY-EDEMA; INCREASED RISK; THERAPY; DOBUTAMINE C1 Northwestern Univ, Feinberg Sch MEd, Div Cardiol, Chicago, IL 60611 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Duke Clin Res Inst, Durham, NC USA. Advocate Illinois Masonic Med Ctr, Chicago, IL USA. RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch MEd, Div Cardiol, Galter 10-240 E Huron St, Chicago, IL 60611 USA. RI Stough, Wendy/R-4287-2016 OI Stough, Wendy/0000-0001-8290-1205 NR 68 TC 41 Z9 51 U1 1 U2 3 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 FEB PY 2003 VL 145 IS 2 SU S BP S3 EP S17 DI 10.1067/mhj.2003.149 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 648TE UT WOS:000181166000002 PM 12594447 ER PT J AU O'Connor, CM Gattis, WA Teerlink, JR Adarns, KF Gheorghiade, M AF O'Connor, CM Gattis, WA Teerlink, JR Adarns, KF Gheorghiade, M TI Design considerations and proposed template for clinical trials in hospitalized patients with decompensated chronic heart failure SO AMERICAN HEART JOURNAL LA English DT Article; Proceedings Paper CT Meeting on the Management of Decompensated Heart Failure Resulting in Hospitalization CY APR 20-22, 2001 CL SPRINGFIELD, VIRGINIA C1 Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27705 USA. Univ Calif San Francisco, San Francisco Sch Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. Univ N Carolina, Chapel Hill, NC USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. RP Gattis, WA (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, 2400 N Pratt St, Durham, NC 27705 USA. RI Teerlink, John/D-2986-2012; Stough, Wendy/R-4287-2016 OI Stough, Wendy/0000-0001-8290-1205 NR 1 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 FEB PY 2003 VL 145 IS 2 SU S BP S47 EP S50 DI 10.1067/mhj.2003.153 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 648TE UT WOS:000181166000006 PM 12594451 ER PT J AU Teerlink, JR AF Teerlink, JR TI Dyspnea as an end point in clinical trials of therapies for acute decompensated heart failure SO AMERICAN HEART JOURNAL LA English DT Article; Proceedings Paper CT Meeting on the Management of Decompensated Heart Failure Resulting in Hospitalization CY APR 20-22, 2001 CL SPRINGFIELD, VIRGINIA ID OBSTRUCTIVE AIRWAY DISEASE; VISUAL ANALOG SCALES; INTRAVENOUS MILRINONE; SCIENTIFIC SESSIONS; OF-CARDIOLOGY; UPDATE; DESCRIPTORS; HIGHLIGHTS; EXERCISE; AMERICAN C1 San Francisco Vet Affairs Med Ctr, Heart Failure Clin, San Francisco, CA 94121 USA. Univ Calif San Francisco, Sch Med, San Francisco, CA USA. RP Teerlink, JR (reprint author), San Francisco Vet Affairs Med Ctr, Heart Failure Clin, 111C,4150 Clement St, San Francisco, CA 94121 USA. RI Teerlink, John/D-2986-2012 NR 31 TC 43 Z9 43 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 FEB PY 2003 VL 145 IS 2 SU S BP S26 EP S33 DI 10.1067/mhj.2003.151 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 648TE UT WOS:000181166000004 PM 12594449 ER PT J AU Murphy, SA Chen, C Gourlay, SG Gibbons, RJ Barron, HV Gibson, CM AF Murphy, SA Chen, C Gourlay, SG Gibbons, RJ Barron, HV Gibson, CM CA LIMIT AMI Study Grp TI Impairment of myocardial perfusion in both culprit and nonculprit arteries in acute myocardial infarction: A LIMIT AMI substudy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID VASOCONSTRICTION; AGENTS; FLOW AB Acute myocardial infarction results in a lower rate of normal TIMI myocardial perfusion grade 3, and when myocardial perfusion was assessed using digital subtraction angiography, both nonculprit and global myocardial perfusion in all beds decreased. These data extend previous findings to demonstrate that there are abnormalities in both epicardial and microvascular flow in nonculprit arteries. C1 TIMI Study Grp, Boston, MA 02115 USA. Beth Israel Hosp, Dept Med, Boston, MA USA. Univ Calif San Francisco, Dept Med, Div Cardiovasc, San Francisco, CA USA. Mayo Clin, Rochester, MN USA. Genentech Inc, San Francisco, CA USA. RP Murphy, SA (reprint author), TIMI Study Grp, 333 Longwood Ave, Boston, MA 02115 USA. NR 11 TC 12 Z9 13 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD FEB 1 PY 2003 VL 91 IS 3 BP 325 EP + DI 10.1016/S0002-9149(02)03160-0 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 645RX UT WOS:000180993800011 PM 12565089 ER PT J AU Hadigaan, C Rabe, J Meininger, G Aliabadi, N Breu, J Grinspoon, S AF Hadigaan, C Rabe, J Meininger, G Aliabadi, N Breu, J Grinspoon, S TI Inhibition of lipolysis improves insulin sensitivity in protease inhibitor-treated HIV-infected men with fat redistribution SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE lipodystrophy; insulin resistance; fatty acids; acipimox; HIV; men ID METABOLIC ABNORMALITIES; ANTIRETROVIRAL THERAPY; COMPUTED-TOMOGRAPHY; GLUCOSE-TOLERANCE; GROWTH-HORMONE; MINIMAL MODEL; RESISTANCE; LIPODYSTROPHY; OBESE; ACID AB Background, Fatty acid concentrations are increased in patients with HIV and fat redistribution and may contribute to insulin resistance in this population. Objective: We determined the effects of acute inhibition of lipolysis on insulin sensitivity in HIV-infected patients with fat redistribution who were receiving a protease inhibitor. Design: Severn HIV-infected men [age: 45 +/- 2 y; body mass index (in kg/m(2)): 28.8 +/- 1.9] with a fasting insulin concentration greater than or equal to 104 pmol/L (15 muIU/mL), combined visceral adiposity and peripheral lipoatrophy, and receiving a protease inhibitor were studied. Tolbutamide-modified frequently sampled intravenous-glucose-tolerance tests (FSIGTTs) were performed after randomized double-blind administration of acipimox (500 mg at -90 and 0 min), a potent inhibitor of lipolysis, and placebo. The subjects completed 2 FSIGTTs separated by 3-7 d. Results: At baseline, fasting insulin and fatty acid concentrations were 27.6 +/- 5.11 muIU/mL and 0.83 +/- 0.08 mmol/L (normal range: 0.1-0.6 mmol/L), respectively. Fatty acid concentrations were significantly reduced after acipimox compared with placebo (fatty acid area under the curve: acipimox = 73 +/- 8 compared with placebo = 122 +/- 12 mmol . 270 min/L, P = 0.002). Acipimox treatment resulted in a significant increase in the insulin sensitivity index (acipimox -1.63 +/- 0.5 compared with placebo = 0.88 +/- 0.3 x 10(-4) . min(-1) = is muIU/mL, P = 0.015). Conclusions: Acute inhibition of lipolysis and reduction in fatty acid concentrations are associated with improved insulin sensitivity in patients with HIV lipodystrophy and hyperinsulinemia. Further studies are needed to determine whether long-term antilipolytic strategies to reduce fatty acid concentrations may be useful in treating the metabolic disturbances associated with HIV lipodystrophy. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Program Nutrit Metab, Boston, MA 02114 USA. MIT, Clin Res Ctr, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hadigaan, C (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457B,55 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [M01-RR300088]; NIDDK NIH HHS [R01-DK59535, P30 DK40561, K23-DK02844] NR 27 TC 40 Z9 40 U1 0 U2 0 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 FEB PY 2003 VL 77 IS 2 BP 490 EP 494 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 637LG UT WOS:000180512200031 PM 12540412 ER PT J AU Proulx, GM Caudra-Garcia, I Ferry, J Harris, N Greco, WR Kaya, U Chan, A Wang, CC AF Proulx, GM Caudra-Garcia, I Ferry, J Harris, N Greco, WR Kaya, U Chan, A Wang, CC TI Lymphoma of the nasal cavity and paranasal sinuses - Treatment and outcome of early-stage disease SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article ID NON-HODGKINS-LYMPHOMA; COMBINED-MODALITY THERAPY; WALDEYERS RING; MALIGNANT-LYMPHOMAS; PROGNOSTIC FACTORS; NECK; HEAD; SINONASAL; CLASSIFICATION; TRACT AB The records of 23 patients diagnosed and treated at the Massachusetts General Hospital for extranodal non-Hodgkin's lymphoma of the paranasal sinus and nasal cavity were reviewed. The majority of patients were Ann Arbor stage I and approximately evenly divided in T1 or T2 (n = 10) and T3 or T4 (n = 13). Eight patients had nasal-type NK/T. cell and 15 patients had diffuse large B-cell lymphoma (DLBCL). The patients with nasal-type NK/T cell lymphoma predominately involved the nasal cavity (5/8), whereas the DLBCL more often had the paranasal sinuses as the primary site (12/15). All patients received radiation as part of their treatment. Only three patients received chemotherapy as part of their initial treatment for three cycles using a cyclophosphamide, doxorubicin, vincristine, and prednisone-based regimen. By coincidence, the estimated overall survival (OS) and disease-free survival rates for both 5 and 10 years were all the same for all analyses. The OS for the entire group at 10 years was 78%. Significant prognostic factors were Ann Arbor stage IEA versus IIEA (p = 0.0001) and T stage with (T1 or T2) versus (T3 or T4) (p = 0.0243). Combining Ann Arbor stage and T stage created a highly significant prognostic variable (IEA & [T1 or T2], IEA & [T3 or T4], IIEA & [T I or T2], IIEA & [T3 or T4]) at p = 0.0001, regardless of site or histology. Patients with local-regional disease appear to be well controlled with radiation alone, but distant failure remains a problem. A combined-modality approach with local-regional radiation and systemic chemotherapy is recommended for these patients. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02129 USA. Roswell Pk Canc Inst, Dept Canc Prevent Epidemiol & Biostat, Buffalo, NY 14263 USA. RP Proulx, GM (reprint author), Robert Packer Hosp, Guthrie Hlth Syst, Dept Radiat Oncol, Sayre, PA 18840 USA. FU NCI NIH HHS [CA 16056] NR 31 TC 24 Z9 29 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD FEB PY 2003 VL 26 IS 1 BP 6 EP 11 DI 10.1097/00000421-200302000-00002 PG 6 WC Oncology SC Oncology GA 693GK UT WOS:000183708600002 PM 12576916 ER PT J AU Metz, DC Soffer, E Forsmark, CE Cryer, B Chey, W Bochenek, W Pisegna, JR AF Metz, DC Soffer, E Forsmark, CE Cryer, B Chey, W Bochenek, W Pisegna, JR TI Maintenance oral pantoprazole therapy is effective for patients with Zollinger-Ellison syndrome and idiopathic hypersecretion SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID GASTRIC-ACID HYPERSECRETION; OMEPRAZOLE; SAFETY; EFFICACY; LANSOPRAZOLE; DEFINITION; SECRETION; SURGERY AB OBJECTIVE: (1)Maintenance proton pump inhibitor (PPI) therapy is effective for gastric acid hypersecretory states, although data with pantoprazole are limited. The aim of this study was to evaluate the safety and efficacy of long term p.o. pantoprazole in individuals with hypersecretion. METHODS: All subjects had Zollinger-Ellison syndrome or idiopathic hypersecretion. Baseline acid output was measured in the presence of prior maintenance antisecretory therapy before pantoprazole exposure. The starting dose was 40 mg b.i.d. in most cases, and the dose was adjusted to document control within the first 2 wk of therapy. The maximal allowable dose was 240 mg daily. Acid output was measured on day 28 and then quarterly from month 3. The primary efficacy endpoint was documented control of acid secretion at 6 months, i.e., acid output in the last I h before the next dose of therapy of <10 mEq/h (<5 mEq/h in subjects with prior acid-reducing surgery). RESULTS: A total of 26 subjects had Zollinger-Ellison syndrome (six with multiple endocrine neoplasia syndrome type 1) and nine had idiopathic hypersecretion. Pre-enrollment therapy included omeprazole in 27 subjects and lansoprazole in eight, and 82.4% of subjects were controlled on their prior regimens. With upward dose titration, acid output was controlled in all subjects by day 10 and in all but two (6%) at the 6-month time point. Median acid secretion on therapy at 6 months was <2 mEq/h (mean 2.2 mEq/h; range 0-10.5 mEq/h) at a dose of 40 mg b.i.d for 24 subjects, 80 mg b.i.d. for seven subjects, and 120 mg b.i.d. for two subjects. During the course of the study, five subjects required doses of 240 mg daily. Pantoprazole was generally well tolerated. No cases of anterior optic ischemic neuropathy occurred. Five subjects died during follow-up, all because of events unrelated to the study drug. CONCLUSIONS: Maintenance p.o. pantoprazole therapy at a dose of 80-240 mg/day in divided doses was both effective and generally well tolerated for patients with Zollinger-Ellison syndrome and idiopathic hypersecretion. (Am J Gastroenterol 2003;98:301-307. (C) 2003 by Am. Coll. of Gastroenterology). C1 Univ Penn, Hlth Syst, Div Gastroenterol, Med Ctr, Philadelphia, PA 19104 USA. Wyeth Ayerst Res, Collegeville, PA USA. Univ Florida, Div Gastroenterol, Gainesville, FL USA. Vet Affairs Med Ctr, Div Gastroenterol, Dallas, TX USA. Rochester Inst Digest Dis & Sci, Rochester, NY USA. Univ Calif Los Angeles, Sch Med, Dept Med, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. RP Metz, DC (reprint author), Univ Penn, Hlth Syst, Div Gastroenterol, Med Ctr, Ravdin Bldg 3rd Floor,3400 Spruce St, Philadelphia, PA 19104 USA. NR 25 TC 16 Z9 17 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD FEB PY 2003 VL 98 IS 2 BP 301 EP 307 DI 10.1016/S0002-9270(02)05930-0 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 645RR UT WOS:000180992700018 PM 12591045 ER PT J AU Strate, LL Syngal, S AF Strate, LL Syngal, S TI Timing of colonoscopy: Impact on length of hospital stay in patients with acute lower intestinal bleeding SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID UPPER GASTROINTESTINAL HEMORRHAGE; URGENT COLONOSCOPY; DIVERTICULAR HEMORRHAGE; MANAGEMENT; DIAGNOSIS; ENDOSCOPY AB OBJECTIVE: Previous studies suggest that urgent colonoscopic evaluation of massive lower intestinal bleeding (LIB) can reduce hospital length of stay (LOS). We sought to determine if time to colonoscopy impacts hospital LOS in patients admitted with all sources and severities of acute LIB. METHODS: A total of 252 consecutive patients admitted to a tertiary care hospital with acute LIB were identified. Cox proportional hazards regression was used to determine independent predictors of hospital LOS. Time from admission to colonoscopy was analyzed as a time-varying covariate. RESULTS: A total of 144 patients (57%) underwent an inpatient colonoscopy: 14 were done in <12 h, 55 in 12-24 h, 46 in 24-48 h, and 29 in >48 h. After controlling for the other independent correlates, earlier colonoscopy was significantly associated with a shorter hospital LOS (hazards ratio = 2.02, 95% CI = 1.5-2.6, p < 0.0001). The absence of visible blood or active bleeding at the time of colonoscopy was also independently related to a shorter hospital LOS (hazards ratio = 1.5, 95% = CI 1.1-2.0, p = 0.01). CONCLUSIONS: Time to colonoscopy is an independent predictor of hospital LOS. In a wide spectrum of patients with LIB, this reduction in hospital LOS seems to be primarily related to improved diagnostic yield rather than therapeutic interventions. (Am J Gastroenterol 2003;98:317-322. (C) 2003 by Am. Coll. of Gastroenterology). C1 Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med,Dept Med,Div Gastroenterol, Boston, MA 02115 USA. RP Strate, LL (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU AHRQ HHS [HS00020]; NIDDK NIH HHS [5T32DK0753315] NR 20 TC 67 Z9 69 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD FEB PY 2003 VL 98 IS 2 BP 317 EP 322 DI 10.1016/S0002-9270(02)05900-2 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 645RR UT WOS:000180992700021 PM 12591048 ER PT J AU Ashton, CM Septimus, J Petersen, NJ Souchek, J Menke, TJ Collins, TC Wray, NP AF Ashton, CM Septimus, J Petersen, NJ Souchek, J Menke, TJ Collins, TC Wray, NP TI Healthcare use by veterans treated for diabetes mellitus in the Veterans Affairs medical care system SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID POPULATION; HOSPITALS; MORTALITY; OUTCOMES; ADULTS AB Objectives: To estimate the burden of comorbid conditions and to describe patterns of inpatient and outpatient service use by veterans with diabetes mellitus. Study Design: Retrospective cohort study of 33 481 veterans conducted by means of secondary analysis of Department of Veterans Affairs (VA) healthcare utilization databases. Patients and Methods: The cohort was constructed enrolling,all veterans treated in the VA medical care syste who had their initial VA hospitalization for diabetes mellitus between 1992 and 1997. To estimate the typical annual pattern of service use for diabetes mellitus, 1497 utilization rates per person-year were analyzed based on cohort members surviving into 1997. Data on comorbid conditions were obtained from outpatient and inpatient contacts. Results: The 3 most prevalent coexisting conditions were hypertension (73.4%), ischemic heart disease (35.2%), and alcohol or drug abuse disorders (29.5%). In 1997, the typical cohort member followed for 12 months had 6 primary care visits, 16 other visits for tests or consultations, and 1.3 unscheduled visits for emergency- or urgent care and spent approximately 8 days in the hospital. One-year survival was 94.0%. Conclusions: In the VA medical care system, beneficiaries with diabetes mellitus have an extremely heavy burden of comorbidities, face a significant risk of dying in a given year (approximately 6% in this population), and are heavy users of hospital and outpatient services. C1 VA Med Ctr, Houston, TX 77030 USA. Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Affiliated Hosp, Dept Internal Med, Houston, TX USA. RP Ashton, CM (reprint author), VA Med Ctr, 152,2002 Holcombe Blvd, Houston, TX 77030 USA. NR 22 TC 20 Z9 21 U1 2 U2 4 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD FEB PY 2003 VL 9 IS 2 BP 145 EP 150 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 644NA UT WOS:000180923200003 PM 12597602 ER PT J AU Ramonas, KM Freilich, BD AF Ramonas, KM Freilich, BD TI Iris abscess as an unusual presentation of endogenous Endophthalmitis in a patient with bacterial endocarditis SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To report the clinical findings and management of a case of endogenous endophthalmitis in a patient with bacterial endocarditis presenting with a septic metastasis to the iris. DESIGN: Observational case report. METHODS: Review of clinical findings and treatment. RESULTS: A 37-year-old intravenous drug user hospitalized with bacterial endocarditis secondary to methicillin-sensitive Staphylococcus aureus bacteremia presented with a painful red left eye, hypopyon, and iris abscess. Roth spots were noted in the fundus of the right eye. Aqueous culture was positive for methicillin-sensitive S aureus. The patient was treated with intravitreal, topical, and intravenous antibiotics. The hypopyon and iris abscess resolved within 2 weeks, and the patient achieved a final visual acuity of 20/25 in the left eye. CONCLUSIONS: Septic metastasis to the iris is a rare occurrence. To our knowledge this is the first reported case of an iris abscess secondary to bacterial endocarditis. (C) 2003 by Elsevier Science Inc. All rights reserved. C1 Bronx Vet Adm Med Ctr, Bronx, NY USA. RP Ramonas, KM (reprint author), CUNY Mt Sinai Sch Med, Dept Ophthalmol, 1 Gustave Levy Pl,Box 1183,Annenberg Bldg,22nd Fl, New York, NY 10029 USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD FEB PY 2003 VL 135 IS 2 BP 228 EP 229 DI 10.1016/S0002-9394(02)01935-9 PG 2 WC Ophthalmology SC Ophthalmology GA 640VV UT WOS:000180709400018 PM 12566031 ER PT J AU Hirakawa, S Hong, YK Harvey, N Schacht, V Matsuda, K Libermann, T Detmar, M AF Hirakawa, S Hong, YK Harvey, N Schacht, V Matsuda, K Libermann, T Detmar, M TI Identification of vascular lineage-specific genes by transcriptional profiling of isolated blood vascular and lymphatic endothelial cells SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID GROWTH-FACTOR-C; TUMOR LYMPHANGIOGENESIS; FACTOR RECEPTOR-3; BREAST-CANCER; VEGF-C; ANGIOGENESIS; PROMOTES; SKIN; EXPRESSION; PROX1 AB In mammals, the lymphatic vascular system develops by budding of lymphatic progenitor endothelial cells from embryonic veins to form a distinct network of draining vessels with important functions in the immune response and in cancer metastasis. However, the lineage-specific molecular characteristics of blood vascular versus lymphatic endothelium have remained poorly defined. We isolated lymphatic endothelial cells (LECs) and blood vascular endothelial cells (BVECs) by immunomagnetic isolation directly from human skin. Cultured LECs but not BVECs expressed the lymphatic markers Prox1 and LYVE-1 and formed LYVE-1-positive vascular tubes after implantation in vivo. Transcriptional profiling studies revealed increased expression of several extracellular matrix and adhesion molecules in BVECs, including versican, collagens, laminin, and N-cadherin, and of the growth factor receptors endoglin and vascular endothelial growth factor receptor-1/Fh-1. Differential immunostains of human skin confirmed the blood vessel-specific expression of these genes. During embryonic development, endoglin expression was gradually down-regulated on lymphatic endothelium whereas vascular endothelial growth factor receptor-1 was absent from lymphatics. We also identified several genes with specific expression in LECs. These results demonstrate that some lineage-specific genes are only expressed during distinct developmental stages and they identify new molecular markers for blood vascular and lymphatic endothelium with important implications for future studies of vascular development and function. C1 Massachusetts Gen Hosp, CBRC, Dept Dermatol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Beth Israel Deaconess Med Ctr, BIDMC Genom Ctr, Boston, MA USA. St Jude Childrens Res Hosp, Dept Genet, Memphis, TN USA. RP Detmar, M (reprint author), Massachusetts Gen Hosp, CBRC, Dept Dermatol, Bldg 149,13th St, Charlestown, MA 02129 USA. EM michael.detmar@cbrc2.mgh.harvard.edu RI Libermann, Towia/F-9866-2010; OI Libermann, Towia/0000-0002-4006-8179 FU NCI NIH HHS [CA69184, CA86410, CA91861, R01 CA069184, R01 CA086410] NR 42 TC 291 Z9 304 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD FEB PY 2003 VL 162 IS 2 BP 575 EP 586 DI 10.1016/S0002-9440(10)63851-5 PG 12 WC Pathology SC Pathology GA 638NL UT WOS:000180577100022 PM 12547715 ER PT J AU Beck, PL Rosenberg, IM Xavier, RJ Koh, T Wong, JF Podolsky, DK AF Beck, PL Rosenberg, IM Xavier, RJ Koh, T Wong, JF Podolsky, DK TI Transforming growth factor-beta mediates intestinal healing and susceptibility to injury in vitro and in vivo through epithelial cells SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; COLON-CANCER CELLS; TGF-BETA; TRANSGENIC MICE; II RECEPTOR; TARGETED DISRUPTION; COLORECTAL-CANCER; GENE-EXPRESSION; RAT COLON; DIFFERENTIATION AB In vitro studies suggest that transforming growth factor (TGF)-beta has potent effects on gastrointestinal mucosal integrity, wound repair, and neoplasia. However, the multiplicity of actions of this peptide on many different cell types confounds efforts to define the role of TGF-beta within the intestinal epithelium in vivo. To delineate these effects selective blockade of intestinal epithelial TGF-beta activity was undertaken through targeted expression of a dominant-negative (DN) TGF-beta RH to intestinal epithelial cells in vitro and in vivo. Stable intestinal epithelial cell (IEC)-6 lines overexpressing TGF-beta RII-DN (nucleotides-7 to 573) were established. Transgenic mice overexpressing TGF-beta RII-DN under the regulation of a modified liver fatty acid-binding promoter (LFABP-PTS4) were constructed. In vitro healing was assessed by wounding of confluent monolayers. Colitis was induced by the addition of dextran sodium sulfate (2.5 to 7.5% w/v) to their drinking water. Overexpression of TGF-beta RII-DN in intestinal epithelial cell-6 cells resulted in a marked reduction in cell migration and TGF-beta-stimulated wound healing in vitro. TGF-beta RII-DN transgenic mice did not exhibit baseline intestinal inflammation or changes in survival, body weight, epithelial cell proliferation, aberrant crypt foci, or tumor formation. TGF-beta RII-DN mice were markedly more susceptible to dextran sodium sulfate-induced colitis and exhibited impaired recovery after colonic injury. TGF-beta is required for intestinal mucosal healing and TGF-beta modulation of the intestinal epithelium plays a central role in determining susceptibillity to injury. C1 Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Gastrointestinal Unit, Boston, MA 02114 USA. Univ Calgary, Gastrointestinal Res Grp, Calgary, AB, Canada. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Gastrointestinal Unit, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK 41557, DK 43352, DK 53304, R01 DK041557, R37 DK041557] NR 38 TC 94 Z9 97 U1 0 U2 5 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 FEB PY 2003 VL 162 IS 2 BP 597 EP 608 DI 10.1016/S0002-9440(10)63853-9 PG 12 WC Pathology SC Pathology GA 638NL UT WOS:000180577100024 PM 12547717 ER PT J AU Lechner, A Habener, JF AF Lechner, A Habener, JF TI Stem/progenitor cells derived from adult tissues: potential for the treatment of diabetes mellitus SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Review DE pancreatic islets; liver oval cells; embryonic stem cells; nestin; insulin; islet-like clusters; beta-cell; transplantation ID GLUCAGON-LIKE PEPTIDE-1; INSULIN-SECRETING CELLS; PANCREATIC BETA-CELLS; EMBRYONIC STEM-CELLS; AR42J CELLS; IN-VITRO; DUODENAL HOMEOBOX-1; ENDOCRINE PANCREAS; MIXED CHIMERISM; ISLETS AB In view of the recent success in pancreatic islet transplantation, interest in treating diabetes by the delivery of insulin-producing beta-cells has been renewed. Because differentiated pancreatic beta-cells cannot be expanded significantly in vitro, beta-cell stem or progenitor cells are seen as a potential source for the preparation of transplantable insulin-producing tissue. In addition to embryonic stem (ES) cells, several potential adult islet/beta-cell progenitors, derived from pancreas, liver, and bone marrow, are being studied. To date, none of the candidate cells has been fully characterized or is clinically applicable, but pancreatic physiology makes the existence of one or more types of adult islet stem cells very likely. It also seems possible that pluripotential stem cells, derived from the bone marrow, contribute to adult islet neogenesis. In future studies, more stringent criteria should be met to clonally define adult islet/beta-cell progenitor cells. If this can be achieved, the utilization of these cells for the generation of insulin-producing beta-cells in vitro seems to be feasible in the near future. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Howard Hughes Med Inst, Mol Endocrinol Lab, Boston, MA 02114 USA. RP Habener, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Howard Hughes Med Inst, Mol Endocrinol Lab, 55 Fruit St,WEL 320, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-55365, DK-30834, DK-60125] NR 64 TC 63 Z9 71 U1 1 U2 4 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 FEB PY 2003 VL 284 IS 2 BP E259 EP E266 DI 10.1152/ajpendo.00393.2002 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 635LN UT WOS:000180400500002 PM 12531740 ER PT J AU Black, BJ McMahan, CA Masoro, EJ Ikeno, Y Katz, MS AF Black, BJ McMahan, CA Masoro, EJ Ikeno, Y Katz, MS TI Senescent terminal weight loss in the male F344 rat SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE caloric restriction; food intake; hypothalamic function ID FED AD-LIBITUM; FISCHER-344 RATS; NUTRITIONAL INFLUENCES; LONGEVITY; PROTEIN; DISEASE; GROWTH; MASS; LIFE AB Loss of weight, often of unknown cause and culminating in death, commonly occurs in humans at advanced ages. Rats that live to old ages, such as the Fischer 344 (F344) strain, also exhibit a terminal loss in body weight. A presently held hypothesis is that the terminal weight loss in the F344 rat model is due to reduced food intake because of an alteration in hypothalamic function resulting in early satiation. We report findings on terminal weight loss and food intake in male F344 rats fed ad libitum (AL group) or a life-prolonging dietary regimen in which caloric intake was restricted (DR group). Rats in both dietary groups that did not exhibit a terminal weight loss died at younger ages than those exhibiting the loss. Terminal weight loss in the AL group was not associated with decreased food intake; indeed, half of the rats in this group had an increased food intake during the period of terminal weight loss. This finding is not in accord with the presently held hypothesis. In the DR group, terminal weight loss was associated with reduced food intake. Pathology (renal disease and neoplasms) did not explain the presence or absence of the association between reduced food intake and weight loss in either dietary group. The duration of the period of terminal weight loss was similar for the AL and DR groups. Apparently, restricting calories delays the occurrence but does not affect the duration of senescent terminal weight loss. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Geriatr & Gerontol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Res Serv, Audie L Murphy Div, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Audie L Murphy Div, San Antonio, TX 78229 USA. RP Katz, MS (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Geriatr & Gerontol, Mail Code 7875,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NIA NIH HHS [AG-01188, AG-13319] NR 33 TC 15 Z9 15 U1 1 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 FEB PY 2003 VL 284 IS 2 BP R336 EP R342 DI 10.1152/ajpregu.00640.2001 PG 7 WC Physiology SC Physiology GA 635LP UT WOS:000180400700009 PM 12388451 ER PT J AU Fernandez-Estivariz, C Gu, LH Gu, L Jonas, CR Wallace, TM Pascal, RR Devaney, KL Farrell, CL Jones, DP Podolsky, DK Ziegler, TR AF Fernandez-Estivariz, C Gu, LH Gu, L Jonas, CR Wallace, TM Pascal, RR Devaney, KL Farrell, CL Jones, DP Podolsky, DK Ziegler, TR TI Trefoil peptide expression and goblet cell number in rat intestine: effects of KGF and fasting-refeeding SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE colon; intestinal mucosa; keratinocyte growth factor ID KERATINOCYTE GROWTH-FACTOR; HUMAN SPASMOLYTIC POLYPEPTIDE; EPITHELIAL-CELLS; BARRIER FUNCTION; INJURY; GUT; FAMILY; COLON; MICE; PS2 AB The trefoil factor family peptides TFF1, TFF2, and TFF3 are important for gut mucosal protection and restitution. Keratinocyte growth factor (KGF) stimulates proliferation and differentiation of epithelial cells with potent effects on goblet cells. To investigate interactions between food intake and KGF, rats were fed ad libitum (control), fasted for 72 h, or fasted for 72 h and then refed for 72 h with or without KGF (3 mg.kg(-1).day(-1)). With fasting, goblet cell number in duodenum increased, TFF3 mRNA in duodenum and jejunum decreased, and TFF3 protein did not change or increased. KGF during fasting stimulated colonic growth, normalized TFF3 mRNA in duodenum and jejunum, and broadly upregulated gut goblet cell number and TFF3 protein expression. With fasting-refeeding, KGF increased small bowel and colonic mucosal growth, goblet cell number, and TFF3 protein but had variable effects on TFF3 mRNA. KGF induced TFF2 mRNA and protein in duodenum and jejunum with both nutritional regimens. We conclude that nutrient availability modifies rat intestinal goblet cell number, TFF3 mRNA, and the gut-trophic effects of KGF in a region-specific manner. KGF enhances TFF2 expression in proximal small bowel and increases goblet cell number and TFF3 protein content throughout the intestine independent of food intake. C1 Emory Univ, Sch Med, Dept Med, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA. Emory Univ, Nutr & Hlth Sci Program, Atlanta, GA 30322 USA. Amgen Inc, Dept Pathol, Thousand Oaks, CA 91320 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02115 USA. RP Ziegler, TR (reprint author), Emory Univ Hosp, Gen Clin Res Ctr, Suite GG-23,1364 Clifton Rd, Atlanta, GA 30322 USA. FU NCRR NIH HHS [RR-00039]; NIDDK NIH HHS [DK-43351, DK-46906, DK-55850] NR 49 TC 34 Z9 34 U1 0 U2 1 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 FEB PY 2003 VL 284 IS 2 BP R564 EP R573 DI 10.1152/ajpregu.00428.2002 PG 10 WC Physiology SC Physiology GA 635LP UT WOS:000180400700038 PM 12388439 ER PT J AU Sultzer, DL Brown, CV Mandelkern, MA Mahler, ME Chen, ST Cummings, JL AF Sultzer, DL Brown, CV Mandelkern, MA Mahler, ME Chen, ST Cummings, JL TI Delusional thoughts and regional frontal/temporal cortex metabolism in Alzheimer's disease SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; NEUROBEHAVIORAL RATING-SCALE; CEREBRAL GLUCOSE-UTILIZATION; PSYCHIATRIC-SYMPTOMS; PSYCHOSIS; DEMENTIA; SPECT; MISIDENTIFICATION; PATHOGENESIS; RELIABILITY AB Objective: Delusional thoughts are common in patients with Alzheimer's disease and contribute prominently to morbidity. The pathophysiologic underpinnings for delusions in Alzheimer's disease are not well understood. in this study the authors examined the relationship between delusional thoughts and regional cortical metabolism in patients with Alzheimer's disease. Method: Twenty-five patients with probable Alzheimer's disease were include. None was taking psychotropic medication. Severity of delusions and other neuropsychiatric symptoms was assessed by using a semistructured interview and the Neurobehavioral Rating Scale just before the imaging procedure. [F-18]Fluorodeoxyglucose positron emission tomography was used to measure resting cerebral glucose metabolic rates in the cortical lobes and in anatomically defined subregions of the frontal and temporal cortexes. Results: A linear regression model, controlling for the effects of cognitive deficits, revealed a significant relationship between severity of delusional thought and the metabolic rates in three frontal regions: the right superior dorsolateral frontal cortex (Brodmann's area 8), the right inferior frontal pole (Brodmann's area 10), and the right lateral orbitofrontal region (Brodmann's area 47). Bivariate partial correlation analysis indicated that severity of delusions was associated with hypometabolism in additional prefrontal and anterior cingulate regions. Robust relationships with metabolism in regions of the temporal cortex were not apparent. Conclusions: Dysmetabolism in specific regions of the right prefrontal cortex may be associated with delusional thought in Alzheimer's disease. Delusions appear to reflect the pathophysiologic state of particular cortical regions. Activity across distributed neuronal networks and the specific content of delusional thoughts may modulate these relationships. C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Sultzer, DL (reprint author), W Los Angeles VA Healthcare Ctr, 3 South,116AF,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIA NIH HHS [AG-16057]; NIMH NIH HHS [MH-56031] NR 56 TC 105 Z9 106 U1 2 U2 7 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2003 VL 160 IS 2 BP 341 EP 349 DI 10.1176/appi.ajp.160.2.341 PG 9 WC Psychiatry SC Psychiatry GA 642DE UT WOS:000180788300020 PM 12562582 ER PT J AU Raskind, MA Peskind, ER Kanter, ED Petrie, EC Radant, A Thompson, CE Dobie, DJ Hoff, D Rein, RJ Straits-Troster, K Thomas, RG McFall, MM AF Raskind, MA Peskind, ER Kanter, ED Petrie, EC Radant, A Thompson, CE Dobie, DJ Hoff, D Rein, RJ Straits-Troster, K Thomas, RG McFall, MM TI Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: A placebo-controlled study SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER AB Objective: Prazosin is a centrally active at adrenergic antagonist. The authors' goal was to evaluate prazosin efficacy for nightmares, sleep disturbance, and overall posttraumatic stress disorder (PTSD) in combat veterans. Method: Ten Vietnam combat veterans with chronic PTSD and severe trauma-related nightmares each received prazosin and placebo in a 20-week double-blind crossover protocol. Results: Prazosin (mean dose=9.5 mg/day at bedtime, SD=0.5) was superior to placebo for the three primary outcome measures: scores on the 1) recurrent distressing dreams item and the 2) difficulty falling/staying asleep item of the Clinician-Administered PTSD Scale and 3) change in overall PTSD severity and functional status according to the Clinical Global Impression of change. Total score and symptom cluster scores for reexperiencing, avoidance/numbing, and hyperarousal,on the Clinician-Administered PTSD Scale also were significantly more improved in the prazosin condition, and prazosin was well tolerated. Conclusions: These data support the efficacy of prazosin for nightmares, sleep disturbance, and other PTSD symptoms. C1 VA Puget Sound Hlth Care Syst, NW Network VISN 20, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Calif San Diego, Dept Family Med & Neurosci, Div Biostat, San Diego, CA 92103 USA. RP Raskind, MA (reprint author), VA Puget Sound Hlth Care Syst, NW Network VISN 20, Mental Illness Res Educ & Clin Ctr, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 15 TC 296 Z9 301 U1 4 U2 20 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD FEB PY 2003 VL 160 IS 2 BP 371 EP 373 DI 10.1176/appi.ajp.160.2.371 PG 3 WC Psychiatry SC Psychiatry GA 642DE UT WOS:000180788300026 PM 12562588 ER PT J AU Tobin, MJ AF Tobin, MJ TI Critical care medicine in AJRCCM 2002 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Div Pulm & Crit Care Med, Chicago, IL 60611 USA. RP Tobin, MJ (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Route 111N, Hines, IL 60141 USA. NR 92 TC 2 Z9 2 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 FEB 1 PY 2003 VL 167 IS 3 BP 294 EP 305 DI 10.1164/rccm.2212004 PG 12 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 640EZ UT WOS:000180676400004 PM 12554619 ER PT J AU Tobin, MJ AF Tobin, MJ TI Sleep-disordered breathing, control of breathing, respiratory muscles, and pulmonary function testing in AJRCCM 2002 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Div Pulm & Crit Care Med, Chicago, IL 60611 USA. RP Tobin, MJ (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Route 111N, Hines, IL 60141 USA. NR 93 TC 2 Z9 2 U1 0 U2 1 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 FEB 1 PY 2003 VL 167 IS 3 BP 306 EP 318 DI 10.1164/rccm.2212006 PG 13 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 640EZ UT WOS:000180676400005 PM 12554620 ER PT J AU Tobin, MJ AF Tobin, MJ TI Asthma, airway biology, and nasal disorders in AJRCCM 2002 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Div Pulm & Crit Care Med, Chicago, IL 60611 USA. RP Tobin, MJ (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Route 111N, Hines, IL 60141 USA. NR 113 TC 3 Z9 3 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 FEB 1 PY 2003 VL 167 IS 3 BP 319 EP 332 DI 10.1164/rccm.2212007 PG 14 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 640EZ UT WOS:000180676400006 PM 12554621 ER PT J AU Tobin, MJ AF Tobin, MJ TI Pediatrics, surfactant, and cystic fibrosis in AJRCCM 2002 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Div Pulm & Crit Care Med, Chicago, IL 60611 USA. RP Tobin, MJ (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Route 111N, Hines, IL 60141 USA. NR 84 TC 0 Z9 2 U1 3 U2 5 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 FEB 1 PY 2003 VL 167 IS 3 BP 333 EP 344 DI 10.1164/rccm.2212005 PG 12 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 640EZ UT WOS:000180676400007 PM 12554622 ER PT J AU Tobin, MJ AF Tobin, MJ TI Tuberculosis, lung infections, interstitial lung disease, and journalology in AJRCCM 2002 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Div Pulm & Crit Care Med, Chicago, IL 60611 USA. RP Tobin, MJ (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Route 111N, Hines, IL 60141 USA. NR 37 TC 4 Z9 4 U1 1 U2 1 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 FEB 1 PY 2003 VL 167 IS 3 BP 345 EP 355 DI 10.1164/rccm.2212002 PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 640EZ UT WOS:000180676400008 PM 12554623 ER PT J AU Tobin, MJ AF Tobin, MJ TI Chronic obstructive pulmonary disease, pollution, pulmonary vascular disease, transplantation, pleural disease, and lung cancer in AJRCCM 2002 SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Div Pulm & Crit Care Med, Chicago, IL 60611 USA. RP Tobin, MJ (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, ROute 111N, Hines, IL 60141 USA. NR 98 TC 3 Z9 10 U1 0 U2 1 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 FEB 1 PY 2003 VL 167 IS 3 BP 356 EP 370 DI 10.1164/rccm.2212003 PG 15 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 640EZ UT WOS:000180676400009 PM 12554624 ER PT J AU Poussaint, TY Jaramillo, D Chang, YC Korf, B AF Poussaint, TY Jaramillo, D Chang, YC Korf, B TI Original report - Interobserver reproducibility of volumetric MR imaging measurements of plexiform neurofibromas SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article AB OBJECTIVE. This article validates the reproducibility of MR imaging volumetric measurements for evaluating the growth of plexiform neurofibromas in neurofibromatosis type 1. CONCLUSION. Volumetric measurements of plexiform neurofibromas in neurofibromatosis I are reproducible. C1 Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Partners Ctr Genet & Geonomics, Boston, MA 02115 USA. RP Poussaint, TY (reprint author), Childrens Hosp, Dept Radiol, 300 Longwood Ave, Boston, MA 02115 USA. NR 9 TC 23 Z9 23 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 2003 VL 180 IS 2 BP 419 EP 423 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 641PD UT WOS:000180753200024 PM 12540445 ER PT J AU Wittram, C Fischman, AJ Mark, E Ko, J Shepard, JAO AF Wittram, C Fischman, AJ Mark, E Ko, J Shepard, JAO TI Original report - Thymic enlargement and FDG uptake in three patients: CT and FDG positron emission tomography correlated with pathology SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CELL LUNG-CANCER; MYASTHENIA-GRAVIS; PET; CHEMOTHERAPY; THYMECTOMY AB OBJECTIVE. Our purpose was to describe three adult patients in whom we found increased thymic uptake of FDG on positron emission tomography and thymic enlargement with convex lateral margins on CT. Subsequent biopsy or resection showed normal thymic tissue. CONCLUSION. In three adults, we found a physiologic uptake of FDG by the thymus with standardized uptake values in the range of thymic neoplasia. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NYU, Dept Radiol, New York, NY 10016 USA. RP Wittram, C (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 12 TC 20 Z9 20 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 2003 VL 180 IS 2 BP 519 EP 522 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 641PD UT WOS:000180753200043 PM 12540464 ER PT J AU Barbareschi, M Murer, B Colby, TV Chilosi, M Macri, E Loda, M Doglioni, C AF Barbareschi, M Murer, B Colby, TV Chilosi, M Macri, E Loda, M Doglioni, C TI CDX-2 homeobox gene expression is a reliable marker of colorectal adenocarcinoma metastases to the lungs SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the US-Canada-Academy-of-Pathology CY FEB, 2002 CL CHICAGO, ILLINOIS SP US Canada Acad Pathol DE CDX-2; colorectal neoplasm; lung; metastases; immunohistochemistry ID THYROID TRANSCRIPTION FACTOR; FACTOR-I; IMMUNOHISTOCHEMICAL MARKER; PULMONARY ADENOCARCINOMAS; CARCINOMAS; CYTOKERATIN-20; FEATURES; SURVIVAL; COLON AB Lung metastases from colorectal carcinomas (CRC) can be resected with improved survival. The distinction between primary lung adenocarcinomas and metastases from CRC may sometimes be difficult, especially on cytologic specimens or small bronchoscopic biopsies. lmmunohistochemistry may be of help in this setting: available markers include TTF-1 and SP-A, which are markers of lung origin, whereas there are no good markers of intestinal origin, besides cytokeratin 7 and 20 coexpression pattern, which is not very specific. The nuclear CDX-2 transcription factor, which is the product of a homeobox gene necessary for intestinal organogenesis, is expressed in normal colonic epithelia and most colorectal adenocarcinomas, and could potentially be of diagnostic usefulness. Our aim was to investigate CDX-2 immunohistochemical expression using a new monoclonal antibody and to verify if CDX-2 can be a reliable marker to identify the colorectal origin of lung metastases. CDX-2 expression was evaluated in formalin-fixed, paraffin-embedded samples of normal adult human tissues (50 samples) and in 299 surgically resected carcinomas of different origins, including 125 non-lung adenocarcinomas, 117 primary lung tumors, 5 mesotheliomas, and 52 adenocarcinomas metastatic to the lung. CDX-2 was also evaluated on a series of 20 bioptic and 10 cytologic specimen., (5 cases of colorectal metastases to the lung, 5 cases of metastases from other organs, and 10 primary lung adenocarcinomas). In normal tissues CDX-2 immunoreactivity was observed only in ileal and colorectal epithelia. CDX-2 was expressed in almost all primary and metastatic CRC (88 of 90) and was never observed in primary lung tumors. CDX-2 was also expressed in a limited group of adenocarcinomas of other sites 4(gastric, bilicipancreatic, and mucinous ovarian adenocarcinomas). CDX-2 could be easily detected in all bioptic and cytologic samples of CRC metastases. CDX-2 is a reliable, specific, and sensitive immunohistochemical marker of normal and neoplastic intestinal epithelium. CDX-2 can be easily applied to routine histologic and cytologic material and is therefore a useful marker in the differential diagnosis of primary versus metastatic adenocarcinomas in the lung, and among metastases from an unknown primary, supports intestinal origin. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Pathol, Boston, MA USA. Mayo Clin Scottsdale, Dept Pathol & Lab Med, Scottsdale, AZ USA. Univ Verona, Dept Pathol, I-37100 Verona, Italy. Osped San Martino Genova, Dept Pathol, I-32100 Belluno, Italy. Umberto 1 Hosp Venice Mestre, Dept Pathol, Mestre, Italy. Santa Chiara Hosp, Dept Pathol, Trent, Italy. RP Doglioni, C (reprint author), Osped San Martino Genova, Dept Pathol, I-32100 Belluno, Italy. OI DOGLIONI, Claudio/0000-0002-4969-5216 NR 23 TC 113 Z9 117 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD FEB PY 2003 VL 27 IS 2 BP 141 EP 149 DI 10.1097/00000478-200302000-00001 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 640RE UT WOS:000180701100001 PM 12548159 ER PT J AU Fishman, JA AF Fishman, JA TI BK nephropathy: What is the role of antiviral therapy? SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material ID TRANSPLANT RECIPIENTS; VIRUS C1 Massachusetts Gen Hosp, Div Infect Dis, Transplant & Immunocompromised Host Serv, Boston, MA 02114 USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Transplant & Immunocompromised Host Serv, 55 Fruit St,GRJ 504, Boston, MA 02114 USA. NR 7 TC 12 Z9 13 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD FEB PY 2003 VL 3 IS 2 BP 99 EP 100 DI 10.1034/j.1600-6143.2003.30201.x PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 653UD UT WOS:000181454700001 PM 12614295 ER PT J AU Alston, TA AF Alston, TA TI The contributions of A. W. Hofmann SO ANESTHESIA AND ANALGESIA LA English DT Article C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Alston, TA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. NR 22 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD FEB PY 2003 VL 96 IS 2 BP 622 EP 625 DI 10.1213/01.ANE.0000044661.76667.57 PG 4 WC Anesthesiology SC Anesthesiology GA 638YV UT WOS:000180601400055 PM 12538223 ER PT J AU Canellos, GP Gollub, J Neuberg, D Mauch, P Shulman, LN AF Canellos, GP Gollub, J Neuberg, D Mauch, P Shulman, LN TI Primary systemic treatment of advanced Hodgkin's disease with EVA (etoposide, vinblastine, doxorubicin): 10-year follow-up SO ANNALS OF ONCOLOGY LA English DT Article DE EVA; Hodgkin's disease chemotherapy ID FIRST-LINE TREATMENT; HYBRID CHEMOTHERAPY; PULMONARY-FUNCTION; COOPERATIVE GROUP; ABVD; MOPP; REGIMEN; TRIAL; PROCARBAZINE; IRRADIATION AB Background: The most commonly used regimen for the treatment of advanced Hodgkin's disease (HD) is ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine). Two of these components, bleomycin and dacarbazine, have defined toxicities such as pulmonary fibrosis and nausea/vomiting, and also uncertain single-drug activity. The EVA regimen (etoposide, vinblastine, doxorubicin) is an attempt to substitute a known active agent, etoposide, for bleomycin and dacarbazine. Patients and methods: A series of 51 patients with advanced HD without prior systemic therapy were treated. The series included 12 stage II patients with bulky (>10 cm) mediastinal tumors, 10 of whom received complementary radiation therapy. The remaining patients received EVA only. Response, duration of response, survival, toxicity and the efficacy of salvage therapy were evaluated in all patients. The median follow-up time was 111 months and permitted an assessment of the long-term effects of treatment and natural history of a cohort of treated patients. Results: EVA achieved a complete response (or clinical complete response) in 48/51 patients (94%). Of these 48 responders, 16 relapsed in a median of 11 months (range 3-48 months). In follow-up, 32/51 patients had no evidence of relapsed HD, although three died from other causes (two from vascular events and one from large cell lymphoma), resulting in progression-free survival for the entire group of 57% at 111 months. Eight of the 16 were alive and free from disease at follow-up at 111 months. In the entire series, only seven patients (14%) died of HD. 37 patients (73%) continued free from disease. There was no pulmonary toxicity. Conclusions: The EVA regimen appears to have an overall survival (OS) outcome comparable to ABVD, but without the lung toxicity. The high salvage rate of second-line therapy, in most instances at conventional dosage, suggests an absence of cross-re si stance to alkylating agents in patients treated with EVA. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Canellos, GP (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 28 TC 15 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD FEB PY 2003 VL 14 IS 2 BP 268 EP 272 DI 10.1093/annonc/mdg076 PG 5 WC Oncology SC Oncology GA 670KJ UT WOS:000182406600015 PM 12562654 ER PT J AU Gross, RD Mahlmann, J Grayhack, JP AF Gross, RD Mahlmann, J Grayhack, JP TI Physiologic effects of open and closed tracheostomy tubes on the pharyngeal swallow SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE aspiration; deglutition; penetration; subglottic air pressure; tracheostomy ID SPINAL STRETCH REFLEX; PASSY-MUIR VALVE; ADAPTIVE PLASTICITY; LARYNGEAL CLOSURE; SPEAKING VALVE; NECK-CANCER; ASPIRATION; COORDINATION; TRACHEOTOMY; ADULTS AB Studies linking aspiration and dysphagia to an open tracheostomy tube exemplify the possibility that the larynx may have an influence on oropharyngeal swallow function. Experiments addressing the effects of tracheostomy tube occlusion during the swallow have looked at the presence and severity of aspiration, but few have included measurements that capture the changes in swallowing physiology. Also, hypotheses for the importance of near-normal subglottic air pressure during the swallow have not been offered to date. As such, the aim of this study was to compare the depth of laryngeal penetration, bolus speed, and duration of pharyngeal muscle contraction during the swallow in individuals with tracheostomy tubes while their tubes were open and closed. The results of this series of experiments indicate that within the same tracheostomized patient, pharyngeal swallowing physiology is measurably different in the absence of subglottic air pressure (open tube) as compared to the closed tube condition. C1 VA Pittsburgh Healthcare Syst, Dept Audiol & Speech Pathol, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA USA. RP Gross, RD (reprint author), VA Pittsburgh Healthcare Syst, Dept Audiol & Speech Pathol, Univ Dr C, Pittsburgh, PA 15240 USA. NR 54 TC 22 Z9 24 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 FEB PY 2003 VL 112 IS 2 BP 143 EP 152 PG 10 WC Otorhinolaryngology SC Otorhinolaryngology GA 644VV UT WOS:000180941400007 PM 12597287 ER PT J AU Zeitels, SM Mauri, M Dailey, SH AF Zeitels, SM Mauri, M Dailey, SH TI Medialization laryngoplasty with Gore-Tex for voice restoration secondary to glottal incompetence: Indications and observations SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE arytenoid dislocation; atrophy; cancer reconstruction; dysphonia; glottal incompetence; Gore-Tex; hoarseness; medialization laryngoplasty; paralysis; paresis; sulcus vocalis; thyroplasty; trauma defect ID ARYTENOID ADDUCTION; CRICOTHYROID SUBLUXATION; THYROPLASTY; EXPERIENCE; SURGERY AB Gore-Tex has been used as an effective implant for medialization laryngoplasty in the management of paralytic dysphonia; however, reporting of large patient cohorts has been limited. Furthermore, the use of Gore-Tex in the treatment of glottal incompetence secondary to soft tissue defects has not yet been described. Finally, a number of the procedural nuances of using Gore-Tex have not been elucidated. A prospective investigation was done on 142 patients who underwent 152 Gore-Tex medialization laryngoplasties in 183 vocal folds from December 1997 to March 2002. The primary diagnoses prompting the 152 procedures were paralysis in 94, paresis in 18, cancer reconstruction in 14, sulcus vocalis in 6, atrophy in 3, trauma defect in 5, arytenoid dislocation in 3, bilateral paralysis in 3, bilateral paresis in 1, parkinsonism in 4, and neurologic aerodynamic dissociation in 1. One patient who underwent reconstruction of a complex cancer defect required endoscopic removal of the Gore-Tex because of persistent granulation. Clinical observations reveal that Gore-Tex is a versatile implant that is ideally suited for phonosurgical reconstruction of aerodynamic glottal incompetence secondary to a variety of causes. Gore-Tex was especially useful for medialization of complex anatomic soft tissue defects such as those resulting from cancer resection, trauma, atrophy, and sulcus vocalis. There was superior ease in handling, placement, and in vivo adjustability. C1 Massachusetts Eye & Ear Infirm, Div Laryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otology & Laryngol, Boston, MA USA. RP Zeitels, SM (reprint author), Massachusetts Eye & Ear Infirm, Div Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 22 TC 45 Z9 47 U1 0 U2 1 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 FEB PY 2003 VL 112 IS 2 BP 180 EP 184 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 644VV UT WOS:000180941400013 PM 12597293 ER PT J AU Hall, P Zhou, XH AF Hall, P Zhou, XH TI Nonparametric estimation of component distributions in a multivariate mixture SO ANNALS OF STATISTICS LA English DT Article DE biased bootstrap; distribution estimation; empirical likelihood; identification; latent model; multivariate analysis; nonparametric maximum likelihood; root-n consistency ID LATENT CLASS ANALYSIS; DIAGNOSTIC-TESTS; MAXIMUM-LIKELIHOOD; PROPORTIONS; MODELS; GEOMETRY AB Suppose k-variate data are drawn from a mixture of two distributions, each having independent components. It is desired to estimate the univariate marginal distributions in each of the products, as well as the mixing proportion. This is the setting of two-class, fully parametrized latent models that has been proposed for estimating the distributions of medical test results when disease status is unavailable. The problem is one of inference in a mixture of distributions without training data, and until now it has been tackled only in a fully parametric setting. We investigate the possibility of using nonparametric methods. Of course, when k = 1 the problem is not identifiable from a nonparametric viewpoint. We show that the problem is "almost" identifiable when k = 2; there, the set of all possible representations can be expressed, in terms of any one of those representations, as a two-parameter family. Furthermore, it is proved that when k greater than or equal to 3 the problem is nonparametrically identifiable under particularly mild regularity conditions. In this case we introduce root-n consistent nonparametric estimators of the 2k univariate marginal distributions and the mixing proportion. Finite-sample and asymptotic properties of the estimators are described. C1 Australian Natl Univ, Ctr Math Applicat, Canberra, ACT 0200, Australia. Univ Washington, NW HRS&D Ctr Excellence, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Hall, P (reprint author), Australian Natl Univ, Ctr Math Applicat, Canberra, ACT 0200, Australia. NR 36 TC 72 Z9 73 U1 1 U2 6 PU INST MATHEMATICAL STATISTICS PI BEACHWOOD PA PO BOX 22718, BEACHWOOD, OH 44122 USA SN 0090-5364 J9 ANN STAT JI Ann. Stat. PD FEB PY 2003 VL 31 IS 1 BP 201 EP 224 PG 24 WC Statistics & Probability SC Mathematics GA 655VW UT WOS:000181574200007 ER PT J AU Gaissert, HA Roper, CL Patterson, GA Grillo, HC AF Gaissert, HA Roper, CL Patterson, GA Grillo, HC TI Infectious necrotizing esophagitis: Outcome after medical and surgical intervention SO ANNALS OF THORACIC SURGERY LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; TRACHEOESOPHAGEAL FISTULA; RISK-FACTORS; MARROW TRANSPLANTATION; CANDIDA ESOPHAGITIS; INVASIVE CANDIDA; PERFORATION; PATIENT; AIDS; DISEASE AB Background. Immunodeficiency predisposes to invasive esophageal infections. The treatment of perforation, respiratory fistula, and necrosis due to transmural esophageal infection is guided by anecdote. We wish to determine treatment and outcome of local complications of necrotizing esophagitis. Methods. We report our experience over a 7-year period and review published reports since 1976. We treated 4 patients and found 21 reported patients with perforation (11/25), fistula (8/25), and necrosis (6/25) at a mean age of 35 years. Twenty-one patients were immunodeficient (84%) due to acquired immunodeficiency syndrome in 8, acute leukemia in 6, renal transplant in 3, diabetes mellitus, renal failure, and corticosteroids in 1 each. Pathogenic organisms were fungal in 15 cases, viral in 7, and bacterial in 7. Results. Treatment consisted of antibiotic therapy in 13 patients and surgical intervention combined with antibi-otic therapy in 12: esophagectomy in 6, esophageal stenting and drainage in 2, drainage alone in 2, and salivary diversion in 2. Overall mortality was 48% (12/25). Mortality without surgical intervention was 90% (9/10) and with surgical intervention 27% (3/11). One of 6 patients undergoing esophagectomy (17%) died. The difference in mortality was due to sepsis, which was the cause of death in 8 patients treated with medical intervention and only 1 treated with surgical intervention. Conclusions. Local complications of necrotizing esophagitis have a high mortality due to sepsis. Surgical intervention, in particular esophagectomy, controls sepsis in published case reports and should be considered in selected patients. Further study is required to determine the true prevalence of these complications and the outcome of intervention. (C) 2003 by The Society of Thoracic Surgeons. C1 Harvard Univ, Thorac Surg Unit, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Washington Univ, Barnes Jewish Hosp, Thorac Surg Unit, St Louis, MO USA. RP Gaissert, HA (reprint author), Harvard Univ, Thorac Surg Unit, Sch Med, Massachusetts Gen Hosp, Blake 1570,Fruit St, Boston, MA 02114 USA. NR 33 TC 12 Z9 12 U1 0 U2 3 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 FEB PY 2003 VL 75 IS 2 BP 342 EP 347 AR PII S0003-4975(02)04343-6 DI 10.1016/S0003-4975(02)04343-6 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 644PA UT WOS:000180926000006 PM 12607636 ER PT J AU Grillo, HC AF Grillo, HC TI Development of tracheal surgery: A historical review. Part 1: Techniques of tracheal surgery SO ANNALS OF THORACIC SURGERY LA English DT Review ID BRONCHOGENIC-CARCINOMA; SLEEVE PNEUMONECTOMY; SUBGLOTTIC LARYNGEAL; CRICOID RESECTION; STENOSIS; RECONSTRUCTION; ANASTOMOSIS; MANAGEMENT; TUMORS; CARINA C1 Harvard Univ, Sch Med, Dept Surg, Boston, MA USA. RP Grillo, HC (reprint author), Massachusetts Gen Hosp, Div Gen Thorac Surg, Blake 1570,55 Fruit St, Boston, MA 02114 USA. NR 80 TC 49 Z9 56 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD FEB PY 2003 VL 75 IS 2 BP 610 EP 619 AR PII S0003-4975(02)04108-5 DI 10.1016/S0003-4975(02)04108-5 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 644PA UT WOS:000180926000077 PM 12607695 ER PT J AU Keel, PK Dorer, DJ Eddy, KT Franko, D Charatan, DL Herzog, DB AF Keel, PK Dorer, DJ Eddy, KT Franko, D Charatan, DL Herzog, DB TI Predictors of mortality in eating disorders SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT International Conference on Eating Disorders CY APR 27, 2002 CL BOSTON, MASSACHUSETTS ID LONG-TERM MORTALITY; ANOREXIA-NERVOSA; FOLLOW-UP; PSYCHIATRIC COMORBIDITY; BULIMIA-NERVOSA AB Background: Anorexia nervosa, but not bulimia nervosa, has one of the highest mortality rates among psychiatric disorders. However, potential predictors of mortality, such as comorbid psychiatric illnesses, remain unclear. We sought to determine mortality ratios and predictors of fatal outcome in women diagnosed as having anorexia or bulimia nervosa. Methods: Women (N = 246) diagnosed as having either DSM-IV anorexia nervosa (n = 136) or bulimia nervosa (n = 110) between January 1, 1987, and December 31, 1991, participated in a prospective longitudinal study. Vital status was determined by ongoing contact and a National Death Index search as of December 1998 (overall ascertainment, 99.8%) and telephone contact as of October 2000 (ascertainment, 95.0%). Results: Eleven women died. Standardized mortality ratios were elevated for all causes of mortality (11.6; 95% confidence interval, 5.5-21.3) and suicide (56.9; 95% confidence interval, 15.3-145.7) in anorexia nervosa but not for death (1.3; 95% confidence interval, 0.0-7.2) in bulimia nervosa. Predictors of mortality in anorexia nervosa included severity of alcohol use disorder during follow-up (P<.001). Hospitalization for an affective disorder before baseline assessment seemed to protect women from a fatal outcome (P<.001). Conclusions: Physicians treating patients with anorexia nervosa should carefully assess patterns of alcohol use during the course of care because one third of women who had alcoholism and died had no history of alcohol use disorder at intake. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Northeastern Univ, Dept Counseling Psychol, Boston, MA 02115 USA. Yeshiva Univ, Ferkauf Grad Sch Psychol, New York, NY 10033 USA. RP Keel, PK (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St,1320 William James Hall, Cambridge, MA 02138 USA. FU NIMH NIH HHS [R01 MH 38333-06A4, R01 MH 61836-02] NR 28 TC 178 Z9 184 U1 2 U2 13 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 FEB PY 2003 VL 60 IS 2 BP 179 EP 183 DI 10.1001/archpsyc.60.2.179 PG 5 WC Psychiatry SC Psychiatry GA 643RA UT WOS:000180873200008 PM 12578435 ER PT J AU Mulsant, BH Pollock, BG Kirshner, M Shen, CY Dodge, H Ganguli, M AF Mulsant, BH Pollock, BG Kirshner, M Shen, CY Dodge, H Ganguli, M TI Serum anticholinergic activity in a community-based sample of older adults - Relationship with cognitive performance SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 15th Annual Meeting of the American-Association-for-Geriatric-Psychiatry CY FEB 24-27, 2002 CL ORLANDO, FLORIDA SP Amer Assoc Geriatr Psychiat ID ELDERLY MEDICAL PATIENTS; MOVIES PROJECT; CHRONIC-SCHIZOPHRENIA; DEPRESSED-PATIENTS; RURAL-POPULATION; ACUTE ILLNESS; DELIRIUM; DRUGS; ASSOCIATION; IMPAIRMENT AB Background: Serum anticholinergic activity (SAA), as measured by a radioreceptor assay, quantifies a person's overall anticholinergic burden caused by all drugs and their metabolites. In several small geriatric patient groups, SAA has been associated with cognitive impairment or frank delirium. To our knowledge, there has not yet been any systematic study of the prevalence of SAA and its effect on cognition in a community-based population. Methods: Serum anticholinergic activity was measured in 201 subjects who were randomly selected among the participants in an epidemiological community study, based on their age and sex. Cognitive performance was assessed with use of the Mini-Mental State Examination. The association between SAA and cognitive performance was examined using a univariate analysis and a multiple logistic regression model, adjusting for age, sex, educational level, and number of medications. Results: Serum anticholinergic activity was detectable in 180 (89.6%) participants (range, 0.50-5.70 pmol/mL). Univariate testing showed a significant association between SAA and Mini-Mental State Examination scores. Logistic regression analysis indicated that subjects with SAA at or above the sample's 90th percentile (ie, SAA greater than or equal to2.80 pmol/mL) were 13 times (odds ratio, 1.08-152.39) more likely than subjects with undetectable SAA to have a Mini-Mental State Examination score of 24 (the sample's 10th percentile) or below. Conclusions: To our knowledge, this is the largest analysis of SAA and the first to examine its extent and relationship with cognitive performance in a community sample. Its results suggest that SAA can be detected in most older persons in the community and confirm that even low SAA is associated with cognitive impairment. C1 Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. RP Mulsant, BH (reprint author), Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, 3811 O Hara St, Pittsburgh, PA 15213 USA. RI Ganguli, Mary/A-3638-2013; MORAN, CATHERINE/C-9539-2015 FU NIA NIH HHS [AG07562]; NIMH NIH HHS [MH01613, MH30915, MH52247, MH59666, MH64173, MH65416] NR 54 TC 163 Z9 167 U1 1 U2 4 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 FEB PY 2003 VL 60 IS 2 BP 198 EP 203 DI 10.1001/archpsyc.60.2.198 PG 6 WC Psychiatry SC Psychiatry GA 643RA UT WOS:000180873200011 PM 12578438 ER PT J AU Fisher, CM AF Fisher, CM TI The reach of neurology SO ARCHIVES OF NEUROLOGY LA English DT Review AB Neurologists experienced in the interpretation of disease in terms of disordered action of the nervous system should be well suited to extend their field of interest to the more complex disorders of human behavior, including hysteria, delirium, ill-defined pain syndromes,. unexplained fatigue, disorders of thought, atypical depression, and delusions. To illustrate the potential of neurology in approaching the more complex disorders of behavior, several examples from clinical neurology are presented in which phenomena calling for inquiry and analysis in neurological terms are described. The categories are temporal lobe epilepsy, delirium, drug toxicity, disease processes of the cerebrum, obscure pain, dyslexia, and hysteria. Inquiry into complex disorders of behavior is inseparable from the broad subject of normal mental activity, the neural organization subserving all human thought, emotion, and action. Because of this close association, the comment on hysteria includes an introduction to the important question of whether we humans possess a free will to choose our course of behavior. C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Fisher, CM (reprint author), Massachusetts Gen Hosp, Neurol Serv, 55 Fruit St, Boston, MA 02114 USA. NR 6 TC 3 Z9 3 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD FEB PY 2003 VL 60 IS 2 BP 173 EP 177 DI 10.1001/archneur.60.2.173 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 644PT UT WOS:000180927900003 PM 12580700 ER PT J AU Foster, BS Fernandez-Suntay, JP Dryja, TP Jakobiec, FA D'Amico, DJ AF Foster, BS Fernandez-Suntay, JP Dryja, TP Jakobiec, FA D'Amico, DJ TI Surgical removal and histopathologic findings of a subfoveal heovascular membrane associated with choroidal osteoma SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID NEOVASCULAR MEMBRANES; SUBRETINAL NEOVASCULARIZATION; EXCISION C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP D'Amico, DJ (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 19 TC 13 Z9 15 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD FEB PY 2003 VL 121 IS 2 BP 273 EP 276 PG 4 WC Ophthalmology SC Ophthalmology GA 644AM UT WOS:000180895800018 PM 12583798 ER PT J AU Dohlman, CH AF Dohlman, CH TI David M. Maurice, PhD (1922-2002) - Obituary SO ARCHIVES OF OPHTHALMOLOGY LA English DT Biographical-Item C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Dohlman, CH (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD FEB PY 2003 VL 121 IS 2 BP 298 EP 298 PG 1 WC Ophthalmology SC Ophthalmology GA 644AM UT WOS:000180895800033 PM 12593404 ER PT J AU Luckey, A Livingston, E Tache, Y AF Luckey, A Livingston, E Tache, Y TI Mechanisms and treatment of postoperative ileus SO ARCHIVES OF SURGERY LA English DT Review ID CORTICOTROPIN-RELEASING-FACTOR; PROSPECTIVE RANDOMIZED TRIAL; GENE-RELATED PEPTIDE; PLACEBO-CONTROLLED TRIAL; MAJOR ABDOMINAL-SURGERY; KAPPA-OPIOID RECEPTORS; GASTRIC-EMPTYING RATE; POST-OPERATIVE ILEUS; PARALYTIC ILEUS; EPIDURAL ANALGESIA AB Objective: To review the pathogenesis and treatment of postoperative ileus. Data Sources: Data collected for this review were identified from a MEDLINE database search of the English-language literature. The exact indexing terms were "postoperative ileus," "treatment," "etiology," and "pathophysiology." Previous review articles and pertinent references from those articles were also used. Study Selection: All relevant studies were included. Only articles that were case presentations or that mentioned postoperative ileus in passing were excluded. Data Synthesis: The pathogenesis of postoperative ileus is complex, with multiple factors contributing either simultaneously or at various times during the development of this entity. These factors include inhibitory effects of sympathetic input; release of hormones, neurotransmitters, and other mediators; an inflammatory reaction; and the effects of anesthetics and analgesics. Numerous treatments have been used to alleviate postoperative ileus without much success. Conclusions: The etiology of postoperative ileus can best be described as multifactorial. A multimodality treatment approach should include limiting the administration of agents known to contribute to postoperative ileus (narcotics), using thoracic epidurals with local anesthetics when possible, and selectively applying nasogastric decompression. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90073 USA. Univ Calif San Francisco E Bay, Oakland, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Bariatr Surg Program, Los Angeles, CA 90073 USA. VA Greater LA Healthcare Syst, Digest Dis Res Ctr, CURE, Los Angeles, CA USA. RP Luckey, A (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 11301 Wilshire Blvd,Bldg 115,Room 217, Los Angeles, CA 90073 USA. NR 137 TC 189 Z9 206 U1 1 U2 22 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD FEB PY 2003 VL 138 IS 2 BP 206 EP 214 DI 10.1001/archsurg.138.2.206 PG 9 WC Surgery SC Surgery GA 644AG UT WOS:000180895300022 PM 12578422 ER PT J AU Steere, AC Falk, B Drouin, EE Baxter-Lowe, LA Hammer, J Nepom, GT AF Steere, AC Falk, B Drouin, EE Baxter-Lowe, LA Hammer, J Nepom, GT TI Binding of outer surface protein A and human lymphocyte function-associated antigen 1 peptides to HLA-DR molecules associated with antibiotic treatment-resistant Lyme arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID BORRELIA-BURGDORFERI DNA; RHEUMATOID-ARTHRITIS; CRYSTAL-STRUCTURE; DISEASE SEVERITY; SYNOVIAL-FLUID; HLA-DRB1 GENES; T-CELLS; ANTIBODY; PREDICTION; RESPONSES AB Objective. To assess the binding of outer surface protein A (OspA) and human lymphocyte function-associated antigen I (hLFA-1) peptides to 5 major histocompatibility complex (MHC) molecules. Methods. Peptide binding to the MHC molecules was determined by in vitro binding assays, and binding was correlated with the frequencies of the 5 MHC molecules in patients with treatment-resistant Lyme arthritis. Results. The HLA-DRB1*0401 molecule bound both OspA(163-175) and hLFA-1alpha(L330-342) well. Although the magnitude of the binding was less, the DRB1*0404 molecule also showed binding of both peptides. The DRB1*0101 molecule bound OspA(163-175) well, but hLFA-1alpha(L330-342) only weakly; the DRB1*0801 or *1101 molecule bound both peptides weakly, if at all. The magnitude of OspA(163-175) binding correlated well with the frequencies of the DRB1 alleles in patients with treatment-resistant arthritis, but the binding of hLFA-1alpha(L330-342) showed only an association with the DRB*04 alleles. Conclusion. These correlations support the hypothesis that OspA(163-175) is the critical epitope in triggering antibiotic treatment-resistant Lyme arthritis. However, the inability of the DRB*0101 molecule to bind hLFA-1alpha(L330-342) suggests that this peptide may not be a relevant autoantigen, at least in DRB1*0101-positive patients. C1 Tufts Univ, Sch Med, New England Med Ctr, Boston, MA 02111 USA. Univ Calif San Francisco, Immunogenet & Transplantat Lab, San Francisco, CA 94143 USA. Hoffmann La Roche Inc, Nutley, NJ 07110 USA. Univ Washington, Sch Med, Virginia Mason Res Ctr, Seattle, WA 98195 USA. RP Steere, AC (reprint author), Massachusetts Gen Hosp, 149 13th St,Room 8301, Charlestown, MA 02129 USA. OI Nepom, Gerald/0000-0002-8063-1464 FU NIAMS NIH HHS [AR-20358] NR 36 TC 46 Z9 47 U1 2 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD FEB PY 2003 VL 48 IS 2 BP 534 EP 540 DI 10.1002/art.10772 PG 7 WC Rheumatology SC Rheumatology GA 645CG UT WOS:000180958200031 PM 12571864 ER PT J AU Katz, JN Phillips, CB Baron, JA Fossel, AH Mahomed, NN Barrett, J Lingard, EA Harris, WH Poss, R Lew, RA Guadagnoli, E Wright, EA Losina, E AF Katz, JN Phillips, CB Baron, JA Fossel, AH Mahomed, NN Barrett, J Lingard, EA Harris, WH Poss, R Lew, RA Guadagnoli, E Wright, EA Losina, E TI Association of hospital and surgeon volume of total hip replacement with functional status and satisfaction three years following surgery SO ARTHRITIS AND RHEUMATISM LA English DT Article ID NEW-YORK-STATE; SURGICAL VOLUME; MORTALITY; OUTCOMES; KNEE; VALIDATION; MORBIDITY; CARE AB Objective. To evaluate whether hospital volume and surgeon volume of total hip replacements (THRs) are associated with patient-reported functional status and satisfaction with surgery 3 years postoperatively. Methods. We performed a population-based cohort study of a stratified random sample of Medicare beneficiaries who underwent elective primary or revision THR in Ohio, Pennsylvania, or Colorado in 1995. The primary outcomes were the self-reported Harris hip score and a validated scale measuring satisfaction with the results of surgery. Both outcomes were assessed 3 years postoperatively. Hospital volume was defined as the aggregate number of elective primary and revision THRs performed on Medicare beneficiaries in the hospital in 1995. High-volume hospitals were defined as those in which > 100 such procedures are performed annually, and low-volume centers were defined as those in which less than or equal to 12 procedures (primary THR cohort) or less than or equal to 30 procedures (revision cohort) are performed annually. Results. In unadjusted analyses, patients who underwent surgery in low-volume centers had worse functional status 3 years following primary and revision THR compared with patients whose surgery was performed in higher-volume centers. Patients whose revision THR was performed by a low-volume surgeon also had worse function. After adjustment for sociodem-ographic and clinical variables, however, the association between higher hospital volume and better functional status following primary THR was weak and statistically nonsignificant, and no statistically significant or clinically important associations between hospital or surgeon volume and functional status following revision THR was observed. Patients who underwent elective primary THR in low-volume centers were more likely to be dissatisfied with the results of surgery compared with patients whose surgeries were performed in high-volume centers. Similarly, patients whose surgeons performed less than or equal to 12 procedures per year were more likely to be dissatisfied with the results of revision THR than were patients whose surgeons performed > 12 procedures per year. Conclusion. Hospital volume and surgeon volume have little effect on 3-year functional outcome following THR, after adjusting for patient sociodemographic and select clinical characteristics. However, satisfaction with primary THR is greater among patients who underwent surgery in high-volume centers, and satisfaction with revisions is greater among patients whose operations were performed by higher-volume surgeons. Referring clinicians should incorporate these findings into their discussion of referral choices with patients considering THR. Conclusions regarding the effect of volume on longevity of the implants must await longer-term followup studies. Finally, further research is warranted to better understand the association between hospital and surgeon procedure volume and patient satisfaction with surgery. C1 Harvard Univ, Div Rheumatol Allergy & Immunol, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Dartmouth Coll Sch Med, Hanover, NH USA. Univ Toronto, Toronto Western Hosp, Toronto, ON M5T 2S8, Canada. Univ Newcastle Upon Tyne, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Univ Bristol, Bristol BS8 1TH, Avon, England. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. RP Katz, JN (reprint author), Harvard Univ, Div Rheumatol Allergy & Immunol, Brigham & Womens Hosp, Sch Med, 75 Francis St,B-3, Boston, MA 02115 USA. FU AHRQ HHS [1R01-HS-09775]; NIAMS NIH HHS [P60-AR-36308, K24-AR-02123, P60-AR-47782] NR 28 TC 110 Z9 111 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD FEB PY 2003 VL 48 IS 2 BP 560 EP 568 DI 10.1002/art.10754 PG 9 WC Rheumatology SC Rheumatology GA 645CG UT WOS:000180958200034 PM 12571867 ER PT J AU Gershuny, BS Cloitre, M Otto, MW AF Gershuny, BS Cloitre, M Otto, MW TI Peritraumatic dissociation and PTSD severity: do event-related fears about death and control mediate their relation? SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE PTSD; dissociation; trauma; fear of death; fear of losing control; mediational model ID POSTTRAUMATIC-STRESS-DISORDER; EMERGENCY SERVICES PERSONNEL; VIETNAM THEATER VETERANS; MOTOR-VEHICLE ACCIDENTS; TRAUMA; PREDICTORS; SYMPTOMS; DISTRESS; SURVIVORS; ASSAULT AB Relations among peritraumatic dissociation, PTSD severity, event-related fear (i.e. fear experienced during traumatic event) about death, and event-related fear about losing control were examined in the current study. Particular emphasis was placed on testing whether or not fears about death and losing control mediate the relation between peritraumatic dissociation and PTSD severity in a sample of 146 nontreatment-seeking university women. Results indicated that event-related fears about death and losing control accounted for the relation between peritraumatic dissociation and PTSD severity; that is, the effect of peritraumatic dissociation on PTSD severity was eliminated after controlling for these fears. Speculations about findings are discussed. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, OCD Clin, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. New York Hosp, Cornell Med Ctr, Payne Whitney Clin, Anxiety & Traumat Stress Program, New York, NY 10021 USA. RP Gershuny, BS (reprint author), Massachusetts Gen Hosp, OCD Clin, E Bldg 149,9th Floor,13th St, Charlestown, MA 02129 USA. NR 30 TC 40 Z9 43 U1 2 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD FEB PY 2003 VL 41 IS 2 BP 157 EP 166 DI 10.1016/S0005-7967(01)00134-6 PG 10 WC Psychology, Clinical SC Psychology GA 647PQ UT WOS:000181102700003 PM 12547377 ER PT J AU Yang, L Mei, Q Zielinska-Kwiatkowska, AZE Matsui, Y Blackburn, ML Benedetti, D Krumm, AA Taborsky, GJ Chansky, HA AF Yang, L Mei, Q Zielinska-Kwiatkowska, AZE Matsui, Y Blackburn, ML Benedetti, D Krumm, AA Taborsky, GJ Chansky, HA TI An ERG (ets-related gene)-associated histone methyltransferase interacts with histone deacetylases 1/2 and transcription co-repressors mSin3A/B SO BIOCHEMICAL JOURNAL LA English DT Article DE chromatin; ERG-associated protein with a SET domain (ESET); SETDB1; trichostatin A; tudor domain ID SPINAL MUSCULAR-ATROPHY; N-COR; COMPLEX; PROTEIN; DROSOPHILA; SU(VAR)3-9; DOMAIN; TUDOR; GENE; DNA AB Covalent modifications of histone tails play important roles in gene transcription and silencing. We recently identified an ERG (ets-related gene)-associated protein with a SET (suppressor of variegation, enhancer of zest and trithorax) domain (ESET) that was found to have the activity of a histone H3-specific methyltransferase. In the present study, we investigated the interaction of ESET with other chromatin remodelling factors. We show that ESET histone methyltransferase associates with histone deacetylase I (HDAC1) and HDAC2, and that ESET also interacts with the transcription co-repressors mSin3A and mSin3B. Deletion analysis of ESET reveals that an N-terminal region containing a tudor domain is responsible for interaction with mSin3A/B and association with HDAC1/2, and that truncation of ESET enhances its binding to mSin3. When bound to a promoter, ESET represses the transcription of a downstream luciferase reporter gene. This repression by ESET is independent of its histone methyltransferase activity, but correlates with its binding to the mSin3 co-repressors. In addition, the repression can be partially reversed by treatment with the HDAC inhibitor trichostatin A. Taken together, these data suggest that ESET histone methyltransferase can form a large, multi-protein complex(es) with mSin3A/B co-repressors and HDAC1/2 that participates in multiple pathways of transcriptional repression. C1 Univ Washington, Sch Med, Dept Orthoped, Seattle, WA 98195 USA. Univ Washington, Sch Med, Div Hematol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Med Res Serv, Seattle, WA 98108 USA. Univ Washington, Sch Med, Div Endocrinol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Div Oncol, Seattle, WA 98195 USA. RP Yang, L (reprint author), Univ Washington, Sch Med, Dept Orthoped, Seattle, WA 98195 USA. FU NCI NIH HHS [1R01CA90941] NR 44 TC 80 Z9 87 U1 0 U2 2 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD FEB 1 PY 2003 VL 369 BP 651 EP 657 DI 10.1042/BJ20020854 PN 3 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 645VU UT WOS:000181001300025 PM 12398767 ER PT J AU Musi, N Yu, H Goodyear, LJ AF Musi, N Yu, H Goodyear, LJ TI AMP-activated protein kinase regulation and action in skeletal muscle during exercise SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT 2nd International Meeting on AMP-activated Protein Kinase (AMPK 2002) CY SEP 12-14, 2002 CL UNIV DUNDEE W PK CTR, DUNDEE, SCOTLAND SP Wellcomt Trust, Biochem Soc, BioDundee, Novo Nordisk, Merck Sante, Aventis Pharma, Eli Lilly, Mercury Therapeut, Merck & Co Inc, Pfizer Inc, Abbott, GlaxoSmithKline, Boehringer, AstraZeneca, Upstate & Roche HO UNIV DUNDEE W PK CTR DE acetyl-CoA carboxylase (ACC); AMP-activated protein kinase (AMPK); fatty acid oxidation; glucose uptake ID ACETYL-COA CARBOXYLASE; NITRIC-OXIDE SYNTHASE; GLUCOSE-TRANSPORT; MALONYL-COA; GLUT4 TRANSLOCATION; GLYCOGEN-SYNTHASE; NO SYNTHASE; FIBER-TYPE; IN-VITRO; CONTRACTION AB Physical exercise increases muscle glucose uptake, enhances insulin sensitivity and leads to fatty acid oxidation in muscle. The AMP-activated protein kinase (AMPK) is an energy-sensing enzyme that is strongly activated during muscle contraction due to acute decreases in ATP/AMP and phosphocreatine/creatine ratios. Accumulating evidence suggests that AMPK plays an important role in mediating these metabolic processes. Furthermore, AMPK has been implicated in regulating gene transcription and therefore may play a role in some of the cellular adaptations to training exercise. There is also evidence that changes in AMPK activity result in altered cellular glycogen content, suggesting that this enzyme regulates glycogen metabolism. Recent studies have shown that the magnitude of AMPK activation and associated metabolic responses are affected by factors such as glycogen content, exercise training and fibre type. In summary, AMPK regulates several metabolic pathways during acute exercise and modifies the expression of many genes involved in the adaptive changes to exercise training. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIAMS NIH HHS [AR45670] NR 62 TC 27 Z9 30 U1 0 U2 1 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD FEB PY 2003 VL 31 BP 191 EP 195 PN 1 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 648QA UT WOS:000181161000041 PM 12546683 ER PT J AU Sundback, C Hadlock, T Cheney, M Vacanti, J AF Sundback, C Hadlock, T Cheney, M Vacanti, J TI Manufacture of porous polymer nerve conduits by a novel low-pressure injection molding process SO BIOMATERIALS LA English DT Article DE peripheral nerve regeneration; polymer processing; nerve conduit; biodegradable polymer; Schwann cells; tissue engineering ID RAT SCIATIC-NERVE; ELECTRON-MICROSCOPIC EVALUATION; EPSILON-CAPROLACTONE POLYMER; LIQUID PHASE-SEPARATION; CULTURED SCHWANN-CELLS; PERIPHERAL-NERVE; BIOLOGICAL PERFORMANCE; POLYGLACTIN TUBE; COLLAGEN-FIBERS; GROWTH-FACTOR AB A method to fabricate porous, biodegradable conduits using a combined injection molding, thermally induced phase transition technique was developed which produced conduits with dimensionally toleranced, longitudinally aligned channels. The geometry of the channels was designed to approximate the architecture of peripheral nerves and to Support the monolayer adherence of physiologically relevant numbers of Schwann cells. The channel configuration could be varied from a single 1.35 mm diameter channel LIP to 100 0.08 mm diameter channels. A conduit with 100 channels has approximately 12.5 times the lumenal Surface area of a single channel conduit and supports the adherence of five times the number of Schwann cells in the native peripheral nerve. In this study, poly(DL-lactide-co-glycolide) (DL-PLGA) was dissolved in acetic acid and injected into a cold mold Which induced solid-liquid phase separation and, ultimately, solidification of the polymer solution. The acetic acid was removed by sublimation and the resulting foam had a macrostructure of high anisotropy. Semi-permeable skins formed on the outer and lumen diameters of the conduit as a consequence of rapid quenching. Macropores were organized into bundles of channels, up to 20 mum wide, in the DL-PLGA matrix and represented remnants of acetic acid that crystallized during solidification. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otolaryngol, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Sundback, C (reprint author), Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Wellman 625 55 Fruit St, Boston, MA 02114 USA. NR 65 TC 77 Z9 83 U1 3 U2 22 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 FEB PY 2003 VL 24 IS 5 BP 819 EP 830 AR PII S0142-9612(02)00409-X DI 10.1016/S0142-9612(02)00409-X PG 12 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 637AH UT WOS:000180489100013 PM 12485800 ER PT J AU Struyk, AF Cannon, SC AF Struyk, AF Cannon, SC TI Slow inactivation of voltage-gated Na channels by pulse-train stimulation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. SW Texas State Univ, Dallas, TX 75390 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 69A EP 69A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800333 ER PT J AU Forman, SA Ruesch, D AF Forman, SA Ruesch, D TI Two general anesthetic actions in GABA(A)Rs attributable to altered gating. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TX SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 87A EP 87A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123800423 ER PT J AU Oh, KJ Meyer, N Korsmeyer, SJ AF Oh, KJ Meyer, N Korsmeyer, SJ TI Interaction of BID, a pro-apoptotic BCL-2 family member, with lipid membranes: A site-directed spin labeling study. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 205A EP 206A PN 2 PG 2 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801005 ER PT J AU Arevalo, E Chiara, DC Cohen, JB Miller, KW AF Arevalo, E Chiara, DC Cohen, JB Miller, KW TI Photolabeling of the open channel state of the nicotinic acetylcholine receptor SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 230A EP 230A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801126 ER PT J AU Neagoe, C Kulke, MT del Monte, F Hajjar, RJ Linke, WA AF Neagoe, C Kulke, MT del Monte, F Hajjar, RJ Linke, WA TI Disease-specific changes of titin isoform expression in human heart SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Univ Heidelberg, D-69120 Heidelberg, Germany. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RI Linke, Wolfgang/E-8662-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 243A EP 243A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801188 ER PT J AU Williamson, PTF Verhoeven, A Miller, KW Watts, A Meier, BH AF Williamson, PTF Verhoeven, A Miller, KW Watts, A Meier, BH TI Structural studies of acetylcholine bound to the nicotinic acetylcholine receptor SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 ETH Honggerberg, CH-8093 Zurich, Switzerland. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Biomembrane Struct Unit, Oxford OX1 3QU, England. RI Williamson, Philip/A-3362-2008 OI Williamson, Philip/0000-0002-0231-8640 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 278A EP 278A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801360 ER PT J AU Dombeck, DA Kasischke, KA Vishwasrao, HD Webb, WW Ingelsson, M Hyman, BT AF Dombeck, DA Kasischke, KA Vishwasrao, HD Webb, WW Ingelsson, M Hyman, BT TI Second harmonic imaging of axonal microtubules SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Cornell Univ, Ithaca, NY 14853 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 284A EP 284A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123801390 ER PT J AU Gordon, VD Valentine, M Gardel, M Andor, D Dennison, S Bogdanov, A Weitz, D Deisboeck, T AF Gordon, VD Valentine, M Gardel, M Andor, D Dennison, S Bogdanov, A Weitz, D Deisboeck, T TI Measuring the mechanical strain induced by a dynamically expanding multicellular tumor system SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 47th Annual Meeting of the Biophysical-Society CY MAR 01-05, 2003 CL SAN ANTONIO, TEXAS SP Biophys Soc, Axon Instruments, ALA Sci Instruments C1 Harvard Univ, McKay Labs, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. MIT, HST Biomed Engn Ctr, Cambridge, MA 02138 USA. RI Gardel, Margaret/D-1703-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 SU S BP 571A EP 571A PN 2 PG 1 WC Biophysics SC Biophysics GA 682ZW UT WOS:000183123802802 ER PT J AU Wei, XB Henke, VG Strubing, C Brown, EB Clapham, DE AF Wei, XB Henke, VG Strubing, C Brown, EB Clapham, DE TI Real-time imaging of nuclear permeation by EGFP in single intact cells SO BIOPHYSICAL JOURNAL LA English DT Article ID GREEN FLUORESCENT PROTEIN; ATOMIC-FORCE MICROSCOPY; PORE COMPLEX; PHOTOBLEACHING RECOVERY; LIVING CELLS; CA2+ STORES; DIFFUSION; TRANSPORT; DEPLETION; ENVELOPE AB The NPC is the portal for the exchange of proteins, mRNA, and ions between nucleus and cytoplasm. Many small molecules (<10 kDa) permeate the nucleus by simple diffusion through the pore, but molecules larger than 70 kDa require ATP and a nuclear localization sequence for their transport. In isolated Xenopus oocyte nuclei, diffusion of intermediate-sized molecules appears to be regulated by the NPC, dependent upon [Ca2+] in the nuclear envelope. We have applied real-time imaging and fluorescence recovery after photobleaching to examine the nuclear pore permeability of 27-kDa EGFP in single intact cells. We found that EGFP diffused bidirectionally via the NPC across the nuclear envelope. Although diffusion is slowed similar to100-fold at the nuclear envelope boundary compared to diffusion within the nucleus or cytoplasm, this delay is expected for the reduced cross-sectional area of the NPCs. We found no evidence for significant nuclear pore gating or block of EGFP diffusion by depletion of perinuclear Ca2+ stores, as assayed by a nuclear cisterna-targeted Ca2+ indicator. We also found that EGFP exchange was not altered significantly during the cell cycle. C1 Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol,EL Steele Lab, Boston, MA 02115 USA. RP Clapham, DE (reprint author), Childrens Hosp, Howard Hughes Med Inst, Rm 1309,Enders Bldg,POB EN-306,320 Longwood Ave, Boston, MA 02115 USA. NR 50 TC 61 Z9 61 U1 0 U2 5 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2003 VL 84 IS 2 BP 1317 EP 1327 PN 1 PG 11 WC Biophysics SC Biophysics GA 682ZV UT WOS:000183123700056 PM 12547812 ER PT J AU Chengappa, KNR Baker, RW Shao, LX Yatham, LN Tohen, M Gershon, S Kupfer, DJ AF Chengappa, KNR Baker, RW Shao, LX Yatham, LN Tohen, M Gershon, S Kupfer, DJ TI Rates of response, euthymia and remission in two placebo-controlled olanzapine trials for bipolar mania SO BIPOLAR DISORDERS LA English DT Article DE bipolar I disorder; euthymia; functional outcomes; mania; olanzapine; placebo; remission; response ID DEPRESSION; RECOVERY; DISORDER; SCALE AB Objective: Clinically meaningful recovery from acute mania may not be captured by conventionally reported response categorizations. We defined new and stringent criteria for remission in bipolar mania. Using a cohort of patients with acute mania randomized to treatment with either olanzapine or placebo, we contrasted remission rates to findings using previously reported but more lenient categorical outcome measures of response and euthymia. Methods: We pooled and reanalyzed results through 3 weeks from two published randomized double-blind trials of olanzapine versus placebo for treating acute bipolar mania (1, 2). Response was previously defined as greater than or equal to 50% decrease from baseline to endpoint total Young Mania Rating Scale (3) (Y-MRS) scores, and euthymia as an endpoint total Y-MRS score of less than or equal to 12. In this report, remission required an endpoint total Y-MRS score of less than or equal to 7, and an endpoint total Hamilton Depression Rating Scale, (HAM-D21) (4) score of less than or equal to 7 and an endpoint Clinical Global Impression Scale - Bipolar version, CGI-BP (5), overall severity score of less than or equal to 2. Results: Olanzapine treated subjects achieved statistically significantly greater rates of clinical response, euthymia and remission than those assigned to placebo, 55% versus 29.5%, 50% versus 27%, and 18% versus 7%, respectively. Conclusions: Olanzapine monotherapy resulted in discernable clinical improvements in mania in over 50% of subjects and just under 20% of subjects achieved a near complete resolution of manic and accompanying depressive symptoms after 3 weeks of treatment. Full remission is an important but potentially elusive goal during short-term management of acute mania. C1 Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA USA. Mayview State Hosp, Special Studies Ctr, Bridgeville, PA USA. Lilly Res Labs, Indianapolis, IN USA. Univ British Columbia, Dept Psychiat, Coll Med, Vancouver, BC, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. RP Chengappa, KNR (reprint author), Univ Pittsburgh, Med Ctr, Mayview State Hosp, Special Studies Ctr,Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA. NR 12 TC 119 Z9 121 U1 2 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD FEB PY 2003 VL 5 IS 1 BP 1 EP 5 DI 10.1034/j.1399-5618.2003.02237.x PG 5 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 645GF UT WOS:000180967300001 PM 12656931 ER EF