FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Arauz, AD Perrin, JM Beal, AC AF Arauz, AD Perrin, JM Beal, AC TI Race/ethnic disparities in lead testing for children SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, MGH Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2002 VL 51 IS 4 SU S MA 1026 BP 176A EP 176A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 536RA UT WOS:000174714601025 ER PT J AU Winickoff, JP Hillis, VJ Palfrey, JS Perrin, JM Rigotti, NA AF Winickoff, JP Hillis, VJ Palfrey, JS Perrin, JM Rigotti, NA TI Does child hospitalization for respiratory illness provide an opportunity for parental smoking cessation: A prospective cohort study SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA USA. Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. Childrens Hosp, Div Gen Pediat, Boston, MA 02115 USA. RI McMillen, Robert/A-9326-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2002 VL 51 IS 4 SU S MA 1119 BP 192A EP 192A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 536RA UT WOS:000174714601118 ER PT J AU Winickoff, JP McMillen, RC Klein, JD Weitzman, M AF Winickoff, JP McMillen, RC Klein, JD Weitzman, M TI Addressing parental smoking in pediatrics and family practice: A national survey of parents SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Harvard Pediat Hlth Serv Res Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. Mississippi State Univ, Social Sci Res Ctr, Mississippi State, MS 39762 USA. Univ Rochester, AAP Ctr Child Hlth Res, Rochester, NY 14627 USA. Univ Rochester, Strong Childrens Res Ctr, Rochester, NY 14627 USA. RI McMillen, Robert/A-9326-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2002 VL 51 IS 4 SU S MA 1117 BP 192A EP 192A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 536RA UT WOS:000174714601116 ER PT J AU Kulthau, K Ferris, TGG Bainbridge, J Perrin, JM Iezzoni, L AF Kulthau, K Ferris, TGG Bainbridge, J Perrin, JM Iezzoni, L TI Do community variables add to risk adjusted models of expenditures in pediatric Medicaid populations? SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 MassGen Hosp Children, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2002 VL 51 IS 4 SU S MA 1250 BP 215A EP 215A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 536RA UT WOS:000174714601249 ER PT J AU Shimamura, A de Oca, RM Svenson, J Moreau, L Garcia-Higuera, I D'Andrea, AD AF Shimamura, A de Oca, RM Svenson, J Moreau, L Garcia-Higuera, I D'Andrea, AD TI FANCD2 monoubiquitination: A functional screen for defects in the Fanconi anemia pathway SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2002 VL 51 IS 4 SU S MA 1424 BP 245A EP 245A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 536RA UT WOS:000174714601423 ER PT J AU Jiang, R Nestoridi, E Kushak, R Ingelfinger, JR Grabowski, EF AF Jiang, R Nestoridi, E Kushak, R Ingelfinger, JR Grabowski, EF TI Shiga toxin x 24 hours in combination with TNF-alpha induces significant tissue factor activity on endothelial cells SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2002 VL 51 IS 4 SU S MA 1456 BP 250A EP 251A PN 2 PG 2 WC Pediatrics SC Pediatrics GA 536RA UT WOS:000174714601455 ER PT J AU Schmidt, EV Contreras, AM He, WP Hiasa, Y Chung, RT AF Schmidt, EV Contreras, AM He, WP Hiasa, Y Chung, RT TI RNA viral mutations are region-specific and increased by ribavirin in a novel hepatitis C replication system SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2002 VL 51 IS 4 SU S MA 1533 BP 263A EP 264A PN 2 PG 2 WC Pediatrics SC Pediatrics GA 536RA UT WOS:000174714601532 ER PT J AU Zeff, S List, J Samuels, RC AF Zeff, S List, J Samuels, RC TI Healthy children do not get Enterobacter bacteremia SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2002 VL 51 IS 4 SU S MA 1662 BP 285A EP 285A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 536RA UT WOS:000174714601661 ER PT J AU Salusky, IB Kuizon, BD Facincani, I Lavigne, J Zahdranik, RJ Jueppner, H Goodman, WG AF Salusky, IB Kuizon, BD Facincani, I Lavigne, J Zahdranik, RJ Jueppner, H Goodman, WG TI Third generation assay for PTH and bone histomorphometry in children on dialysis SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Immutopies, San Clemente, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2002 VL 51 IS 4 SU S MA 2515 BP 432A EP 432A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 536RA UT WOS:000174714602513 ER PT J AU Husson, I Daire, JL Dumont, E Kosofsky, BE Sebag, G Gressens, P AF Husson, I Daire, JL Dumont, E Kosofsky, BE Sebag, G Gressens, P TI Diffusion weight imaging in a rabbit model of neonatal excitotoxic brain lesions SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Hop Robert Debre, INSERM, E 9935, F-75019 Paris, France. Hop Robert Debre, Lab Dev Imaging, F-75019 Paris, France. Philips Med Syst, Suresnes, France. Massachusetts Gen Hosp, Lab Mol & Dev Neurosci, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2002 VL 51 IS 4 SU S MA 2581 BP 443A EP 444A PN 2 PG 2 WC Pediatrics SC Pediatrics GA 536RA UT WOS:000174714602579 ER PT J AU Kemper, KJ Amata-Kynvi, A Dvorkin, L Whelan, JS Samuels, R Hibberd, P AF Kemper, KJ Amata-Kynvi, A Dvorkin, L Whelan, JS Samuels, R Hibberd, P TI Clinicians' knowledge, attitudes and practices about herbs and other dietary supplements SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Childrens Hosp, Boston, MA 02115 USA. Massachusetts Coll Pharm & Hlth Sci, Boston, MA USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Massachusetts Gen Hosp, Informat Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2002 VL 51 IS 4 SU S MA 2701 BP 463A EP 464A PN 2 PG 2 WC Pediatrics SC Pediatrics GA 536RA UT WOS:000174714602699 ER PT J AU Fungaloi, P van Eps, RS Wu, YP Blankensteijn, J de Groot, P van Urk, H van Hillegersberg, R LaMuraglia, G AF Fungaloi, P van Eps, RS Wu, YP Blankensteijn, J de Groot, P van Urk, H van Hillegersberg, R LaMuraglia, G TI Platelet adhesion to photodynamic therapy-treated extracellular matrix proteins SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID VON-WILLEBRAND-FACTOR; HUMAN ENDOTHELIAL-CELLS; COLLAGEN TYPE-I; FLOWING BLOOD; INTIMAL HYPERPLASIA; VESSEL WALL; AGGREGATION; VIII; PREVENTION; MECHANISMS AB Photodynamic therapy (PDT) produces reactive species that alter vascular wall biology and vessel wall proteins. In this study, we examined platelet adhesion to PDT-treated (photosensitizer = Photofrin; fluence 100 J/cm(2); lambda = 630 nm) extracellular matrix (ECM), fibrinogen, von Willebrand factor (vWF) and collagen Types I and 111, under flow conditions in a recirculating perfusion chamber. Platelet adhesion was quantified by image analysis. The effect of PDT on vWF was assessed by measuring the binding of domain-specific antibodies to treated vWF. PDT significantly decreased platelet adhesion to the ECM, fibrinogen and vWF. However, PDT of collagen resulted in significantly increased platelet adhesion, with large aggregate formation. PDT affected mostly the A1 (glycoprotein [GP]-Ib-binding site), A2 and A3 (collagen-binding site) domains of vWF but not the D'-D3 (factor VIII-binding site) and B-Cl (GP-IIb/IIIa-binding site) domains. In conclusion, PDT can alter the ECM, resulting in decreased platelet adhesion. However, vessels with high collagen content, such as veins and small arteries, may become increasingly prone to thrombosis. The results of this study may thus play a role in understanding the thrombogenic properties and mechanisms of vascular PDT. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Div Vasc Surg, Boston, MA USA. Univ Rotterdam Hosp, Dept Surg, Rotterdam, Netherlands. Univ Utrecht Hosp, Dept Hematol, Utrecht, Netherlands. Univ Utrecht Hosp, Dept Vasc Surg, Utrecht, Netherlands. RP Fungaloi, P (reprint author), Erasmus Med Ctr, Dept Surg, Dr Molewaterpl 40, NL-3015 GD Rotterdam, Netherlands. RI Blankensteijn, Jan/Q-9291-2016 OI Blankensteijn, Jan/0000-0002-2062-8749 NR 31 TC 13 Z9 14 U1 0 U2 0 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD APR PY 2002 VL 75 IS 4 BP 412 EP 417 DI 10.1562/0031-8655(2002)075<0412:PATPTT>2.0.CO;2 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 542HY UT WOS:000175038500013 PM 12003132 ER PT J AU Gu, YQ Wildermuth, MC Chakravarthy, S Loh, YT Yang, CM He, XH Han, Y Martin, GB AF Gu, YQ Wildermuth, MC Chakravarthy, S Loh, YT Yang, CM He, XH Han, Y Martin, GB TI Tomato transcription factors Pti4, Pti5, and Pti6 activate defense responses when expressed in Arabidopsis SO PLANT CELL LA English DT Article ID SYSTEMIC ACQUIRED-RESISTANCE; PATHOGENESIS-RELATED GENES; DNA-BINDING PROTEINS; SYRINGAE PV TOMATO; DISEASE RESISTANCE; SALICYLIC-ACID; ENHANCES RESISTANCE; PTO KINASE; PHYTOTOXIN CORONATINE; METHYL JASMONATE AB The Pti4, Pti5, and Pti6 proteins from tomato were identified based on their interaction with the product of the Pto disease resistance gene, a Ser-Thr protein kinase. They belong to the ethylene-response factor (ERF) family of plant-unique transcription factors and bind specifically to the GCC-box cis element present in the promoters of many pathogenesis-related (PR) genes. Here, we show that these tomato ERFs are localized to the nucleus and function in vivo as transcription activators that regulate the expression of GCC box-containing PR genes. Expression of Pti4, Pti5, or Pti6 in Arabidopsis activated the expression of the salicylic acid-regulated genes PR1 and PR2. Expression of jasmonic acid- and ethylene-regulated genes, such as PR3, PR4, PDF1.2, and Thi2.1, was affected differently by each of the three tomato ERFs, with Arabidopsis-Pti4 plants having very high levels of PDF1.2 transcripts. Exogenous application of salicylic acid to Arabidopsis-Pti4 plants suppressed the increased expression of PDF1.2 but further stimulated PR1 expression. Arabidopsis plants expressing Pti4 displayed increased resistance to the fungal pathogen Erysiphe orontii and increased tolerance to the bacterial pathogen Pseudomonas syringae pv tomato. These results indicate that Pti4, Pti5, and Pti6 activate the expression of a wide array of PR genes and play important and distinct roles in plant defense. C1 Boyce Thompson Inst Plant Res, Ithaca, NY 14853 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Purdue Univ, Dept Agron, W Lafayette, IN 47907 USA. Cornell Univ, Dept Plant Pathol, Ithaca, NY 14853 USA. RP Martin, GB (reprint author), Boyce Thompson Inst Plant Res, Ithaca, NY 14853 USA. RI Martin, Gregory/F-6262-2011 OI Martin, Gregory/0000-0003-0044-6830 FU NIGMS NIH HHS [GM 48707, R01 GM048707, R37 GM048707] NR 65 TC 202 Z9 261 U1 3 U2 31 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 1040-4651 J9 PLANT CELL JI Plant Cell PD APR PY 2002 VL 14 IS 4 BP 817 EP 831 DI 10.1105/tpc.000794 PG 15 WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology GA 547UG UT WOS:000175350100007 PM 11971137 ER PT J AU Rivas-Vazquez, RA Johnson, SL Rey, GJ Blais, MA Rivas-Vazquez, A AF Rivas-Vazquez, RA Johnson, SL Rey, GJ Blais, MA Rivas-Vazquez, A TI Current treatments for bipolar disorder: A review and update for psychologists SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Review ID RANDOMIZED CONTROLLED TRIAL; MAINTENANCE THERAPY; MOOD STABILIZER; LIFE EVENTS; ACUTE MANIA; LITHIUM; OLANZAPINE; EFFICACY; PLACEBO; RISPERIDONE AB Practicing psychologists are likely to be confronted with the diagnostic and treatment challenges associated with bipolar disorder, particularly the various classes of medication currently used in pharmacotherapy for the disorder. Although lithium remains a valuable resource, limitations associated with its use have prompted clinicians and researchers to explore the application of several different classes of agents, including anticonvulsants, calcium channel blockers, atypical antipsychotics, benzodiazepines and antidepressants, to the acute and long-term management of bipolar disorder. A review of these agents, as well as a summary of various psychotherapeutic modalities that can serve as adjunctive interventions to pharmacotherapy, is provided for psychologists. C1 Neurol Ctr S Florida, Miami, FL 33176 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Miami, Sch Med, Dept Psychiat, Coral Gables, FL 33124 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Rivas-Vazquez, RA (reprint author), Neurol Ctr S Florida, Baptist Med Arts Bldg,8940 N Kendall Dr,Suite 802, Miami, FL 33176 USA. RI johnson, sheri/D-8712-2014 OI johnson, sheri/0000-0002-9945-4816 NR 82 TC 6 Z9 6 U1 6 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7028 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD APR PY 2002 VL 33 IS 2 BP 212 EP 223 DI 10.1037//0735-7028.33.2.212 PG 12 WC Psychology, Multidisciplinary SC Psychology GA 533BU UT WOS:000174510200014 ER PT J AU Sonawalla, SB Farabaugh, AH Leslie, VM Pava, JA Matthews, JD Fava, M AF Sonawalla, SB Farabaugh, AH Leslie, VM Pava, JA Matthews, JD Fava, M TI Early drop-outs, late drop-outs and completers: Differences in the continuation phase of a clinical trial SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE age clinical trial; completers; early drop-outs; late drop-outs; major depression ID DEPRESSION; TERMINATION; FLUOXETINE; COST AB Objective: The purpose of this study was to assess the differences between early and late drop-outs and completers in the continuation phase of a clinical trial. Methods: The authors studied It 9 outpatients who were treatment responders in an 8-week open trial with fluoxetine 20 mg/day, and who were then enrolled in a 26-week clinical trial comparing the efficacy of fluoxetine versus fluoxetine and cognitive behavior therapy (CBT). Patients were assessed using the Structured Clinical Interview for DSM-III-R - Axis I (SCID - Patient Edition), Hamilton Depression Rating Scale (HAMD-17) and the following self-rated scales: Beck Depression Inventory (BDI), Beck Hopelessness Scale (BHS), Anxiety Sensitivity Index (ASI) and the Symptom Questionnaire (SQ) prior to starting the 26-week continuation phase. We defined "early drop-outs" (EDs) as patients who dropped out either at or prior to Visit 2 (which was at 2 months into the 6-month continuation phase); those dropping out at Visit 3 or later were defined as "late drop-outs" (LDs) (ED less than or equal to 2 months; LD > 2 months). The Kruskal-Wallis and the Mann-Whitney U tests were used for data analysis. Results: Of the 119 patients. 83 were completers (mean age: 42.1 +/- 9.0 years;46 [55%] women; age of onset of major depressive disorder [MDD] = 24.3 +/- 12.5 years), 11 were EDs(mean age: 38.1 +/- 13.0 years; 4 [36%] women; age of onset of MDD = 22.0 +/- 11.1 years) and 25 were LDs (mean age: 35.2 +/- 10.4 years; 12 [48%] women: age of onset of MDD = 24.6 +/- 11.6 years). LDs were significantly younger than completers ( P < .01). There was no significant difference in age between EDs and LDs, nor between EDs and completers. EDs were more likely to have been depressed for a longer period of time compared to LDs (P < .05). EDs completers were depressed for a longer period of time compared to LDs (P < .05). Conclusions: Our data suggest that late drop-outs are significantly younger than completers, although age is not a predictor between early drop-outs and late drop-outs. Further, early drop-outs are depressed for a longer duration compared to late drop-outs completers are depressed for a longer duration than late dropouts, and Early drop-outs have significantly more social impairment compared to completers. Our study identified some patient characteristics significantly associated with dropping out of a long-term clinical trial. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Depress Clin & Res Program, Boston, MA 02114 USA. RP Sonawalla, SB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Depress Clin & Res Program, WACC 812,15 Parkman St, Boston, MA 02114 USA. FU NIMH NIH HHS [R01-MH-48483-05] NR 22 TC 4 Z9 4 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD APR PY 2002 VL 26 IS 3 BP 415 EP 419 AR PII S0278-5846(01)00265-2 DI 10.1016/S0278-5846(01)00265-2 PG 5 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 536KB UT WOS:000174698300001 PM 11999889 ER PT J AU Chance, MR Bresnick, AR Burley, SK Jiang, JS Lima, CD Sali, A Almo, SC Bonanno, JB Buglino, JA Boulton, S Chen, H Eswar, N He, GS Huang, R Ilyin, V McMahan, L Pieper, U Ray, S Vidal, M Wang, LK AF Chance, MR Bresnick, AR Burley, SK Jiang, JS Lima, CD Sali, A Almo, SC Bonanno, JB Buglino, JA Boulton, S Chen, H Eswar, N He, GS Huang, R Ilyin, V McMahan, L Pieper, U Ray, S Vidal, M Wang, LK TI Structural genomics: A pipeline for providing structures for the biologist SO PROTEIN SCIENCE LA English DT Article ID CRYSTAL-STRUCTURE; PSI-BLAST; PROTEIN; SYNTHASE; REFINEMENT; DATABASE; MATRICES C1 Yeshiva Univ Albert Einstein Coll Med, Ctr Synchrotron Biosci, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Phys & Biophys, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA. Rockefeller Univ, New York, NY 10021 USA. Howard Hughes Med Inst, Coconut Grove, FL 33133 USA. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. Cornell Univ, Weill Med Coll, Dept Biochem, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Struct Biol Program, New York, NY 10021 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Sloan Kettering Inst, Program Mol Biol, New York, NY 10021 USA. RP Chance, MR (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Biochem, 1300 Morris Pk Ave, Bronx, NY 10461 USA. RI Pieper, Ursula/E-4444-2010; OI Huang, Raymond/0000-0001-7661-797X; Lima, Christopher/0000-0002-9163-6092 FU NCI NIH HHS [CA81658]; NCRR NIH HHS [P41-RR12408, P41-RR01633, P41 RR012408]; NIGMS NIH HHS [GM54762, R29 GM054762, GM62529, P50 GM062529, R01 GM054762] NR 53 TC 117 Z9 123 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD APR PY 2002 VL 11 IS 4 BP 723 EP 738 DI 10.1110/ps.470102 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 534PF UT WOS:000174594200001 PM 11910018 ER PT J AU Lupien, SJ Wilkinson, CW Briere, S Menard, C Kin, NMKNY Nair, NPV AF Lupien, SJ Wilkinson, CW Briere, S Menard, C Kin, NMKNY Nair, NPV TI The modulatory effects of corticosteroids on cognition: studies in young human populations SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE corticosteroids; memory; mineralocorticoids; glucocorticoids; humans ID PRIMED BURST POTENTIATION; PITUITARY-ADRENAL AXIS; LONG-TERM POTENTIATION; CA1 PYRAMIDAL NEURONS; DECLARATIVE MEMORY; CORTISOL-LEVELS; GLUCOCORTICOID RECEPTORS; BRAIN; STRESS; HIPPOCAMPUS AB In the present article, we report on two studies performed in young human populations which tested the cognitive impact of glucocorticoids (GC) in situations of decreased or increased ratio of mineralocorticoid (MR) and glucocorticoid (GR) receptor occupation. In the first study, we used a hormone replacement protocol in which we pharmacologically decreased cortisol levels by administration of metyrapone and then restored baseline cortisol levels by a subsequent hydrocortisone replacement treatment, Memory function was tested after each pharmacological manipulation. We observed that metyrapone treatment significantly impaired delayed recall, while hydrocortisone replacement restored performance at placebo level. In the second study, we took advantage of the circadian variation of circulating levels in cortisol and tested the impact of a bolus injection of 35 mg of hydrocortisone in the late afternoon. at a time of very low cortisol concentrations. In a previous study with young normal controls, we injected a similar dose of hydrocortisone in the morning, at the time of the circadian peak, and reported detrimental effects of GC on cognitive function. Here, when we injected a similar dose of hydrocortisone in the afternoon, at the time of the circadian trough, we observed positive effects of GC on memory function. The results of these two studies provide evidence that GC are necessary for learning and memory in human populations. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 McGill Univ, Dept Psychiat, Douglas Hosp Res Ctr, Lab Human Psychoneuroendocrine Res, Verdun, PQ H4H 1R3, Canada. Geriat Inst Montreal, Montreal, PQ H3W 1W5, Canada. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, GRECC, Seattle, WA USA. RP Lupien, SJ (reprint author), McGill Univ, Dept Psychiat, Douglas Hosp Res Ctr, Lab Human Psychoneuroendocrine Res, 6875 Bld Lasalle, Verdun, PQ H4H 1R3, Canada. NR 48 TC 190 Z9 199 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD APR PY 2002 VL 27 IS 3 BP 401 EP 416 AR PII S0306-4530(01)00061-0 DI 10.1016/S0306-4530(01)00061-0 PG 16 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 543AU UT WOS:000175079200007 PM 11818174 ER PT J AU Zhang, KH Davids, E Tarazi, FI Baldessarini, RJ AF Zhang, KH Davids, E Tarazi, FI Baldessarini, RJ TI Effects of dopamine D-4 receptor-selective antagonists on motor hyperactivity in rats with neonatal 6-hydroxydopamine lesions SO PSYCHOPHARMACOLOGY LA English DT Article DE attention deficit hyperactivity disorder (ADHD) antagonist; dopamine; D-4 receptor; 6-hydroxydopamine; motor activity ID PREFRONTAL CORTEX; ANTIPSYCHOTIC AGENTS; EXCITOTOXIC LESIONS; NOVELTY SEEKING; PRIMATE BRAIN; D-AMPHETAMINE; DRD4 GENE; IN-VITRO; L-745,870; DISORDER AB Rationale: Dopamine D-4 receptor gene polymorphism has been repeatedly associated with attention deficit hyperactivity disorder (ADHD) and related personality traits. We recently reported that motor hyperactivity in an animal model of ADHD was dose-dependently reversed by CP-293,019, a D-4 receptor-selective antagonist. However, behavioral effects of this agent may not be attributed exclusively to D-4 receptor blockade, since it interacts with other sites including serotonin receptors. Objectives: To test further the hypothesis that D-4 receptor blockade can reduce motor hyperactivity, behavioral effects of three chemically and pharmacologically dissimilar D-4 antagonists were compared to that of ketanserin, a serotonin 5-HT2A/2C antagonist. Methods: Selective dopamine lesions were made in male rats at postnatal day (PD) 5 with intracisternal 6-hydroxydopamine (100 mug) after desipramine pretreatment (25 mg/kg, SC) to protect nor-adrenergic neurons. Effects of D-4 receptor-selective antagonists and ketanserin on lesion-induced motor hyperactivity were examined during the periadolescent period (postnatal days 23-26) with an infrared photobeam activity system. Results: The D-4 antagonists L-745,870 and U-101,958 dose-dependently inhibited motor hyperactivity in rats with neonatal lesions, whereas S-18126 lacked this effect at doses up to 30 mg/kg. None of these drugs affected motor behavior in sham control rats. In contrast, ketanserin produced apparent sedative effects in both lesioned and intact control rats without normalizing hyperactivity. Conclusions: Motor hyperactivity in this ADHD model was selectively antagonized by three of four dopamine D-4 receptor antagonists evaluated, encouraging clinical assessment of D4 antagonists in patients with ADHD. C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Zhang, KH (reprint author), Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. FU NIMH NIH HHS [MH-34006, MH-47370] NR 49 TC 37 Z9 37 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD APR PY 2002 VL 161 IS 1 BP 100 EP 106 DI 10.1007/s00213-002-1018-1 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 552GA UT WOS:000175610100013 PM 11967637 ER PT J AU Smith-Bindman, R Chu, PW Ecker, JL Feldstein, VA Filly, RA Bacchetti, P AF Smith-Bindman, R Chu, PW Ecker, JL Feldstein, VA Filly, RA Bacchetti, P TI US evaluation of fetal growth: Prediction of neonatal outcomes SO RADIOLOGY LA English DT Article DE fetus, growth and development; fetus, US; infants, newborn; pregnancy, US ID BIRTH-WEIGHT; SONOGRAPHIC EVALUATION; RETARDATION; ULTRASOUND; AGE; RESTRICTION; POPULATION; MORBIDITY; MORTALITY; DIAGNOSIS AB PURPOSE: To determine whether fetal growth measured at serial ultrasonographic (US) can predict neonatal morbidity, independent of whether gestational age is known. MATERIALS AND METHODS: Women (n = 321) who had singleton pregnancies and underwent two or more second- or third-trimester obstetric US examinations were included in a retrospective cohort analysis. Inadequate fetal growth was defined as growth at or below the 10th percentile. The relative risk of each poor outcome was calculated for fetuses with inadequate growth, compared with the risk for fetuses with normal growth. RESULTS: inadequate fetal growth was associated with 3.9 times the risk of a birth weight less than 2,500 g, 17.7 times the risk of a birth weight less than the 3rd percentile for gestational age, 2.3 times the risk of preterm birth, 2.6 times the risk of a long newborn hospital stay, and 3.6 times the risk of neonatal intensive care unit admission. After adjusting for confounding variables, including fetal weight, fetal growth remained a significant predictor of small birth size and poor outcomes. inadequate growth predicted the risk of poor outcomes, even when gestational age was unknown. When inadequate growth was used to identify fetuses at risk, 21-67% of neonates who were small at birth or had poor outcomes were identified at false-positive rates of only 5%-9%. For all outcomes, inadequate growth enabled identification of more fetuses with poor birth outcomes than low estimated fetal weight. CONCLUSION: Morbidity is significantly increased among fetuses who demonstrate less than expected growth. Growth between two US examinations can be used to estimate the risk of neonatal morbidity, even when gestational age is unknown. (C) RSNA, 2002. C1 Univ Calif San Francisco, UCSF Mt Zion Med Ctr, Dept Radiol, San Francisco, CA 94115 USA. Univ Calif San Francisco, UCSF Mt Zion Med Ctr, Dept Epidemiol & Biostat, San Francisco, CA 94115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02129 USA. RP Smith-Bindman, R (reprint author), Univ Calif San Francisco, UCSF Mt Zion Med Ctr, Dept Radiol, 1600 Divisadero St,Box 1667, San Francisco, CA 94115 USA. NR 29 TC 24 Z9 25 U1 0 U2 3 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 APR PY 2002 VL 223 IS 1 BP 153 EP 161 DI 10.1148/radiol.2231010876 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 534WC UT WOS:000174611900021 PM 11930060 ER PT J AU Starkebaum, G AF Starkebaum, G TI Chronic neutropenia associated with autoimmune disease SO SEMINARS IN HEMATOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; GRANULAR LYMPHOCYTE LEUKEMIA; COLONY-STIMULATING FACTOR; LOW-DOSE METHOTREXATE; FELTYS-SYNDROME; RHEUMATOID-ARTHRITIS; IMMUNE-COMPLEXES; FAS LIGAND; CYCLOSPORINE-A; REACTIVE IGG C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Starkebaum, G (reprint author), VA Puget Sound Hlth Care Syst, S-01 CMO,1660 S Columbian Way, Seattle, WA 98108 USA. NR 59 TC 36 Z9 40 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD APR PY 2002 VL 39 IS 2 BP 121 EP 127 DI 10.1053/shem.2002.31918 PG 7 WC Hematology SC Hematology GA 540WV UT WOS:000174954600009 PM 11957195 ER PT J AU Willett, CG AF Willett, CG TI Results of radiation therapy in gastric cancer SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID RANDOMIZED TRIAL; STOMACH; CARCINOMA; ADJUVANT; ADENOCARCINOMA; RADIOTHERAPY; CHEMOTHERAPY; FAILURE; SURGERY; 2ND C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Willett, CG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 17 TC 6 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD APR PY 2002 VL 12 IS 2 BP 170 EP 175 DI 10.1053/srao.2002.30819 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 548JL UT WOS:000175384800007 PM 11979418 ER PT J AU Meyerhardt, JA Fuchs, CS AF Meyerhardt, JA Fuchs, CS TI Chemotherapy options for gastric cancer SO SEMINARS IN RADIATION ONCOLOGY LA English DT Review ID PHASE-II TRIAL; CONTINUOUS-INFUSION 5-FLUOROURACIL; GROWTH-FACTOR RECEPTOR; UPPER GASTROINTESTINAL-TRACT; CARBON-ADSORBED MITOMYCIN; HIGH-DOSE METHOTREXATE; LONG-TERM SURVIVAL; PREOPERATIVE CHEMOTHERAPY; PERITONEAL RECURRENCE; CURATIVE RESECTION C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Internal Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Internal Med, Div Med Oncol, Boston, MA 02114 USA. RP Fuchs, CS (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 11 Binney St, Boston, MA 02115 USA. NR 106 TC 16 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD APR PY 2002 VL 12 IS 2 BP 176 EP 186 DI 10.1053/srao.2002.30823 PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 548JL UT WOS:000175384800008 PM 11979419 ER PT J AU Salgado, DM Vogt, DS King, LA King, DW AF Salgado, DM Vogt, DS King, LA King, DW TI Gender Awareness Inventory-VA: A measure of ideology, sensitivity, and knowledge related to women veterans' health care SO SEX ROLES LA English DT Article DE gender; employee attitudes; women's health; female patients ID ROLE EGALITARIANISM SCALE; MENTAL-HEALTH; PATIENT SATISFACTION; FEMALE VETERANS; SEX BIAS; PHYSICIAN; ATTITUDES; DEPRESSION; DIAGNOSIS AB Within the Veterans Health Administration, it has become increasingly important to assess health-care workers' attitudes toward and beliefs about female patients, sensitivity to the unique needs of female patients, and knowledge about women veterans and the programs and services available to them. The current study describes the development of the Gender Awareness Inventory-VA, an instrument that assesses 3 components: gender-role ideology, gender sensitivity, and knowledge among health-care staff. Data were drawn from various samples of Veterans Health Administration employees in a large geographical region (overall N > 1,100; nationally, this population includes roughly 37% minorities). In a series of psychometric inquiries, evidence for reliability and validity was established, and preliminary evidence was provided for the instrument's underlying factor structure. C1 VA Boston Healthcare Syst, Natl Ctr Posttraumat Stress Disorder 116B3, Boston, MA USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP King, LA (reprint author), Natl Ctr Posttraumat Stress Disorder, 150 S Huntington Ave, Boston, MA 02130 USA. NR 62 TC 7 Z9 7 U1 1 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0360-0025 J9 SEX ROLES JI Sex Roles PD APR PY 2002 VL 46 IS 7-8 BP 247 EP 262 AR UNSP pp561-sers-378200 DI 10.1023/A:1020171416038 PG 16 WC Psychology, Developmental; Psychology, Social; Women's Studies SC Psychology; Women's Studies GA 588VY UT WOS:000177723800005 ER PT J AU Ezzeddine, MA Lev, MH McDonald, CT Rordorf, G Oliveira-Filho, J Aksoy, FG Farkas, J Segal, AZ Schwamm, LH Gonzalez, RG Koroshetz, WJ AF Ezzeddine, MA Lev, MH McDonald, CT Rordorf, G Oliveira-Filho, J Aksoy, FG Farkas, J Segal, AZ Schwamm, LH Gonzalez, RG Koroshetz, WJ TI CT angiography with whole brain perfused blood volume imaging - Added clinical value in the assessment of acute stroke SO STROKE LA English DT Article DE angiography; diagnostic imaging; stroke assessment; stroke classification; tomography, x-ray computed ID ACUTE ISCHEMIC STROKE; ACUTE CEREBRAL-ISCHEMIA; INTEROBSERVER AGREEMENT; INTERRATER RELIABILITY; TRANSCRANIAL DOPPLER; SUBTYPE DIAGNOSIS; CLASSIFICATION; ARTERY; TRIAL; INFARCTION AB Background and Purpose-In CT angiographic and perfusion imaging (CTA/CTP), rapid CT scanning is performed during the brief steady state administration of a contrast bolus, creating both vascular phase images of the major intracranial vessels and perfused blood volume-weighted parenchymal phase images of the entire brain. We assessed the added clinical value of the data provided by CTA/CTP over that of clinical examination and noncontrast CT (NCCT) alone. Methods-NCCT and CTA/CTP imaging was performed in 40 patients presenting with an acute stroke. Short clinical vignettes were retrospectively prepared. After concurrent review of the vignettes and NCCT, a stroke neurologist rated infarct location, vascular territory, vessel(s) occluded, and Trial of Org 10172 in Acute Stroke Treatment (TOAST) and Oxfordshire Community Stroke Project classifications. The ratings were repeated after serial review of each of the CTA/CTP components: (1) axial CTA source images; (2) CTP whole brain blood volume-weighted source images; and (3) maximum-intensity projection 3-dimensional reformatted images. The sequential ratings for each case were compared with the final discharge assessment. Results-Compared with the initial review after NCCT, CTA/CTP improved the overall accuracy of infarct localization (P<0.001), vascular territory determination (P=0.003), vessel occlusion identification (P<0.001), TOAST classification (P=0.039), and Oxfordshire Community Stroke Project classification (P<0.001) by 40%, 28%, 38%, 18%, and 32%, respectively. Conclusions-Admission CTA/CTP imaging significantly improves accuracy, over that of initial clinical assessment and NCCT imaging alone, in the determination of infarct localization, site of vascular occlusion, and Oxfordshire classification in acute stroke patients. C1 Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NINCDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. Cornell Univ, Med Ctr, Dept Neurol, New York, NY 10021 USA. RP Lev, MH (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, 55 Fruit St, Boston, MA 02114 USA. OI Schwamm, Lee/0000-0003-0592-9145 FU NCRR NIH HHS [RR-13213]; NINDS NIH HHS [NS-34626] NR 29 TC 83 Z9 89 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2002 VL 33 IS 4 BP 959 EP 966 DI 10.1161/hs0402.105388 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 539EL UT WOS:000174857400014 PM 11935044 ER PT J AU Nakatani, Y AF Nakatani, Y TI HIV-1 transcription: Activation mediated by acetylation of Tat SO STRUCTURE LA English DT Editorial Material ID ELONGATION; BINDING; RNA AB Acetylation of HIV-1 Tat stimulates transcriptional elongation by dissociating Tat from TAR, a transactivation response RNA element in nascent HIV-1 transcripts. In the March issue of Molecular Cell, Mujtaba et al. show that the bromodomain of PCAF acetylase specifically binds to acetylated,rat and leads to dissociation of Tat from TAR. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Nakatani, Y (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 10 TC 7 Z9 7 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD APR PY 2002 VL 10 IS 4 BP 443 EP 444 AR PII S0969-2126(02)00754-2 DI 10.1016/S0969-2126(02)00754-2 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 539GX UT WOS:000174863100001 PM 11937047 ER PT J AU Brewster, DC AF Brewster, DC TI Do current results of endovascular abdominal aortic aneurysm repair justify more widespread use? SO SURGERY LA English DT Article ID STENT-GRAFT TREATMENT; MULTICENTER; COMPLICATIONS; INTERMEDIATE; REGISTRY; 6-YEAR C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Brewster, DC (reprint author), 1 Hawthorne Pl,Suite 111, Boston, MA 02114 USA. NR 26 TC 7 Z9 7 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD APR PY 2002 VL 131 IS 4 BP 363 EP 367 DI 10.1067/msy.2002.118449 PG 5 WC Surgery SC Surgery GA 542VD UT WOS:000175064200001 PM 11935124 ER PT J AU Machens, HG Morgan, JR Berthiaume, F Stefanovich, P Siemers, F Krapohl, B Berger, A Mailander, P AF Machens, HG Morgan, JR Berthiaume, F Stefanovich, P Siemers, F Krapohl, B Berger, A Mailander, P TI Platelet-derived growth factor-AA-mediated functional angiogenesis in the rat epigastric island flap after genetic modification of fibroblasts is ischemia dependent SO SURGERY LA English DT Article ID SKIN FLAPS; RECOMBINANT RETROVIRUSES; EXPRESSION; DELIVERY; SURVIVAL; VEGF AB Background. The aim of this study was to induce therapeutic angiogenesis in ischemically challenged flap tissue by means of gene transfer. Methods. isogenic rat fibroblasts were retrovirally transfected to produce platelet-derived growth factor (PDGF)-AA. Stable gene expression was monitored by PDGF-AA enzyme-linked immunosorbent assay. Eighty animals were divided into 2 groups (1 and 2), each with 4 subgroups. The angiogenic target was a 7 X 7-cm epigastric island flap used as a necrosis model. Group 1 ' 1 received flap treatment I week before flap elevation: 101 genetically modified fibroblasts, expressing PDGF-AA (genetically modified fibroblasts) plus 1 mL of Dulbecco's modified Eagle's medium (DMEM) (1A), 10(7) nonmodified fibroblasts (NMFB) plus 1 mL of DMEM (1B), 1 mL of DMEM (1C), and 1 mL of sodium chloride 0.9% (ID). All substances were injected at evenly distributed spots into the panniculus carnosus of the entire flap, Group 2 had the same flap treatment at the day of flap elevation. All flaps were sutured back. Seven days later, the flaps were harvested and examined both clinically, histologically, and immunohistochemically. Results. In vitro, the GMFB produced up to 117.9 +/- 57.2 ng of PDGF-AA/mL medium during a 4-day period, compared with 0.7 +/- 0.6 ng of PDGF-AA/mL medium produced by NMFB in the same time period. In vivo production of PDGF-AA in flaps amounted to 1.3 +/- 0.7 ng of PDGF-AA/1 muL flap tissue for group 1A and 1.7 +/- 1.1 ng of PDGF-AA/1 muL flap tissue for group 2A seven days after cell transplantation. Fibroblasts persisted in allflaps from groups 1A, 113, 2A, and 213 without major inflammatory reaction. Clinically, group 2.4 developed significantly lessflap necrosis compared with all other groups, including group 1A. Accordingly, only group 2A gave significant histologic and immunohistochemical evidence for enhanced angiogenesis within the flap tissue. Conclusions. After retroviral gene transfer, isogenic ratfibroblasts produce high amounts of PDGF-AA in vitro. In vivo, PDGF-AA can be detected in flaps receiving genetically modified fibroblasts, which suggests survival of the implanted fibroblasts in this model. PDGF-AA proiiuced by GALFB can induceflap angiogenesis only under ischernic conditions in this model. Transplantation o PDGFL-AA-overexpressing fibroblasts results in higherflap survival in this model. C1 Lubeck Univ Clin, Clin Plast Hand & Reconstruct Surg, Burn Ctr, D-23562 Lubeck, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Serv, Boston, MA USA. Shriners Burn Hosp, Boston, MA USA. Hannover Med Sch, Clin Plast Hand & Reconstruct Surg, Hannover, Germany. RP Machens, HG (reprint author), Lubeck Univ Clin, Clin Plast Hand & Reconstruct Surg, Burn Ctr, Ratzeburger Allee 160, D-23562 Lubeck, Germany. OI Morgan, Jeffrey/0000-0002-7546-3443 NR 18 TC 13 Z9 15 U1 1 U2 1 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 APR PY 2002 VL 131 IS 4 BP 393 EP 400 DI 10.1067/msy.2002.121887 PG 8 WC Surgery SC Surgery GA 542VD UT WOS:000175064200006 PM 11935129 ER PT J AU Warshaw, AL AF Warshaw, AL TI Revisiting our surgical heritage SO SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, Dept Surg, White 506, Boston, MA 02114 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD APR PY 2002 VL 131 IS 4 BP 470 EP 471 DI 10.1067/msy.2002.121095 PG 2 WC Surgery SC Surgery GA 542VD UT WOS:000175064200017 ER PT J AU Greenlee, DJ Fan, H Lawless, K Harrison, CR Gulley, ML AF Greenlee, DJ Fan, H Lawless, K Harrison, CR Gulley, ML TI Quantitation of CMV by real-time PCR in transfusable RBC units SO TRANSFUSION LA English DT Article ID POLYMERASE-CHAIN-REACTION; HUMAN CYTOMEGALOVIRUS DNA; BLOOD MONONUCLEAR-CELLS; HUMAN IMMUNODEFICIENCY VIRUS; PERIPHERAL-BLOOD; TRANSPLANT RECIPIENTS; MARROW TRANSPLANT; PP65 ANTIGENEMIA; ENZYMATIC AMPLIFICATION; RAPID DETECTION AB BACKGROUND: CMV is one of the most significant pathogens infecting immunocompromised individuals CMV is transmissible through transfusion of blood components. The goal of this study was to measure CMV levels in RBC units using a sensitive and quantitative DNA amplification assay. STUDY DESIGN AND METHODS: An assay to measure CMV load was developed by using real-time PCR to target the major immediate early viral gene. A probe (TaqMan, Applied Biosystems) was used to confirm product specificity and to permit quantitation of CMV in blood samples on a sequence detection system (ABI Prism 7700, Applied Biosystems). RESULTS: The assay was shown to be accurate, linear, and sensitive to as few as five copies of CMV DNA per PCR. The assay was applied to aliquots of RBC units from 203 healthy donors, 110 of whom were seropositive for CMV. CMV DNA was not detected in any of the 203 RBC samples. CONCLUSION: The findings statistically imply that at least 98.5 percent of RBC units have a CMV load of less than 250 copies per mL. Future clinical studies on larger numbers of units are required to determine the utility of real-time PCR in evaluating the risk of CMV transmission and in confirming the efficacy of WBC reduction. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Hlth Syst, San Antonio, TX USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. RP Gulley, ML (reprint author), Univ N Carolina, Dept Pathol, 101 Manning Dr,Brinkhous Bullitt Bldg, Chapel Hill, NC 27599 USA. NR 39 TC 13 Z9 13 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD APR PY 2002 VL 42 IS 4 BP 403 EP 408 DI 10.1046/j.1525-1438.2002.00020.x PG 6 WC Hematology SC Hematology GA 550MM UT WOS:000175506900005 PM 12076285 ER PT J AU Pasquinelli, AE AF Pasquinelli, AE TI MicroRNAs: deviants no longer SO TRENDS IN GENETICS LA English DT Article ID C-ELEGANS; REGULATORY RNA; GENE; LIN-14; EXPRESSION AB Almost ten years ago, the Ambros laboratory made the extraordinary discovery that a gene essential for development in Caenorhabditis elegans encoded a 22-nucleotide, untranslated RNA. Further genetic studies in this nematode revealed the existence of a second tiny RNA gene that turned out to be conserved in animals as diverse as flies and humans. Now, the Ambros, Bartel and Tuschl laboratories have proven that those odd RNAs were just the first examples of a large family of RNAs, termed microRNAs (miRNAs). Although untranslated RNA genes, such as transfer RNAs and ribosomal RNAs, perform essential housekeeping roles in all living organisms, growing numbers of other RNAs, some widely conserved across phyla and others limited to certain species, are being uncovered and shown to fulfill specific duties. The discovery of miRNAs establishes a new class of regulatory RNAs and highlights the existence of unexpected RNA genes that, although ancient, are not extinct. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Pasquinelli, AE (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Wellman 8,50 Blossom St, Boston, MA 02114 USA. NR 20 TC 52 Z9 75 U1 0 U2 3 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD APR PY 2002 VL 18 IS 4 BP 171 EP 173 DI 10.1016/S0168-9525(01)02624-5 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 537QL UT WOS:000174770300003 PM 11932009 ER PT J AU Vamvakas, EC Carven, JH AF Vamvakas, EC Carven, JH TI Allogeneic blood transfusion and postoperative duration of mechanical ventilation: effects of red cell supernatant, platelet supernatant, plasma components and total transfused fluid SO VOX SANGUINIS LA English DT Article DE cardiac surgery; endotracheal intubation; pulmonary failure/insufficiency; transfusion-related immunomodulation ID STORED HUMAN-BLOOD; MULTIPLE ORGAN FAILURE; LEUKOCYTE DEPLETION; CARDIAC-SURGERY; LUNG-FUNCTION; BIOACTIVE SUBSTANCES; THALASSEMIA MAJOR; CLINICAL-TRIAL; RELEASE; BYPASS AB Background and Objectives In patients undergoing open-heart surgery, allogeneic blood transfusion (ABT) may be related to an enhanced inflammatory response and impaired pulmonary function, resulting in a need for prolonged mechanical ventilation. Transfused red blood cell (RBC) supernatant, platelet supernatant or plasma components, may exercise varying effects on pulmonary function, because these fluids differ in their content of soluble biological-response modifiers. Materials and Methods The records of 416 patients undergoing coronary artery bypass graft operations at the Massachusetts General Hospital were reviewed. Possible predictors and the number of days of postoperative ventilation, as well as the number of all transfused blood components, were recorded. The association between mechanical ventilation past the day of operation and the volume of transfused RBC supernatant, platelet supernatant, or plasma components, was calculated by logistic regression analyses. Results The volume of each transfused fluid differed (P < 0.0001) among patients ventilated for 0, 1, 2, 3, or : 4 days after the day of the operation. After adjusting for the effects of confounding factors, the volume of administered RBC supernatant was associated (P = 0.0312) with the likelihood of postoperative ventilation past the day of operation, but the volume of platelet supernatant, plasma components, or total transfused fluid was not (P = 0.1528, P = 0.1847, and P = 0.0504, respectively). Conclusions These results are congruent with the hypotheses that ABT may impair postoperative pulmonary function and that any such adverse effect of ABT is probably mediated by the supernatant fluid of stored RBCs. Both hypotheses should be examined further, in future studies of the outcomes of ABT, C1 NYU Med Ctr, Sch Med, Dept Pathol, Blood Bank, New York, NY 10016 USA. Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. RP Vamvakas, EC (reprint author), NYU Med Ctr, Sch Med, Dept Pathol, Blood Bank, RRG-17,400 E 34th St, New York, NY 10016 USA. NR 43 TC 49 Z9 50 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PD APR PY 2002 VL 82 IS 3 BP 141 EP 149 DI 10.1046/j.1423-0410.2002.00155.x PG 9 WC Hematology SC Hematology GA 541DK UT WOS:000174969800007 PM 11952989 ER PT J AU Laybutt, DR Sharma, A Sgroi, DC Gaudet, J Bonner-Weir, S Weir, GC AF Laybutt, DR Sharma, A Sgroi, DC Gaudet, J Bonner-Weir, S Weir, GC TI Genetic regulation of metabolic pathways in beta-cells disrupted by hyperglycemia SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STIMULATED INSULIN-SECRETION; ACTIVATED RECEPTOR-ALPHA; RAT PANCREATIC-ISLETS; DIABETIC FATTY RATS; UNCOUPLING PROTEIN-2; GLUCOSE-TOLERANCE; OBESE RATS; EXPRESSION; OVEREXPRESSION; APOPTOSIS AB In models of type 2 diabetes the expression of beta-cell genes is altered, but these changes have not fully explained the impairment in beta-cell function. We hypothesized that changes in beta-cell phenotype and global alterations in both carbohydrate and lipid pathways are likely to contribute to secretory abnormalities. Therefore, expression of genes involved in carbohydrate and lipid metabolism were analyzed in islets 4 weeks after 85-95% partial pancreatectomy (Px) when beta-cells have impaired glucose-induced insulin secretion and ATP synthesis. Px rats after 1 week developed mild to severe hyperglycemia that was stable for the next 3 weeks, whereas neither plasma triglyceride, non-esterified fatty acid, or islet triglyceride levels were altered. Expression of peroxisome proliferator-activated receptors (PPARs), with several target genes, were reciprocally regulated; PPARalpha was markedly reduced even at low level hyperglycemia, whereas PPARgamma was progressively increased with increasing hyperglycemia. Uncoupling protein 2 (UCP-2) was increased as were other genes barely expressed in sham islets including lactate dehydrogenase-A (LDH-A), lactate (monocarboxylate) transporters, glucose-6-phosphatase, fructose-1,6-bisphosphatase, 12-lipoxygenase, and cyclooxygenase 2. On the other hand, the expression of beta-cell-associated genes, insulin, and GLUT2 were decreased. Treating Px rats with phlorizin normalized hyperglycemia without effecting plasma fatty acids and reversed the changes in gene expression implicating the importance of hyperglycemia per se in the loss of beta-cell phenotype. In addition, parallel changes were observed in beta-cell-enriched tissue dissected by laser capture microdissection from the central core of islets. In conclusion, chronic hyperglycemia leads to a critical loss of beta-cell differentiation with altered expression of genes involved in multiple metabolic pathways diversionary to normal beta-cell glucose metabolism. This global maladaptation in gene expression at the time of increased secretory demand may contribute to the beta-cell dysfunction found in diabetes. C1 Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02129 USA. RP Weir, GC (reprint author), Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-35449, DK-36836] NR 57 TC 127 Z9 132 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 29 PY 2002 VL 277 IS 13 BP 10912 EP 10921 DI 10.1074/jbc.M111751200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 534WQ UT WOS:000174613100022 PM 11782487 ER PT J AU Xu, L Fukumura, D Jain, RK AF Xu, L Fukumura, D Jain, RK TI Acidic extracellular pH induces vascular endothelial growth factor (VEGF) in human glioblastoma cells via ERK1/2 MAPK signaling pathway - Mechanism of low pH-induced VEGF SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; INDUCED GENE-EXPRESSION; INDUCED TRANSCRIPTIONAL ACTIVATION; OVARIAN-CARCINOMA CELLS; NIH 3T3 CELLS; PERMEABILITY FACTOR; INTERLEUKIN-8 EXPRESSION; NUCLEAR TRANSLOCATION; INDUCED ELEVATION; IN-VIVO AB Overexpression of vascular endothelial growth factor (VEGF) is associated with disease progression in human glioblastomas. We recently showed that VEGF promoter activity is inversely correlated with tumor extracellular pH (pH(o)) in vivo in the human glioma (U87 MG) xenografts. Here we show that substitution of the neutral culture medium (pH 7.3) with acidic pH medium (pH 6.6) up-regulates VEGF mRNA and protein production in human glioblastoma cells as reflected by Northern blot analysis and enzyme-linked immunosorbent assay. Functional analysis of the VEGF promoter reveals that the sequence between -961 bp and -683 bp upstream of the transcription start site is responsible for the transcriptional activation of the VEGF gene by acidic pH. This region contains the binding site for AP-1. Consequently, AP-1 luciferase reporter gene was activated by acidic pH. Gel-shift analysis confirmed that AP-1 DNA binding activity is induced under acidic pH. While investigating the upstream signaling pathways, we found that ERK1/2 MAPK is activated and translocates to the nucleus to activate Elk-1, and inhibition of the activation of ERK by specific inhibitors of MEK1 blocks the up-regulation of VEGF by low pH. Dominant negative forms of Ras and Raf abolished the activation of VEGF promoter by acidic pH. These results show that acidic pH activates Ras and the ERK1/2 MAPK pathway to enhance VEGF transcription via AP-1, leading to increased VEGF production. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, 100 Blossom St Cox 7, Boston, MA 02114 USA. NR 58 TC 152 Z9 159 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 29 PY 2002 VL 277 IS 13 BP 11368 EP 11374 DI 10.1074/jbc.M108347200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 534WQ UT WOS:000174613100079 PM 11741977 ER PT J AU Xu, K Xu, YH Chen, JF Schwarzschild, MA AF Xu, K Xu, YH Chen, JF Schwarzschild, MA TI Caffeine's neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity shows no tolerance to chronic caffeine administration in mice SO NEUROSCIENCE LETTERS LA English DT Article DE dopamine; dopamine transporter; A(2A) adenosine receptor; locomotion; neuroprotection; striatum ID ADENOSINE RECEPTOR-BINDING; PARKINSONS-DISEASE; A(2A) RECEPTORS; MESSENGER-RNA; BRAIN; ANTAGONIST; EXPRESSION; COFFEE; A(1); RATS AB We investigated the effect of chronic daily caffeine treatment on caffeine's neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic toxicity. Mice received either caffeine (20 mg/kg) or saline daily for 9 days. Caffeine-induced locomotion tolerance developed within 3 days of treatment and persisted for the duration of the experiment. On day 10, mice were treated with MPTP (20 mg/kg, x 4). Caffeine (20 mg/kg) or saline was administered 10 min before each MPTP dose. Acute pretreatment with caffeine attenuated MPTP-induced loss of striatal dopamine and dopamine transporter binding sites, and this attenuation was identical in mice pretreated chronically with caffeine or with saline. Thus, in contrast to the locomotor stimulant effect of caffeine, its neuroprotectant effect did not show tolerance to prior caffeine exposure. These data raise the possibility that caffeine may induce neuroprotection and locomotion by distinct mechanisms. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. RP Chen, JF (reprint author), Boston Univ, Sch Med, Dept Neurol, 715 Albany St C314, Boston, MA 02118 USA. FU NIA NIH HHS [AG18167]; NIEHS NIH HHS [ES10804]; NINDS NIH HHS [NS37403] NR 20 TC 61 Z9 61 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAR 29 PY 2002 VL 322 IS 1 BP 13 EP 16 AR PII S0304-3940(02)00069-1 DI 10.1016/S0304-3940(02)00069-1 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 539CT UT WOS:000174852700004 PM 11958832 ER PT J AU Shang, YF Brown, M AF Shang, YF Brown, M TI Molecular determinants for the tissue specificity of SERMs SO SCIENCE LA English DT Article ID HUMAN ESTROGEN-RECEPTOR; PROMOTER-CONTEXT; C-MYC; ACTIVATION; TRANSCRIPTION; COACTIVATOR; CANCER; GENE; 4-HYDROXYTAMOXIFEN; ANTIESTROGEN AB Selective estrogen receptor modulators (SERMs) mimic estrogen action in certain tissues while opposing it in others. The therapeutic effectiveness of SERMS such as tamoxifen and raloxifene in breast cancer depends on their antiestrogenic activity. In the uterus, however, tamoxifen is estrogenic. Here, we show that both tamoxifen and raloxifene induce the recruitment of corepressors to target gene promoters in mammary cells. In endometrial cells, tamoxifen, but not raloxifene, acts like estrogen by stimulating the recruitment of coactivators to a subset of genes. The estrogen-like activity of tamoxifen in the uterus requires a high level of steroid receptor coactivator 1 (SRC-1) expression. Thus cell type- and promoter-specific differences in coregulator recruitment determine the cellular response to SERMs. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Brown, M (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Myles, Brown/B-6906-2008; Marion-Poll, Frederic/D-8882-2011; OI Marion-Poll, Frederic/0000-0001-6824-0180; Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [CA57374] NR 28 TC 782 Z9 806 U1 6 U2 39 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 MAR 29 PY 2002 VL 295 IS 5564 BP 2465 EP 2468 DI 10.1126/science.1068537 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 536QD UT WOS:000174712600060 PM 11923541 ER PT J AU Allison, DB Gadbury, GL Heo, MS Fernandez, JR Lee, CK Prolla, TA Weindruch, R AF Allison, DB Gadbury, GL Heo, MS Fernandez, JR Lee, CK Prolla, TA Weindruch, R TI A mixture model approach for the analysis of microarray gene expression data SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article ID INFERENCE; PROFILE; GROWTH; CDNA AB Microarrays have emerged as powerful tools allowing investigators to assess the expression of thousands of genes in different tissues and organisms. Statistical treatment of the resulting data remains a substantial challenge. Investigators using microarray expression studies may wish to answer questions about the statistical significance of differences in expression of any of the genes under study, avoiding false positive and false negative results. We have developed a sequence of procedures involving finite mixture modeling and bootstrap inference to address these issues in studies involving many thousands of genes. We illustrate the use of these techniques with a dataset involving calorically restricted mice. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. Univ Alabama, Ctr Res Clin Nutr, Birmingham, AL 35294 USA. Univ Missouri, Dept Math & Stat, Rolla, MO 65401 USA. Columbia Univ Coll Phys & Surg, Inst Human Nutr, St Lukes Roosevelt Hosp, Obes Res Ctr, New York, NY 10032 USA. Univ Wisconsin, Ctr Environm Toxicol, Madison, WI 53706 USA. Univ Wisconsin, Dept Genet, Madison, WI 53706 USA. Univ Wisconsin, Dept Med Genet, Madison, WI 53706 USA. Univ Wisconsin, Dept Med, Madison, WI USA. Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI USA. William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. RI Lee, Cheol-Koo/F-2103-2013; OI Lee, Cheol-Koo/0000-0003-3927-9195; Allison, David/0000-0003-3566-9399 NR 32 TC 219 Z9 224 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD MAR 28 PY 2002 VL 39 IS 1 BP 1 EP 20 AR PII S0167-9473(01)00046-9 DI 10.1016/S0167-9473(01)00046-9 PG 20 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 542CQ UT WOS:000175026300002 ER PT J AU Blagosklonny, MV Pardee, AB AF Blagosklonny, MV Pardee, AB TI Conceptual biology: Unearthing the gems SO NATURE LA English DT Editorial Material C1 New York Med Coll, Brander Canc Res Inst, Hawthorne, NY 10532 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Blagosklonny, MV (reprint author), New York Med Coll, Brander Canc Res Inst, Hawthorne, NY 10532 USA. NR 5 TC 51 Z9 54 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 28 PY 2002 VL 416 IS 6879 BP 373 EP 373 DI 10.1038/416373a PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 534UX UT WOS:000174607800024 PM 11919607 ER PT J AU Wyszynski, M Kim, E Dunah, AW Passafaro, M Valtschanoff, JG Serra-Pages, C Streuli, M Weinberg, RJ Sheng, M AF Wyszynski, M Kim, E Dunah, AW Passafaro, M Valtschanoff, JG Serra-Pages, C Streuli, M Weinberg, RJ Sheng, M TI Interaction between GRIP and liprin-alpha/SYD2 is required for AMPA receptor targeting SO NEURON LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; MOTOR AXON GUIDANCE; FAMILY; LAR; BINDING; DROSOPHILA; PLASTICITY; EXPRESSION; LIGANDS; CLUSTER AB Interaction with the multi-PDZ protein GRIP is required for the synaptic targeting of AMPA receptors, but the underlying mechanism is unknown. We show that GRIP binds to the liprin-alpha/SYD2 family of proteins that interact with LAR receptor protein tyrosine phosphatases (LAR-RPTPs) and that are implicated in presynaptic development. In neurons, liprin-alpha and LAR-RPTP are enriched at synapses and coimmunoprecipitate with GRIP and AMPA receptors. Dominant-negative constructs that interfere with the GRIP-liprin interaction disrupt the surface expression and dendritic clustering of AMPA receptors in cultured neurons. Thus, by mediating the targeting of liprin/GRIP-associated proteins, liprin-alpha is important for postsynaptic as well as presynaptic maturation. C1 Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MIT, Ctr Learning & Memory, RIKEN MIT Neurosci Res Ctr, Cambridge, MA 02139 USA. MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. Korea Adv Inst Sci & Technol, Dept Biol Sci, Taejon 305701, South Korea. Univ N Carolina, Dept Cell Biol & Anat, Chapel Hill, NC 27599 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Sheng, M (reprint author), Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. RI Kim, Eunjoon/C-1566-2011 FU NCI NIH HHS [CA 55547]; NINDS NIH HHS [NS35050] NR 34 TC 165 Z9 179 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD MAR 28 PY 2002 VL 34 IS 1 BP 39 EP 52 DI 10.1016/S0896-6273(02)00640-2 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 536HR UT WOS:000174695100008 PM 11931740 ER PT J AU Dellon, ES Szczepiorkowski, ZM Dzik, WH Graeme-Cook, F Ades, A Bloomer, JR Cosimi, AB Chung, RT AF Dellon, ES Szczepiorkowski, ZM Dzik, WH Graeme-Cook, F Ades, A Bloomer, JR Cosimi, AB Chung, RT TI Treatment of recurrent allograft dysfunction with intravenous hematin after liver transplantation for erythropoietic protoporphyria SO TRANSPLANTATION LA English DT Article ID DISEASE; COMPLICATIONS; THERAPY AB Erythropoietic protoporphyria (EPP) is a rare inherited disorder of the heme biosynthetic pathway in which toxic levels of protoporphyrins often precipitate in the liver, leading to cirrhosis, liver failure, and the need for liver transplantation (OLT). Because the underlying enzyme defect in EPP is bone marrow derived, the risk for recurrent EPP allograft dysfunction is high. Although plasmapheresis may ameliorate acute allograft disease, strategies to maintain disease remission are needed. A 59-year-old man who underwent OLT for hepatic EPP experienced increased bilirubin and aminotransferases on postoperative day 700. Allograft biopsy demonstrated recurrent EPP. He was managed initially with plasmapheresis, hypertransfusion, and infusions of i.v. hematin. After normalization of liver tests, the hematin infusions have been given intermittently, are well tolerated, and associated with normal allograft function for nearly 2 years. This is the first case of the use of hematin given post-OLT to help achieve and maintain remission of allograft EPP disease. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Alabama, Ctr Liver, Birmingham, AL USA. Exeter Hosp, Exeter, NH USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. RI Szczepiorkowski, Zbigniew/A-1359-2007 OI Szczepiorkowski, Zbigniew/0000-0003-2357-9564 NR 18 TC 33 Z9 33 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 MAR 27 PY 2002 VL 73 IS 6 BP 911 EP 915 AR UNSP 0041-1337/02/7306-911/0 DI 10.1097/00007890-200203270-00014 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 539LB UT WOS:000174870600014 PM 11923691 ER PT J AU Palacios, IF Sanchez, PL Harrell, LC Weyman, AE Block, PC AF Palacios, IF Sanchez, PL Harrell, LC Weyman, AE Block, PC TI Which patients benefit from percutaneous mitral balloon valvuloplasty? Prevalvuloplasty and postvalvuloplasty variables that predict long-term outcome SO CIRCULATION LA English DT Article DE valvuloplasty; echocardiography; follow-up studies; mitral valve ID INOUE BALLOON; FOLLOW-UP; SURGICAL COMMISSUROTOMY; CLOSED COMMISSUROTOMY; VALVOTOMY; STENOSIS; IMMEDIATE; REGURGITATION; VALVE AB Background-Percutaneous mitral balloon valvuloplasty (PMV) results in good immediate results, particularly in patients with echocardiographic scores (Echo-Sc) less than or equal to8. However, which variables relate to long-term outcome is unclear. Methods and Results-We report the immediate and long-term clinical follow-up (mean, 4.2 +/- 3.7 years; range, 0.5 to 15) of 879 patients who underwent 939 PMV procedures. Patients were divided into 2 groups, Echo-Sc less than or equal to8 (n=601) and Echo-Sc >8 (n=278). PMV resulted in an increase in mitral valve area from 1.0 +/- 0.3 to 2.0 +/- 0.6 cm(2) in patients with Echo-Sc less than or equal to8 and from 0.8 +/- 3 to 1.6 +/- 6 cm(2) in patients with Echo-Sc >8 (P<0.0001). Although adverse events (death, mitral valve surgery, and redo PMV) were low within the first 5 years of follow-up, a progressive number of events occurred beyond this period. Nevertheless, survival (82% versus 57%) and event-free survival (38% versus 22%) at 12-year follow-up was greater in patients with Echo-Sc >58 (P<0.0001). Cox regression analysis identified post-PMV mitral regurgitation greater than or equal to3+, Echo-Sc >8, age, prior surgical commissurotomy, NYHA functional class IV, pre-PMV mitral regurgitation greater than or equal to2+, and higher post-PMV pulmonary artery pressure as independent predictors of combined events at long-term follow-up. Conclusions-The immediate and long-term outcome of patients undergoing PMV is multifactorial. The use of the Echo-Sc in conjunction with other clinical and morphological predictors of PMV outcome allows identification of patients who will obtain the best outcome from PMV. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiac Unit, Boston, MA 02114 USA. RP Palacios, IF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiac Unit, Boston, MA 02114 USA. OI Sanchez, Pedro L/0000-0002-4288-345X NR 35 TC 105 Z9 121 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 26 PY 2002 VL 105 IS 12 BP 1465 EP 1471 DI 10.1161/01.CIR.0000012143.27196.F4 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 536EC UT WOS:000174686900024 PM 11914256 ER PT J AU Zile, MR Brutsaert, DL AF Zile, MR Brutsaert, DL TI New concepts in diastolic dysfunction and diastolic heart failure: Part II - Causal mechanisms and treatment SO CIRCULATION LA English DT Article ID LEFT-VENTRICULAR HYPERTROPHY; PATHOLOGICAL HYPERTROPHY; EXERCISE INTOLERANCE; CARDIAC INTERSTITIUM; MYOCARDIAL FIBROSIS; FIBRILLAR COLLAGEN; DISEASE; MATRIX; CARDIOMYOPATHY; PERFORMANCE C1 Med Univ S Carolina, Div Cardiol, Dept Med, Charleston, SC 29425 USA. Gazes Cardiac Res Inst, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA. Univ Antwerp, Dept Physiol & Med, B-2020 Antwerp, Belgium. RP Zile, MR (reprint author), Med Univ S Carolina, Div Cardiol, Dept Med, 96 Jonathan Lucas St,Suite 816, Charleston, SC 29425 USA. NR 53 TC 396 Z9 427 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 26 PY 2002 VL 105 IS 12 BP 1503 EP 1508 DI 10.1161/hc1202.105290 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 536EC UT WOS:000174686900030 PM 11914262 ER PT J AU Singhal, AB Dijkhuizen, RM Rosen, BR Lo, EH AF Singhal, AB Dijkhuizen, RM Rosen, BR Lo, EH TI Normobaric hyperoxia reduces MRI diffusion abnormalities and infarct size in experimental stroke SO NEUROLOGY LA English DT Article ID FOCAL CEREBRAL-ISCHEMIA; DELAYED NEURONAL DEATH; HYPERBARIC-OXYGEN; ARTERY OCCLUSION; BLOOD-FLOW; LIPID-PEROXIDATION; RAT-BRAIN; VOLUME; COEFFICIENT; RESOLUTION AB Background: Hyperbaric oxygen therapy is considered an important stroke treatment strategy. Objective: To determine whether normobaric oxygen is neuroprotective, and, if so, what the therapeutic time window is. Methods: Experiment 1-Serial diffusion- and perfusion-weighted MRI (DWI and PWI) was performed after middle cerebral artery filament occlusion (MCAO) in rats randomized to FiO(2) 30% (normoxia) or FiO(2) 100% (hyperoxia). Experiment 2-48-hour lesion volumes were analyzed in rats subjected to 2-hour MCAO and randomized to normoxia or hyperoxia starting 15, 30, or 45 minutes after MCAO and ending 15 minutes after reperfusion. Results: Experiment I-Lesion apparent diffusion coefficient (ADC) values were persistently low in normoxic animals. In hyperoxia-treated rats, ADC values in cortical border zones showed progressive recovery from 66 +/- 3% of contralateral before hyperoxia, to 104 +/- 20% at similar to2 hours. Striatal ADC values showed early but ill-sustained improvement. ADC lesion volumes increased progressively in the normoxia group. In the hyperoxia group, ADC lesion volumes tended to decrease after starting hyperoxia; however, lesions later increased in size, and 2-hour lesion volumes were not significantly different from baseline. PWI showed stable right MCA hypoperfusion in all animals. Experiment 2-Hyperoxia within 30 minutes significantly reduced total and cortical lesion volumes at 48 hours after stroke. Striatal lesion volumes were significantly reduced in the hyperoxia-15 group. Conclusion: In rats subjected to transient stroke, 100% oxygen administered within 30 minutes salvages ischemic brain tissue, especially in the cerebral cortex. Reducing the time to treatment enhances the degree of neuroprotection. C1 Harvard Univ, Sch Med, Program Neurosci, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA USA. Massachusetts Gen Hosp, Neuroprotect Res Lab, Charlestown, MA USA. RP Singhal, AB (reprint author), MGH E 149-2322, Charlestown, MA 02129 USA. RI Dijkhuizen, Richard/A-6506-2008 FU NHLBI NIH HHS [HL39810]; NINDS NIH HHS [R01-NS37074, R01-NS38731, R29-NS32806] NR 42 TC 126 Z9 134 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 26 PY 2002 VL 58 IS 6 BP 945 EP 952 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 533BB UT WOS:000174508600020 PM 11914413 ER PT J AU Zareparsi, S James, DM Kaye, JA Bird, TD Schellenberg, GD Payami, H AF Zareparsi, S James, DM Kaye, JA Bird, TD Schellenberg, GD Payami, H TI HLA-A2 homozygosity but not heterozygosity is associated with Alzheimer disease SO NEUROLOGY LA English DT Article ID AGE-OF-ONSET; ALLELE AB AD is associated with the A2 allele of the human leukocyte antigen (HLA). However, it is not currently known whether there is any difference between A2 homozygotes and A2 heterozygotes. The authors studied 458 patients with AD and found that A2 homozygotes had earlier onset of AD than either A2 heterozygotes (5.4 years, p = 0.002) or those without A2 (5.2 years, p = 0.003). The "recessive" nature of this association suggests that loss of function at the HLA-A locus or a closely linked gene is associated with AD. C1 Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Med & Pharmacol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Zareparsi, S (reprint author), Oregon Hlth Sci Univ, Dept Neurol, 3181 SW Sam Jackson Pk Rd,CR-131, Portland, OR 97201 USA. OI Kaye, Jeffrey/0000-0002-9971-3478 FU NIA NIH HHS [AG-08017, AG05136, P30 AG 10133, U24 AG021886] NR 10 TC 20 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 26 PY 2002 VL 58 IS 6 BP 973 EP 975 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 533BB UT WOS:000174508600028 PM 11914421 ER PT J AU Sakakibara, Y Mitha, AP Ayoub, IA Ogilvy, CS Maynard, KI AF Sakakibara, Y Mitha, AP Ayoub, IA Ogilvy, CS Maynard, KI TI Delayed treatment with nicotinamide (vitamin B-3) reduces the infarct volume following focal cerebral ischemia in spontaneously hypertensive rats, diabetic and non-diabetic Fischer 344 rats SO BRAIN RESEARCH LA English DT Article DE neuroprotection; niacinamide; stroke; Poly(ADP ribose polymerase inhibitor; hypertension; diabetes ID WISTAR RATS; POLY(ADP-RIBOSE) POLYMERASE; GLUCOSE CONCENTRATION; ADENINE-DINUCLEOTIDE; THERAPEUTIC APPROACH; INTRALUMINAL SUTURE; SPRAGUE-DAWLEY; STROKE; HYPERGLYCEMIA; PERMANENT AB Since hypertension and/or hyperglycemia are risk factors for stroke, we examined whether the putative neuroprotectant, nicotinamide (NAm), could protect spontaneously hypertensive rats (SHR) or diabetic Fischer 344 rats against focal cerebral ischemia using a model of permanent middle cerebral artery occlusion (MCAo). Intravenous NAm given 2 h after MCAo significantly reduced the infarct volume of SHR (750 mg/kg, 31%, P<0.01) and diabetic (500 mg/kg, 56%, P<0.01) as well as non-diabetic (500 mg/kg, 73%, P<0.01) Fischer 344 rats when compared with saline-injected controls. Thus delayed treatment with NAm protected hypertensive and hyperglycemic rats against a robust model of stroke. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Neurosurg Serv, Neurophysiol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Maynard, KI (reprint author), Aventis Pharmaceut Inc, Rte 202-206,L-103A, Bridgewater, NJ 08807 USA. FU NINDS NIH HHS [NS 01732] NR 45 TC 34 Z9 34 U1 0 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 MAR 22 PY 2002 VL 931 IS 1 BP 68 EP 73 AR PII S0006-8993(02)02263-1 DI 10.1016/S0006-8993(02)02263-1 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 537UC UT WOS:000174777100008 PM 11897090 ER PT J AU Baron, C Blanc, AL McMorrow, I Germana, S Sachs, DH LeGuern, C AF Baron, C Blanc, AL McMorrow, I Germana, S Sachs, DH LeGuern, C TI Emergence of functional hybrid TCR repertoires in allotransplantation. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, TBRC, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 22 PY 2002 VL 16 IS 5 BP A1075 EP A1075 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 534PC UT WOS:000174593901931 ER PT J AU Baron, C McMorrow, I Yamada, K Wu, A Germana, S Sachs, DH LeGuern, C AF Baron, C McMorrow, I Yamada, K Wu, A Germana, S Sachs, DH LeGuern, C TI Selectivity of alpha/beta T cell subsets infiltrating renal allografts: Correlation with the clinical status SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, TBRC, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 22 PY 2002 VL 16 IS 5 BP A1034 EP A1034 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 534PC UT WOS:000174593901704 ER PT J AU Clavijo, JA Sims, CA Menconi, M Shim, I Ochoa, C Puyana, JC AF Clavijo, JA Sims, CA Menconi, M Shim, I Ochoa, C Puyana, JC TI Multiparameter monitoring of subcutaneous tissue as a surrogate of gut tissue perfusion in hemorrhagic shock SO FASEB JOURNAL LA English DT Meeting Abstract C1 UPMC, Pittsburgh, PA 15213 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 22 PY 2002 VL 16 IS 5 BP A1122 EP A1123 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 534PC UT WOS:000174593902199 ER PT J AU El Annan, J Breton, S Brown, D Ausiello, D Bourgoin, S Marshansky, V AF El Annan, J Breton, S Brown, D Ausiello, D Bourgoin, S Marshansky, V TI Comparative study of differential expression and distribution of Arf-isoforms in kidney, epithelial cells in situ and in vitro. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Membrane Biol, Boston, MA 02129 USA. Univ Laval, Ctr Rech CHUQ, St Foy, PQ G1K 7P4, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 22 PY 2002 VL 16 IS 5 BP A803 EP A803 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 534PC UT WOS:000174593900433 ER PT J AU Gu, XG Wan, JM Dubey, DP Swamy, M AF Gu, XG Wan, JM Dubey, DP Swamy, M TI The NK cell inhibitory receptor, gp49 is selectively expressed in effector cytotoxic T lymphocytes. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 22 PY 2002 VL 16 IS 5 BP A1226 EP A1227 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 534PC UT WOS:000174593902772 ER PT J AU Marshansky, V El Annan, J Yu, ASL Brown, D Ausiello, D AF Marshansky, V El Annan, J Yu, ASL Brown, D Ausiello, D TI Possible role of Arf6 small GTPase in pathogenesis of Dent's disease and Fanconi syndrome. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Membrane Biol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 22 PY 2002 VL 16 IS 5 BP A844 EP A844 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 534PC UT WOS:000174593900660 ER PT J AU Monney, L Sabatos, C Gaglia, J Ryu, A Greenfield, E Sobel, R Freeman, G Kuchroo, V AF Monney, L Sabatos, C Gaglia, J Ryu, A Greenfield, E Sobel, R Freeman, G Kuchroo, V TI A novel cell surface protein, TIM-3, expressed on Th1 cells promotes macrophage activation and enhances autoimmune disease SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Stanford Univ, Med Ctr, Sch Med, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 22 PY 2002 VL 16 IS 5 BP A1062 EP A1062 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 534PC UT WOS:000174593901854 ER PT J AU Mountz, JM Zhang, HG Wu, Q Young, P REnda, J Hsu, HC Mountz, JD AF Mountz, JM Zhang, HG Wu, Q Young, P REnda, J Hsu, HC Mountz, JD TI Tc-99m NeoTect imaging in vivo of T cells from hCAR transgenic mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Alabama, Birmingham, AL 35294 USA. Birmingham VAMC, Birmingham, AL 35294 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 22 PY 2002 VL 16 IS 5 BP A1211 EP A1211 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 534PC UT WOS:000174593902687 ER PT J AU Pastor-Soler, N Beaulieu, V Da Silva, N Brown, C McKee, M Kwiatkowski, D Smith, P Brown, D Breton, S AF Pastor-Soler, N Beaulieu, V Da Silva, N Brown, C McKee, M Kwiatkowski, D Smith, P Brown, D Breton, S TI Role of the actin cytoskeleton in the regulation of H+ secretion in the epididymis and vas deferens SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Prog Membr Biol, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. BioCurrents Res Ctr, Woods Hole, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 22 PY 2002 VL 16 IS 5 BP A803 EP A803 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 534PC UT WOS:000174593900430 ER PT J AU Rathbun, G Giarratani, L O'Neill, T AF Rathbun, G Giarratani, L O'Neill, T TI Utilization of peptide libraries to determine substrate motifs for human Chk1 and hCds1/Chk2 SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 22 PY 2002 VL 16 IS 5 BP A1242 EP A1242 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 534PC UT WOS:000174593902861 ER PT J AU Reddy, J Bettelli, E Nicholson, L Waldner, H Wucherpfennig, K Kuchroo, VK AF Reddy, J Bettelli, E Nicholson, L Waldner, H Wucherpfennig, K Kuchroo, VK TI Enumeration of proteolipid protein 139-151-reactive T cells using MHC II (I-As) tetramers in murine experimental autoimmune encephelomyelitis. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RI Reddy, Jay/K-7200-2014 OI Reddy, Jay/0000-0003-4082-9254 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 22 PY 2002 VL 16 IS 5 BP A1220 EP A1221 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 534PC UT WOS:000174593902738 ER PT J AU Traber, DL Murakami, K Yu, YM Young, VR Tompkins, RG AF Traber, DL Murakami, K Yu, YM Young, VR Tompkins, RG TI Arginine levels in an ovine model of burn injury SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Texas, Med Branch, Shriners Burns Hosp, Galveston, TX 77555 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Shriners Burns Hosp, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 22 PY 2002 VL 16 IS 5 BP A853 EP A854 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 534PC UT WOS:000174593900711 ER PT J AU Wan, JM Swamy, M AF Wan, JM Swamy, M TI Expression of the pro-apoptotic molecule, BNIP-3 is posttranscriptionally regulated in effector cytotoxic T lymhocytes. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 22 PY 2002 VL 16 IS 5 BP A1228 EP A1228 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 534PC UT WOS:000174593902778 ER PT J AU Won, JS Im, YB Pannu, R Khan, M Singh, AK Inderjit, S AF Won, JS Im, YB Pannu, R Khan, M Singh, AK Inderjit, S TI The role of neutral sphingomyelinase produced ceramide in lipopolysaccharide-mediated expression of inducible nitric oxide synthase SO FASEB JOURNAL LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 22 PY 2002 VL 16 IS 5 BP A912 EP A912 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 534PC UT WOS:000174593901035 ER PT J AU Wong, JS Wang, XS Carvou, N Chang, HC AF Wong, JS Wang, XS Carvou, N Chang, HC TI Replacement of the CD8 alpha stalk region with that of CD8 beta enhances the efficiency of the CD8 alpha alpha coreceptor function SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 22 PY 2002 VL 16 IS 5 BP A1227 EP A1227 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 534PC UT WOS:000174593902773 ER PT J AU Yoshida, K Kufe, D AF Yoshida, K Kufe, D TI Protein kinase C delta regulates the human Rad9 checkpoint protein in response to DNA damage SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 22 PY 2002 VL 16 IS 5 BP A1196 EP A1196 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 534PC UT WOS:000174593902602 ER PT J AU Zhang, SL Janos, FG Tang, SS Ingelfinger, JR Chan, JSD AF Zhang, SL Janos, FG Tang, SS Ingelfinger, JR Chan, JSD TI Insulin inhibits dexamethasone effect on angiotensinogen gene expression and induction of hypertrophy in kidney proximal tubular cells in high glucose SO FASEB JOURNAL LA English DT Meeting Abstract C1 Hop Hotel Dieu, CHUM, Montreal, PQ H2W 1T8, Canada. Hop Maison Neuve Rosemont, Montreal, PQ H1T 2M4, Canada. Massachusetts Gen Hosp, Pediat Neurol Units, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 22 PY 2002 VL 16 IS 5 BP A888 EP A888 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 534PC UT WOS:000174593900899 ER PT J AU Arystarkhova, E Donnet, C Asinovski, NK Sweadner, KJ AF Arystarkhova, E Donnet, C Asinovski, NK Sweadner, KJ TI Differential regulation of renal Na,K-ATPase by splice variants of the gamma subunit SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NA+-K+-ATPASE; CYTOPLASMIC-BINDING SITES; PIG VENTRICULAR MYOCYTES; NA/K PUMP CURRENT; SODIUM-PUMP; ALPHA-SUBUNIT; IMMUNOCYTOCHEMICAL LOCALIZATION; CONVOLUTED TUBULE; COLLECTING DUCT; ION SELECTIVITY AB Sodium and Potassium-exchanging adenosine triphosphatase (Na,K-ATPase) in the kidney is associated with the gamma subunit (gamma, FXYD2), a single-span membrane protein that modulates ATPase properties. Rat and human gamma occur in two splice variants, gammaa and gammab, with different N termini. Here we investigated their structural heterogeneity and functional effects on Na,K-ATPase properties. Both forms were post-translationally modified during in vitro translation with microsomes, indicating that there are four possible forms of gamma. Site-directed mutagenesis revealed Thr(2) and Ser(5) as potential sites for post-translational modification. Similar modification can occur in cells, with consequences for Na,K-ATPase properties. We showed previously that stable transfection of gammaa into NRK-52E cells resulted in reduction of apparent affinities for Na(+) and K(+). Individual clones differed in gamma post-translational modification, however, and the effect on Na affinity was absent in clones with full modification. Here, transfection of gammab also resulted in clones with or without post-translational modification. Both groups showed a reduction in Na(+) affinity, but modification was required for the effect on K(+) affinity. There were minor increases in ATP affinity. The physiological importance of the reduction in Na(+) affinity was shown by the slower growth of gammaa, gammab, and gammab' transfectants in culture. The differential influence of the four structural variants of gamma on affinities of the Na,K-ATPase for Na(+) and K(+), together with our previous finding of different distributions of gammaa and gammab along the rat nephron, suggests a highly specific mode of regulation of sodium pump properties in kidney. C1 Massachusetts Gen Hosp, Ctr Neurosci, Lab Membrane Biol, Charlestown, MA 02129 USA. RP Sweadner, KJ (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Lab Membrane Biol, 149 13th St,149-6118, Charlestown, MA 02129 USA. EM sweadner@helix.mgh.harvard.edu FU NHLBI NIH HHS [HL27653] NR 73 TC 52 Z9 53 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 MAR 22 PY 2002 VL 277 IS 12 BP 10162 EP 10172 DI 10.1074/jbc.M111552200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 533UR UT WOS:000174549200075 PM 11756431 ER PT J AU Ma, Q Shimaoka, M Lu, C Jing, H Carman, CV Springer, TA AF Ma, Q Shimaoka, M Lu, C Jing, H Carman, CV Springer, TA TI Activation-induced conformational changes in the I domain region of lymphocyte function-associated antigen 1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADHESION MOLECULE-1 ICAM-1; BETA-PROPELLER DOMAIN; LIGAND-BINDING; A-DOMAIN; CR3-DEPENDENT ADHESION; CRYSTAL-STRUCTURE; DIVALENT-CATION; INTEGRIN; AFFINITY; LFA-1 AB Conformational changes in integrins are important for efficient ligand binding during activation. We proposed that the I domain of the integrin lymphocyte function-associated antigen 1 (LFA-1) could exist in both open and closed conformations and generated constitutively activated LFA-1 by locking the I domain in the open conformation. Here we provide structural and biochemical evidence to validate conformational change in the I domain of LFA-1 upon activation. Two monoclonal antibodies to alpha(L), HI111 and CBR LFA-1/1, bind wild-type LFA-1 well, but their binding is significantly reduced when LFA-1 is locked in the open conformation. Furthermore, this reduction in monoclonal antibody binding also occurs when LFA-1 is activated by divalent cations. HI111 maps to the top region of the I domain that is close to the putative ligand-binding site surrounding the MIDAS (metal ion-dependent adhesion site). The epitope of CBR LFA-1/1 is at the C-terminal segment of the I domain that links to the beta-propeller, and undergoes a large movement between the open and closed conformations. Our data demonstrate that these two regions undergo significant conformational changes during LFA-1 activation and that the I domain of activated LFA-1 adopts a similar tertiary structure as the predicted locked open form. C1 Ctr Blood Res, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Springer, TA (reprint author), Ctr Blood Res, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. RI Carman, Christopher/L-8108-2016 OI Carman, Christopher/0000-0001-7358-2548 FU NCI NIH HHS [CA317988] NR 41 TC 36 Z9 37 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 MAR 22 PY 2002 VL 277 IS 12 BP 10638 EP 10641 DI 10.1074/jbc.M112417200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 533UR UT WOS:000174549200135 PM 11792712 ER PT J AU Ben-Zeev, O Mao, HZ Doolittle, MH AF Ben-Zeev, O Mao, HZ Doolittle, MH TI Maturation of lipoprotein lipase in the endoplasmic reticulum - Concurrent formation of functional dimers and inactive aggregates SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN DISULFIDE-ISOMERASE; CULTURED MOUSE ADIPOCYTES; ANTI-CHAPERONE ACTIVITY; QUALITY-CONTROL; SECRETORY PATHWAY; INTRACELLULAR-TRANSPORT; TRANSIENT AGGREGATION; MOLECULAR CHAPERONES; GOLGI COMPARTMENT; TRICORN PROTEASE AB The maturation of lipoprotein lipase (LPL) into a catalytically active enzyme was believed to occur only after its transport from the endoplasmic reticulum (ER) to the Golgi apparatus. To test this hypothesis, LPL located in these two subcellular compartments was separated and compared. Heparin affinity chromatography resolved low affinity, inactive LPL displaying ER characteristics from a high affinity, active fraction exhibiting both ER and Golgi forms. The latter forms were further separated by beta-ricin chromatography and were found to have comparable activities per unit of LPL mass. Thus, LPL must reach a functional conformation in the ER. Active LPL, regardless of its cellular location, exhibited the expected dimer conformation. However, inactive LPL, found only in the ER, was highly aggregated. Kinetic analysis indicated a concurrent formation of LPL dimer and aggregate and indicated that the two forms have dissimilar fates. Whereas the dimer remained stable even when confined to the ER, the aggregate was degraded. Degradation rates were not affected by proteasomal or lysosomal inhibitors but were markedly reduced by ATP depletion. Lowering the redox potential in the ER by dithiothreitol caused the dimer to associate with calnexin, BiP, and protein-disulfide isomerase to form large, inactive complexes; dithiothreitol removal induced complex dissociation with restoration of the functional LPL dimer. In contrast, the LPL aggregate was only poorly associated with ER chaperones, appearing to be trapped in an irreversible, inactive conformation destined for ER degradation. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. RP Doolittle, MH (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 113,Rm 312, Los Angeles, CA 90073 USA. FU NHLBI NIH HHS [HL28481] NR 78 TC 55 Z9 55 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 MAR 22 PY 2002 VL 277 IS 12 BP 10727 EP 10738 DI 10.1074/jbc.M108128200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 533UR UT WOS:000174549200148 PM 11796709 ER PT J AU Izumi, Y Xu, L di Tomaso, E Fukumura, D Jain, RK AF Izumi, Y Xu, L di Tomaso, E Fukumura, D Jain, RK TI Tumor biology - Herceptin acts as an anti-angiogenic cocktail SO NATURE LA English DT Article C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA. RP Izumi, Y (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA. NR 12 TC 392 Z9 417 U1 1 U2 22 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 21 PY 2002 VL 416 IS 6878 BP 279 EP 280 DI 10.1038/416279b PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 532NP UT WOS:000174482200031 PM 11907566 ER PT J AU Barouch, LA Harrison, RW Skaf, MW Rosas, GO Cappola, TP Kobeissi, ZA Hobai, IA Lemmon, CA Burnett, AL O'Rourke, B Rodriguez, ER Huang, PL Lima, JAC Berkowitz, DE Hare, JM AF Barouch, LA Harrison, RW Skaf, MW Rosas, GO Cappola, TP Kobeissi, ZA Hobai, IA Lemmon, CA Burnett, AL O'Rourke, B Rodriguez, ER Huang, PL Lima, JAC Berkowitz, DE Hare, JM TI Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms SO NATURE LA English DT Article ID CARDIAC-SPECIFIC OVEREXPRESSION; CALCIUM-RELEASE CHANNEL; FUNCTION IN-VIVO; SKELETAL-MUSCLE; INHIBITION; POTENTIATION; HYPERTROPHY; ACTIVATION; RECEPTOR; FAILURE AB Subcellular localization of nitric oxide (NO) synthases with effector molecules is an important regulatory mechanism for NO signalling(1). In the heart, NO inhibits L-type Ca2+ channels 2 but stimulates sarcoplasmic reticulum (SR) Ca2+ release(3-5), leading to variable effects on myocardial contractility. Here we show that spatial confinement of specific NO synthase isoforms regulates this process. Endothelial NO synthase (NOS3) localizes to caveolae(6-8), where compartmentalization with beta-adrenergic receptors and L-type Ca2+ channels(9) allows NO to inhibit beta-adrenergic-induced inotropy(8,10). Neuronal NO synthase (NOS1), however, is targeted to cardiac SR11. NO stimulation of SR Ca2+ release via the ryanodine receptor (RyR) in vitro(3,4) suggests that NOS1 has an opposite, facilitative effect on contractility. We demonstrate that NOS1-deficient mice have suppressed inotropic response, whereas NOS3-deficient mice have enhanced contractility, owing to corresponding changes in SR Ca2+ release. Both NOS1(-/-) and NOS3(-/-) mice develop age-related hypertrophy, although only NOS3(-/-) mice are hypertensive. NOS1/3(-/-) double knockout mice have suppressed beta-adrenergic responses and an additive phenotype of marked ventricular remodelling. Thus, NOS1 and NOS3 mediate independent, and in some cases opposite, effects on cardiac structure and function. C1 Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21287 USA. Johns Hopkins Med Inst, Dept Biomed Engn, Baltimore, MD 21287 USA. Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21287 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21287 USA. Johns Hopkins Med Inst, Dept Anaesthesiol & Crit Care Med, Baltimore, MD 21287 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Hare, JM (reprint author), Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21287 USA. NR 29 TC 526 Z9 548 U1 1 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 21 PY 2002 VL 416 IS 6878 BP 337 EP 340 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 532NP UT WOS:000174482200047 PM 11907582 ER PT J AU Wong, JC Lee, SB Bell, MD Reynolds, PA Fiore, E Stamenkovic, I Truong, V Oliner, JD Gerald, WL Haber, DA AF Wong, JC Lee, SB Bell, MD Reynolds, PA Fiore, E Stamenkovic, I Truong, V Oliner, JD Gerald, WL Haber, DA TI Induction of the interleukin-2/15 receptor beta-chain by the EWS-WT1 translocation product SO ONCOGENE LA English DT Article DE EWS-WT1; desmoplastic small round cell tumor; Wilms tumor; interleukin-2/15 receptor; microarrays; tumor-stromal interaction ID ROUND-CELL TUMOR; RNA-POLYMERASE-II; IL-2 RECEPTOR; GENE-PRODUCT; ALPHA-CHAIN; TRANSCRIPTIONAL ACTIVATOR; GROWTH-FACTOR; DNA-BINDING; EXPRESSION; PROTEIN AB EWS - WT1 is a chimeric transcription factor resulting from fusion of the N-terminal domain of the Ewing sarcoma gene EWS to the three C-terminal zinc fingers of the Wilms tumor suppressor WT1. This translocation underlies desmoplastic small round cell tumor (DSRCT), which is noted for the abundance of reactive stroma surrounding islets of tumor cells, suggestive of paracrine signals contributing to tumor cell proliferation. Hybridization to high-density oligonucleotide microarrays can be used to identify targets of EWS - WT1. Expression of EWS - WT1 from a tetracycline-regulated promoter leads to the induction of growth-associated genes, of which the most remarkable is the beta-chain of the interleukin-2/15 receptor (IL-2/15Rbeta). Potent transcriptional activation by the chimeric protein maps to two bindings sites within the IL-2/15Rbeta promoter. Analysis of primary DSRCT tumor specimens demonstrates high levels of IL-2/15Rbeta within the tumor cells, along with expression of IL-2 and IL-15 by the abundant hyperplastic endothelial cells within the reactive stroma. Activation of this cytokine signaling pathway is consistent with the nuclear localization of its downstream effectors, phosphorylated STAT3 and STAT5. These observations suggest that the transcriptional induction of a cytokine receptor by a tumor-associated translocation product enables a proliferative response of epithelial cancer cells to ligands secreted by the surrounding stroma. C1 Massachusetts Gen Hosp, Canc Ctr CNY 7, Mol Genet Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. Affymetrix, Santa Clara, CA 95051 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Canc Ctr CNY 7, Mol Genet Lab, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA68273, CA58596] NR 51 TC 26 Z9 26 U1 0 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 MAR 21 PY 2002 VL 21 IS 13 BP 2009 EP 2019 DI 10.1038/sj/onc/1205262 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 538QR UT WOS:000174827000007 PM 11960373 ER PT J AU Lein, M Jung, K Ortel, B Stephan, C Rothaug, W Juchem, R Johannsen, M Deger, S Schnorr, D Loening, S Krell, HW AF Lein, M Jung, K Ortel, B Stephan, C Rothaug, W Juchem, R Johannsen, M Deger, S Schnorr, D Loening, S Krell, HW TI The new synthetic matrix metalloproteinase inhibitor (Roche 28-2653) reduces tumor growth and prolongs survival in a prostate cancer standard rat model SO ONCOGENE LA English DT Article DE prostate cancer; Dunning tumor; metalloproteinases; synthetic inhibitor; animal model ID TISSUE INHIBITOR; BATIMASTAT BB-94; TIMP-2; ANGIOGENESIS; PROGRESSION; EXPRESSION; CARCINOMA; SECRETION; CULTURES; BENIGN AB The therapeutic efficacy of synthetic inhibitors of matrix-metalloproteinases (MMPs) in various cancers has been demonstrated. A novel inhibitor, Ro 28-2653, with high selectivity for MMP2, MMP9 and membrane type 1-MMP was evaluated in an orthotopic prostate cancer rat model. Efficacy was determined by recording tumor growth and survival endpoints. Prostate cancer was induced by inoculating R3327 Dunning tumor cells (MatLyLu) into the ventral lobe of the prostates of 148 Copenhagen rats. Daily oral treatment with Ro 282653 (10-300 mg/kg per day) was started on day 1 or on day 6 after tumor cell injection. Animals were sacrificed on day 20 for determination of tumor weights. For survival studies, rats received daily oral Ro 28-2653 (100 mg/kg per day) or vehicle for up to 30 days. Tumor induction was successful in 100% of the animals. Ro 282653 reproducibly reduced the tumor weights by up to 90% in a dose-dependent manner. In addition, an inhibitory effect in rats with established tumors (treatment start at day 6) was shown. A significantly prolonged survival of Ro 28-2653-treated rats was also demonstrated. Selective inhibition of MMP activity is a novel therapeutic approach, which bears promise for studies in patients with prostate cancer. C1 Humboldt Univ, Univ Hosp Charite, Dept Urol, D-10098 Berlin, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. Roche Diagnost GmbH, Pharma Res Penzberg, Penzberg, Germany. RP Lein, M (reprint author), Humboldt Univ, Univ Hosp Charite, Dept Urol, D-10098 Berlin, Germany. NR 36 TC 56 Z9 58 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 21 PY 2002 VL 21 IS 13 BP 2089 EP 2096 DI 10.1038/sj/onc/1205267 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 538QR UT WOS:000174827000015 PM 11960381 ER PT J AU Attinger, A Leishman, AJ Naidenko, OV Koning, F Reinherz, E Kronenberg, M Cheroutre, H AF Attinger, A Leishman, AJ Naidenko, OV Koning, F Reinherz, E Kronenberg, M Cheroutre, H TI Modulation of T cell response through the high affinity interaction between CD8 alpha alpha and the non classical MHC class I molecule, TL SO FASEB JOURNAL LA English DT Meeting Abstract C1 La Jolla Inst Allergy & Immunol, San Diego, CA 92121 USA. Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 2002 VL 16 IS 4 BP A678 EP A678 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533603767 ER PT J AU Boyson, JE Rybalov, B Racke, F Exley, M Balk, SP Koopman, LA Schatz, F Mash, R Wilson, SB Strominger, JL AF Boyson, JE Rybalov, B Racke, F Exley, M Balk, SP Koopman, LA Schatz, F Mash, R Wilson, SB Strominger, JL TI Human decidual iNKT cells are biased toward GM-CSF production and are highly reactive toward endogenous CD1d ligands SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NYU Med Ctr, Dept Obstet & Gynecol, New York, NY 10016 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 2002 VL 16 IS 4 BP A725 EP A725 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533604025 ER PT J AU Brown, JA Chernova, T Dorfman, DM Boussiotis, VA Woods, CR Freeman, GJ AF Brown, JA Chernova, T Dorfman, DM Boussiotis, VA Woods, CR Freeman, GJ TI Blockade of PD-1 Ligands on dendritic cells enhances T cell activation and cytokine production SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Genet Inst Inc, Cambridge, MA 02140 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 2002 VL 16 IS 4 BP A710 EP A710 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533603943 ER PT J AU DePaolo, RW Rollins, BJ Karpus, WJ AF DePaolo, RW Rollins, BJ Karpus, WJ TI CCL2 is critical for the induction of oral, but not peripheral, immune tolerance induction. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Northwestern Univ, Sch Med, Dept Pathol, Chicago, IL 60611 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 2002 VL 16 IS 4 BP A285 EP A285 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533601579 ER PT J AU Durda, PJ Rose, LB Dunn, IS Butera, D Benson, E Kurnick, JT AF Durda, PJ Rose, LB Dunn, IS Butera, D Benson, E Kurnick, JT TI Tumor escape from immune destruction: Oncostatin-M down-modulation of melanoma antigen expression. SO FASEB JOURNAL LA English DT Meeting Abstract C1 CytoCure LLC, Beverly, MA 01915 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Westmead Hosp, Sydney, NSW, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 2002 VL 16 IS 4 BP A670 EP A670 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533603721 ER PT J AU Goldrath, AW Benoist, C Mathis, D AF Goldrath, AW Benoist, C Mathis, D TI Interplay of T cell receptor and IL-7 receptor mediated survival of naive T cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 2002 VL 16 IS 4 BP A345 EP A345 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533601910 ER PT J AU Hsu, HC Zhang, HG Allison, DB Young, PA Geiger, H Van Zant, G Mountz, JD AF Hsu, HC Zhang, HG Allison, DB Young, PA Geiger, H Van Zant, G Mountz, JD TI Peripheral T-cell response to anti-CD3 stimulation correlates with longevity in C57BL/6J X DBA/2 recombinant inbred strains of mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Alabama, Birmingham, AL 35294 USA. Univ Kentucky, Med Ctr, Lucille P Markey Canc Ctr, Lexington, KY 40536 USA. Birmingham VAMC, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 2002 VL 16 IS 4 BP A695 EP A695 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533603860 ER PT J AU Husain, Z Alper, CA Dubey, DP AF Husain, Z Alper, CA Dubey, DP TI Antibody-mediated cross-linking of NK receptors induces specific cytokines SO FASEB JOURNAL LA English DT Meeting Abstract C1 Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 2002 VL 16 IS 4 BP A323 EP A323 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533601783 ER PT J AU Ichinose, F Ullrich, R Sapirstein, A Jones, RC Bloch, KD Zapol, WM AF Ichinose, F Ullrich, R Sapirstein, A Jones, RC Bloch, KD Zapol, WM TI A key role of cytosolic phospholipase A(2) in hypoxic pulmonary vasoconstriction SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anaesthesia & Critical Care, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiovasc Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 2002 VL 16 IS 4 BP A70 EP A70 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533600392 ER PT J AU Kling, DE Aidlen, JT Kinane, TB Schnitzer, JJ AF Kling, DE Aidlen, JT Kinane, TB Schnitzer, JJ TI Nitrofen induced apoptosis in P19 cells is rescued by glutathione or retinoic acid SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 2002 VL 16 IS 4 BP A37 EP A37 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533600208 ER PT J AU Li, LF Ouyang, B Jafari, B Hales, CA Quinn, DA AF Li, LF Ouyang, B Jafari, B Hales, CA Quinn, DA TI Stretch induces IL-8 promoter activity and IL-8 mRNA expression in a in vitro model of ventilator induced lung injury (VILI) SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 2002 VL 16 IS 4 BP A409 EP A409 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533602268 ER PT J AU Mahadevan, K Burns, AR Smith, CW Rumbaut, RE AF Mahadevan, K Burns, AR Smith, CW Rumbaut, RE TI Influence of FMLP-stimulated neutrophil activation on endothelial cell permeability SO FASEB JOURNAL LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Houston VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 2002 VL 16 IS 4 BP A509 EP A509 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533602822 ER PT J AU Mascarenhas, MM Day, R Garg, HG Hales, CA Quinn, DA AF Mascarenhas, MM Day, R Garg, HG Hales, CA Quinn, DA TI Mechanisms of stretch-induced hyaluronan production in an in vitro model of ventialtor induced lung injury SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. Tufts Univ, Pulm & Crit Care Unit, Sch Med, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 2002 VL 16 IS 4 BP A411 EP A411 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533602277 ER PT J AU Mehrengise, C Noviski, N Lu, A Lu, XM Young, VR Castillo, L AF Mehrengise, C Noviski, N Lu, A Lu, XM Young, VR Castillo, L TI Sulfur amino acid metabolism in septic children SO FASEB JOURNAL LA English DT Meeting Abstract C1 Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Shriners Burns Hosp, Boston, MA USA. MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 2002 VL 16 IS 4 BP A257 EP A258 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533601424 ER PT J AU Morra, M Lu, J Poy, F Calpe, S Martin, M Gullo, C Howie, D Denny, C Engel, P Eck, MJ Terhorst, C AF Morra, M Lu, J Poy, F Calpe, S Martin, M Gullo, C Howie, D Denny, C Engel, P Eck, MJ Terhorst, C TI The "free SH2-domain" EAT-2 binds CD150-related receptors in hematopoietic cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Div Immunol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02215 USA. Univ Barcelona, Barcelona 08035, Spain. Univ Calif Los Angeles, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 2002 VL 16 IS 4 BP A321 EP A321 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533601772 ER PT J AU Mukhin, YV Garnovsky, EA Raymond, JR Garnovskaya, MN AF Mukhin, YV Garnovsky, EA Raymond, JR Garnovskaya, MN TI Bradykinin beta(2) receptor activates ERK in mIMCD-3 cells via epidermal growth factor receptor transactivation. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 2002 VL 16 IS 4 BP A171 EP A172 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533600956 ER PT J AU Norris, PJ Brander, C Sumaroka, M Moffett, HF Sykulev, Y Walker, BD Rosenberg, ES AF Norris, PJ Brander, C Sumaroka, M Moffett, HF Sykulev, Y Walker, BD Rosenberg, ES TI Multiple effector functions of HIV-specific T helper cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Thomas Jefferson Univ, Kimmel Canc Inst, Philadelphia, PA 19107 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 2002 VL 16 IS 4 BP A294 EP A295 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533601629 ER PT J AU Ouyang, B Hales, CA Quinn, DA AF Ouyang, B Hales, CA Quinn, DA TI Stretch induced gene expression in an in vitro model of ventilator induced lung injury (VILI) SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 2002 VL 16 IS 4 BP A410 EP A410 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533602274 ER PT J AU Shankar, P Lee, SK Lieberman, J AF Shankar, P Lee, SK Lieberman, J TI The dominant CD8 T cell response is focused on type specific epitopes at later stages of HIV disease SO FASEB JOURNAL LA English DT Meeting Abstract C1 Ctr Blood Res, Boston, MA 02115 USA. RI Lieberman, Judy/A-2717-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 2002 VL 16 IS 4 BP A295 EP A295 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533601634 ER PT J AU Syrkina, OL Quinn, DA Moufarrej, R Hales, CA AF Syrkina, OL Quinn, DA Moufarrej, R Hales, CA TI N-acetylcysteine(NAC), an antioxidant, decreased lung neutrophil influx in a rat model of ventilator-induced lung injury(VILI) SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 2002 VL 16 IS 4 BP A410 EP A410 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533602275 ER PT J AU Vidal, M AF Vidal, M TI Toward a proteome atlas for C-elegans SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 2002 VL 16 IS 4 BP A13 EP A13 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533600073 ER PT J AU Yu, YM Ryan, CM Schulz, JT Lu, XM Xu, J Tompkins, RG Young, VR AF Yu, YM Ryan, CM Schulz, JT Lu, XM Xu, J Tompkins, RG Young, VR TI Whole blood glutathione kinetics in severely burned patients after short-term TPN with glutamine supplementation SO FASEB JOURNAL LA English DT Meeting Abstract C1 Shriners Burns Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 2002 VL 16 IS 4 BP A245 EP A245 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533601354 ER PT J AU Zhang, SL Chen, X Filep, JG Tang, SS Ingelfinger, JR Chan, JSD AF Zhang, SL Chen, X Filep, JG Tang, SS Ingelfinger, JR Chan, JSD TI High glucose induces insulin resistance on angiotensinogen gene expression in rat kidney proximal tubular cells: Defect in Raf-1 activation SO FASEB JOURNAL LA English DT Meeting Abstract C1 Hop Hotel Dieu, Ctr Rech, Montreal, PQ H2W 1T8, Canada. Univ Montreal, Hop Maison Neuve Rosemont, Montreal, PQ H1T 2M4, Canada. Massachusetts Gen Hosp, Pediat Nephrol Units, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 2002 VL 16 IS 4 BP A420 EP A420 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533602326 ER PT J AU Zhuang, SG Simon, G Kochevar, IE AF Zhuang, SG Simon, G Kochevar, IE TI Activation of protein kinase B/Akt by singlet oxygen in fibroblasts (dependence of phosphatidylinositol-3-OH kinase but not growth factor receptors and focal adhesion kinase) SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Wellman Lab Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 2002 VL 16 IS 4 BP A140 EP A140 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533600773 ER PT J AU Sviderskaya, EV Hill, SP Evans-Whipp, TJ Chin, L Orlow, SJ Easty, DJ Cheong, SC Beach, D DePinho, RA Bennett, DC AF Sviderskaya, EV Hill, SP Evans-Whipp, TJ Chin, L Orlow, SJ Easty, DJ Cheong, SC Beach, D DePinho, RA Bennett, DC TI p16(Ink4a) in melanocyte senescence and differentiation SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SUPPRESSOR GENE-PRODUCT; TUMOR-SUPPRESSOR; MOUSE MELANOCYTES; INK4A LOCUS; IN-VIVO; P53; EXPRESSION; MDM2; MICE; MUTATIONS AB The Ink4a-Arf tumor suppressor locus encodes two growth inhibitors, p16 and Arf, both of which are also implicated as effectors in cellular senescence. Because human germline defects in the INK4A-ARF locus are associated with familial melanoma, melanocytes may have unusual INK4A-ARF functions or controls of cell senescence. Because senescence is believed to be an anticancer mechanism, we investigated the role of Ink4a-Arf and its individual components in melanocyte senescence. Methods: Melanocytes were cultured from littermate mice with zero, one, or two functional copies of the Ink4a-Arf locus. Senescence was evaluated by cumulative population doubling curves and by the assessment of acidic beta-galactosidase (an indicator of senescence) expression. Pigmentation and cell size were evaluated by spectrophotometry and microscopy. p16 and Arf expression in primary and spontaneously immortalized melanocyte or melanocyte precursor cell lines were evaluated by immunoblotting. Retroviral vectors containing normal p16 and Arf complementary DNAs were used to restore expression of these genes in Ink4a-Arf(-/-) melanocytes. Results: Wild-type melanocytes (i.e., Ink4a-Arf(+/+)) senesced within 4-5 weeks of culture. Ink4a-Arf(-/-) melanocytes did not senesce and readily became immortal. Ink4a-Arf(+/-) melanocytes showed defective senescence. Senescent Ink4a-Arf(+/+) melanocytes were heavily pigmented, but lnk4a-Arf(+/-) and Ink4a-Arf(-/-) melanocytes were less pigmented. All of six spontaneously immortalized melanocyte or melanocyte precursor lines from Ink4a-Arf(+/+) mice lacked p16 protein expression, although most retained Arf protein expression. After restoration of p16 but not Arf expression, Ink4a-Arf(-/-) melanocytes stopped growing, became highly melanized, and expressed acidic beta-galactosidase. By contrast, restoration of Arf but not p16 expression led to cell death without evidence of senescence. Conclusion: Normal mouse melanocyte senescence and associated pigmentation require both copies of Ink4a-Arf and appear to depend more on p16 than on Arf function. Mutations of the INK4A-ARF locus may favor tumorigenesis from melanocytes by impairing senescence, cell differentiation, and (where ARF is disrupted) cell death. C1 St George Hosp, Sch Med, Dept Anat & Dev Biol, London SW17 0RE, England. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA USA. NYU Med Ctr, New York, NY 10016 USA. UCL, Wolfson Inst Biomed Res, London, England. RP Bennett, DC (reprint author), St George Hosp, Sch Med, Dept Anat & Dev Biol, Cranmer Terrace, London SW17 0RE, England. EM dbennett@sghms.ac.uk RI Bennett, Dorothy/C-2418-2008; Sviderskaya, Elena/D-2419-2009; OI Bennett, Dorothy/0000-0002-3639-7527; Evans-Whipp, Tracy/0000-0002-1993-6023 FU NCI NIH HHS [U02 CA 84313] NR 49 TC 115 Z9 116 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD MAR 20 PY 2002 VL 94 IS 6 BP 446 EP 454 PG 9 WC Oncology SC Oncology GA 531VF UT WOS:000174437400011 PM 11904317 ER PT J AU Salton, CJ Chuang, ML O'Donnell, CJ Kupka, MJ Larson, MG Kissinger, KV Edelman, RR Levy, D Manning, WJ AF Salton, CJ Chuang, ML O'Donnell, CJ Kupka, MJ Larson, MG Kissinger, KV Edelman, RR Levy, D Manning, WJ TI Gender differences and normal left ventricular anatomy in an adult population free of hypertension - A cardiovascular magnetic resonance study of the Framingham Heart Study Offspring Cohort SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID BODY-SIZE; 3-DIMENSIONAL ECHOCARDIOGRAPHY; EJECTION FRACTION; SYSTOLIC FUNCTION; MASS; DISEASE; AGE; HYPERTROPHY; VOLUMES; FAILURE AB OBJECTIVES We sought to derive gender-specific cardiovascular magnetic resonance (CMR) reference values for normative left ventricular (LV) anatomy and function in a healthy adult population of clinically relevant age. BACKGROUND Cardiovascular magnetic resonance imaging is increasingly applied in the clinical setting, but age-relevant, gender-specific normative values are currently unavailable. METHODS A representative sample of 318 Framingham Heart Study (FHS) Offspring participants free of clinically overt cardiovascular disease underwent CMR examination to determine LV end-diastolic and end-systolic volume (EDV and ESV, respectively), mass, ejection fraction (EF) and linear dimensions (wall thickness, cavity length). Subjects with a clinical history of hypertension or those with a systolic blood pressure greater than or equal to140 mm Hg or diastolic pressure greater than or equal to90 mm Hg at any FHS cycle examination were excluded, leaving 142 subjects (63 men, 79 women; age 57 +/- 9 years). RESULTS All volumetric (EDV, ESV, mass) and unidimensional measures were significantly greater (p < 0.001) in men than in women and remained greater (p < 0.02) after adjustment for subject height. Volumetric measures were greater (p < 0.001) in men than in women after adjustment for body surface area (BSA), but there were increased linear dimensions in women after adjustment for BSA. In particular, end-diastolic dimension indexed to BSA was greater in women (p < 0.001) than in men. There were no gender differences in global LVEF (men = 0.69; women = 0.70). CONCLUSIONS Cardiovascular magnetic resonance measures of LV volumes, mass and linear dimensions differ significantly according to gender and body size. This study provides gender-specific normal CMR reference values, uniquely derived from a population-based sample of persons free of cardiovascular disease and clinical hypertension. These data may serve as a reference to identify LV pathology in the adult population. (J Am Coll Cardiol 2002;39:1055-60) (C) 2002 by the American College of Cardiology Foundation. C1 Beth Israel Deaconess Med Ctr, Charles A Dana Res Inst, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Harvard Thorndike Lab, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Dept Radiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Manning, WJ (reprint author), Beth Israel Deaconess Med Ctr, Charles A Dana Res Inst, 330 Brookline Ave, Boston, MA 02215 USA. FU NHLBI NIH HHS [N01-HC-38038] NR 32 TC 182 Z9 185 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 20 PY 2002 VL 39 IS 6 BP 1055 EP 1060 AR PII S0735-1097(02)01712-6 DI 10.1016/S0735-1097(02)01712-6 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 532CB UT WOS:000174453100020 PM 11897450 ER PT J AU Talcott, JA AF Talcott, JA TI Androgen deprivation as primary treatment for early prostate cancer: Should we "just do something"? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID QUALITY-OF-LIFE; RADICAL PROSTATECTOMY; MEDICARE BENEFICIARIES; RADIATION-THERAPY; OUTCOMES; RADIOTHERAPY; ANTIGEN; GOSERELIN; IMPOTENCE; TRENDS C1 Massachusetts Gen Hosp, Ctr Outcomes Res, Boston, MA 02114 USA. RP Talcott, JA (reprint author), Massachusetts Gen Hosp, Ctr Outcomes Res, B75 230,55 Fruit St, Boston, MA 02114 USA. NR 29 TC 4 Z9 4 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 20 PY 2002 VL 94 IS 6 BP 407 EP 409 PG 3 WC Oncology SC Oncology GA 531VF UT WOS:000174437400002 PM 11904307 ER PT J AU Jain, RK Fenton, BT AF Jain, RK Fenton, BT TI Intratumoral lymphatic vessels: A case of mistaken identity or malfunction? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID ENDOTHELIAL GROWTH-FACTOR; FACTOR-C EXPRESSION; NODE METASTASIS; VEGF-C; BLOOD-VESSEL; CANCER; TUMORS; ANGIOGENESIS; CELLS; LYMPHANGIOGENESIS C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 7, Boston, MA 02114 USA. FU NCI NIH HHS [R24 CA 85140, T32 CA 73479] NR 60 TC 100 Z9 116 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 20 PY 2002 VL 94 IS 6 BP 417 EP 421 PG 5 WC Oncology SC Oncology GA 531VF UT WOS:000174437400007 PM 11904313 ER PT J AU Wu, K Willett, WC Fuchs, CS Colditz, GA Giovannucci, EL AF Wu, K Willett, WC Fuchs, CS Colditz, GA Giovannucci, EL TI Calcium intake and risk of colon cancer in women and men SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; EPITHELIAL-CELL PROLIFERATION; COLORECTAL-CANCER; VITAMIN-D; DAIRY-PRODUCTS; DIETARY-FAT; SUPPLEMENTATION; CARCINOGENESIS; PREVENTION; REPRODUCIBILITY AB Calcium has been hypothesized to reduce the risk of colon cancer, and in a recent randomized trial, calcium supplementation was associated with reduction in the risk of recurrent colorectal adenomas. We examined the association between calcium intake and colon cancer risk in two prospective cohorts, the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS). Methods: Our study population included 87998 women in NHS and 47 344 men in HPFS who, at baseline (1980 for NHS and 1986 for HPFS), completed a food frequency questionnaire and provided information on medical history and lifestyle factors. Dietary information was updated at least every 4 years. During the follow-up period (1980 to May 31, 1996 for the NHS cohort; 1986 to January 31, 1996 for the HPFS cohort), 626 and 399 colon cancer cases were identified in women and men, respectively. Pooled logistic regression was used to estimate relative risks (RRs), and all statistical tests were two-sided. Results: In women and men considered together, we found an inverse association between higher total calcium intake (>1250 mg/day versus less than or equal to500 mg/day) and distal colon cancer (women: multivariate RR = 0.73, 95% confidence interval [CI] = 0.41 to 1.27; men: RR = 0.58, 95 % CI = 0.32 to 1.05; pooled RR = 0.65, 95% CI = 0.43 to 0.98). No such association was found for proximal colon cancer (women: RR = 1.28, 95 % CI = 0.75 to 2.16; men: RR 0.92, 95 % CI = 0.45 to 1.87; pooled RR = 1.14, 95% CI 0.72 to 1.81). The incremental benefit of additional calcium intake beyond approximately 700 mg/day appeared to be minimal. Conclusions: Higher calcium intake is associated with a reduced risk of distal colon cancer. The observed risk pattern was consistent with a threshold effect, suggesting that calcium intake beyond moderate levels may not be associated with a further risk reduction. Future investigations on this association should concentrate on specific cancer subsites and on the dose-response relationship. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. RP Giovannucci, EL (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave,Bldg 2, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA 55075, CA 87969] NR 61 TC 200 Z9 205 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 20 PY 2002 VL 94 IS 6 BP 437 EP 446 PG 10 WC Oncology SC Oncology GA 531VF UT WOS:000174437400010 PM 11904316 ER PT J AU Lu, S Gu, X Hoestje, S Epner, DE AF Lu, S Gu, X Hoestje, S Epner, DE TI Identification of an additional hypoxia responsive element in the glyceraldehyde-3-phosphate dehydrogenase gene promoter SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE glyceraldehyde-3-phosphate dehydrogenase (GAPDH); hypoxia inducible factor-1 (HIF-1); prostatic neoplasm; hypoxia; glycolysis ID HUMAN PROSTATE-CANCER; INDUCIBLE FACTOR-1; EXPRESSION; CELLS; RAT; APOPTOSIS; PROTEIN; TISSUE AB Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a multifunctional enzyme overexpressed in many tumors and induced by hypoxia in normal and malignant cells. The degree to which hypoxia transcriptionally activates GAPDH is cell type specific. The GAPDH promoter region contains a hypoxia responsive element (HRE) consisting of a hypoxia inducible factor-1 (HIF-1) consensus binding site plus adjacent sequence [Graven et al. (1999) Biochim. Biophys. Acta 1447, 208-218]. Using transient transfection experiments with the GAPDH promoter region linked to a luciferase reporter gene, we found that GAPDH was transcriptionally activated by hypoxia in each of three human prostate cancer cell lines tested, with the greatest level of induction in the most differentiated cell line. Using sequence analysis of the GAPDH promoter region, we identified a novel HRE distinct from the previously characterized one that consists of two consensus HIF-1 sites arranged as inverted repeats separated by 5 bp. Hypoxia transcriptionally activated a promoter construct in which the previously characterized HRE was mutated and the novel HRE remained intact. Heterologous promoter constructs containing only one or two copies of the novel HRE plus a minimal promoter consisting of a TATA box drove hypoxia inducible expression of the luciferase reporter gene in transient transfection assays. Mutation of HIF-1 sites within the novel HRE resulted in complete loss of function. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Baylor Coll Med, VA Med Ctr, Dept Med, Houston, TX 77030 USA. RP Epner, DE (reprint author), Baylor Coll Med, VA Med Ctr, Dept Med, Houston, TX 77030 USA. FU NCI NIH HHS [R29 CA78355] NR 24 TC 58 Z9 60 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD MAR 19 PY 2002 VL 1574 IS 2 BP 152 EP 156 AR PII S0167-4781(01)00359-1 DI 10.1016/S0167-4781(01)00359-1 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 547EX UT WOS:000175321000005 PM 11955624 ER PT J AU Victal, OA Teerlink, JR Gaxiola, E Wallace, AW Najar, S Camacho, DH Gutierrez, A Herrera, G Zuniga, G Mercado-Rios, F Ratcliffe, MB AF Victal, OA Teerlink, JR Gaxiola, E Wallace, AW Najar, S Camacho, DH Gutierrez, A Herrera, G Zuniga, G Mercado-Rios, F Ratcliffe, MB TI Left ventricular volume reduction by radiofrequency heating of chronic myocardial infarction in patients with congestive heart failure SO CIRCULATION LA English DT Article DE heart failure; myocardial infarction; remodeling; surgery; cardiac volume ID COLLAGENOUS TISSUE; DOUBLE-BLIND; DYSFUNCTION; CAPTOPRIL; SURVIVAL; MECHANICS; SHRINKAGE; MORTALITY; TRIALS AB Background-Myocardial infarct expansion and left ventricular (LV) remodeling are integral components in the evolution of chronic heart failure and predict morbidity and mortality. Radiofrequency (RF) heating and patch placement of chronic LV aneurysms caused a sustained reduction in LV infarct area and volume in an ovine infarct model. This study evaluated the effect of RF heating and epicardial patch as an adjunct to coronary artery bypass graft on LV volumes in patients with prior myocardial infarction. evidence of akinetic/dyskinetic scar, and LV ejection fraction less than or equal to40%. Methods and Results-Ten patients (3 female: mean age. 64 +/- 11 years) scheduled for coronary artery bypass graft were enrolled (Canadian Cardiovascular Society angina class 2.1 +/- 1.1; New York Heart Association class 3.1 +/- 0.5). Intraoperative digital photography demonstrated an acute 39% reduction in infarct area (n=5 P=0.01), and transesophageal ECGs demonstrated a 16% acute reduction in LV end-diastolic volumes (n=9: P=0.002) after RF treatment. There were no intraoperative or procedure-related postoperative complications, and during an average follow-up of >180 days, there have been no safety issues. All patients had complete relief of their angina and improvement in exercise tolerance. Serial transthoracic ECGs over the 6 months of follow-up after RF treatment demonstrated persistent reductions in LV end-diastolic volume (29%: P<0.0001) and LV end-systolic volume (37%; P<0.0001) with improved ejection fraction (P<0.02). Conclusions-RF heating and patch placement in these 10 patients resulted in acute reduction in infarct area and ventricular volumes that were maintained 180 days after procedure. This technique may reduce the incidence of congestive heart failure and mortality in these patients and warrants investigation in larger clinical trials. C1 San Francisco Vet Affairs Med Ctr, Cardiol Sect, San Francisco, CA 94121 USA. San Francisco Vet Affairs Med Ctr, Sect Anesthesiol, San Francisco, CA 94121 USA. San Francisco Vet Affairs Med Ctr, Sect Cardiothorac Surg, San Francisco, CA 94121 USA. Social Secur Hosp, Guadalajara, Jalisco, Mexico. Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. RP Ratcliffe, MB (reprint author), San Francisco Vet Affairs Med Ctr, Cardiol Sect, 112D,4150 Clement St, San Francisco, CA 94121 USA. RI Teerlink, John/D-2986-2012 NR 24 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 19 PY 2002 VL 105 IS 11 BP 1317 EP 1322 DI 10.1161/hc1102.105566 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 533NA UT WOS:000174535500011 PM 11901042 ER PT J AU Zile, MR Brutsaert, DL AF Zile, MR Brutsaert, DL TI New concepts in diastolic dysfunction and diastolic heart failure: Part I Diagnosis, prognosis, and measurements of diastolic function SO CIRCULATION LA English DT Editorial Material DE heart failure; diastole; systole ID VENTRICULAR SYSTOLIC FUNCTION; DOPPLER-ECHOCARDIOGRAPHY; CLINICAL CHARACTERISTICS; CARDIAC INTERSTITIUM; NATURAL-HISTORY; MATRIX; DISEASE; HEALTH C1 Med Univ S Carolina, Gazes Cardiac Res Inst, Div Cardiol, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. Univ Antwerp, Dept Physiol, B-2020 Antwerp, Belgium. Univ Antwerp, Dept Med, B-2020 Antwerp, Belgium. RP Zile, MR (reprint author), Med Univ S Carolina, Gazes Cardiac Res Inst, Div Cardiol, Dept Med, 96 Jonathan Lucas St,Suite 816, Charleston, SC 29425 USA. NR 53 TC 619 Z9 681 U1 1 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 19 PY 2002 VL 105 IS 11 BP 1387 EP 1393 DI 10.1161/hc1102.105289 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 533NA UT WOS:000174535500022 PM 11901053 ER PT J AU Serluca, FC Drummond, IA Fishman, MC AF Serluca, FC Drummond, IA Fishman, MC TI Endothelial signaling in kidney morphogenesis: A role for hemodynamic forces SO CURRENT BIOLOGY LA English DT Article ID MATRIX METALLOPROTEINASES; CARDIOVASCULAR-SYSTEM; SHEAR-STRESS; ZEBRAFISH; MUTATIONS; FLOW; INHIBITOR; ABSENCE; MUTANTS; CELLS AB The local presence of endothelial cells seems necessary for proper embryonic development of several organs. However, the signals involved are unknown. The glomerulus is generated by the coalescence of podocytes around an ingrowing capillary and is the site of blood ultrafiltration. In the absence of vessels, glomerular assembly does not occur. We describe mutations in the zebrafish that prevent glomerulogenesis. All mutants display cardiac dysfunction. Pharmacological interference with cardiac output and focal laser occlusion of the vessel similarly prevent glomerular formation. The unifying feature of all these perturbations is absence of blood flow. We find that expression of matrix metalloproteinase-2 (MMP-2), known in other systems to be regulated in a stretch-responsive manner, is in renal endothelial cells and is regulated by flow, suggesting that an MMP-2-sensitive event may be downstream of the flow-related signal. In support of this, blockade of MMP-2 activity by injection of TIMP-2 does not perturb circulation but does prevent glomerular assembly. Thus, vascular flow is required for glomerular assembly, most probably acting via a stretch-responsive signaling system in the vessel wall. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02119 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dev Biol Lab, Boston, MA 02119 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02119 USA. RP Fishman, MC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02119 USA. FU NHLBI NIH HHS [R01HL49579, R01HL63206]; NIDDK NIH HHS [P01DK54711, R01DK53093, R01DK55383] NR 36 TC 84 Z9 89 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAR 19 PY 2002 VL 12 IS 6 BP 492 EP 497 AR PII S0960-9822(02)00694-2 DI 10.1016/S0960-9822(02)00694-2 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 533NC UT WOS:000174535700023 PM 11909536 ER PT J AU Kitareewan, S Pitha-Rowe, I Sekula, D Lowrey, CH Nemeth, MJ Golub, TR Freemantle, SJ Dmitrovsky, E AF Kitareewan, S Pitha-Rowe, I Sekula, D Lowrey, CH Nemeth, MJ Golub, TR Freemantle, SJ Dmitrovsky, E TI UBE1L is a retinoid target that triggers PML/RAR alpha degradation and apoptosis in acute promyelocytic leukemia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID UBIQUITIN-ACTIVATING ENZYME; LUNG-CANCER; CYCLIN D1; HISTONE DEACETYLASE; REDUCED EXPRESSION; FUSION PROTEINS; CELL-LINE; ACID; GENE; PROTEASOME AB All-trans-retinoic acid (RA) treatment induces remissions in acute promyelocytic leukemia (APL) cases expressing the t(15;17) product, promyelocytic leukemia (PML)/RA receptor alpha (RARalpha). Microarray analyses previously revealed induction of UBE1L (ubiquitin-activating enzyme E1-like) after RA treatment of NB4 APL cells. We report here that this occurs within 3 h in RA-sensitive but not RA-resistant APL cells, implicating UBE1L as a direct retinoid target. A 1.3-kb fragment of the UBE1L promoter was capable of mediating transcriptional response to RA in a retinoid receptor-selective manner. PML/RARalpha, a repressor of RA target genes, abolished this UBE1L promoter activity. A hallmark of retinoid response in APL is the proteasome-dependent PML/RARalpha degradation. UBE1L transfection triggered PML/RARalpha degradation, but transfection of a truncated UBE1L or E1 did not cause this degradation. A tight link was shown between UBE1L induction and PML/RARalpha degradation. Notably, retroviral expression of UBE1L rapidly induced apoptosis in NB4 APL cells, but not in cells lacking PML/RARalpha expression. UBE1L has been implicated directly in retinoid effects in APL and may be targeted for repression by PML/RARalpha. UBE1L is proposed as a direct pharmacological target that overcomes oncogenic effects of PML/RARalpha by triggering its degradation and signaling apoptosis in APL cells. C1 Dartmouth Coll Sch Med, Dept Pharmacol & Toxicol, Hanover, NH 03755 USA. Dartmouth Coll Sch Med, Dept Med, Hanover, NH 03755 USA. Dartmouth Coll Sch Med, Norris Cotton Canc Ctr, Hanover, NH 03755 USA. Whitehead Inst Biomed Res, Cambridge, MA 02139 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kitareewan, S (reprint author), Dartmouth Coll Sch Med, Dept Pharmacol & Toxicol, Hanover, NH 03755 USA. FU NCI NIH HHS [R01 CA087546, R01-CA87546, R01-CA62275, R01 CA062275]; NHLBI NIH HHS [R01 HL052243, R01-HL52243] NR 31 TC 75 Z9 82 U1 0 U2 0 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 19 PY 2002 VL 99 IS 6 BP 3806 EP 3811 DI 10.1073/pnas.052011299 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 533CC UT WOS:000174511000081 PM 11891284 ER PT J AU Koike, C McKee, TD Pluen, A Ramanujan, S Burton, K Munn, LL Boucher, Y Jain, RK AF Koike, C McKee, TD Pluen, A Ramanujan, S Burton, K Munn, LL Boucher, Y Jain, RK TI Solid stress facilitates spheroid formation: potential involvement of hyaluronan SO BRITISH JOURNAL OF CANCER LA English DT Article DE solid stress; spheroid; hyaluronan; agarose; Gompertz equation ID RAT PROSTATIC-CANCER; E-CADHERIN; CARCINOMA CELLS; GROWTH; EXPRESSION; TUMORS; LINES AB When neoplastic cells grow in confined spaces in vivo, they exert a finite force on the surrounding tissue resulting in the generation of solid stress. By growing multicellular spheroids in agarose gels of defined mechanical proper-ties, we have recently shown that solid stress inhibits the growth of spheroids and that this growth-inhibiting stress ranges from 45 to 120 mmHg. Here we show that solid stress facilitates the formation of spheroids in the highly metastatic Dunning R3327 rat prostate carcinoma AT3.1 cells, which predominantly do not grow as spheroids in free suspension. The maximum size and the growth rate of the resulting spheroids decreased with increasing stress. Relieving solid stress by enzymatic digestion of gels resulted in gradual loss of spheroidal morphology in 8 days. In contrast, the low metastatic variant AT2.1 cells, which grow as spheroids in free suspension as well as in the gels, maintained their spheroidal morphology even after stress removal. Histological examination revealed that most cells in AT2.1 spheroids are in close apposition whereas a regular matrix separates the cells in the AT3.1 gel spheroids. Staining with the hyaluronan binding protein revealed that the matrix between AT3.1 cells in agarose contained hyaluronan, while AT3.1 cells had negligible or no hyaluronan when grown in free suspension. Hyaluronan was found to be present in both free suspensions and agarose gel spheroids of AT2.1. We suggest that cell-cell adhesion may be adequate for spheroid formation, whereas solid stress may be required to form spheroids when cell-matrix adhesion is predominant. These findings have significant implications for tumour growth, invasion and metastasis. (C) 2002 Cancer Research UK. C1 Harvard Univ, Dept Radiat Oncol, Edwin L Steele Lab, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA. MIT, Div Bioengn & Environm Hlth, Cambridge, MA 02139 USA. RP Jain, RK (reprint author), Harvard Univ, Dept Radiat Oncol, Edwin L Steele Lab, Massachusetts Gen Hosp,Sch Med, 100 Blossom St,Cox-7, Boston, MA 02114 USA. RI Pluen, Alain/F-5300-2015; Munn, Lance/L-3950-2016; OI Pluen, Alain/0000-0002-5953-8011; Munn, Lance/0000-0003-0698-7232; McKee, Trevor/0000-0002-2195-6146 FU NCI NIH HHS [R24 CA 85146, R35 CA 56591, U01 CA085146]; NIGMS NIH HHS [5T32 GM 08334, T32 GM008334] NR 20 TC 39 Z9 42 U1 2 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAR 18 PY 2002 VL 86 IS 6 BP 947 EP 953 DI 10.1038/sj/bjc/6600158 PG 7 WC Oncology SC Oncology GA 540MN UT WOS:000174932900016 PM 11953828 ER PT J AU da Silveira, SA Kikuchi, S Fossati-Jimack, L Moll, T Saito, T Verbeek, JS Botto, M Walport, MJ Carroll, M Izui, S AF da Silveira, SA Kikuchi, S Fossati-Jimack, L Moll, T Saito, T Verbeek, JS Botto, M Walport, MJ Carroll, M Izui, S TI Complement activation selectively potentiates the pathogenicity of the IgG2b and IgG3 Isotypes of a high affinity anti-erythrocyte autoantibody SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE autoimmune hemolytic anemia; complement receptor; Fc receptor; IgG isotype; phagocytosis ID AUTOIMMUNE HEMOLYTIC-ANEMIA; REVERSE ARTHUS REACTION; GAMMA-RIII CD16; FC-RECEPTORS; IN-VIVO; DEFICIENT MICE; CHAIN GENE; INFLAMMATORY RESPONSES; MOUSE MACROPHAGES; GLOMERULONEPHRITIS AB By generating four IgG isotype-switch variants of the high affinity 34-3C anti-erythrocyte autoantibody, and comparing them to the IgG variants of the low affinity 4C8 anti-erythrocyte autoantibody that we have previously studied, we evaluated in this study how high affinity binding to erythrocytes influences the pathogenicity of each IgG isotype in relation to the respective contributions of Fcgamma receptor (FcgammaR) and complement. The 34-3C autoantibody opsonizing extensively circulating erythrocytes efficiently activated complement in vivo (IgG2a = IgG2b > IgG3), except for the IgG1 isotype, while the 4C8 IgG autoantibody filled to activate complement. The pathogenicity of the 34-3C autoantibody of IgG2b and IgG3 isotypes was dramatically higher (>200-fold) than that of the corresponding isotypes of the 4C8 antibody. This enhanced activity was highly (IgG2b) or totally (IgG3) dependent oil complement. In contrast, erythrocyte-binding affinities only played a minor role in in vivo hemolytic activities of the IgG1 and IgG2a isotypes of 34-3C and 4C8 antibodies, where complement was not or only partially involved, respectively. The remarkably different capacities of four different IgG isotypes of low and high affinity anti-erythrocyte autoantibodies to activate FcgammaR-bearing effector cells and complement in vivo demonstrate the role of autoantibody affinity maturation and of IgG isotype switching in autoantibody-mediated pathology. C1 Univ Geneva, CMU, Dept Pathol, CH-1211 Geneva 4, Switzerland. Univ London Imperial Coll Sci Technol & Med, Rheumatol Sect, London W12 0NN, England. Chiba Univ, Grad Sch Med, Dept Mol Genet, Chiba 260, Japan. Leiden Univ, Ctr Med, Dept Human & Clin Genet, NL-2300 RA Leiden, Netherlands. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Izui, S (reprint author), Univ Geneva, CMU, Dept Pathol, CH-1211 Geneva 4, Switzerland. RI Saito, Takashi/C-9684-2009; OI Saito, Takashi/0000-0001-9495-3547; Walport, Mark/0000-0001-7220-5273 NR 39 TC 52 Z9 53 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 MAR 18 PY 2002 VL 195 IS 6 BP 665 EP 672 DI 10.1084/jem.20012024 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 560ZC UT WOS:000176110400002 ER PT J AU Murray, M Alland, D AF Murray, M Alland, D TI Methodological problems in the molecular epidemiology of tuberculosis SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE communicable diseases; DNA fingerprinting; epidemiologic methods; epidemiology; molecular; tuberculosis ID NEW-YORK-CITY; RESISTANT MYCOBACTERIUM-TUBERCULOSIS; FRAGMENT-LENGTH-POLYMORPHISM; HUMAN-IMMUNODEFICIENCY-VIRUS; EXOGENOUS REINFECTION; COMPLEX STRAINS; HIV-INFECTION; TRANSMISSION; SEQUENCE; IS6110 AB In systematic studies of the molecular epidemiology of tuberculosis, DNA fingerprinting is used to estimate the fraction of incident cases attributable to recent transmission of Mycobacterium tuberculosis rather than reactivation disease and to identify risk factors for recent transmission. This approach is based on the premise that tuberculosis cases that share a DNA fingerprint are epidemiologically related while cases in which fingerprints are unique are due to remote infection that has reactivated. In this paper, the authors review the objectives and design of molecular epidemiologic studies of tuberculosis, describe current analytical approaches, and consider the impact of these different approaches on study results. Using data from a previously published investigation of the epidemiology of tuberculosis conducted from 1990 to 1993 among tuberculosis patients in New York City, New York, the authors show how selecting different measures of disease frequency, comparison groups, and sampling strategies may impact the results and interpretability of the study. They demonstrate ways to conduct sensitivity analyses of estimated results and suggest strategies that may improve the usefulness of this approach to studying tuberculosis. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Montefiore Med Ctr, Div Infect Dis, Bronx, NY 10467 USA. RP Murray, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [K08 AI-01430-01] NR 39 TC 75 Z9 79 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 15 PY 2002 VL 155 IS 6 BP 565 EP 571 DI 10.1093/aje/155.6.565 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 532GE UT WOS:000174465300009 PM 11882530 ER PT J AU Lorberbaum, JP Newman, JD Horwitz, AR Dubno, JR Lydiard, RB Hamner, MB Bohning, DE George, MS AF Lorberbaum, JP Newman, JD Horwitz, AR Dubno, JR Lydiard, RB Hamner, MB Bohning, DE George, MS TI A potential role for thalamocingulate circuitry in human maternal behavior SO BIOLOGICAL PSYCHIATRY LA English DT Article DE maternal behavior; infant crying; brain imaging; functional magnetic resonance imaging; human; auditory perception ID MEDIAL PREOPTIC AREA; RIGHT-HEMISPHERE; LACTATING RATS; PERIPEDUNCULAR NUCLEUS; PERIAQUEDUCTAL GRAY; AUDITORY-CORTEX; BRAIN ACTIVITY; FEMALE RATS; C-FOS; LESIONS AB Background: Little is known about the regional brain basis of human. maternal behavior. To understand this better, we have been examining brain activity in mothers listening to infant cries. Methods: We measured functional Magnetic Resonance Imaging brain activity in healthy, breastfeeding first-time mothers with young infants while they listened to infant cries, white noise control sounds, and a rest condition. Based on the thalamocingulate theory of maternal behavior and pilot work, we hypothesized that the cingulate, medial thalamus, medial prefrontal cortex, and right orbitofrontal cortex would display more activity with infant cries than with white noise (comparison 1) and would uniquely activate with the cries, meaning that these regions would display activity with cry minus rest but not with white noise minus rest (comparison 2). Results: In hypothesized regions, the group displayed more activity in the medial thalamus, medial prefrontal and right orbitofrontal cortices with both comparisons. The anterior and posterior cingulate cortex displayed more activity only with comparison 1. In non-hypothesized brain regions, several other structures thought important in rodent maternal behavior displayed activity with both comparisons including the midbrain, hypothalamus, dorsal and ventral striatum, and vicinity of the lateral septal region. Conclusions: Our results partially support our hypotheses and are generally consistent with neuroanatomical studies of rodent maternal behavior. (C) 2002 Society of Biological Psychiatry. C1 Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. NICHHD, Bethesda, MD USA. RP Lorberbaum, JP (reprint author), Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. FU NINDS NIH HHS [R01 NS 40259] NR 77 TC 175 Z9 177 U1 3 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 15 PY 2002 VL 51 IS 6 BP 431 EP 445 DI 10.1016/S0006-3223(01)01284-7 PG 15 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 537CD UT WOS:000174739000001 PM 11922877 ER PT J AU Goff, DC Hennen, J Lyoo, IK Tsai, G Wald, LL Evins, AE Yurgelun-Todd, DA Renshaw, PF AF Goff, DC Hennen, J Lyoo, IK Tsai, G Wald, LL Evins, AE Yurgelun-Todd, DA Renshaw, PF TI Modulation of brain and serum glutamatergic concentrations following a switch from conventional neuroleptics to olanzapine SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; negative symptoms; glutamate; olanzapine; clozapine; spectroscopy ID MAGNETIC-RESONANCE SPECTROSCOPY; NEGATIVE SYMPTOMS; DOUBLE-BLIND; SCHIZOPHRENIA; PLACEBO; TRIAL; HALOPERIDOL; CLOZAPINE; CORTEX; REGION AB Background: Recent evidence suggests that effects upon glutamatergic transmission may contribute to the therapeutic action of certain atypical antipsychotic agents. Methods: Glutamate concentrations were measured in serum and were estimated (Glx/Cr) in cingulate cortex by proton magnetic resonance spectroscopy (MRS) in schizophrenia patients while they were being treated with conventional neuroleptics and then 8 weeks after switching to olanzapine. Serum glutamate concentrations were obtained from 11 subjects, and MRS estimates of Glx/Cr were available from 10 subjects at both time points. Results: Serum glutamate concentrations significantly increased after the switch from conventional agents to olanzapine; brain glutamate (Glx/Cr) did not change significantly; however, brain glutamate (Glx/Cr) concentrations increased significantly in patients who exhibited an improvement in negative symptoms with olanzapine compared with patients with no change or worsening of negative symptoms. Conclusions: Comparisons performed following the switch tom conventional agents to olanzapine are consistent with previous studies of clozapine and provide additional preliminary evidence supporting the hypothesis that effects on excitatory amino acid activity may contribute to olanzapine's efficacy for treating negative symptoms. (C) 2002 Society of Biological Psychiatry. C1 Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. McLean Hosp, Brain Imaging Ctr, Boston, MA USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA 02115 USA. RP Goff, DC (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. RI Wald, Lawrence/D-4151-2009 NR 23 TC 72 Z9 74 U1 0 U2 1 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 15 PY 2002 VL 51 IS 6 BP 493 EP 497 DI 10.1016/S0006-3223(01)01321-X PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 537CD UT WOS:000174739000009 PM 11922885 ER PT J AU Talpaz, M Silver, RT Druker, BJ Goldman, JM Gambacorti-Passerini, C Guilhot, F Schiffer, CA Fischer, T Deininger, MWN Lennard, AL Hochhaus, A Ottmann, OG Gratwohl, A Baccarani, M Stone, R Tura, S Mahon, FX Fernandes-Reese, S Gathmann, I Capdeville, R Kantarjian, HM Sawyers, CL AF Talpaz, M Silver, RT Druker, BJ Goldman, JM Gambacorti-Passerini, C Guilhot, F Schiffer, CA Fischer, T Deininger, MWN Lennard, AL Hochhaus, A Ottmann, OG Gratwohl, A Baccarani, M Stone, R Tura, S Mahon, FX Fernandes-Reese, S Gathmann, I Capdeville, R Kantarjian, HM Sawyers, CL TI Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study SO BLOOD LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; BONE-MARROW TRANSPLANTATION; TYROSINE KINASE INHIBITOR; LOW-DOSE CYTARABINE; ABL-POSITIVE CELLS; BCR-ABL; PHILADELPHIA-CHROMOSOME; RESISTANCE; MICE; INDUCTION AB Chronic myelogenous leukemia (CML) is caused by expression of the BCR-ABL tyrosine kinase oncogene, the product of the t(9;22) Philadelphia translocation. Patients with CML in accelerated phase have rapidly progressive disease and are characteristically unresponsive to existing therapies. Imatinib (formerly STI571) is a rationally developed, orally administered inhibitor of the Bcr-Abl kinase. A total of 235 CML patients were enrolled in this study, of whom 181 had a confirmed diagnosis of accelerated phase. Patients were treated with imatinib at 400 or 600 mg/d and were evaluated for hematologic and cytogenetic response, time to progression, survival, and toxicity. Imatinib induced hematologic response in 82% of patients and sustained hematologic responses lasting at least 4 weeks in 69% (complete in 34%). The rate of major cytogenetic response was 24% (complete in 17%). Estimated 12-month progression-free and overall survival rates were 59% and 74%, respectively. Nonhematologic toxicity was usually mild or moderate, and hematologic toxicity was manageable. In comparison to 400 mg, imatinib doses of 600 mg/d led to more cytogenetic responses (28% compared to 16%), longer duration of response (79% compared to 57% at 12 months), time to disease progression (67% compared to 44% at 12 months), and overall survival (78% compared to 65% at 12 months), with no clinically relevant increase In toxicity. Orally administered Imatinib is an effective and well-tolerated treatment for patients with CML in accelerated phase. A daily dose of 600 mg is more effective than 400 mg, with similar toxicity. C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, New York, NY USA. Oregon Hlth Sci Univ, Div Hematol, Portland, OR 97201 USA. Univ London Imperial Coll Sci Technol & Med, Sch Med, Hammersmith Hosp, Dept Haematol, London, England. San Gerardo Hosp, Hematol Sect, Monza, Italy. Natl Canc Inst, Dept Expt Oncol, I-20133 Milan, Italy. CHU Poitiers, Dept Oncol Hematol & Cell Therapy, Poitiers, France. Wayne State Univ, Barabara Ann Karmanos Canc Inst, Detroit, MI USA. Univ Mainz Klinikum, Med Klin & Poliklin, Mainz, Germany. Univ Leipzig, Abt Haematol Onkol, Leipzig, Germany. Univ Newcastle Upon Tyne, Royal Victoria Infirm, Dept Haematol, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England. Univ Heidelberg, Med Klin, D-6800 Mannheim, Germany. Univ Frankfurt, Med Klin 3, D-6000 Frankfurt, Germany. Kantonsspital, Div Hematol, Univ Klin, CH-4031 Basel, Switzerland. Udine Univ Hosp, Div Hematol, Udine, Italy. Dana Farber Canc Inst, Boston, MA 02115 USA. Osped Policlin Sant Orsola Malpighi, Inst Ematol, Bologna, Italy. Univ Victor Segalen, Lab Greffe Moelle, Bordeaux, France. RP Talpaz, M (reprint author), Univ Texas, MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM mtalpaz@mail.mdanderson.org RI Ottmann, Oliver/D-5007-2016; Sawyers, Charles/G-5327-2016; OI Ottmann, Oliver/0000-0001-9559-1330; GAMBACORTI PASSERINI, CARLO/0000-0001-6058-515X; Hochhaus, Andreas/0000-0003-0626-0834 NR 41 TC 734 Z9 787 U1 2 U2 12 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 2002 VL 99 IS 6 BP 1928 EP 1937 DI 10.1182/blood.V99.6.1928 PG 10 WC Hematology SC Hematology GA 530KA UT WOS:000174355800009 PM 11877262 ER PT J AU Weisdorf, DJ Anasetti, C Antin, JH Kernan, NA Kollman, C Snyder, D Petersdorf, E Nelson, G McGlave, P AF Weisdorf, DJ Anasetti, C Antin, JH Kernan, NA Kollman, C Snyder, D Petersdorf, E Nelson, G McGlave, P TI Allogeneic bone marrow transplantation for chronic myelogenous leukemia: comparative analysis of unrelated versus matched sibling donor transplantation SO BLOOD LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; T-CELL DEPLETION; HLA CLASS-I; CHRONIC PHASE; INTERFERON; SURVIVAL; CHILDREN; RELAPSE; ENGRAFTMENT; HYDROXYUREA AB Allogeneic bane marrow transplantation (BMT) offers the only curative therapy for chronic myelogenous leukemia. We compared prospectively collected results of 2464 unrelated donor (URD) transplantations with 450 HLA-identical, matched sibling donor (MSD) transplantations performed at collaborating National Marrow Donor Program institutions. A total of 63% of URDs were matched at HLA-A, -B, and at -DRB1 alleles; all MSDs were genotypically identical at major histocompatibility loci. URD recipients were younger (median 36 vs 39, P = .001) than MSDs and underwent BMT later after diagnosis (median 17 [0-325 months] vs 7 [1-118 months], P = .001) and less often in chronic phase (CP) (67% vs 82%, P = .001). Multivariate analysis demonstrated a significantly increased risk of graft failure and acute graft versus host disease after URD BMT The risk of hematologic relapse was low after either matched URD or MSD transplantations. We observed significantly though modestly poorer survival and disease-free survival (DFS) after URD transplantations. However, for those undergoing transplantation during CP within 1 year from diagnosis, 5-year DFS was similar or only slightly inferior after matched URD versus MSD transplantation (age < 30: URD 61% +/- 8% vs MSD 68% +/- 15%, P = .18; 30-40: URD 57% +/- 9% vs MSD 67% +/- 10%, P = .05; > 40: URD 46% +/- 9% vs MSD 57% +/- 9%, P = .02). Delay from diagnosis to BMT in CP patients led to substantially poorer 5-year DFS after matched URD than MSD BMT (CP 1-2 years: URD 39% +/- 6% vs MSD 63% +/- 12%; beyond 2 years: URD 33% +/- 7% vs MSD 50% +/- 20%). Outcome of matched URD BMT for early CP chronic myelogenous leukemia yields survival and DFS approaching that of MSD transplantation. However, delay may compromise URD outcomes to a greater extent. Improvements in URD and MSD transplantation are still needed, and results of newer, nontransplantation therapies should be evaluated against the established curative potential of URD and MSD marrow transplantation. C1 Univ Minnesota, Minneapolis, MN 55455 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Natl Marrow Donor Program, Minneapolis, MN USA. RP Weisdorf, DJ (reprint author), Univ Minnesota, Mayo Mail Code 480,420 Delaware St SE, Minneapolis, MN 55455 USA. NR 36 TC 134 Z9 146 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 2002 VL 99 IS 6 BP 1971 EP 1977 DI 10.1182/blood.V99.6.1971 PG 7 WC Hematology SC Hematology GA 530KA UT WOS:000174355800015 PM 11877268 ER PT J AU Mitsiades, N Mitsiades, CS Poulaki, V Anderson, KC Treon, SP AF Mitsiades, N Mitsiades, CS Poulaki, V Anderson, KC Treon, SP TI Intracellular regulation of tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in human multiple myeloma cells SO BLOOD LA English DT Article ID FLICE-INHIBITORY PROTEIN; TRAIL-INDUCED APOPTOSIS; FAS-MEDIATED APOPTOSIS; DNA FRAGMENTATION; DENDRITIC CELLS; DEATH RECEPTORS; MELANOMA-CELLS; CANCER-CELLS; APO2 LIGAND; ACTIVATION AB Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, Apo2 ligand) effectively kills multiple myeloma (MM) cells in vitro irrespective of refractoriness to dexamethasone and chemotherapy. Because clinical trials with this anticancer agent are expected shortly, we investigated the signaling pathway of TRAIL-induced apoptosis in MM. We detected rapid cleavage of caspases-8, -9, -3, and -6, as well as the caspase substrates poly(ADP-ribose) polymerase (PARP) and DNA fragmentation factor-45 (DFF45), but not caspase-10, upon TRAIL treatment in sensitive MM cells, pointing to caspase-8 as the apical caspase of TRAIL signaling in MM cells. These phenomena were not observed or were significantly delayed in TRAIL-resistant MM cells, suggesting that resistance may arise from inhibition at the level of caspase-8 activation. Higher levels of expression for various apoptosis inhibitors, including FLICE-inhibitory protein (FLIP), and lower procaspase-8 levels were present in TRAIL-resistant cells and sensitivity was restored by the protein synthesis inhibitor cycloheximide (CHX) and the protein kinase C (PKC) inhibitor bisindolylmaleimide (BIM), which both lowered FLIP and cellular inhibitor of apoptosis protein-2 (cIAP-2) protein levels. Forced expression of procaspase-8 or FLIP antisense oligonucleotides also sensitized TRAIL-resistant cells to TRAIL. Moreover, the cell permeable nuclear factor (NF)-kappaB inhibitor SN50, which sensitizes TRAIL-resistant cells to TRAIL, also inhibited cIAP2 protein expression. Finally, CHX, BIM, and SN50 facilitated the cleavage and activation of procaspase-8 in TRAIL-resistant cells, confirming that inhibition of TRAIL-induced apoptosis occurs at this level and that these agents sensitize MM cells by relieving this block. Our data set a framework for the clinical use of approaches that sensitize MM cells to TRAIL by agents that Inhibit FLIP and cIAP-2 expression or augment caspase-8 activity. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Treon, SP (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St,Mayer Bldg,Rm M557, Boston, MA 02115 USA. NR 53 TC 120 Z9 124 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 MAR 15 PY 2002 VL 99 IS 6 BP 2162 EP 2171 DI 10.1182/blood.V99.6.2162 PG 10 WC Hematology SC Hematology GA 530KA UT WOS:000174355800040 PM 11877293 ER PT J AU Cantuti-Castelvetri, I Keller-McGandy, CE Albers, DS Beal, MF Vonsattel, JP Standaert, DG Augood, SJ AF Cantuti-Castelvetri, I Keller-McGandy, CE Albers, DS Beal, MF Vonsattel, JP Standaert, DG Augood, SJ TI Expression and activity of antioxidants in the brain in progressive supranuclear palsy SO BRAIN RESEARCH LA English DT Article DE progressive supranuclear palsy; parkinsonism; tau; superoxide dismutase; neurodegeneration; oxidative stress ID MANGANESE SUPEROXIDE-DISMUTASE; OXIDATIVE STRESS; CORTICOBASAL DEGENERATION; PROTEIN-TAU; NEURODEGENERATIVE DISORDERS; PARKINSONS-DISEASE; BASAL GANGLIA; GLUTATHIONE; DYSFUNCTION; NEURONS AB Recent evidence implicates oxidative stress in the pathophysiology of progressive supranuclear palsy (PSP). Thus, we undertook a study of the activity and localization of two essential antioxidant systems (superoxide dismutase [SOD] enzymes and total glutathione) in the human post-mortem PSP and control brain. Marked increases in SOD1 (Cu/ZnSOD) activity and glutathione levels were measured within most PSP brain regions examined, whereas, only the subthalamic nucleus exhibited a significant increase (+68%) in SOD2 (MnSOD) activity. Two additional cases with mild pathological abnormalities were studied. The first (case A) may represent an example of an asymptomatic PSP case, while the second (case B) had mild pathological abnormalities consistent with typical PSP. In case A, only the STN had elevated levels of SOD activity, in the absence of an increase in tissue glutathione content. In case B, SOD activities and tissue glutathione content were elevated in several regions. Immunolocalization of the SOD1 and SOD2 proteins in paraffin-embedded tissue sections revealed a marked increase in the density of SOD immunopositive profiles (particularly glia) in the typical PSP brain, particularly within the white matter. Together, our data argues strongly in favor of the involvement of oxidative stress in the etiology and progression of PSP, and suggests that deficit in SOD or glutathione metabolism are not causative. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. RP Cantuti-Castelvetri, I (reprint author), Massachusetts Gen Hosp, Neurol Res CNY B114-2300,114 16th St, Charlestown, MA 02129 USA. OI Standaert, David/0000-0003-2921-8348 FU NIMH NIH HHS [MH/NS 31862] NR 50 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 15 PY 2002 VL 930 IS 1-2 BP 170 EP 181 AR PII S0006-8993(02)02244-8 DI 10.1016/S0006-8993(02)02244-8 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 534ME UT WOS:000174589500019 PM 11879807 ER PT J AU Matranga, CB Shapiro, GI AF Matranga, CB Shapiro, GI TI Selective sensitization of transformed cells to flavopiridol-induced apoptosis following recruitment to S-phase SO CANCER RESEARCH LA English DT Article ID CYCLIN-DEPENDENT KINASES; BREAST-CARCINOMA CELLS; CDK INHIBITORS; CANCER; PROGRESSION; ARREST; GROWTH; DNA; AGENTS; BINDS AB Flavopiridol is a potent inhibitor of cyclin-dependent kinases (cdks). In a large proportion of solid tumor cell lines, the initial response to flavopiridol is cell cycle arrest. NCI-H661 non-small cell lung cancer cells are representative of a subset of more sensitive cell lines in which apoptosis is observed during the first 24 h of drug exposure. Analysis of the apoptotic population indicates that cells in S-phase are preferentially dying. In addition, cells are sensitized to flavopiridol following recruitment to S-phase, whether accomplished by synchronization or by treatment with noncytotoxic concentrations of chemotherapy agents that impose an S-phase delay. Combinations of gemcitabine or cisplatin, followed by flavopiridol at concentrations that correlate with cdk inhibition, produce sequence-dependent cytotoxic synergy. A survey of paired cell lines, including WI38 diploid fibroblasts or normal human bronchial epithelial cells, along with their SV40-transformed counterparts, demonstrates that treatment with flavopiridol during S-phase is selectively cytotoxic to transformed cells. These data suggest that treatment during S-phase may maximize responses to flavopiridol and that the administration of flavopiridol after chemotherapy agents that cause S-phase accumulation may be an efficacious antitumor strategy. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Shapiro, GI (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA090687, R01 CA90687] NR 39 TC 46 Z9 51 U1 1 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 MAR 15 PY 2002 VL 62 IS 6 BP 1707 EP 1717 PG 11 WC Oncology SC Oncology GA 533ZM UT WOS:000174560200021 PM 11912144 ER PT J AU Sasaki, H Betensky, RA Cairncross, JG Louis, DN AF Sasaki, H Betensky, RA Cairncross, JG Louis, DN TI DMBT1 polymorphisms: Relationship to malignant glioma tumorigenesis SO CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENES; PROSTATE-CANCER; LUNG-CANCER; HUMAN BRAIN; IN-VIVO; DELETION; IDENTIFICATION; CHROMOSOME-10; PROGRESSION; EXPRESSION AB The deleted in malignant brain tumors 1 (DMBT1) gene on 10q25-26 is a candidate tumor suppressor gene in malignant gliomas, but its role is controversial, e.g., some DMBT1 homozygous deletions reflect unmasking of constitutional deletion polymorphisms by 10q loss. To clarify the role of DMBT1 in gliomagenesis, we investigated three reported deletion hot spots. Homozygous deletions at DMBT1 repeat 2-4 to 2-7 were found in 10 of 73 gliomas with 10q loss, but all 10 deletions reflected unmasking of constitutional hemizygous deletions. Alleles bearing deletion 2-4/2-7 were not selected significantly for by 10q loss, with retention of only 10 of 16 deleted alleles. No homozygous deletion was detected at locus 74k in the 5' upstream region of DMBT1, and four tightly linked polymorphisms were found around this region; chromosome 10q loss randomly affected alleles with or without the variant sequences around locus 74k. Moreover, no significant selection pressure was detected for the haplotype with both deletion 2-4/2-7 and 5' polymorphisms. There was no segregation of deletion 2-4/2-7 in glioma patients compared with unrelated individuals from reference families but a suggestion of a difference in the distribution of the 5' polymorphisms between the reference individuals and glioma patients. Constitutional polymorphisms at DMBT1 repeat 2-9/2-10 appeared common in patients with both benign brain tumors and gliomas. A homozygote for both the 2-4/2-7 deletion and the 5' polymorphisms had a glioma arise at a typical age and without an apparent family cancer predisposition. These data suggest that DMBT1 polymorphisms are not likely primary targets of 10q loss in malignant gliomas and do not support a major role for DMBT1 in gliomagenesis. C1 Massachusetts Gen Hosp, Dept Pathol, Mol Neurooncol & Pathol Labs, Boston, MA 02129 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Western Ontario, Dept Clin Neurol Sci, London, ON N6A 4L6, Canada. Univ Western Ontario, Dept Oncol, London, ON N6A 4L6, Canada. London Reg Canc Ctr, London, ON N6A 4L6, Canada. RP Louis, DN (reprint author), Massachusetts Gen Hosp, Mol Neurooncol Lab, 149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA57683] NR 36 TC 31 Z9 31 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 MAR 15 PY 2002 VL 62 IS 6 BP 1790 EP 1796 PG 7 WC Oncology SC Oncology GA 533ZM UT WOS:000174560200033 PM 11912156 ER PT J AU Sherman, KE Rouster, SD Chung, RT Rajicic, N AF Sherman, KE Rouster, SD Chung, RT Rajicic, N TI Hepatitis C virus prevalence among patients infected with human immunodeficiency virus: A cross-sectional analysis of the US adult AIDS clinical trials group SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 10th International Symposium on Viral Hepatitis and Liver Disease CY APR 09-13, 2000 CL ATLANTA, GEORGIA ID ANTIRETROVIRAL THERAPY; UNITED-STATES; HEMOPHILIC MEN; HCV ANTIBODY; HIV; PROGRESSION; COINFECTION; POPULATION; VIREMIA; GENOTYPES AB Hepatitis C virus (HCV) has emerged as an important etiologic agent of liver injury and failure in patients infected with human immunodeficiency virus (HIV). The prevalence and characteristics of HCV in a representative cohort of HIV-infected patients have not been described. Therefore, a representative sample of 1687 HIV-infected patients was studied; a 213-sample subcohort was selected by use of risk-based sampling from 2 large prospective US Adult AIDS Clinical Trials Group clinical trials. HCV prevalence, HCV RNA level, and genotype were determined. The weighted overall estimate of HCV prevalence in the study cohort was 16.1% (95% weighted confidence interval, 14.3%-17.8%), with significant variability depending on risk factors and HIV RNA levels. Among patients defined as being "at risk," 72.7% were HCV positive, whereas, among low-risk patients, the positivity rate was 3.5%. Genotype 1 was found in 83.3% of infected patients. Median HCV RNA level was 6.08 x 10(6) IU/mL. High virus loads and genotype 1 prevalence may be important to interferon-based antiviral response rates among coinfected patients. C1 Univ Cincinnati, Coll Med, Div Digest Dis, Cincinnati, OH 45267 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Sherman, KE (reprint author), Univ Cincinnati, Coll Med, Div Digest Dis, 231 Albert Sabin Way, Cincinnati, OH 45267 USA. FU NIAID NIH HHS [AI25987, U01AI38858] NR 29 TC 481 Z9 502 U1 2 U2 10 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 15 PY 2002 VL 34 IS 6 BP 831 EP 837 DI 10.1086/339042 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 525BL UT WOS:000174047300014 PM 11833007 ER PT J AU Jiang, P Song, JW Gu, GQ Slonimsky, E Li, E Rosenthal, N AF Jiang, P Song, JW Gu, GQ Slonimsky, E Li, E Rosenthal, N TI Targeted deletion of the MLC1f/3f downstream enhancer results in precocious MLC expression and mesoderm ablation SO DEVELOPMENTAL BIOLOGY LA English DT Article DE enhancer; myosin; mouse development ID REGULATORY LIGHT-CHAIN; NONMUSCLE MYOSIN-II; SKELETAL-MUSCLE; GENE-EXPRESSION; CHROMOSOMAL DOMAINS; TRANSGENIC MICE; LOCUS; CELLS; POSITION; EMBRYOS AB The expression of skeletal muscle contractile proteins is tightly regulated during embryonic development. In the mouse, the myosin light chain (MLC) 1f/3f gene locus is not activated until E9.5, exclusively in skeletal muscle precursor cells. A potent enhancer downstream of the MLC1f/3f locus confers correct temporal and spatial activation of linked reporter gene in transgenic mouse embryos. To examine roles of the MLC downstream enhancer (MLCE) in its native context of the MLC1f/3f gene locus, we eliminated a 1.5-kb DNA segment containing the enhancer from the mouse genome by targeted deletion, leaving no exogenous sequences at the deletion site. Mouse embryos homozygous for the MLCE deletion were smaller and developmentally delayed, formed no mesoderm by E7.5, and were resorbed almost completely at E8.5. In situ hybridization and RT-PCR analyses of affected mutant embryos at E7.5 revealed ectopic MLC transcripts, whose products would be predicted to interfere with a variety of nonmuscle cell functions determining differentiation of mesoderm. These results suggest that the MLC downstream enhancer and its flanking sequences include negative regulatory elements which block precocious activation of MLC expression in mesodermal precursors during a critical window of development, as well as positive elements which subsequently permit tissue-restricted MLC transcription in differentiating skeletal Muscles. (C) 2002 Elsevier Science (USA). C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Med Sch, Charlestown, MA 02129 USA. RP Rosenthal, N (reprint author), European Mol Biol Lab, Mouse Biol Programme, Via Ramarini 32, I-00016 Monterotondo, Rome, Italy. OI Rosenthal, Nadia/0000-0002-7599-7365 FU NIAMS NIH HHS [AR 41926] NR 55 TC 11 Z9 15 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAR 15 PY 2002 VL 243 IS 2 BP 281 EP 293 DI 10.1006/dbio.2002.0574 PG 13 WC Developmental Biology SC Developmental Biology GA 532GG UT WOS:000174465500007 PM 11884037 ER PT J AU Pani, L Horal, M Loeken, MR AF Pani, L Horal, M Loeken, MR TI Rescue of neural tube defects in Pax-3-deficient embryos by p53 loss of function: implications for Pax-3-dependent development and tumorigenesis SO GENES & DEVELOPMENT LA English DT Article DE Pax-3; P53; neural tube; apoptosis ID TUMOR ALVEOLAR RHABDOMYOSARCOMA; TRANSCRIPTION ACTIVATION; CANCER-THERAPY; PAIRED DOMAIN; PAX-3 GENE; EXPRESSION; MICE; APOPTOSIS; CELLS; MOUSE AB Pax-3 is a transcription factor that is expressed in the neural tube, neural crest, and dermomyotome. We previously showed that apoptosis is associated with neural tube defects (NTDs) in Pax-3-deficient Splotch (Sp/Sp) embryos. Here we show that p53 deficiency, caused by germ-fine mutation or by pifithrin-alpha, an inhibitor of p53-dependent apoptosis, rescues not only apoptosis, but also NTDs, in Sp/Sp embryos. Pax-3 deficiency had no effect on p53 mRNA, but increased p53 protein levels. These results suggest that Pax-3 regulates neural tube closure by inhibiting p53-dependent apoptosis, rather than by inducing neural tube-specific gene expression. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Cellular & Mol Physiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Loeken, MR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Cellular & Mol Physiol, Boston, MA 02215 USA. OI Loeken, Mary/0000-0002-8056-9816 NR 37 TC 131 Z9 138 U1 1 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAR 15 PY 2002 VL 16 IS 6 BP 676 EP 680 DI 10.1101/gad.969302 PG 5 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 533EM UT WOS:000174516500003 PM 11914272 ER PT J AU Silverman, EK Mosley, JD Palmer, LJ Barth, M Senter, JM Brown, A Drazen, JM Kwiatkowski, DJ Chapman, HA Campbell, EJ Province, MA Rao, DC Reilly, JJ Ginns, LC Speizer, FE Weiss, ST AF Silverman, EK Mosley, JD Palmer, LJ Barth, M Senter, JM Brown, A Drazen, JM Kwiatkowski, DJ Chapman, HA Campbell, EJ Province, MA Rao, DC Reilly, JJ Ginns, LC Speizer, FE Weiss, ST TI Genome-wide linkage analysis of severe, early-onset chronic obstructive pulmonary disease: airflow obstruction and chronic bronchitis phenotypes SO HUMAN MOLECULAR GENETICS LA English DT Article ID ASTHMA; SEARCH; EPIDEMIOLOGY; IDENTIFICATION; POPULATION; FAMILIES; PROGRAM; VALUES; POWER; LOCI AB Familial aggregation of chronic obstructive pulmonary disease (COPD) has been demonstrated, but linkage analysis of COPD-related phenotypes has not been reported previously. An autosomal 10 cM genome-wide scan of short tandem repeat (STR) polymorphic markers was analyzed for linkage to COPD-related phenotypes in 585 members of 72 pedigrees ascertained through severe, early-onset COPD probands without severe alpha1-antitrypsin deficiency. Multipoint non-parametric linkage analysis (using the ALLEGRO program) was performed for qualitative phenotypes including moderate airflow obstruction [forced expiratory volume at one second (FEV1) < 60% predicted, FEV1/FVC < 90% predicted], mild airflow obstruction (FEV1 < 80% predicted, FEV1/FVC < 90% predicted) and chronic bronchitis. The strongest evidence for linkage in all subjects was observed at chromosomes 12 (LOD = 1.70) and 19 (LOD = 1.54) for moderate airflow obstruction, chromosomes 8 (LOD = 1.36) and 19 (LOD = 1.09) for mild airflow obstruction and chromosomes 19 (LOD = 1.21) and 22 (LOD = 1.37) for chronic bronchitis. Restricting analysis to cigarette smokers only provided increased evidence for linkage of mild airflow obstruction and chronic bronchitis to several genomic regions; for mild airflow obstruction in smokers only, the maximum LOD was 1.64 at chromosome 19, whereas for chronic bronchitis in smokers only, the maximum LOD was 2.08 at chromosome 22. On chromosome 12p, 12 additional STR markers were genotyped, which provided additional support for an airflow obstruction locus in that region with a non-parametric multipoint approach for moderate airflow obstruction (LOD = 2.13) and mild airflow obstruction (LOD = 1.43). Using a dominant model with the STR markers on 12p, two point parametric linkage analysis of all subjects demonstrated a maximum LOD score of 2.09 for moderate airflow obstruction and 2.61 for mild airflow obstruction. In smokers only, the maximum two point LOD score for mild airflow obstruction was 3.14. These observations provide suggestive evidence that there is a locus on chromosome 12p which contributes to susceptibility to early-onset COPD. C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA. Univ Calif San Francisco, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. RP Silverman, EK (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. RI Drazen, Jeffrey/E-5841-2012; Palmer, Lyle/K-3196-2014 OI Palmer, Lyle/0000-0002-1628-3055 FU NCRR NIH HHS [M01 RR 02635]; NHLBI NIH HHS [HL 07427, HL 46440, HL 48621, HL 61575, P50 HL 56383, U01 HL 66795] NR 42 TC 68 Z9 71 U1 0 U2 0 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 15 PY 2002 VL 11 IS 6 BP 623 EP 632 DI 10.1093/hmg/11.6.623 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 535QC UT WOS:000174654300002 PM 11912177 ER PT J AU Wheeler, VC Gutekunst, CA Vrbanac, V Lebel, LA Schilling, G Hersch, S Friedlander, RM Gusella, JF Vonsattel, JP Borchelt, DR MacDonald, ME AF Wheeler, VC Gutekunst, CA Vrbanac, V Lebel, LA Schilling, G Hersch, S Friedlander, RM Gusella, JF Vonsattel, JP Borchelt, DR MacDonald, ME TI Early phenotypes that presage late-onset neurodegenerative disease allow testing of modifiers in Hdh CAG knock-in mice SO HUMAN MOLECULAR GENETICS LA English DT Article ID DOMINANT-NEGATIVE MUTANT; AMYLOID-LIKE FIBRILS; HUNTINGTONS-DISEASE; TRANSGENIC MICE; INTRANUCLEAR INCLUSIONS; POLYGLUTAMINE PROTEINS; AGGREGATE FORMATION; STRIATAL NEURONS; BRAIN INJURY; MOUSE MODEL AB In Huntington's disease (HD), CAG repeats extend a glutamine tract in huntingtin to initiate the dominant loss of striatal neurons and chorea. Neuropathological changes include the formation of insoluble mutant N-terminal fragment, as nuclear/neuropil inclusions and filter-trap amyloid, which may either participate in the disease process or be a degradative by-product. In young Hdh knock-in mice, CAGs that expand the glutamine tract in mouse huntingtin to childhood-onset HD lengths lead to nuclear accumulation of full-length mutant huntingtin and later accumulation of insoluble fragment. Here we report late-onset neurodegeneration and gait deficits in older Hdh(Q111) knock-in mice, demonstrating that the nuclear phenotypes comprise early stages in a disease process that conforms to genetic and pathologic criteria determined in HD patients. Furthermore, using the early nuclear-accumulation phenotypes as surrogate markers, we show in genetic experiments that the disease process, initiated by full-length mutant protein, is hastened by co-expression of mutant fragment; therefore, accrual of insoluble-product in already compromised neurons may exacerbate pathogenesis. In contrast, timing of early disease events was not altered by normal huntingtin or by mutant caspase-1, two proteins shown to reduce inclusions and glutamine toxicity in other HD models. Thus, potential HD therapies in man might be directed at different levels: preventing the disease-initiating mechanism or slowing the subsequent progression of pathogenesis. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21205 USA. RP MacDonald, ME (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. RI Friedlander, Robert/A-2845-2016 OI Friedlander, Robert/0000-0003-4423-9219 FU NINDS NIH HHS [NS 34172, NS 16367, NS 32765, NS 38144]; ONDIEH CDC HHS [ND 35255] NR 38 TC 114 Z9 115 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 15 PY 2002 VL 11 IS 6 BP 633 EP 640 DI 10.1093/hmg/11.6.633 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 535QC UT WOS:000174654300003 PM 11912178 ER PT J AU Wallner, K AF Wallner, K TI MR imaging for prostate cancer staging: Beauty or beast? SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material ID EXTENSION C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Vet Affairs, Seattle, WA 98108 USA. RP Wallner, K (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Vet Affairs, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 11 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 15 PY 2002 VL 52 IS 4 BP 886 EP 887 AR PII S0360-3016(01)02737-7 DI 10.1016/S0360-3016(01)02737-7 PG 2 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 529UQ UT WOS:000174318500002 PM 11958879 ER PT J AU Hug, EB Sweeney, RA Nurre, PM Holloway, KC Slater, JD Munzenrider, JE AF Hug, EB Sweeney, RA Nurre, PM Holloway, KC Slater, JD Munzenrider, JE TI Proton radiotherapy in management of pediatric base of skull tumors SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE protons; base of skull tumors; particle therapy; conformal therapy; pediatric malignancies ID RADIATION-THERAPY; CONFORMAL RADIOTHERAPY; CHORDOMAS; CHONDROSARCOMAS; MEDULLOBLASTOMA; IRRADIATION; CHILDREN; PHOTONS; TERM AB Purpose: Primary skull base tumors of the developing child are rare and present a formidable challenge to both surgeons and radiation oncologists. Gross total resection with negative margins is rarely achieved, and the risks of functional, structural, and cosmetic deficits limit the radiation dose using conventional radiation techniques. Twenty-nine children and adolescents treated with conformal proton radiotherapy (proton RT) were analyzed to assess treatment efficacy and safety. Methods and Materials: Between July 1992 and April 1999, 29 patients with mesenchymal tumors underwent fractionated proton (13 patients) or fractionated combined proton and photon (16 patients) irradiation. The age at treatment ranged from 1 to 19 years (median 12); 14 patients were male and 15 female. Tumors were grouped as malignant or benign. Twenty patients had malignant histologic findings, including chordoma (n = 10), chondrosarcoma (n = 3), rhabdomyosarcoma (n = 4), and other sarcomas (n = 3). Target doses ranged between 50.4 and 78.6 Gy/cobalt Gray equivalent (CGE), delivered at doses of 1.8-2.0 Gy/CGE per fraction. The benign histologic findings included giant cell tumors (n = 6), angiofibromas (n = 2), and chondroblastoma (n = 1). RT doses for this group ranged from 45.0 to 71.8 Gy/CGE. Despite maximal surgical resection, 28 (97%) of 29 patients had gross disease at the time of proton RT. Follow-up after proton RT ranged from 13 to 92 months (mean 40). Results: Of the 20 patients with malignant tumors, 5 (25%) had local failure; 1 patient had failure in the surgical access route and 3 patients developed distant metastases. Seven patients had died of progressive disease at the time of analysis. Local tumor control was maintained in 6 (60%) of 10 patients with chordoma, 3 (100%) of 3 with chondrosarcoma, 4 (100%) of 4 with rhabdomyosarcoma, and 2 (66%) of 3 with other sarcomas. The actuarial 5-year local control and overall survival rate was 72% and 56%, respectively, and the overall survival of the males was significantly superior to that of the female patients (p = 0.002). Of the patients with benign tumors, I patient (giant cell tumor) had local failure at 10 months. The other 8 patients continued to have local tumor control; all 9 patients were alive at last follow-up (actuarial 5-year local control and overall survival rate of 89% and 100%, respectively). Severe late effects (motor weakness and sensory deficits) were observed in 2 (7%) of 29 patients. Conclusion: Proton RT for children with aggressively recurring tumors after major skull base surgery can offer a considerable prospect of tumor control and survival. Longer follow-up is necessary to assess the real value of protons, in particular with regard to bone growth and cosmetic outcome. (C) 2002 Elsevier Science Inc. C1 Loma Linda Univ, Med Ctr, Dept Pediat, Loma Linda, CA USA. Loma Linda Univ, Med Ctr, Dept Radiat Med, Loma Linda, CA USA. Harvard Cyclotron Lab, Cambridge, MA USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Hug, EB (reprint author), Dartmouth Hitchcock Med Ctr, Dept Radiat Oncol, 1 Med Ctr Dr, Lebanon, NH 03756 USA. NR 25 TC 75 Z9 77 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 15 PY 2002 VL 52 IS 4 BP 1017 EP 1024 AR PII S0360-3016(01)02725-0 DI 10.1016/S0360-3016(01)02725-0 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 529UQ UT WOS:000174318500020 PM 11958897 ER PT J AU Hitchcock, S Ng, AK Fisher, DC Silver, B Bernardo, MP Dorfman, DM Mauch, PM AF Hitchcock, S Ng, AK Fisher, DC Silver, B Bernardo, MP Dorfman, DM Mauch, PM TI Treatment outcome of mucosa-associated lymphoid tissue/marginal zone non-Hodgkin's lymphoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE MALT lymphoma; marginal zone non-Hodgkin's lymphoma; indolent lymphoma; radiation therapy ID B-CELL LYMPHOMA; MALT-LYMPHOMA; LOW-GRADE; TISSUE LYMPHOMA; HELICOBACTER-PYLORI; MALIGNANT-LYMPHOMA; SJOGRENS-SYNDROME; GASTRIC LYMPHOMA; STOMACH; CONJUNCTIVA AB Purpose: To evaluate the treatment outcome in patients with mucosa-associated lymphoid tissue (MALT)/marginal zone (MZ) non-Hodgkin's lymphoma (NHL). Methods and Materials: Between 1986 and 2000,66 patients with clinical stage (CS) I-IV MALT/MZ NHL were treated; these comprise the study population. The progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier technique. Forty-five patients (68%) had CS I-II and 21 (32%) had CS III-IV disease. Twenty-nine of the 45 CS I-II patients received radiation therapy (RT) alone, and 6 patients had surgery and RT. The median RT dose was 3350 cGy. Among the 21 CS III-IV patients, treatment included chemotherapy alone (15), chemotherapy + RT (3), surgery (1), surgery + chemotherapy (1), and RT alone (1). Median follow-up was 48 months. Results: All 35 early-stage and all 4 advanced-stage patients who received RT as part of initial treatment achieved local control. Among the 63 evaluable patients, the 5-year OS and PFS were 90 and 57%, respectively. The 5-year OS was 93% and PFS was 75% among CS I-II patients; the corresponding estimates in CS III-IV patients were 83% and 14%, respectively. Conclusions: Modest doses of RT provide excellent local control in patients with MALT/MZ NHL. The poor PFS in advanced-stage patients suggests the need to develop alternative systemic treatment strategies for this disease. (C) 2002 Elsevier Science Inc. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Mauch, PM (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. NR 26 TC 30 Z9 33 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 15 PY 2002 VL 52 IS 4 BP 1058 EP 1066 AR PII S0360-3016(01)02714-6 DI 10.1016/S0360-3016(01)02714-6 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 529UQ UT WOS:000174318500025 PM 11958902 ER PT J AU Keating, NL Guadagnoli, E Landrum, MB Borbas, C Weeks, JC AF Keating, NL Guadagnoli, E Landrum, MB Borbas, C Weeks, JC TI Treatment decision making in early-stage breast cancer: Should surgeons match patients' desired level of involvement? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COMPARING TOTAL MASTECTOMY; MEDICAL-CARE; PARTICIPATION; PREFERENCES; WOMEN; INFORMATION; COMMUNICATION; CONSERVATION; LUMPECTOMY; ATTITUDES AB Purpose: To describe desired and actual roles in treatment decision making among patients with early-stage breast cancer, identify how often patients' actual roles matched their desired roles, and examine whether matching of actual and desired roles was associated with type of treatment received and satisfaction. Patients and Methods: We surveyed 1,081 women (response, 70%) diagnosed with early-stage breast cancer in Massachusetts or Minnesota about their desired and actual roles in treatment decision making with their surgeon and used logistic regression to assess whether matching of actual to desired roles was associated with type of surgery and satisfaction. Results: Most patients (64%) desired a collaborative role in decision making, but only 33% reported actually having such a collaborative role when they discussed treatments with their surgeons. Overall, 49% of women reported an actual role that matched the desired role they reported, 25% had a less active role than desired, and 26% had a more active role than desired. In adjusted analyses, patients whose reported actual role matched their desired role were no more likely than others to undergo breast-conserving surgery (P>.2), but these women were more satisfied with their treatment choice (83.5% very satisfied; reference) than those whose role was less active than desired (72.9% very satisfied; P=.02) or more active than desired (72.2% very satisfied; P=.005). Conclusion. Only approximately half of patients reported an actual role in decision making that matched the desired role they reported. These patients were more satisfied with their treatment choice than other patients, suggesting that women with early-stage breast cancer may benefit from surgeons' efforts to identify their preferences for participation in decisions and tailor the decision-making process to them. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, Sect Hlth Serv & Policy Res, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Healthcare Educ & Res Fdn Inc, St Paul, MN USA. RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA57755, CA59408] NR 41 TC 154 Z9 157 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 15 PY 2002 VL 20 IS 6 BP 1473 EP 1479 DI 10.1200/JCO.20.6.1473 PG 7 WC Oncology SC Oncology GA 534QF UT WOS:000174597100010 PM 11896094 ER PT J AU Kemeny, MM Adak, S Gray, B Macdonald, JS Smith, T Lipsitz, S Sigurdson, ER O'Dwyer, PJ Benson, AB AF Kemeny, MM Adak, S Gray, B Macdonald, JS Smith, T Lipsitz, S Sigurdson, ER O'Dwyer, PJ Benson, AB TI Combined-modality treatment for resectable metastatic colorectal carcinoma to the liver: Surgical resection of hepatic metastases in combination with continuous infusion of chemotherapy - An intergroup study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PROSPECTIVE RANDOMIZED TRIAL; ARTERIAL INFUSION; PHASE-II; CANCER; FLOXURIDINE; LEUCOVORIN; FLUOROURACIL; SURGERY; TABLES; LIFE AB Purpose: Despite technical improvements that have minimized the morbidity and mortality of hepatic surgery, the long-term outcome of resection of hepatic metastases of colorectal cancer remains poor, with the majority of patients experiencing treatment failure in the liver. Because arterial chemotherapy regimens targeted to the liver have demonstrated high response rates, an intergroup trial of adjuvant therapy for patients undergoing hepatic resection of liver metastases from colorectal cancer was initiated. Patients and Methods: Patients with one to three potentially resectable metastases were randomized preoperatively to receive no further therapy (control arm, 56 patients) or postoperative hepatic arterial floxuridine combined with intravenous continuous-infusion fluorouracil (chemotherapy arm, 53 patients). After exclusion of patients identified as ineligible for the planned treatment at the time of surgery, there were 45 control patients and 30 on the chemotherapy arm. The study was powered to evaluate improvement in time to recurrence and hepatic disease-free survival, not overall survival. Results: The 4-year recurrence-free rate was 25% for the control arm and 46% for the chemotherapy group (P=.04). The 4-year liver recurrence-free rate was 43% in the control group and 67% in the chemotherapy group (P=.03). The median survival of the 75 assessable patients was 49 months for the control arm and 63.7 months for the chemotherapy arm (P=.60). The median survival of all 109 patients was 47 months for the control arm compared with 34 months for the chemotherapy arm (P=.19) Conclusion: These data demonstrate that adjuvant intra-arterial and intravenous chemotherapy was beneficial in prolonging time to recurrence and preventing hepatic recurrence after hepatic resection of colorectal cancer. C1 Long Isl Jewish Med Ctr, Queens Hosp Ctr, Canc Ctr Queens, Jamaica, NY 11432 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Morristown Mem Hosp, Morristown, NJ USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Penn, Philadelphia, PA 19104 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Royal Perth Hosp, Perth, WA, Australia. RP Kemeny, MM (reprint author), Long Isl Jewish Med Ctr, Queens Hosp Ctr, Canc Ctr Queens, 82-68 164th St,N Bldg,Rm 634, Jamaica, NY 11432 USA. FU NCI NIH HHS [CA17145, CA66636, CA35279, CA23318, CA21115] NR 23 TC 248 Z9 261 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 15 PY 2002 VL 20 IS 6 BP 1499 EP 1505 DI 10.1200/JCO.20.6.1499 PG 7 WC Oncology SC Oncology GA 534QF UT WOS:000174597100013 PM 11896097 ER PT J AU Vauthey, JN Lauwers, GY Esnaola, NF Do, KA Belghiti, J Mirza, N Curley, SA Ellis, LM Regimbeau, JM Rashid, A Cleary, KR Nagorney, DM AF Vauthey, JN Lauwers, GY Esnaola, NF Do, KA Belghiti, J Mirza, N Curley, SA Ellis, LM Regimbeau, JM Rashid, A Cleary, KR Nagorney, DM TI Simplified staging for hepatocellular carcinoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LONG-TERM PROGNOSIS; HEPATIC RESECTION; SURGICAL RESECTION; SYSTEM; RECURRENCE; PROPOSAL; CLASSIFICATION; CIRRHOSIS; PATTERNS; SURVIVAL AB Purpose: The current American Joint Committee on Cancer (AJCC) staging system for hepatocellular carcinoma (HCC) fails to stratify patients adequately with respect to prognosis. Patients and Methods. The ability of the currently proposed tumor (T) categories to effectively stratify the survival of 557 patients who underwent complete resection for HCC at four centers was examined. Independent predictors of survival were combined into a new staging system. Results: Using the current AJCC T classification, patients with T1 and T2 tumors had similar 5-year survivals (P=.6). In addition, the survival of patients with multiple bilobar tumors (T4) matched that of T3 patients (P=.5). Independent predictors of death were major vascular invasion (P<.001), microvascular invasion (P=.001), severe fibrosis/cirrhosis of the host liver (P=.001), multiple tumors (P=.007), and tumor size greater than 5 cm (P=.01). Based on our results, a simplified stratification is proposed: (a) patients with a single tumor and no microvascular invasion, (b) patients with a single tumor and microvascular invasion or multiple tumors, none more than 5 cm, and (c) patients with either multiple tumors, any more than 5 cm, or tumor with major vascular invasion (P<.001). Severe fibrosis/cirrhosis had a negative impact on survival within all categories. The survival of patients with lymph node involvement matched that of patients with major vascular invasion (P=.3). Conclusion: The current AJCC staging system for HCC is unnecessarily complex. We propose a simplified model of stratification that is based on vascular invasion, tumor number, and tumor size and incorporates the effect of fibrosis on survival. C1 Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. Int Cooperat Study Grp Hepatocellular Carcinoma, Houston, TX USA. Univ Texas, MD Anderson Canc Ctr, Dept Biostat & Biomath, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Mayo Clin, Dept Gen Surg, Rochester, MN USA. Hop Beaujon, Dept Surg, Paris, France. RP Vauthey, JN (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Box 444,1515 Holcombe Blvd, Houston, TX 77030 USA. FU NCI NIH HHS [P30 CA016672] NR 41 TC 415 Z9 431 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 15 PY 2002 VL 20 IS 6 BP 1527 EP 1536 DI 10.1200/JCO.20.6.1527 PG 10 WC Oncology SC Oncology GA 534QF UT WOS:000174597100017 PM 11896101 ER PT J AU Vasey, PA Shulman, LN Campos, S Davis, J Gore, M Johnston, S Kirn, DH O'Neill, V Siddiqui, N Seiden, MV Kaye, SB AF Vasey, PA Shulman, LN Campos, S Davis, J Gore, M Johnston, S Kirn, DH O'Neill, V Siddiqui, N Seiden, MV Kaye, SB TI Phase I trial of intraperitoneal injection of the E1B-55-kd-Gene - Deleted adenovirus ONYX-015 (dl1520) given on days 1 through 5 every 3 weeks in patients with recurrent/refractory epithelial ovarian cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NECK-CANCER; P53 STATUS; ATTENUATED ADENOVIRUS; RECURRENT HEAD; GENE; CHEMOTHERAPY; CARCINOMA; E1B; APOPTOSIS; EFFICACY AB Purpose: Resistance to chemotherapy in ovarian cancer is frequently associated with mutations in the p53 gene. The adenovirus dl1520 (ONYX-015) with the EIS 55-kd gene deleted, allowing selective replication in and lysis of p53-deficient tumor cells, has shown preclinical efficacy against p53-deficient nude mouse-human ovarian carcinomatosis xenografts. Patients and Methods: We undertook a phase I trial of intraperitoneal dl1520 in patients with recurrent ovarian cancer. Sixteen women with recurrent/refractory ovarian cancer received 35 cycles (median, two cycles) of dl1520 delivered on days 1 through 5 in four dose cohorts: 1 x 10(9) plaque forming units (pfu), 1 x 10(10) pfu, 3 x 10(10) pfu, and 1 x 10(11) pfu. Results: The most common significant toxicities related to virus administration were flu-like symptoms, emesis, and abdominal pain. One patient receiving 1 x 10(10) pfu developed common toxicity criteria grade 3 abdominal pain and diarrhea, which was dose-limiting. The maximum-tolerated dose was not reached at 10(11) pfu, and at this dose level patients did not experience significant toxicity. There was no clear-cut evidence of clinical or radiologic response in any patient. Blood samples were taken for adenovirus DNA and neutralizing antibodies. Polymerase chain reaction data indicating presence of virus up to 10 days after the final (day 5) infusion of dl1520 are suggestive of continuing viral replication. Conclusion: This article therefore describes the first clinical experience with the intraperitoneal delivery of any replication-competent/-selective virus in cancer patients. C1 Beatson Oncol Ctr, Canc Res Campaign, Dept Med Oncol, Beatson Labs, Glasgow G61 1BD, Lanark, Scotland. Stobhill Gen Hosp, Glasgow G21 3UW, Lanark, Scotland. Royal Marsden Hosp, Surrey, England. Univ London Imperial Coll Sci Technol & Med, London, England. Imperial Canc Res Fund, London WC2A 3PX, England. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Vasey, PA (reprint author), Beatson Oncol Ctr, Canc Res Campaign, Dept Med Oncol, Beatson Labs, Garscube Estate,Switchback Rd, Glasgow G61 1BD, Lanark, Scotland. NR 35 TC 166 Z9 179 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 15 PY 2002 VL 20 IS 6 BP 1562 EP 1569 DI 10.1200/JCO.20.6.1562 PG 8 WC Oncology SC Oncology GA 534QF UT WOS:000174597100021 PM 11896105 ER PT J AU Emmons, K Li, FP Whitton, J Mertens, AC Hutchinson, R Diller, L Robison, LL AF Emmons, K Li, FP Whitton, J Mertens, AC Hutchinson, R Diller, L Robison, LL CA Childhood Canc Survivor Study TI Predictors of smoking initiation and cessation among childhood cancer survivors: A report from the Childhood Cancer Survivor Study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LONG-TERM SURVIVORS; CIGARETTE-SMOKING; NUTRITION AB Purpose: To examine the determinants of smoking behavior among participants in the Childhood Cancer Survivors Study (CCSS). Methods: This retrospective cohort survey study was conducted among 9,709 childhood cancer survivors. Main outcomes included smoking initiation and cessation. Results: Twenty-eight percent of patients reported ever smoking and 17% reported being current smokers. Standardized to United States population rates, the observed to expected (O/E) ratios and corresponding 95% confidence limits (95% CL) of cigarette smoking were 0.72 (95% CL, 0.69, 0.75) among all survivors and 0.71 (95% CL, 0.68 to 0.74) and 0.81 (95% CL, 0.70, 0.93) among whites and nonwhites, respectively. Significantly lower O/E ratios were present among both males (O/E, 0.73) and females (O/E, 0.70). Factors independently associated with a statistically significant relative risk of smoking initiation included older age at cancer diagnosis, lower household income, less education, not having had pulmonary-related cancer treatment, and not having had brain radiation. Blacks were less likely to start smoking. Survivors who smoked were significantly more likely to quit (O/E, 1.22, 95% CL, 1.15, 1.30). Among ever-smokers, factors associated with the likelihood of being a current smoker included age less than 13 years at smoking initiation, less education, and having had brain radiation; those age less than 3 years at cancer diagnosis were significantly more likely to be ex-smokers. Conclusions: Although survivors in the CCSS cohort seem to be smoking at rates below the general population, interventions are needed to prevent smoking initiation and promote cessation in this distinct population. C1 Dana Farber Canc Inst, Div Community Based Res, Boston, MA 02067 USA. Harvard Sch Publ Hlth, Boston, MA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Minnesota, Minneapolis, MN USA. RP Emmons, K (reprint author), Dana Farber Canc Inst, Div Community Based Res, 44 Binney St, Boston, MA 02067 USA. FU NCI NIH HHS [R01-CA77780, U24-CA55727] NR 22 TC 127 Z9 127 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 15 PY 2002 VL 20 IS 6 BP 1608 EP 1616 DI 10.1200/JCO.20.6.1608 PG 9 WC Oncology SC Oncology GA 534QF UT WOS:000174597100027 PM 11896111 ER PT J AU Lipshultz, SE Giantris, AL Lipsitz, SR Dalton, VK Asselin, BL Barr, RD Clavell, LA Hurwitz, CA Moghrabi, A Samson, Y Schorin, MA Gelber, RD Sallan, SE Colan, SD AF Lipshultz, SE Giantris, AL Lipsitz, SR Dalton, VK Asselin, BL Barr, RD Clavell, LA Hurwitz, CA Moghrabi, A Samson, Y Schorin, MA Gelber, RD Sallan, SE Colan, SD TI Doxorubicin administration by continuous infusion is not cardioprotective: The Dana-Farber 91-01 acute lymphoblastic leukemia protocol SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CONTINUOUS INTRAVENOUS-INFUSION; REDUCED CARDIOTOXICITY; CARDIAC TOXICITY; WEEKLY SCHEDULE; ADRIAMYCIN; THERAPY; CHILDHOOD; CHILDREN; CANCER; RISK AB Purpose: Acute doxorubicin-induced cardiotoxicity can be prevented in adults by continuous infusion of the drug, but mechanisms of cardiotoxicity are different in children. We compared cardiac outcomes in children receiving bolus or continuous infusion of doxorubicin. Patients and Methods: In a randomized study, children with high-risk acute lymphoblastic leukemia received doxorubicin 360 mg/m(2) in 30-mg/m(2) doses every 3 weeks either by bolus (within 1 hour, n = 57) or by continuous infusion (over 48 hours, n = 64). Echocardiograms obtained before doxorubicin and at longest follow-up times were centrally remeasured, and z scores of cardiac measurements were calculated based on a healthy population. Results: The groups were similar in age, sex distribution, doxorubicin dose, and duration of follow-up. Before treatment, measures of left ventricular (LV) structure and function did not reveal dilated cardiomyapathy and were not statistically different between bolus and continuous-infusion groups. The follow-up echocardiograms demonstrated no significant difference between the two groups for any cardiac characteristic, but both groups showed significant abnormalities of LV structure and function compared with normal and with baseline. For example, the mean LV fractional shortening fell by approximately two SD in both groups between the two echocardiograms. LV contractility was depressed in both groups (for bolus patients, median z score = -0.70 SD, P = .006; for continuous-infusion patients, median z score = -0.765, P = .005). Dilated cardiomyopathy and inadequate LV hypertrophy were noted in both groups. Clinical cardiac manifestations and event-free survival did not differ. Conclusion: Continuous doxorubicin infusion over 48 hours for childhood leukemia did not offer a cardioprotective advantage over bolus infusion. Both regimens were associated with progressive subclinical cardiotoxicity. Other cardioprotective strategies should be explored. C1 Strong Childrens Hosp, Div Pediat Cardiol, Rochester, NY USA. Strong Childrens Hosp, Div Pediat Hematol Oncol, Rochester, NY USA. Univ Rochester, Med Ctr, Sch Med & Dent, James P Wilmot Canc Ctr,Dept Pediat, Rochester, NY 14642 USA. Dana Farber Canc Inst, Div Hematol Oncol, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Hematol Oncol, Dept Biostat Sci, Boston, MA 02115 USA. Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. McMaster Univ, Dept Pediat, Hamilton, ON, Canada. Hop St Justine, Montreal, PQ H3T 1C5, Canada. Ctr Hosp Univ, Laval, PQ, Canada. San Jorge Childrens Hosp, San Juan, PR 00912 USA. Maine Med Ctr, Barbara Bush Childrens Hosp, Maine Childrens Canc Program, Portland, ME 04102 USA. Oschsner Inst, Dept Pediat, New Orleans, LA USA. RP Lipshultz, SE (reprint author), Univ Rochester, Med Ctr, Div Pediat Cardiol, 601 Elmwood Ave,Box 631, Rochester, NY 14642 USA. FU NCI NIH HHS [CA 55576, CA 68484, CA 06516] NR 22 TC 107 Z9 112 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 15 PY 2002 VL 20 IS 6 BP 1677 EP 1682 DI 10.1200/JCO.20.6.1677 PG 6 WC Oncology SC Oncology GA 534QF UT WOS:000174597100035 PM 11896119 ER PT J AU Heinrich, MC Blanke, CD Druker, BJ Corless, CL AF Heinrich, MC Blanke, CD Druker, BJ Corless, CL TI Inhibition of KIT tyrosine kinase activity: A novel molecular approach to the treatment of KIT-positive malignancies SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID GASTROINTESTINAL STROMAL TUMORS; STEM-CELL FACTOR; ACUTE MYELOID-LEUKEMIA; PROTOONCOGENE C-KIT; GROWTH-FACTOR; IN-VIVO; LUNG-CANCER; SIGNAL-TRANSDUCTION; ACTIVATING MUTATION; PHOSPHATASE SHP-1 AB Purpose: Activation of the KIT tyrosine kinase by somatic mutation has been documented in a number of human malignancies, including gastrointestinal stromal tumor (GIST), seminoma, acute myelogenous leukemia (AML), and mastocytosis. In addition, paracrine or autocrine activation of this kinase has been postulated in numerous other malignancies, including small-cell lung cancer and ovarian cancer. In this review, we discuss the rationale for and development of KIT tyrosine kinase inhibitors for the treatment of human malignancies. Materials and Methods: Studies were identified through a MEDLINE search, review of bibliographies of relevant articles, and review of abstracts from national meetings. Results: Four tyrosine kinase inhibitors that have activity against KIT are currently being used in clinical trials, and one, ST1571, has recently been approved by the United States Food and Drug Administration for treating patients with chronic myelogenous leukemia. The role of KIT inhibitors in treating KIT-positive malignancies is reviewed. Conclusion: Targeted therapy to inhibit the kinase activity of KIT is a rational approach to the treatment of KIT-positive malignancies. Two key factors are the potency of a given inhibitor and the relative contribution of KIT activation to the growth of the tumor. Given our current understanding of KIT activity in human malignancy, the best candidate diseases for treatment with KIT inhibitors are GIST, mastocytosis, seminoma and possibly some cases of AML. Additionally, KIT inhibitors may play an adjunctive role in diseases such as small-cell lung cancer, in which KIT activation is secondary to ligand binding rather than an acquired mutation. C1 Oregon Hlth Sci Univ, Dept Med, Div Hematol Oncol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Pathol & Lab Med, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Heinrich, MC (reprint author), R&D-19 3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. NR 133 TC 444 Z9 475 U1 0 U2 20 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 15 PY 2002 VL 20 IS 6 BP 1692 EP 1703 DI 10.1200/JCO.20.6.1692 PG 12 WC Oncology SC Oncology GA 534QF UT WOS:000174597100037 PM 11896121 ER PT J AU Appleman, LJ van Puijenbroek, AAFL Shu, KM Nadler, LM Boussiotis, VA AF Appleman, LJ van Puijenbroek, AAFL Shu, KM Nadler, LM Boussiotis, VA TI CD28 costimulation mediates down-regulation of p27(kip1) and cell cycle progression by activation of the PI3K/PKB signaling pathway in primary human T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-KINASE-B; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; GLYCOGEN-SYNTHASE KINASE-3; TRANSCRIPTION FACTOR; SURVIVAL SIGNALS; INHIBITOR; PHOSPHORYLATION; LYMPHOCYTES; RECEPTOR; COMPLEX AB CD28 provides a costimulatory signal that cooperates with the TCR/CD3 complex to induce T cell activation, cytokine production, and clonal expansion. We have recently shown that CD28 directly regulates progression of T lymphocytes through the cell cycle. Although a number of signaling pathways have been linked to the TCR/CD3 and to CD28, it is not known how these two receptors cooperate to induce cell cycle progression. Here, using cell-permeable pharmacologic inhibitors of phosphatidylinositol 3-hydroxykinase (P13K) and mitogen-activated protein kinase kinase (MEK1/2), we show that cell cycle progression of primary T lymphocytes requires simultaneous activation of P13K- and MEK 1/2-dependent pathways. Decreased abundance of cyclin-dependent kinase inhibitor p27(kip1), which requires simultaneous TCR/CD3 and CD28 ligation, was dependent upon both MEK and P13K activity. Ligation of TCR/CD3, but not CD28 alone, resulted in activation of MEK targets extracellular signal-related kinase 1/2, whereas ligation of CD28 alone was sufficient for activation of P13K target protein kinase B (PKB; c-Akt). CD28 ligation alone was also sufficient to mediate inactivating phosphorylation of PKB target glycogen synthase kinase-3 (GSK-3). Moreover, direct inactivation of GSK-3 by LiCl in the presence of anti-CD3, but not in the presence of anti-CD28, resulted in down-regulation of p27(kip1), hyperphosphorylation of retinoblastoma tumor suppressor gene product, and cellular proliferation. Thus, inactivation of the P13K-PKB target GSK-3 could substitute for CD28 but not for CD3 signals. These results show that the P13K-PKB pathway links CD28 to cell cycle progression and suggest that p27(kip1) integrates mitogenic MEK- and P13K-dependent signals from TCR and CD28 in primary T lymphocytes. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Div Med Oncol, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Boussiotis, VA (reprint author), Dana Farber Canc Inst, Mayer 547,44 Binney St, Boston, MA 02115 USA. EM vassiliki_boussiotis@dfci.harvard.edu OI Appleman, Leonard/0000-0003-4951-7388 FU NIAID NIH HHS [AI 43552, AI 46548, AI41584] NR 54 TC 126 Z9 131 U1 1 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 MAR 15 PY 2002 VL 168 IS 6 BP 2729 EP 2736 PG 8 WC Immunology SC Immunology GA 529BP UT WOS:000174280400021 PM 11884439 ER PT J AU Drouin, EE Schrader, CE Stavnezer, J Hansen, U AF Drouin, EE Schrader, CE Stavnezer, J Hansen, U TI The ubiquitously expressed DNA-binding protein late SV40 factor binds Ig switch regions and represses class switching to IgA SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TRANSCRIPTION FACTOR CP2; IMMUNODEFICIENCY-VIRUS TYPE-1; HEAVY-CHAIN GENES; HISTONE DEACETYLASE COMPLEX; LONG TERMINAL REPEAT; HUMAN-FACTORS YY1; B-CELL LINE; FACTOR LSF; IN-VITRO; ACTIVATES TRANSCRIPTION AB Ig heavy chain class switch recombination (CSR) determines the expression of Ig isotypes. The molecular mechanism of CSR and the factors regulating this process have remained elusive. Recombination occurs primarily within switch (S) regions, located upstream of each heavy chain gene (except Cdelta). These repetitive sequences contain consensus DNA-binding sites for the DNA-binding protein late SV40 factor (LSF) (CP2/leader-binding protein-1c). In this study, we demonstrate by EMSA that purified rLSF, as well as LSF within B cell extracts, directly binds both Smu and Sa sequences. To determine whether LSF is involved in regulating CSR, two different LSF dominant negative variants were stably expressed in the mouse B cell line 1.29 mu, which can be induced to switch from IgM to IgA. Overexpression of these dominant negative LSF proteins results in decreased levels of endogenous LSF DNA-binding activity and an increase in cells undergoing CSR. Thus, LSF represses class switching to IgA. In agreement, LSF DNA-binding activity was found to decrease in whole cell extracts from splenic B cells induced to undergo class switching. To elucidate the mechanism of CSR regulation by LSF, the interactions of LSF with proteins involved in chromatin modification were tested in vitro. LSF interacts with both histone deacetylases and the corepressor Sin3A. We propose that LSF represses CSR by histone deacetylation of chromatin within S regions, thereby limiting accessibility to the switch recombination machinery. C1 Boston Univ, Dept Biol, Boston, MA 02215 USA. Dana Farber Canc Inst, Div Mol Genet, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Massachusetts, Med Ctr, Program Immunol & Virol, Dept Mol Genet & Microbiol, Worcester, MA 01655 USA. RP Hansen, U (reprint author), Boston Univ, Dept Biol, 5 Cummington St, Boston, MA 02215 USA. OI Schrader, Carol/0000-0001-8920-6803 FU NCI NIH HHS [R01 CA081157, R01 CA081157-05, CA81157, T32-CA09361]; NIAID NIH HHS [AI23283, AI42108] NR 78 TC 21 Z9 22 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2002 VL 168 IS 6 BP 2847 EP 2856 PG 10 WC Immunology SC Immunology GA 529BP UT WOS:000174280400036 PM 11884454 ER PT J AU Kumar, A Zou, LL Yuan, XQ Long, Y Yang, K AF Kumar, A Zou, LL Yuan, XQ Long, Y Yang, K TI N-methyl-D-aspartate receptors: Transient loss of NR1/NR2A/NR2B subunits after traumatic brain injury in a rodent model SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE N-methyl-D-aspartate receptor; hippocampus; brain injury; memory; rodent model ID CORTICAL IMPACT INJURY; NMDA RECEPTORS; RAT-BRAIN; MEDIATED REGULATION; CALPAIN ACTIVATION; MESSENGER-RNA; EXPRESSION; MEMORY; CELLS; NR1 AB Hippocampal N-methyl-D-aspartate (NMDA) receptor subunits, by virtue of their involvement in excitotoxic injury as well as memory association, may play an important role in the pathophysiologic mechanisms of traumatic brain injury (TBI). In this study, temporal changes in NMDA receptor subunit (NR1, NR2A, and NR2B) levels in rat hippocampus after TBI were investigated by Western blot and mRNA expression levels by RT-PCR methods. Sprague-Dawley rats (250-350 g) were employed, and a controlled cortical impact injury device was used to produce the TBI in rodents. At different postinjury time points (2, 6, 12, 24, and 48 hr), the rat hippocampi were dissected out for protein and RNA preparation. Western blot analysis revealed significant decreases of NR1, NR2A, and NR2B subunit proteins at 6 and 12 hr postinjury in rat hippocampus. Complete recovery of NR1, NR2A, and NR2B subunit protein to the levels of sham controls was observed at 24 hr postinjury. However, RT-PCR analysis did not show any significant change in the mRNA levels at 2, 6, and 12 hr postinjury in comparison with sham controls, suggesting nontranscriptional change in the levels of these subunits. Thus, TBI can produce transient degradation of NMDA receptor subunits in the hippocampus, which might contribute to temporary memory impairment after 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. Dept Vet Affairs Med Ctr, Neurol Care Line, Houston, TX USA. RP Yang, K (reprint author), Baylor Coll Med, Dept Neurosurg, 1 Baylor Plaza, Houston, TX 77030 USA. FU NINDS NIH HHS [R01-NS35502-04] NR 25 TC 41 Z9 69 U1 0 U2 0 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 15 PY 2002 VL 67 IS 6 BP 781 EP 786 DI 10.1002/jnr.10181 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 526ZC UT WOS:000174158700010 PM 11891792 ER PT J AU Tripathi, R Nassif, N Nelson, JS Park, BH de Boer, JF AF Tripathi, R Nassif, N Nelson, JS Park, BH de Boer, JF TI Spectral shaping for non-Gaussian source spectra in optical coherence tomography SO OPTICS LETTERS LA English DT Article AB We present a digital spectral shaping technique to reduce the sidelobes (ringing) of the axial point-spread function in optical coherence tomography for non-Gaussian-shaped source spectra. The spectra of two superluminescent diodes were combined to generate a spectrum with significant modulation. Images of onion cells demonstrate the improved image quality in a turbid biological sample. A quantitative analysis of the accompanying penalty in signal-to-noise ratio is given. (C) 2002 Optical Society of America. C1 MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. Univ Calif Irvine, Beckman Laser Inst & Med Clin, Irvine, CA 92612 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Tripathi, R (reprint author), MIT, Dept Elect Engn & Comp Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 NR 14 TC 71 Z9 73 U1 1 U2 11 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD MAR 15 PY 2002 VL 27 IS 6 BP 406 EP 408 DI 10.1364/OL.27.000406 PG 3 WC Optics SC Optics GA 531WT UT WOS:000174440800010 PM 18007816 ER PT J AU Tearney, GJ Shishkov, M Bouma, BE AF Tearney, GJ Shishkov, M Bouma, BE TI Spectrally encoded miniature endoscopy SO OPTICS LETTERS LA English DT Article ID DIAGNOSIS; EMBRYOSCOPY AB A method for performing miniature endoscopy with a high number of resolvable points is presented. This approach, spectrally encoded endoscopy (SEE), uses a broad-bandwidth light source and a diffraction grating to simultaneously detected the reflectivity at multiple points along a transverse line within the sample. As opposed to images from miniature optical fiber bundle endoscopes, the number of resolvable points in SEE images is dependent on the spectral width and the groove density of the diffraction grating. We acquired images of a human finger in vivo, using a 550-mum-diameter SEE system to demonstrate the feasibility of this technique. (C) 2002 Optical Society of America. C1 Harvard Univ, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Tearney, GJ (reprint author), Harvard Univ, Sch Med, Wellman Labs Photomed, 50 Blossom St,BAR 703, Boston, MA 02114 USA. NR 14 TC 56 Z9 59 U1 0 U2 3 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD MAR 15 PY 2002 VL 27 IS 6 BP 412 EP 414 DI 10.1364/OL.27.000412 PG 3 WC Optics SC Optics GA 531WT UT WOS:000174440800012 PM 18007818 ER PT J AU Littner, M Hirshkowitz, M Davila, D Anderson, WM Kushida, CA Woodson, T Johnson, SF Wise, MS AF Littner, M Hirshkowitz, M Davila, D Anderson, WM Kushida, CA Woodson, T Johnson, SF Wise, MS TI Practice parameters for the use of auto-titrating continuous positive airway pressure devices for titrating pressures and treating adult patients with obstructive sleep apnea syndrome SO SLEEP LA English DT Article DE obstructive sleep apnea; continuous positive airway pressure; CPAP; sleep-disordered breathing; auto-titrating; APAP ID SNORING DETECTION; CPAP TITRATION AB Continuous positive airway pressure (CPAP) is used to treat patients with the obstructive sleep apnea syndrome (OSAS). The current standard is for an attendant technician to titrate CPAP during full polysomnography to obtain a fixed single pressure. The patient uses CPAP nightly at this fixed single pressure. Recently, devices using new technology that automatically titrate positive airway pressure (APAP) have become available. Such devices continually adjust pressure, as needed, to maintain airway patency (APAP titration). These adjustments can be made with or without attendant technician intervention. Data obtained during APAP titration can be used to provide a fixed single pressure for subsequent treatment. Alternatively, APAP devices can be used in self-adjusting mode for treatment (APAP treatment). A task force of the Standards of Practice Committee of the American Academy of Sleep Medicine reviewed the available literature. Based on this review, the Standards of Practice Committee developed these practice parameters as a guide to the appropriate use of APAP Recommendations are as follows: 1) A diagnosis of OSAS must be established by an acceptable method. 2) APAP titration and APAP treatment are not currently recommended for patients with congestive heart failure, significant lung disease (e.g., chronic obstructive pulmonary disease), daytime hypoxemia and respiratory failure from any cause, or prominent nocturnal desaturation other than from OSA (e.g., obesity hypoventilation syndrome). In addition, patients who do not snore (either due to palate surgery or naturally) should not be titrated with an APAP device that relies on vibration or sound in the device's algorithm. 3) APAP devices are not currently recommended for split-night studies since none of the reviewed research studies examined this issue. 4) Certain APAP devices may be used during attended titration to identify by polysomnography a single pressure for use with standard CPAP for treatment of OSA. 5) Once an initial successful attended CPAP or APAP titration has been determined by polysomnography, certain APAP devices may be used in the self-adjusting mode for unattended treatment of patients with OSA. 6) Use of unattended APAP to either initially determine pressures for fixed CPAP or for self-adjusting APAP treatment in CPAP naive patients is not currently established. 7) Patients being treated with fixed CPAP on the basis of APAP titration or being treated with APAP must be followed to determine treatment effectiveness and safety, and 8) a re-evaluation and, if necessary, a standard attended CPAP titration should be performed if symptoms do not resolve or the CPAP or APAP treatment otherwise appears to lack efficacy. C1 VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Med, Sepulveda, CA USA. Baylor Coll Med, Houston VAMC Sleep Disorders & Res, Houston, TX 77030 USA. Baptist Med Ctr, Little Rock, AR USA. Univ S Florida, Coll Med, Tampa, FL 33620 USA. Stanford Univ, Ctr Excellence Sleep Disorders, Stanford, CA 94305 USA. Med Coll Wisconsin, Dept Otolaryngol & Commun Sci, Milwaukee, WI 53226 USA. St Patricks Hosp, Sleep Ctr, Missoula, MT USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. RP Littner, M (reprint author), VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. NR 28 TC 98 Z9 102 U1 0 U2 5 PU AMER ACAD SLEEP MEDICINE PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAR 15 PY 2002 VL 25 IS 2 BP 143 EP 147 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 528ZK UT WOS:000174275400003 PM 11902424 ER PT J AU Giovino, MA Down, JD Jackson, JD Sykes, M Monroy, RL White-Scharf, ME AF Giovino, MA Down, JD Jackson, JD Sykes, M Monroy, RL White-Scharf, ME TI Porcine hematopoiesis on primate stroma in long-term cultures: Enhanced growth with neutralizing tumor necrosis factor-alpha and tumor growth factor-beta antibodies SO TRANSPLANTATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; CYTOKINE-INDUCED PROLIFERATION; NONLETHAL PREPARATIVE REGIMEN; MIXED XENOGENEIC CHIMERAS; RENAL-ALLOGRAFT TOLERANCE; STEM-CELL PROLIFERATION; LARGE-ANIMAL-MODEL; P75 TNF RECEPTORS; CLASS II+ CELLS; PROGENITOR CELLS AB Background. Donor hematopoiesis is at a competitive disadvantage when bone marrow transplantation is across species barriers. This could present major limitations to xenogeneic stem cell transplantation as an approach to tolerance induction. An in vitro model of xenogeneic engraftment was established to identify inhibitors of porcine hematopoiesis in a primate environment. Methods. Porcine bone marrow cells (BMC), in the presence or absence of primate CD34(+) positive cells, were cultured for 4-6 weeks on primate stroma with porcine cytokines. Cellularity and growth of colony-forming cells were indicators of hematopoietic growth. Effects of soluble factors were determined by using Transwell inserts to separate porcine cells from stroma. Neutralizing antibodies for human transforming growth factor-beta (TGF-beta) and tumor necrosis factor-alpha (TNF-alpha) were added to cultures. Results. Porcine hematopoiesis can be maintained in long-term cultures on primate stroma with pig cytokines. Adding BMC to the stroma below Transwell-containing porcine cells dramatically inhibited porcine hematopoiesis, showing an inhibitory role for soluble factors. Neutralizing antibodies against TNF-alpha or TGF-beta caused a modest enhancement of porcine hematopoiesis; however, the combination of both led to a substantial increase. Inhibitory effects of these cytokines were confirmed by adding TNF-alpha and TGF-beta to porcine cultures. Conclusions. Porcine cells may be more sensitive to inhibitory effects of TNF-alpha and TGF-beta than primate cells and are at a disadvantage when in a primate environment. Potential implications of this observation are discussed in the context of establishing specific immune tolerance via mixed chimerism to facilitate xenotransplantation. C1 BioTransplant Inc, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Univ Nebraska, Ctr Med, Omaha, NE 68198 USA. RP Giovino, MA (reprint author), BioTransplant Inc, Bldg 75,3rd Ave,Charlesstown Navy Yard, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [R01 HL54038] NR 69 TC 4 Z9 4 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 MAR 15 PY 2002 VL 73 IS 5 BP 723 EP 731 AR UNSP 0041-1337/01/7305-723/0 DI 10.1097/00007890-200203150-00011 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 536TC UT WOS:000174717100011 PM 11907417 ER PT J AU LaMattina, JC Kumagai, N Barth, RN Yamamoto, S Kitamura, H Moran, SG Mezrich, JD Sachs, DH Yamada, K AF LaMattina, JC Kumagai, N Barth, RN Yamamoto, S Kitamura, H Moran, SG Mezrich, JD Sachs, DH Yamada, K TI Vascularized thymic lobe transplantation in miniature swine: I. Vascularized thymic lobe allografts support thymopoiesis SO TRANSPLANTATION LA English DT Article ID TOLERANCE; INDUCTION AB Background. Vascularized thymokidney transplants have previously been shown to induce tolerance across major histocompatibility complex barriers. The ability to perform vascularized thymic lobe transplantation could permit such tolerance to be induced with any cotransplanted solid organ or tissue. For this reason, we have developed a technique for vascularized thymic lobe transplantation in miniature swine. Methods. Thymic vessels (n=2) were anastomosed to the carotid artery and the external jugular vein of naive minor-mismatched recipients treated with a 12-day course of cyclosporine A (10 mg/kg/day). Graft survival and thymopoiesis were assessed by histology, immunohistochemistry, and fluorescence-activated cell sorting. Allele-specific antibodies 74-12-4 and pig allelic antigen (PAA) were used to distinguish donor and recipient cells. Results. Allografts showed intact cortical and medullary structure posttransplantation, without evidence of rejection or ischemia. Recipient thymocytes repopulated the donor cortical thymus by POD30 and increased in the cortex and medulla by POD60. Conclusions. Our study demonstrates the technical feasibility of vascularized thymic lobe transplantation and the support of thymopoiesis by such transplants in a large animal model. This technique may offer a novel strategy to induce transplant tolerance across allogeneic and xenogeneic barriers, and to support long-term thymopoiesis in immunodeficient hosts. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. RP Yamada, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. RI Barth, Rolf/B-2542-2014; LaMattina, John/B-2976-2014 OI LaMattina, John/0000-0001-7016-0382 FU NIAID NIH HHS [P01 AI45897, P01 AI39755] NR 10 TC 33 Z9 34 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 MAR 15 PY 2002 VL 73 IS 5 BP 826 EP 831 DI 10.1097/00007890-200203150-00032 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 536TC UT WOS:000174717100032 PM 11907438 ER PT J AU Goltz, M Ericsson, T Patience, C Huang, CA Noack, S Sachs, DH Ehlers, B AF Goltz, M Ericsson, T Patience, C Huang, CA Noack, S Sachs, DH Ehlers, B TI Sequence analysis of the genome of porcine lymphotropic herpesvirus 1 and gene expression during posttransplant lymphoproliferative disease of pigs SO VIROLOGY LA English DT Article DE porcine lymphotropic herpesvirus; post-transplant lymphoproliferative disease; xenotransplantation. ID EPSTEIN-BARR-VIRUS; SARCOMA-ASSOCIATED HERPESVIRUS; PROTEIN-COUPLED RECEPTOR; ORGAN-TRANSPLANTATION; OVINE HERPESVIRUS-2; B-CELLS; IDENTIFICATION; APOPTOSIS; ONCOGENE; ENCODES AB The porcine lymphotropic herpesvirus 1 (PLHV-1), the first gammaherpesvirus of pigs, has been detected at a high prevalence in healthy pig populations. A porcine gammaherpesvirus has also been detected at high copy numbers in animals suffering from posttransplant lymphoproliferative disease (PTLD). While human PTLD is a EBV-associated complication following clinical transplantation, porcine PTLD is a disease recently described in pigs undergoing experimental allogeneic hematopoietic stem cell transplantation. Here we demonstrate that PLHV-1 and the virus present in porcine PTLD are indistinguishable, and present the characterization of 73 kbp of the genome of PLHV-1. We identified homologs of cellular genes, including a putative G protein-coupled receptor (GCR) as well as a viral homolog of the bcl-2 oncogene (v-bcl-2) and show significant transcription of these genes as well as of several other PLHV-1 genes in lymph nodes of a PTLD-affected pig, These data indicate that PLHV-1 is active during PTLD and may be involved in the etiology of this lymphoproliferative disease. (C) 2002 Elsevier Science (USA). C1 Robert Koch Inst, D-13353 Berlin, Germany. Immerge Biotherapeut Inc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplatat Biol Res Ctr, Boston, MA 02129 USA. RP Goltz, M (reprint author), Robert Koch Inst, Nordufer 20, D-13353 Berlin, Germany. NR 44 TC 39 Z9 40 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAR 15 PY 2002 VL 294 IS 2 BP 383 EP 393 DI 10.1006/viro.2002.1390 PG 11 WC Virology SC Virology GA 542DA UT WOS:000175027200016 PM 12009880 ER PT J AU Lewis, JH Schonlau, M Munoz, JA Asch, SM Rosen, MR Yang, H Escarce, JJ AF Lewis, JH Schonlau, M Munoz, JA Asch, SM Rosen, MR Yang, H Escarce, JJ TI Compliance among pharmacies in California with a prescription-drug discount program for Medicare beneficiaries SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID IMPACT AB Background: Several states have developed prescription-drug discount programs for Medicare beneficiaries. In California, Senate Bill 393, enacted in 1999, requires pharmacies participating in the state Medicaid program (Medi-Cal) to charge customers who present a Medicare card amounts based on Medi-Cal rates. Because Medicare beneficiaries may not be accustomed to presenting their Medicare cards at pharmacies, we assessed the compliance of pharmacies with Senate Bill 393. Methods: Fifteen Medicare beneficiaries who received special training and acted as ``standardized patients'' visited a random sample of pharmacies in the San Francisco Bay area and Los Angeles County in April and May 2001. According to a script, they asked for the prices of three commonly prescribed drugs: rofecoxib, sertraline, and atorvastatin. The script enabled us to determine whether and when, during their interactions with pharmacists or salespeople, the discounts specified in Senate Bill 393 were offered. Pharmacies at which the appropriate discounts were offered were considered compliant. Results: The patients completed visits to 494 pharmacies. Seventy-five percent of the pharmacies complied with the prescription-drug discount program; at only 45 percent, however, was the discount offered before it was specifically requested. The discount was offered at 91 percent of pharmacies that were part of a chain, as compared with 58 percent of independent pharmacies (P<0.001). Compliance was higher in the San Francisco Bay area than in Los Angeles County (84 percent vs. 72 percent, P=0.004) and was higher in high-income than low-income neighborhoods (81 percent vs. 69 percent, P=0.002). A Medicare beneficiary taking all three drugs would have saved an average of $55.70 per month as compared with retail prices (a savings of 20 percent). Conclusions: Discounts required under California's prescription-drug discount program for Medicare beneficiaries offer substantial savings. Many patients, however, especially those who use independent pharmacies or who live in low-income neighborhoods, may not receive the discounts. (N Engl J Med 2002;346:830-5.) Copyright (C) 2002 Massachusetts Medical Society. C1 RAND Corp, Hlth, Santa Monica, CA 90407 USA. Greater Los Angeles Vet Affairs Hlth Care Syst, Los Angeles, CA USA. RP Lewis, JH (reprint author), RAND Corp, Hlth, 1700 Main St, Santa Monica, CA 90407 USA. NR 21 TC 4 Z9 4 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 MAR 14 PY 2002 VL 346 IS 11 BP 830 EP 835 DI 10.1056/NEJMsa122601 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 529YM UT WOS:000174328900007 PM 11893795 ER PT J AU Quinn, DA Mark, EJ McLoud, TC Arena, JF AF Quinn, DA Mark, EJ McLoud, TC Arena, JF TI A 56-year-old woman with a persistent left-sided pleural effusion - Rheumatoid pleuritis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID COMPUTED-TOMOGRAPHY; FLUID PH; ARTHRITIS; METHOTREXATE; DISEASES; THERAPY; INVOLVEMENT; EXPERIENCE; FEATURES; TRIAL C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Quinn, DA (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. NR 40 TC 3 Z9 3 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 MAR 14 PY 2002 VL 346 IS 11 BP 843 EP 850 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 529YM UT WOS:000174328900009 ER PT J AU Rosas, HD Liu, AK Hersch, S Glessner, M Ferrante, RJ Salat, DH van der Kouwe, A Jenkins, BG Dale, AM Fischl, B AF Rosas, HD Liu, AK Hersch, S Glessner, M Ferrante, RJ Salat, DH van der Kouwe, A Jenkins, BG Dale, AM Fischl, B TI Regional and progressive thinning of the cortical ribbon in Huntington's disease SO NEUROLOGY LA English DT Article ID SURFACE-BASED ANALYSIS; BASAL GANGLIA; COORDINATE SYSTEM; CEREBRAL-CORTEX; BRAIN ATROPHY; FRONTAL-LOBE; PROJECTIONS; ORGANIZATION; SPECTROSCOPY; PERCEPTION AB Background: Huntington's disease (HD) is a fatal and progressive neurodegenerative disease that is accompanied by involuntary movements, cognitive dysfunction, and psychiatric symptoms. Although progressive striatal degeneration is known to occur, little is known about how the disease affects the cortex, including which cortical regions are affected, how degeneration proceeds, and the relationship of the cortical degeneration to clinical symptoms. The cortex has been difficult to study in neurodegenerative diseases primarily because of its complex folding patterns and regional variability; however, an understanding of how the cortex is affected by the disease may provide important new insights into it. Methods: Novel automated surface reconstruction and high-resolution MR images of 11 patients with HD and 13 age-matched subjects were used to obtain cortical thickness measurements. The same analyses were performed on two postmortem brains to validate these methods. Results: Regionally specific heterogeneous thinning of the cortical ribbon was found in subjects with HD. Thinning occurred early, differed among patients in different clinical stages of disease, and appeared to proceed from posterior to anterior cortical regions with disease progression. The sensorimotor region was statistically most affected. Measurements performed on MR images of autopsy brains analyzed similarly were within 0.25 mm of those obtained using traditional neuropathologic methods and were statistically indistinguishable. Conclusions: The authors propose that the cortex degenerates early in disease and that regionally selective cortical degeneration may explain the heterogeneity of clinical expression in HD. These measures might provide a sensitive prospective surrogate marker for clinical trials of neuroprotective medications. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Bedford VA Med Ctr, Ctr Geriatr Res Educ & Clin, Bedford, MA USA. Massachusetts Gen Hosp, Dept Neurol, MGH NMR Ctr, Charlestown, MA 02129 USA. RP Rosas, HD (reprint author), Massachusetts Gen Hosp, Dept Neurol, MGH NMR Ctr, MGH E,Bldg 114,Suite 2000,114 16th St, Charlestown, MA 02129 USA. RI Dale, Anders/A-5180-2010 FU NCCIH NIH HHS [AT00613]; NIA NIH HHS [AG05886]; NINDS NIH HHS [NS02060, NS35255, NS37102, NS39581] NR 30 TC 570 Z9 576 U1 1 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 12 PY 2002 VL 58 IS 5 BP 695 EP 701 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 529LQ UT WOS:000174301300005 PM 11889230 ER PT J AU Thadhani, R Camargo, CA Stampfer, MJ Curhan, GC Willett, WC Rimm, EB AF Thadhani, R Camargo, CA Stampfer, MJ Curhan, GC Willett, WC Rimm, EB TI Prospective study of moderate alcohol consumption and risk of hypertension in young women SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID BLOOD-PRESSURE; DRINKING PATTERN; CARDIOVASCULAR-DISEASE; QUESTIONNAIRE; STROKE; WEIGHT; DEATH AB Background: Heavy alcohol consumption is associated with an increased risk of hypertension, However, the effect of moderate alcohol consumption; the specific effects of wine, beer, and liquor; and the pattern of drinking in relation to risk of hypertension among young women are unclear. Methods: We prospectively examined the association between alcohol consumption and subsequent risk of hypertension among 70891 women 25 to 42 years of age. Results: During the 8 years of follow-up, 4188 cases (5.9%) of incident hypertension were reported. After adjustment for multiple covariates, the association between alcohol consumption and risk of hypertension followed a J-shaped curve. Compared with nondrinkers, the risk of developing hypertension according to average number of drinks consumed per day was as follows: 0.25 or less, 0.96 (95% confidence interval 101, 0.89-1.03); 0.26 to 0,50,0.86 (95% CI, 0.75-0.98); 0.51 to 1.00, 0.92 (95% CI, 0.82-1.04); 1.01 to 1.50, 1.00 (95% CI, 0.80-1.24); 1.51 to 2.00, 1.20 (95% Cl, 0.92-1.58); and more than 2.0 drinks, 1.31 (95% CI, 1.02-1.68). Exclusion of past drinkers yielded similar results. Among women in the highest category of alcohol consumption, there was a suggestion that the increased risk of hypertension was present regardless of the specific beverage consumed (beer, wine, or liquor). Episodic drinking, defined as consumption of more than 10.5 drinks over 3 or fewer days per week, was not associated with increased risk of hypertension (relative risk, 0.80; 95% CI, 0.51-1.23). Conclusions: The association between alcohol consumption and risk of chronic hypertension in young women follows a J-shaped curve, with light drinkers demonstrating a modest decrease in risk and more regular heavy drinkers demonstrating an increase in risk. C1 Channing Labs, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Harvard Univ, Med Sch, Boston, MA USA. RP Thadhani, R (reprint author), Channing Labs, Brigham & Womens Hosp, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-03533, HL-03804]; NIAAA NIH HHS [AA-11181] NR 34 TC 75 Z9 86 U1 0 U2 5 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 11 PY 2002 VL 162 IS 5 BP 569 EP 574 DI 10.1001/archinte.162.5.569 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 528XN UT WOS:000174270400009 PM 11871925 ER PT J AU Madras, BK Miller, GM Fischman, AJ AF Madras, BK Miller, GM Fischman, AJ TI The dopamine transporter: relevance to attention deficit hyperactivity disorder (ADHD) SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article; Proceedings Paper CT Symposium on Dopamine Hypothesis of ADHD CY FEB 14-25, 2000 CL UNIV CASTILLA LA MANCHA, CASTILLA LA MANCHA, SPAIN HO UNIV CASTILLA LA MANCHA DE attention deficit hyperactivity disorder; dopamine; monoamine transporters; polymorphisms; SPECT imaging; altropane ID PET IMAGING PROBE; I-123 BETA-CIT; POSITRON-EMISSION-TOMOGRAPHY; PARKINSONS-DISEASE; DEFICIT/HYPERACTIVITY DISORDER; GENE POLYMORPHISM; TOURETTE-SYNDROME; IN-VIVO; PRIMATE BRAIN; RECEPTOR GENE AB The dopamine transporter is elevated in adults with attention deficit hyperactivity disorder (ADHD) compared with healthy controls [Lancet 354 (1999) 2132]. The findings have been confirmed by others in a different population using a different probe for the dopamine transporter. Notwithstanding the need to confirm these findings in a multi-center trial, several hypotheses are presented to account for these observations. A premise that elevated transporter levels result from medication is not supported by current data. Other possibilities, including hypertrophy of dopamine neuronal terminals in the striatum, dysfunctional regulation of dopamine or dopamine receptors, or anomalies in the dopamine transporter gene are presented as hypotheses. The feasibility of exploring these mechanisms in animal models or in human subjects is explored. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Dept Psychiat, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Madras, BK (reprint author), Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Dept Psychiat, 1 Pine Hall Dr, Southborough, MA 01772 USA. FU NCRR NIH HHS [RR00168]; NIDA NIH HHS [DA11558, DA00304]; NINDS NIH HHS [NS30556] NR 84 TC 62 Z9 62 U1 6 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD MAR 10 PY 2002 VL 130 IS 1-2 SI SI BP 57 EP 63 AR PII S0166-4328(01)00439-9 DI 10.1016/S0166-4328(01)00439-9 PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 536VF UT WOS:000174722000006 PM 11864718 ER PT J AU Yoshida, T Tang, SS Hsiao, LL Jensen, RV Ingelfinger, JR Gullans, SR AF Yoshida, T Tang, SS Hsiao, LL Jensen, RV Ingelfinger, JR Gullans, SR TI Global analysis of gene expression in renal ischemia-reperfusion in the mouse SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE microarray; ischemia reperfusion; renal failure; extracellular matrix; tissue repair ID SURFACE-MEMBRANE POLARITY; EPIDERMAL GROWTH-FACTOR; EPITHELIAL POLARITY; TUBULAR CELLS; INJURY; FAILURE; KIDNEY; CALCIUM; ADHESION; RECEPTOR AB Ischemia-induced acute renal failure (ARF) is a relatively common disorder with major morbidity and mortality. To study global gene expression during ARF, 6-week-old C57BL/6 male mice underwent 30 min of bilateral renal ischemia followed by reperfusion [I/R] or sham operation. Oligonucleotide microarrays [Affymetrix] with approximately 10,000 genes, 6,643 of which were present in mouse kidney, were used to analyze mRNA expression for up to 4 days following I/R. Fifty-two genes at day 1 and 40 at day 4 were up-regulated more than 4-fold [400%]. Seventy genes at day 1 and 30 genes at day 4 were down-regulated to under 0.25-fold from baseline [25%]. Real-time quantitative RT-PCR confirmed changes in expression for 8 genes of interest. Most of the induced transcripts are involved in cell structure, extracellular matrix, intracellular calcium binding, and cell division/differentiation. Our data identified several novel genes that may be important in renal repair after ischemia. (C) 2002 Elsevier Science (USA). C1 Brigham & Womens Hosp, Dept Med, Div Renal, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA USA. Wesleyan Univ, Dept Phys, Middletown, CT 06459 USA. RP Gullans, SR (reprint author), Brigham & Womens Hosp, Dept Med, Div Renal, 65 Landsdowne St, Cambridge, MA 02139 USA. FU NHLBI NIH HHS [HL-48455]; NIDDK NIH HHS [DK58950, DK50835, DK58849, DK36031] NR 44 TC 40 Z9 42 U1 2 U2 3 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 MAR 8 PY 2002 VL 291 IS 4 BP 787 EP 794 DI 10.1006/bbrc.2002.6535 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 532EJ UT WOS:000174458400011 PM 11866434 ER PT J AU Xie, Y Chen, CM Stevenson, MA Hume, DA Auron, PE Calderwood, SK AF Xie, Y Chen, CM Stevenson, MA Hume, DA Auron, PE Calderwood, SK TI NF-IL6 and HSF1 have mutually antagonistic effects on transcription in monocytic cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE HSF-1; NF-IL6; transcriptional repression ID HEAT-SHOCK FACTOR; COLONY-STIMULATING FACTOR; NECROSIS-FACTOR-ALPHA; PROINTERLEUKIN 1-BETA GENE; FACTOR-I RECEPTOR; C-FMS; ANTIINFLAMMATORY DRUGS; MOLECULAR-CLONING; SODIUM-SALICYLATE; BINDING-ACTIVITY AB We have examined the functional antagonism between the regulator of the heat shock response, HSF1, and NF-IL6, which plays a major role in control of the acute phase response (A-PR). Agents that activate HSF1 such as heat shock and sodium salicylate inhibit NF-IL6 induced transcription while NF-IL6 activators such as lipopolysaccharide (LPS) and interleukin 6 (IL-6) repressed the stress responsive HSP70B promoter. In transfection studies, the inhibitory effects of HSF1 and NF-IL6 on the c-fms promoter were shown to be highly dose-dependent. Furthermore, heat shock is inhibitory to differentiation-linked expression of macrophage colony stimulating factor (M-CSF) receptor, product of the c-fms gene, which is transcriptionally activated by NF-IL6 but repressed by HSF1. Our studies suggest a strong mutual antagonism between the heat shock response and APR, which may influence the sensitivity and duration of inflammatory responses. (C) 2002 Elsevier Science (USA). C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Univ Queensland, Ctr Cellular & Mol Biol, Dept Microbiol & Biochem, Brisbane, Qld 4072, Australia. Harvard Univ, Sch Med, Beth Israel & Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. RP Calderwood, SK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. RI Hume, David/C-7695-2013 FU NCI NIH HHS [CA31303, CA47407, CA50642, CA68544] NR 54 TC 28 Z9 31 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 MAR 8 PY 2002 VL 291 IS 4 BP 1071 EP 1080 DI 10.1006/bbrc.2002.6562 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 532EJ UT WOS:000174458400051 PM 11866474 ER PT J AU Barker, HJ Alpert, LC Compton, CC Maslen, A Kirby, GM AF Barker, HJ Alpert, LC Compton, CC Maslen, A Kirby, GM TI Loss of glutathione S-transferase (GST) mu phenotype in colorectal adenocarcinomas from patients with a GSTM1 positive genotype SO CANCER LETTERS LA English DT Article DE glutathione S-transferase; genotype; phenotype; colon ID RAT HEPATOCYTES; HUMAN COLON; HEPATIC GLUTATHIONE; PRIMARY CULTURE; LUNG-CANCER; EXPRESSION; SUSCEPTIBILITY; TISSUE; CARCINOMA; COLITIS AB Glutathione S-transferase (GST) mu phenotype was assessed in colon tissue from patients with ulcerative colitis and colorectal neoplasms that were positive for GSTM1 genotype. GST mu protein (enzyme linked immunosorbent assay) was absent in 2/9 unaffected colon tissue (22.3%), 4/13 tissues with chronic ulcerative colitis (CUC) (30.7%), 4/11 adenomas (36.4%) and 7/14 adenocarcinomas (50.0%; P less than or equal to 0.05). GST-H-3-trans-stilbene oxide activity was detected in all tissues except 1/13 (7.6%) CUC tissues and 7/14 (50.0%, P less than or equal to 0.05) colorectal adenocarcinomas. Immunoreactive GST mu was observed in colonic epithelial cells but not in adjacent neoplastic cells by immunohistochemistry. Two-dimensional electrophoresis revealed several mu class isoforms in cytosol from unaffected colon that were absent in matched tumor cytosol. These results indicate that GSTM1 genotype may not necessarily reflect GST mu phenotype in colorectal tumors. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Guelph, Dept Biomed Sci, Guelph, ON N1G 2W1, Canada. McGill Univ, Sir Mortimer B Davis Jewish Hosp, Lady Davis Res Inst, Ctr Translat Res Canc, Montreal, PQ H3T 1E2, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kirby, GM (reprint author), Univ Guelph, Dept Biomed Sci, Guelph, ON N1G 2W1, Canada. NR 46 TC 6 Z9 7 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD MAR 8 PY 2002 VL 177 IS 1 BP 65 EP 74 AR PII S0304-3835(01)00765-0 DI 10.1016/S0304-3835(01)00765-0 PG 10 WC Oncology SC Oncology GA 538UJ UT WOS:000174833200009 PM 11809532 ER PT J AU Podar, K Tai, YT Lin, BK Narsimhan, RP Sattler, M Kijima, T Salgia, R Gupta, D Chauhan, D Anderson, KC AF Podar, K Tai, YT Lin, BK Narsimhan, RP Sattler, M Kijima, T Salgia, R Gupta, D Chauhan, D Anderson, KC TI Vascular endothelial growth factor-induced migration of multiple myeloma cells is associated with beta(1) integrin- and phosphatidylinositol 3-kinase-dependent PKC alpha activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; FOCAL ADHESION KINASE; TYROSINE KINASE; CELLULAR-RESPONSES; GENE-EXPRESSION; PHORBOL ESTER; RECEPTOR; CALCIUM; LINES; MOTILITY AB In multiple myeloma (MM), migration is necessary for the homing of tumor cells to bone marrow (BM), for expansion within the BM microenvironment, and for egress into the peripheral blood. In the present study we characterize the role of vascular endothelial growth factor (VEGF) and beta(1) integrin (CD29) in MM cell migration. We show that protein kinase C (PKC) alpha is translocated to the plasma membrane and activated by adhesion of MM cells to fibronectin and VEGF. We identify beta(1) integrin modulating VEGF-triggered MM cell migration on fibronectin. We show that transient enhancement of MM cell adhesion to fibronectin triggered by VEGF is dependent on the activity of both PKC and beta(1) integrin. Moreover, we demonstrate that PKCalpha is constitutively associated with beta(1) integrin. These data are consistent with PKCalpha-dependent exocytosis of activated beta(1) integrin to the plasma membrane, where its increased surface expression mediates binding to fibronectin; conversely, catalytically active PKCalpha-driven internalization of beta(1) integrin results in MM cell de-adhesion. We show that the regulatory subunit of phosphatidylinositol (PI) 3-kinase (p85) is constitutively associated with FMS-like tyrosine kinase-1 (Flt-1). VEGF stimulates activation of PI 3-kinase, and both MM cell adhesion and migration are PI 3-kinase-dependent. Moreover, both VEGF-induced PI 3-kinase activation and beta(1) integrin-mediated binding to fibronectin are required for the recruitment and activation of PKCa. Time-lapse phase contrast video microscopy (TLVM) studies confirm the importance of these signaling components in VEGF-triggered AM cell migration on fibronectin. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Res Ctr, 44 Binney St, Boston, MA 02115 USA. FU PHS HHS [P0-1 78378] NR 54 TC 136 Z9 140 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 MAR 8 PY 2002 VL 277 IS 10 BP 7875 EP 7881 DI 10.1074/jbc.M109068200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 528WR UT WOS:000174268000033 PM 11751905 ER PT J AU Furman, C Short, SM Subramanian, RR Zetter, BR Roberts, TM AF Furman, C Short, SM Subramanian, RR Zetter, BR Roberts, TM TI DEF-1/ASAP1 is a GTPase-activating protein (GAP) for ARF1 that enhances cell motility through a GAP-dependent mechanism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SWISS 3T3 FIBROBLASTS; ACTIN STRESS FIBERS; FOCAL ADHESIONS; BINDING-PROTEIN; ADP-RIBOSYLATION; PAXILLIN RECRUITMENT; MEMBRANE; RHO; TRANSPORT; CYTOSKELETON AB DEF-1/ASAP1 is an ADP-ribosylation factor GTPase-activating protein (ARF GAP) that localizes to focal adhesions and is involved in cytoskeletal regulation. In this paper, we use a cell-based ARF GAP assay to demonstrate that DEF-1 functions as a GAP for ARF1 and not ARF6 in vivo. This degree of substrate preference was unique to DEF-1, as other ARF GAP proteins, ACAP1, ACAP2, and ARFGAP1, were able to function on both ARF1 and ARF6. Since transient overexpression of DEF-1 has been shown to interfere with focal adhesion formation and platelet-derived growth factor-induced membrane ruffling, we investigated whether NIH 3T3 cells stably expressing DEF-1 have altered cell motility. Here we report that ectopic DEF-1 enhances cell migration toward PDGF as well as IGF-1. This chemotactic effect appears to result from a general increase in cell motility, as DEF-1-expressing cells also exhibit enhanced levels of basal and chemokinetic motility. The increase in cell motility is dependent on DEF-1 GAP activity, since a DEF-1 mutant lacking the GAP domain failed to stimulate motility. This suggests that DEF-1 alters cell motility through the deactivation of ARF1. In contrast, the inhibition of cell spreading by DEF-1 was not dependent on GAP activity, indicating that spreading and motility are altered by DEF-1 through different pathways. C1 Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Surg Res, Boston, MA 02115 USA. RP Roberts, TM (reprint author), Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 37 TC 54 Z9 55 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 8 PY 2002 VL 277 IS 10 BP 7962 EP 7969 DI 10.1074/jbc.M109149200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 528WR UT WOS:000174268000044 PM 11773070 ER PT J AU Xiao, H Yin, TG Wang, XY Uchida, T Chung, J White, MF Yang, YC AF Xiao, H Yin, TG Wang, XY Uchida, T Chung, J White, MF Yang, YC TI Specificity of interleukin-2 receptor gamma chain superfamily cytokines is mediated by insulin receptor substrate-dependent pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PLECKSTRIN HOMOLOGY DOMAIN; PHOSPHOTYROSINE-BINDING DOMAIN; FACTOR-I RECEPTOR; TYROSINE PHOSPHORYLATION; THYMIC LYMPHOMAS; TRANSGENIC MICE; IL-2 RECEPTOR; ALPHA-CHAIN; NPEY MOTIF; BETA-CHAIN AB Interleukins 9 (IL-9) and 4 are cytokines within the IL-2 receptor gamma chain (IL-2Rgamma) superfamily that possess similar and unique biological functions. The signaling mechanisms, which may determine cytokine specificity and redundancy, are not well understood. IRS proteins are tyrosine-phosphorylated following IL-9 and IL-4 stimulation, a process in part mediated by JAR tyrosine kinases (Yin, T. G., Keller, S. R., Quelle, F. W., Witthuhn, B. A., Tsang, M. L., Lienhard, G. E., Ihle, J. N., and Yang, Y. C. (1995) J. BioL Chem 270, 20497-20502). In the present study, we used 32D cells stably transfected with insulin receptor (32D(IR)), which do not express any IRS proteins, as a model system to study the requirement of different structural domains of IRS proteins in IL-9- and IL-4-mediated functions. Overexpression of IRS-1 and IRS-2, but not IRS-4, induced proliferation of 32D(IR) cells in response to IL-9. The pleckstrin homology (PH) domain of IRS proteins is required for IRS-mediated proliferation stimulated by IL-9. The phosphotyrosine binding and She and IRS-1 NPXY binding domains are interchangeable for IRS to transduce the proliferative effect of IL-4. Therefore, the PH domain plays different roles in coupling IRS proteins to activated IL-9 and IL-4 receptors. The role of IRS proteins in determining cytokine specificity was corroborated by their ability to interact with different downstream signaling molecules. Although phosphatidylinositol 3'-kinase (PI3K) and Grb-2 interact with tyrosine-phosphorylated IRS proteins, Shp-2 only binds to IRS proteins following IL-4, but not IL-9, stimulation. Although PI3K activity is necessary for the IRS-1/2-mediated proliferative effect of IL-9 and IL-4, Akt activation is only required for cell proliferation induced by IL-4, but not IL-9. These data suggest that IRS-dependent signaling pathways work by recruiting different signaling molecules to determine specificity of IL-2Rgamma superfamily cytokines. C1 Case Western Reserve Univ, Sch Med, Dept Pharmacol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Ctr Canc, Cleveland, OH 44106 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Joslin Diabet Ctr, Boston, MA 02115 USA. Eli Lilly Inc, Indianapolis, IN 46285 USA. Pharmacia & Upjohn Inc, Kalamazoo, MI 49007 USA. RP Yang, YC (reprint author), Case Western Reserve Univ, Sch Med, Dept Pharmacol, 2109 Adelbert Rd,W353, Cleveland, OH 44106 USA. FU NCI NIH HHS [CA74833]; NHLBI NIH HHS [HL48819]; NIDDK NIH HHS [DK50570] NR 52 TC 22 Z9 22 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 MAR 8 PY 2002 VL 277 IS 10 BP 8091 EP 8098 DI 10.1074/jbc.M106650200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 528WR UT WOS:000174268000060 PM 11788580 ER PT J AU Chang, DD Hoang, BQ Liu, J Springer, TA AF Chang, DD Hoang, BQ Liu, J Springer, TA TI Molecular basis for interaction between Icap1 alpha PTB domain and beta(1) integrin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMYLOID PRECURSOR PROTEIN; FOCAL ADHESION KINASE; CYTOPLASMIC DOMAIN; SIGNAL-TRANSDUCTION; CELL-ADHESION; ALPHA-ACTININ; SUBUNIT; BINDING; MODULATION; BETA-1 AB Icap1alpha is a 200-amino acid protein that binds to the COOH-terminal 13 amino acids ((788)AVTTVVNPKYE-GK(798)) of the integrin beta(1) subunit. Alanine scanning mutagenesis of this region revealed that Val(787), Val(790), and (NPKY795)-N-792 are critical for Icap1alpha binding. The NPXY motif is a known binding substrate for phosphotyrosine binding (PTB) domain proteins. The sequences of Icap1alpha, residues 58-200, and the beta(1) integrin, residues 786-797, were aligned to the available PTB-peptide structures to generate a high quality structural model. Site-directed mutagenesis showed that Leu(135), Ile(138), and Ile(139) of Icap1alpha, residues predicted by the model to be in close proximity to (NPKY795)-N-792, and LeU(82) and Tyr(144), residues expected to form a hydrophobic pocket near Val(787), are required for the Icap1alpha-beta(1), integrin interaction. These findings indicate that Icap1alpha is a PTB domain protein, which recognizes the NPXY motif of beta(1) integrin. Furthermore, our date suggest that an interaction between Val(787) and the hydrophobic pocket created by Leu(82) and Tyr(144) of Icap1alpha forms the basis for the specificity of Icap1alpha for the beta(1) integrin subunit. C1 Univ Calif Los Angeles, Sch Med, Div Heme One, Dept Med Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Chang, DD (reprint author), Univ Calif Los Angeles, Sch Med, Div Heme One, Dept Med Microbiol Immunol & Mol Genet, Factor 11-934,10833 Le Conte Ave, Los Angeles, CA 90095 USA. FU NCI NIH HHS [CA78375]; NHLBI NIH HHS [HL48675]; NIDCR NIH HHS [T32DE007926] NR 50 TC 37 Z9 38 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 MAR 8 PY 2002 VL 277 IS 10 BP 8140 EP 8145 DI 10.1074/jbc.M109031200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 528WR UT WOS:000174268000066 PM 11741908 ER PT J AU Souza, SC Muliro, KV Liscum, L Lien, P Yamamoto, MT Schaffer, JE Dallal, GE Wang, XZ Kraemer, FB Obin, M Greenberg, AS AF Souza, SC Muliro, KV Liscum, L Lien, P Yamamoto, MT Schaffer, JE Dallal, GE Wang, XZ Kraemer, FB Obin, M Greenberg, AS TI Modulation of hormone-sensitive lipase and protein kinase A-mediated lipolysis by perilipin A in an adenoviral reconstituted system SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article; Proceedings Paper CT 60th Scientific Sessions of the American-Diabetes-Association CY JUN 09-13, 2000 CL SAN ANTONIO, TEXAS SP Amer Diabet Assoc ID NECROSIS-FACTOR-ALPHA; DIFFERENTIATION-RELATED PROTEIN; INTRACELLULAR LIPID DROPLETS; ACID TRANSPORT PROTEIN; ACYL-COA SYNTHETASE; DENSITY LIPOPROTEIN; STORAGE DROPLET; ADIPOCYTES; CELLS; EXPRESSION AB Perilipin (Peri) A is a phosphoprotein located at the surface of intracellular lipid droplets in adipocytes. Activation of cyclic AMP-dependent protein kinase (PKA) results in the phosphorylation of Peri A and hormone-sensitive lipase (HSL), the predominant lipase in adipocytes, with concurrent stimulation of adipocyte lipolysis. To investigate the relative contributions of Peri A and HSL in basal and PKA-mediated lipolysis, we utilized NIH 3T3 fibroblasts lacking Peri A and HSL but stably overexpressing acyl-CoA synthetase 1 (ACS1) and fatty acid transport protein I (FATP1). When incubated with exogenous fatty acids, ACS1/FATP1 cells accumulated 5 times more triacylglycerol (TG) as compared with NIH 3T3 fibroblasts. Adenoviral-mediated expression of Peri A in ACS1/FATP1 cells enhanced TG accumulation and inhibited lipolysis, whereas expression of HSL fused to green fluorescent protein (GFPHSL) reduced TG accumulation and enhanced lipolysis. Forskolin treatment induced Peri A hyperphosphorylation and abrogated the inhibitory effect of Peri A on lipolysis. Expression of a mutated Peri ADelta3 (Ser to Ala substitutions at PKA consensus sites Ser-81, Ser-222, and Ser-276) reduced Peri A hyperphosphorylation and blocked constitutive and forskolin-stimulated lipolysis. Thus, perilipin expression and phosphorylation state are critical regulators of lipid storage and hydrolysis in ACSI/FATP1 cells. C1 Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Physiol, Boston, MA 02111 USA. Washington Univ, Dept Med, St Louis, MO 63110 USA. Washington Univ, Dept Mol Biol, St Louis, MO 63110 USA. Washington Univ, Dept Pharmacol, St Louis, MO 63110 USA. Massachusetts Gen Hosp, Nessel Gene Therapy Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med & Mol Biol, Boston, MA 02114 USA. Stanford Univ, Dept Med, Div Endocrinol, Stanford, CA 94305 USA. VA Palo Alto Hlth Care Syst, Stanford, CA 94305 USA. New England Med Ctr, Div Endocrinol Metab & Mol Med, Boston, MA 02111 USA. RP Greenberg, AS (reprint author), Tufts Univ, USDA, Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA. FU NIDDK NIH HHS [DK 46942, P30 DK 34928, DK 50647] NR 36 TC 161 Z9 168 U1 1 U2 7 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 8 PY 2002 VL 277 IS 10 BP 8267 EP 8272 DI 10.1074/jbc.M108329200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 528WR UT WOS:000174268000083 PM 11751901 ER PT J AU Braganca, J Swingler, T Marques, FIR Jones, T Eloranta, JJ Hurst, HC Shioda, T Bhattacharya, S AF Braganca, J Swingler, T Marques, FIR Jones, T Eloranta, JJ Hurst, HC Shioda, T Bhattacharya, S TI Human CREB-binding protein/p300-interacting transactivator with ED-rich tail (CITED) 4, a new member of the CITED family, functions as a co-activator for transcription factor AP-2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MELANOCYTE-SPECIFIC GENE; MICE LACKING; PROTEIN; MSG1; CBP; EXPRESSION; COACTIVATOR; P300/CBP; DEFECTS; GROWTH AB Members of the CREB-binding protein/p300-interacting transactivator with ED-rich tail (CITED) family bind CREB-binding protein and p300 with high affinity and regulate gene transcription. Gene knockout studies indicate that CITED2 is required for neural crest and neural tube development and that it functions as a co-activator for transcription factor AP-2 (TFAP2). Here we describe human CITED4, a new member of this family, which is encoded by a single exon mapping to chromosome lp34-lp35. CITED4 and p300/CREB-binding protein are present in endogenous naturally occurring complexes, indicating that they interact physiologically. The interaction occurs between the cwysteine-histidine-rich domain 1 of p300 and the carboxyl terminus of CITED4. In keeping with this, CITED4 functions as a transactivator when artificially targeted to a promoter element. CITED4 physically interacts with all TFAP2 isoforms in vitro and strongly co-activates all TFAP2 isoforms in Hep3B cells. Co-activation of TFAP2 requires amino-terminal and carboxyl-terminal residues of CITED4. In HepG2 cells, CITED4 is significantly weaker than CITED2 for TFAP2C co-activation. These results suggest that CITED4 may function as a co-activator for TFAP2. They also suggest the existence of cell type- and TFAP2 isoform-specific co-activation by CITED2 and CITED4, which may result in differential modulation of TFAP2 function. C1 Massachusetts Gen Hosp, Ctr Canc, Lab Tumor Biol, Charlestown, MA 02129 USA. Hammersmith Hosp, Imperial Canc Res Fund, Mol Oncol Unit, London W12 0NN, England. Imperial Canc Res Fund, Human Cytogenet Lab, London WC2A 3PX, England. RP Bhattacharya, S (reprint author), Univ Oxford, Dept Cardiovasc Med, Wellcome Trust Ctr Human Genet, Henry Wellcome Bldg Genomic Med,Roosevelt Dr, Oxford OX3 7BN, England. RI Jones, Tania/C-8912-2011; Bhattacharya, Shoumo/F-4127-2010; Braganca, Jose/F-4410-2012; Corbett-Jones, Tania/E-4891-2013 OI Jones, Tania/0000-0002-0067-3382; Braganca, Jose/0000-0001-9566-400X; Corbett-Jones, Tania/0000-0002-0067-3382 NR 39 TC 61 Z9 68 U1 0 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 8 PY 2002 VL 277 IS 10 BP 8559 EP 8565 DI 10.1074/jbc.M110850200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 528WR UT WOS:000174268000119 PM 11744733 ER PT J AU Pasternak, R AF Pasternak, R TI Adult treatment panel II versus adult treatment panel III: What has changed and why? SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 14th Symposium on Drugs Affecting Lipid Management (DALM 2001) CY SEP 10, 2001 CL NEW YORK, NEW YORK AB The Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel [ATP] III) differs in several ways from the ATP II guidelines. Several principal advances include (1) new risk levels for major lipid measures, (2) increased emphasis on primary prevention, (3) inclusion of high-risk groups in secondary prevention, (4) broader lifestyle program, and (5) increased focus on implementation and adherence. The purpose of this article is to discuss the major changes in ATP III and to highlight the benefits of the new guidelines in the management of hypercholesterolemia in adults. (C) 2002 by Excerpta Medica, Inc. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Pasternak, R (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St, Boston, MA 02114 USA. NR 7 TC 13 Z9 13 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 MAR 7 PY 2002 VL 89 IS 5A SI SI BP 3C EP 7C AR PII S0002-9149(02)02221-X PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 531BL UT WOS:000174395000002 PM 11900712 ER PT J AU Duan, Z Lamendola, DE Penson, RT Kronish, KM Seide, MV AF Duan, Z Lamendola, DE Penson, RT Kronish, KM Seide, MV TI Overexpression of IL-6 but not IL-8 increases paclitaxel resistance of U-20S human osteosarcoma cells SO CYTOKINE LA English DT Article DE drug resistance; IL-6; paclitaxei; ovarian cancer ID OVARIAN-CANCER; CARCINOMA-CELLS; LEUKEMIC-CELLS; SERUM LEVELS; INTERLEUKIN-6; CYTOKINES; PROTEIN; LINES; EXPRESSION; PROGNOSIS AB The cytokines IL-6, initially recognized as a regulator of immune and inflammatory response and IL-8, a potential regulator of angiogenesis, also regulate the growth of many tumor cells. Human cancer cells selected for multidrug resistance to common chemotherapeutic agents demonstrate increased expression of IL-6 and IL-8. To determine whether IL-6 or IL-8 overexpression contributes directly to the drug resistant phenotype, IL-6 or IL-8 cDNA were introduced into the paclitaxel sensitive human osteosarcoma cell line U-20S using the pIRESneo bicistronic expression vector. Interleukin-6 and IL-8 transfectants were selected for either high IL-6 or IL-8 secretion and evaluated in drug resistance assays. Two IL-6 and two IL-8 secreting clones express IL-6 or IL-8 levels of 10 ng/ml and I ng/ml in culture, while parental U-20S and pIRESneo vector transfected control cells express IL-6 and IL-8 levels of 0.005 ng/ml and 0.1 ng/ml, respectively. NITT cytotoxicity with IL-6 transfected cells demonstrates a five-fold increase in resistance to paclitaxel and a four-fold increase in resistance to doxorubicin as compared to U-20S. There are no changes in mitoxantrone or topotecan resistance in the IL-6 transfectants as compared to parental U-20S. Northern analysis of IL-6 transfectants demonstrates that the resistant phenotype is not related to increased levels of MDR-1, MRP-1, or LRP. Western analysis also confirms that P-glycoprotein levels are not altered in IL-6 transfectants. Further supporting an MDR-1 independent mechanism of drug resistance, verapamil cannot reverse paclitaxel resistance in transfected cells, findings further supported by rhodamine 123 exclusion data. Treatment of IL-6 transfected cells with paclitaxel, compared with drug-sensitive parental U-2OS shows U-2OS(IL-6) are significantly more resistant to apoptosis induced by paclitaxel and exhibit decreased proteolytic activation of caspase-3. In contrast U-2OS(IL-8) transfectants demonstrate no appreciable increase in paclitaxel resistance when compared with parental cells. In summary, while both IL-6 and IL-8 are overexpressed in paclitaxel resistant cell lines, only IL-6 has the potential to contribute directly to paclitaxel and doxorubicin resistance in U-20S. This resistance is through a non-MDR-1 pathway. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. RP Seide, MV (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, Cox 640, Boston, MA 02114 USA. NR 36 TC 45 Z9 51 U1 0 U2 3 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 2002 VL 17 IS 5 BP 234 EP 242 DI 10.1006/cyto.2001.1008 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 563KZ UT WOS:000176256000002 PM 12027404 ER PT J AU Smith, ZM Delgutte, B Oxenham, AJ AF Smith, ZM Delgutte, B Oxenham, AJ TI Chimaeric sounds reveal dichotomies in auditory perception SO NATURE LA English DT Article ID INTERAURAL TIME DIFFERENCES; SPEECH RECOGNITION; LOW-FREQUENCY; MECHANISMS; CORTEX; CAT AB By Fourier's theorem(1), signals can be decomposed into a sum of sinusoids of different frequencies. This is especially relevant for hearing, because the inner ear performs a form of mechanical Fourier transform by mapping frequencies along the length of the cochlear partition. An alternative signal decomposition, originated by Hilbert(2), is to factor a signal into the product of a slowly varying envelope and a rapidly varying fine time structure. Neurons in the auditory brainstem(3-6) sensitive to these features have been found in mammalian physiological studies. To investigate the relative perceptual importance of envelope and fine structure, we synthesized stimuli that we call 'auditory chimaeras', which have the envelope of one sound and the fine structure of another. Here we show that the envelope is most important for speech reception, and the fine structure is most important for pitch perception and sound localization. When the two features are in conflict, the sound of speech is heard at a location determined by the fine structure, but the words are identified according to the envelope. This finding reveals a possible acoustic basis for the hypothesized 'what' and 'where' pathways in the auditory cortex(7-10). C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. RP Delgutte, B (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RI Smith, Zachary/B-2879-2009; OI Smith, Zachary/0000-0002-0819-4562; , /0000-0003-1349-9608; Oxenham, Andrew/0000-0002-9365-1157 FU NIDCD NIH HHS [R01 DC005216, R01 DC002258, R01 DC002258-07, R01 DC005216-02] NR 28 TC 408 Z9 434 U1 3 U2 22 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 7 PY 2002 VL 416 IS 6876 BP 87 EP 90 DI 10.1038/416087a PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 527WU UT WOS:000174211600044 PM 11882898 ER PT J AU Paganetti, H AF Paganetti, H TI Nuclear interactions in proton therapy: dose and relative biological effect distributions originating from primary and secondary particles SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID REACTION CROSS-SECTIONS; LOW-ENERGY PROTONS; MONTE-CARLO; MAMMALIAN-CELLS; CELLULAR RADIOSENSITIVITY; 160-MEV PROTONS; STOPPING-POWER; FAST-NEUTRONS; V79 CELLS; BEAM AB The dose distribution delivered in charged particle therapy is due to both primary and secondary particles. The secondaries, originating from nonelastic nuclear interactions, are of interest for three reasons. First, if fast Monte Carlo treatment planning is envisaged, the question arises whether all nuclear interaction products deliver a significant contribution to the total dose and, hence, need to be tracked. Second, there could be an enhanced relative biological effectiveness (RBE) due to low energy and/or heavy secondaries. Third, neutrons originating from nuclear interactions may deliver dose outside the target volume. The particle yield from different nuclear interaction channels as a function of proton penetration depth was studied theoretically for different proton beam energies. Three-dimensional dose distributions from primary and secondary particles were simulated for an unmodulated 160 MeV proton beam with and without including a slice of bone material and for a spread-out Bragg peak (SOBP) of 3 x 3 x 3 cm(3) in water. Secondary protons deliver up to approximate to10% of the total dose proximal to the Bragg peak of an unmodulated proton beam and they affect the flatness of the SOBP. Furthermore, they cause a dose build-up due to forward emission of secondary particles from nuclear interactions. The dose deposited by d, t, (3)He and alpha-particles was found to contribute less than 0.1% of the total dose. The dose distal to the target volume caused by liberated neutrons was studied for four proton beam energies in the range of 160-250 MeV and found to be below 0.05% (2 cm distal to SOBP) of the prescribed target dose for a 3 x 3 x 3 cm(3) target. RBE values relative to (60)Co were calculated proximal to and within the SOBP. The RBE proximal to the Bragg peak (100% dose) is influenced by secondary particles (mainly protons and alpha-particles) with a strong dose dependency resulting in RBE values up to 1.2 (2 Gy; inactivation of V79). Depending, on the endpoint considered, secondary particles cause a shift in RBE by up to 8% at 2 Gy. In contrast, the RBE in the Bragg peak is almost entirely determined by primary protons due to a decreasing secondary particle fluence with depth. RBE values up to 1.3 (2 Gy; inactivation of V79) at I cm distal to the Bragg peak maximum were found. The inactivations of human skin fibroblasts and mouse lymphoma cells were also analysed and reveal a substantial tissue dependency of the total RBE. The outcome of this study shows that elevated RBE values occur not only at the distal edge of the SOBP. Although the variations are modest, and in most cases might have no observable clinical effect, they might have to be considered in certain treatment situations. The biological effect downstream of the target caused by neutrons was analysed using a radiation quality factor of 10. The biological dose was found to be below 0.5% of the prescribed target dose (for a 3 x 3 x 3 cm(3) SOBP) but depends on the size of the SOBP. This dose should not be significant with respect to late effects, e.g. cancer induction. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Med Sch, Cambridge, MA 02138 USA. RP Paganetti, H (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM hpaganetti@partners.org NR 62 TC 94 Z9 99 U1 5 U2 16 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD MAR 7 PY 2002 VL 47 IS 5 BP 747 EP 764 AR PII S0031-9155(02)28374-8 DI 10.1088/0031-9155/47/5/305 PG 18 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 533LJ UT WOS:000174531200005 PM 11931469 ER PT J AU Williams, JW Noel, PH Cordes, JA Ramirez, G Pignone, M AF Williams, JW Noel, PH Cordes, JA Ramirez, G Pignone, M TI Is this patient clinically depressed? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID DSM-III-R; RANDOMIZED CONTROLLED TRIAL; DIAGNOSING MENTAL-DISORDERS; CASE-FINDING INSTRUMENTS; PRIMARY-CARE; MAJOR DEPRESSION; MEDICAL OUTPATIENTS; COLLABORATIVE MANAGEMENT; TREATMENT GUIDELINES; LIKELIHOOD RATIOS AB Context Depressive disorders are highly prevalent in the general population, but recognition and accurate diagnosis are made difficult by the lack of a simple confirmatory test. Objective To review the accuracy and precision of depression questionnaires and the clinical examination for diagnosing clinical depression. Data Sources We searched the English-language literature from 1970 through July 2000 using MEDLINE, a specialized registry of depression trials, and bibliographies of selected articles. Study Selection Case-finding studies were included if they used depression questionnaires with easy to average literacy requirements, evaluated at least 100 primary care patients, and compared questionnaire results with accepted diagnostic criteria for major depression. Eleven questionnaires, ranging in length from 1 to 30 questions, were assessed in 28 published studies. Reliability studies for the clinical examination required criterion-based diagnoses made by at least 2 clinicians who interviewed the patient or reviewed a taped examination. Fourteen studies evaluated interrater reliability. Data Extraction Pairs of authors independently reviewed articles. For case-finding studies, quality assessment addressed sample size and whether patients were selected consecutively or randomly, the criterion standard was administered and interpreted independently of and blind to the results of the case-finding instrument, and the proportion of persons receiving the criterion standard assessment was less than or more than 50% of those approached for criterion standard assessment. For reliability studies, quality assessment addressed whether key patient characteristics were described, the interviewers collected clinical history independently, and diagnoses were made blinded to other clinicians' evaluations. Data Synthesis In case-finding studies, average questionnaire administration times ranged from less than 1 minute to 5 minutes. The median likelihood ratio positive for major depression was 3.3 (range, 2.3-12.2) and the median likelihood ratio negative was 0.19 (range, 0.14-0.35). No significant differences between questionnaires were found. For mental health care professionals using a semistructured interview, agreement was substantial to almost perfect for major depression (kappa=0.64-0.93), Non-standardized interviews yielded somewhat lower agreement (kappa=0.55-0.74). A single study showed that primary care clinicians using a semistructured interview have high agreement with mental health care professionals (kappa=0.71). Conclusions Multiple, practical questionnaires with reasonable performance characteristics are available to help clinicians identify and diagnose patients with major depression. Diagnostic confirmation by mental health care professionals using a clinical interview or by primary care physicians using a semistructured interview can be made with high reliability. C1 S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio Evidence Based Practice Ctr, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Univ N Carolina, Dept Med, Chapel Hill, NC USA. RTI UNC Evidence Based Practice Ctr, Chapel Hill, NC USA. RP Williams, JW (reprint author), Dept Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, HSR&D, 508 Fulton St,Bldg 6, Durham, NC 27705 USA. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 97 TC 198 Z9 202 U1 4 U2 8 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 MAR 6 PY 2002 VL 287 IS 9 BP 1160 EP 1170 DI 10.1001/jama.287.9.1160 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 527KV UT WOS:000174186000032 PM 11879114 ER PT J AU Hernandez, PJC Rubenstein, M Martin, F Sanchez, PL Harrell, LC Palacios, IF AF Hernandez, PJC Rubenstein, M Martin, F Sanchez, PL Harrell, LC Palacios, IF TI The impact of stenting in the very elderly SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER 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 6 PY 2002 VL 39 IS 5 SU A BP 4A EP 4A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106700016 ER PT J AU Ammer, R Hsin, M Aretz, T AF Ammer, R Hsin, M Aretz, T TI Transmyocardial laser revascularization and AdVEGF-transfection promotes angiogenesis in ischemic myocardium SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 6 PY 2002 VL 39 IS 5 SU A BP 11A EP 11A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106700047 ER PT J AU Walters, D Harding, S Walsh, C Wong, P Pomerantsev, E Jang, IK AF Walters, D Harding, S Walsh, C Wong, P Pomerantsev, E Jang, IK TI Acute coronary syndrome is a common clinical presentation of in-stent restenosis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER 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 6 PY 2002 VL 39 IS 5 SU A BP 43A EP 43A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106700187 ER PT J AU Oesterle, H Davidson, C Kuntz, R Nordhausen, C Vonesh, M Ulm, M Macri, N AF Oesterle, H Davidson, C Kuntz, R Nordhausen, C Vonesh, M Ulm, M Macri, N TI In-vivo evaluation of a novel ePTFE-covered self-expanding stent for the treatment of diseased saphenous vein bypass grafts SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER 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 6 PY 2002 VL 39 IS 5 SU A BP 52A EP 53A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106700228 ER PT J AU Thompson, CA Nasseri, BA Makower, J Pomerantseva, I Lamson, T Chang, JY McGarry, M Fishman, MC Vacanti, JP Oesterle, SN AF Thompson, CA Nasseri, BA Makower, J Pomerantseva, I Lamson, T Chang, JY McGarry, M Fishman, MC Vacanti, JP Oesterle, SN TI Percutaneous transvenous cellular cardiomyoplasty: A novel nonsurgical approach for myocardial cell transplantation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. TransVasc Inc, Menlo Pk, CA USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2002 VL 39 IS 5 SU A BP 75A EP 75A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106700326 ER PT J AU Sun, W Chen, FH Esmallian, F Sarma, JS Wetzel, GT Klitzner, TS Singh, BN AF Sun, W Chen, FH Esmallian, F Sarma, JS Wetzel, GT Klitzner, TS Singh, BN TI Acute effects of dronedarone on the potassium currents in human atrial cells SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 VA Greater LA Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2002 VL 39 IS 5 SU A BP 105A EP 105A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106700457 ER PT J AU Ammer, R Keane, D Aretz, T Ruskin, JN AF Ammer, R Keane, D Aretz, T Ruskin, JN TI Apoptosis in atrial myocytes and Bcl2-upregulation in ventricular myocytes are transient phenomenona in persistent atrial fibrillation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER 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 6 PY 2002 VL 39 IS 5 SU A BP 123A EP 123A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106700543 ER PT J AU Go, AS Hylek, EM Chang, YC Henault, LE Phillips, KA Singer, DE AF Go, AS Hylek, EM Chang, YC Henault, LE Phillips, KA Singer, DE TI What is the optimal anticoagulation intensity to prevent stroke in patients with atrial fibrillation >=75 versus < 75 years old? The anticoagulation and risk falls factors in atrial fibrillation (ATRIA) study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Kaiser Permanente No Calif, Oakland, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2002 VL 39 IS 5 SU A BP 133A EP 133A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106700587 ER PT J AU Yoerger, DM Picard, MH Palacios, IF Vlahakes, GJ Fifer, MA AF Yoerger, DM Picard, MH Palacios, IF Vlahakes, GJ Fifer, MA TI Triphasic response to alcohol septal ablation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2002 VL 39 IS 5 SU A BP 157A EP 157A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106700696 ER PT J AU Sonel, AF Shalaby, A McConnell, JP Hogan, S Feldman, AM AF Sonel, AF Shalaby, A McConnell, JP Hogan, S Feldman, AM TI Detectable troponin T level predicts high mortality in patients with heart failure undergoing internal defibrillator implantation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2002 VL 39 IS 5 SU A BP 159A EP 159A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106700706 ER PT J AU Schafhalter-Zoppoth, I Gray, MO Teerlink, JR AF Schafhalter-Zoppoth, I Gray, MO Teerlink, JR TI Endothelin antagonism with bosentan, a dual receptor blocker, normalizes dysregulated transforming growth factor beta signaling pathways in rats with chronic heart failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RI Teerlink, John/D-2986-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2002 VL 39 IS 5 SU A BP 168A EP 168A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106700745 ER PT J AU Schafhalter-Zoppoth, I Teerlink, JR AF Schafhalter-Zoppoth, I Teerlink, JR TI Endothelin antagonism with bosentan improves myocardial mechanics and ventricular remodeling in rats with chronic heart failure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. RI Teerlink, John/D-2986-2012 NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2002 VL 39 IS 5 SU A BP 171A EP 171A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106700758 ER PT J AU Lipshultz, SE Rifai, N Dalton, V Levy, D Lipsitz, SR Gelber, RD Colan, SD Shaikh, S Sallan, SE AF Lipshultz, SE Rifai, N Dalton, V Levy, D Lipsitz, SR Gelber, RD Colan, SD Shaikh, S Sallan, SE CA Dana Farber Canc Inst Protocol TI Dexrazoxane is cardioprotective against doxorubicin cardiotoxicity SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Univ Rochester, Rochester, NY 14627 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 6 PY 2002 VL 39 IS 5 SU A BP 174A EP 174A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106700770 ER PT J AU Aepfelbacher, FC Yeon, SB Weinrauch, LA D'Elia, J Burger, AJ AF Aepfelbacher, FC Yeon, SB Weinrauch, LA D'Elia, J Burger, AJ TI Improved glycemic control induces regression of left ventricular mass in patients with type 1 diabetes mellitus SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2002 VL 39 IS 5 SU A BP 179A EP 179A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106700796 ER PT J AU Beeri, R Guerrero, LJ Sullivan, S Supple, G Levine, RA Hajjar, RJ AF Beeri, R Guerrero, LJ Sullivan, S Supple, G Levine, RA Hajjar, RJ TI A novel efficient percutaneous myocardial gene delivery system SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Beeri, Ronen/A-4035-2009 OI Beeri, Ronen/0000-0002-8014-0702 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2002 VL 39 IS 5 SU A BP 185A EP 186A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106700823 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 Maximal lipid lowering therapy decreases calcified plaque volume and increases calcified plaque density SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Univ Vienna, A-1010 Vienna, Austria. Gen Hosp, Vienna, Austria. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 6 PY 2002 VL 39 IS 5 SU A BP 235A EP 236A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106701053 ER PT J AU Tawakol, A Fischman, A Hasan, T Zahra, T Muller, J Hamblin, M AF Tawakol, A Fischman, A Hasan, T Zahra, T Muller, J Hamblin, M TI Accumulation of a novel macrophage-targeting photodynamic compound within lipid-rich atherosclerotic plaques SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER 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 6 PY 2002 VL 39 IS 5 SU A BP 248A EP 248A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106701110 ER PT J AU Shaw, JA Walton, AS Kingwell, BA Cameron, JD Dart, AM AF Shaw, JA Walton, AS Kingwell, BA Cameron, JD Dart, AM TI Determinants of coronary artery compliance in subjects with and without angiographic coronary artery disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Alfred Hosp, Melbourne, Vic, Australia. Baker Med Res Inst, Melbourne, Vic, Australia. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Shaw, James/F-1522-2010 NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2002 VL 39 IS 5 SU A BP 268A EP 268A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106701205 ER PT J AU Rubenstein, MH Garabedian, HD Guerrero, L Sullivan, SM Aretz, T Virmani, R Hollenbach, S Leinbach, RC Gold, HK AF Rubenstein, MH Garabedian, HD Guerrero, L Sullivan, SM Aretz, T Virmani, R Hollenbach, S Leinbach, RC Gold, HK TI Coronary artery passivation: A mechanism for the prevention of recurrent ischemia after thrombolysis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Cor Therapeut Inc, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2002 VL 39 IS 5 SU A BP 280A EP 280A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106701259 ER PT J AU de Lemos, JA Morrow, DA Gibson, M Murphy, SA Rifai, N Sabatine, MS Cooper, HA McCabe, CH Antman, EM Cannon, CP Braunwald, E AF de Lemos, JA Morrow, DA Gibson, M Murphy, SA Rifai, N Sabatine, MS Cooper, HA McCabe, CH Antman, EM Cannon, CP Braunwald, E TI Elevated serum myoglobin is associated with increased long-term mortality, independent of cardiac troponin I, electrocardiographic variables, and other baseline variables: Combined analyses from TIMI 11B and TACTICS/TIMI 18 SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 TIMI Study Grp, Boston, MA USA. Univ Texas, SW Med Sch, Dallas, TX 75230 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2002 VL 39 IS 5 SU A BP 305A EP 305A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106701372 ER PT J AU Nikolaidis, LA Hentosz, T Doverspike, A Huerbin, R Zourelias, L Stolarski, C Elahi, D Shannon, RP AF Nikolaidis, LA Hentosz, T Doverspike, A Huerbin, R Zourelias, L Stolarski, C Elahi, D Shannon, RP TI Glucagon-like peptide-1 (GLP-1) limits myocardial stunning following acute coronary occlusion and reperfusion in conscious canines SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2002 VL 39 IS 5 SU A BP 312A EP 312A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106701405 ER PT J AU Sonel, AF Whittle, J Kelley, M Wilensky, RL AF Sonel, AF Whittle, J Kelley, M Wilensky, RL TI Is there still a role for physician assessment in the emergency department in the era of novel cardiac markers? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2002 VL 39 IS 5 SU A BP 316A EP 316A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106701419 ER PT J AU Messas, E Chow, CM Sagie, A Rudski, L Gilon, D Levine, RA AF Messas, E Chow, CM Sagie, A Rudski, L Gilon, D Levine, RA TI A new noninvasive bedside hemodynamic index of early prognosis after acute myocardial infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2002 VL 39 IS 5 SU A BP 373A EP 373A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106701678 ER PT J AU Wu, JC Ichinose, F Bloch, KD Picard, MH Scherrer-Crosbie, M AF Wu, JC Ichinose, F Bloch, KD Picard, MH Scherrer-Crosbie, M TI Echocardiographic detection and quantification of early left ventricular hypertrophy after aortic banding in mice SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER 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 6 PY 2002 VL 39 IS 5 SU A BP 396A EP 396A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106701784 ER PT J AU Uemura, T Otsuji, Y Kumanohoso, T Yoshifuku, S Kisanuki, A Minagoe, S Levine, RA Tei, C AF Uemura, T Otsuji, Y Kumanohoso, T Yoshifuku, S Kisanuki, A Minagoe, S Levine, RA Tei, C TI Ischemic mitral regurgitation is independent of papillary muscle dysfunction: Clinical demonstration by quantitative echocardiography in patients with inferior myocardial infarction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Kagoshima Univ, Kagoshima 890, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2002 VL 39 IS 5 SU A BP 417A EP 418A PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106701876 ER PT J AU Messas, E Guerrero, JL Handschumacher, MD Hung, J Liel-Cohen, N Sullivan, S Vlahakes, G Levine, RA AF Messas, E Guerrero, JL Handschumacher, MD Hung, J Liel-Cohen, N Sullivan, S Vlahakes, G Levine, RA TI Chronic persistent efficacy of basal chordal cutting to relieve ischemic mitral regurgitation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2002 VL 39 IS 5 SU A BP 431A EP 431A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106701938 ER PT J AU Oesterle, SN Gillinov, AM Chin, CH Xing, YQ Prado, AD Pandian, NG AF Oesterle, SN Gillinov, AM Chin, CH Xing, YQ Prado, AD Pandian, NG TI Percutaneous catheter-based mitral valve repair SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2002 VL 39 IS 5 SU A BP 432A EP 432A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106701941 ER PT J AU Limbourg, FP Huang, ZH Moskowitz, MA Liao, JK AF Limbourg, FP Huang, ZH Moskowitz, MA Liao, JK TI Acute neuroprotective effects of cortico steriods mediated by nontranscriptional activation of endothelial nitric oxide synthase SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2002 VL 39 IS 5 SU A BP 442A EP 442A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106701989 ER PT J AU Ansari, MN Shlipak, MG Heidenreich, PA Massie, BM AF Ansari, MN Shlipak, MG Heidenreich, PA Massie, BM TI Strategies to improve guideline adherence: A randomized clinical trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 6 PY 2002 VL 39 IS 5 SU A BP 453A EP 453A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106702037 ER PT J AU Samaha, FF Klugherz, BD Wilensky, RL Locallo, AR Williams, M Kimmel, SE AF Samaha, FF Klugherz, BD Wilensky, RL Locallo, AR Williams, M Kimmel, SE TI Prediction rule for insignificant coronary artery disease in patients being considered for elective coronary angiography SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2002 VL 39 IS 5 SU A BP 454A EP 454A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106702043 ER PT J AU Sonel, AF Whittle, J Good, CB Kelley, M AF Sonel, AF Whittle, J Good, CB Kelley, M TI Prediction of risk in patients with unstable angina and non-ST elevation myocardial infarction: A prospective comparison of the new ACC/AHA guidelines and physician predicted risk SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 6 PY 2002 VL 39 IS 5 SU A BP 457A EP 457A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526AR UT WOS:000174106702056 ER PT J AU Shanafelt, TD Bradley, KA Wipf, JE Back, AL AF Shanafelt, TD Bradley, KA Wipf, JE Back, AL TI Burnout and self-reported patient care in an internal medicine residency program SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID EMERGENCY PHYSICIANS; ALCOHOL-CONSUMPTION; NATIONAL SURVEY; HOUSE OFFICERS; DEPRESSION; DISTRESS; STRESS; SATISFACTION; MANAGEMENT; QUESTIONS AB Background: Burnout is a syndrome of depersonalization, emotional exhaustion, and a sense of low personal accomplishment. Little is known about burnout in residents or its relationship to patient care. Objective: To determine the prevalence of burnout in medical residents and explore its relationship to self-reported patient care practices. Design: Cross-sectional study using an anonymous, mailed survey. Setting: University-based residency program in Seattle, Washington. Participants: 115 internal medicine residents. Measurements: Burnout was measured by using the Maslach Burnout Inventory and was defined as scores in the high range for medical professionals on the depersonalization or emotional exhaustion subscales. Five questions developed for this study assessed self-reported patient care practices that suggested suboptimal care (for example, "I did not fully discuss treatment options or answer a patient's questions" or "I made ... errors that were not due to a lack of knowledge or inexperience"). Depression and at-risk alcohol use were assessed by using validated screening questionnaires. Results: Of 115 (76%) responding residents, 87 (76%) met the criteria for burnout. Compared with non-burned-out residents, burned-out residents were significantly more likely to self-report providing at least one type of suboptimal patient care at least monthly (53% vs. 21%; P=0.004). In multivariate analyses, burnout-but not sex, depression, or at-risk alcohol use-was strongly associated with self-report of one or more suboptimal patient care practices at least monthly (odds ratio, 8.3 [95% Cl, 2.6 to 26.5]). When each domain of burnout was evaluated separately, only a high score for depersonalization was associated with self-reported suboptimal patient care practices (in a dose-response relationship). Conclusion: Burnout was common among resident physicians and was associated with self-reported suboptimal patient care practices. C1 Univ Washington, Vet Affairs NW Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98195 USA. RP Back, AL (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 1660 S Columbian Way S-111, Seattle, WA 98108 USA. FU NIAAA NIH HHS [K23AA00313] NR 45 TC 643 Z9 665 U1 11 U2 68 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 5 PY 2002 VL 136 IS 5 BP 358 EP 367 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 525VT UT WOS:000174095300003 PM 11874308 ER PT J AU Kohane, DS Lipp, M Kinney, RC Anthony, DC Louis, DN Lotan, N Langer, R AF Kohane, DS Lipp, M Kinney, RC Anthony, DC Louis, DN Lotan, N Langer, R TI Biocompatibility of lipid-protein-sugar particles containing bupivacaine in the epineurium SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article DE prolonged duration local anesthesia; controlled release; sciatic nerve; biocompatibility; bupivacaine; inflammation ID POLYLACTIC ACID MICROSPHERES; LOCAL-ANESTHETICS; NERVE BLOCKADE; IN-VIVO; POLYMER MICROSPHERES; CONTROLLED-RELEASE; EVALUATION INVITRO; MYOTOXICITY AB Novel lipid-protein-sugar particles (LPSPs) are potentially biocompatible because they are composed of naturally occurring ingredients and their expected tissue dwell times are relatively short. In this research, we used histological sections to study tissue reaction to LPSPs (4.4-mum median diameter) when used for sciatic nerve block in the rat. As a reference, we compared LPSPs to 60-mum median diameter poly(lactic-co-glycolic) acid (PLGA) microspheres (110,000 MW PLGA, glycolic/lactic ratio 65:35). Four days after injection, both particle types produced acute inflammation within the confines of the injectate, inflammation in adjacent tissues, and myotoxicity. Bupivacaine-free particles did not display myotoxicity, and inflammation in adjacent tissues was reduced. At 2 weeks, inflammation from LPSPs had almost disappeared, whereas PLGA microspheres had a foreign-body giant cell reaction until at least 8 weeks after injection. In contrast, 3.6-mum median diameter, 20,000-MW PLGA microspheres produced a primarily histiocytic reaction 2 weeks after injection. In summary, the LPSPs and PLGA microspheres studied herein have excellent biocompatibility, but tissue reaction to the former is of much shorter duration. Myotoxicity and inflammation of surrounding tissue is largely attributed to bupivacaine. Foreign-body giant cells may be attributed to particle size rather than a specific reaction to PLGA. (C) 2001 John Wiley & Sons, Inc. J Biomed Mater Res 59: 450-459, 2002. C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Technion Israel Inst Technol, Dept Biomed Engn, IL-32000 Haifa, Israel. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Langer, R (reprint author), MIT, Dept Chem Engn, Bldg E-25,Room 342,77 Main St, Cambridge, MA 02139 USA. OI Anthony, Daniel/0000-0003-1380-6655 FU NIGMS NIH HHS [GM00684, GM26698] NR 19 TC 55 Z9 56 U1 0 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD MAR 5 PY 2002 VL 59 IS 3 BP 450 EP 459 DI 10.1002/jbm.1261 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 507GX UT WOS:000173019600006 PM 11774302 ER PT J AU Shera, CA Guinan, JJ Oxenham, AJ AF Shera, CA Guinan, JJ Oxenham, AJ TI Revised estimates of human cochlear tuning from otoacoustic and behavioral measurements SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID AUDITORY-NERVE FIBERS; NORMAL-HEARING LISTENERS; CHARACTERISTIC FREQUENCY; BASILAR-MEMBRANE; FILTER SHAPES; NOTCHED-NOISE; GUINEA-PIG; MASKING; EMISSIONS; LEVEL AB We develop an objective, noninvasive method for determining the frequency selectivity of cochlear tuning at low and moderate sound levels. Applicable in humans at frequencies of 1 kHz and above, the method is based on the measurement of stimulus-frequency otoacoustic emissions and, unlike previous noninvasive physiological methods, does not depend on the frequency selectivity of masking or suppression. The otoacoustic measurements indicate that at low sound levels human cochlear tuning is more than twice as sharp as implied by standard behavioral studies and has a different dependence on frequency. New behavioral measurements designed to minimize the influence of nonlinear effects such as suppression agree with the emission-based values. A comparison of cochlear tuning in cat guinea pig, and human indicates that contrary to common belief, tuning in the human cochlea is considerably sharper than that found in the other mammals. The sharper tuning may facilitate human speech communication. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. RP Shera, CA (reprint author), Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM shera@epl.meei.harvard.edu OI Oxenham, Andrew/0000-0002-9365-1157 FU NIDCD NIH HHS [DC00235, DC03687, DC03909, R01 DC000235, R01 DC003687, R01 DC003909, R01 DC003909-03, R01 DC005216] NR 49 TC 229 Z9 230 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 MAR 5 PY 2002 VL 99 IS 5 BP 3318 EP 3323 DI 10.1073/pnas.032675099 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 529DK UT WOS:000174284600128 PM 11867706 ER PT J AU Brunet, A Kanai, F Stehn, J Xu, J Sarbassova, D Frangioni, JV Dalal, SN DeCaprio, JA Greenberg, ME Yaffe, MB AF Brunet, A Kanai, F Stehn, J Xu, J Sarbassova, D Frangioni, JV Dalal, SN DeCaprio, JA Greenberg, ME Yaffe, MB TI 14-3-3 transits to the nucleus and participates in dynamic nucleocytoplasmic transport SO JOURNAL OF CELL BIOLOGY LA English DT Article DE 14-3-3; FKHRL1; phosphoserine; nuclear export; Crm1 ID FORKHEAD TRANSCRIPTION FACTOR; SUBCELLULAR-LOCALIZATION; HISTONE DEACETYLASE-4; SIGNALING PROTEINS; AMPHIPATHIC GROOVE; KINASE-ACTIVITY; EXPORT SIGNAL; INDUCER CDC25; BINDING; 14-3-3-PROTEINS AB 14-3-3 proteins regulate the cell cycle and prevent apoptosis by controlling the nuclear and cytoplasmic distribution of signaling molecules with which they interact. Although the majority of 14-3-3 molecules are present in the cytoplasm, we show here that in the absence of bound ligands 14-3-3 homes to the nucleus. We demonstrate that phosphorylation of one important 14-3-3 binding molecule, the transcription factor FKHRL1, at the 14-3-3 binding site occurs within the nucleus immediately before FKHRL1 relocalization to the cytoplasm. We show that the leucine-rich region within the COOH-terminal alpha-helix of 14-3-3, which had been proposed to function as a nuclear export signal (NES), instead functions globally in ligand binding and does not directly mediate nuclear transport. Efficient nuclear export of FKHRL1 requires both intrinsic NES sequences within FKHRL1 and phosphorylation/14-3-3 binding. Finally, we present evidence that phosphorylation/14-3-3 binding may also prevent FKHRL1 nuclear reimport. These results indicate that 14-3-3 can mediate the relocalization of nuclear ligands by several mechanisms that ensure complete sequestration of the bound 14-3-3 complex in the cytoplasm. C1 MIT, Ctr Canc Res, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Signal Transduct, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Childrens Hosp, Div Neurosci, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Yaffe, MB (reprint author), MIT, Ctr Canc Res, 77 Massachusetts Ave,E18-580, Cambridge, MA 02139 USA. RI Stehn, Justine/G-5115-2013 OI Stehn, Justine/0000-0002-2136-5450 FU NICHD NIH HHS [HD18655, HD24926, P30 HD018655]; NIGMS NIH HHS [GM60594, R01 GM060594] NR 37 TC 321 Z9 332 U1 2 U2 15 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 MAR 4 PY 2002 VL 156 IS 5 BP 817 EP 828 DI 10.1083/jcb.200112059 PG 12 WC Cell Biology SC Cell Biology GA 566KC UT WOS:000176426300007 PM 11864996 ER PT J AU Green, AR Betancourt, JR Carrillo, JE AF Green, AR Betancourt, JR Carrillo, JE TI Integrating social factors into cross-cultural medical education SO ACADEMIC MEDICINE LA English DT Article ID CARE; HEALTH AB The field of cross-cultural medical education has blossomed in an environment of increasing diversity and increasing awareness of the effect Of race and ethnicity on health Outcomes, However, there is stilt no standardized approach to teaching doctors in training how best to care for diverse patient populations. As standards are developed, it is crucial to realize that medical educators cannot teach about culture in a vacuum. Caring for Patients of diverse Cultural backgrounds is inextricably linked to caring for patients of diverse social backgrounds. In this article, the authors discuss the importance of social issues in caring for patients of all cultures, and propose a practical, patient-based approach to social analysis covering four major domains-(1) social stress and support networks, (2) change in environment, (3) life control, and (4) literacy. By emphasizing and expanding the role of the social history in cross-cultural medical education, faculty can better train medical Students, residents, and other health care providers to care for socioculturally diverse patient populations. C1 Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, New York Presbyterian Hosp Network, New York, NY USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Multicultural Affairs Off, Boston, MA 02115 USA. RP Green, AR (reprint author), Cornell Internal Med Associates, 505 E 70th St,HT4, New York, NY 10021 USA. NR 15 TC 56 Z9 56 U1 1 U2 3 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 2002 VL 77 IS 3 BP 193 EP 197 DI 10.1097/00001888-200203000-00003 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 530HX UT WOS:000174353200002 PM 11891153 ER PT J AU Reddick, BH Beresin, EV AF Reddick, BH Beresin, EV TI Rebellious rhapsody - Metal, rap, community, and individuation SO ACADEMIC PSYCHIATRY LA English DT Article ID MUSIC; ADOLESCENTS; SUICIDE AB Music can be a powerful force and tool in the life of an adolescent. It forms a social context anti informs the adolescent about the adult world through the lens of artists' lives, language, and presence as models. Allegiance to a form of music is allegiance to those who make it, a way to friendship and kinship, and a road to personal identity through belonging. In their relationships formed through music, teens can create a sense of community that may be lacking in the life of family. The rebellious music of earlier generations has given rise to complex musical genres, rap and heavy metal, that are strong in defiance and controversial in their violent and sexual content. What do these musical affiliations fell us about certain segments of adolescent development and culture? The authors consider this question by exploring the form and content of the music while using it to illuminate psychodynamic and psychosocial aspects of adolescent development. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Reddick, BH (reprint author), Massachusetts Gen Hosp, Bulfinch 449, Boston, MA 02114 USA. NR 17 TC 5 Z9 5 U1 1 U2 6 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 2002 VL 26 IS 1 BP 51 EP 59 DI 10.1176/appi.ap.26.1.51 PG 9 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 531JA UT WOS:000174411200009 ER PT J AU Seltzer, SE Getty, DJ Pickett, RM Swets, JA Sica, G Brown, J Saini, S Mattrey, RF Harmon, B Francis, IR Chezmar, J Schnall, MO Siegelman, ES Ballerini, R Bhat, S AF Seltzer, SE Getty, DJ Pickett, RM Swets, JA Sica, G Brown, J Saini, S Mattrey, RF Harmon, B Francis, IR Chezmar, J Schnall, MO Siegelman, ES Ballerini, R Bhat, S TI Multimodality diagnosis of liver tumors: Feature analysis with CT, liver-specific and contrast-enhanced MR, and a computer model SO ACADEMIC RADIOLOGY LA English DT Article DE liver; tumors; computer-aided diagnosis ID PROSTATE-CANCER; HEPATIC-LESIONS; MN-DPDP; ACCURACY AB Rationale and Objectives. The purpose of this study was to measure and to clarify the diagnostic contributions of image-based features in differentiating benign from malignant and hepatocyte-containing from non-hepatocyte-containing liver lesions. Materials and Methods. Six experienced abdominal radiologists each read images from 146 cases (including a contrast material-enhanced computed tomographic [CT] scan and contrast-enhanced and unenhanced magnetic resonance [MR] images) following a checklist-questionnaire requiring them to rate quantitatively each of as many as 131 image features and then reported on each of the two differentiations. The diagnostic value of each feature was assessed, and linear discriminant analysis was used to develop statistical prediction rules (SPRs) for merging feature data into computerized "second opinions." For the two differentiations, accuracy (area under the receiver operating characteristic curve [A(z)]) was then determined for the radiologists' readings by themselves and for each of three SPRs. Results. Thirty-seven candidate features had diagnostic value for each of the two differentiations (a slightly different feature set for each). Radiologists' performance at both differentiations was excellent (A(z) = 0.929 [benign vs malignant] and 0.926 [hepatocyte-containing vs non-hepatocyte-containing]). Performance of the SPR that operated on the features from all modalities together was better than that of radiologists (A(z) = 0.936 [benign vs malignant] and 0.951 [hepatocyte-containing vs non-hepatocyte-containing]), but this difference was of marginal statistical significance (P = .11). Contrast-enhanced MR imaging and contrast-enhanced CT each made significant adjunctive contributions to accuracy compared with unenhanced MR imaging alone. Conclusion. Many CT- and MR imaging-based features have diagnostic value in differentiating benign from malignant and hepatocyte-containing from non-hepatocyte-containing liver lesions. Radiologists could also benefit from the fully informed SPR's "second opinions.". C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. BBN Technol, Cambridge, MA USA. Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA. Methodist Hosp, Dept Radiol, Indianapolis, IN USA. Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA. Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. Nycomed Amersham, Princeton, NJ USA. RP Seltzer, SE (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. NR 13 TC 17 Z9 20 U1 0 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 2002 VL 9 IS 3 BP 256 EP 269 DI 10.1016/S1076-6332(03)80368-9 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 527VQ UT WOS:000174209000002 PM 11887942 ER PT J AU Harlow, BL Cohen, LS Otto, MW Liberman, RF Spiegelman, D Cramer, DW AF Harlow, BL Cohen, LS Otto, MW Liberman, RF Spiegelman, D Cramer, DW TI Demographic, family, and occupational characteristics associated with major depression: the Harvard study of moods and cycles SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE major depression; risk factors; sibship; occupation; epidemiologic studies ID COMMUNITY SAMPLE; PREVALENCE; CONSEQUENCES; IMIPRAMINE; PREDICTORS; DISORDER; SYMPTOMS; PATTERN; WEIGHT; HEALTH AB Objective: This study assesses the extent to which women with and without major depression differ by demographic, familial, and occupational characteristics. Method: From a community-based sample, the authors identified 332 women with and 644 women without current or past major depression based on Structured Clinical Interviews for DSM-IV. Demographic and background interviews were conducted in-person. Results: Depressed women were more likely to have gained greater than or equal to35 lbs between age 18 and study enrolment (OR = 1.6. 95% Cl 1,1-2.5) experienced divorce (OR = 2.0, 95% CI 1.4-2.8), or changed occupations (OR = 1.5, 95% CI 1.1-2.1) compared with nondepressed women. Compared with women with no brothers. those with greater than or equal to1 brothers were less likely to have a history of depression (OR = 0.8, 95% CI 0.6-1.1), whereas compared with women with no sisters, those with greater than or equal to1 sisters were more likely to have current or past depression (OR = 1.4, 95% Cl 1.0-1.9). These findings were not influenced by family sibship size. Conclusion: These results illustrate demographic differences between women with and without major depression and that sibship gender rather than size may also influence risk. C1 Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Perinatal Psychiat Clin Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Epidemiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Biostat, Cambridge, MA 02138 USA. RP Harlow, BL (reprint author), Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, 221 Longwood Ave, Boston, MA 02115 USA. FU NIMH NIH HHS [R01-MH-50013] NR 31 TC 22 Z9 22 U1 4 U2 5 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD MAR PY 2002 VL 105 IS 3 BP 209 EP 217 DI 10.1034/j.1600-0447.2002.1o102.x PG 9 WC Psychiatry SC Psychiatry GA 539PV UT WOS:000174880400008 PM 11939975 ER PT J AU Kampman, KM Volpicelli, JR Mulvaney, F Rukstalis, M Alterman, AI Pettinati, H Weinrieb, RM O'Brien, CP AF Kampman, KM Volpicelli, JR Mulvaney, F Rukstalis, M Alterman, AI Pettinati, H Weinrieb, RM O'Brien, CP TI Cocaine withdrawal severity and urine toxicology results from treatment entry predict outcome in medication trials for cocaine dependence SO ADDICTIVE BEHAVIORS LA English DT Article DE cocaine withdrawal; clinical trial; treatment outcome ID PSYCHOTHERAPY; ABSTINENCE; ABUSERS; PHARMACOTHERAPY; ATTRITION AB Both cocaine withdrawal symptoms, measured by an instrument called the Cocaine Selective Severity Assessment (CSSA), and urine toxicology results obtained at the start of treatment have been shown to predict treatment outcome in outpatient cocaine dependence treatment. This study further evaluates the predictive validity of the CSSA and urine toxicology results, alone and in combination. Subjects included 76 cocaine-dependent individuals who participated in 7-week, outpatient, pilot medication trials for cocaine dependence. Predictor variables included CSSA scores and results from a urine toxicology screen obtained on the first day of medication treatment. Successful outcome was defined as 3 continuous weeks of self-reported abstinence from cocaine confirmed by urine toxicology screens. Predictive validity was assessed by logistic regression analysis. Both the urine toxicology screen and the CSSA scores were significant predictors of 3 weeks of continuous abstinence from cocaine, and the inclusion of both variables significantly improved the predictive validity of either variable alone. Urine toxicology results and CSSA scores obtained at treatment entry are useful predictors of outcome in outpatient cocaine dependence treatment. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Univ Penn, Treatment Res Ctr, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Kampman, KM (reprint author), Univ Penn, Treatment Res Ctr, Sch Med, Dept Psychiat, 3900 Chestnut St, Philadelphia, PA 19104 USA. FU NIDA NIH HHS [K20 DA00238, Y01 DA30012] NR 21 TC 51 Z9 51 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD MAR-APR PY 2002 VL 27 IS 2 BP 251 EP 260 DI 10.1016/S0306-4603(01)00171-X PG 10 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 504UL UT WOS:000172874200008 PM 11817766 ER PT J AU Agostini, I Popov, S Hao, T Li, JH Dubrovsky, L Chaika, O Chaika, N Lewis, R Bukrinsky, M AF Agostini, I Popov, S Hao, T Li, JH Dubrovsky, L Chaika, O Chaika, N Lewis, R Bukrinsky, M TI Phosphorylation of Vpr regulates HIV type 1 nuclear import and macrophage infection SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; VIRAL PROTEIN-R; PREINTEGRATION COMPLEX; LOCALIZATION SIGNAL; MATRIX PROTEIN; PORE COMPLEX; VIRION; PATHWAY; CELLS; REPLICATION AB Viral protein R (Vpr) of human immunodeficiency virus type 1 (HIV-1) is a small accessory protein that regulates nuclear import of the viral preintegration complex and facilitates infection of nondividing cells, such as macrophages. Studies demonstrated that a fraction of Vpr molecules is phosphorylated in the virions and in HIV-1-infected cells, but the role of phosphorylation in nuclear import activity of Vpr has not been established. We found that Vpr is phosphorylated predominantly on the serine residue in position 79, and mutations affecting Vpr phosphorylation significantly attenuated viral replication in macrophages, but not in activated T lymphocytes or cell lines. The replication defect was mapped by polymerase chain reaction analysis to the step of nuclear import. These results suggest that phosphorylation of Vpr regulates its activity in the nuclear import of the HIV-1 preintegration complex. C1 George Washington Univ, Dept Microbiol & Trop Med, Washington, DC 20037 USA. Picower Inst Med Res, Manhasset, NY 11030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Zycos, Cambridge, MA 02138 USA. Eppley Canc Inst, Omaha, NE 68198 USA. RP Bukrinsky, M (reprint author), George Washington Univ, Dept Microbiol & Trop Med, Ross Hall,Room 734,2300 Eye St NW, Washington, DC 20037 USA. FU NIAID NIH HHS [AI33776] NR 29 TC 34 Z9 36 U1 0 U2 1 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 1 PY 2002 VL 18 IS 4 BP 283 EP 288 DI 10.1089/088922202753472856 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 524LX UT WOS:000174015800007 PM 11860675 ER PT J AU LaMontagne, AD Herrick, RF Van Dyke, MV Martyny, JW Ruttenber, AJ AF LaMontagne, AD Herrick, RF Van Dyke, MV Martyny, JW Ruttenber, AJ TI Exposure Databases and exposure surveillance: Promise and practice SO AIHAJ LA English DT Article DE exposure database; exposure surveillance; hazard surveillance; industrial hygiene database; intervention effectiveness research; public health surveillance ID PUBLIC-HEALTH; OCCUPATIONAL EXPOSURE; HAZARD SURVEILLANCE; RECOMMENDATIONS; INFORMATION; POLICY AB Based on recent developments in occupational health and a review of industry practices, it is argued that integrated exposure database and surveillance systems hold considerable promise for improving workplace health and safety. A foundation from which to build practical and effective exposure surveillance systems is proposed based on the integration of recent developments in electronic exposure databases, the codification of exposure assessment practice, and the theory and practice of public health surveillance. The merging of parallel, but until now largely separate, efforts in these areas into exposure surveillance systems combines unique strengths from each subdiscipline. The promise of exposure database and surveillance systems, however, is yet to be realized. Exposure surveillance practices in general industry are reviewed based on the published literature as well as an Internet survey of three prominent industrial hygiene e-mail lists. Although the benefits of exposure surveillance are many, relatively few organizations use electronic exposure databases, and even fewer have active exposure surveillance systems. Implementation of exposure databases and surveillance systems can likely be improved by the development of systems that are more responsive to workplace or organizational-level needs. An overview of exposure database software packages provides guidance to readers considering the implementation of commercially available systems. Strategies for improving the implementation of exposure database and surveillance systems are outlined. A companion report in this issue on the development and pilot testing of a workplace-level exposure surveillance system concretely illustrates the application of the conceptual framework proposed. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm Sci & Engn Program, Boston, MA 02115 USA. TriCty Hlth Dept, Commerce City, CO 80222 USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. RP LaMontagne, AD (reprint author), Alfred Hosp, Monash Med Sch, Dept Epidemiol & Prevent Med, Commercial Rd, Prahran, Vic 3181, Australia. FU NIEHS NIH HHS [ES00002]; ODCDC CDC HHS [R01/CCR 812044-01] NR 64 TC 18 Z9 18 U1 1 U2 2 PU AMER INDUSTRIAL HYGIENE ASSOC PI FAIRFAX PA 2700 PROSPERITY AVE #250, FAIRFAX, VA 22031-4307 USA SN 1529-8663 J9 AIHAJ JI AIHAJ PD MAR-APR PY 2002 VL 63 IS 2 BP 205 EP 212 DI 10.1202/0002-8894(2002)063<0205:EDAESP>2.0.CO;2 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 541NX UT WOS:000174991600016 PM 11975658 ER PT J AU LaMontagne, AD Van Dyke, MV Martyny, JW Simpson, MW Holwager, LA Clausen, BM Ruttenber, AJ AF LaMontagne, AD Van Dyke, MV Martyny, JW Simpson, MW Holwager, LA Clausen, BM Ruttenber, AJ TI Development and piloting of an exposure database and surveillance system for DOE cleanup operations SO AIHAJ LA English DT Article DE exposure database; exposure surveillance; hazard surveillance; industrial hygiene database; intervention effectiveness research; public health surveillance AB An industrial hygiene exposure database and surveillance system was developed in partnership between National Institute for Occupational Safety and Health (NIOSH)-funded independent investigators and practicing industrial hygienists at the Rocky Flats Environmental Technology Site (RFETS) in Golden, Colo. RFETS is a former U.S. Department of Energy nuclear weapons plant that is now in cleanup phase. This project is presented as a case study in the development of an exposure database and surveillance system in terms that are generalizable to most other industries and work contexts. Steps include gaining organizational support; defining system purpose and scope; defining database elements and coding; planning practical and efficient analysis strategies; incorporating reporting capabilities; and anticipating communication strategies that maximize the probability that surveillance findings will feed back to preventive applications. For each of these topics, the authors describe both general considerations as well as the specific choices made for this system. An important feature of the system is a two-tier task-coding scheme comprising 33 categories of task groups. Examples of grouped analyses of exposure data captured during the system pilot period demonstrate applications to exposure control, medical surveillance, and other preventive measures. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. TriCty Hlth Dept, Commerce City, CO 80022 USA. Safe Sites Colorado LLC, Rocky Flats Environm Technol Site, Golden, CO 80402 USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. RP LaMontagne, AD (reprint author), Alfred Hosp, Monash Med Sch, Dept Epidemiol & Prevent Med, Commercial Rd, Prahran, Vic 3181, Australia. FU ODCDC CDC HHS [R01/CCR 812044-01] NR 31 TC 1 Z9 1 U1 1 U2 1 PU AMER INDUSTRIAL HYGIENE ASSOC PI FAIRFAX PA 2700 PROSPERITY AVE #250, FAIRFAX, VA 22031-4307 USA SN 1529-8663 J9 AIHAJ JI AIHAJ PD MAR-APR PY 2002 VL 63 IS 2 BP 213 EP 224 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 541NX UT WOS:000174991600017 PM 11975659 ER PT J AU Sands, BE Winston, BD Salzberg, B Safdi, M Barish, C Wruble, L Wilkins, R Shapiro, M Schwertschlag, US AF Sands, BE Winston, BD Salzberg, B Safdi, M Barish, C Wruble, L Wilkins, R Shapiro, M Schwertschlag, US CA Rhil-11 Crohns Study Grp TI Randomized, controlled trial of recombinant: human interleukin-11 in patients with active Crohn's disease SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID INFLAMMATORY BOWEL-DISEASE; INTESTINAL EPITHELIAL-CELLS; CYTOKINES; RATS; PHARMACOKINETICS; PATHOGENESIS; ACTIVATION; EXPRESSION; ETIOLOGY; BIOLOGY AB Background: Interleukin-11 is a mesenchymally derived cytokine with pleiotropic activities. A pilot study suggested therapeutic benefit of recombinant human interleukin-11 (rhIL-11) in patients with Crohn's disease. Aim: To determine the safety and preliminary estimate of efficacy of rhIL-11 in treating active Crohn's disease. Methods: Patients with mild to moderately active Crohn's disease, defined as a Crohn's disease activity index (CDAI) greater than or equal to220 and less than or equal to450, were enrolled in a multicentre trial. Stable doses of 5-aminosalicylates, antibiotics, 6-mercaptopurine or azathioprine were permitted with appropriate wash-in periods. Oral, intravenous or rectally administered corticosteroids were not allowed. Patients were randomized to 6 weeks of subcutaneous injection with rhIL-11 15 mug/kg or placebo weekly, or rhIL-11 7.5 mug/kg or placebo twice weekly. The primary end-point was per cent change in CDAI at week 6; the major secondary end-point was the proportion of patients in remission, defined as a 100 point decrease in CDAI and absolute CDAIless than or equal to150. Results: Baseline characteristics were similar among the 148 evaluated patients (49 placebo, 49 rhIL-11 15 mug/kg once weekly, 50 rhIL-11 7.5 mug/kg twice weekly). Treatment was well-tolerated, with mild injection site reactions occurring more frequently among patients treated with rhIL-11. Headache, oedema, and increased platelet count occurred significantly more often in the rhIL-11 7.5 mug/kg twice weekly group, but not the 15 mug/kg once weekly group. There was a trend toward decreased mean per cent change in CDAI in the rhIL-11 15 mug/kg once weekly group vs. placebo (-31.5% vs. -18.5%, 95% confidence interval for the difference -27.9-1.61%). A significantly greater proportion of patients receiving rhIL-11 15 mug/kg once weekly achieved remission compared to placebo (36.70% vs. 16.3%, 95% confidence interval for the difference 3.4-37.4%; 16.4% for rhIL-11 7.5 mug/kg, N.S.). Conclusions: Weekly subcutaneous injection with rhIL11 15 mug/kg is safe and effective in inducing remission in a subset of patients with active Crohn's disease. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. N Houston Med Res Ctr, Houston, TX USA. Atlanta Gastroenterol Associates, Atlanta, GA USA. Wake Res Associates, Raleigh, NC USA. Consultants Clin Res, Cincinnati, OH USA. Mid S Clin Res Inst, Memphis, TN USA. Genet Inst Inc, Cambridge, MA 02140 USA. RP Sands, BE (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 27 TC 101 Z9 105 U1 0 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD MAR PY 2002 VL 16 IS 3 BP 399 EP 406 DI 10.1046/j.1365-2036.2002.01179.x PG 8 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 531PH UT WOS:000174423800008 PM 11876692 ER PT J AU Voland, P Weeks, DL Vaira, D Prinz, C Sachs, G AF Voland, P Weeks, DL Vaira, D Prinz, C Sachs, G TI Specific identification of three low molecular weight membrane-associated antigens of Helicobacter pylori SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID SEROLOGICAL ASSESSMENT; CAMPYLOBACTER-JEJUNI; ERADICATION THERAPY; PROTEIN; SEQUENCE; ADHESIN; EXPRESSION; DIAGNOSIS; INFECTION; GENE AB Background: A large number of Helicobacter pylori proteins are antigenic, but antibodies to these proteins persist in spite of the eradication of the infection. Methods and results: The analysis of sera from H. pylori-infected and non-infected patients, before and 3 and 5 months after eradication, showed that the antibody response against unknown H. pylori antigens at 32, 30, 22 and 14 kDa in sodium dodecylsulphate polyacrylamide gel electrophoresis decreased by greater than or equal to 60% at 3 months and greater than or equal to 70% at 5 months after treatment. Two-dimensional gel electrophoresis and mass spectrometry allowed the identification of eight proteins at these positions: neuraminyl-lactose-binding haemagglutinin precursor, 3-oxoadipate CoA-transferase subunit A. elongation factor P. peptidoglycan-associated lipoprotein precursor, hypothetical protein HP0596, adhesin-thiol peroxidase, 50S ribosomal protein L7/L12 and subunit b' of the F-0 ATP synthase. Three of these eight. expressed as recombinant proteins (32 kDa neuraminyl-lactose-binding haemagglutinin precursor, 30 kDa peptidoglycan-associated lipoprotein precursor and 22 kDa hypothetical protein HP0596), reacted specifically with sera from infected patients, while the 14 kDa 50S ribosomal protein L7/L12 cross-reacted with one out of live sera from H. pylori-negative patients. The other recombinant proteins did not show significant immunoreactivity. Conclusions: Four low molecular weight antigens were identified by these methods. three of which were specific. Immunoreaction with these three proteins (neuraminyl-lactose-binding haemagglutinin precursor, peptidoglycan-associated lipoprotein precursor and hypothetical protein HP0596) could provide a serological assessment not only of H. pylori infection, but also of eradication. C1 VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. Tech Univ Munich, Dept Med 2, D-8000 Munich, Germany. Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90024 USA. St Orsola Hosp, Bologna, Italy. RP Sachs, G (reprint author), VA Greater Los Angeles Hlth Care Syst, Bldg 113,Rm 324,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK53462, DK41301, DK46917] NR 23 TC 28 Z9 29 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD MAR PY 2002 VL 16 IS 3 BP 533 EP 544 DI 10.1046/j.1365-2036.2002.01221.x PG 12 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 531PH UT WOS:000174423800024 PM 11876708 ER PT J AU Cannon, CP AF Cannon, CP TI To cath or not to cath? That used to be the question SO AMERICAN HEART JOURNAL LA English DT Editorial Material ID WAVE MYOCARDIAL-INFARCTION; ACUTE CORONARY SYNDROMES; ST-SEGMENT ELEVATION; UNSTABLE ANGINA; RANDOMIZED TRIAL; MANAGEMENT; OUTCOMES; STRATEGY; DISEASE C1 Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Cannon, CP (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Dept Med, 75 Francis St, Boston, MA 02115 USA. NR 15 TC 0 Z9 0 U1 1 U2 2 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 2002 VL 143 IS 3 BP 377 EP 380 DI 10.1067/mhj.2002.120971 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 528VU UT WOS:000174265600002 PM 11868039 ER PT J AU Walters, DL Harding, SA Walsh, CR Wong, P Pomerantsev, E Jang, IK AF Walters, DL Harding, SA Walsh, CR Wong, P Pomerantsev, E Jang, IK TI Acute coronary syndrome is a common clinical presentation of in-stent restenosis SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID BALLOON ANGIOPLASTY; ARTERY DISEASE; FOLLOW-UP; THROMBOSIS; PLACEMENT; IMPLANTATION; EXPERIENCE; CARDIOLOGY; REGISTRY; INJURY AB Coronary stents have been the major advancement in percutaneous coronary intervention in the last decade and are used in 60% to 80% of patients. However, in-stent restenosis continues to be a problem, occurring in 20% to 30% of cases. The clinical presentation of patients who develop restenosis after stenting has not been well characterized. In this study we compared the clinical presentation of in-stent restenosis with that of restenosis without stenting. Of 739 patients who underwent percutaneous coronary intervention and had repeat catheterization between October 1, 1997, and June 30, 2000, 262 consecutive patients with recurrent ischemia and restenosis were identified: 191 patients with (group A) and 71 without (Group B) stenting. Patients who underwent interventions in bypass grafts and those who developed early acute stent thrombosis were excluded from the study. Recurrent clinical ischemia occurred at a mean of 5.5 months in group A and 6.5 months in group B (p = 0.24). Rest angina (Braunwald class 11 and 111) was more frequent in group A (48% vs 32%, P = 0.032). Acute coronary syndromes, the combination of rest angina, and acute myocardial infarction were also more frequent in group A (68% vs 46%, p = 0.03). Patients in group A were more likely to have angiographically visible thrombus than those in group B (9% vs 0%, p = 0.02). Thus, acute coronary syndromes are a common clinical presentation of restenosis among patients whose follow-up angiogram is obtained for clinical reasons, and occur more frequently in patients with in-stent restenosis than in those with restenosis without stenting. (C)2002 by Excerpta Medica, Inc. C1 Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Jang, IK (reprint author), Harvard Univ, Div Cardiol, Massachusetts Gen Hosp, Sch Med, Bulfinch 105,55 Fruit St, Boston, MA 02114 USA. RI Walters, Darren/A-7069-2011 NR 29 TC 58 Z9 63 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 1 PY 2002 VL 89 IS 5 BP 491 EP 494 AR PII S0002-9149(01)02285-8 DI 10.1016/S0002-9149(01)02285-8 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526QJ UT WOS:000174140900001 PM 11867029 ER PT J AU Januzzi, JL Sabatine, MS Eagle, KA Evangelista, A Bruckman, D Fattori, R Oh, JK Moore, AG Sechtem, U Llovet, A Gilon, D Pape, L O'Gara, PT Mehta, R Cooper, JV Hagan, PG Armstrong, WF Deeb, GM Suzuki, T Nienaber, CA Isselbacher, EM AF Januzzi, JL Sabatine, MS Eagle, KA Evangelista, A Bruckman, D Fattori, R Oh, JK Moore, AG Sechtem, U Llovet, A Gilon, D Pape, L O'Gara, PT Mehta, R Cooper, JV Hagan, PG Armstrong, WF Deeb, GM Suzuki, T Nienaber, CA Isselbacher, EM CA Int Registry of Aortic Dissection TI Iatrogenic aortic dissection SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article AB As the prevalence of vascular disease increases, the use of invasive diagnostic and therapeutic vascular techniques such as percutaneous revascularization and coronary artery bypass grafting (CABG) will continue to grow. Although relatively rare, aortic dissection (AD) is a major complication of these procedures, and may be life threatening. Despite the potentially catastrophic nature of iatrogenic AD, its associated predisposing risk factors, clinical presentation, and outcome have not been systematically studied. To more accurately define the phenomenon of iatrogenic AD, we utilized the resources of the International Registry of Aortic Dissection (IRAD) to identify such patients and to determine if the risk profile, presentation, and outcome of these patients differed from those with spontaneous AD. C1 Massachusetts Gen Hosp, Thorac Aort Ctr, Boston, MA 02114 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Hosp Gen Univ Vall Hebron, Barcelona, Spain. Univ Hosp S Orsola, Bologna, Italy. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Robert Bosch Krankenhaus, Stuttgart, Germany. Hosp Univ 12 Octubre, Madrid, Spain. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. Univ Massachusetts, Med Ctr, Worcester, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Tokyo, Tokyo, Japan. Univ Hosp Eppendorf, Hamburg, Germany. RP Isselbacher, EM (reprint author), Massachusetts Gen Hosp, Thorac Aort Ctr, 15 Parkman St,WAC-469, Boston, MA 02114 USA. NR 7 TC 68 Z9 73 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 1 PY 2002 VL 89 IS 5 BP 623 EP + AR PII S0002-9149(01)02312-8 DI 10.1016/S0002-9149(01)02312-8 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526QJ UT WOS:000174140900029 PM 11867057 ER PT J AU Dominitz, JA Young, JCC Boyko, EJ AF Dominitz, JA Young, JCC Boyko, EJ TI Outcomes of infants born to mothers with inflammatory bowel disease: A population-based cohort study SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID CARE UTILIZATION INDEX; CROHNS-DISEASE; ULCERATIVE-COLITIS; OLMSTED COUNTY; PRETERM BIRTH; PREGNANCY; WOMEN; FERTILITY; SULPHASALAZINE; MESALAZINE AB OBJECTIVE: Limited population-based data on inflammatory bowel disease (IBD) and pregnancy outcomes exist. The purpose of this study is to determine the association between maternal IBD status and adverse pregnancy outcomes. METHODS: Using computerized birth records of infants born to mothers with Crohn's disease (CD) or ulcerative colitis (UC) and mothers without diagnoses of IBD (no-IBD) in Washington State, we performed a cross-sectional retrospective study to determine gestational age, birth weight, and congenital malformations. RESULTS: Preterm delivery was seen in 15.2% of CD births, 10.4% of UC births, and 7.2% of no-LBD births. Low birth weight was found in 16.8% of CD births, 7.6% of UC births, and 5.3% of no-IBD births. Smallness for gestational age was present in 15.2% of CD births, 10.5% of UC births, and 6.9% of no-IBD births. Only CD births were at significantly increased risk of preterm delivery (p < 0.0025), low birth weight (p < 0.001), and smallness for gestational age (p < 0.001). Congenital malformations were more commonly recorded in UC births than in controls (7.9% vs 1.7%, p < 0.001), whereas 3.4% of CD births had malformations recorded. Using multivariable logistic regression, CD births were more likely to be preterm (odds ratio [OR] 2.3, 95% Cl = 1.4-3.8) and have low birth weights (OR 3.6, CI = 2.2-5.9) and smallness for gestational age (OR 2.3, Cl = 1.3-3.9). UC births were more likely to have congenital malformations reported (OR = 3.8, CI = 1.5-9.8). CONCLUSIONS: Maternal IBD is associated with increased odds of preterm delivery, low birth weight, smallness for gestational age (CD), and reporting of congenital malformations (UC). (Am J Gastroenterol 2002;97:641-648. (C) 2002 by Am. Coll. of Gastroenterology). C1 VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle Div Gastro 111S, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Hlth Serv Res & Dev, Seattle, WA 98195 USA. Childrens Hosp Reg Med Ctr, Dept Pediat, Div Gen Pediat, Seattle, WA USA. RP Dominitz, JA (reprint author), VA Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle Div Gastro 111S, 1660 S Columbian Way, Seattle, WA 98108 USA. OI Dominitz, Jason/0000-0002-8070-7086 FU BHP HRSA HHS [5 T32 PE10002] NR 53 TC 132 Z9 134 U1 2 U2 9 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 MAR PY 2002 VL 97 IS 3 BP 641 EP 648 AR PII S0002-9270(01)04105-3 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 532JA UT WOS:000174469700022 PM 11926208 ER PT J AU Sultzer, DL AF Sultzer, DL TI Neuroimaging: Mapping psychosis in Alzheimer's disease. SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 10 IS 2 SU 1 BP 19 EP 19 PG 1 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 538CB UT WOS:000174795500053 ER PT J AU Samuels, SC Evers, M Lantz, M Datto, CJ Snowden, M Cohen, CI Katz, IR AF Samuels, SC Evers, M Lantz, M Datto, CJ Snowden, M Cohen, CI Katz, IR TI Depression in demented nursing home aged: Optimizing recognition and treatment. SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract C1 Bronx Vet Adm Med Ctr, Bronx, NY USA. Mt Sinai Sch Med, New York, NY USA. Jewish Home & Hosp, New York, NY USA. Univ Penn, Philadelphia, PA 19104 USA. Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 10 IS 2 SU 1 BP 42 EP 43 PG 2 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 538CB UT WOS:000174795500123 ER PT J AU Lantz, M Samuels, SC Evers, M Marin, DB Purohit, D Khan, K Haroutunian, VH AF Lantz, M Samuels, SC Evers, M Marin, DB Purohit, D Khan, K Haroutunian, VH TI Depression screening in the nursing home results in documentation changes. SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract C1 Jewish Home & Hosp, New York, NY USA. Mt Sinai Sch Med, New York, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 10 IS 2 SU 1 BP 43 EP 44 PG 2 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 538CB UT WOS:000174795500125 ER PT J AU Mulsant, BH Pollock, BG Kirshner, M Shen, C Dodge, H Ganguli, M AF Mulsant, BH Pollock, BG Kirshner, M Shen, C Dodge, H Ganguli, M TI Serum anticholinergic activity in a community-based geriatric sample: Relationship with cognitive performance. SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. RI Ganguli, Mary/A-3638-2013; MORAN, CATHERINE/C-9539-2015 NR 0 TC 1 Z9 1 U1 0 U2 0 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 2002 VL 10 IS 2 SU 1 BP 58 EP 58 PG 1 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 538CB UT WOS:000174795500136 ER PT J AU Mulsant, BH Houck, PH Gildengers, AG Dew, MA Pollock, BB Miller, MD Stack, JA Mazumdar, S Reynolds, CF AF Mulsant, BH Houck, PH Gildengers, AG Dew, MA Pollock, BB Miller, MD Stack, JA Mazumdar, S Reynolds, CF TI What is the optimal duration of an acute antidepressant trial when treating geriatric depression? SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 2002 VL 10 IS 2 SU 1 BP 75 EP 75 PG 1 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 538CB UT WOS:000174795500163 ER PT J AU Shores, MM Peskind, ER Wilkinson, CW Raskind, MA AF Shores, MM Peskind, ER Wilkinson, CW Raskind, MA TI Differential response of plasma norepinephrine to antidepressants in Alzheimer's disease and aging. SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Meeting Abstract C1 VA Puget Sound, GRECC, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 10 IS 2 SU 1 BP 91 EP 92 PG 2 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 538CB UT WOS:000174795500201 ER PT J AU Jones, CA Francis, ME Eberhardt, MS Chavers, B Coresh, J Engelgau, M Kusek, JW Byrd-Holt, D Narayan, V Herman, WH Jones, CP Salive, M Agodoa, LY AF Jones, CA Francis, ME Eberhardt, MS Chavers, B Coresh, J Engelgau, M Kusek, JW Byrd-Holt, D Narayan, V Herman, WH Jones, CP Salive, M Agodoa, LY TI Microalbuminuria in the US population: Third National Health and Nutrition Examination Survey SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE Third National Health and Nutrition Examination Survey (NHANES III); population survey; cross-sectional survey; prevalence; microalbuminuria (MA); proteinuria; albuminuria; random untimed urine; albumin-creatinine ratio (ACR); hypertension; diabetes ID URINARY ALBUMIN EXCRETION; DEPENDENT DIABETES-MELLITUS; CARDIOVASCULAR RISK-FACTORS; INSULIN-RESISTANCE SYNDROME; ESSENTIAL-HYPERTENSION; NONDIABETIC SUBJECTS; BLOOD-PRESSURE; RENAL-FUNCTION; CREATININE CLEARANCE; GENERAL-POPULATION AB Microalbuminuria (MA) is associated with adverse health outcomes in diabetic and hypertensive adults. The prevalence and clinical significance of MA in nondiabetic populations is less clear. The purpose of this study was to generate national estimates of the prevalence of MA in the US population. Untimed urinary albumin concentrations (UACs) and creatinine concentrations were evaluated in a nationally representative sample of 22,244 participants aged 6 years and older. Persons with hematuria and menstruating or pregnant women were excluded from analysis. The percent prevalence of clinical proteinuria (UAC greater than or equal to 300 mg/L) was similar for males and females. However, the prevalence of MA (urinary albumin-creatinine ratio [ACR], 30 to 299 mg/g) was significantly lower in males (6.1%) compared with females (9.7%). MA prevalence was greater in children than young adults and increased continuously starting at 40 years of age. MA prevalence was greater in non-Hispanic blacks and Mexican Americans aged 40 to 79 years compared with similar-aged non-Hispanic whites. MA prevalence was 28.8% in persons with previously diagnosed diabetes, 16.0% in those with hypertension, and 5.1% in those without diabetes, hypertension, cardiovascular disease, or elevated serum creatinine levels. In adults aged 40+ years, after excluding persons with clinical proteinuria, albuminuria (defined as ACR 30 mg/g) was independently associated with older age, non-Hispanic black and Mexican American ethnicity, diabetes, hypertension, and elevated serum creatinine concentration. MA is common, even among persons without diabetes or hypertension. Age, sex, race/ethnicity, and concomitant disease contribute to the variability of MA prevalence estimates. (C) 2002 by the National Kidney Foundation, Inc. C1 Joslin Diabet Ctr, Div Genet & Epidemiol, Sect Genet & Epidemiol, Boston, MA 02215 USA. Social & Sci Syst, Silver Spring, MD USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Epidemiol, Hyattsville, MD 20782 USA. Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Univ, Dept Biostat & Med, Baltimore, MD USA. Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. NIDDKD, Clin Trials Program, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. Univ Michigan, Med Ctr, Dept Internal Med, Div Endocrinol & Metab, Ann Arbor, MI 48109 USA. Univ Michigan, Med Ctr, Dept Epidemiol, Div Endocrinol & Metab, Ann Arbor, MI 48109 USA. Assoc Black Cardiologists Inc, Epidemiol & Clin Trials Ctr, Atlanta, GA USA. NHLBI, Div Epidemiol & Clin Applicat, Prevent Sci Res Grp, NIH, Bethesda, MD 20892 USA. NIDDKD, End Stage Renal Dis Program, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. NIDDKD, Minor Hlth Program, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. RP Jones, CA (reprint author), Joslin Diabet Ctr, Div Genet & Epidemiol, Sect Genet & Epidemiol, Rm 368,1 Joslin Pl, Boston, MA 02215 USA. NR 69 TC 251 Z9 269 U1 1 U2 5 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 2002 VL 39 IS 3 BP 445 EP 459 DI 10.1053/ajkd.2002.31388 PG 15 WC Urology & Nephrology SC Urology & Nephrology GA 525UW UT WOS:000174093300001 PM 11877563 ER PT J AU Rabb, H Chandran, PKG Arnaout, MA Kehrli, ME AF Rabb, H Chandran, PKG Arnaout, MA Kehrli, ME TI Use of a bovine model to study the role of adhesion molecule CD11/CD18 in hemodialysis-induced neutropenia SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE hemodialysis (HD); integrins; leukocyte adhesion; neutropenia; cows ID ACUTE-RENAL-FAILURE; HOLSTEIN CATTLE; L-SELECTIN; COMPLEMENT; ACTIVATION; MEMBRANE; DEFICIENCY; DIALYSIS; CD18 AB The early neutropenia that occurs with cellulose-based dialysis membranes is believed to result from a cascade of immune events: complement activation, engagement of leukocyte adhesion molecules, cytokine release, and leukocyte sequestration. The beta(2) integrin CR3 (CD11b/CD18) is upregulated during hemodialysis, binds complement factor iC3b, and mediates leukocyte adhesion to endothelium and leukoaggregation. Despite being invoked in dialysis-induced neutropenia, there is no direct evidence of a role for CD11b/CD18 in the neutropenla. A unique animal model of beta(2)-integrin deficiency was discovered in calves experiencing recurrent infections and a paucity of leukocytes in infected tissue. We hypothesized that beta(2) integrins mediate the neutropenia of dialysis and directly tested this hypothesis using beta(2)-integrin-deficient calves. Two 3-month old beta(2)-integrin-deficient and two age-matched Holstein calves were dialyzed using cuprophane dialyzers. beta(2)-integrin-deficient calves had less than 2% of normal neutrophil CD18 expression by flow cytometry. Normal calves had a marked decrease in circulating neutrophils (P < 0.05) to 15% of normal 15 minutes into dialysis (total, four treatments), as well as a decrease in monocytes to 39% (P < 0.05) and lymphocytes to 58% (P < 0.05). CD18-deficient calves had an attenuated decrease in neutrophils (65%; P = not significant), monocytes (78%; P = not significant), and lymphocytes (105%; P = not significant) at 15 minutes. These data, although obtained in a small sample, show that a bovine model can be used to study the early neutropenia of dialysis. These data also suggest that a direct role of beta(2) integrins may be occurring in this process. (C) 2002 by the National Kidney Foundation, Inc. C1 Johns Hopkins Univ Hosp, Div Nephrol, Baltimore, MD 21205 USA. Nephrol Clin, Des Moines, IA USA. USDA ARS, Natl Anim Dis Ctr, Ames, IA 50010 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Rabb, H (reprint author), Johns Hopkins Univ, Div Nephrol, Ross 970,720 Rutland Ave, Baltimore, MD 21025 USA. NR 20 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAR PY 2002 VL 39 IS 3 BP 587 EP 593 DI 10.1053/ajkd.2002.31416 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 525UW UT WOS:000174093300016 PM 11877578 ER PT J AU Polanczyk, CA Lane, A Coburn, M Philbin, EF Dec, GW DiSalvo, TG AF Polanczyk, CA Lane, A Coburn, M Philbin, EF Dec, GW DiSalvo, TG TI Hospital outcomes in major teaching, minor teaching, and nonteaching hospitals in New York state SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID SEVERITY-ADJUSTED MORTALITY; ACUTE MYOCARDIAL-INFARCTION; MEDICARE BENEFICIARIES; QUALITY; RATES; CARE; PREDICTIONS; ASSOCIATION; DIAGNOSES; LENGTH AB PURPOSE: The possible benefit that hospital teaching status may confer in the care of patients with cardiovascular disease is unknown. Our purpose was to determine the effect of hospital teaching status on in-hospital mortality, use of invasive procedures, length of stay, and charges in patients with myocardial infarction, heart failure, or stroke. SUBJECTS AND METHODS: We analyzed a New York State hospital administrative database containing information on 388 964 consecutive patients who had been admitted with heart failure (n = 173 799), myocardial infarction (n = 121 209), or stroke (n = 93 956) from 1993 to 1995. We classified the 248 participating acute care hospitals by teaching status (major, minor, nonteaching). The primary outcomes were standardized in-hospital mortality ratios, defined as the ratio of observed to predicted mortality. RESULTS: Standardized in-hospital mortality ratios were significantly lower in major teaching hospitals (0.976 for heart failure, 0.945 for myocardial infarction, 0.958 for stroke) than in nonteaching hospitals (1.01 for heart failure, 1.01 for myocardial infarction, 0.995 for stroke). Standardized in-hospital mortality ratios were significantly higher for patients with stroke (1.06) but not heart failure (1.0) or myocardial infarction (1.06) in minor teaching hospitals than in nonteaching hospitals. Compared with nonteaching hospitals, use of invasive cardiac procedures and adjusted hospital charges were significantly greater in major and minor teaching hospitals for all three conditions. The adjusted length of stay was also shorter for myocardial infarction in major teaching hospitals and longer for stroke in minor teaching hospitals. CONCLUSION: Major teaching hospital status was an important determinant of outcomes in patients hospitalized with myocardial infarction, heart failure, or stroke in New York State. (C)2002 by Excerpta Medica, Inc. C1 Massachusetts Gen Hosp, MGH Heart Failure Ctr, Heart Failure & Cardiac Transplantat Unit, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Henry Ford Hlth Syst, Div Cardiovasc Med, Sect Heart Failure & Heart Transplantat, Detroit, MI USA. RP DiSalvo, TG (reprint author), Massachusetts Gen Hosp, MGH Heart Failure Ctr, Heart Failure & Cardiac Transplantat Unit, Div Cardiol, Bigelow 628,55 Fruit St, Boston, MA 02114 USA. RI Polanczyk, Carisi/D-6208-2013 NR 24 TC 62 Z9 63 U1 0 U2 6 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD MAR PY 2002 VL 112 IS 4 BP 255 EP 261 AR PII S0002-9343(01)01112-3 DI 10.1016/S0002-9343(01)01112-3 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 534TE UT WOS:000174602200001 PM 11893363 ER PT J AU Lev, MH AF Lev, MH TI Gliomatosis cerebri has normal relative blood volume: Really?! Who cares? Should you? SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA USA. RP Lev, MH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA USA. NR 3 TC 3 Z9 3 U1 0 U2 0 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 2002 VL 23 IS 3 BP 345 EP 346 PG 2 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 550PT UT WOS:000175512000001 PM 11900995 ER PT J AU Berg, AO Allan, JD Frame, PS Homer, CJ Johnson, MS Klein, JD Lieu, TA Mulrow, CD Murphy, AL Orleans, CT Peipert, JF Pender, NJ Siu, AL Teutsch, SM Westhoff, C Woolf, SH AF Berg, AO Allan, JD Frame, PS Homer, CJ Johnson, MS Klein, JD Lieu, TA Mulrow, CD Murphy, AL Orleans, CT Peipert, JF Pender, NJ Siu, AL Teutsch, SM Westhoff, C Woolf, SH TI Aspirin for the primary prevention of cardiovascular events: Recommendations and rationale SO AMERICAN JOURNAL OF NURSING LA English DT Article ID DISEASE; RISK C1 Univ Washington, Dept Family Med, Seattle, WA 98195 USA. Univ Texas, Hlth Sci Ctr, Sch Nursing, San Antonio, TX USA. Univ Rochester, Sch Med, Rochester, NY USA. Tri Cty Family Med, Cohocton, NY USA. Natl Initiat Childrens Healthcare Qual, Boston, MA USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Family Med, Newark, NJ 07103 USA. Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Texas, Hlth Sci Ctr, Audie L Murphy Mem Vet Hosp, San Antonio, TX USA. Robert Wood Johnson Fdn, Princeton, NJ 08540 USA. Women & Infants Hosp Rhode Isl, Providence, RI 02908 USA. Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. Mt Sinai Sch Med, Div Gen Internal Med, New York, NY USA. Mt Sinai Sch Med, Primary Care & Med Serv Care Ctr, New York, NY USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Merck & Co Inc, Outcomes Res & Management, W Point, PA USA. Columbia Univ Coll Phys & Surg, Dept Obstet & Gynecol, New York, NY 10032 USA. Virginia Commonwealth Univ Med Coll Virginia, Dept Family Practice, Fairfax, VA USA. RP Berg, AO (reprint author), Care Of Atkins D, Agcy Healthcare Res & Qual, Ctr Practice & Technol Assessment, 6010 Execut Blvd,Suite 300, Rockville, MD 20852 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD MAR PY 2002 VL 102 IS 3 BP 67 EP + PG 3 WC Nursing SC Nursing GA 531HR UT WOS:000174410400030 ER PT J AU Barbour, LA Shao, JH Qiao, LP Pulawa, LK Jensen, DR Bartke, A Garrity, M Draznin, B Friedman, JE AF Barbour, LA Shao, JH Qiao, LP Pulawa, LK Jensen, DR Bartke, A Garrity, M Draznin, B Friedman, JE TI Human placental growth hormone causes severe insulin resistance in transgenic mice SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE placental growth hormone; pregnancy; insulin resistance; gestational diabetes ID GESTATIONAL DIABETES-MELLITUS; GLUCOSE-TRANSPORTER PROTEIN; TYROSINE PHOSPHORYLATION; SKELETAL-MUSCLE; FETAL GROWTH; OBESE WOMEN; EXPRESSION; PREGNANCY; METABOLISM; LACTOGEN AB OBJECTIVE: The insulin resistance of pregnancy is considered to be mediated by human placental lactogen, but the metabolic effects of human placental growth hormone have not been well defined. Our aim was to evaluate the effect of placental growth hormone on insulin sensitivity in vivo using transgenic mice that overexpress the human placental growth hormone gene. STUDY DESIGN: Glucose and insulin tolerance tests were performed on 6 transgenic mice that overexpressed the human placental growth hormone variant gene and 6 normal littermate controls. The body composition of the mice was assessed by dual-energy radiograph absorptiometry, and free fatty acid levels were measured as a marker of lipolysis. RESULTS: The human placental growth hormone levels in the transgenic mice were comparable to those attained in the third trimester of pregnancy. These mice were nearly twice as heavy as the control mice, and their body composition differed by a significant increase in bone density and a small decrease in percentage of body fat. Fasting insulin levels in the transgenic mice that overexpressed placental growth hormone were approximately 4-fold higher than the control mice (1.57 +/- 0.22 ng/mL vs 0.38 +/- 0.07 ng/mL; P <.001) and 7 times higher 30 minutes after glucose stimulation (4.17 +/- 0.54 ng/mL vs 0.62 +/- 0.10 ng/mL; P <.0001) with no significant difference in either fasting or postchallenge glucose levels. Insulin sensitivity was markedly decreased in the transgenic mice, as demonstrated by an insignificant decline in glucose levels after insulin injection compared with the control mice, which demonstrated more than a 65% reduction in glucose levels (P <.001). CONCLUSION: Human placental growth hormone causes insulin resistance as manifested by fasting and postprandial hyperinsulinemia and minimal glucose lowering in response to insulin injection. Human placental growth hormone is a highly likely candidate to mediate the insulin resistance of pregnancy. C1 Univ Colorado, Hlth Sci Ctr, Dept Med Obstet & Gynecol, Boulder, CO 80309 USA. Univ Colorado, Hlth Sci Ctr, Dept Pediat, Boulder, CO 80309 USA. So Illinois Univ, Sch Med, Dept Physiol, Chicago, IL 60680 USA. Denver Vet Affais Med Ctr, Div Endocrinol, Denver, CO USA. RP Barbour, LA (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Med Obstet & Gynecol, Boulder, CO 80309 USA. RI Bartke, Andzej/D-6640-2017 OI Bartke, Andzej/0000-0002-2569-557X FU PHS HHS [11089] NR 25 TC 80 Z9 83 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 2002 VL 186 IS 3 BP 512 EP 517 DI 10.1067/mob.2002.121256 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 533WD UT WOS:000174552500030 PM 11904616 ER PT J AU Tolentino, MJ McLeod, DS Taomoto, M Otsuji, T Adamis, AP Lutty, GA AF Tolentino, MJ McLeod, DS Taomoto, M Otsuji, T Adamis, AP Lutty, GA TI Pathologic features of vascular endothelial growth factor-induced retinopathy in the nonhuman primate SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID PROLIFERATIVE DIABETIC-RETINOPATHY; IN-VIVO; RETINAL NEOVASCULARIZATION; IRIS NEOVASCULARIZATION; INHIBITION; PERMEABILITY; ANGIOGENESIS; ISCHEMIA; RATS; LOCALIZATION AB Purpose: Vascular endothelial growth factor (VEGF) is a potent ischemia-upregulated angiogenic protein that has been implicated in diabetic retinopathy. Intravitreal VEGF injections have not previously been shown to produce preretinal neovascularization. The purpose of this study was to further characterize the angiopathic changes that occur after intravitreal injections in a nonhuman primate and determine if preretinal neovascularization develops. Design: Experimental animal study. Methods: Vascular endothelial growth factor 165 was injected into the eyes of normal cynomolgus monkeys at regular intervals. As a control, normal eyes were injected with phosphate buffered saline. Color photography and fluorescein angiography were performed at regular intervals. The retinas were incubated for adenosine diphosphatase (ADPase) activity to visualize retinal vessels. The retinas were flat-embedded and areas of potential preretinal neovascularization were identified en bloc and serially sectioned. Results: Areas of capillary nonperfusion and vessel dilation and tortuousity were seen by angiography. In serial sections, the nonperfused areas were found to be associated with endothelial cell hyperplasia in vessel lumens. Preretinal neovascularization originating only from superficial veins and venules was observed throughout peripheral retina, but was not seen in the posterior pole. Lacunae,like veins were subdivided by the process of intussusception and endothelial cell bridging. Arterioles demonstrated endothelial cell hyperplasia and microaneurysms. Conclusion: Intraocular injections of VEGF were sufficient to produce preretinal neovascularization in the nonhuman primate. Most vasculopathic structures were associated with endothelial cell hyperplasia. These results demonstrate that VEGF alone can produce many features of both nonproliferative and proliferative diabetic retinopathy including the previously undescribed development of preretinal neovascularization. This wells characterized VEGF-induced primate model of retinal neovascularization may be useful as a means of testing new treatments for retinal neovascularization. (Am J Ophthalmol 2002;133:373-385. (C) 2002 by Elsevier Science Inc. All rights reserved.). C1 Univ Penn, Scheie Eye Inst, FM Kirby Ctr Mol Ophthalmol, Philadelphia, PA 19104 USA. Univ Penn, Scheie Eye Inst, Retina Serv, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Wilmer Eye Inst, Dept Ophthalmol, Baltimore, MD 21218 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA USA. RP Lutty, GA (reprint author), Johns Hopkins Univ Hosp, Wilmer Ophthalmol Inst, 170 Woods Res Bldg,600 N Wolfe St, Baltimore, MD 21287 USA. NR 35 TC 142 Z9 154 U1 0 U2 3 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 2002 VL 133 IS 3 BP 373 EP 385 AR PII S0002-9394(01)01381-2 DI 10.1016/S0002-9394(01)01381-2 PG 13 WC Ophthalmology SC Ophthalmology GA 528WX UT WOS:000174268600011 PM 11860975 ER PT J AU Morikawa, S Baluk, P Kaidoh, T Haskell, A Jain, RK McDonald, DM AF Morikawa, S Baluk, P Kaidoh, T Haskell, A Jain, RK McDonald, DM TI Abnormalities in pericytes on blood vessels and endothelial sprouts in tumors SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SMOOTH-MUSCLE CELLS; IN-VITRO; AMINOPEPTIDASE-N; HEALING WOUNDS; STROMAL CELLS; PDGF-B; ANGIOGENESIS; GROWTH; EXPRESSION; MOUSE AB Endothelial cells of tumor vessels have well-documented alterations, but it is less clear whether pericytes on these vessels are abnormal or even absent. Here we report that alpha-smooth muscle actin (alpha-SMA) and desmin-immunoreactive pericytes; were present on >97% of blood vessels viewed by confocal microscopy in 100-mum-thick sections of three different spontaneous or implanted tumors In mice. However, the cells had multiple abnormalities. Unlike pericytes; on capillaries in normal pancreatic islets, which had desmin but not alpha-SMA immunoreactivity, pericytes on capillary-size vessels in insulinomas in RIP-Tag2 transgenic mice expressed both desmin and alpha-SMA. Furthermore, pericytes in RIP-Tag2 tumors, as well as those in MCa-IV breast carcinomas and Lewis lung carcinomas, had an abnormally loose association with endothelial cells and extended cytoplasmic processes deep into the tumor tissue. alpha-SMA-positive pericytes also covered 73% of endothelial sprouts in RIP-Tag2 tumors and 92% of sprouts in the other tumors. Indeed, pericyte sleeves were significantly longer than the CD31-immunoreactive endothelial cell sprouts themselves in all three types of tumors. All three tumors also contained alpha-SMA-positive myo-fibroblasts that resembled pericytes but were not associated with blood vessels. We conclude that pericytes are present on most tumor vessels but have multiple abnormalities, including altered expression of marker proteins. In contrast to some previous studies, the almost ubiquitous presence of pericytes on tumor vessels found in the present study may be attributed to our use of both desmin and alpha-SMA as markers and 100-mum-thick tissue sections. The association of pericytes with endothelial sprouts raises the possibility of an involvement in sprout growth or retraction in tumors. C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Edwin L Steele Lab, Dept Radiat Oncol, Boston, MA 02114 USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Cardiovasc Res Inst S1363, San Francisco, CA 94143 USA. RP McDonald, DM (reprint author), Univ Calif San Francisco, Cardiovasc Res Inst S1363, 513 Parnassus Ave, San Francisco, CA 94143 USA. FU NHLBI NIH HHS [HL24136, HL59157, P01 HL024136, R01 HL059157] NR 67 TC 509 Z9 544 U1 4 U2 34 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 MAR PY 2002 VL 160 IS 3 BP 985 EP 1000 DI 10.1016/S0002-9440(10)64920-6 PG 16 WC Pathology SC Pathology GA 528QU UT WOS:000174255100025 PM 11891196 ER PT J AU Beil, M Leser, J Lutz, MP Gukovskaya, A Seufferlein, T Lynch, G Pandol, SJ Adler, G AF Beil, M Leser, J Lutz, MP Gukovskaya, A Seufferlein, T Lynch, G Pandol, SJ Adler, G TI Caspase 8-mediated cleavage of plectin precedes F-actin breakdown in acinar cells during pancreatitis SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE cholecystokinin; cytoskeleton; pancreas; secretion ID INTERMEDIATE FILAMENTS; EPIDERMOLYSIS-BULLOSA; MUSCULAR-DYSTROPHY; ENZYME ACTIVATION; CYTOSKELETON; APOPTOSIS; ORGANIZATION; BINDING; KINASE; IDENTIFICATION AB Pancreatic acinar cells depend on the integrity of the cytoskeleton for regulated secretion. Stimulation of isolated rat pancreatic acini with the secretagogue CCK serves as a model for human acute edematous pancreatitis. It induces the breakdown of the actin filament system (F-actin) with the consecutive inhibition of secretion and premature activation of digestive enzymes. However, the mechanisms that regulate F-actin breakdown are largely unknown. Plectin is a versatile cytolinker protein regulating F-actin dynamics in fibroblasts. It was recently demonstrated that plectin is a substrate of caspase 8. In pancreatic acinar cells, plectin strongly colocalizes with apical and basolateral F-actin. Supramaximal secretory stimulation of acini with CCK leads to a rapid redistribution and activation of caspase 8, followed by degradation of plectin that in turn precedes the F-actin breakdown. Inhibition of caspase 8 before CCK hyperstimulation prevents plectin cleavage, stabilizes F-actin morphology, and reverses the inhibition of secretion. Thus we propose that the caspase 8-mediated degradation of plectin represents a critical biochemical event during CCK-induced secretory blockade and cell injury. C1 Univ Ulm, Dept Internal Med 1, D-89070 Ulm, Germany. Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Adler, G (reprint author), Univ Ulm, Dept Internal Med 1, D-89070 Ulm, Germany. OI Lutz, Manfred/0000-0003-1989-4553 NR 52 TC 34 Z9 35 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAR PY 2002 VL 282 IS 3 BP G450 EP G460 DI 10.1152/ajpgi.00042.2001 PG 11 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 525UE UT WOS:000174091800007 PM 11841995 ER PT J AU Dai, DW Nanthakumar, NN Savidge, TC Newburg, DS Walker, WA AF Dai, DW Nanthakumar, NN Savidge, TC Newburg, DS Walker, WA TI Region-specific ontogeny of alpha-2,6-sialyltransferase during normal and cortisone-induced maturation in mouse intestine SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE sialyl alpha-2,6 glycoconjugates; hormonal regulation; ontogeny of the gut; lectin ID BETA-GALACTOSIDE ALPHA-2,6-SIALYLTRANSFERASE; RAT SMALL-INTESTINE; TISSUE-SPECIFIC EXPRESSION; EPITHELIAL-CELLS; GENE-EXPRESSION; SUCKLING RATS; PHOSPHOENOLPYRUVATE CARBOXYKINASE; TRANSCRIPTIONAL REGULATION; POSTNATAL-DEVELOPMENT; HORMONAL-REGULATION AB Regional differences in the ontogeny of mouse intestinal alpha-2,6-sialyltransferase activities (alpha-2,6-ST) and the influence of cortisone acetate (CA) on this expression were determined. High ST activity and alpha-2,6-ST mRNA levels were detected in immature small and large intestine, with activity increasing distally from the duodenum. As the mice matured, ST activity (predominantly alpha-2,6-ST) in the small intestine decreased rapidly to adult levels by the fourth postnatal week. CA precociously accelerated this region-specific ontogenic decline. A similar decline of ST mRNA levels reflected ST activity in the small, but not the large, intestine. Small intestinal sialyl alpha-2,6-linked glycoconjugates displayed similar developmental and CA induced-precocious declines when probed using Sambucus nigra agglutinin (SNA) lectin. SNA labeling demonstrated age-dependent diminished sialyl alpha2,6 glycoconjugate expression in goblet cells in the small (but not large) intestine, but no such regional specificity was apparent in microvillus membrane. This suggests differential regulation of sialyl alpha-2,6 glycoconjugates in absorptive vs. globlet cells. These age-dependent and region-specific differences in sialyl alpha-2,6 glycoconjugates may be mediated in part by altered alpha-2,6-ST gene expression regulated by trophic factors such as glucocorticoids. C1 Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Dev Gastroenterol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Eunice Kennedy Shriver Ctr Mental Retardat Inc, Program Glycobiol, Waltham, MA 02452 USA. RP Walker, WA (reprint author), Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Dev Gastroenterol Lab, 114 16th St,114-3510, Charlestown, MA 02129 USA. FU FIC NIH HHS [D43-TW-01265]; NIAID NIH HHS [AI-434472]; NICHD NIH HHS [HD-12437, HD-31852, HD-13021]; NIDDK NIH HHS [P30-DK-40561, P01-DK-33506] NR 65 TC 17 Z9 18 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAR PY 2002 VL 282 IS 3 BP G480 EP G490 DI 10.1152/ajpgi.00531.2002 PG 11 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 525UE UT WOS:000174091800010 PM 11841998 ER PT J AU Holschneider, DP Scremin, OU Roos, KP Chialvo, DR Chen, K Shih, JC AF Holschneider, DP Scremin, OU Roos, KP Chialvo, DR Chen, K Shih, JC TI Increased baroreceptor response in mice deficient in monoamine oxidase A and B SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE arterial baroreceptor reflex; serotonin; norepinephrine; phenylethylamine; dopamine; blood pressure; heart rate; sympathetic nervous system ID NUCLEUS-TRACTUS-SOLITARIUS; SPONTANEOUSLY HYPERTENSIVE RATS; AUTONOMIC NERVOUS-SYSTEM; BLOOD-PRESSURE RESPONSE; HEART-RATE; CONSCIOUS RABBITS; BAROREFLEX CONTROL; TRANSGENIC MICE; REFLEX; RECEPTORS AB The recent development of mice doubly deficient for monoamine oxidase A and B (MAO-A/B, respectively) has raised questions about the impact of these mutations on cardiovascular function, in so far as these animals demonstrate increased tissue levels of the vasoactive amines serotonin, norepinephrine, dopamine, and phenylethylamine. We recorded femoral arterial pressures and electrocardiograms in adult MAO-A/B-deficient mice during halothane-nitrous oxide anesthesia as well as 30 min postoperatively. During both anesthesia and recovery, systolic, diastolic, and mean arterial pressures were 10-15 mmHg lower in MAO-A/B-deficient mice compared with normal controls (P < 0.01). Mutants also showed a greater baroreceptor-mediated reduction in heart rate in response to hypertension after intravenous pulses of phenylephrine or angiotensin II. Tachycardia elicited in response to hypotension after nitroprusside was greater in mutants than in controls. Heart rate responsiveness to changes in arterial pressure was abolished after administration of glycopyrrolate, with no differences in this phenomenon noted between genotypes. These data suggest that prevention of hypertension may occur in chronic states of catecholaminergic/indoleaminergic excess by increased gain of the baroreflex. C1 Univ So Calif, Dept Psychiat & Behav Sci, Keck Sch Med, Los Angeles, CA 90089 USA. Univ So Calif, Dept Neurol, Keck Sch Med, Los Angeles, CA 90089 USA. Univ So Calif, Dept Cell & Neurobiol, Keck Sch Med, Los Angeles, CA 90089 USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Physiol, Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Cardiovasc Res Lab, Sch Med, Los Angeles, CA 90024 USA. Rockefeller Univ, Ctr Studies Phys & Biol, New York, NY 10021 USA. Univ So Calif, Sch Pharm, Dept Mol Pharmacol & Toxicol, Los Angeles, CA 90089 USA. RP Holschneider, DP (reprint author), Univ So Calif, Keck Sch Med, LAC USC Hosp, Dept Psychiat, 1200 N State St,Rm 10-621, Los Angeles, CA 90033 USA. RI Chialvo, Dante/A-4658-2009 OI Chialvo, Dante/0000-0002-1038-3637 FU NIMH NIH HHS [R01 MH-37020, KO5 MH-00796, R01 MH-NS-62148, R37 MH-39085] NR 50 TC 11 Z9 12 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAR PY 2002 VL 282 IS 3 BP H964 EP H972 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 520JT UT WOS:000173779300023 PM 11834493 ER PT J AU Kling, DE Lorenzo, HK Trbovich, AM Kinane, TB Donahoe, PK Schnitzer, JJ AF Kling, DE Lorenzo, HK Trbovich, AM Kinane, TB Donahoe, PK Schnitzer, JJ TI Pre- and postnatal lung development, maturation, and plasticity - MEK-1/2 inhibition reduces branching morphogenesis and causes mesenchymal cell apoptosis in fetal rat lungs SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE lung development; mitogen-activated protein kinase; extracellular signal-regulated kinase; U-0126 ID PROTEIN-KINASE KINASE; CONGENITAL DIAPHRAGMATIC-HERNIA; NUCLEAR ANTIGEN; PROGENITOR CELLS; MOUSE LUNG; GROWTH; RECEPTOR; PROLIFERATION; ACTIVATION; EXPRESSION AB The roles of the mitogen-activated protein (MAP) kinases extracellular signal-regulated kinases-1 and -2 (ERK-1/2) in fetal lung development have not been extensively characterized. To determine if ERK-1/2 signaling plays a role in fetal lung branching morphogenesis, U-0126, an inhibitor of the upstream kinase MAP ERK kinase (MEK), was added to fetal lung explants in vitro. Morphometry as measured by branching, area, perimeter, and complexity were significantly reduced in U-0126-treated lungs. At the same time, U-0126 treatment reduced ERK-1/2, slightly increased p38 kinase, but did not change c-Jun NH2-terminal kinase activities, indicating that U-0126 specifically inhibited the ERK-1/2 enzymes. These changes were associated with increased apoptosis as measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and immunofluorescent labeling of anti-active caspase-3 in the mesenchyme of explants after U-0126 treatment compared with the control. Mitosis characterized by immunolocalization of proliferating cell nuclear antigen was found predominantly in the epithelium and was reduced in U-0126-treated explants. Thus U-0126 causes specific inhibition of ERK-1/2 signaling, diminished branching morphogenesis, characterized by increased mesenchymal apoptosis, and decreased epithelial proliferation in fetal lung explants. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Surg Serv,Pediat Surg Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Schnitzer, JJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Surg Serv,Pediat Surg Res Labs, 55 Fruit St,WRN 1159, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-62615]; NICHD NIH HHS [P01 HD-39942] NR 38 TC 41 Z9 43 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD MAR PY 2002 VL 282 IS 3 BP L370 EP L378 PG 9 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 521HA UT WOS:000173832100004 PM 11839529 ER PT J AU Arystarkhova, E Wetzel, RK Sweadner, KJ AF Arystarkhova, E Wetzel, RK Sweadner, KJ TI Distribution and oligomeric association of splice forms of Na(+)-K(+)-ATPase regulatory gamma-subunit in rat kidney SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE sodium pump; nephron; immunofluorescence; confocal microscopy ID ACTIVATED ADENOSINE-TRIPHOSPHATASE; PROXIMAL CONVOLUTED TUBULE; ALPHA-BETA-UNITS; PROTEIN-KINASE-C; IMMUNOCYTOCHEMICAL LOCALIZATION; CROSS-LINKING; EXTRACELLULAR SURFACE; RENAL NA+,K+-ATPASE; MONOCLONAL-ANTIBODY; XENOPUS OOCYTES AB Renal Na(+)-K(+)-ATPase is associated with the gamma-subunit (FXYD2), a single-span membrane protein that modifies ATPase properties. There are two splice variants with different amino termini, gamma(a) and gamma(b). Both were found in the inner stripe of the outer medulla in the thick ascending limb. Coimmunoprecipitation with each other and the alpha-subunit indicated that they were associated in macromolecular complexes. Association was controlled by ligands that affect Na(+)-K(+)-ATPase conformation. In the cortex, the proportion of the gamma(b)-subunit was markedly lower, and the gamma(a)-subunit predominated in isolated proximal tubule cells. By immunofluorescence, the gamma(b)-subunit was detected in the superficial cortex only in the distal convoluted tubule and connecting tubule, which are rich in Na(+)-K(+)-ATPase but comprise a minor fraction of cortex mass. In the outer stripe of the outer medulla and for a short distance in the deep cortex, the thick ascending limb predominantly expressed the gamma(b)-subunit. Because different mechanisms maintain and regulate Na(+) homeostasis in different nephron segments, the splice forms of the gamma-subunit may have evolved to control the renal Na(+) pump through pump properties, gene expression, or both. C1 Massachusetts Gen Hosp, Ctr Neurosci, Lab Membrane Biol, Charlestown, MA 02129 USA. RP Sweadner, KJ (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Lab Membrane Biol, 149-6118,149 13th St, Charlestown, MA 02129 USA. EM sweadner@helix.mgh.harvard.edu FU NHLBI NIH HHS [HL36271] NR 63 TC 49 Z9 50 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 2002 VL 282 IS 3 BP F393 EP F407 PG 15 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 520JQ UT WOS:000173779100003 PM 11832419 ER PT J AU Breton, S Inoue, T Knepper, MA Brown, D AF Breton, S Inoue, T Knepper, MA Brown, D TI Antigen retrieval reveals widespread basolateral expression of syntaxin 3 in renal epithelia SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE soluble N-ethylmaleimide-sensitive factor attachment protein receptor; urinary tubule; basolateral membrane ID CANINE KIDNEY-CELLS; MEMBRANE-FUSION; TRANSPORT; SNARES; SPECIFICITY; RECEPTORS; VESICLES; DOCKING AB Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins play a key role in docking and fusion of intracellular transport vesicles and may regulate apical and basolateral membrane protein delivery in epithelial cells. In a previous study, syntaxin 3 (a target SNARE) protein was detectable in the kidney only in intercalated cells. We now report a more widespread distribution of syntaxin 3 in a variety of renal epithelial cells after antigen retrieval. Sections of rat kidney were treated with SDS and incubated with antisyntaxin 3 antibodies. Strong basolateral membrane staining was seen in descending and ascending thin limbs of Henle, thick ascending limbs of Henle, the macula densa, distal and connecting tubules, and all cells of the collecting duct including A- and B-intercalated cells. The papillary surface epithelium and the transitional epithelium of the ureter were also stained, but proximal tubules were negative. Western blotting revealed a strong signal at 37 kDa in all regions, and the antigen was restricted to membrane fractions. SDS treatment was not necessary to reveal syntaxin 3 in intercalated cells. These data show that syntaxin 3 might be involved in basolateral trafficking pathways in most renal epithelial cell types. The exclusive basolateral location of syntaxin 3 in situ, however, contrasts with the apical location of this SNARE protein in some kidney epithelial cells in culture. C1 Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Brown, D (reprint author), Massachusetts Gen Hosp E, Program Membrane Biol, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. EM brown@receptor.mgh.harvard.edu FU Intramural NIH HHS [Z99 HL999999, Z01 HL001285-21]; NHLBI NIH HHS [Z01-HL-01282-KE]; NIDDK NIH HHS [DK-42956] NR 23 TC 10 Z9 11 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 2002 VL 282 IS 3 BP F523 EP F529 PG 7 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 520JQ UT WOS:000173779100019 PM 11832435 ER PT J AU Nagami, GT AF Nagami, GT TI Enhanced ammonia secretion by proximal tubules from mice receiving NH(4)Cl: role of angiotensin II SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE transport; ammoniagenesis; acid-base physiology; losartan; ammonium chloride ID METABOLIC-ACIDOSIS; PERFUSED INVITRO; RAT; TRANSPORT; KIDNEY; BASE AB Acidosis and angiotensin II (ANG II) stimulate ammonia production and transport by the proximal tubule. We examined the effect of short-term (18 h) in vivo acid loading with NH(4)Cl on ammonia production and secretion rates by mouse S2 proximal tubule segments microperfused in vitro with or without ANG II in the luminal microperfusion solution. S2 tubules from NH(4)Cl-treated mice displayed higher rates of luminal ammonia secretion compared with those from control mice. The adaptive increase in ammonia secretion in NH(4)Cl-treated mice was eliminated when losartan was coadministered in vivo with NH(4)Cl. Ammonia secretion rates from both NH(4)Cl-treated and control mice were largely inhibited by amiloride. Addition of ANG II to the microperfusion solution enhanced ammonia secretion and production rates to a greater extent in tubules from NH(4)Cl-treated mice compared with those from controls, and the stimulatory effects of ANG II were blocked by losartan. These results demonstrate that a short-term acid challenge induces an adaptive increase in ammonia secretion by the proximal tubule and suggest that ANG II plays an important role in the adaptive enhancement of ammonia secretion that is observed with short-term acid challenges. C1 Vet Affairs Greater Los Angeles Healthcare Syst W, Med Serv, Nephrol Sect 111L, Los Angeles, CA 90073 USA. Vet Affairs Greater Los Angeles Healthcare Syst W, Res Serv, Nephrol Sect 111L, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA. RP Nagami, GT (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst W, Med Serv, Nephrol Sect 111L, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM gnagami@ucla.edu NR 30 TC 19 Z9 20 U1 0 U2 1 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 2002 VL 282 IS 3 BP F472 EP F477 PG 6 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 520JQ UT WOS:000173779100012 PM 11832428 ER PT J AU Yoder, BK Tousson, A Millican, L Wu, JH Bugg, CE Schafer, JA Balkovetz, DF AF Yoder, BK Tousson, A Millican, L Wu, JH Bugg, CE Schafer, JA Balkovetz, DF TI Polaris, a protein disrupted in orpk mutant mice, is required for assembly of renal cilium SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE Tg737; ciliogenesis; cell line; polycystic kidney disease; Madin-Darby canine kidney cells; Oak Ridge Polycystic Kidney ID POLYCYSTIC KIDNEY-DISEASE; CELL-CELL ADHESION; INTRAFLAGELLAR TRANSPORT IFT; CAENORHABDITIS-ELEGANS; EPITHELIAL-CELLS; C-ELEGANS; CPK GENE; MOUSE; MUTATION; MEMBRANE AB Cilia are organelles that play diverse roles, from fluid movement to sensory reception. Polaris, a protein associated with cystic kidney disease in Tg737(orpk) mice, functions in a ciliogenic pathway. Here, we explore the role of polaris in primary cilia on Madin-Darby canine kidney cells. The results indicate that polaris localization and solubility change dramatically during cilia formation. These changes correlate with the formation of basal bodies and large protein rafts at the apical surface of the epithelia. A cortical collecting duct cell line has been derived from mice with a mutation in the Tg737 gene. These cells do not develop normal cilia, which can be corrected by reexpression of the wild-type Tg737 gene. These data suggest that the primary cilia are important for normal renal function and/or development and that the ciliary defect may be a contributing factor to the cystic disease in Tg737(orpk) mice. Further characterization of these cells will be important in elucidating the physiological role of renal cilia and in determining their relationship to cystic disease. C1 Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA. Univ Alabama, High Resolut Imaging Facil, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. Univ Alabama, Dept Physiol & Biophys, Birmingham, AL 35294 USA. Univ Alabama, Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. RP Yoder, BK (reprint author), Univ Alabama, Dept Cell Biol, 1530 3rd Ave S,MCLM652, Birmingham, AL 35294 USA. EM Byoder@uab.edu FU NIDDK NIH HHS [1RO1-DK-55007-01] NR 57 TC 114 Z9 118 U1 0 U2 4 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 2002 VL 282 IS 3 BP F541 EP F552 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 520JQ UT WOS:000173779100021 PM 11832437 ER PT J AU Pollock, BG Mulsant, BH Rosen, J Sweet, RA Mazumdar, S Bharucha, A Marin, R Jacob, NJ Huber, KA Kastango, KB Chew, ML AF Pollock, BG Mulsant, BH Rosen, J Sweet, RA Mazumdar, S Bharucha, A Marin, R Jacob, NJ Huber, KA Kastango, KB Chew, ML TI Comparison of citalopram, perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbances in hospitalized, demented patients SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 14th Annual Meeting of the American-Association-for-Geriatric-Psychiatry CY FEB 23-26, 2001 CL SAN FRANCISCO, CALIFORNIA SP Amer Assoc Geriatr Psychiat ID ALZHEIMERS-DISEASE; DOUBLE-BLIND; NEUROLEPTIC TREATMENT; CLINICIAN; SEROTONIN; DIAGNOSIS; AGITATION; TRIAL; AD AB Objective: Until recently, conventional antipsychotics were the standard pharmacotherapy for psychosis and behavioral disturbances associated with dementia. This double-blind, placebo-controlled study compared the acute efficacy of the selective serotonin reuptake inhibitor citalopram and the neuroleptic perphenazine with placebo for the treatment of psychosis and behavioral disturbances in nondepressed patients with dementia. Method: Eighty-five hospitalized patients with at least one moderate to severe target symptom (aggression, agitation, hostility, suspiciousness, hallucinations, or delusions) were randomly assigned to receive either citalopram, perphenazine, or placebo under double-blind conditions for up to 17 days. Results: Patients treated with citalopram or perphenazine showed statistically significant improvement on several Neurobehavioral Rating Scale factor scores. Compared to those receiving placebo, only patients treated with citalopram showed significantly greater improvement in their total Neurobehavioral Rating Scale score as well as in the scores for the agitation/aggression and lability/tension factors. Side effect scores were similar among the three treatment groups. Conclusions: Citalopram was found to be more efficacious than placebo in the short-term hospital treatment of psychotic symptoms and behavioral disturbances in nondepressed, demented patients. C1 Univ Pittsburgh, Sch Med, Geriatr Psychopharmacol Program, Acad Div Geriatr & Neuropsychiat,Dept Psychiat, Pittsburgh, PA USA. VA Pittsburgh Hlth Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Pollock, BG (reprint author), Western Psychiat Inst & Clin, Geriatr Psychopharmacol Program, 3811 OHara St, Pittsburgh, PA 15213 USA. FU NCRR NIH HHS [RR-00056]; NIMH NIH HHS [MH-01509, MH-01613, MH-52247, MH-55106, MH-59666] NR 32 TC 157 Z9 162 U1 0 U2 6 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 2002 VL 159 IS 3 BP 460 EP 465 DI 10.1176/appi.ajp.159.3.460 PG 6 WC Psychiatry SC Psychiatry GA 527KZ UT WOS:000174186400019 PM 11870012 ER PT J AU Tsuang, MT Williams, WM Simpson, JC Lyons, MJ AF Tsuang, MT Williams, WM Simpson, JC Lyons, MJ TI Pilot study of spirituality and mental health in twins SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PERSONALITY; MODEL AB Objective: The goal of this study was to investigate associations between empirically defined dimensions of spirituality, personality variables, and psychiatric disorders in Vietnam era veterans. Method: One hundred pairs of male twins from the Vietnam Era Twin Registry were administered the self-report Spiritual Well-Being Scale and a pilot index of Spiritual Involvement. Correlation analyses were supplemented with regression analyses that examined the relative influence of genetic and environmental factors on aspects of spirituality. Results: Existential well-being was significantly associated with seven of 11 dimensions of personality and was significantly negatively associated with alcohol abuse or dependence and with two of three clusters of personality disorder symptoms. Associations between mental health variables and religious well-being or spiritual involvement were much more limited. Conclusions: Useful distinctions can be made between major dimensions of spirituality in studies of spirituality, religious coping, and mental health. C1 Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr,Dept Psychiat, Harvard Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, VA Boston Healthcare Syst, Boston, MA 02115 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP Tsuang, MT (reprint author), Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr,Dept Psychiat, Harvard Inst Psychiat Epidemiol & Genet, 74 Fenwood Rd, Boston, MA 02115 USA. RI Lyons, Michael/B-6119-2011; OI Lyons, Michael/0000-0001-6516-9219 FU NIDA NIH HHS [DA-04604]; NIMH NIH HHS [MH-60485] NR 8 TC 28 Z9 29 U1 1 U2 6 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 2002 VL 159 IS 3 BP 486 EP 488 DI 10.1176/appi.ajp.159.3.486 PG 3 WC Psychiatry SC Psychiatry GA 527KZ UT WOS:000174186400026 PM 11870019 ER PT J AU Thorndike, AN Biener, L Rigotti, NA AF Thorndike, AN Biener, L Rigotti, NA TI Effect on smoking cessation of switching nicotine replacement therapy to over-the-counter status SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID PATCH USERS; METAANALYSIS AB Objectives. This study examined whether the change in nicotine replacement therapy sales from prescription to over the counter (OTC) status affected smoking cessation. Methods. We used the 1993-1999 Massachusetts Tobacco Surveys to compare data from adult current smokers and recent quitters before and after the OTC switch. Results. No significant change over time occurred in the proportion of smokers who used nicotine replacement therapy at a quit attempt in the past year (20.1% pre-OTC vs 21.4% post-OTC), made a quit attempt in the past year (48.1% vs 45.2%), or quit smoking in the past year (8.1% vs 11.1%). Fewer non-Whites used nicotine replacement therapy after the switch (20.7% pre-OTC vs 3.2% post-OTC, P = .002), but the proportion of Whites using nicotine replacement therapy did not change significantly (20.6% vs 24.0%). Conclusions. We observed no increase in Massachusetts smokers' rates of using nicotine replacement therapy, making a quit attempt, or stopping smoking after nicotine replacement therapy became available for OTC sale. There appear to be other barriers to the use of nicotine replacement therapy besides visiting a physician, especially among minority smokers. C1 Massachusetts Gen Hosp, Gen Med Unit, Div Gen Med, Tobacco Res & Treatment Ctr,Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Massachusetts, Surg Res Ctr, Boston, MA 02125 USA. Massachusetts Gen Hosp, Partners HealthCare Syst Inc, Inst Hlth Policy, Boston, MA 02114 USA. RP Thorndike, AN (reprint author), Massachusetts Gen Hosp, Gen Med Unit, Div Gen Med, Tobacco Res & Treatment Ctr,Med Serv, S50-9, Boston, MA 02114 USA. OI Biener, Lois/0000-0002-4130-8138 NR 21 TC 72 Z9 72 U1 1 U2 4 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAR PY 2002 VL 92 IS 3 BP 437 EP 442 DI 10.2105/AJPH.92.3.437 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 525MU UT WOS:000174076200032 PM 11867326 ER PT J AU Smith, JJ Berlin, L AF Smith, JJ Berlin, L TI The infected or substance abuse-impaired radiologist SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 Rush N Shore Med Ctr, Dept Radiol, Skokie, IL 60076 USA. Rush Med Coll, Dept Radiol, Chicago, IL 60612 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Berlin, L (reprint author), Rush N Shore Med Ctr, Dept Radiol, 9600 Gross Point Rd, Skokie, IL 60076 USA. NR 4 TC 3 Z9 4 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 2002 VL 178 IS 3 BP 567 EP 571 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 525EH UT WOS:000174055400006 PM 11856675 ER PT J AU Maher, MM Lucey, BC Boland, G Gervais, DA Mueller, PR AF Maher, MM Lucey, BC Boland, G Gervais, DA Mueller, PR TI The role of interventional radiology in the treatment of mediastinal collections caused by esophageal anastomotic leaks SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CONTRAST C1 Harvard Univ, Sch Med, Div Abdominal Imaging & Interventional Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mueller, PR (reprint author), Harvard Univ, Sch Med, Div Abdominal Imaging & Interventional Radiol, 55 Fruit St White 270, Boston, MA 02114 USA. NR 8 TC 7 Z9 10 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 2002 VL 178 IS 3 BP 649 EP 653 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 525EH UT WOS:000174055400020 PM 11856691 ER PT J AU Wunderbaldinger, P Harisinghani, MG Hahn, PF Daniels, GH Turetschek, K Simeone, J O'Neill, MJ Mueller, PR AF Wunderbaldinger, P Harisinghani, MG Hahn, PF Daniels, GH Turetschek, K Simeone, J O'Neill, MJ Mueller, PR TI Cystic lymph node metastases in papillary thyroid carcinoma SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID ULTRASOUND; NECK AB OBJECTIVE. The aim of this study was to illustrate and discuss the sonographic spectrum of surgically proven cystic nodal metastases from papillary thyroid carcinoma. By correlative evaluation of the sonographic imaging findings to gross pathology and histology, our purpose was to provide useful hints to differentiate cystic lymph node metastases from other benign cystic neck lesions such as branchial cysts. MATERIALS AND METHODS. Sonographic examinations of 74 patients (47 women, 27 men; mean age, 49 years) with 97 histologically confirmed cystic lymph nodes metastases from papillary thyroid carcinoma were included in the study. The anatomic relationship of the nodes relative to the primary tumor was recorded, and all cystic nodes were qualitatively categorized as either simple (purely cystic) or complex (thickened outer wall, internal nodules, internal septations, and calcifications). All imaging findings were compared with gross pathologic specimens. RESULTS. Most of the cystic metastases were ipsilateral to the primary tumor (87.8%) and located in the mid or lower jugular chain (73.2%). In 14.9% of all patients, cystic lymph node metastases were the initial manifestation of disease. Only 6.2% of all lymph node metastases were purely cystic (all of these occurred in patients less than 35 years old). Of the 91 complex metastases, a thickened outer wall was present in 35.2% of patients, internal nodules in 42.9%, and internal septations in 57.1%. No calcifications were seen in the 91 complex metastases, and two or more findings were seen in 23.1%. All sonographic findings were verified by surgery. CONCLUSION. In most of the patients, cystic lymph node metastases are characterized sonographically by the presence of a thickened outer wall, internal echoes, internal nodularity, and septations. However, in younger patients. the lymph nodes might appear purely cystic, thereby mimicking branchial cysts and thus requiring biopsy for final diagnosis and therapy planning. C1 Univ Vienna, Dept Radiol, A-1030 Vienna, Austria. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Thyroid Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. RP Wunderbaldinger, P (reprint author), Univ Vienna, Dept Radiol, Waehringer Guertel 18-20, A-1030 Vienna, Austria. NR 12 TC 50 Z9 56 U1 0 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2002 VL 178 IS 3 BP 693 EP 697 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 525EH UT WOS:000174055400028 PM 11856700 ER PT J AU Provenzale, JM Wang, GR Brenner, T Petrella, JR Sorensen, AG AF Provenzale, JM Wang, GR Brenner, T Petrella, JR Sorensen, AG TI Comparison of permeability in high-grade and low-grade brain tumors using dynamic susceptibility contrast MR imaging SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT 101st Annual Meeting of the American-Roentgen-Ray-Society CY APR 29-MAY 04, 2001 CL SEATTLE, WASHINGTON SP Amer Roentgen Ray Soc ID ENDOTHELIAL GROWTH-FACTOR; MICROVASCULAR HYPERPERMEABILITY; ANGIOGENESIS AB OBJECTIVE. The purpose of this study was to compare permeability measurements in high-grade and low-grade glial neoplasms using a T2*-weighted method. Our hypothesis was that permeability measurements using a T2*-weighted technique would show permeability in high-grade neoplasms to be higher than that in low-grade neoplasms. MATERIALS AND METHODS. Twelve patients with biopsy-proven high-grade neoplasms and 10 patients with biopsy-proven low-grade neoplasms underwent dynamic susceptibility contrast MR perfusion imaging (TR/TE, 1500/80) after bolus infusion of 0.2 mmol/kg of MR contrast material. Color-coded permeability-weighted maps were created using a model that weights relative contributions to signal intensity from intravascular T2* effects and extravascular T1 effects from blood-brain barrier permeability. Two measures of permeability were performed: mean value of highest permeability found on three images through the tumor (mean regional value) and highest value found at any region of interest in the tumor (single area of maximum permeability). Depending on the normality of the data sets, we used the Wilcoxon's rank sum test or the two-tailed Student's t test for statistical analysis. RESULTS. For low-grade tumors, the range was 0.006-0.041, and the median of the mean regional value for each image was 0.017. For high-grade tumors, the range was 0.005-0.092, and the median of the mean regional value was 0.035 (p = 0.025). For low-grade tumors, the range was 0.008-0.045, and the mean of the single area of maximum values was 0.02. For high-grade tumors, the range was 0.007-0.136, and the mean of the single area of maximum values was 0.054 (p = 0.018). CONCLUSION. Permeability values for high-grade tumors obtained using a T2*-weighted method were significantly greater than those for low-grade tumors and are consistent with previous studies reporting results using T1-weighted methods. C1 Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Provenzale, JM (reprint author), Duke Univ, Med Ctr, Dept Radiol, Box 3808, Durham, NC 27710 USA. NR 13 TC 142 Z9 154 U1 1 U2 5 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2002 VL 178 IS 3 BP 711 EP 716 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 525EH UT WOS:000174055400031 PM 11856703 ER PT J AU Malcolm, R Myrick, H Roberts, J Wang, W Anton, RF AF Malcolm, R Myrick, H Roberts, J Wang, W Anton, RF TI The differential effects of medication on mood, sleep disturbance, and work ability in outpatient alcohol detoxification SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID ADMISSION PREDICTS RELAPSE; WITHDRAWAL SYNDROME; INPATIENT ALCOHOLICS; SEIZURES; ANXIETY; CARBAMAZEPINE; PREVENTION; DIAGNOSIS AB A double-blind, randomized controlled trial of patients (n = 136) meeting DSM-IV criteria for alcohol withdrawal and stratified based on detoxification history were treated with carbamazepine or lorazepam for 5 days on a fixed dose tapering schedule. Mood symptoms improved for all subjects regardless of medication or detoxification history. There was a significant main effect favoring carbamazepine in reducing anxiety (p = 0.0007). Anxiety was highest in those individuals who had multiple previous detoxifications (p = 0.02). Visual analog measures of sleep quality indicated a statistically significant main effect of medication on sleep that again favored carbamazepine (p = 0.0186). Visual analog rating of perceived ability to return to work was decreased in individuals who had multiple previous detoxifications (p = 0.025). In this study of outpatients with mild to moderate alcohol withdrawal, carbamazepine was superior to lorazepam in reducing anxiety and improving sleep. C1 Med Univ S Carolina, Alcohol Res Ctr, Charleston, SC 29425 USA. Ralph H Johnson VAMC, Charleston, SC USA. Univ Maryland, Dept Measurements Stat & Evaluat, College Pk, MD USA. RP Malcolm, R (reprint author), Med Univ S Carolina, Alcohol Res Ctr, 67 President St, Charleston, SC 29425 USA. FU NIAAA NIH HHS [AA10761] NR 42 TC 32 Z9 35 U1 3 U2 5 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 SPR PY 2002 VL 11 IS 2 BP 141 EP 150 DI 10.1080/10550490290087910 PG 10 WC Substance Abuse SC Substance Abuse GA 551KX UT WOS:000175561800006 PM 12028744 ER PT J AU Hirakura, Y Carreras, I Sipe, JD Kagan, BL AF Hirakura, Y Carreras, I Sipe, JD Kagan, BL TI Channel formation by serum amyloid A: a potential mechanism for amyloid pathogenesis and host defense SO AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS LA English DT Article DE acute phase reactants; inflammation; cytotoxicity; pores; membranes ID VOLTAGE-DEPENDENT CHANNELS; HIGH-DENSITY-LIPOPROTEIN; LIPID BILAYER-MEMBRANES; PRION PROTEIN-FRAGMENT; C-REACTIVE PROTEIN; ACUTE-PHASE; CONGO-RED; ANTIMICROBIAL PEPTIDES; BETA-PROTEIN; A PROTEIN AB Serum amyloid A (SAA) is a family of closely, related apolipoproteins associated with high density lipoprotein (HDL). Subclasses of SAA isoforms are differentially expressed constitutively, and during inflammation. During states of infection or inflammation, levels of HDL bound, acute phase isoforms of SAA rise as much as 1000-fold in the serum, suggesting that it might play a role in host defense. Following recurrent or chronic inflammation, an N-terminal peptide fragment of SAA known as amyloid A (AA) assembles into fibrils causing extensive damage to spleen, liver, and kidney, and rapidly, progressing to death. In the present paper, we report the novel finding that a recombinant acute phase isoform variant of human SAA1.1 (SAAp) readily forms ion-channels in planar lipid bilayer membranes at physiologic concentrations. These channels are voltage-independent, poorly selective, and are relatively, long-lived This type of channel would place a severe metabolic strain on various kinds of cells. Expression of human SAA1.1 in bacteria induces lysis of bacterial cells, while expression of the constitutive isoform (human SAA4) does not. Secondary structural analysis of the SAA isoforms indicates a strong hydrophobicity of the N-terminal of the acute phase isoform relative to the constitutive SAA4 isoform, which may be responsible for the bactericidal activity of the former, in keeping with the notion that SAA1 targets cell membranes and forms channels in them Channel formation may thus be related to a host defense role of acute phase SAA isoforms and may, also be the mechanism of end organ damage in AA and other amyloidoses. C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat, Inst Neuropsychiat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Mental Retardat Res Ctr, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. RP Kagan, BL (reprint author), Univ Calif Los Angeles, Sch Med, Dept Psychiat, Inst Neuropsychiat, 760 Westwood Pl, Los Angeles, CA 90024 USA. FU NIMH NIH HHS [MH 01174] NR 63 TC 58 Z9 60 U1 0 U2 5 PU PARTHENON PUBLISHING GROUP PI LANCASTER PA RICHMOND HOUSE, WHITE CROSS, SOUTH ROAD, LANCASTER LA1 4XQ, ENGLAND SN 1350-6129 J9 AMYLOID JI Amyloid-J. Protein Fold. Disord. PD MAR PY 2002 VL 9 IS 1 BP 13 EP 23 DI 10.3109/13506120209072440 PG 11 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA 549FB UT WOS:000175432900002 PM 12000193 ER PT J AU Mehta, RP Harris, JP Nadol, JB AF Mehta, RP Harris, JP Nadol, JB TI Malleus fixation: Clinical and histopathologic findings SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE conductive hearing loss; malleus fixation; otology; otosclerosis AB The goals of this study were to review important clinical and histopathologic features of malleus fixation. Ten clinical cases and 10 histopathologic cases of malleus fixation were identified. For the clinical cases, preoperative clinical data, surgical findings, and preoperative and postoperative audiometric findings were reviewed. Ninety percent of the clinical cases achieved significant reduction of the air-bone gap after operation. Two thirds of these cases had an air-bone gap of 10 dB or less, and the remainder had air-bone gaps between 20 and 28 dB after operation. For the temporal bone cases, clinical data, histopathologic findings, and other otologic diagnoses were reviewed. Malleus fixation can be idiopathic or a result of trauma, chronic otitis media. or developmental anomalies. It is a cause of hearing loss that is likely to be more common than the number of diagnoses would indicate. Certain audiometric findings may lead one to suspect the diagnosis. The surgical approach used depends on the individual anatomy, and surgery is usually highly effective in improving hearing. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Univ Calif San Diego, Sch Med, Div Otolaryngol, San Diego, CA 92103 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Harris, JP (reprint author), Univ Calif San Diego, Sch Med, Div Otolaryngol, 200 W Arbor Dr, San Diego, CA 92103 USA. NR 11 TC 7 Z9 7 U1 0 U2 0 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 MAR PY 2002 VL 111 IS 3 BP 246 EP 254 PN 1 PG 9 WC Otorhinolaryngology SC Otorhinolaryngology GA 532KA UT WOS:000174472800009 ER PT J AU Hartnick, CJ Emery, KH Chung, S Myer, CM AF Hartnick, CJ Emery, KH Chung, S Myer, CM TI Imaging case study of the month - Pediatric virtual bronchoscopy SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article ID REALITY; RECONSTRUCTION; SIMULATION; SURGERY; HEAD C1 Childrens Hosp & Med Ctr, Dept Otolaryngol, Cincinnati, OH USA. Childrens Hosp & Med Ctr, Dept Radiol, Cincinnati, OH USA. RP Hartnick, CJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 14 TC 2 Z9 2 U1 0 U2 0 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 MAR PY 2002 VL 111 IS 3 BP 281 EP 283 PN 1 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA 532KA UT WOS:000174472800014 PM 11913689 ER PT J AU Wong, JS Harris, JR AF Wong, JS Harris, JR TI Can specific axillary radiotherapy be omitted in undissected, clinically node-negative patients who undergo breast-conserving therapy? SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material ID RADIATION-THERAPY; LYMPH-NODES; STAGE-I; CANCER; DISSECTION; MANAGEMENT; CARCINOMA; SURGERY; FIELD C1 Harvard Univ, Dept Radiat Oncol, Dana Farber Canc Inst, Brigham & Womens Hosp,Med Sch, Boston, MA 02115 USA. RP Wong, JS (reprint author), Harvard Univ, Dept Radiat Oncol, Dana Farber Canc Inst, Brigham & Womens Hosp,Med Sch, 75 Francis St, Boston, MA 02115 USA. NR 24 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAR PY 2002 VL 9 IS 2 BP 117 EP 119 DI 10.1245/aso.2002.9.2.117 PG 3 WC Oncology; Surgery SC Oncology; Surgery GA 528YK UT WOS:000174273100003 PM 11888866 ER PT J AU Mangi, AA Giassert, HA Wright, CD Allan, JS Wain, JC Grillo, HC Mathisen, DJ AF Mangi, AA Giassert, HA Wright, CD Allan, JS Wain, JC Grillo, HC Mathisen, DJ TI Benign broncho-esophageal fistula in the adult SO ANNALS OF THORACIC SURGERY LA English DT Article ID CONGENITAL BRONCHOESOPHAGEAL FISTULA AB Background. Benign broncho-esophageal fistula (BEF) in the adult is rare, and occurs as a complication of inflammatory disorders, foreign body ingestion, or congenital anomalies. Nonspecific symptoms lead to a delay in diagnosis. Methods. The charts of 13 patients from 1960 to 2001 at, the Massachusetts General Hospital were retrospectively reviewed. Results. Nine patients had chronic cough, which worsened upon ingestion. Four patients developed BEF after prior thoracic surgery, and 3 after histoplasmosis. Silicosis, foreign body ingestion, lye ingestion, bronchogenic cyst, esophageal diverticulum, and a congenital anomaly caused BEF in 1 patient each. Barium swallow was the most useful diagnostic test. Fistulas most often arose from the right bronchial tree and communicated with the distal esophagus. Management involved excision of the tract, primary closure of the bronchus and esophagus, and interposition of vascularized tissue. There was one perioperative failure, but no long-term recurrences after successful surgical closure. Conclusions. The majority of benign BEF in adults are acquired, and result from mediastinal inflammation. Accurate recognition and surgical closure prevents persistent uncontrolled aspiration and pulmonary sepsis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Thorac Surg,Dept Surg, Boston, MA 02114 USA. RP Mathisen, DJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Thorac Surg,Dept Surg, Blake 1570,55 Fruit St, Boston, MA 02114 USA. NR 13 TC 27 Z9 29 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 2002 VL 73 IS 3 BP 911 EP 915 AR PII S0003-4975(01)03582-2 DI 10.1016/S0003-4975(01)03582-2 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 527UH UT WOS:000174205900060 PM 11899200 ER PT J AU Melendez, PA Capriles, VA AF Melendez, PA Capriles, VA TI Molluscicidal activity of plants from Puerto Rico SO ANNALS OF TROPICAL MEDICINE AND PARASITOLOGY LA English DT Article ID BIOLOGICAL-CONTROL; SNAIL HOSTS; SCHISTOSOMIASIS AB Overall, 173 tropical plants from 72 different families, collected from the north-western and western regions of Puerto Rico, were screened for their molluscicidal properties against Biomphalaria glabrata, the intermediate host of Schistosoma mansoni, Six plant extracts were effective at 50 ppm. The two most effective extracts were those from the leaves of Didymopanax morototoni (Araliaceae) and Mammea americana (Guttiferae), which, at 50 ppm, killed all snails after 24 h of exposure and a day for recovery. Under the same conditions, extracts of Furcraea tuberosa, Argemone mexicana and Paullinia pinnata killed 50% of the snails and that of Solamon americanum killed 33%. The most effective extracts (or their active components or compounds based on them) may have potential as molluscides for the relatively cheap control of human schistosomiasis. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Inter Amer Univ Puerto Rico, Dept Biol, San German, PR USA. RP Melendez, PA (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl,Room 645, Boston, MA 02215 USA. NR 32 TC 13 Z9 19 U1 0 U2 3 PU MANEY PUBLISHING PI LEEDS PA HUDSON RD, LEEDS LS9 7DL, ENGLAND SN 0003-4983 J9 ANN TROP MED PARASIT JI Ann. Trop. Med. Parasitol. PD MAR PY 2002 VL 96 IS 2 BP 209 EP 218 DI 10.1179/000349802125000600 PG 10 WC Public, Environmental & Occupational Health; Parasitology; Tropical Medicine SC Public, Environmental & Occupational Health; Parasitology; Tropical Medicine GA 543TV UT WOS:000175118000013 PM 12080983 ER PT J AU Heikkila, P Teronen, O Moilanen, M Konttinen, YT Hanemaaijer, R Laitinen, M Maisi, P van der Pluijm, G Bartlett, JD Salo, T Sorsa, T AF Heikkila, P Teronen, O Moilanen, M Konttinen, YT Hanemaaijer, R Laitinen, M Maisi, P van der Pluijm, G Bartlett, JD Salo, T Sorsa, T TI Bisphosphonates inhibit stromelysin-1 (MMP-3), matrix metalloelastase (MMP-12), collagenase-3 (MMP-13) and enamelysin (MMP-20), but not urokinase-type plasminogen activator, and diminish invasion and migration of human malignant and endothelial cell lines SO ANTI-CANCER DRUGS LA English DT Article DE bisphosphonates; inhibition; invasion; matrix metalloproteinases; migration ID CHEMICALLY-MODIFIED TETRACYCLINES; BREAST-CANCER; TISSUE INHIBITOR; HUMAN NEUTROPHIL; BONE METASTASES; TUMOR; METALLOPROTEINASES; ALENDRONATE; EXPRESSION; COMBINATION AB Bisphosphonates (clodronate, alendronate, pamidronate and zoledronate) at therapeutically attainable non-cytotoxic concentrations Inhibited MMP-3, -12, -13 and -20 as well as MMP-1, -2, -8 and -9, but not urokinase-type plasminogen activator (uPA), a serine proteinase and a pro-MMP activator. Dose-dependent Inhibition was shown by three Independent MMP assays. The inhibition was reduced In the presence of an Increased concentration of Ca2+ when compared to physiologic Ca2+ concentration. Alendronate inhibited the In vitro Invasion (Matrigel) of human HT1080 fibrosarcoma and C8161 melanoma cells, and the random migration of these malignant and endothelial cell lines capable of expressing MMPs and uPA. The concentration of alendronate required to inhibit 50% of the activity (IC50 = 40-70 muM) of MMPs corresponded to the IC50 of down-regulation of In vitro invasion and migration. The ability of bisphosphonates to down-regulate the in vitro invasion and random migration was comparable or slightly better in relation to the selective gelatinase inhibitor CTTHWGFTLC peptide. Alendronate but not CTTHWGFTLC peptide promoted the adhesion of HT1080 fibrosarcoma and C8161 melanoma cell lines on fibronectin. Bisphosphonates are broad-spectrum MMP inhibitors and this Inhibition Involves cation chelation. Bisphosphonates further exert antimetastatic, anti-invasive and cell adhesion-promoting properties, which may prevent metastases not only into hard tissues but also to soft tissues. [(C) 2002 Lippincott Williams Wilkins.]. C1 Univ Helsinki, Cent Hosp, Dept Med Biomedicum & Oral Med, Diagnost Lab, FIN-00014 Helsinki, Finland. Invalid Fdn, ORTON Res Inst, Helsinki, Finland. TNO Prevent & Hlth, Leiden, Netherlands. Univ Oulu, Dept Diagnost & Oral med, Oulu, Finland. Oulu Univ, Cent Hosp, SF-90220 Oulu, Finland. Univ Tampere, Inst Med Technol, FIN-33101 Tampere, Finland. Tampere Univ, Cent Hosp, Dept Surg, SF-33520 Tampere, Finland. Tampere Univ, Cent Hosp, Dept Oral & Maxillofacial Surg, SF-33520 Tampere, Finland. Univ Helsinki, Fac Med Vet, Dept Vet Clin Sci, Helsinki, Finland. Leiden Univ, Med Ctr, Dept Endocrinol, Leiden, Netherlands. Forsyth Inst, Harvard Forsyth Dept Oral Biol, Boston, MA 02115 USA. RP Heikkila, P (reprint author), Univ Helsinki, Inst Dent, Res Lab, Medicum Helsinki, POB 63 Haartmaninkatu 8, FIN-00014 Helsinki, Finland. OI Heikkila, Pia/0000-0002-5925-1993 FU NIDCR NIH HHS [R01 DE014084] NR 41 TC 80 Z9 86 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD MAR PY 2002 VL 13 IS 3 BP 245 EP 254 DI 10.1097/00001813-200203000-00006 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 546YP UT WOS:000175304800006 PM 11984068 ER PT J AU Ge, YL Chen, ZH Kang, ZB Cluette-Brown, J Laposata, M Kang, JX AF Ge, YL Chen, ZH Kang, ZB Cluette-Brown, J Laposata, M Kang, JX TI Effects of adenoviral gene transfer of C-elegans n-3 fatty acid desaturase on the lipid profile and growth of human breast cancer cells SO ANTICANCER RESEARCH LA English DT Article DE gene transfer; n-3 fatty acid desaturase; n-6/n-3 fatty acid ratio; breast cancer; proliferation and apopotosis ID OMEGA-3; DIET; OIL AB Background: Current evidence from both experimental and human studies indicates that omega-6 polyunsaturated fatty acids (n-6 PUFAs) promote breast tumor development, whereas long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) exert suppressive effects. The ratio of n-6 to n-3 fatty acids appears to be an important factor in controlling tumor development. Human cells usually have a very high n-6/n-3 fatty acid ratio because they cannot convert n-6 PUFAs to n-3 PUFAs due to lack of an n-3 desaturase found in C. elegans. Materials and Methods: Adenoviral strategies were used to introduce the C. elegans fat-1 gene encoding an n-3 fatty acid desaturase into human breast cancer cells followed by examination of the n-6/n-3 fatty acid ratio and growth of the cells. Results: Infection of MCF-7 cells with an adenovirus carrying the fat-1 gene resulted in a high expression of the n-3 fatty acid desaturase. Lipid analysis indicated a remarkable increase in the levels of n-3 PUFAs accompanied with a large decrease in the contents of n-6 PUFAs, leading to a change of the n-6/n-3 ratio from 12.0 to 0.8. Accordingly, production of the eicosanoids derived from n-6 PUFA was reduced significantly in cells expressing the fat-1 gene. Importantly, the gene transfer induced mass cell death and inhibited cell proliferation. Conclusion: The gene transfer of the n-3 fatty acid desaturase, as a novel approach, can effectively modify the n-6/n-3 fatty acid ratio of human tumor cells and provide an anticancer effect, without the need of exogenous n-3 PUFA supplementation. These data also increase the understanding of the effects of n-3 fatty acids and the n-6/n-3 ratio on cancer prevention and treatment. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Room 4433,149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA79553] NR 20 TC 36 Z9 49 U1 0 U2 5 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAR-APR PY 2002 VL 22 IS 2A BP 537 EP 543 PG 7 WC Oncology SC Oncology GA 547VB UT WOS:000175352100001 PM 12014621 ER PT J AU Nelson, RG Rosowsky, A AF Nelson, RG Rosowsky, A TI Dicyclic and tricyclic diaminopyrimidine derivatives as potent inhibitors of Cryptosporidium parvum dihydrofolate reductase: Structure-activity and structure-selectivity correlations (vol 45, pg 3293, 2001) SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Correction C1 Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Nelson, RG (reprint author), Univ Calif San Francisco, Dept Med, Div Infect Dis, San Francisco, CA 94143 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAR PY 2002 VL 46 IS 3 BP 940 EP 940 PG 1 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 522QR UT WOS:000173908900059 ER PT J AU Granter, SR Weilbaecher, KN Quigley, C Fisher, DE AF Granter, SR Weilbaecher, KN Quigley, C Fisher, DE TI Role for microphthalmia transcription factor in the diagnosis of metastatic malignant melanoma SO APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY LA English DT Article DE immunohistochemistry; immunoperoxide; melanoma; metastatic; microphthalmia transcription factor; nevi ID GENE-PRODUCT; EXPRESSION; DIFFERENTIATION; MELANOCYTES; ACTIVATION; MI AB Microphthalmia transcription factor (Mitf), a protein critical for the embryonic development and postnatal viability of melanocytes. is a master lineage regulator and modulates extracellular signals. Recently, an anti-Mitf antibody. D5, was shown to be both a sensitive and a specific marker of epithelioid melanoma (1). Those data suggested that Mitf expression was specific for melanocytic differentiation because it was not detected in six different carcinoma types, To broaden the spectrum of melanomatous and nonmelanomatous tumor, tested with this antibody, the authors investigated the sensitivity and specificity of the D5 anti-Mitf antibody in 36 metastatic melanomas and 102 nonmelanomatous tumors. Twenty-nine of 36 (81%) melanomas examined were reactive for D5. Of these. 29 of 32 (91%) epithelioid melanomas were reactive, whereas all 4 melanomas with spindle cell morphology were nonreactive. Six of 102 (5.8%) nonmelanomatous tumors ( I breast carcinoma, I malignant mixed mullerian tumor. 2 renal cell carcinomas, and 2 leiomyosarcomas) were reactive for D5. All melanomas were reactive for S-100 protein (a criteria for inclusion in the study). whereas 8 of 102 (7.8%) of nonmelanomatous tumor,,, were reactive. Twenty-five of 36 melanomas (69%) were reactive for HMB-45, whereas no nonmelanomatous, tumors were reactive. Twenty-one of 28 (75%) melanomas were reactive for MelanA. Reactivity for Melan-A was detected in 5 of 102 (4.9%) nonmelanomatous tumors. As with D5, HMB-45 and Melan-A failed to detect all spindle-cell melanomas. Results of this study confirm that D5 is a sensitive marker for epithelioid melanomas: however, the authors found D5 neither quite as sensitive nor quite as specific as in previous studies. Nevertheless, the authors believe that positive staining for D5 when taken in clinical, histologic, and immunohistochemical context may be diagnostically useful. In particular, D5 is helpful in the evaluation of epithelioid neoplasms, but not spindle-cell tumors. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA USA. Childrens Hosp, Boston, MA 02115 USA. RP Granter, SR (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 22 TC 47 Z9 50 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-3345 J9 APPL IMMUNOHISTO M M JI Appl. Immunohistochem. PD MAR PY 2002 VL 10 IS 1 BP 47 EP 51 DI 10.1097/00022744-200203000-00008 PG 5 WC Anatomy & Morphology; Medical Laboratory Technology; Pathology SC Anatomy & Morphology; Medical Laboratory Technology; Pathology GA 525EF UT WOS:000174055200008 PM 11893035 ER PT J AU Chan, LS Ahmed, AR Anhalt, GJ Bernauer, W Cooper, KD Elder, MJ Fine, JD Foster, S Ghohestani, R Hashimoto, T Hoang-Xuan, T Kirtschig, G Korman, NJ Lightman, S Lozado-Nur, F Marinkovich, MP Mondino, BJ Prost-Squarcioni, C Rogers, RS Setterfield, JF West, DP Wojnarowska, F Woodley, DT Yancey, KB Zillikens, D Zone, JJ AF Chan, LS Ahmed, AR Anhalt, GJ Bernauer, W Cooper, KD Elder, MJ Fine, JD Foster, S Ghohestani, R Hashimoto, T Hoang-Xuan, T Kirtschig, G Korman, NJ Lightman, S Lozado-Nur, F Marinkovich, MP Mondino, BJ Prost-Squarcioni, C Rogers, RS Setterfield, JF West, DP Wojnarowska, F Woodley, DT Yancey, KB Zillikens, D Zone, JJ TI The first international consensus on mucous membrane pemphigoid - Definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators SO ARCHIVES OF DERMATOLOGY LA English DT Article ID THIOPURINE METHYLTRANSFERASE ACTIVITY; INTRAVENOUS IMMUNOGLOBULIN THERAPY; SUBEPITHELIAL BLISTERING DISEASES; ORAL VESICULOEROSIVE DISEASES; BASEMENT-MEMBRANE; INDIRECT IMMUNOFLUORESCENCE; SUBEPIDERMAL BLISTERS; AUTOANTIBODIES REACT; CLINICAL VARIANTS; PASSIVE TRANSFER AB Objective: We aimed to develop consensus-based recommendations for streamlining medical communication among various health care professionals, to improve accuracy of diagnosis and treatment, and to facilitate future investigations for mucous membrane pemphigoid. Participants: Because of the highly specific nature of this group of diseases, the 26 invited participants included either international scholars in the field of mucous membrane pemphigoid or experts in cutaneous pharmacology representing the 3 medical disciplines ophthalmology, oral medicine, and dermatology. Evidence: The first author (L.S.C,) conducted a literature search. Based on the information obtained, inter-national experts who had contributed to the literature in the clinical care, diagnosis, and laboratory investigation for mucous membrane pemphigoid were invited to participate in a consensus meeting aimed at developing a consensus statement. Consensus Process: A consensus meeting was convened and conducted on May 10, 1999, in Chicago, 111, to discuss the relevant issues. The First author drafted die statement based on the consensus developed at the meeting and the participants' written comments. The draft was submitted to all participants for 3 separate rounds of review, and disagreements were reconciled based on literature evidence. The third and final statement incorporated all relevant evidence obtained in the literature search and the consensus developed by the participants. The final statement was approved and endorsed by all 26 participants. Conclusions: Specific consensus-based recommendations were made regarding the definition, diagnostic criteria, pathogenic factors, medical treatment, and prognostic indicators for mucous membrane pemphigoid. A system of standard reporting for these patients was proposed to facilitate a uniform data collection. C1 Northwestern Univ, Sch Med, Dept Dermatol, Chicago, IL 60611 USA. Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Boston, MA 02115 USA. Johns Hopkins Med Inst, Dept Dermatol, Baltimore, MD 21205 USA. Univ Zurich, Dept Ophthalmol, Zurich, Switzerland. Case Western Reserve Univ, Sch Med, Dept Dermatol, Cleveland, OH 44106 USA. Christchurch Hosp, Dept Ophthalmol, Christchurch, New Zealand. Univ N Carolina, Dept Dermatol, Chapel Hill, NC 27514 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Thomas Jefferson Med Coll, Dept Dermatol, Philadelphia, PA USA. Kurume Univ, Sch Med, Dept Dermatol, Fukuoka, Japan. Hop Bichat Claude Bernard, F-75877 Paris, France. Urije Univ, Dept Dermatol, Amsterdam, Netherlands. Moorfields Eye Hosp, London, England. UCL, Inst Ophthalmol, London, England. Univ Calif San Francisco, Sch Dent, Dept Stomatol, San Francisco, CA 94143 USA. Stanford Univ, Sch Med, Dept Dermatol, Stanford, CA 94305 USA. Vet Affairs Hlth Care Syst, Palo Alto, CA USA. Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Ophthalmol, Los Angeles, CA 90024 USA. Hop St Louis, Dept Dermatol, Paris, France. Hop St Louis, Policlin Dermatol, Paris, France. Mayo Clin, Dept Dermatol, Rochester, MN USA. St Thomas Hosp, St Johns Inst Dermatol, London, England. Churchill Hosp, Dept Dermatol, Oxford OX3 7LJ, England. Univ So Calif, Div Dermatol, Los Angeles, CA 90089 USA. NCI, Div Clin Sci, Dermatol Branch, NIH, Bethesda, MD 20892 USA. Univ Wurzburg, Dept Dermatol, D-8700 Wurzburg, Germany. Univ Utah, Dept Dermatol, Salt Lake City, UT USA. RP Chan, LS (reprint author), Northwestern Univ, Sch Med, Dept Dermatol, 675 N St Clair St,Suite 19-150, Chicago, IL 60611 USA. EM larrychan@northwestern.edu RI Zillikens, Detlef/C-8572-2011; OI West, Dennis/0000-0002-9107-6697 NR 95 TC 267 Z9 278 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-987X EI 1538-3652 J9 ARCH DERMATOL JI Arch. Dermatol. PD MAR PY 2002 VL 138 IS 3 BP 370 EP 379 DI 10.1001/archderm.138.3.370 PG 10 WC Dermatology SC Dermatology GA 530PC UT WOS:000174367300010 PM 11902988 ER PT J AU Krzystolik, MG Afshari, MA Adamis, AP Gaudreault, J Gragoudas, ES Michaud, NA Li, WJ Connolly, E O'Neill, CA Miller, JW AF Krzystolik, MG Afshari, MA Adamis, AP Gaudreault, J Gragoudas, ES Michaud, NA Li, WJ Connolly, E O'Neill, CA Miller, JW TI Prevention of experimental choroidal neovascularization with intravitreal anti-vascular endothelial growth factor antibody fragment SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 30-MAY 05, 2000 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol ID PHOTODYNAMIC THERAPY; VERTEPORFIN AB Objective: To evaluate the safety and efficacy of intravitreal injections of an antigen-binding, fragment of a recombinant humanized monoclonal antibody directed toward vascular endothelial growth factor (rhuFab VEGF) in a monkey model of choroidal neovascularization (CNV). Methods: In phase 1 of the study, each animal received intravitreal injections, 500 mug per eye, of rhuFab VEGF in one eye (prevention eye), while the contralateral eye received rhuFab VEGF vehicle (control eye) at 2-week intervals. On day 21, laser photocoagulation was performed to induce CNV. In phase 2, the vehicle-treated eye was crossed over and both eyes received 500 mug of rhuFab VEGF beginning 21 days following laser-induced injury at days 42 and 56. The eyes were monitored by ophthalmic examinations, color photographs, and fluorescein angiography. Results: rhuFab VEGF did not cause any ocular hemorrhages. All eyes treated with rhuFab VEGF developed acute anterior chamber inflammation within 24 hours of the first injection that resolved within 1 week, and this inflammation was less severe with subsequent injections. The incidence of CNV, defined angiographically, was significantly lower in the prevention eyes than the control eyes (P < .001). Subsequent treatments were associated with less leakage in eyes with established CNV that were crossed over from the control eyes to the treatment eyes (P = .001). Conclusions: Intravitreal rhuFab VEGF injections prevented formation of clinically significant CNV in cynomolgus monkeys and decreased leakage of already formed CNV with no significant toxic effects. Clinical Relevance: This study provides the nonclinical proof of principle for ongoing clinical studies of intravitreally injected rhuFab VEGF in patients with neovascular age-related macular degeneration. C1 Retina Consultants, Providence, RI USA. Harvard Univ, Sch Med, Angiogenesis Lab, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Harvard Univ, Sch Med, Laser Lab, Massachusetts Eye & Ear Infirm,Retina Res Inst, Boston, MA 02115 USA. RP Miller, JW (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. RI Li, Wenjun/F-5634-2015 OI Li, Wenjun/0000-0001-5335-7386 NR 16 TC 349 Z9 377 U1 2 U2 4 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 2002 VL 120 IS 3 SI SI BP 338 EP 346 PG 9 WC Ophthalmology SC Ophthalmology GA 529LL UT WOS:000174300900011 PM 11879138 ER PT J AU DeAngelis, MM Grimsby, JL Sandberg, MA Berson, EL Dryja, TP AF DeAngelis, MM Grimsby, JL Sandberg, MA Berson, EL Dryja, TP TI Novel mutations in the NRL gene and associated clinical findings in patients with dominant retinitis pigmentosa SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID OCULAR FINDINGS; LEUCINE-ZIPPER; RHODOPSIN; EXPRESSION; CRX; HOMEODOMAIN; PROTEIN; SYSTEM AB Objectives: To search for mutations in the neural retina leucine zipper (NRL) gene in patients with dominant retinitis pigmentosa and to compare the severity of disease in these patients with that observed previously in patients with dominant rhodopsin mutations. Methods: Single-strand conformation analysis was used to survey 189 unrelated patients for mutations. The available relatives of index patients with mutations were also evaluated. In our clinical examination of patients, we measured visual acuity, final dark-adaptation threshold equivalent visual field diameter, and electroretinogram amplitudes among other parameters of visual function. We compared the clinical findings with those obtained earlier from similar evaluations of a group of 39 patients with the dominant rhodopsin mutation Pro23His and a group of 25 patients with the dominant rhodopsin mutation Pro347Leu, Results: We identified 3 novel missense mutations in a total of 4 unrelated patients with dominant retinitis pigmentosa: Ser50Pro, Ser50Leu (2 patients), and Pro51Thr. Each mutation cosegregated with dominant retinitis pigmentosa. None of these mutations were found among 91 unrelated control individuals. The visual acuities among the 4 index patients and 3 relatives with NRL mutations who were clinically evaluated ranged from 20/20 (in a 9-year-old patient) to 20/200 (in a 73-year-old patient). All patients had bone-spicule pigment deposits in their fundi. Average rod-plus-cone and cone-isolated electroretinogram amplitudes were both decreased by 99% or more compared with normal amplitudes. The dark-adaptation thresholds, equivalent visual field diameters, and electroretinogram amplitudes (all corrected for age and refractive error) indicated that the disease caused by the NRL mutations was more severe than that caused by the dominant rhodopsin mutation Pro23His and was similar in severity to that produced by the rhodopsin mutation Pro347Leu. Conclusion: The 3 novel NRL mutations we discovered bring the total number of reported mutations in this gene to 6. Five of the 6 mutations affect residues 50 or 51, suggesting that these residues are important in a structural or functional domain of the encoded protein. Clinical Relevance: Rod and cone function is affected to a similar degree in patients with these mutations. The disease caused by NRL mutations found in this study appears to be more severe than that caused by the rhodopsin mutation Pro23His and is similar in severity to that caused by the rhodopsin mutation Pro347Leu, even after correcting for age. 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 02114 USA. RP Dryja, TP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, 243 Charles St, Boston, MA 02114 USA. RI DeAngelis, e/J-7863-2015 FU NEI NIH HHS [EY07076, R01 EY00169, R01 EY08683, R01 EY11655] NR 23 TC 34 Z9 34 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 MAR PY 2002 VL 120 IS 3 SI SI BP 369 EP 375 PG 7 WC Ophthalmology SC Ophthalmology GA 529LL UT WOS:000174300900016 PM 11879142 ER PT J AU Young, IA Burns, SP Little, JW AF Young, IA Burns, SP Little, JW TI Sudden onset of cervical spondylotic myelopathy during sleep: A case report SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Spinal-Injury-Association CY APR 14-16, 2000 CL CHICAGO, ILLINOIS SP Amer Spinal Injury Assoc DE case report; quadriplegia; rehabilitation; spinal cord injuries; spinal osteophytosis; spinal stenosis ID SPINAL-CORD INFARCTION; QUADRIPLEGIA; INJURY AB Cervical spondylotic myelopathy is a common cause of compressive spinal cord dysfunction. The typical course involves either a gradual or an episodic increase in symptoms and neurologic deficits, with impairment evolving over a period of months to years. Acute neurologic deterioration in conjunction with cervical spondylosis has been described almost exclusively in traumatic situations such as disk herniation. We report a case of an acute, nontraumatic onset of tetraplegia in association with cervical spondylosis. A 56-year-old man developed tetraplegia during a 1-hour nap, with loss of volitional control of his extremities, impaired sensation below the C3 dermatome, and increased muscle tone. Magnetic resonance imaging of the cervical spine revealed canal stenosis and increased T2 signal within the cord. This case report describes the rehabilitation course for this patient and reviews the clinical spectrum of onset and progression of cervical spondylotic myelopathy. C1 Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Spinal Cord Injury Serv, Seattle, WA USA. RP Burns, SP (reprint author), VA Puget Sound, SCI Serv 128, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 25 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 2002 VL 83 IS 3 BP 427 EP 429 DI 10.1053/apmr.2002.29621 PG 3 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 529AM UT WOS:000174277900021 PM 11887127 ER PT J AU Kunjathoor, VV Chiu, DS O'Brien, KD LeBoeuf, RC AF Kunjathoor, VV Chiu, DS O'Brien, KD LeBoeuf, RC TI Accumulation of biglycan and perlecan, but not versican, in lesions of murine models of atherosclerosis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE apoE deficiency; LDL receptor deficiency; atherosclerosis; proteoglycans; apolipoproteins ID AMERICAN-HEART-ASSOCIATION; APOLIPOPROTEIN-E; DEFICIENT MICE; EXTRACELLULAR-MATRIX; VASCULAR-LESIONS; GROWTH-FACTOR; FATTY STREAK; PROTEOGLYCAN; CHOLESTEROL; LDL AB Proteoglycan accumulation within the arterial intima has been implicated in lipoprotein retention and in atherosclerosis progression in humans. Two commonly studied murine models of atherosclerosis, the apolipoprotein E (apoE)-deficient (apoE-/-) mouse and the low density lipoprotein receptor-deficient (LDLR-/-) mouse, develop arterial lesions similar to those of human atherosclerosis. However, specific proteoglycan classes that accumulate in lesions of these mice and their relation to the retention of specific apolipoproteins have not been previously determined. In this report, we characterized the distribution of proteoglycans (versican, biglycan, and perlecan) and apolipoproteins (apoB, apoA-1, and apoE) in proximal aortic lesions of chow-fed apoE-/- and LDLR -/- mice at 10, 52, and 73 weeks of age. We observed that similar to the apoE-/- mice, the LDLR-/- mice develop intermediate and advanced plaques within 52 weeks of age. Perlecan and biglycan (both are proteoglycans) appeared early in lesion development with distinct expression patterns as the plaques advanced. Versican, a major proteoglycan detected in human plaques, was mostly absent in both strains. ApoA-I and apoB were detected in early through advanced lesions in regions of proteoglycan accumulation in both strains. Our results indicate that proteoglycans may contribute to the retention of lipoproteins at the earliest stage of atherosclerosis in murine models of atherosclerosis. C1 Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02115 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Nutr Sci, Seattle, WA 98195 USA. RP LeBoeuf, RC (reprint author), Univ Washington, Dept Pathobiol, Box 353410,Room 305,Raitt Hall, Seattle, WA 98195 USA. FU NHLBI NIH HHS [HL-02788, HL-52848]; NIDDK NIH HHS [DK-02345] NR 40 TC 77 Z9 77 U1 0 U2 1 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 2002 VL 22 IS 3 BP 462 EP 468 DI 10.1161/hq0302.105378 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 532FP UT WOS:000174461700018 PM 11884291 ER PT J AU Oates, JC Reilly, CM Crosby, MB Gilkeson, GS AF Oates, JC Reilly, CM Crosby, MB Gilkeson, GS TI Peroxisome proliferator-activated receptor gamma agonists - Potential use for treating chronic inflammatory diseases SO ARTHRITIS AND RHEUMATISM LA English DT Review ID NITRIC-OXIDE SYNTHASE; NECROSIS-FACTOR-ALPHA; PPAR-GAMMA; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); INSULIN-RESISTANCE; IN-VITRO; NUCLEAR RECEPTORS; GENE-EXPRESSION; INHIBIT; CELLS C1 Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Med Res Serv, Charleston, SC USA. RP Oates, JC (reprint author), Med Univ S Carolina, Div Rheumatol & Immunol, 96 Jonathan Lucas St,Suite 912, Charleston, SC 29425 USA. FU NIAMS NIH HHS [AR-40837, R01 AR047451]; NIGMS NIH HHS [GM08716] NR 65 TC 25 Z9 31 U1 0 U2 0 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 MAR PY 2002 VL 46 IS 3 BP 598 EP 605 DI 10.1002/art.10052 PG 8 WC Rheumatology SC Rheumatology GA 531HD UT WOS:000174409200006 PM 11920394 ER PT J AU Gribben, JG AF Gribben, JG TI Monitoring disease in lymphoma and CLL patients using molecular techniques SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Article DE non-Hodgkin's lymphoma; chronic lymphocytic leukaemia; residual disease; polymerase chain reaction; chromosomal translocation; immunoglobulin gene rearrangement ID POLYMERASE-CHAIN-REACTION; MINIMAL RESIDUAL DISEASE; NON-HODGKINS-LYMPHOMA; BONE-MARROW TRANSPLANTATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; B-CELL LYMPHOMA; REED-STERNBERG CELLS; IMMUNOGLOBULIN GENE REARRANGEMENT; T(11-14) CHROMOSOME-TRANSLOCATION AB Over the past decade considerable advances have been made in the sensitivity of detection of residual lymphoma and leukaemia cells. Assays based on the polymerase chain reaction (PCR) can detect one tumour cell in up to 10(5) to 10(6) normal cells. The identification and cloning of breakpoints associated with specific chromosomal translocations has made possible the application of these techniques to a variety of lymphoid malignancies. In parallel, B cell malignancies exhibit rearrangements of their immunoglobulin genes that are also suitable targets for PCR amplification to identify residual cells. Although these techniques provide a useful adjunct to standard methods of detection and diagnosis, their role in determining disease outcome remains investigational. There is confusion as to whether it is necessary to eradicate PCR-detectable lymphoma cells for cure, so it is not yet possible to determine whether the detection of residual lymphoma cells by PCR is an indication to continue therapy. C1 Harvard Univ, Dept Med, Div Hematol Malignancies, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gribben, JG (reprint author), Harvard Univ, Dept Med, Div Hematol Malignancies, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 85 TC 11 Z9 11 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1521-6926 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PD MAR PY 2002 VL 15 IS 1 BP 179 EP 195 DI 10.1053/beha.2002.0191 PG 17 WC Hematology SC Hematology GA 538VL UT WOS:000174835700012 PM 11987923 ER PT J AU Solomon, CS Goalstone, ML AF Solomon, CS Goalstone, ML TI Dominant negative alpha-subunit of FTase inhibits effects of insulin and IGF-I in MCF-7 cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE farnesyltransferase; insulin; geranylgeranyltransferase I; dominant negative alpha-subunit; MCF-7 cells ID FARNESYL-PROTEIN TRANSFERASE; BREAST-CANCER CELLS; SMOOTH-MUSCLE CELLS; GROWTH-FACTOR-I; MOLECULAR MECHANISMS; P21 RAS; FARNESYLTRANSFERASE; HYPERINSULINEMIA; POTENTIATION; ACTIVATION AB We recently designed a dominant negative (DN) farnesyltransferase (FTase)/geranyl-gerahyltransferase I (GGTase I) alpha-subunit that when expressed in vascular smooth muscle cells decreased insulin-stimulated phosphorylation of FTase, FTase activity, amounts of farnesylated p21Ras, DNA synthesis, and cell migration. Currently, we explored the inhibitory effects of DN FTase/GGTase I alpha-subunit in MCF-7 cells on IGF-1- and insulin-stimulated DNA synthesis and cell proliferation. Expression of the DN FTase/GGTase I alpha-subunit completely blocked IGF-1- and insulin-stimulated BrdU incorporation and cell count. DN FTase/GGTase I alpha-subunit inhibited insulin-stimulated phosphorylation of FTase/GGTase I alpha-subunit, FTase and GGTase I activity, and prenylation of p21Ras and RhoA. Expression of DN FTase/GGTase I alpha-subunit diminished IGF-1- and insulin-stimulated phosphorylation of ERK (extracellular signal-regulated kinase), but had no effect on IGF-1- and insulin-stimulated phosphorylation of Akt. Taken together, these data suggest that DN FTase/GGTase I alpha-subunit can assuage the mitogenic effects of IGF-1 and insulin on MCF-7 breast cancer cells. C1 Denver VA Med Ctr, Res Serv, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. RP Goalstone, ML (reprint author), Denver VA Med Ctr, Res Serv, 111H,1055 Clermont St, Denver, CO 80220 USA. NR 46 TC 8 Z9 8 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 MAR 1 PY 2002 VL 291 IS 3 BP 458 EP 465 DI 10.1006/bbrc.2002.6471 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 527TD UT WOS:000174202700005 PM 11855811 ER PT J AU Wunderbaldinger, P Josephson, L Weissleder, R AF Wunderbaldinger, P Josephson, L Weissleder, R TI Tat peptide directs enhanced clearance and hepatic permeability of magnetic nanoparticles SO BIOCONJUGATE CHEMISTRY LA English DT Article ID MR CONTRAST AGENTS; DELIVERY; CELLS; TRANSDUCTION; FERUMOXIDES; FERUMOXTRAN AB Superparamagnetic nanoparticles have a number of important biomedical applications, serving as MR contrast agents for imaging specific molecular targets, as reagents for cell labeling and cell tracking, and for the isolation of specific classes of cells. We have determined the physical and biological properties of MION-47 and amino-CLIO, nanoparticles which serve as precursors for the synthesis of targeted MR contrast agents, and Tat-CLIO, a nanoparticle used as a cell labeling reagent. Blood half-lives for MION-47 and amino-CLIO were 682 +/- 34 and 655 +/- 37 min, respectively. The attachment of 9.7 tat peptides per crystal to amino-CLIO resulted in a reduction in blood half-life to 47 +/- 6 min. MION-47, amino-CLIO, and Tat-CLIO were present in highest concentrations in liver and spleen and lymph nodes, where concentrations for all three nanoparticles ranged from 8.80 to 6.11% of injected dose per gram. Twenty-four hours after the intravenous injection of amino-CLIO, the nanoparticle was concentrated in cells surrounding hepatic blood vessels (endothelial and Kupffer cells), in a fashion similar to that obtained with other nanoparticle preparations. In contrast, Tat-CLIO was present as numerous discrete foci of intense fluorescence throughout the parenchyma. Using the peptide as a component of future nanoparticles, it might be possible to design sensors for the detection of macromolecules present in intracellular compartments. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. RP Josephson, L (reprint author), MGH CMIR, Bldg 149,13th St,Room 5406, Charlestown, MA 02129 USA. NR 23 TC 241 Z9 246 U1 4 U2 34 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAR-APR PY 2002 VL 13 IS 2 BP 264 EP 268 DI 10.1021/bc015563u PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 534NN UT WOS:000174592600014 PM 11906263 ER PT J AU Zupan, LH Merfeld, DM Darlot, C AF Zupan, LH Merfeld, DM Darlot, C TI Using sensory weighting to model the influence of canal, otolith and visual cues on spatial orientation and eye movements SO BIOLOGICAL CYBERNETICS LA English DT Article ID ANGULAR VESTIBULOOCULAR REFLEX; VERTICAL AXIS ROTATION; HUMAN OPTOKINETIC AFTERNYSTAGMUS; EARTH-HORIZONTAL AXIS; SQUIRREL-MONKEY; VESTIBULAR SYSTEM; SEMICIRCULAR CANALS; OCULAR RESPONSES; VIEWING DISTANCE; INERTIAL REPRESENTATION AB The sensory weighting model is a general model of sensory integration that consists of three processing layers. First, each sensor provides the central nervous system (CNS) with information regarding a specific physical variable. Due to sensor dynamics, this measure is only reliable for the frequency range over which the sensor is accurate. Therefore, we hypothesize that the CNS improves on the reliability of the individual sensor outside this frequency range by using information from other sensors, a process referred to as "frequency completion." Frequency completion uses internal models of sensory dynamics. This "improved" sensory signal is designated as the "sensory estimate" of the physical variable. Second, before being combined, information with different physical meanings is first transformed into a common representation; sensory estimates are converted to intermediate estimates. This conversion uses internal models of body dynamics and physical relationships. Third, several sensory systems may provide information about the same physical variable (e.g., semicircular canals and vision both measure self-rotation). Therefore, we hypothesize that the "central estimate" of a physical variable is computed as a weighted sum of all available intermediate estimates of this physical variable, a process referred to as "multicue weighted averaging." The resulting central estimate is fed back to the first two layers. The sensory weighting model is applied to three-dimensional (3D) visual-vestibular interactions and their associated eye movements and perceptual responses. The model inputs are 3D angular and translational stimuli. The sensory inputs are the 3D sensory signals coming from the semicircular canals, otolith organs, and the visual system. The angular and translational components of visual movement are assumed to be available as separate stimuli measured by the visual system using retinal slip and image deformation. In addition, both tonic ("regular") and phasic ("irregular") otolithic afferents are implemented. Whereas neither tonic nor phasic otolithic afferents distinguish gravity from linear acceleration, the model uses tonic afferents to estimate gravity and phasic afferents to estimate linear acceleration. The model outputs are the internal estimates of physical motion variables and 3D slow-phase eye movements. The model also includes a smooth pursuit module. The model matches eye responses and perceptual effects measured during various motion paradigms in darkness (e.g., centered and eccentric yaw rotation about an earthvertical axis, yaw rotation about an earth-horizontal axis) and with visual cues (e.g., stabilized visual stimulation or optokinetic stimulation). C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol,Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. Ecole Natl Super Telecommun Bretagne, CNRS, URA 820, F-75634 Paris, France. RP Zupan, LH (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol,Jenks Vestibular Physiol Lab, 243 Charles St,Suite 421, Boston, MA 02114 USA. FU NIDCD NIH HHS [DC03065, DC04644] NR 105 TC 138 Z9 141 U1 1 U2 8 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-1200 J9 BIOL CYBERN JI Biol. Cybern. PD MAR PY 2002 VL 86 IS 3 BP 209 EP 230 DI 10.1007/s00422-001-0290-1 PG 22 WC Computer Science, Cybernetics; Neurosciences SC Computer Science; Neurosciences & Neurology GA 538AY UT WOS:000174792900004 PM 12068787 ER PT J AU Parmigiani, G Skates, S Zelen, M AF Parmigiani, G Skates, S Zelen, M TI Modeling and optimization in early detection programs with a single exam SO BIOMETRICS LA English DT Article DE chronic disease; colorectal cancer screening; competing risks; decision analysis; overdiagnosis ID ONCE-ONLY SIGMOIDOSCOPY; COLORECTAL-CANCER; SIMULATION-MODEL; OVARIAN-CANCER; DISEASE; UTILITY; PREVENTION; TIME; AGES AB The choice of timing of screening examinations is an important element in determining the efficacy of strategies for the early detection of occult disease. In this article, we describe a flexible decision-making framework for the design of early detection programs, and we investigate the choice of timing when each individual in the screening program is examined only once. We focus on the theoretical relation between the optimal examination time and the distributions of sojourn times in health-related states. Specifically, we derive closed-form solutions of the optimal age using two specifications of utility functions, discuss the effects of natural history and utility specifications on the optimal solution, and present an application to early detection of colorectal cancer by once-only sigmoidoscopy or colonoscopy. C1 Johns Hopkins Univ, Dept Oncol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21205 USA. Harvard Med Sch, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Sch Publ Hlth, Boston, MA USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Parmigiani, G (reprint author), Johns Hopkins Univ, Dept Oncol, Baltimore, MD 21205 USA. FU NCI NIH HHS [CA-57397, CA-78607, P50 CA 62924] NR 35 TC 9 Z9 9 U1 1 U2 2 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 2002 VL 58 IS 1 BP 30 EP 36 DI 10.1111/j.0006-341X.2002.00030.x PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 528DN UT WOS:000174229300004 PM 11890325 ER PT J AU Betensky, RA Finkelstein, DM AF Betensky, RA Finkelstein, DM TI Testing for dependence between failure time and visit compliance with interval-censored data SO BIOMETRICS LA English DT Article DE AIDS; dependent censoring; missing data; screening AB Interval-censored failure-time data arise when subjects miss prescheduled visits at which the failure is to be assessed. The resulting intervals in which the failure is known to have occurred are overlapping. Most approaches to the analysis of these data assume that the visit-compliance process is ignorable with respect to likelihood analysis of the failure-time distribution. While this assumption offers considerable simplification, it is not always plausible. Here we test for dependence between the failure- and visit-compliance processes, applicable to studies in which data collection continues after the occurrence of the failure. We do not make any of the assumptions made by previous authors about the joint distribution of the visit-compliance process, a covariate process, and the failure time. Instead, we consider conditional models of the true failure history given the current visit compliance at each visit time, allowing for correlation across visit dines. Because failure status is not known at some visit times due to missed visits, only models of the observed failure history given current visit compliance are estimable. We describe how the parameters from these models can be used to test for a negative association and how bounds on unestimable parameters provided by the observed data are needed additionally to infer a positive association. We illustrate the method with data from an AIDS study and we investigate the power of the test through a simulation study. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Betensky, RA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA74302, CA75791]; NIAID NIH HHS [N01-AI-38855] NR 11 TC 12 Z9 12 U1 1 U2 2 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 2002 VL 58 IS 1 BP 58 EP 63 DI 10.1111/j.0006-341X.2002.00058.x PG 6 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 528DN UT WOS:000174229300007 PM 11890327 ER PT J AU Li, Y Betensky, RA Louis, DN Cairncross, JG AF Li, Y Betensky, RA Louis, DN Cairncross, JG TI The use of frailty hazard models for unrecognized heterogeneity that interacts with treatment: Considerations of efficiency and power SO BIOMETRICS LA English DT Article DE omitted covariate ID COVARIATE; TESTS AB Increasingly, genetic studies of tumors of the same histologic diagnosis are elucidating subtypes that are distinct with respect to clinical endpoints such as response to treatment and survival. This raises concerns about the efficiency of using the simple log-rank test for analysis of treatment effect oil survival in studies of possibly heterogeneous tumors. Furthermore, such studies, designed under the assumption of homogeneity, may be severely underpowered. We derive analytic approximations for the asymptotic relative efficiency of the simple log-rank test relative to the optimally weighted log-rank test and for the power of the simple log-rank test when applied to subjects with unobserved Heterogeneity, as reflected in a continuous frailty, that may interact with treatment. Numerical studies demonstrate that the simple log-rank test may be quite inefficient if the frailty interacts with treatment. Further, there may be a substantial loss of power in the presence of the frailty with or without an interaction with treatment. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Western Ontario, Dept Oncol, London, ON, Canada. London Reg Canc Ctr, London, ON N6A 4L6, Canada. RP Li, Y (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. FU NCI NIH HHS [CA75971, CA57683, CA57253] NR 10 TC 14 Z9 14 U1 0 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 2002 VL 58 IS 1 BP 232 EP 236 DI 10.1111/j.0006-341X.2002.00232.x PG 5 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 528DN UT WOS:000174229300028 PM 11890320 ER PT J AU Wright, JE Rosowsky, A AF Wright, JE Rosowsky, A TI Synthesis and enzymatic activation of N-[N-alpha-(4-amino-4-deoxypteroyl)-N-delta-hemiphthaloyl-L-ornithiny]-L -phenylalanine, a candidate for antibody-directed enzyme prodrug therapy (ADEPT) SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID NONPOLYGLUTAMATABLE ANTIFOLATE N-ALPHA-(4-AMINO-4-DEOXYPTEROYL)-N-DELTA-HEMIPHTH; HUMAN CARBOXYPEPTIDASE A1; DIHYDROFOLATE-REDUCTASE; IN-VIVO; SIDE-CHAIN; METHOTREXATE ANALOGS; TARGETED ENZYMES; T268G MUTANT; NUDE-MICE; PT523 AB N-[N-alpha-(4-Amino-4-deoxypteroyl)-N-delta-hemiphthaloyl-L-ornithinyl]-L-phenylalanine (1), a carboxypeptidase A (CPA) cleavable prodrug was synthesized for use in an antibody directed strategy to improve the therapeutic selectivity of N-alpha-(4-amino-4-deoxypteroyl)-N-delta-hemiphthaloyl-L-ornithine (2), an extremely potent nonpoly-glutamatable DHFR inhibitor which is also highly cytotoxic. Compound I was shown by HPLC analysis to give a >99% yield of 2 upon incubation with bovine CPA (bCPA) for 20 min at 25degreesC. In a spectrophotometric kinetic assay with 50 muM dihydrofolate as the competing substrate in the presence of 65 muM NADPH. 1+bCPA stoichiometrically inhibited recombinant human DHFR (rhDHFR) with a K-i of 0.35 pM. In contrast, I without bCPA was a poor inhibitor of rhDHFR (K-i > 10 muM). In a 72 h growth inhibition assay against cultured CCRF-CEM human leukemic lymphoblasts. the growth inhibitory activities of 1+bCPA, 2+bCPA, and 2 alone were the same (IC50 1.3-1.4 nM), whereas I in the absence of bCPA was > 100-fold less potent (IC50 155 nM). (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Wright, JE (reprint author), 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA 25394] NR 32 TC 5 Z9 5 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD MAR PY 2002 VL 10 IS 3 BP 493 EP 500 DI 10.1016/S0968-0896(01)00298-X PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 517CR UT WOS:000173594000003 PM 11814834 ER PT J AU Schiffmann, R Mankin, H Dambrosia, JM Xavier, RJ Kreps, C Hill, SC Barton, NW Rosenthal, DI AF Schiffmann, R Mankin, H Dambrosia, JM Xavier, RJ Kreps, C Hill, SC Barton, NW Rosenthal, DI TI Decreased bone density in splenectomized Gaucher patients receiving enzyme replacement therapy SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article ID MACROPHAGE-TARGETED GLUCOCEREBROSIDASE; SEVERE SKELETAL INVOLVEMENT; POSTMENOPAUSAL WOMEN; MINERAL DENSITY; QUANTITATIVE CT; LUMBAR SPINE; DISEASE; MARROW; OSTEOPOROSIS; ALENDRONATE AB Little is known about the effect of enzyme replacement therapy (ERT) on the bone abnormalities in Gaucher disease. Splenectornized Gaucher patients tend to suffer the most severe skeletal complications. We hypothesized that vitamin D supplementation would act synergistically with glucocerebrosidase infusions to increase bone density in splenectomized Gaucher patients. In a 24-month study, 29 splenectomized Gaucher patients were randomized to three groups: Group 1, calcitriol (1,25-dihydroxy vitamin D-3; 0.25-3.0 mug/day) alone for the first 6 months with the addition of ceredase/cerezyme at 60 IU/kg every 2 weeks during months 7-12; Group 2, calcitriol together with ceredase/cerezyme at 60 IU/kg every 2 weeks during months 1-6; and Group 3, enzyme only at 60 IU/kg body wt every 2 weeks. In all three groups, enzyme dose was halved after [he first 6 months of therapy. The primary outcome measure was bone mineral density of the lumbar spine measured by single-energy quantitative CT. Bone density by single-energy CT (P = 0.001) and by dual-energy CT (P = 0.06) declined overall, but there was no significant difference between the groups. Calcitriol had no significant, effect on bone density. Fat fraction in lumbar spine increased (P = 0.000) and skeletal MRI scores improved. Bone-specific alkaline phosphatase (P = 0.002) and serum osteocalcin increased (P = 0.008), while blood cyclic AMP and urinary deoxypyridinoline did not change appreciably. Hemoglobin, platelet counts, and liver volume significantly improved. We conclude that ERT alone, or in combination with calcitriol, cannot repair the bone composition in splenectomized adult Gaucher patients. Alternatively, measuring trabecular bone density may be an inadequate marker of clinical efficacy for treating skeletal involvement in Gaucher disease. (C) 2002 Elsevier Science (USA). C1 NINCDS, Dev & Metab Branch, NIH, Bethesda, MD 20892 USA. NINCDS, Biostat Branch, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Orthopaed Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med & Mol Biol, Boston, MA 02114 USA. NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Schiffmann, R (reprint author), NINCDS, Dev & Metab Branch, NIH, Bldg 10,Room 3D03,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 35 TC 42 Z9 42 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAR PY 2002 VL 28 IS 2 BP 288 EP 296 DI 10.1006/bcmd.2002.0517 PG 9 WC Hematology SC Hematology GA 565HC UT WOS:000176362900024 PM 12064924 ER PT J AU Antin, JH Lee, SJ Neuberg, D Alyea, E Soiffer, RJ Sonis, S Ferrara, JLM AF Antin, JH Lee, SJ Neuberg, D Alyea, E Soiffer, RJ Sonis, S Ferrara, JLM TI A phase I/II double-blind, placebo-controlled study of recombinant human interleukin-11 for mucositis and acute GVHD prevention in allogeneic stem cell transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article DE interleukin-11; graft-versus-host disease; stem cell transplantation ID VERSUS-HOST DISEASE; BONE-MARROW TRANSPLANTATION; CYTOKINE PRODUCTION; GRAFT; RADIATION; MICE; PRETREATMENT; RECEPTOR; RECOVERY; SEVERITY AB Interleukin-11 (IL-11) decreases cytokine release and increases survival in murine BMT models. In these systems, it reduces gut permeability, partially polarizes T cells to a Th2 phenotype, down-regulates IL-12, prevents mucositis, and accelerates recovery of oral and bowel mucosa. We conducted a randomized double-blind pilot study of rhIL-11 administered with cyclosporine/MTX prophylaxis after cytoxan/TBI conditioning and allogeneic stem cell transplantation for hematologic malignancies. Patients received rhIL-11, 50 mug/kg subcutaneously daily or placebo in a 3:1 ratio. Treatment was administered prior to the start of conditioning and continued up to 21 days. The study was designed to assess safety with stopping rules for cardiac arrhythmias and mortality. Although projected to accrue 20 patients, only 13 patients (10 IL-11, three placebo) were enrolled because the early stopping rule for mortality was triggered. Of 10 evaluable patients who received IL-11, four died by day 40 and one died on day 85. Deaths were attributable to transplant-related toxicity. One of three placebo recipients died of suicide, the other two are alive. Patients receiving IL-11 had severe fluid retention and early mortality, making it impossible to determine whether IL-11 given in this schedule can reduce the rate of GVHD. Grade B-D acute GVHD occurred in two of eight evaluable patients on IL-11 and one of three patients on placebo. The primary adverse events of the study were severe fluid retention resistant to diuresis (average weight gain 9 4%) and multiorgan failure in five of 10 evaluable patients. The use of IL-11 as GVHD prophylaxis in allogeneic transplantation cannot be recommended as administered in this trial. C1 Dana Farber Canc Inst, Dept Adult Oncol & Biostat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA USA. Brigham & Womens Hosp, Dept Surg, Boston, MA USA. RP Antin, JH (reprint author), Dana Farber Canc Inst, Dept Adult Oncol & Biostat Sci, 44 Binney St, Boston, MA 02115 USA. NR 32 TC 49 Z9 51 U1 0 U2 3 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 2002 VL 29 IS 5 BP 373 EP 377 DI 10.1038/sj/bmt/1703394 PG 5 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 534VX UT WOS:000174611400002 PM 11919725 ER PT J AU Colby, C Koziol, S McAfee, SL Yeap, B Spitzer, TR AF Colby, C Koziol, S McAfee, SL Yeap, B Spitzer, TR TI High-dose carboplatin and regimen-related toxicity following autologous bone marrow transplant SO BONE MARROW TRANSPLANTATION LA English DT Article DE autologous bone marrow transplant; carboplatin; AUC; regimen-related toxicity ID EPITHELIAL OVARIAN-CANCER; COMBINATION CHEMOTHERAPY; RENAL-FUNCTION; PHASE-I; CYCLOPHOSPHAMIDE; PHARMACOKINETICS; CLEARANCE; SUPPORT; OPTIMIZATION; PREDICTION AB Pharmacokinetic analysis of carboplatin dosing suggests a more accurate prediction of toxicity when the dose is based on the area under the plasma concentration vs time curve (AUC) instead of body surface area (BSA). We retrospectively calculated the carboplatin AUC of 117 patients who received an autologous stem cell transplant following a conditioning regimen consisting of carboplatin 1800 mg/m(2) and cyclophosphamide 6000 mg/m(2) to identify whether higher carboplatin exposure resulted in an increase in regimen-related non-hematologic toxicities. The most common non-hematologic toxicities were gastrointestinal and hepatic. Twenty (17%) patients experienced additional greater than or equal tograde 2 toxicity, specifically, renal toxicity significantly associated with a higher median AUC of 10.2 mg/ml(-1) min (P = 0.001). Prior platinum therapy was also significantly associated with toxicity (P = 0.052). While carboplatin dose based on BSA varied minimally (median 990 (range 450-1340) mg, the calculated AUC showed a near four-fold range of exposure (median 7.8 (range 3.6 to 13.8) mg/ml(-1) min). These data suggest a relationship between nonhematologic adverse events and the estimated AUC. Prospective trials will be necessary to identify the target carboplatin AUC which optimizes outcome and minimizes toxicity in the autologous transplant setting. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplantat Program,Dept Med, Boston, MA USA. RP Spitzer, TR (reprint author), Massachusetts Gen Hosp, Bone Marrow Transplant Program, Cox 640,55 Fruit St, Boston, MA 02114 USA. NR 34 TC 6 Z9 6 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 2002 VL 29 IS 6 BP 467 EP 472 DI 10.1038/sj/bmt/1703417 PG 6 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 541ZX UT WOS:000175018500002 PM 11960264 ER PT J AU Yampolsky, S Waters, G Caplan, D Matthies, M Chiu, P AF Yampolsky, S Waters, G Caplan, D Matthies, M Chiu, P TI Effects of acoustic degradation on syntactic processing: Implications for the nature of the resource system used in language processing SO BRAIN AND COGNITION LA English DT Article; Proceedings Paper CT 12th Annual Meeting on Tennet - Theoretical and Experimental Neuropsychology CY JUN 21-23, 2001 CL UNIV QUEBEC, MONTREAL, CANADA HO UNIV QUEBEC ID WORKING-MEMORY; INDIVIDUAL-DIFFERENCES; RELATIVE-CLAUSE; COMPREHENSION; SENTENCES; MORPHOLOGY; COMPLEXITY; NORMALS AB This study investigated the effect of noise masking on on-line syntactic processing. Ninety college students were tested on measures of working memory and on-line sentence comprehension. Subjects were divided equally into three listening conditions: no noise masking, -3 dB signal-to-noise ratio (S: N), -4.5 dB S: N. The auditory moving windows (AMW) paradigm was used to measure on-line sentence processing. In the AMW paradigm, subjects pressed a button for the successive presentation of each phrase in two types of sentences (syntactically simple and complex), and listening times were recorded for each phrase. Previous studies have shown that the verb in the more complex sentence type is the most capacity demanding portion of the sentence. Listening times were longer overall with increased noise masking, and listening times were longer overall at the verb of the harder sentence type. However, the increase at the verb was not larger with increased noise masking. All three groups showed similar effects of syntactic structure in the on-line data. The on-line syntactic effects were not due to problems in word recognition. Correlational analyses did not indicate a relationship between the increase in processing time at the capacity demanding region of the harder sentence types and any of the measures of working memory capacity in any of the three listening conditions. Results indicate that on-line sentence processing is not affected by noise masking if lexical access (e.g.. word recognition) remains intact. (C) 2002 Elsevier Science (USA). C1 Boston Univ, Sargent Coll Hlth & Rehabil Sci, Dept Commun Disorders, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Cincinnati, Cincinnati, OH 45221 USA. RP Yampolsky, S (reprint author), Boston Univ, Sargent Coll Hlth & Rehabil Sci, Dept Commun Disorders, Room 351,635 Commonwealth Ave, Boston, MA 02215 USA. NR 18 TC 1 Z9 1 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD MAR-APR PY 2002 VL 48 IS 2-3 BP 617 EP 625 DI 10.1006/brcg.2001.1428 PG 9 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 536ED UT WOS:000174687000125 PM 12030518 ER PT J AU Pejchal, T Foley, MA Kosofsky, BE Waeber, C AF Pejchal, T Foley, MA Kosofsky, BE Waeber, C TI Chronic fluoxetine treatment selectively uncouples raphe 5-HT1A receptors as measured by [S-35]-GTP gamma S autoradiography SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE Selective Serotonin Reuptake Inhibitors; G protein coupling; [S-35]-GTP gamma S autoradiography; serotonin receptors; serotonin autoreceptors; chronic fluoxetine treatment ID ACTIVATED G-PROTEINS; IN-VITRO AUTORADIOGRAPHY; GAMMA-S BINDING; KNOCK-OUT MICE; RAT-BRAIN; ANTIDEPRESSANT TREATMENTS; SEROTONIN 5-HT1A; AGONIST; DESENSITIZATION; AUTORECEPTORS AB 1 Selective Serotonin Reuptake Inhibitors (SSRIs) are thought to have a delay in therapeutic efficacy because of the need to overcome the inhibitory influence of raphe 5-HT1A autoreceptors. Prolonged SSRI administration has been reported to desensitize these autoreceptors. We have used [S-35]-GTPgammaS autoradiography to determine whether this desensitization occurs at the level of receptor/G protein coupling. 2 Male mice were injected intraperitoneally once a day with saline or 20 mg kg(-1) fluoxetine for either 2 days or 14 days. 5-HT1A receptor binding and coupling to G proteins were assessed using [H-3]-8-OH-DPAT and [S-35]-GTPgammaS autoradiography, respectively. 3 The 5-HT receptor agonist 5-carboxamidotryptamine (5-CT) stimulated [S-35]-GTPgammaS binding in the substantia nigra, as well as in hippocampus and dorsal raphe nucleus. The 5-HT1A receptor antagonist p-MPPF (4-fluoro-N-(2-(4-(2-methoxyphenyl)l-piperazinyl]ethyl)-N-(2-pyridinyl)benzamide) blocked this effect in the latter regions, whereas the 5-HT1B/D antagonist GR-127,935 (2'methyl-4'-(5-methyl-[1,2,4]oxadiazol-3-yi)-biphenyl-4-carboxylic acid [4-methoxy-3-(4-methyl-piperazin-1-yl)-phenyl]-amide) only decreased labelling in substantia nigra. 4 Fourteen-day fluoxetine treatment decreased 5-CT-stimulated [S-35]-GTPgammaS binding in dorsal raphe (saline: 112+/-12% stimulation, fluoxetine: 66+/-13%), but not in substantia nigra (99+/-14% vs 103+/-7%) or hippocampus (157+/-3% vs 148+/-18%). Two-day fluoxetine treatment did not alter 5-CT-stimulated [S-35]-GTPgammaS binding in any of the brain areas investigated. 5 Decreased [S-35]-GTPgammaS binding was not due to receptor down-regulation, since the density of raphe [H-3]-8-OH-DPAT binding sites was unaffected by fluoxetine treatment. 6 These results suggest that the desensitization of presynaptic 5-HT1A receptor function occurs at the level of receptor-G protein interaction on dorsal raphe neurons, and may underlie the therapeutic efficacy of long-term SSRI treatment. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Neurosci, Charlestown, MA 02129 USA. RP Waeber, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Neurosci, Room 6403, Charlestown, MA 02129 USA. RI Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 NR 38 TC 49 Z9 50 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD MAR PY 2002 VL 135 IS 5 BP 1115 EP 1122 DI 10.1038/sj.bjp.0704555 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 530XN UT WOS:000174384400005 PM 11877317 ER PT J AU Louis, DN Pomeroy, SL Cairncross, JG AF Louis, DN Pomeroy, SL Cairncross, JG TI Focus on central nervous system neoplasia SO CANCER CELL LA English DT Article ID GLIOBLASTOMA-MULTIFORME; ANAPLASTIC OLIGODENDROGLIOMA; EGFR AMPLIFICATION; BRAIN-TUMORS; MEDULLOBLASTOMA; EXPRESSION; SURVIVAL; ASTROCYTOMAS; PREDICTORS C1 Massachusetts Gen Hosp, Dept Pathol & Neurosurg Serv, Boston, MA 02114 USA. Univ Western Ontario, Dept Oncol, London, ON N6A 4L6, Canada. London Reg Canc Ctr, London, ON N6A 4L6, Canada. Childrens Hosp, Dept Neurol, Div Neurosci, Boston, MA 02115 USA. RP Louis, DN (reprint author), Massachusetts Gen Hosp, Dept Pathol & Neurosurg Serv, Boston, MA 02114 USA. NR 23 TC 102 Z9 103 U1 0 U2 0 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 2002 VL 1 IS 2 BP 125 EP 128 DI 10.1016/S1535-6108(02)00040-5 PG 4 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 599TG UT WOS:000178350800005 PM 12086870 ER PT J AU Xiao, A Wu, H Pandolfi, PP Louis, DN Van Dyke, T AF Xiao, A Wu, H Pandolfi, PP Louis, DN Van Dyke, T TI Astrocyte inactivation of the pRb pathway predisposes mice to malignant astrocytoma development that is accelerated by PTEN mutation SO CANCER CELL LA English DT Article ID LARGE T-ANTIGEN; TUMOR-SUPPRESSOR GENE; TRANSGENIC MICE; IN-VIVO; RETINOBLASTOMA GENE; TARGETED DISRUPTION; NEURAL PROGENITORS; CHIMERIC MICE; MUTANT MICE; J-DOMAIN AB We have inactivated pRb, p107, and p130 in astrocytes by transgenic expression of T-121 (a truncated SV40 T antigen) under the GFAP promoter. Founder mice died perinatally with extensive expansion of neural precursor and anaplastic astrocyte populations. In astrocytes, aberrant proliferation and extensive apoptosis were induced. Using a conditional allele of T-121, early lethality was circumvented, and adult mice developed high-grade astrocytoma, in which regions of decreased apoptosis expressed activated Akt. Indeed, astrocytoma development was accelerated in a PTEN+/-, but not p53(+/-), background. These studies establish a highly penetrant preclinical model for astrocytoma based on events observed in the human disease and further provide insight into the role of PTEN mutation in astrocytoma progression. C1 Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Dept Pathol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA. Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neurol Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Van Dyke, T (reprint author), Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. FU NCI NIH HHS [1 R01 CA 46283, 5 U01 CA84314] NR 44 TC 113 Z9 117 U1 0 U2 0 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 2002 VL 1 IS 2 BP 157 EP 168 DI 10.1016/S1535-6108(02)00029-6 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 599TG UT WOS:000178350800009 PM 12086874 ER PT J AU Singh, D Febbo, PG Ross, K Jackson, DG Manola, J Ladd, C Tamayo, P Renshaw, AA D'Amico, AV Richie, JP Lander, ES Loda, M Kantoff, PW Golub, TR Sellers, WR AF Singh, D Febbo, PG Ross, K Jackson, DG Manola, J Ladd, C Tamayo, P Renshaw, AA D'Amico, AV Richie, JP Lander, ES Loda, M Kantoff, PW Golub, TR Sellers, WR TI Gene expression correlates of clinical prostate cancer behavior SO CANCER CELL LA English DT Article ID RADICAL PROSTATECTOMY; CLASSIFICATION; ADENOCARCINOMA; RECURRENCE; SURVIVAL AB Prostate tumors are among the most heterogeneous of cancers, both histologically and clinically. Microarray expression analysis was used to determine whether global-biological differences underlie common pathological features of prostate cancer and to identify genes that might anticipate the clinical behavior of this disease. While no expression correlates of age, serum prostate specific antigen (PSA), and measures of local invasion were found, a set of genes was identified that strongly correlated with the state of tumor differentiation as measured by Gleason score. Moreover, a model using gene expression data alone accurately predicted patient outcome following prostatectomy. These results support the notion that the clinical behavior of prostate cancer is linked to underlying gene expression differences that are detectable at the time of diagnosis. C1 Harvard Univ, Sch Med, Dept Adult Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biostat Sci, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Internal Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Urol Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Bristol Myers Squibb Co, Pharmaceut Res Inst, Princeton, NJ 08543 USA. RP Febbo, PG (reprint author), Harvard Univ, Sch Med, Dept Adult Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. FU NCI NIH HHS [CA84995, CA89031, K23 CA089031, K23 CA089031-02] NR 23 TC 1285 Z9 1347 U1 10 U2 56 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 2002 VL 1 IS 2 BP 203 EP 209 DI 10.1016/S1535-6108(02)00030-2 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 599TG UT WOS:000178350800013 PM 12086878 ER PT J AU Fuchs, CS Willett, WC Colditz, GA Hunter, DJ Stampfer, MJ Speizer, FE Giovannucci, EL AF Fuchs, CS Willett, WC Colditz, GA Hunter, DJ Stampfer, MJ Speizer, FE Giovannucci, EL TI The influence of folate and multivitamin use on the familial risk of colon cancer in women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID METHYLENETETRAHYDROFOLATE REDUCTASE POLYMORPHISM; SELF-ADMINISTERED QUESTIONNAIRE; METHIONINE SYNTHASE GENE; COLORECTAL-CANCER; ALCOHOL-CONSUMPTION; ADENOMATOUS POLYPS; ULCERATIVE-COLITIS; CIGARETTE-SMOKING; PLASMA FOLATE; UNITED-STATES AB Low intake of folate and methionine and heavy alcohol consumption have been associated with an increased overall risk of colon cancer, possibly related to their role in methylation pathways. We estimated the relative risk (RR) of colon cancer according to a history of colorectal cancer in a first-degree relative and categories of folate, methionine, and alcohol intake in a prospective cohort study of 88,758 women who completed family history and detailed food frequency questionnaires. During 16 years of follow-up, colon cancer was diagnosed in 535 women. The inverse association of folic acid with colon cancer risk was greater in women with a family history. Compared with women who consumed 200 tug or less of folic acid/day, the age-adjusted RR of colon cancer for those who consumed >400 mug/day was 0.81 (95% confidence interval, 0.62-1.07) in women without a family history of colorectal cancer and 0.48 (95% confidence interval, 0.28-0.83) in women with a family history (P for interaction = 0.02). The influence of family history was markedly diminished by use of multivitamins containing folic acid (P for interaction = 0.04). High levels of dietary methionine also reduced the effect of family history (P for interaction = 0.05), whereas moderate to heavy alcohol consumption increased the risk associated with family history (P for interaction = 0.004). Other risk factors for colorectal cancer did not significantly modify the influence of family history. Our results suggest that higher intake of folate and methionine, regular use of multivitamins containing folate, and avoidance of moderate to heavy alcohol consumption may diminish the excess risk of colon cancer associated with a family history of the disease. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. RP Fuchs, CS (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [P01 CA87969] NR 52 TC 93 Z9 95 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2002 VL 11 IS 3 BP 227 EP 234 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 534AC UT WOS:000174561600001 PM 11895870 ER PT J AU Abe, T Wakimoto, H Bookstein, R Maneval, DC Chiocca, EA Basilion, JP AF Abe, T Wakimoto, H Bookstein, R Maneval, DC Chiocca, EA Basilion, JP TI Intra-arterial delivery of p53-containing adenoviral vector into experimental brain tumors SO CANCER GENE THERAPY LA English DT Article DE gliomas; gene therapy; p53; adenovirus; systemic administration ID WILD-TYPE P53; HUMAN-MALIGNANT GLIOMA; SIMPLEX VIRUS MUTANT; ENCODING HUMAN P53; GENE-THERAPY; RECOMBINANT ADENOVIRUS; IN-VIVO; INTRAARTERIAL DELIVERY; GROWTH; SUPPRESSOR AB Human tumor xenografts established in athymic rat brains were used to determine the feasibility of intravascular delivery of tumor suppressor genes to brain tumors. Both tumor size and number were compared to characterize the effect of tumor burden on tumor transduction efficacy by a control LacZ-containing adenoviral vector. Experiments with tumors grown in vivo for either 3, 5, or 7 days demonstrated that 5-day-old tumors provided the best target for vector infection and transgene expression by this mode of administration. Intra-arterial mannitol facilitated transduction efficiency. Tumor burden did not seem to affect transduction, while tumor location appeared to be an important factor. Based on these results, intra-arterial infusion of a p53-containing adenoviral vector was carried out and resulted in significant retardation of brain tumor growth 3 days after administration. Effects at longer time points were not as significant. These findings indicate that intra-arterial administration of adenoviral vectors containing p53 is efficient and can result in changes in tumor size, but that long-term control of tumor growth may require multiple adenoviral treatments. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv,Mol Neuro Oncol Labs, Charlestown, MA USA. Canji Inc, San Diego, CA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA USA. Oita Med Univ, Dept Neurosurg, Oita, Japan. RP Basilion, JP (reprint author), MGH E, Ctr Mol Imaging Res, Bldg 149,13th St,5406, Charlestown, MA 02129 USA. NR 35 TC 24 Z9 26 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD MAR PY 2002 VL 9 IS 3 BP 228 EP 235 DI 10.1038/sj/cgt/7700437 PG 8 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 527ZD UT WOS:000174217200002 PM 11896438 ER PT J AU Zhou, W Liu, G Miller, DP Thurston, SW Xu, LL Wain, JC Lynch, TJ Su, L Christiani, DC AF Zhou, W Liu, G Miller, DP Thurston, SW Xu, LL Wain, JC Lynch, TJ Su, L Christiani, DC TI Gene-environment interaction for the ERCC2 polymorphisms and cumulative cigarette smoking exposure in lung cancer SO CANCER RESEARCH LA English DT Article ID INDUCED DNA-ADDUCTS; REPAIR; DAMAGE; RISK; STRAND; GENDER; XPD; AGE AB Excision repair cross-complementing group 2 (ERCC2), a major DNA repair protein, is involved in nucleotide excision repair and basal transcription. The ERCC2 polymorphisms have been associated with altered DNA repair capacity. We investigated two ERCC2 polymorphisms, Asp312Asn and Lys751Gln, in 1092 Caucasian lung cancer patients and 1240 spouse and friend controls. The results were analyzed using generalized additive models and logistic regression, adjusting for relevant covariates. The overall adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 1.47 (95% CI, 1.1-2.0) for the Asp312Asn polymorphism (Asn/Asn versus Asp/Asp) and 1.06 (95% CI, 0.8-1.4) for the Lys751Gln polymorphism (Gln/Gln versus Lys/Lys). Gene-smoking interaction analyses revealed that the adjusted ORs for each of the two polymorphisms decreased significantly as pack-years increased. When comparing individuals with Asn/Asn + Gln/Gln versus individuals with Asp/Asp + Lys/Lys, the fitted ORs (95% CIs) were 2.56 (95% CI, 1.3-5.0) in nonsmokers and 0.69 (95% CI, 0.4-1.2) in heavy smokers (80 pack-years; P < 0.01 for the interaction term). Consistent and robust results were found when models incorporated different definitions of cumulative cigarette smoking. A stronger gene-smoking interaction was observed for the Asp312Asn polymorphism than for the Lys751Gln polymorphism. In conclusion, cumulative cigarette smoking modifies the associations between ERCC2 polymorphisms and lung cancer risk. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Thorac Surg Unit, Boston, MA 02114 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, 665 Huntington Ave, Boston, MA 02115 USA. RI Liu, Geoffrey/N-4421-2016 FU FIC NIH HHS [TW00828]; NCI NIH HHS [CA74386]; NIEHS NIH HHS [ES/CA 06409, ES00002] NR 28 TC 119 Z9 128 U1 0 U2 2 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 2002 VL 62 IS 5 BP 1377 EP 1381 PG 5 WC Oncology SC Oncology GA 530AP UT WOS:000174333700027 PM 11888908 ER PT J AU Bradham, WS Bozkurt, B Gunasinghe, H Mann, D Spinale, FG AF Bradham, WS Bozkurt, B Gunasinghe, H Mann, D Spinale, FG TI Tumor necrosis factor-alpha and myocardial remodeling in progression of heart failure: a current perspective SO CARDIOVASCULAR RESEARCH LA English DT Review DE cytokines; extracellular matrix; heart failure; remodeling ID MATRIX-METALLOPROTEINASE ACTIVITY; VENTRICULAR EJECTION FRACTION; ADULT FELINE MYOCARDIUM; SMOOTH-MUSCLE CELLS; FAILING HUMAN HEART; DILATED CARDIOMYOPATHY; CIRCULATING LEVELS; TRANSGENIC MICE; INFLAMMATORY CYTOKINES; SIGNAL-TRANSDUCTION AB A milestone in the progression of congestive heart failure (CHF) is myocardial remodeling. Left ventricular (LV) remodeling during the progression of CHF is accompanied by changes in the structure of the myocardial extracellular matrix. Recent clinical and experimental studies have noted that increased release of tumor necrosis factor alpha (TNF-alpha) can contribute to LV myocardial remodeling. Experimental studies have noted that the induction of TNF-alpha can result in LV dilation and proceed to LV pump dysfunction. The biological effects of TNF-alpha are mediated through TNF receptors that are present on all nucleated cells in the heart. TNF receptor activation can induce a number of cellular and molecular events which contribute to LV remodeling in CHF, and include changes in myocyte size and viability and alterations in myocardial structure/composition. In vitro studies have demonstrated that TNF receptor activation can cause the induction of a proteolytic system. This proteolytic system, the matrix metalloproteinases (MMPs), is upregulated in models of LV dysfunction and possesses the capacity to degrade a wide variety of extracellular matrix components. Therefore, one pathway by which TNF-alpha can influence LV myocardial remodeling is through the induction of a specific portfolio of MMP species. Future basic and clinical studies which directly alter TNF receptor activity and measure myocarddial MMP species and the relation to LV remodeling will provide new insight into this disease process and future therapeutic modalities. (C) 2002 Elsevier Science BY All rights reserved. C1 Med Univ S Carolina, Charleston, SC 29425 USA. Houston VAMC, Winters Ctr Heart Failure Res, Cardiol Sect, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP Spinale, FG (reprint author), Med Univ S Carolina, Room 625,Strom Thurmond Res Bldg,770 MUSC Complex, Charleston, SC 29425 USA. OI Mann, Douglas /0000-0002-2516-0145 NR 82 TC 95 Z9 117 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD MAR PY 2002 VL 53 IS 4 BP 822 EP 830 AR PII S0008-6363(01)00503-X DI 10.1016/S0008-6363(01)00503-X PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 547DB UT WOS:000175316800004 PM 11922892 ER PT J AU Lemos, PA Martinez, EE Quintella, E Harrell, LC Ramires, JAF Ribeiro, EE da Gama, MN Horta, PE Kajita, LJ Esteves, A Perin, MA Soares, PR Zalc, S Palacios, IF AF Lemos, PA Martinez, EE Quintella, E Harrell, LC Ramires, JAF Ribeiro, EE da Gama, MN Horta, PE Kajita, LJ Esteves, A Perin, MA Soares, PR Zalc, S Palacios, IF TI Stenting vs. balloon angioplasty with provisional stenting for the treatment of vessels with small reference diameter SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article; Proceedings Paper CT 72nd Annual Scientific Session of the American-Heart-Association CY NOV 07-10, 1999 CL ATLANTA, GEORGIA SP Amer Heart Assoc DE coronary percutaneous intervention outcome; operator decision ID TRANSLUMINAL CORONARY ANGIOPLASTY; REVASCULARIZATION PROCEDURES; RANDOMIZED TRIAL; LUMINAL DIAMETER; ARTERIES; SIZE; CARDIOLOGISTS; STENOSIS; RISK AB A consecutive series of interventions in vessels with reference diameter less than or equal to 2.75 mm was retrospectively analyzed according to preprocedure strategy: balloon angioplasty with provisional stenting (PTCA group, 73 patients) and primary stenting (PS group, 122 patients). In the PS group, there were more patients with single-vessel disease (54.1% vs. 37.0%; P = 0.021), less patients with three-vessel disease (9.0% vs. 24.7%; P = 0.003), more LAD interventions (54.9% vs. 31.5; P = 0.002), and less left circumflex interventions (22.1% vs. 45.2%; P < 0.001). Reference diameter was larger in the PS group (2.28 +/- 0.35 mm vs. 2.11 +/- 0.36 mm; P = 0.001). Provisional stenting was performed in 39.7% of PTCA group. At long-term outcome, the incidence of composite major events was similar between the PTCA and the PS groups (20.5% vs. 17.2%, respectively; P = NS). Treatment of small vessels with balloon dilatation and provisional stenting or with primary stenting yielded similar late outcomes. Operators' choice of treatment strategy was based on particular angiographic characteristics. (C) 2002 Wiley-Liss, Inc. C1 Univ Sao Paulo, Sch Med, Inst Heart, Catheterizat Lab, BR-05403000 Sao Paulo, Brazil. Massachusetts Gen Hosp, Cardiac Catheterizat Lab, Boston, MA USA. RP Martinez, EE (reprint author), Univ Sao Paulo, Sch Med, Inst Heart, Catheterizat Lab, Av Dr Eneas De Carvalho Aguiar,44 Sao Paulo, BR-05403000 Sao Paulo, Brazil. RI Perin, Marco/O-2309-2014; Lemos, Pedro/G-5758-2013 OI Lemos, Pedro/0000-0002-6782-750X NR 24 TC 3 Z9 4 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD MAR PY 2002 VL 55 IS 3 BP 309 EP 314 DI 10.1002/ccd.10121 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 526CC UT WOS:000174110000007 PM 11870933 ER PT J AU Blagosklonny, MV Pardee, AB AF Blagosklonny, Mikhail V. Pardee, Arthur B. TI The Restriction Point of the Cell Cycle SO CELL CYCLE LA English DT Review DE Cell cycle; Cyclins; Growth factors; Oncogenes AB As formulated in 1974, the concept of the restriction point of the cell cycle was based on cell biological experiments, yet allowing accurate molecular predictions and spurring a search for the restriction factor. Although cyclin D meets the criteria of the R-factor, the picture as outlined here is more interesting and far more complex. We discuss the relationship between the restriction knot and DNA damage-checkpoints. Finally, we discuss how loss of the restriction point in cancer leads to loss of checkpoint control and to insensitivity to antimitogens including some mechanism-based anticancer therapeutics. C1 [Blagosklonny, Mikhail V.] NCI, NIH, Bethesda, MD 20892 USA. [Blagosklonny, Mikhail V.] New York Med Coll, Brander Canc Res Inst, Hawthorne, NY 10532 USA. [Pardee, Arthur B.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pardee, Arthur B.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Blagosklonny, MV (reprint author), New York Med Coll, Brander Canc Res Inst, Dept Med, 19 Bradhurst Ave, Hawthorne, NY 10532 USA. EM mikhailb@mail.nih.gov NR 138 TC 202 Z9 217 U1 1 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1538-4101 EI 1551-4005 J9 CELL CYCLE JI Cell Cycle PD MAR-APR PY 2002 VL 1 IS 2 BP 103 EP 110 DI 10.4161/cc.1.2.108 PG 8 WC Cell Biology SC Cell Biology GA V40PW UT WOS:000209491500002 PM 12429916 ER PT J AU Halamay, KE Kirkman, RL Sun, LH Yamada, A Fragoso, RC Shimizu, K Mitchell, RN McKay, DB AF Halamay, KE Kirkman, RL Sun, LH Yamada, A Fragoso, RC Shimizu, K Mitchell, RN McKay, DB TI CD8 T cells are sufficient to mediate allorecognition and allograft rejection SO CELLULAR IMMUNOLOGY LA English DT Article DE CD8 T cells; allorecognition; transplantation; acute allograft rejection; transgenic mouse; 2C mouse ID CLASS-I; MONOCLONAL-ANTIBODIES; SUPPRESSOR CELLS; ANTIGEN RECEPTOR; GRAFT TOLERANCE; TRANSGENIC MICE; LYMPHOCYTES-T; MOUSE; INDUCTION; SUBSETS AB Different T cell subsets may play different roles in allorecognition and allograft rejection. It has been suggested that CD8 T cells can only initiate rejection with help from CD4 T cells. Since CD8 T cells may have different requirements for allorecognition and for costimulation. it is important to clarify the role of CD8 cells in rejection. We examined the role of CD8 cells in allorecognition using a TCR transgenic mouse transplantation model. In our study, CD8 cells were able to recognize alloantigens and reject allografts in the absence of help from CD4 T cells. Furthermore our study provides a model to study the mechanisms of CD8-mediated allograft rejection. It may be important in the future, to consider that CD8 T cells may need to be targeted independently of CD4 T cells in strategies used to prevent rejection and induce tolerance. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol,Div Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Renal & Transplantat Div, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Cardiovasc Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplantat Unit, Boston, MA 02114 USA. RP McKay, DB (reprint author), The Scripps Res Inst, Res Inst, Dept Immunol IMM1, 10550 N Torrey Piens Rd, La Jolla, CA 92073 USA. FU NIDDK NIH HHS [R03-DK58814-01, KO8-DK02472-04] NR 33 TC 10 Z9 12 U1 2 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD MAR-APR PY 2002 VL 216 IS 1-2 BP 6 EP 14 AR PII S0008-8749(02)00530-0 DI 10.1016/S0008-8749(02)00530-0 PG 9 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 622ZA UT WOS:000179677100002 PM 12381345 ER PT J AU Tung, CH Gerszten, RE Jaffer, FA Weissleder, R AF Tung, CH Gerszten, RE Jaffer, FA Weissleder, R TI A novel near-infrared fluorescence sensor for detection of thrombin activation in blood SO CHEMBIOCHEM LA English DT Article DE enzyme activation; fluorescent probes; near-infrared fluorescence; peptides; thrombin ID ACUTE CORONARY SYNDROMES; PATHOGENESIS; TUMORS AB Thrombosis is an important pathophysiologic component of many cardiovascular diseases. Thrombin, a serine protease, plays a central role in thrombosis formation. Detection and imaging of thrombin activity may thus be of considerable biomedical interest. The goal of this study was to design, synthesize, and characterize a novel thrombin-activated near-infrared fluorescence (NIRF) probe. The probe consisted of a thrombin-cleavable peptide spacer (...D- Phe-Pip-Arg...; Pip=pipecolic acid) and contained a terminal fluorescence reporter which was quenched when conjugated to a compatible delivery vehicle. A control peptide spacer was synthesized that differed by one amino acid. Following thrombin the probe was activated within minutes. The NIRF signal increased by a factor of 27-fold within 20 minutes, and was inhibited by hirudin, a specific thrombin inhibitor. NIRF optical imaging experiments confirmed rapid activation of the probe in both buffer and human blood. The control probe showed minimal activation in all experiments. In addition to potentially furthering our understanding of thrombin regulation in vivo, the thrombin-activated near-infrared probe may have broad clinical application to the diagnosis of arterial and venous thrombosis. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. RP Tung, CH (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St,Room 5406, Charlestown, MA 02129 USA. OI Jaffer, Farouc/0000-0001-7980-384X; Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [P50 CA86355, R33 CA88365] NR 16 TC 60 Z9 66 U1 2 U2 22 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1439-4227 J9 CHEMBIOCHEM JI Chembiochem PD MAR 1 PY 2002 VL 3 IS 2-3 BP 207 EP 211 DI 10.1002/1439-7633(20020301)3:2/3<207::AID-CBIC207>3.0.CO;2-B PG 5 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 530XF UT WOS:000174383700010 PM 11921399 ER PT J AU Cohen, AJ Belinsky, S Franklin, W Beard, S AF Cohen, AJ Belinsky, S Franklin, W Beard, S TI Molecular and Physiologic evidence for 5 ' CpG island methylation of the endothelin B receptor gene in lung cancer SO CHEST LA English DT Article; Proceedings Paper CT 44th Annual Thomas L Petty Aspen Lung Conference CY JUN 06-09, 2001 CL ASPEN, COLORADO C1 Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Div Pulm Sci & Crit Care Med, Denver, CO 80220 USA. Lovelace Res Inst, Albuquerque, NM USA. RP Cohen, AJ (reprint author), Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Div Pulm Sci & Crit Care Med, 1055 Clermont Ave,Resp 111A, Denver, CO 80220 USA. NR 0 TC 8 Z9 8 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 2002 VL 121 IS 3 SU S BP 27S EP 28S DI 10.1378/chest.121.3_suppl.27S-a PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 532NH UT WOS:000174481400016 PM 11893663 ER PT J AU Evans, C Kheradmand, F Corry, D Tuvim, M Densmore, C Waldrep, C Knight, V Dickey, B AF Evans, C Kheradmand, F Corry, D Tuvim, M Densmore, C Waldrep, C Knight, V Dickey, B TI Gene therapy of mucus hypersecretion in experimental asthma SO CHEST LA English DT Article; Proceedings Paper CT 44th Annual Thomas L Petty Aspen Lung Conference CY JUN 06-09, 2001 CL ASPEN, COLORADO C1 Baylor Coll Med, Houston, TX USA. Houston Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Dickey, B (reprint author), Houston Vet Affairs Med Ctr, MS 151 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 1 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 2002 VL 121 IS 3 SU S BP 90S EP 91S DI 10.1378/chest.121.3_suppl.90S-a PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 532NH UT WOS:000174481400071 PM 11893719 ER PT J AU Garcia-Carbonero, R Supko, JG AF Garcia-Carbonero, R Supko, JG TI Current perspectives on the clinical experience, pharmacology, and continued development of the camptothecins SO CLINICAL CANCER RESEARCH LA English DT Review ID TOPOISOMERASE-I INHIBITOR; CELL LUNG-CANCER; EVERY 3 WEEKS; COLLOIDAL DISPERSION FORMULATION; COLONY-STIMULATING FACTOR; METASTATIC COLORECTAL-CANCER; 24-HOUR CONTINUOUS-INFUSION; 21-DAY CONTINUOUS-INFUSION; CEREBROSPINAL-FLUID PHARMACOKINETICS; CHRONIC MYELOMONOCYTIC LEUKEMIA AB The camptothecins are a maturing class of anticancer agents. In this article, we review the pharmacology and antitumor activity of the camptothecin analogues that are approved for clinical use and those investigational agents undergoing clinical evaluation. Camptothecin is a naturally occurring cytotoxic alkaloid that has a unique intracellular target, topoisomerase 1, a nuclear enzyme that reduces the torsional stress of supercoiled DNA during the replication, recombination, transcription, and repair of DNA. Topotecan and irinotecan are synthetic analogues designed to facilitate parenteral administration of the active lactone form of the compound by introducing functional groups to enhance solubility. They are now well-established components in the chemotherapeutic management of several neoplasms. Topotecan has modest activity in patients treated previously with ovarian and small cell lung cancer and is currently approved for use in the United States as second-line therapy in these diseases. Preliminary evidence of activity against hematological malignancies is also promising. Irinotecan is a prodrug that undergoes enzymatic conversion to the biologically active metabolite 7-ethyl-10-hydroxy-camptothecin. It is presently the treatment of choice when used in combination with fluoropyrimidines as first-line therapy for patients with advanced colorectal cancer or as a single agent after failure of 5-fluorouracil-based chemotherapy. Encouraging preliminary results suggest that irinotecan may have an increasing role in the treatment of other solid tumors, including small and non-small cell lung cancer, cervical cancer, ovarian cancer, gastric cancer, and malignant gliomas. Several additional camptothecin analogues are in various stages of clinical development, including 9-aminocamptothecin, 9-nitrocamptothecin, 7-(4-methylpiperazinomethylene)-10,11-ethylenedioxy-20(S)-camptothecin, exatecan mesylate, and karenitecin. Efforts to further optimize therapeutic effectiveness through drug delivery strategies that prolong tumor exposure to these S phase-specific agents, such as improving oral bioavailability through structure modification and innovative formulation approaches, alternative parenteral dosage forms, and administration schedules, are being actively pursued. Combining camptothecins with other anticancer drugs and treatment modalities, as well as gaining a better understanding of the factors contributing to tumor sensitivity and resistance, continues to be the object of considerable interest. C1 Harvard Univ, Sch Med, Div Hematol Oncol, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Supko, JG (reprint author), Harvard Univ, Sch Med, Div Hematol Oncol, Massachusetts Gen Hosp, Jackson Bldg,Room 1025,55 Fruit St, Boston, MA 02114 USA. NR 194 TC 325 Z9 338 U1 5 U2 33 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 2002 VL 8 IS 3 BP 641 EP 661 PG 21 WC Oncology SC Oncology GA 531EP UT WOS:000174403300003 PM 11895891 ER PT J AU Toppmeyer, D Seidman, AD Pollak, M Russell, C Tkaczuk, K Verma, S Overmoyer, B Garg, V Ette, E Harding, MW Demetri, GD AF Toppmeyer, D Seidman, AD Pollak, M Russell, C Tkaczuk, K Verma, S Overmoyer, B Garg, V Ette, E Harding, MW Demetri, GD TI Safety and efficacy of the multidrug resistance inhibitor Incel (Biricodar; VX-710) in combination with paclitaxel for advanced breast cancer refractory to paclitaxel SO CLINICAL CANCER RESEARCH LA English DT Article ID PHASE-II TRIAL; TUBULIN ISOTYPE EXPRESSION; P-GLYCOPROTEIN EXPRESSION; COLONY-STIMULATING FACTOR; BETA-TUBULIN; OVARIAN-CANCER; CELL-DEATH; RANDOMIZED TRIAL; 3-HOUR INFUSION; MOLECULAR MECHANISMS AB Purpose: VX-710 (biricodar, Incel) restores drug sensitivity to P-glycoprotein (MDR1) and multidrug resistance-associated protein (MRP1)-expressing cells. This Phase 11 study evaluated the safety/tolerability, pharmacokinetics, and efficacy of VX-710 plus paclitaxel in women with locally advanced or metastatic breast cancer who were refractory to prior paclitaxel therapy. Experimental Design: Eligible patients had paclitaxel-refractory disease defined as progressive disease after a minimum of two cycles of paclitaxel (weekly or 3-week schedule) or relapsed/progressive disease within 6 months of prior paclitaxel therapy. Patients received 80 mg/m(2) paclitaxel over 3 h starting 4 It after initiation of a 24-h continuous i.v. infusion of 120 mg/m(2)/h VX-710. Cycles were repeated every 3 weeks. Results: Thirty-seven patients received study treatment and 35 were evaluable for response. VX-710 + paclitaxel therapy was generally well tolerated. Myelosuppression was the principal toxicity, with a median nadir ANC cycle I of 0.76 X 10(9) cells/liter and a 40% overall incidence of Grade 4 neutropenia. Nonhematological side effects (asthenia, paresthesia, headache, myalgia, nausea, and diarrhea) were generally mild to moderate and reversible. Paclitaxel AUC (16.8 +/- 5.0 mug X h/ml) and clearance (5.1 +/- 1.3 liters/h/m(2)) during the first treatment cycle were comparable with standard 175 mg/m(2) paclitaxel administered in a 3-h schedule. Four patients achieved partial responses (three of the four had progressive disease on prior paclitaxel) with a mean response duration of 5.5 months. Conclusions: The 11.4% (4 of 35) objective response rate observed in this study suggests that VX-710 can resensitize a subgroup of paclitaxel-refractory patients to paclitaxel. The safety and pharmacokinetics of the VX-710/pacitaxel regimen support further evaluation in breast cancer patients with initial paclitaxel therapy to prevent emergence of the MDR phenotype in recurrent disease. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Vertex Pharmaceut Inc, Cambridge, MA 02139 USA. Cleveland Clin, Cleveland, OH 44195 USA. Ottawa Reg Canc Ctr, Ottawa, ON K1H 8L6, Canada. Univ Maryland, Greenbaum Canc Ctr, Baltimore, MD 21201 USA. Univ So Calif, Norris Canc Ctr, Los Angeles, CA 90033 USA. Sir Mortimer B Davis Jewish Hosp, Montreal, PQ H3T 1E2, Canada. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Canc Inst New Jersey, New Brunswick, NJ 08903 USA. RP Harding, MW (reprint author), Vertex Pharmaceut Inc, 130 Waverly St, Cambridge, MA 02139 USA. RI Pollak, Michael/G-9094-2011 OI Pollak, Michael/0000-0003-3047-0604 NR 65 TC 61 Z9 63 U1 0 U2 1 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 2002 VL 8 IS 3 BP 670 EP 678 PG 9 WC Oncology SC Oncology GA 531EP UT WOS:000174403300006 PM 11895894 ER PT J AU Seiden, MV Ng, SW Supko, JG Ryan, DP Clark, JW Lynch, T Huang, KC Kwiatkowski, D Skarin, A Eder, JP AF Seiden, MV Ng, SW Supko, JG Ryan, DP Clark, JW Lynch, T Huang, KC Kwiatkowski, D Skarin, A Eder, JP TI A phase I clinical trial of sequentially administered doxorubicin and topotecan in refractory solid tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID DNA TOPOISOMERASE-II; CLEAVABLE COMPLEX; TARGETED DRUGS; RESISTANCE; PHARMACODYNAMICS; PHARMACOKINETICS; CAMPTOTHECIN; INHIBITORS; PLASMA; CELLS AB Purpose: To determine whether agents that target topoisomerase I and 11 could be administered sequentially. Design: A Phase I study was conducted to evaluate sequential treatment with bolus IV doxorubicin followed 48 h later by topotecan given as a 30-min i.v. infusion on 3 consecutive days, with additional cycles of therapy repeated every 3 weeks. Characteristics of the 22 patients entered into the study were: 13 male and 9 female; median age, 49.5 (range 33-66) years; Eastern Cooperative Oncology Group performance status, 0-1; and normal cardiac, hematological, hepatic, and renal function. All patients had received prior therapy (median greater than or equal to2 prior regimens). Results: The maximum tolerated dose of the combination was 25 mg/m(2) doxorubicin and 5.25 mg/m(2) topotecan (1.75 mg/m(2)/day X 3). Neutropenia was the dose-limiting toxicity. Attempts to further escalate the dose using 5 mug/kg granulocyte colony-stimulating factor proved unsuccessful because of thrombocytopenia. Among the 17 patients who were evaluable for response, 6 had a partial response, and 4 showed evidence of disease stabilization. The partial responses occurred in patients with small cell lung cancer (3 of 7), non-small cell lung cancer (1 of 6), esophageal adenocarcinoma (1 of 2), and ovarian carcinoma (I of 1), and it lasted for 3-6 months. Administration of doxorubicin 2 days be fore topotecan did not alter topotecan pharmacokinetics. Changes in topoisomerase mRNA levels were observed during chemotherapy. Conclusions: The sequential combination of doxorubicin followed by topotecan is highly active in several chemotherapy refractory long, ovary, and esophageal cancers. Despite significant neutropenia, toxicity is manageable and well tolerated. Phase 11 trials to further evaluate the efficacy of this promising combination regimen against non-Hodgkin's lymphoma and lung cancer have been initiated. C1 Harvard Univ, Sch Med, Dana Farber Harvard Canc Ctr,Div Hematol & Oncol, Beth Israel Deaconess Med Ctr,Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Div Hematol & Oncol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Dept Med, Div Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Seiden, MV (reprint author), Massachusetts Gen Hosp, Cox 640,100 Blossom St, Boston, MA 02114 USA. NR 31 TC 21 Z9 21 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 2002 VL 8 IS 3 BP 691 EP 697 PG 7 WC Oncology SC Oncology GA 531EP UT WOS:000174403300009 PM 11895897 ER PT J AU Ito, A Buenafe, AC Matejuk, A Zamora, A Silverman, M Dwyer, J Vandenbark, AA Offner, H AF Ito, A Buenafe, AC Matejuk, A Zamora, A Silverman, M Dwyer, J Vandenbark, AA Offner, H TI Estrogen inhibits systemic T cell expression of TNF-alpha and recruitment of TNF-alpha(+) T cells and macrophages into the CNS of mice developing experimental encephalomyelitis SO CLINICAL IMMUNOLOGY LA English DT Article DE EAE; CNS; T cells; macrophages; 17 beta-estradiol; TNF-alpha ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; DELAYED-TYPE HYPERSENSITIVITY; TUMOR-NECROSIS-FACTOR; COLLAGEN-INDUCED ARTHRITIS; MULTIPLE-SCLEROSIS; INFLAMMATORY RESPONSES; ESTRADIOL SUPPRESSION; BETA-ESTRADIOL AB Estrogen treatment has been found to have suppressive activity in several models of autoimmunity. To investigate the mechanism of 17beta-estradiol (E2) suppression of experimental autoimmune encephalomyelitis, we evaluated E2 effects on TNF-alpha expression in the central nervous system (CNS) and spleen of C57BL/6 mice immunized with MOG 35-55/CFA. Kinetic analysis demonstrated that E2 treatment drastically decreased the recruitment of total inflammatory cells as well as TNF-alpha(+) macrophages and T cells into the CNS at disease onset. In contrast, E2 had only moderate effects on the relatively high constitutive TNF-alpha expression by resident CNS microglial cells. E2 treatment also had profound inhibitory effects on expression of TNF-alpha by splenic CD4(+) T cells, including those responsive to MOG 35-55 peptide. We propose that the mechanism of E2 protection may involve both systemic inhibition of TNF-alpha expression and local (CNS) recruitment of inflammatory cells, with modest effects on TNF-alpha expression by resident CNS microglial cells. (C) 2002 Elsevier Science (USA). C1 Portland VA Med Ctr, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. Polish Acad Sci, L Hirszfeld Inst Immunol & Expt Therapy, Wroclaw, Poland. Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. RP Offner, H (reprint author), Portland VA Med Ctr, R&D-31,3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. FU NIAID NIH HHS [AI42376]; NINDS NIH HHS [NS23444] NR 40 TC 41 Z9 44 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD MAR PY 2002 VL 102 IS 3 BP 275 EP 282 DI 10.1006/clim.2001.5175 PG 8 WC Immunology SC Immunology GA 534MV UT WOS:000174590900008 PM 11890714 ER PT J AU Roemer, L Orsillo, SM AF Roemer, L Orsillo, SM TI Expanding our conceptualization of and treatment for generalized anxiety disorder: Integrating mindfulness/acceptance-based approaches with existing cognitive-behavioral models SO CLINICAL PSYCHOLOGY-SCIENCE AND PRACTICE LA English DT Review DE worry; generalized anxiety disorder; acceptance-based therapy; mindfulness; experiential avoidance ID APPLIED RELAXATION; FOLLOW-UP; WORRY; THERAPY; IMAGERY; PSYCHOTHERAPY; COMORBIDITY; THOUGHTS; BELIEFS; STRESS AB Generalized anxiety disorder (GAD) is a chronic, pervasive disorder for which we have yet to develop sufficiently efficacious interventions. In this article we propose that recent research and theory regarding this disorder supports the integration of acceptance-based treatments with existing cognitive-behavioral treatments for GAD to improve the efficacy and clinical significance of such approaches. The bases for this proposal (from both the GAD and the acceptance-based treatment literature) are reviewed, and a new treatment stemming from this conceptual integration is described. C1 Boston VA Healthcare Syst, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Roemer, L (reprint author), Univ Massachusetts, Dept Psychol, 100 Morrissey Blvd, Boston, MA 02125 USA. EM Lizabeth.Roemer@umb.edu OI Roemer, Lizabeth/0000-0002-2453-5435 NR 102 TC 203 Z9 209 U1 15 U2 74 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0969-5893 J9 CLIN PSYCHOL-SCI PR JI Clin. Psychol.-Sci. Pract. PD SPR PY 2002 VL 9 IS 1 BP 54 EP 68 DI 10.1093/clipsy/9.1.54 PG 15 WC Psychology, Clinical SC Psychology GA 518UF UT WOS:000173685700010 ER PT J AU McLoud, TC AF McLoud, TC TI Imaging techniques for diagnosis and staging of lung cancer SO CLINICS IN CHEST MEDICINE LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; SOLITARY PULMONARY NODULE; MEDIASTINAL LYMPH-NODES; HIGH-RESOLUTION CT; BRONCHOGENIC-CARCINOMA; FDG-PET; F-18 FLUORODEOXYGLUCOSE; COMPUTED-TOMOGRAPHY; ADRENAL MASSES; TUMORS AB Noninvasive imaging modalities continue to offer opportunities in the diagnosis and staging of lung cancer. Positron emission tomography with fluorodeoxyglucose imaging in lung cancer represents art important, new and accurate tool in the armamentarium of the radiologist. Computed tomography, magnetic resonance imaging, and PET play a significant role in the selection of patients for curative lung cancer surgery, decreasing the number of unnecessary thoracotomies. The imaging modalities also help to direct the choice of appropriate invasive and surgical procedures. 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, 32 Fruit St, Boston, MA 02114 USA. NR 63 TC 9 Z9 10 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-5231 J9 CLIN CHEST MED JI Clin. Chest Med. PD MAR PY 2002 VL 23 IS 1 BP 123 EP + DI 10.1016/S0272-5231(03)00064-9 PG 15 WC Respiratory System SC Respiratory System GA 532UN UT WOS:000174493600010 PM 11901907 ER PT J AU Evans, TL Donahue, DM Mathisen, DJ Lynch, TJ AF Evans, TL Donahue, DM Mathisen, DJ Lynch, TJ TI Building a better therapy for stage IIIA non-small cell lung cancer SO CLINICS IN CHEST MEDICINE LA English DT Article ID HYPERFRACTIONATED ACCELERATED RADIOTHERAPY; COMPARING PERIOPERATIVE CHEMOTHERAPY; RANDOMIZED MULTICENTER TRIAL; THORACIC RADIATION-THERAPY; COOPERATIVE-ONCOLOGY-GROUP; LYMPH-NODE DISSECTION; CHEST-WALL INVASION; PHASE-III; PREOPERATIVE CHEMOTHERAPY; BRONCHOGENIC-CARCINOMA AB The management of stage IIIA non-small-cell lung cancer (NSCLC) is controversial, and there is no standard of care. Surgery and radiation can each alone cure a small subset of patients with stage IIIA NSCLC, but the overwhelming majority ultimately die of their disease. Mutimodality therapy can improve cure rates. For this reason, it is imperative that thoracic surgeons, radiation oncologists and medical oncologists have a clear understanding of the diagnosis and management of stage IIIA lung cancer. C1 Massachusetts Gen Hosp, Thorac Oncol Ctr, Hematol Oncol Unit, Boston, MA 02114 USA. Dana Farber, Partners Canc Care, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. RP Massachusetts Gen Hosp, Thorac Oncol Ctr, Hematol Oncol Unit, Cox 640,100 Blossom St, Boston, MA 02114 USA. EM TEvans@Partners.org NR 84 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-5231 EI 1557-8216 J9 CLIN CHEST MED JI Clin. Chest Med. PD MAR PY 2002 VL 23 IS 1 BP 191 EP + DI 10.1016/S0272-5231(03)00068-6 PG 18 WC Respiratory System SC Respiratory System GA 532UN UT WOS:000174493600014 PM 11901911 ER PT J AU Johnson, BE AF Johnson, BE TI Management of small cell lung cancer SO CLINICS IN CHEST MEDICINE LA English DT Review ID PROPHYLACTIC CRANIAL IRRADIATION; ATRIAL-NATRIURETIC-PEPTIDE; PHASE-II TRIAL; INTENSIVE WEEKLY CHEMOTHERAPY; MULTICENTER RANDOMIZED TRIAL; SOUTHWEST-ONCOLOGY-GROUP; ANTIDIURETIC-HORMONE SECRETION; CROSS-RESISTANT CHEMOTHERAPY; PROGNOSTIC STAGING SYSTEM; EATON MYASTHENIC SYNDROME AB Small-cell lung carcinoma typically presents as a central endobronchial lesion in chronic cigarette smokers with hilar enlargement and disseminated disease. The diagnostic pathology should be reviewed by a pathologist accomplished in reading pulmonary pathology. If any doubts exist in the diagnosis, additional special stains or diagnostic materials should be obtained. The introduction of combination chemotherapy as treatment for this disease has resulted in high response rates and prolonged survival. The management of small-cell lung cancer largely is based on systemic treatment with combination chemotherapy rather than surgical resection, which typically is used for non-small-cell lung cancers. C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Johnson, BE (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Room D1234,44 Binney St, Boston, MA 02115 USA. NR 150 TC 18 Z9 19 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-5231 J9 CLIN CHEST MED JI Clin. Chest Med. PD MAR PY 2002 VL 23 IS 1 BP 225 EP + DI 10.1016/S0272-5231(03)00070-4 PG 16 WC Respiratory System SC Respiratory System GA 532UN UT WOS:000174493600016 PM 11901913 ER PT J AU Ledden, PJ Wald, LL Hinton, DP AF Ledden, PJ Wald, LL Hinton, DP TI A detunable elliptic transmission line resonator for body imaging at 3 Tesla SO CONCEPTS IN MAGNETIC RESONANCE LA English DT Article DE MRI; 3 Tesla; cardiac; RF coil ID SIGNAL-TO-NOISE; NMR; SPECTROSCOPY; FIELD; COILS AB In this work, we demonstrate and characterize a large-volume radiofrequency (RF) coil insert used to perform human torso magnetic resonance imaging at 3 T. The coil is a transmission line resonator of elliptic cross-section that can be actively detuned for operation with localized receive-only surface coils. The coil fits within the 55 cm inner bore liner of a 3 T whole body imager and accommodates small- to medium-sized torsos. Sixteen flat transmission line elements are used; each is 32 cm in length and composed of multiple microstrip capacitors spaced equally inside the elliptic shield (52 cm and 40 cm major and minor axes, respectively). A four-port electrical drive was used to improve B, homogeneity and power efficiency. The power required for a 90degrees 2 ms single side-lobe sinc pulse for the chest loaded coil was less than 2 kW. Active detuning for operation with receive-only surface coils was achieved by placement of a low-voltage PIN diode network on each individual transmission line element. A quadrature pair of 10 X 15 cm(2) rectangular surface coils with active detuning traps was used for high spatial resolution cardiac and spine imaging. Since the coil is completely portable, any anatomical region of interest may be centered within the active volume. The head loaded coil required less power and enabled the use of standard 1800 pulses well within specific absorption rate limits. occipital lobe images using a receive-only quadrature 8 cm loop surface coil pair are also presented. As the number of high-held whole body systems increases, an RF coil insert optimized for the torso provides an economical and efficient strategy for extending the capabilities of these systems beyond neuroimaging. (C) 2002 Wiley Periodicals, Inc. C1 Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, Charlestown, MA 02129 USA. Nova Med Inc, Wakefield, MA 01880 USA. RP Hinton, DP (reprint author), Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, 149 13th St,Room 2301, Charlestown, MA 02129 USA. RI Wald, Lawrence/D-4151-2009 NR 16 TC 2 Z9 2 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1043-7347 J9 CONCEPT MAGNETIC RES JI Concepts Magn. Resonance PD MAR PY 2002 VL 15 IS 1 BP 92 EP 100 DI 10.1002/mre.10014 PG 9 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Chemistry; Physics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 685RW UT WOS:000183277900008 ER PT J AU Demers, PE Steinert, RF Gould, EM AF Demers, PE Steinert, RF Gould, EM TI Topographic analysis of corneal regularity after penetrating keratoplasty SO CORNEA LA English DT Article DE astigmatism; corneal topography; penetrating keratoplasty ID LASER PHOTOREFRACTIVE KERATECTOMY; POSTOPERATIVE SUTURE ADJUSTMENT; SINGLE RUNNING SUTURE; POSTKERATOPLASTY ASTIGMATISM; VISUAL-ACUITY; VIDEOKERATOGRAPHY; REMOVAL AB Purpose. To evaluate the accuracy of the Holladay Diagnostic Summary of the EyeSys Corneal Analysis System in predicting the corneal visual acuity potential in patients who have undergone penetrating keratoplasty (PKP). Methods. Astigmatism patterns refractive and topographic astigmatism, best spectacle-corrected visual acuity (BSCVA), and hard contact lens (HCL) visual acuity of 54 patients were analyzed 3 months after PKP and compared with the Potential Corneal Acuity (PCA) value predicted by the Holladay Diagnostic Summary. Results. Qualitative patterns of astigmatism (p = 0.01) and refractive (p = 0.002) and topographic (p = 0.0002) astigmatism were significantly correlated with PCA values. Using HCL visual acuities to correct the BSCVA (HCL-corrected BSCVA) for noncorneal causes of reduced vision, we found that the PCA values of 48.1% of the patients were within one line of the HCL-corrected BSCVA 81.5% were within two lines and 93.0% were within three lines. Conclusion. The Holladay PCA measurement may be Useful in the postoperative evaluation of the optical quality of the central corneal surface in patients who have undergone PKP. C1 Notre Dame Hosp, Dept Ophthalmol, Montreal, PQ H2L 4M1, Canada. New England Eye Ctr, Dept Ophthalmol, Boston, MA USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. Ophthalm Consultants Boston, Boston, MA USA. Univ Montreal, Montreal, PQ, Canada. RP Demers, PE (reprint author), Notre Dame Hosp, Dept Ophthalmol, 1560 Sherbrooke E, Montreal, PQ H2L 4M1, Canada. NR 33 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD MAR PY 2002 VL 21 IS 2 BP 140 EP 147 DI 10.1097/00003226-200203000-00002 PG 8 WC Ophthalmology SC Ophthalmology GA 525XT UT WOS:000174099900002 PM 11862082 ER PT J AU Borghesani, PR Peyrin, JM Klein, R Rubin, J Carter, AR Schwartz, PM Luster, A Corfas, G Segal, RA AF Borghesani, PR Peyrin, JM Klein, R Rubin, J Carter, AR Schwartz, PM Luster, A Corfas, G Segal, RA TI BDNF stimulates migration of cerebellar granule cells SO DEVELOPMENT LA English DT Article DE BDNF; granule cells; cell migration; CNS; mouse ID NEUROTROPHIC FACTOR; NERVOUS-SYSTEM; DIFFERENTIAL EXPRESSION; NEURONAL MIGRATION; PROTEIN-KINASE; IN-VITRO; BRAIN; RECEPTORS; GROWTH; MICE AB During development of the nervous system, neural progenitors arise in proliferative zones, then exit the cell cycle and migrate away from these zones. Here we show that migration of cerebellar granule cells out of their proliferative zone, the external granule cell layer (EGL), is impaired in Bdnf(-/-) mice. The reason for impaired migration is that BDNF directly and acutely stimulates granule cell migration. Purified Bdnf(-/-) granule cells show defects in initiation of migration along glial fibers and in Boyden chamber assays. This phenotype can be rescued by exogenous BDNF Using time-lapse video microscopy we find that BDNF is acutely motogenic as it stimulates migration of individual granule cells immediately after addition. The stimulation of migration reflects both a chemokinetic and chemotactic effect of BDNF Collectively, these data demonstrate that BDNF is directly motogenic for granule cells and provides a directional cue promoting migration from the EGL to the internal granule cell layer (IGL). C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Neurosci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. RP Segal, RA (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI46999]; NICHD NIH HHS [P30-HD 18655]; NIDA NIH HHS [DA000522]; NINDS NIH HHS [NS35884, NS37757] NR 40 TC 150 Z9 153 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD MAR PY 2002 VL 129 IS 6 BP 1435 EP 1442 PG 8 WC Developmental Biology SC Developmental Biology GA 538PJ UT WOS:000174824000014 PM 11880352 ER PT J AU Peterson, C Carney, GE Taylor, BJ White, K AF Peterson, C Carney, GE Taylor, BJ White, K TI reaper is required for neuroblast apoptosis during Drosophila development SO DEVELOPMENT LA English DT Article DE Drosophila melanogaster; apoptosis; reaper; p53; neuroblast ID PROGRAMMED CELL-DEATH; CENTRAL-NERVOUS-SYSTEM; RADIATION-INDUCED APOPTOSIS; ECDYSONE RECEPTOR ISOFORMS; DECREASED APOPTOSIS; CASPASE ACTIVATION; MAMMALIAN-CELLS; GENETIC-CONTROL; C-ELEGANS; INHIBITOR AB Developmentally regulated apoptosis in Drosophila requires the activity of the reaper (rpr), grim and head involution defective (hid) genes. The expression of these genes is differentially regulated, suggesting that there are distinct requirements for their proapoptotic activity in response to diverse developmental and environmental inputs. To examine this hypothesis, a mutation that removes the rpr gene was generated. In flies that lack rpr function, most developmental apoptosis was unaffected. however, the central nervous systems of rpr null flies were very enlarged. This was due to the inappropriate survival of both larval neurons and neuroblasts. Importantly, neuroblasts rescued from apoptosis remained functional, continuing to proliferate and generating many extra neurons. Males mutant for rpr exhibited behavioral defects resulting in sterility. Although both the ecdysone hormone receptor complex and p53 directly regulate rpr transcription, rpr was found to play a limited role in inducing apoptosis in response to either of these signals. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, CBRC, Charlestown, MA 02129 USA. Oregon State Univ, Dept Zool, Corvallis, OR 97331 USA. RP White, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, CBRC, Bldg 149,13th St, Charlestown, MA 02129 USA. RI White, Kristin/D-7936-2013 FU NIGMS NIH HHS [GM55568, GM20030, GM56920] NR 77 TC 112 Z9 113 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD MAR PY 2002 VL 129 IS 6 BP 1467 EP 1476 PG 10 WC Developmental Biology SC Developmental Biology GA 538PJ UT WOS:000174824000017 PM 11880355 ER PT J AU Baksa, K Parke, T Dobens, LL Dearolf, CR AF Baksa, K Parke, T Dobens, LL Dearolf, CR TI The Drosophila STAT protein, Stat92E, regulates follicle cell differentiation during oogenesis SO DEVELOPMENTAL BIOLOGY LA English DT Article ID EGG CHAMBER FORMATION; OVARIAN FOLLICLE; SIGNALING PATHWAY; INTERFERON-ALPHA; NEUROGENIC GENES; JAK/STAT PATHWAY; KINASE; OOCYTE; IDENTIFICATION; PROLIFERATION AB Signal transducer and activator of transcription (STAT) proteins are transcription factors that play a critical role in the response of a variety of eukaryotic cells to cytokine and growth factor signaling. In Drosophila, the STAT homolog encoded by the stat92E gene is required for the normal development of multiple tissues, including embryonic segmentation, imaginal discs, blood cells, male germ cells, and sex determination. We used multiple approaches to study the role of stat92E in oogenesis. Stat92E RNA expression is strongest in the differentiating follicle cells in the germarium, as determined by in situ hybridization. We generated an ethylmethane sulfonate-induced, temperature-sensitive allele, stat92E', in which the mutant protein contains a P506S substitution, located in the DNA binding domain. At the restrictive temperature, mutant females are sterile. Mutant ovaries have multiple defects, including fused egg chambers and an absence of interfollicular stalks cells and functional polar follicle cells. An analysis of mosaic clones, using an apparent null stat92E allele, indicates that Stat92E is required in the polar/stalk follicle cell lineage. We conclude that stat92E is necessary for the early differentiation of follicle cells and for proper germ line cell encapsulation during Drosophila oogenesis. (C) 2002 Elsevier Science (USA). C1 Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Univ Missouri, Sch Biol Sci, Kansas City, MO 64110 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Dearolf, CR (reprint author), Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. FU NCI NIH HHS [CA73158] NR 51 TC 59 Z9 59 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAR 1 PY 2002 VL 243 IS 1 BP 166 EP 175 DI 10.1006/dbio.2001.0539 PG 10 WC Developmental Biology SC Developmental Biology GA 527PU UT WOS:000174195600013 PM 11846485 ER PT J AU Lei, EP Silver, PA AF Lei, EP Silver, PA TI Protein and RNA export from the nucleus SO DEVELOPMENTAL CELL LA English DT Review ID PRE-MESSENGER-RNA; 60S RIBOSOMAL-SUBUNITS; EXON JUNCTION COMPLEX; BINDING PROTEIN; PORE COMPLEX; SACCHAROMYCES-CEREVISIAE; IN-VIVO; NUCLEOCYTOPLASMIC TRANSPORT; ASYMMETRIC LOCALIZATION; CYTOPLASMIC TRANSPORT AB The presence of the nuclear envelope necessitates the movement of proteins and RNAs between the nucleus and the cytoplasm. Elaborate cellular machinery exists to promote the nuclear transport of macromolecules. Recent advances in the field have illuminated our comprehension of both nuclear import and export as powerful means of gene regulation. As our appreciation of the importance of the process has grown, its study has matured, moving beyond the single cell to the entire organism. This review discusses basic mechanisms and regulation of protein, mRNA, and ribosome export with an emphasis on developmental examples. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Silver, PA (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. NR 113 TC 107 Z9 108 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD MAR PY 2002 VL 2 IS 3 BP 261 EP 272 DI 10.1016/S1534-5807(02)00134-X PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 548KV UT WOS:000175387900006 PM 11879632 ER PT J AU Aschenbach, WG Hirshman, MF Fujii, N Sakamoto, K Howlett, KF Goodyear, LJ AF Aschenbach, WG Hirshman, MF Fujii, N Sakamoto, K Howlett, KF Goodyear, LJ TI Effect of AICAR treatment on glycogen metabolism in skeletal muscle SO DIABETES LA English DT Article ID ACTIVATED PROTEIN-KINASE; ACETYL-COA CARBOXYLASE; GLUCOSE-TRANSPORT; SYNTHASE PHOSPHORYLATION; AMP; INSULIN; CONTRACTION; HEXOKINASE; SUBSTRATE; SPECIFICITY AB AMP-activated protein kinase (AMPK) is proposed to stimulate fat and carbohydrate catabolism to maintain cellular energy status. Recent studies demonstrate that pharmacologic activation of AMPK and mutations in the enzyme are associated with elevated muscle glycogen content in vivo. Our purpose was to determine the mechanism for increased muscle glycogen associated with AMPK activity in vivo. AMPK activity and glycogen metabolism were studied in red and white gastrocnemius muscles from rats treated with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) in vivo, and also in muscles incubated with AICAR in vitro. In vivo AICAR treatment reduced blood glucose and increased blood lactate compared with basal values. AICAR increased muscle alpha2 AMPK activity, glycogen, and glucose-6-phosphate concentrations. Glycogen synthase activity was increased in the red gastrocnemius but was decreased in the white gastrocnemius. Glycogen phosphorylase activity increased in both muscles, with an inhibition initially observed in the red gastrocnemius. In vitro incubation with AICAR activated alpha2 AMPK but had no effect on either glycogen synthase or glycogen phosphorylase. These results suggest that AICAR treatment does not promote glycogen accumulation in skeletal muscle in vivo by altering glycogen synthase and glycogen phosphorylase. Rather, the increased glycogen is due to the well-known effects of AICAR to increase glucose uptake. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Goodyear, LJ (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu RI Fujii, Nobuharu/J-2724-2014; OI Fujii, Nobuharu/0000-0002-0974-3033; Howlett, Kirsten/0000-0002-8571-4867 FU NIAMS NIH HHS [AR45670, AR42238]; NIDDK NIH HHS [DK59769] NR 49 TC 76 Z9 78 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2002 VL 51 IS 3 BP 567 EP 573 DI 10.2337/diabetes.51.3.567 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 527CD UT WOS:000174167400003 PM 11872652 ER PT J AU Mur, C Valverde, AM Kahn, CR Benito, M AF Mur, C Valverde, AM Kahn, CR Benito, M TI Increased insulin sensitivity in IGF-I receptor-deficient brown adipocytes SO DIABETES LA English DT Article ID GROWTH-FACTOR-I; TYROSINE-PHOSPHATASE 1B; PHOSPHOTYROSINE PROTEIN; TARGETED DISRUPTION; CELL-PROLIFERATION; SUBSTRATE FAMILY; GENE-EXPRESSION; MICE LACKING; SHC; ASSOCIATION AB Immortalized brown adipocyte cell lines have been generated from fetuses of mice deficient in the insulin-like growth factor I receptor gene (IGF-IR-/-) as well as from fetuses of wild-type mice (IGF-IR+/+). These cell lines maintained the expression of adipogenic- and thermogenic differentiation markers and show a multilocular fat droplets phenotype. IGF-IR-/- brown adipocytes lacked IGF-IR protein expression; insulin receptor (IR) expression remained unchanged as compared with wild-type cells. Insulin-induced tyrosine autophosphorylation of the IR P-chain was augmented in IGF-IR- deficient cells. Upon insulin stimulation, tyrosine phosphorylation of (insulin receptor substrate-1) IRS-1 was much higher in IGF-IR(-/-)brown adipocytes, although IRS-1 protein content was reduced. In contrast, tyrosine phosphorylation of IRS-2 decreased in IGF-IR- deficient cells; its protein content was unchanged as compared with wild-type cells. Downstream, the association IRS-1/growth factor receptor binding protein-2 (Grb-2) was augmented in the IGF-IR-/brown adipocyte cell line. However, SHC expression and SHC tyrosine phosphorylation and its association with Grb-2 were unaltered in response to insulin in IGF-IR deficient brown adipocytes. These cells also showed an enhanced activation of mitogen-activated protein kinase (MAPK) kinase (MEK1/2) and p42/p44 mitogen-activated protein kinase (MAPK) upon insulin stimulation. In addition, the lack of IGF-IR in brown adipocytes resulted in a higher mitogenic response (DNA synthesis, cell number, and proliferating cell nuclear antigen expression) to insulin than wild-type cells. Finally, cells lacking IGF-IR showed a much lower association between IR or IRS-1 and phosphotyrosine phosphatase 1B (PTP1B) and also a decreased PTP1B activity upon insulin stimulation. However, PTP1B/Grb-2 association remained unchanged in both cell types, regardless of insulin stimulation. Data presented here provide strong evidence that IGF-IR-deficient brown adipocytes show an increased insulin sensitivity via IRS-1/Grb-2/MAPK, resulting in an increased mitogenesis in response to insulin. C1 Univ Complutense Madrid, CSIC,Fac Farm, Ctr Mixto, Dept Bioquim & Biol Mol, E-28040 Madrid, Spain. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Univ Complutense Madrid, CSIC,Fac Farm, Ctr Mixto, Dept Bioquim & Biol Mol, Ciudad Univ, E-28040 Madrid, Spain. EM benito@eucmax.sim.ucm.es NR 48 TC 23 Z9 24 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD MAR PY 2002 VL 51 IS 3 BP 743 EP 754 DI 10.2337/diabetes.51.3.743 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 527CD UT WOS:000174167400026 PM 11872675 ER PT J AU Meigs, JB Panhuysen, CIM Myers, RH Wilson, PWF Cupples, LA AF Meigs, JB Panhuysen, CIM Myers, RH Wilson, PWF Cupples, LA TI A genome-wide scan for loci linked to plasma levels of glucose and HbA(1c) in a community-based sample of Caucasian pedigrees - The Framingham Offspring Study SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; QUANTITATIVE-TRAIT LOCI; MEXICAN-AMERICANS; SUSCEPTIBILITY LOCUS; UNITED-STATES; PIMA-INDIANS; GLYCATED HEMOGLOBIN; INSULIN-RESISTANCE; GENETICS FUSION; BETA-CELL AB Elevated blood glucose levels are the hallmark of type 2 diabetes as well as a powerful risk factor for development of the disease. We conducted a genome-wide search for diabetes-related genes, using measures of glycemia as quantitative traits in 330 pedigrees from the Framingham Heart Study. Of 3,799 attendees at the 5th Offspring Study exam cycle (1991-1995), 1,461, 1,251, and 771 men (49%) and women provided information on levels of 20-year mean fasting glucose, current fasting glucose, and HbA(1c), respectively, and 1,308 contributed genotype data (using 401 microsatellite markers with an average spacing of 10 cM). Levels of glycemic traits were adjusted for age, cigarette smoking, alcohol and estrogen use, physical activity, and BMI. We ranked standardized residuals from these models, created normalized deviates from the ranks, and used the variance component model implemented in SOLAR (Sequential Oligogenic Linkage Analysis Routines) to evaluate linkage to normalized deviates as quantitative traits. We found peak evidence for linkage to 20-year mean fasting glucose levels on chromosome 1 at similar to247 cM from p-telomere (pter) (multipoint logarithm of odds [LOD] 2.33) and on chromosome 10 at similar to86 cM from pter (multipoint LOD 2.07); to current fasting glucose levels on chromosome 1 at similar to218 cM from pter (multipoint LOD 1.80) and on chromosome 10 at similar to96 cM from pter (multipoint LOD 2.15); and to HbAl, levels on chromosome 1 at similar to187 cM (multipoint LOD 2.81). This analysis of anselected European Caucasian pedigrees suggests localization of quantitative trait loci influencing glucose homeostasis on chromosomes 1q and 10q. Findings at similar to187-218 cM on chromosome 1 appear to replicate linkage reported in previous studies of other populations, Pointing to this large chromosomal region as worthy of more detailed scrutiny in the search for type 2 diabetes susceptibility genes. C1 Massachusetts Gen Hosp, Div Gen Med, Gen Internal Med Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gen Med, Clin Epidemiol Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02215 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, Gen Internal Med Unit, Dept Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. FU NHLBI NIH HHS [N01-HC-38083, P01-HL41484] NR 65 TC 137 Z9 146 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2002 VL 51 IS 3 BP 833 EP 840 DI 10.2337/diabetes.51.3.833 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 527CD UT WOS:000174167400039 PM 11872688 ER PT J AU Perkins, BA Olaleye, D Bril, V AF Perkins, BA Olaleye, D Bril, V TI Carpal tunnel syndrome in patients with diabetic polyneuropathy SO DIABETES CARE LA English DT Article ID MEDIAN NERVE; CONDUCTION; PREVALENCE; NEUROPATHY AB OBJECTIVE - Carpal tunnel syndrome (CTS) and diabetic polyneuropathy (DPN) are common conditions in patients with diabetes and therefore frequently occur concomitantly. Diagnosis of CTS in patients with DPN is important, as therapeutic interventions directed toward relief of CTS may be effective irrespective of diffuse neuropathy, The prevalence of clinical CTS and the most efficient electrodiagnostic discriminators of CTS from diffuse neuropathy are uncertain. RESEARCH DESIGN AND METHODS - A total (if 478 subjects, including reference subjects (without diabetes and without neuropathy, nonneuropathic subjects with diabetes, and diabetic subjects with mild, moderate, and severe neuropathy, were evaluated in a cross-sectional design for clinical features of CTS. In the ascertainment of the cohort, a clinical stratification method was used to ensure a broad spectrum of neuropathy severity. All subjects underwent nerve conduction study determinations of median, ulnar, and sural nerve parameters. RESULTS - The prevalence of clinical CTS was 2% in the reference population, 14% in diabetic subjects without DPN, and 30% in those with DPN Multiple linear regression analysis revealed that mean electrodiagnostic parameters are not significant predictors of clinical CTS in patients with diabetes, Generally, the parameters worsened with seventy of neuropathy, but none reliably distinguished diabetic patients with and without CTS. CONCLUSIONS - Given the high prevalence of CTS in patients with DPN and that electrodiagnostic criteria Cannot distinguish those with clinical CTS, it is recommended that therapeutic decisions for CTS be made independently. of electrodiagnostic findings. C1 Univ Toronto, Univ Hlth Network, Toronto Gen Hosp, Toronto, ON M5G 2C4, Canada. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Biomat, Cary, NC USA. RP Bril, V (reprint author), Univ Toronto, Univ Hlth Network, Toronto Gen Hosp, EN 11-209,200 Elizabeth St, Toronto, ON M5G 2C4, Canada. NR 19 TC 102 Z9 107 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2002 VL 25 IS 3 BP 565 EP 569 DI 10.2337/diacare.25.3.565 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 527CN UT WOS:000174168500025 PM 11874948 ER PT J AU Epstein, FH Veves, A Prasad, PV AF Epstein, FH Veves, A Prasad, PV TI Effect of diabetes on renal medullary oxygenation during water diuresis SO DIABETES CARE LA English DT Article ID INTRARENAL OXYGENATION; RISK-FACTORS; VASODILATION; MELLITUS; HYPOXIA AB OBJECTIVE- To study the effect of water diuresis on renal medullary and cortical oxygenation in patients with diabetes using blood oxygenation level-dependent magnetic resonance imaging (BOLD MRI). RESEARCH DESIGN AND METHODS- Nine mild diabetic subjects (48 +/- 2.7 years of age, six women) and nine nondiabetic subjects of similar age and sex, all without known vascular or renal disease, were studied noninvasively by MRI before and during water diuresis. RESULTS- Water diuresis induced an increase in medullary oxygenation in control subjects, producing a decrease in R-2* (apparent spin-spin relaxation time) of 1.89 +/- 0.27 (P < 0.01), but no significant change in the group of diabetic subjects. CONCLUSIONS- These findings in middle-aged diabetic subjects, which resembled those previously described in elderly subjects >65 years of age, suggest early impairment of adaptive vasodilatation within the renal medulla in diabetes. C1 Beth Israel Deaconess Med Ctr, Joslin Diabet Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Joslin Diabet Ctr, Dept Radiol, Boston, MA 02215 USA. RP Epstein, FH (reprint author), Beth Israel Deaconess Med Ctr E, 330 Brookline Ave,Dana 517, Boston, MA 02215 USA. OI Prasad, Pottumarthi/0000-0002-4214-5465 FU NCRR NIH HHS [MO RRO-1032]; PHS HHS [D53221] NR 12 TC 73 Z9 79 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2002 VL 25 IS 3 BP 575 EP 578 DI 10.2337/diacare.25.3.575 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 527CN UT WOS:000174168500027 PM 11874950 ER PT J AU McHorney, CA Robbins, J Lomax, K Rosenbek, JC Chignell, K Kramer, AE Bricker, DE AF McHorney, CA Robbins, J Lomax, K Rosenbek, JC Chignell, K Kramer, AE Bricker, DE TI The SWAL-QOL and SWAL-CARE outcomes tool for oropharyngeal dysphagia in adults: III. Documentation of reliability and validity SO DYSPHAGIA LA English DT Article DE deglutition; deglutition disorders ID IMPROVING HEALTH-CARE; GENERAL-PRACTICE CARE; PREPAID GROUP PLAN; QUALITY-OF-LIFE; MOS SHORT-FORM; MEDICAL OUTCOMES; PATIENT SATISFACTION; CONCEPTUAL-FRAMEWORK; DEPRESSED-PATIENTS; CATEGORICAL-DATA AB Advances in the measurement of swallowing physiologic parameters have been clinician-driven, as has the development of intervention techniques to modify swallowing pathophysiology. However, a critical element to determining the success of such efforts will be established by the patients themselves. We conceptualized, developed, and validated the SWAL-QOL, a 93-item quality-of-life and quality-of-care outcomes tool for dysphagia researchers and clinicians. With 93 items, the SWAL-QOL was too long for practical and routine use in clinical research and practice. We used an array of psychometric techniques to reduce the 93-item instrument into two patient-centered outcomes tools: (1) the SWAL-QOL, a 44-item tool that assesses ten quality-of-life concepts, and (2) the SWAL-CARE, a 15-item tool that assesses quality of care and patient satisfaction. All scales exhibit excellent internal-consistency reliability and short-term reproducibility. The scales differentiate normal swallowers from patients with oropharyngeal dysphagia and are sensitive to differences in the severity of dysphagia as clinically defined. It is intended that the standardization and publication of the SWAL-QOL and the SWAL-CARE will facilitate their use in clinical research and clinical practice to better understand treatment effectiveness as a critical step toward improving patients' quality of life and quality of care. C1 Regenstrief Inst Hlth Care, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Internal Med & Geriatr, Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN USA. Indiana Univ, Ctr Aging Res, Indianapolis, IN USA. William S Middleton Mem Vet Adm Med Ctr, Sch Med, Madison, WI USA. Univ Kentucky, Sanders Brown Ctr Aging, PhD Program Gerontol, Louisville, KY USA. Univ Florida, Dept Communicat Disorders, Gainesville, FL USA. Univ Wisconsin, Sch Med, Dept Surg, Madison, WI USA. ACHOICE, Milwaukee, WI USA. Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. NW Mem Hosp, Chicago, IL 60611 USA. RP McHorney, CA (reprint author), Regenstrief Inst Hlth Care, 1050 Wishard Blvd,RG,6th Floor, Indianapolis, IN 46202 USA. NR 87 TC 165 Z9 183 U1 2 U2 16 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0179-051X J9 DYSPHAGIA JI Dysphagia PD SPR PY 2002 VL 17 IS 2 BP 97 EP 114 DI 10.1007/s00455-001-0109-1 PG 18 WC Otorhinolaryngology SC Otorhinolaryngology GA 534XU UT WOS:000174615700002 PM 11956835 ER PT J AU Schlozman, SC AF Schlozman, SC TI Feast or famine SO EDUCATIONAL LEADERSHIP LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA. RP Schlozman, SC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 1 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 2002 VL 59 IS 6 BP 86 EP 87 PG 2 WC Education & Educational Research SC Education & Educational Research GA 529AT UT WOS:000174278400020 ER PT J AU Sohn, EH Wolden-Hanson, T Matsumoto, AM AF Sohn, EH Wolden-Hanson, T Matsumoto, AM TI Testosterone (T)-induced changes in arcuate nucleus cocaine-amphetamine-regulated transcript and NPY mRNA are attenuated in old compared to young male brown Norway rats: Contribution of T to age-related changes in cocaine-amphetamine-regulated transcript and NPY gene expression SO ENDOCRINOLOGY LA English DT Article ID NEUROPEPTIDE-Y; MESSENGER-RNA; BODY-COMPOSITION; ANATOMICAL DISTRIBUTION; INSITU HYBRIDIZATION; HYPOTHALAMIC CART; FEEDING-BEHAVIOR; FOOD-INTAKE; IN-VITRO; LEPTIN AB The age-related decrease in serum T levels is associated with impairments in food intake and weight regulation and alterations in brain peptides that regulate energy balance. To test the hypothesis that reduced T levels contribute to altered hypothalamic cocaine-amphetamine-regulated transcript (CART) and NPY gene expression, the mRNA content of these neuropeptides was measured by in situ hybridization in sham-operated (intact), castrated, and T-replaced castrated young and old male Brown Norway rats. T levels in T-replaced young and old rats were similar to those in intact young animals. Compared with castrated rats, arcuate nucleus CART mRNA was lower and NPY mRNA was higher in both young and old T-replaced castrated animals, suggesting reciprocal regulation of these peptides by T; these T-induced changes were localized primarily in the rostral arcuate and were markedly attenuated in old animals. Compared with intact animals, paraventricular nucleus CART mRNA was lower in castrated animals and similar in T-replaced young and old rats. We conclude that hypothalamic CART and NPY neurons remain responsive to T regulation in old rats, albeit less so than in young animals, suggesting that the age-related reduction of T contributes in part to altered brain neuropeptide gene expression favoring anorexia and wasting with aging. C1 Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Washington, Sch Med, Div Gerontol & Geriatr Med, Dept Med, Seattle, WA 98108 USA. Univ Washington, Sch Med, Populat Ctr Res Reprod, Seattle, WA 98108 USA. RP Matsumoto, AM (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, S-182-GRECC,1660 S Columbian Way, Seattle, WA 98108 USA. FU NICHD NIH HHS [P50-HD-12629] NR 50 TC 40 Z9 40 U1 0 U2 1 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 2002 VL 143 IS 3 BP 954 EP 963 DI 10.1210/en.143.3.954 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 524WA UT WOS:000174034800026 PM 11861518 ER PT J AU John, MR Arai, M Rubin, DA Jonsson, KB Juppner, H AF John, MR Arai, M Rubin, DA Jonsson, KB Juppner, H TI Identification and characterization of the murine and human gene encoding the tuberoinfundibular peptide of 39 residues SO ENDOCRINOLOGY LA English DT Article ID HUMAN PARATHYROID-HORMONE; PTH2 RECEPTOR; SIGNAL PEPTIDES; NERVOUS-SYSTEM; EXPRESSION; AGONIST; RAT; ZEBRAFISH; SEQUENCE; PROTEIN AB By screening public databases, we identified human and mouse genomic DNA clones that encode the tuberoinfundibular peptide of 39 residues (TIP39). The TIP39 precursor is encoded by at least three exons; a noncoding exon 131, exon 1 encoding residues -61 (initiator methionine) to -19 of the leader sequence, and exon 2 encoding residues - 18 to - 1 and residues +1 to +39. Secreted human TIP39 is identical to the previously isolated bovine TIP39, whereas mouse TIP39 differs by four amino acids. Phylogenetic analyses suggested that TIP39, PTH, and PTHrP may have evolved from a common ancestor. Synthetic human and mouse TIP39 showed indistinguishable potencies [EC50: 0.54 (human) vs. 0.74 mM (mouse)] at the human PTH2-receptor stably expressed in LL-CPK1 cells; furthermore, TIP-(9-39) was an inhibitor of cAMP accumulation stimulated by either [Tyr(34)]PTH(1-34)amide or human/bovine TIP39. In the mouse, an approximately 4.5-kb mRNA encoding TIP39 was identified by Northern blot analysis in testis and, less abundantly, in liver and kidney, whereas other tissues revealed additional smaller transcripts. In situ hybridizations revealed TIP39 expression in seminiferous tubuli and several brain regions, including nucleus ruber, nucleus centralis pontis, and nucleus subparafascicularis thalami. Because PTH2 receptor expression was previously shown to be highest in brain, pancreas, and testis, our findings are consistent with the notion that TIP39 is a neuropeptide which may also have a role in spermatogenesis. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, MassGen Hosp Children, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Illinois State Univ, Dept Biol Sci, Normal, IL 61790 USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Wellman 5,50 Blossom St, Boston, MA 02114 USA. EM jueppner@helix.mgh.harvard.edu NR 44 TC 26 Z9 31 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 2002 VL 143 IS 3 BP 1047 EP 1057 DI 10.1210/en.143.3.1047 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 524WA UT WOS:000174034800036 PM 11861531 ER PT J AU Langton, JE Brent, GA AF Langton, JE Brent, GA TI Nonthyroidal illness syndrome: evaluation of thyroid function in sick patients SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article ID TUMOR-NECROSIS-FACTOR; TYPE-3 IODOTHYRONINE DEIODINASE; SERUM THYROXINE CONCENTRATION; EUTHYROID SYNDROME; RECEPTOR COACTIVATORS; HOSPITALIZED-PATIENTS; FREE TRIIODOTHYRONINE; HORMONE METABOLISM; THYROTROPIN ASSAY; BINDING GLOBULIN AB Changes in thyroid function in the setting of systemic illness, surgery, or fasting are referred to as nonthyroidal illness syndrome (also called "sick euthyroid syndrome"). Nonthyroidal illness influences thyroid hormone production and action at multiple levels including the hypothalamic-pituitary-thyroid axis, thyroid hormone transport, and metabolism. This article reviews the pathophysiology of these changes and the influence on interpretation of thyroid function tests. Guidelines are provided for the assessment of thyroid function in sick patients and the options for treatment. C1 VA Greater Los Angeles Healthcare Syst, Dept Med, Div Endocrinol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Brent, GA (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Med, Div Endocrinol, 11301 Wilshire Blvd, Los Angeles, CA USA. FU NIDDK NIH HHS [DK43714] NR 65 TC 20 Z9 23 U1 1 U2 2 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 2002 VL 31 IS 1 BP 159 EP + AR PII S0889-8529(01)00008-1 DI 10.1016/S0889-8529(01)00008-1 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 557RX UT WOS:000175922900010 PM 12055987 ER PT J AU Hauser, R Altshul, L Chen, ZY Ryan, L Overstreet, J Schiff, I Christiani, DC AF Hauser, R Altshul, L Chen, ZY Ryan, L Overstreet, J Schiff, I Christiani, DC TI Environmental organochlorines and semen quality: Results of a pilot study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE male reproductive health; organochlorines; pesticides; polychlorinated biphenyls; semen quality; sperm concentration ID POLYCHLORINATED-BIPHENYLS; PREDICTIVE VALUE; SPERM FUNCTION; PCB CONGENERS; FERTILE MEN; P,P'-DDE; BLOOD; EXPOSURE; DECLINE; INVITRO AB There have been numerous studies that suggest that sperm concentrations (sperm counts) are declining in men. However, other studies suggest that sperm counts are not declining or may be increasing in some areas. Although there is disagreement on whether there is a downward temporal trend in sperm counts, the studies provide evidence that sperm counts vary by geographic location. It has been hypothesized that the geographic variation in sperm concentrations may be due to environmental exposures, lifestyle factors, or some unknown causes. To determine whether contemporary ambient levels of polychlorinated biphenyls (PCBs) and p,p'-DDE are associated with altered semen quantity and quality, we selected a study population without specific exposure to PCBs or p,p'-DDE. The present study presents the results from a pilot study on the relationship between serum PCBs and p,p'-DDE and semen quality in 29 subjects recruited from the Massachusetts General Hospital Andrology Laboratory. Of the 29 subjects, 3 had sperm concentrations < 20 million/mL, 7 had < 50% motile sperm, 9 had < 4% normal morphology, and 6 were below normal in more than one semen parameter. The 18 subjects with normal spermatozoa concentration, motility, and morphology were used as comparison subjects. The mean (SE) concentration of the sum of PCBs and p,p'-DDE was 242 ng/g lipids (34.0) and 354 ng/g lipids (120), respectively, for men with below normal motility as compared to 202 ng/g lipids (16.6) and 240 ng/g lipids (31-1), respectively, for the comparison subjects. The data showed general trends that were suggestive of an association between PCBs and p,p'-DDE and abnormal motility, as well as with sperm concentration and morphology. A full-scale study is currently in progress. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Androl Lab, Vincent Mem Obstet & Gynecol Serv, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vitro Fertilizat Unit, Boston, MA USA. Univ Calif Davis, Inst Toxicol & Environm Hlth, Davis, CA 95616 USA. RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Bldg 1,Room 1405,655 Huntington Ave, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NIEHS NIH HHS [ES 00002, R01 ES 09718] NR 36 TC 47 Z9 55 U1 1 U2 7 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 2002 VL 110 IS 3 BP 229 EP 233 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 529RA UT WOS:000174311300020 PM 11882472 ER PT J AU Gelber, R Bonetti, M Goldhirsch, A AF Gelber, R Bonetti, M Goldhirsch, A TI Tailored treatment investigations using predictive factors SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. IBCSG, Dept Biostat Sci, Boston, MA USA. European Inst Oncol, Milan, Italy. IBCSG, Dept Med Oncol, Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD MAR PY 2002 VL 38 SU 3 MA 316 BP S125 EP S125 DI 10.1016/S0959-8049(02)80402-6 PG 1 WC Oncology SC Oncology GA 542PE UT WOS:000175052800321 ER PT J AU Goldhirsch, A Gelber, R AF Goldhirsch, A Gelber, R TI Adjuvant systemic treatment for the very young (< 35 years) SO EUROPEAN JOURNAL OF CANCER LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. European Inst Oncol, Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD MAR PY 2002 VL 38 SU 3 MA 321 BP S126 EP S126 DI 10.1016/S0959-8049(02)80407-5 PG 1 WC Oncology SC Oncology GA 542PE UT WOS:000175052800326 ER PT J AU Vidal-Trecan, GM Stahl, JE Durand-Zaleski, I AF Vidal-Trecan, GM Stahl, JE Durand-Zaleski, I TI Managing toxic thyroid adenoma: a cost-effectiveness analysis SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID RADIOACTIVE IODINE THERAPY; QUALITY-OF-LIFE; I-131 THERAPY; FOLLOW-UP; DECISION-ANALYSIS; INDUCED AGRANULOCYTOSIS; RADIOIODINE TREATMENT; SURGICAL-TREATMENT; PERSONAL-COMPUTER; CANCER INCIDENCE AB Objective: To examine the cost-effectiveness of therapeutic strategies for patients with toxic thyroid adenoma. Design: A decision analytic model was used to examine strategies, including thyroid lobectomy after a 3-month course of antithyroid drugs (ATDs), radioactive iodine (RAI), and lifelong ATDs followed by either RAI (ATD-RAI) or surgery (ATD-surgery) in patients suffering severe drug reactions. Methods: Outcomes were measured in quality-adjusted life years. Data on the prevalence of co-incident thyroid cancer, complications and treatment efficacies were derived from a systematic review of the literature (1966-2000). Costs were examined from the health care system perspective. Costs and effectiveness were examined at their present values. Discounting (3% per year), variations of major cost components, and every variable for which disagreements exist among studies or expert opinion were examined by sensitivity analyses. Results: For a 40-year-old woman, surgery was both the most effective and the least costly strategy (Euro1391),while ATD-RAI cost the most (Euro5760). RAI was more effective than surgery if surgical mortality exceeded 0.6% (basc-case 0.001%). RAI become less costly for women of more than 72 years (more than 66 in discounted analyses). For women of 85, ATD-RAI may be more effective than RAI and have an inexpensive marginal cost-effectiveness ratio (Euro4975) if lifelong follow-up results in no decrement in quality of life. Conclusions: Age, surgical mortality, therapeutic costs and patient preference must all be considered in choosing an appropriate therapy. C1 Univ Paris 05, Dept Sante Publ, Assistance Publ Hop Paris, CHU Cochin Port Royal, F-75014 Paris, France. Massachusetts Gen Hosp, Decis Anal & Technol Assessment Grp, Boston, MA 02114 USA. CHU Henri Mondor, F-94010 Creteil, France. RP Vidal-Trecan, GM (reprint author), Univ Paris 05, Dept Sante Publ, Assistance Publ Hop Paris, CHU Cochin Port Royal, 24 Rue Faubourg St Jacques, F-75014 Paris, France. OI Vidal-Trecan, Gwenaelle/0000-0002-2010-0207 NR 81 TC 17 Z9 17 U1 0 U2 3 PU BIO SCIENTIFICA LTD PI BRISTOL PA 16 THE COURTYARD, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4NQ, ENGLAND SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD MAR PY 2002 VL 146 IS 3 BP 283 EP 294 DI 10.1530/eje.0.1460283 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 606PT UT WOS:000178742900003 PM 11888833 ER PT J AU Carter, LL Fouser, LA Jussif, J Fitz, L Deng, B Wood, CR Collins, M Honjo, T Freeman, GJ Carreno, BM AF Carter, LL Fouser, LA Jussif, J Fitz, L Deng, B Wood, CR Collins, M Honjo, T Freeman, GJ Carreno, BM TI PD-1 : PD-L inhibitory pathway affects both CD4(+)and CD8(+) T cells and is overcome by IL-2 SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE PD-1; PD-L1; inhibitory receptor ID IN-VIVO; LYMPHOCYTE RESPONSE; ANTIGEN RECEPTOR; TRANSGENIC MICE; CUTTING EDGE; B7 FAMILY; CTLA-4; ACTIVATION; PROLIFERATION; ANERGY AB Programmed death-1 (PD-1) is an immunoreceptor tyrosine-based inhibitory motif (ITIM)containing receptor expressed upon T cell activation. PD-1(-/-) animals develop autoimmune diseases, suggesting an inhibitory role for PD-1 in immune responses. Members of the B7 family, PD-L1 and PD-L2, are ligands for PD-1. This study examines the functional consequences of PD-1:PD-L engagement on murine CD4 and CD8 T cells and shows that these interactions result in inhibition of proliferation and cytokine production. T cells stimulated with anti-CD3/PD-L1. Fc-coated beads display dramatically decreased proliferation and IL-2 production, while CSFE analysis shows fewer cells cycling and a slower division rate. Costimulation with soluble anti-CD28 mAb can overcome PD-1-mediated inhibition by augmenting IL-2 production. However, PD-1:PD-L interactions inhibit IL-2 production even in the presence of costimulation and, thus, after prolonged activation, the PD-1:PD-L inhibitory pathway dominates. Exogenous IL-2 is able to overcome PD-L1-mediated inhibition at all times, indicating that cells maintain IL-2 responsiveness. Experiments using TCR transgenic CD4(+) or CD8(+) T cells stimulated with antigen-presenting cells expressing PD-L1 show that both T cell subsets are susceptible to this inhibitory pathway. However, CD8(+) T cells may be more sensitive to modulation by the PD-1:PD-L pathway because of their intrinsic inability to produce significant levels of IL-2. C1 Wyeth Genet Inst Inc, Cambridge, MA 02140 USA. Kyoto Univ, Grad Sch Med, Kyoto, Japan. Harvard Med Sch, Dana Farber Canc Res Inst, Boston, MA USA. RP Carter, LL (reprint author), Wyeth Genet Inst Inc, 200 Cambridge Pk Dr, Cambridge, MA 02140 USA. RI Honjo, Tasuku/N-4470-2016 NR 41 TC 342 Z9 385 U1 4 U2 24 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 2002 VL 32 IS 3 BP 634 EP 643 DI 10.1002/1521-4141(200203)32:3<634::AID-IMMU634>3.0.CO;2-9 PG 10 WC Immunology SC Immunology GA 531VY UT WOS:000174439000005 PM 11857337 ER PT J AU Cicchetti, F Brownell, AL Williams, K Chen, YI Livni, E Isacson, O AF Cicchetti, F Brownell, AL Williams, K Chen, YI Livni, E Isacson, O TI Neuroinflammation of the nigrostriatal pathway during progressive 6-OHDA dopamine degeneration in rats monitored by immunohistochemistry and PET imaging SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE 6-OHDA; inflammation; Parkinson's disease; PET imaging; PK11195; Sprague-Dawley rats ID PERIPHERAL BENZODIAZEPINE RECEPTOR; POSITRON-EMISSION-TOMOGRAPHY; SUBSTANTIA-NIGRA; ACTIVATED MICROGLIA; PARKINSONS-DISEASE; IN-VIVO; REACTIVE MICROGLIA; PK11195 BINDING; ISCHEMIC STROKE; PRIMATE MODEL AB We investigated the microglial response to progressive dopamine neuron degeneration using in vivo positron emission tomography (PET) imaging and postmortem analyses in a Parkinson's disease (PD) rat model induced by unilateral (right side) intrastriatal administration of 6-hydroxydopamine (6-OHDA). Degeneration of the dopamine system was monitored by PET imaging of presynaptic dopamine transporters using a specific ligand (11) C-CFT (2beta-carbomethoxy-3beta-(4-fluorophenyl) tropane). Binding of (11) C-CFT was markedly reduced in the striatum indicating dopaminergic degeneration. Parallel PET studies of (11) C-PK11195 (1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3 isoquinoline carboxamide) (specific ligand for activated microglia) showed increased binding in the striatum and substantia nigra indicative of a microglial response. Postmortem immunohistochemical analyses were performed with antibodies against CR3 for microglia/macrophage activation. Using a qualitative postmortem index for microglial activation we found an initially focal, then widespread microglial response at striatal and nigral levels at 4 weeks postlesion. These data support the hypothesis that inflammation is a significant component of progressive dopaminergic degeneration that can be monitored by PET imaging. C1 Harvard Univ, McLean Hosp, Sch Med, Neuroregenerat Lab, Belmont, MA 02478 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Viral Pathogenesis, Boston, MA 02215 USA. RP Isacson, O (reprint author), Harvard Univ, McLean Hosp, Sch Med, Neuroregenerat Lab, MRC119,115 Mill St, Belmont, MA 02478 USA. FU NINDS NIH HHS [NS 37654, NS 41263-02] NR 41 TC 230 Z9 240 U1 0 U2 8 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAR PY 2002 VL 15 IS 6 BP 991 EP 998 DI 10.1046/j.1460-9568.2002.01938.x PG 8 WC Neurosciences SC Neurosciences & Neurology GA 536HU UT WOS:000174695300007 PM 11918659 ER PT J AU Hogemann, D Basilion, JP AF Hogemann, D Basilion, JP TI "Seeing inside the body": MR imaging of gene expression SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE transgene; expression profiling; MRI; contrast agent; molecular signature ID MAGNETIC-RESONANCE MICROSCOPY; CELL-SURFACE GLYCOPROTEIN; TRANSFERRIN RECEPTOR; CONTRAST AGENTS; IN-VIVO; AFFINITY; TISSUE; CLASSIFICATION; PROLIFERATION; CARCINOMA AB The goal of this review is to describe the developments and recent advances that are enabling applications of magnetic resonance (MR) imaging for noninvasive imaging of gene expression. Guiding application of this technology has been the need to test, in vivo and in real time. hypotheses developed in multiple scientific fields. Advances made in the human genome project and our increasing understanding of the molecular basis of normal and disease physiology have defined questions that will only be answered when specific molecular imaging modalities are developed. In this review we will briefly summarize the salient features of MR imaging to provide the backdrop for a more detailed discussion of specific applications of MR imaging of gene expression. We will conclude with the insights gained from genomic approaches and how they might he exploited for MR imaging of gene expression in the future. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Ctr Mol Imaging Res, Ctr Mol Anal & Imaging,NFCR,Dept Radiol, Boston, MA USA. RP Basilion, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Ctr Mol Imaging Res, Ctr Mol Anal & Imaging,NFCR,Dept Radiol, Boston, MA USA. NR 36 TC 26 Z9 29 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD MAR PY 2002 VL 29 IS 3 BP 400 EP 408 DI 10.1007/s00259-002-0765-x PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 553ZE UT WOS:000175707600018 PM 12002717 ER PT J AU Pahlavani, MA Vargas, DA Evans, TR Shu, JH Nelson, JF AF Pahlavani, MA Vargas, DA Evans, TR Shu, JH Nelson, JF TI Melatonin fails to modulate immune parameters influenced by calorie restriction in aging Fischer 344 rats SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article DE melatonin; caloric restriction; immunomodulation; aging; rat ID INDUCED LYMPHOCYTE-PROLIFERATION; T-CELL PROLIFERATION; PINEAL-GLAND; OPIATERGIC MECHANISM; DIETARY RESTRICTION; ANTIBODY-RESPONSE; GENE-EXPRESSION; F344 RATS; MICE; SPLEEN AB The aim of this study was to determine if long-term treatment with melatonin (MEL), a purported anti-aging agent, was as effective as calorie restriction (CR) in modulating immune parameters in aging Fischer 344 male rats. Splenic lymphocytes were isolated from 17-month-old rats that, beginning at 6 weeks of age, were treated with MEL (4 or 16 mug/ml in drinking water) and from 17-month-old rats fed ad libitum (AL) or rats fed a CR diet (55% of AL intake). The number of splenic T cell populations and T cell subsets was measured by flow cytometry, the proliferative response of splenocytes to Concanavalin A (Con A) and lipopolysaccharide (LPS) was measured by [H-3]thymidine incorporation, and the induction of cytokine production (IL-2 and IFN-gamma) was measured by ELISA assay. In addition, the level of the natural killer (NK) cell activity was assessed by fluorimetric assay. CR rats had a higher number of lymphocytes expressing the naive T cell marker (CD3 OX22) than AL rats (P < 0.05). CR rats also showed greater induction of proliferative response, IL-2 and IFN-γ levels following Con A simulation, and NK cell activity than AL rats (P < 0.05). MEL-treated rats did not differ from AL rats in any of these parameters or in any other measurement. These results indicate that MEL treatment is unable to modulate immune function in a manner comparable with that of CR. C1 Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. RP Pahlavani, MA (reprint author), Audie L Murphy Mem Vet Adm Med Ctr, GRECC 182, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NIA NIH HHS [AG14088, AG00677, AG14932] NR 45 TC 9 Z9 10 U1 0 U2 0 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD MAR PY 2002 VL 227 IS 3 BP 201 EP 207 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 522VM UT WOS:000173917700008 PM 11856819 ER PT J AU Tai, YT Podar, K Kraeft, SK Wang, FF Young, G Lin, B Gupta, D Bo Chen, L Anderson, KC AF Tai, YT Podar, K Kraeft, SK Wang, FF Young, G Lin, B Gupta, D Bo Chen, L Anderson, KC TI Translocation of Ku86/Ku70 to the multiple myeloma cell membrane: Functional implications SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID B-CELLS; CD40; KU; EXPRESSION; ADHESION; NUCLEUS; INTERLEUKIN-6; RECOMBINATION; AUTOANTIGEN; ANTIBODIES AB Objective. Since the central hallmarks of human multiple myeloma (MM) are abnormalities in immunoglobulin (Ig) gene rearrangement, IgH class switching, and DNA damage repair, and since Ku86 and Ku70 proteins are central to these processes, aberrant Ku function may play a role in MM pathogenesis. Our prior studies demonstrated a 69-kDa Ku86 variant in freshly isolated patient MM cells that confers sensitivity to DNA damage. We also showed that Ku86 on the cell surface of CD40-activated MM cells mediates homotypic tumor cell adhesion, as well as heterotypic adhesion to bone marrow stromal cells. We here define the mechanism and functional significance of CD40-induced Ku translocation from the cytoplasm to the cell membrane in MM cells vs normal B cells. Materials and Methods. We examined Ku86 and Ku70 translocation following CD40 activation in human MM cells vs normal tonsillar B lymphocytes. We then identified the functional sequelae of membrane Ku86 and Ku70 expression on CD40-activated human MM cells. Results. CD40 activation induces translocation of both Ku86 and Ku70 to the cell surface of MM cells. but not normal tonsillar B cells. Moreover, CD40 activation triggers Ku association with CD40 only in CD40-activated MM cells. Finally, CD40-activated MM cells adhere to fibronectin and are protected against apoptosis triggered by irradiation or doxorubicin; conversely. antibodies to Ku both inhibit tumor cell binding and restore sensitivity to these agents. Conclusion. These results demonstrate functional significance of Ku translocation to the cell membrane of CD40-activated human MM cells. Therefore, targeting Ku86 and Ku70, with blocking peptides for example, might serve as a novel treatment strategy in human MM. (C) 2002 International Society for Experimental Hematology. Published by Elsevier Science Inc. C1 Dana Farber Canc Inst, Dept Adult Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Jerome Lipper Multiple Myeloma Ctr, M557,44 Binney St, Boston, MA 02115 USA. NR 28 TC 30 Z9 32 U1 0 U2 3 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 2002 VL 30 IS 3 BP 212 EP 220 AR PII S0301-472X(01)00786-X DI 10.1016/S0301-472X(01)00786-X PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 532QJ UT WOS:000174486300004 PM 11882358 ER PT J AU Seifer, DB MacLaughlin, DT Christian, BP Feng, B Shelden, RM AF Seifer, DB MacLaughlin, DT Christian, BP Feng, B Shelden, RM TI Early follicular serum mullerian-inhibiting substance levels are associated with ovarian response during assisted reproductive technology cycles SO FERTILITY AND STERILITY LA English DT Article DE serum MIS; ovarian response; ART ID GRANULOSA-CELLS; II RECEPTOR; HORMONE; EXPRESSION; IMMUNOASSAY; SERTOLI; GROWTH AB Objective: To test the hypothesis that the concentration of early follicular phase serum mullerian-inhibiting substance (MIS) is associated with ovarian response in women undergoing ovulation induction in preparation for assisted reproductive technology (ART). Design: Retrospective analysis of frozen day 3 serum samples. Setting: Academic ART program. Patient(s): One sample of frozen day 3 serum from women with less than or equal to6 retrieved oocytes (n = 28) compared with women with less than or equal to11 oocytes retrieved (n = 79) in preparation for IVF. Intervention(s): None. Main Outcome Measure(s): Comparison of day 3 serum MIS levels between two groups of women. Other comparisons included maximum serum E, concentrations, number of retrieved oocytes, and percentage of mature oocytes between groups. Result(s): Mean serum MIS concentrations were 1.0 +/- 0.4 ng/mL compared with 2.5 +/- 0.3 ng/mL, or more than a 2.5-fold greater serum concentration of MIS in the group with greater than or equal to11 oocytes retrieved compared with in the group with 56 retrieved oocytes. Conclusion(s): These data demonstrate an association between early follicular phase serum MIS and the number of retrieved oocytes. Higher day 3 serum MIS concentrations were associated with greater number of retrieved oocytes. (Fertil Steril(R) 2002 77:468-77. (C)2002 by American Society for Reproductive Medicine.). C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ 08901 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Seifer, DB (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, 303 George St,Suite 250, New Brunswick, NJ 08901 USA. OI Seifer, David/0000-0003-3950-9341 NR 17 TC 273 Z9 286 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAR PY 2002 VL 77 IS 3 BP 468 EP 471 AR PII S0015-0282(01)03201-0 DI 10.1016/S0015-0282(01)03201-0 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 531AT UT WOS:000174393000007 PM 11872196 ER PT J AU Dulai, GS AF Dulai, GS TI Surveying the case for surveillance SO GASTROENTEROLOGY LA English DT Editorial Material ID BARRETTS-ESOPHAGUS; CANCER RISK; ADENOCARCINOMA; DYSPLASIA; DIAGNOSIS; PATTERNS; PROGRAM; IMPACT C1 VA Greater Los Angeles Healtcare Syst, Ctr Study Digest Healthcare Qual & Outcomes, CURE Digest Dis Res Ctr, Los Angeles, CA USA. RP Dulai, GS (reprint author), VA Greater Los Angeles Healtcare Syst, Ctr Study Digest Healthcare Qual & Outcomes, CURE Digest Dis Res Ctr, Los Angeles, CA USA. FU NCRR NIH HHS [1K23 RR DK 00198-01] NR 26 TC 22 Z9 22 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAR PY 2002 VL 122 IS 3 BP 820 EP 823 DI 10.1053/gast.2002.32093 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 525EY UT WOS:000174056900030 PM 11875016 ER PT J AU Dulai, GS Gralnek, IM Oei, TT Chang, D Alofaituli, G Gornbein, J Kahn, K AF Dulai, GS Gralnek, IM Oei, TT Chang, D Alofaituli, G Gornbein, J Kahn, K TI Utilization of health care resources for low-risk patients with acute, nonvariceal upper GI hemorrhage: an historical cohort study SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-for-Gastrointestinal-Endoscopy CY MAY 21-24, 2000 CL SAN DIEGO, CALIFORNIA SP Amer Soc Gastrointestinal Endoscopy ID UPPER GASTROINTESTINAL HEMORRHAGE; PEPTIC-ULCER HEMORRHAGE; OUTPATIENT MANAGEMENT; EARLY DISCHARGE; HOSPITALIZATION; ENDOSCOPY; SAFETY; TRIAL AB Background: Adults hospitalized with acute, nonvariceal upper GI hemorrhage can be accurately stratified according to their risk of subsequent adverse outcomes by using the Rockall score. Low-risk patients (Rockall score: 2) may be candidates for early discharge. Methods: Cases were identified with ICD-9-CM codes for calendar years 1997 and 1998. Medical record data to determine patient Rockall risk score, health care resource utilization, and adverse outcomes were abstracted with standardized forms. Results: Fifty-three of 175 (30%) cases had Rockall scores less than or equal to2. As predicted, those patients with Rockall scores less than or equal to2 had a low risk of adverse outcomes with only 2 of 53 (4%) meeting criteria for recurrent bleeding as defined by the "Rebleed" variable, and no mortality. These low-risk patients had a mean hospital stay of 2.6 +/- 2.1 days; 49% were admitted to an intermediate or intensive care unit bed and 57% were given H-2 receptor antagonists intravenously. Conclusions: The proportion of patients admitted with acute, nonvariceal, upper GI hemorrhage with Rockall Scores less than or equal to2 was substantial. Adverse outcomes were rare. In contrast, the level of health care resource utilization appeared high. The Rockall score has potential as a clinically based concurrent decision rule to improve the quality of care by finding those patients less likely to require intensive health care services. C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, CURE Digest Res Ctr, Ctr Study Digest Healthcare Qual & Outcomes, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Biostat, Los Angeles, CA 90073 USA. RP Gralnek, IM (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, CURE Digest Res Ctr, Ctr Study Digest Healthcare Qual & Outcomes, Bldg 115,Room 318,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 25 TC 31 Z9 31 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD MAR PY 2002 VL 55 IS 3 BP 321 EP 327 DI 10.1067/mge.2002.121880 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 528KY UT WOS:000174244000003 PM 11868003 ER PT J AU Mhashilkar, AM Doebis, C Seifert, M Busch, A Zani, C Hoo, JS Nagy, M Ritter, T Volk, HD Marasco, WA AF Mhashilkar, AM Doebis, C Seifert, M Busch, A Zani, C Hoo, JS Nagy, M Ritter, T Volk, HD Marasco, WA TI Intrabody-mediated phenotypic knockout of major histocompatibility complex class I expression in human and monkey cell lines and in primary human keratinocytes SO GENE THERAPY LA English DT Article DE gene therapy; MHC-I; transplantation; MHC class I; tolerance; intracellular antibody ID MHC CLASS-I; SINGLE-CHAIN ANTIBODY; CULTURED ALLOGENEIC KERATINOCYTES; HUMAN SKIN EQUIVALENT; MONOCLONAL-ANTIBODIES; INTRACELLULAR EXPRESSION; DEFICIENT MICE; GENE-TRANSFER; MUTANT MICE; T-CELLS AB Cultured keratinocyte allografts from unrelated donors can be readily grown as sheets in large-scale cell culture and have been used as an immediate skin cover for severely burned patients. Despite the absence of passenger leukocytes and the unlimited amount of material that can be obtained for permanent skin coverage, the allografts are susceptible to rejection. Since MHC class I (MHCI) antigens serve as targets for allograft rejection, we investigated whether 'phenotypic knockout' of human MHCI could be achieved through expression of an ER-directed anti-human MHCI single-chain intrabody (sFvhMHCI) that is directed against a monomorphic, conformational epitope, expressed across species lines, on the MHCI heavy chain. Co-immunoprecipitation of both MHCI heavy chain and 2-microglobulin occurred in transfected monkey COS-1 cells, while Jurkat T cells stably expressing the ER-directed sFvhMHCI intrabody showed that complete phenotypic knockout of MHCI cell surface expression could be achieved. Infection of several human cell lines of divergent tissue sources and different HLA haplotypes resulted in marked down-regulation of MHCI expression, even under conditions where inflammatory cytokines (eg gamma-IFN) which up-regulate MHCI expression were used. Finally, when adenovirus encoding the anti-human MHCI intrabody was used to transduce primary human keratinocytes, a marked reduction of surface MHCI expression was observed, These in vitro studies set the groundwork for in vivo studies to determine if intrabody-mediated knockout of MHCI can impair alloantigen expression and prolong the survival of keratinocyte allografts. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Med Sch Charite, Inst Med Immunol, D-10117 Berlin, Germany. Harvard Univ, Sch Med, Boston, MA USA. Sch Med, Inst Med Immunol, Berlin, Germany. Sch Med, Inst Forens Med, Berlin, Germany. RP Marasco, WA (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, JFB 824,44 Binney St, Boston, MA 02115 USA. RI Ritter, Thomas/C-1695-2009 FU NCI NIH HHS [CA06516]; NIAID NIH HHS [AI28785, AI41954] NR 92 TC 28 Z9 34 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD MAR PY 2002 VL 9 IS 5 BP 307 EP 319 DI 10.1038/sj/gt/3301656 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 533EQ UT WOS:000174516800001 PM 11938450 ER PT J AU Joo, WS Jeffrey, PD Cantor, SB Finnin, MS Livingston, DM Pavletich, NP AF Joo, WS Jeffrey, PD Cantor, SB Finnin, MS Livingston, DM Pavletich, NP TI Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brcal1 BRCT structure SO GENES & DEVELOPMENT LA English DT Article DE 53BP1; p53; DNA damage; BRCT domain; Brca1; BACH1 ID DNA-DAMAGE RESPONSE; LIGASE-III; CONSERVED DOMAINS; PROTEIN; REPAIR; COMPLEX; PHOSPHORYLATION; BINDING; MUTANT; TRANSCRIPTION AB Brca1 C-terminal (BRCT) domains are a common protein-protein interaction motif in proteins involved in the DNA damage response and DNA repair. The DNA-damage response protein 53BP1 has two BRCT domains that bind to the DNA-binding domain of p53. The 53BP1 tandem-BRCT region is homologous to the tandem-BRCT region of Brca1, which is involved in double-strand break repair and homologous recombination and which binds BACH1, a member of the DEAH helicase family. Here we report the structures of a human 53BP1-p53 complex and of the rat Brca1 BRCT repeats. The 53BP1-p53 structure shows that the two BRCT repeats are arranged tandemly and pack extensively through an interface that also involves the inter-repeat linker. The first BRCT repeat and the linker together bind p53 on a region that overlaps with the DNA-binding surface of p53 and involves p53 residues that are mutated in cancer and are important for DNA binding. Comparison with the structure of the tandem-BRCT region of Brca1 shows a remarkable conservation of the repeat arrangement and of the inter-BRCT repeat interface. Analysis of human BRCA1 tumor-derived mutations and conservation identifies a potential protein-binding site that we show through mutagenesis is involved in BACH1 binding. The BACH1-binding region of Brca1 consists of a unique insertion in the first BRCT repeat and the inter-repeat linker and is analogous to the region of 53BP1 that binds p53. C1 Mem Sloan Kettering Canc Ctr, Cellular Biochem & Biophys Program, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Howard Hughes Med Inst, New York, NY 10021 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pavletich, NP (reprint author), Mem Sloan Kettering Canc Ctr, Cellular Biochem & Biophys Program, New York, NY 10021 USA. NR 42 TC 140 Z9 146 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAR 1 PY 2002 VL 16 IS 5 BP 583 EP 593 DI 10.1101/gad.959202 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 529TG UT WOS:000174314200006 PM 11877378 ER PT J AU Buxbaum, SG Elston, RC Tishler, PV Redline, S AF Buxbaum, SG Elston, RC Tishler, PV Redline, S TI Genetics of the apnea hypopnea index in Caucasians and African Americans: I. Segregation analysis SO GENETIC EPIDEMIOLOGY LA English DT Article DE obstructive sleep apnea; segregation analysis; commingling analysis; AHI; family studies ID FAMILIAL AGGREGATION; SLEEP; OBESITY; AGE AB Differences in age of presentation and anatomic risk factors for obstructive sleep apnea (OSA) in Caucasians and African Americans suggest possible racial differences in the genetic underpinnings of the disorder. In this study, we assess transmission patterns in a Caucasian sample consisting of 177 families (N = 1,195) and in an African American sample consisting of 125 families (N = 720) for two variables: 1) apnea hypopnea index (AHI) log transformed and adjusted for age, and 2) AHI log transformed and adjusted for age and body mass index (BMI). We allowed for residual familial correlations and sex-specific means in all models. Analysis of the Caucasian sample showed transmission patterns consistent with that of a major gene that were stronger in the age-adjusted variable than in the age- and BMI-adjusted variable. However, in the African American families, adjusting for BMI in addition to age gave stronger evidence for segregation of a codominant gene with an allele frequency of 0.14, accounting for 35% of the total variance. These results provide support for an underlying genetic basis for OSA that in African Americans is independent of the contribution of BMI. Genet. Epidemiol. 22:243-253, 2002. (C) 2002 Wiley-Liss, Inc. C1 Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. VA Boston Healthcare Syst, Boston, MA 02115 USA. Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA. RP Buxbaum, SG (reprint author), Metrohlth Med Ctr, Dept Biostat & Epidemiol, 2500 Metrohealth Dr,Room R259, Cleveland, OH 44109 USA. RI Buxbaum, Sarah/E-1970-2013 OI Buxbaum, Sarah/0000-0002-4886-3564 FU NCRR NIH HHS [1 P41 RR03655]; NHLBI NIH HHS [HL07567, HL43680]; NIGMS NIH HHS [GM28356] NR 24 TC 75 Z9 76 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD MAR PY 2002 VL 22 IS 3 BP 243 EP 253 DI 10.1002/gepi.0170 PG 11 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 534EW UT WOS:000174572500004 PM 11921084 ER PT J AU Antonellis, A Rogus, JJ Canani, LH Makita, Y Pezzolesi, MG Nam, M Ng, D Moczulski, D Warram, JH Krolewski, AS AF Antonellis, A Rogus, JJ Canani, LH Makita, Y Pezzolesi, MG Nam, M Ng, D Moczulski, D Warram, JH Krolewski, AS TI A method for developing high-density SNP maps and its application at the type 1 angiotensin II receptor (AGTR1) locus SO GENOMICS LA English DT Article DE methods; polymorphism; sequence analysis; sequence alignment; genetic screening; linkage disequilibrium; genotype; variation; AGTR1; diabetic nephropathies ID SINGLE-NUCLEOTIDE POLYMORPHISMS; LINKAGE DISEQUILIBRIUM; NEPHROPATHY; DISEASES; APOE; GENE AB Evaluating the potential genetic components of complex disease will likely be aided through the use of dense polymorphism maps. Previously, we reported evidence for linkage with diabetic nephropathy on chromosome 3q in a region encompassing the type I angiotensin 11 receptor (AGTR1) gene. To further investigate any role for this gene in disease onset, we set out to design a dense polymorphism map spanning the AGTR1 locus for the purpose of association studies. Toward this goal, we have developed a technique for rapid identification of polymorphisms in long stretches of genomic DNA. This approach uses long-range PCR, DNA pooling, and transposon-based DNA sequencing. Using this technique, we efficiently validated and genotyped 18 polymorphisms spanning the 60.5-kb AGTR1 locus. Our panel of polymorphisms has an average spacing of 3.2 kb and an average minor allele frequency of 24%. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Harvard Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. RI Canani, Luis/G-9686-2012 OI Canani, Luis/0000-0002-1813-4491 FU NIDDK NIH HHS [DK53534] NR 18 TC 12 Z9 12 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD MAR PY 2002 VL 79 IS 3 BP 326 EP 332 DI 10.1006/geno.2002.6713 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 528BR UT WOS:000174224200008 PM 11863362 ER PT J AU Kaiserman, D Knaggs, S Scarff, KL Gillard, A Mirza, G Cadman, M McKeone, R Denny, P Cooley, J Benarafa, C Remold-O'Donnell, E Ragoussis, J Bird, PI AF Kaiserman, D Knaggs, S Scarff, KL Gillard, A Mirza, G Cadman, M McKeone, R Denny, P Cooley, J Benarafa, C Remold-O'Donnell, E Ragoussis, J Bird, PI TI Comparison of human chromosome 6p25 with mouse chromosome 13 reveals a greatly expanded ov-serpin gene repertoire in the mouse SO GENOMICS LA English DT Article DE serpin; ov-serpin; SPI3; SPI6; PI-6; PI-9; MNEI; phylogeny; gene structure ID MOLECULAR CHARACTERIZATION; PROTEINASE-INHIBITOR; ELASTASE INHIBITOR; GENOMIC DNA; FAMILY; MAP; PROTEINASE-INHIBITOR-9; EXPRESSION; APOPTOSIS; PROTEASE AB Ov-serpins are intracellular proteinase inhibitors implicated in the regulation of tumor progression, inflammation, and cell death. The 13 human ov-serpin genes are clustered at 6p25 (3 genes) and 18q21 (10 genes), and share common structures. We show here that a 1-Mb region on mouse chromosome 13 contains at least 15 ov-serpin genes compared with the three ov-serpin genes within 0.35 Mb at human 6p25: (SERPINB1 (MNEI), SERPINB6 (PI-6), SERPINB9 (PI-9)). The mouse serpins have characteristics of functional inhibitors and fall into three groups on the basis of similarity to MNEI, PI-6, or PI-9. The genes map between the mouse orthologs of the Werner helicase interacting protein and NAD(P)H menadioine oxidoreductase 2 genes, in a region that contains the markers D13Mit136 and D13Mit116. They have the seven-exon structure, typical of human 6p25 ov-serpin genes, with identical intron phasing. Most show restricted patterns of expression, with common sites of synthesis being the placenta and immune tissue. Compared with human, this larger mouse serpin repertoire probably reflects the need to regulate a larger proteinase repertoire arising from differing evolutionary pressures on the reproductive and immune systems. C1 Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia. Kings Coll London, GKT Med Sch, Div Med Mol Genet, Genomics Lab, London SE1 9RT, England. MRC, UK Mouse Genome Ctr, Didcot OX11 ORD, Oxon, England. MRC, Mammalian Genet Unit, Didcot OX11 ORD, Oxon, England. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Bird, PI (reprint author), Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia. EM phil.bird@med.monashi.edu.au OI Denny, Paul/0000-0003-4659-6893; Benarafa, Charaf/0000-0002-2049-7769; Bird, Phillip/0000-0002-6695-606X FU NHLBI NIH HHS [HL66548] NR 36 TC 45 Z9 48 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 2002 VL 79 IS 3 BP 349 EP 362 DI 10.1006/geno.2002.6716 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 528BR UT WOS:000174224200011 PM 11863365 ER PT J AU El-Serag, HB Mason, AC Petersen, N Key, CR AF El-Serag, HB Mason, AC Petersen, N Key, CR TI Epidemiological differences between adenocarcinoma of the oesophagus and adenocarcinoma of the gastric cardia in the USA SO GUT LA English DT Article ID HELICOBACTER-PYLORI INFECTION; GASTROESOPHAGEAL REFLUX DISEASE; BARRETTS-ESOPHAGUS; INTESTINAL METAPLASIA; RISING INCIDENCE; PEPTIC-ULCER; ALCOHOL-USE; CANCER; PREVALENCE; TOBACCO AB Background and aims: It has been suggested that gastric cardia adenocarcinoma (GCA) is a distinct entity from oesophageal adenocarcinoma (OA). We examined several epidemiological features of GCA and OA in the USA to elucidate differences/similarities between these malignancies. Methods: Using the database of Surveillance, Epidemiology, and End Results (SEER) program, we examined incidence rates for temporal changes, and ethnic and age distributions, and performed birth cohort analyses for cases with morphologically and histologically confirmed OA or GCA. Results: The age adjusted incidence rates of OA rose progressively, reaching 1.8 per 100 000 (95% confidence interval 1.7-1.9) during 1987-1991 and 2.5 per 100 000 (2.3-2.6) during 1992-1996. In 1992-1996, Whites were affected five times more than Blacks, and men eight times more than women. A significant increase in incidence occurred among younger persons aged 45-65 years. Irrespective of age, OA was characterised by higher incidence rates among more recent birth cohorts: a 40% increase in incidence for each five year increase in the date of birth-a "birth cohort effect". On the other hand, the incidence rates of GCA reached their highest level of 3.3 per 100 000 (3.2-3.4) in 1987-1991 and subsequently declined during 1992-1996 to 3.1 per 100 000 (3.0-3.3). Whites were affected twice more than blacks and men five times more than women. Most patients with GCA were older than 60 years with no increase among younger persons and no birth cohort effect (p=0.99). Conclusion: Several significant epidemiological differences exist between OA and GCA. These differences suggest that these two malignancies are separate entities with different risk factors. C1 Houston Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ New Mexico, Albuquerque, NM 87131 USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr, Gastroenterol Sect, 152,2002 Holcombe Blvd, Houston, TX 77030 USA. NR 31 TC 168 Z9 172 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD MAR PY 2002 VL 50 IS 3 BP 368 EP 372 DI 10.1136/gut.50.3.368 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 524FZ UT WOS:000174003600017 PM 11839716 ER PT J AU Ottowitz, WE Dougherty, DD Savage, CR AF Ottowitz, WE Dougherty, DD Savage, CR TI The neural network basis for abnormalities of attention and executive function in major depressive disorder: Implications for application of the medical disease model to psychiatric disorders SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID POSITRON EMISSION TOMOGRAPHY; CARD SORTING TEST; CEREBRAL BLOOD-FLOW; FRONTAL-SUBCORTICAL CIRCUITS; PROCESSING RESOURCE DEFICIT; ANTERIOR CINGULATE CORTEX; UNIPOLAR DEPRESSION; NEUROPSYCHOLOGICAL FUNCTION; SUSTAINED ATTENTION; MOOD DISORDERS AB The deficits in attention and executive function characteristic of major depressive disorder (MDD) are reviewed. The networks underlying attention and executive function, the neuropsychological tests commonly used to evaluate these domains, and the neuroanatomy of MDD are also discussed. A neural network approach to the attentional and executive function deficits of MDD has ramifications for hypothesis-guided research, the cognitive model of depression, and application of the medical disease model to psychiatric disorders. C1 Massachusetts Gen Hosp, Psychiat Neurosci Program, Charlestown, MA USA. RP Ottowitz, WE (reprint author), Massachusetts Gen Hosp, Psychiat Neurosci Program, Charlestown, MA USA. NR 128 TC 97 Z9 100 U1 11 U2 26 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAR-APR PY 2002 VL 10 IS 2 BP 86 EP 99 DI 10.1080/10673220216210 PG 14 WC Psychiatry SC Psychiatry GA 536GH UT WOS:000174692000003 PM 11897749 ER PT J AU Perlis, RH Fava, M Nierenberg, AA Pollack, MH Falk, WE Kienke, AS Rosenbaum, JF AF Perlis, RH Fava, M Nierenberg, AA Pollack, MH Falk, WE Kienke, AS Rosenbaum, JF TI Strategies for treatment of SSRI-associated sexual dysfunction: A survey of an academic psychopharmacology practice SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; DOUBLE-BLIND; INDUCED ANORGASMIA; OPEN TRIAL; FLUOXETINE; PAROXETINE; SERTRALINE; ANTIDEPRESSANTS; PSYCHIATRISTS; GRANISETRON C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 50 Staniford St 4th Floor, Boston, MA 02114 USA. NR 50 TC 13 Z9 15 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD MAR-APR PY 2002 VL 10 IS 2 BP 109 EP 114 DI 10.1093/hrp/10.2.109 PG 6 WC Psychiatry SC Psychiatry GA 536GH UT WOS:000174692000005 PM 11897751 ER PT J AU Wang, Y Liberman, MC AF Wang, Y Liberman, MC TI Restraint stress and protection from acoustic injury in mice SO HEARING RESEARCH LA English DT Article DE hearing; noise; conditioning; corticosterone ID COCHLEAR GLUCOCORTICOID PROTEIN; INNER-EAR; TRAUMA; NA,K-ATPASE; RECEPTOR; RAT AB The phenomenon of 'conditioning'. whereby prior exposure to moderate-level non-traumatic sound reduces the permanent injury to subsequent high-level sound exposures, is suggestive of protective effects mediated by stress-induced gene expression in other systems. To test the role of stress pathways in acoustic injury, this study investigated the effect of mild physical restraint, a classic non-acoustic elicitor of stress, on vulnerability to subsequent noise-induced hearing loss. CBA/CaJ mice were divided into groups (control, restraint-only. restraint pre-trauma. and trauma-only). and cochlear sensitivity was assessed via compound action potentials and distortion product otoacoustic emissions. Results showed that two 12-h epochs of mild physical restraint significantly reduced permanent threshold shifts from a subsequent acoustic overexposure, as long as the treatment-trauma interval was short (2 h). Concurrent measures of circulating glucocorticoids showed that the period of protection coincided with the period of elevated corticosterone. Results are consistent with the idea that cochlear protective effects may be mediated by stress pathways and that glucocorticoid levels may be an important upstream regulator of these effects. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Liberman, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [P30 DC005209, R01 DC 0188] NR 18 TC 67 Z9 71 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAR PY 2002 VL 165 IS 1-2 BP 96 EP 102 AR PII S0378-5955(02)00289-7 DI 10.1016/S0378-5955(02)00289-7 PG 7 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 559BZ UT WOS:000176006000011 PM 12031519 ER PT J AU Litovsky, RY Fligor, BJ Traino, MJ AF Litovsky, RY Fligor, BJ Traino, MJ TI Functional role of the human inferior colliculus in binaural hearing SO HEARING RESEARCH LA English DT Article; Proceedings Paper CT 23rd Meeting of the Association-for-Research-in-Otolaryngology CY FEB 21-23, 2000 CL ST PETERSBURG, FLORIDA SP Assoc Res Otolaryngol DE binaural; inferior colliculus; lesion; precedence; localization; speech ID SOUND LOCALIZATION; LATERAL LEMNISCUS; DORSAL NUCLEUS; BRAIN-STEM; SPEECH-INTELLIGIBILITY; UNANESTHETIZED RABBIT; MULTIPLE-SCLEROSIS; UNILATERAL LESIONS; INHIBITORY INPUTS; NEURAL RESPONSES AB Psychophysical experiments were carried out in a rare case involving a 48 year old man (RJC) with a small traumatic hemorrhage of the right dorsal midbrain, including the inferior colliculus (IC). RJC had normal audiograms bilaterally, but there was a marked decrease in wave V amplitude on click-evoked brainstem auditory evoked potentials following left ear stimulation. RJC demonstrated a deficit in sound localization identification when the loudspeakers lay within the auditory hemifield contralateral to his IC lesion. Errors showed a consistent bias towards the hemifield ipsilateral to the lesion. Echo suppression was abnormally weak compared with that seen in control subjects, but only for sources contralateral to the lesion. Finally, speech intelligibility tests showed normal ability to benefit from spatial separation of target and competing speech sources. These results suggest that: (1) localizing sounds within a given hemifield relies on the integrity of the contralateral IC, (2) unilateral IC lesions give the illusion that sound sources in the 'bad' hemifield are displaced towards the 'good' hernifield, (3) the IC mediates aspects of echo suppression, and (4) lesion in the IC does not impede spatial release from masking in speech intelligibility, possibly due to that ability being more heavily mediated by cortical regions. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Boston Univ, Hearing Res Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Litovsky, RY (reprint author), Univ Wisconsin, Waisman Ctr, Room 567,1500 Highland Ave, Madison, WI 53706 USA. FU NIDCD NIH HHS [DC00100, R29-DC02696] NR 43 TC 35 Z9 36 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAR PY 2002 VL 165 IS 1-2 BP 177 EP 188 AR PII S0378-5955(02)00304-0 DI 10.1016/S0378-5955(02)00304-0 PG 12 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 559BZ UT WOS:000176006000019 PM 12031527 ER PT J AU McHutchison, JG Poynard, T Esteban-Mur, R Davis, GL Goodman, ZD Harvey, J Ling, MH Garaud, JJ Albrecht, JK Patel, K Dienstag, JL AF McHutchison, JG Poynard, T Esteban-Mur, R Davis, GL Goodman, ZD Harvey, J Ling, MH Garaud, JJ Albrecht, JK Patel, K Dienstag, JL CA Int Hepatitis Interventional Ther TI Hepatic HCV RNA before and after treatment with interferon alone or combined with ribavirin SO HEPATOLOGY LA English DT Article ID C VIRUS-RNA; ALPHA THERAPY; SUSTAINED RESPONSE; UNITED-STATES; FOLLOW-UP; LIVER; INFECTION; SERUM; COMBINATION AB The clinical use of measuring hepatic hepatitis C virus (HCV) RNA before and after therapy in patients with chronic hepatitis C has been assessed in a number of small clinical trials. Viral clearance from the liver may be a better marker of long-term response than eradication of serum HCV RNA. The aim of this study was to evaluate quantitative hepatic HCV-RNA measurements before and after antiviral therapy. Two thousand eighty-nine chronic hepatitis C patients were enrolled in 3 published clinical trials evaluating interferon alfa-2b alone or with ribavirin either as initial therapy or for interferon relapse. Hepatic HCV-RNA quantitation was performed with a modified reverse-transcription polymerase chain reaction (RT-PCR) before and 24 weeks after therapy in 951 and 1,316 patients, respectively. Pre-therapy hepatic HCV-RNA concentrations correlated best with serum HCV-RNA concentrations (R =.236, P =.0001) and negatively correlated with alanine transaminase (ALT) values (-0.178, P =.0001), duration of infection (-0.09, P =.02), parenchymal injury (-0.135, P =.0001), histologic activity index (HAI) inflammatory score (-0.085, P =.01), Knodell fibrosis score (-0.072, P =.03), and bodyweight (-0.078, P =.02). In paired liver biopsy specimens (n = 534), change in hepatic HCV RNA correlated with the change in the HAI (R =.346, P =.0001). Of 400 sustained virologic responders (SVR), 393 (98%) had undetectable hepatic HCV RNA, whereas 7 (2%) had detectable hepatic HCV RNA; 5 have been followed and 2 have had reappearance of serum HCV RNA 12 months after therapy. In conclusion, measurement of hepatic HCV RNA before or after therapy reflects changes observed in serum HCV RNA, and correlates inversely with hepatic inflammation and fibrosis, but otherwise has minimal clinical use. C1 Scripps Res Inst, Div Gastroenterol, La Jolla, CA 92037 USA. Grp Hosp Pitie Salpetriere, F-75634 Paris, France. Univ Florida, Sect Hepatobiliary Dis, Gainesville, FL 32611 USA. Hosp Gen Valle Hebron, Barcelona, Spain. Armed Forces Inst Pathol, Washington, DC 20306 USA. Schering Plough Res Inst, Kenilworth, NJ USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP McHutchison, JG (reprint author), Scripps Res Inst, Div Gastroenterol Hepatol, 10666 N Torrey Pines Rd,N203, La Jolla, CA 92037 USA. OI Poynard, Thierry/0000-0002-2050-640X FU NCRR NIH HHS [M01 RR 00833, M01 RR 01066] NR 28 TC 76 Z9 78 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 2002 VL 35 IS 3 BP 688 EP 693 DI 10.1053/jhep.2002.31870 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 525WH UT WOS:000174096700025 PM 11870385 ER PT J AU Hsich, G Sena-Esteves, M Breakefield, XO AF Hsich, G Sena-Esteves, M Breakefield, XO TI Critical issues in gene therapy for neurologic disease SO HUMAN GENE THERAPY LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; MUCOPOLYSACCHARIDOSIS TYPE-VII; BONE-MARROW TRANSPLANTATION; SIMPLEX-VIRUS TYPE-1; RECOMBINANT ADENOASSOCIATED VIRUS; LYSOSOMAL STORAGE DISEASE; MANNOSE 6-PHOSPHATE RECEPTOR; THYMIDINE KINASE GENE; AMYOTROPHIC-LATERAL-SCLEROSIS; ENZYME REPLACEMENT THERAPY AB Gene therapy for the nervous system is a newly emerging field with special issues related to modes of delivery, potential toxicity, and realistic expectations for treatment of this vital and highly complex tissue. This review focuses on the potential for gene delivery to the brain, as well as possible risks and benefits of these procedures. This includes discussion of appropriate vectors, such as adeno- associated virus, lentivirus, gutless adenovirus, and herpes simplex virus hybrid amplicons, and cell vehicles, such as neuroprogenitor cells. Routes of delivery for focal and global diseases are enumerated, including use of migratory cells, facilitation of vascular delivery across the blood- brain barrier, cerebrospinal fluid delivery, and convection injection. Attention is given to examples of diseases falling into different etiologic types: metabolic deficiency states, including Canavan disease and lysosomal storage disorders; and degenerative conditions, including Parkinson's disease and other neurodegenerative conditions. C1 Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02114 USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Childrens Hosp Philadelphia, Abramson Res Ctr, Biochem Genet Unit, Philadelphia, PA 19104 USA. RP Massachusetts Gen Hosp E, Dept Mol Neurogenet, 13th St,Bldg 149,6th Floor, Charlestown, MA 02129 USA. EM breakefi@helix.mgh.harvard.edu FU NINDS NIH HHS [NS 24279] NR 286 TC 65 Z9 69 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 EI 1557-7422 J9 HUM GENE THER JI Hum. Gene Ther. PD MAR PY 2002 VL 13 IS 5 BP 579 EP 604 DI 10.1089/10430340252837198 PG 26 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 533LH UT WOS:000174531000001 PM 11916483 ER PT J AU Krawczyk, C Oliveira-Dos-Santos, A Sasaki, T Griffiths, E Ohashi, PS Snapper, S Alt, F Penninger, JM AF Krawczyk, C Oliveira-Dos-Santos, A Sasaki, T Griffiths, E Ohashi, PS Snapper, S Alt, F Penninger, JM TI Vav1 controls integrin clustering and MHC/peptide-specific cell adhesion to antigen-presenting cells SO IMMUNITY LA English DT Article ID EXCHANGE FACTOR VAV; T-CELL; SIGNAL-TRANSDUCTION; TYROSINE PHOSPHORYLATION; IMMUNOLOGICAL SYNAPSE; RECEPTOR; ACTIVATION; PROTEIN; REGULATOR; LFA-1 AB Integrin-mediated adhesion is essential for the formation of stable contacts between T cells and antigen-presenting cells (APCs). We show that Vav1 controls integrin-mediated adhesion of thymocytes and T cells to ECM proteins and ICAM1 following TCR stimulation. In a peptide-specific system, Vav1 is required for T cell adhesion to peptide-loaded APCs. Intriguingly, TCR-induced cell adhesion and aggregation of integrins occurs independent of WASP. Whereas LFA-1 and actin caps colocalize in wasp(-/-) T cells in response to TCR stimulation, loss of WASP uncouples TCR caps from actin patches. Our data reveal a novel role for Vav1 and WASP in the regulation of TCR-induced integrin clustering and cell adhesion and show that integrin and TCR clustering are controlled by distinct pathways. C1 Univ Toronto, Amgen Inst, Toronto, ON M5G 2C1, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2C1, Canada. Univ Toronto, Dept Immunol, Toronto, ON M5G 2C1, Canada. Austrian Acad Sci, IMBA, Inst Mol Biotechnol, A-1030 Vienna, Austria. Tokyo Metropolitan Inst Med Sci, Dept Pharmacol, Bunkyo Ku, Tokyo 1138613, Japan. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Penninger, JM (reprint author), Univ Toronto, Amgen Inst, 620 Univ Ave, Toronto, ON M5G 2C1, Canada. RI Penninger, Josef/I-6860-2013 OI Penninger, Josef/0000-0002-8194-3777 NR 49 TC 148 Z9 151 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR PY 2002 VL 16 IS 3 BP 331 EP 343 DI 10.1016/S1074-7613(02)00291-1 PG 13 WC Immunology SC Immunology GA 534EZ UT WOS:000174572800003 PM 11911819 ER PT J AU Kohler, H Rodrigues, SP McCormick, BA AF Kohler, H Rodrigues, SP McCormick, BA TI Shigella flexneri interactions with the basolateral membrane domain of polarized model intestinal epithelium: Role of lipopolysaccharide in cell invasion and in activation of the mitogen-activated protein kinase ERK SO INFECTION AND IMMUNITY LA English DT Article ID POLYMORPHONUCLEAR LEUKOCYTE TRANSMIGRATION; TOLL-LIKE RECEPTORS; NF-KAPPA-B; SALMONELLA-TYPHIMURIUM; CYTOSKELETAL REARRANGEMENTS; NEUTROPHIL MIGRATION; MAMMALIAN-CELLS; BINDING-PROTEIN; FUNCTIONAL-ROLE; PATHWAY AB An early step governing Shigella flexneri pathogenesis is the invasion of the colonic epithelium from the basolateral surface followed by disruption of the colonic epithelial barrier. Despite recent insight into S. flexneri-host interactions, much remains to be determined regarding the nature of the initial contact between S. flexneri and the host epithelial basolateral membrane domain. Since the lipopolysaccharide (LPS) is located at the outermost part of the bacterial membrane, we considered that this component might be used by S. flexneri to attach to the basolateral surface of the intestinal epithelium and promote a proinflammatory response. Therefore, polarized human T84 intestinal epithelial cells were infected from the basolateral surface with either wild-type S. flexneri or one of its isogenic LPS-defective strains with mutations in either rfc, rfaL, or galU. We found that both adherence to and internalization into the basolateral surface of a polarized intestinal epithelium with S. flexneri were highly dependent on the length of the LPS (i.e., rfc > rfaL > galU). Furthermore, the addition of the anti-inflammatory LPS (RsDPLA) considerably decreased the invasion profile of wild-type S. flexneri by nearly 50%. Since LPS is associated with host inflammation, we further examined whether this molecule was involved in Shigella-induced inflammatory events. We found that S. flexneri LPS plays an important role in mediating epithelial-derived signaling, which leads to directed migration of polymorphonuclear leukocytes across model intestinal epithelium. This signaling most likely involves the activation of the mitogen-activated protein kinase extracellular regulated kinase. Thus, our findings have important implications on the understanding of the mechanisms by which S. flexneri can elicit mucosal inflammation. C1 Massachusetts Gen Hosp, Dept Pediat Gastroenterol & Nutr, Mucosal Immunol Lab, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Cambridge, MA 02139 USA. RP McCormick, BA (reprint author), Massachusetts Gen Hosp, Dept Pediat Gastroenterol & Nutr, Mucosal Immunol Lab, 114 16th St,114-3503, Cambridge, MA 02139 USA. FU NIDDK NIH HHS [DK33506, DK56745, P01 DK033506, R01 DK056754] NR 57 TC 44 Z9 46 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 2002 VL 70 IS 3 BP 1150 EP 1158 DI 10.1128/IAI.70.3.1150-1158.2002 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 522EQ UT WOS:000173883100016 PM 11854195 ER PT J AU Ghigo, E Capo, C Aurouze, M Tung, CH Gorvel, JP Raoult, D Mege, JL AF Ghigo, E Capo, C Aurouze, M Tung, CH Gorvel, JP Raoult, D Mege, JL TI Survival of Tropheryma whipplei, the agent of Whipple's disease, requires phagosome acidification SO INFECTION AND IMMUNITY LA English DT Article ID COXIELLA-BURNETII; SALMONELLA-TYPHIMURIUM; CONTAINING VACUOLES; MACROPHAGES; MATURATION; BIOGENESIS; BACILLUS; CELLS AB Tropheryma whipplei was established as the agent of Whipple's disease in 2000, but the mechanisms by which it survives within host cells are still unknown. We show here that T. whipplei survives within HeLa cells by controlling the biogenesis of its phagosome. Indeed, T. whipplei colocalized with lysosome-associated membrane protein 1, a membrane marker of late endosomal and lysosomal compartments, but not with cathepsin D, a lysosomal hydrolase. This defect in phagosome maturation is specific to live organisms, since heat-killed bacilli colocalized with cathepsin D. In addition, T. whipplei survived within HeLa cells by adapting to acidic pH. The vacuoles containing T. whipplei were acidic (pH 4.7 +/- 0.3) and acquired vacuolar ATPase, responsible for the acidic pH of late phagosomes. The treatment of HeLa cells with pH-neutralizing reagents, such as ammonium chloride, N-ethylmaleimide, bafilomycin A1, and chloroquine, increased the intravacuolar pH and promoted the killing of T. whipplei. The ability of T. whipplei to survive in an acidic environment and to interfere with phagosome-lysosome fusion is likely critical for its prolonged persistence in host cells during the course of Whipple's disease. Our results suggest that manipulating the intravacuolar pH may provide a new approach for the treatment of Whipple's disease. C1 Univ Mediterranee, Fac Med, CNRS, UMR 6020,Unite Rickettsies, F-13385 Marseille 5, France. Ctr Immunol Marseille Luminy, F-13288 Marseille, France. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. RP Mege, JL (reprint author), Univ Mediterranee, Fac Med, CNRS, UMR 6020,Unite Rickettsies, 27 Bd Jean Moulin, F-13385 Marseille 5, France. RI Eric, Ghigo/N-9427-2016; MEGE, JEAN-LOUIS/O-6063-2016; OI Gorvel, Jean-Pierre/0000-0002-2829-9804; Tung, Ching-Hsuan/0000-0001-6648-6195 NR 34 TC 55 Z9 58 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 2002 VL 70 IS 3 BP 1501 EP 1506 DI 10.1128/IAI.70.3.1501-1506.2002 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 522EQ UT WOS:000173883100059 PM 11854238 ER PT J AU Gupta, SN Flaherty, JP Shaw, JC AF Gupta, SN Flaherty, JP Shaw, JC TI Erythema nodosum associated with reactivation tuberculous lymphadenitis (scrofula) SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Article ID EXTRAPULMONARY AB A 73-year-old African American female presented to our clinic with painful lower extremity lesions of 2 weeks duration. She was in her usual state of health until 3 months prior to presentation when she reported symptoms of fatigue and weakness, She also noticed an enlarging mass on the left side of her neck. She denied fevers, chills, night sweats or cough. Her symptoms were unresponsive to a course of oral dicloxacillin. The neck mass enlarged over 8 weeks and she was referred to our institution for evaluation. CT scan of the neck showed an enlarged lymph node. Ten days prior to her presentation in dermatology, a fine needle aspirate of the enlarging lymph node revealed necrotizing granulomas. Tissue was sent for routine mycobacterial and fungal cultures. Routine blood work, chest radiograph, and a tuberculin skin test were also performed. At the time of her dermatology visit she described the development of multiple new painful, non-pruritic lesions, bilaterally on the lower extremities. She also reported a red crusted area that appeared at the site of her tuberculin test that was placed subsequent to the development of her lower extremity lesions. Her past medical history was significant for Parkinson's disease, hypothyroidism and hypertension. Her current medications included L-thyroxine, estrogen and diltiazem. Her travel history was only remarkable for a trip to Jamaica the previous spring. She was born and raised in Haiti. She reported a history of a positive tuberculin skin test 20 years ago, but received no therapy. Physical examination revealed a 2 x 3 centimeter firm, nontender left lateral neck mass (Fig. 1). Her right forearm revealed an erythematous, ulcerated, indurated plaque 1.5 cm in diameter (Fig. 2.). Her lower extremities revealed tender 0.5 to 1 cm erythematous nodules below the knees bilaterally (Fig. 3). A punch biopsy of a lower extremity nodule revealed a mild pervisacular dermal infiltrate. Within the subcutaneous tissue there was septal widening. There was also a lymphohistiocytic infiltrate with a slight admixture of neutrophils within the septa of the fat lobules. There was no evidence of necrotizing vasculitis or collagen necrosis. An acid-fast stain was not performed. The histologic findings were consistent with a diagnosis of erythema nodosum. Her laboratory evaluation including CBC, electrolytes, thyroid studies, angiotensin converting enzyme level and chest radiograph were normal. Approximately 1 week after her dermatological evaluation, the fine-needle aspirate culture grew Mycobacterium tuberculosis. A diagnosis of tuberculous lymphadenitis associated with erythema nodosum was confirmed. The patient was started on quadruple therapy of isoniazid, rifampin, ethambutol and pyrazinamide. Her lower limb skins lesions rapidly resolved over the subsequent month and her neck mass also diminished in size. She completed 6 months of antituberculous therapy with complete resolution of her lymphadenopathy. C1 Harvard Univ, Dept Dermatol, Boston, MA USA. Univ Chicago, Infect Dis Sect, Chicago, IL 60637 USA. Univ Chicago, Dermatol Sect, Chicago, IL 60637 USA. RP Gupta, SN (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Wellman Labs, 55 Fruit St,BAR 413, Boston, MA 02114 USA. NR 22 TC 5 Z9 6 U1 0 U2 0 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 2002 VL 41 IS 3 BP 173 EP 175 DI 10.1046/j.1365-4362.2002.01390.x PG 3 WC Dermatology SC Dermatology GA 553GY UT WOS:000175668300011 PM 12010345 ER PT J AU Eddy, KT Keel, PK Dorer, DJ Delinsky, SS Franko, DL Herzog, DB AF Eddy, KT Keel, PK Dorer, DJ Delinsky, SS Franko, DL Herzog, DB TI Longitudinal comparison of anorexia nervosa subtypes SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE longitudinal comparison; anorexia nervosa subtypes; classification ID LONG-TERM COURSE; EATING DISORDERS; FOLLOW-UP; SURVIVAL ANALYSIS; BULIMIA-NERVOSA; PREDICTORS; VALIDITY; RECOVERY; CRITERIA; WOMEN AB Objective: To compare patients with restricting anorexia nervosa (ANR) and binge/ purge anorexia nervosa (ANBP) on measures of impulsivity; course, and outcome. Methods: One hundred thirty-six treatment-seeking women with AN followed prospectively for 8-12 years were reclassified at intake as 51 ANRs and 85 ANBPs according to the DSM-IV subtyping classification. Lifetime Axis I and Axis 11 disorders were assessed using structured interviews; follow-up interviews were conducted at 6-12-month intervals to collect weekly data on eating disorder symptomatology. Results: Women with ANR and ANBP did not differ on history of substance abuse, kleptomania, suicidality, or borderline personality diagnosis at intake, or on rates of recovery, relapse, or mortality. By 8 years of follow-up, 62% of women with ANR crossed over to ANBP prospectively and only 12% of women with AN never reported regular binge/purge behaviors. Conclusions: The findings on impulsivity; course, and outcome do not support the current subtyping system. The high crossover rate in our sample from ANR to ANBP suggests that ANR represents a phase in the course of AN rather than a distinct subtype. (C) 2002 by Wiley Periodicals, Inc. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Rutgers State Univ, Dept Psychol, New Brunswick, NJ 08903 USA. Harvard Univ, Eating Disorders Ctr, Boston, MA 02115 USA. Univ Massachusetts, Dept Psychol, Dartmouth, MA USA. RP Herzog, DB (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 725 WACC,15 Parkman St, Boston, MA 02114 USA. FU NIMH NIH HHS [5R01 MH 38333 05] NR 33 TC 122 Z9 127 U1 5 U2 15 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 2002 VL 31 IS 2 BP 191 EP 201 DI 10.1002/eat.10016 PG 11 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 524XF UT WOS:000174037600008 PM 11920980 ER PT J AU Suerbaum, S Kraft, C Dewhirst, FE Fox, JG AF Suerbaum, S Kraft, C Dewhirst, FE Fox, JG TI Helicobacter nemestrinae ATCC 49396(T) is a strain of Helicobacter pylori (Marshall et al. 1985) Goodwin et al. 1989, and Helicobacter nemestrinae Brondson et al. 1991 is therefore a junior heterotypic synonym of Helicobacter pylori SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article DE Helicobacter pylori; Helicobacter nemestrinae; taxonomy; multilocus sequence analysis; 16S rDNA sequencing ID SP-NOV; RECOMBINATION AB Helicobacter nemestrinae Bronsdon et al. 1991, a gastric helicobacter species isolated from a pigtailed macaque, is thought to be the species most closely related to the important human pathogen Helicobacter pylori. The only available strain of this taxon is the type strain, ATCC 49396(T). We sequenced seven housekeeping genes and two flagellin genes for H. nemestrinae ATCC 49396 T. If ATCC 49396T were a separate species, these sequences should have been distinct from those of H. pylori. instead, all sequences clustered together with sequences obtained previously for 20 or more H. pylori isolates from diverse geographical locations. The 16S rDNA sequence differed from that reported previously for this strain by 38 nucleotides and was most similar to that of H. pylori 8511308 (accession no. U00769), which was isolated from a rhesus macaque. it differed by less than I% from 16S rDNA sequences of numerous other H. pylori strains, including the type strain, NCTC 11637(T) (= ATCC 43504(T)). These data indicate that the strain currently distributed as H. nemestrinae ATCC 49396T is really a strain of H. pylori and that H. nemestrinae Bronsdon et al. 1991 is a junior heterotypic synonym of Helicobacter pylori (Marshall et al. 1985) Goodwin et al. 1989. C1 Univ Wurzburg, Inst Hyg & Mikrobiol, D-97080 Wurzburg, Germany. Forsyth Inst, Dept Mol Genet, Boston, MA USA. MIT, Div Comparat Med, Cambridge, MA 02139 USA. RP Suerbaum, S (reprint author), Univ Wurzburg, Inst Hyg & Mikrobiol, Josef Schneider Str 2, D-97080 Wurzburg, Germany. NR 9 TC 20 Z9 20 U1 0 U2 0 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 2002 VL 52 BP 437 EP 439 DI 10.1099/ijs.0.01991-0 PN 2 PG 3 WC Microbiology SC Microbiology GA 533ER UT WOS:000174516900014 PM 11931154 ER PT J AU Jeong, BH Jin, JK Choi, EK Kim, KH Choi, KW Oh, MD Shin, KC Kim, YS AF Jeong, BH Jin, JK Choi, EK Kim, KH Choi, KW Oh, MD Shin, KC Kim, YS TI Detection of JC virus type 1 in peripheral lymphocytes, brain and cerebrospinal fluid from two Korean AIDS patients with progressive multifocal leukoencephalopathy SO INTERVIROLOGY LA English DT Article DE progressive multifocal leukoencephalopathy; AIDS; JC virus; genotyping; phylogenetic tree; type 1 JC virus ID HUMAN POLYOMAVIRUS JC; COMPLETE GENOMES; DNA-SEQUENCE; EVOLUTION; INDIVIDUALS; PAPOVAVIRUS; AMERICANS; GENOTYPES; DISEASE; REGIONS AB The human polyomavirus JC virus (JCV) is the etiologic agent of the fatal demyelinating central nervous system disease progressive multifocal leukoencephalopathy (PML), which occurs in 4-7% of AIDS patients. Two Korean AIDS patients with PML were assayed for JCV, and the virus was genotyped by polymerase chain reaction, DNA sequencing and phylogenetic analysis. Using immunohistochemical analysis, we also examined the distribution of JCV antigen in the brains of the patients. The JCV genome was detected in peripheral lymphocytes, brain and cerebrospinal fluid from these Korean PML patients. Although type 2 is the most common genotype in Asia, the genotype of the JCV in these two AIDS patients was characterized as type 1, which is of European origin. We found that JCV antigen was selectively detected in oligodendrocytes and astrocytes of the brains from these patients. Compared to the prototype type 1 (Mad-1), two different nucleotides (G-4C) in the KOR-1 strain identified here were found at positions 2488 and 2490 of the major capsid protein VP1 gene. In summary, this is the first report of PML in Korean AIDS patients; it is also the first isolation of JCV type 1 in PML in East Asians. Copyright (C) 2002 S. Karger AG, Basel. C1 Hallym Univ, Coll Med, Inst Environm & Life Sci, Chunchon, South Korea. Hallym Univ, Coll Med, Dept Microbiol, Chunchon, South Korea. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Res Unit,Dept Neurol, Charlestown, MA USA. Kangwon Natl Univ, Div Biol Sci, Chunchon, South Korea. Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea. RP Kim, YS (reprint author), Hallym Acad Sci, Inst Environm & Life Sci, 1 Ockchon Dong, Chunchon 200702, South Korea. NR 30 TC 4 Z9 4 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0300-5526 J9 INTERVIROLOGY JI Intervirology PD MAR-APR PY 2002 VL 45 IS 2 BP 94 EP 100 DI 10.1159/000063229 PG 7 WC Virology SC Virology GA 583EF UT WOS:000177393100005 PM 12145541 ER PT J AU Batchu, RB Shammas, MA Wang, JY Reis, RJS Munshi, NC AF Batchu, RB Shammas, MA Wang, JY Reis, RJS Munshi, NC TI Interaction of Adeno-associated virus Rep78 with SV40 T antigen: Implications in Rep protein expression leading to the inhibition of SV40-mediated cell proliferation SO INTERVIROLOGY LA English DT Article DE Adeno-associated virus type 2; SV40; Rep78; T antigen ID HERPES-SIMPLEX VIRUS; ADENOASSOCIATED VIRUS; DNA AMPLIFICATION; HAMSTER-CELLS; REPLICATION; GENE; TRANSFORMATION; ANTIBODIES; PARVOVIRUS AB Adeno-associated virus (AAV) type 2 is a nonpathogenic human parvovirus that is dependent on a helper virus, usually adenovirus, for its replication. The left half of AAV encodes the multifunctional nonstructural proteins required for replication of its DNA. Here, we present evidence that SV40 provides a helper function for the expression of AAV Rep protein, as demonstrated by Western blot analysis of cell extracts from SV40-transformed human fibroblasts infected with AAV. We also show, using a luciferase reporter system, that SV40-mediated transcriptional transactivation of 'S'-phase genes is substantially inhibited by the presence of AAV. Because the SV40 T antigen is critical to oncogenicity and cellular DNA proliferation, we investigated its interaction with AAV Rep protein. The physical interaction between these two molecules was confirmed by electrophoretic mobility supershift assay and affinity chromatography. These results show, for the first time, the possible molecular mechanisms behind the AAV-mediated inhibition of SV40 oncogenicity and provide the basis for further investigation into the direct and indirect role of AAV Rep in controlling viral transforming activity. Copyright (C) 2002 S. Karger AG, Basel. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Arkansas Med Sci, Myeloma & Transplantat Res Ctr, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Cent Arkansas Vet Hlth Care Syst, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Geriatr, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. Boston VA Hlth Care Syst, Boston, MA USA. RP Munshi, NC (reprint author), Dana Farber Canc Inst, 44 Binney St,M557, Boston, MA 02115 USA. RI Shmookler Reis, Robert/C-4112-2009 FU NCI NIH HHS [CA71092] NR 26 TC 3 Z9 4 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0300-5526 J9 INTERVIROLOGY JI Intervirology PD MAR-APR PY 2002 VL 45 IS 2 BP 115 EP 118 DI 10.1159/000063235 PG 4 WC Virology SC Virology GA 583EF UT WOS:000177393100009 PM 12145545 ER PT J AU Lewis, RF Crawford, TO AF Lewis, RF Crawford, TO TI Slow target-directed eye movements in ataxia-telangiectasia SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID VESTIBULOOCULAR REFLEX; OCULAR DRIFT; HEAD; LESIONS; BEHAVIOR; SACCADES; NEURONS; BRAIN; CAT AB PURPOSE. To analyze the slow eye movements that shift the direction of gaze in patients with ataxia-telangiectasia (A-T). METHODS. Eye and head movements were recorded with search coils in three patients with A-T during attempted gaze shifts, both with the head immobilized and free to move. RESULTS. Gaze shifts frequently included both saccadic and slow components. The slow movements were recorded after 42% of saccades and had an average peak velocity of 6.1 deg/sec and a mean amplitude of 2.0degrees. They occurred with the head stationary and moving, could be directed centripetally or centrifugally, had velocity waveforms that were relatively linear or exponential, and always moved the eyes toward the visual target. CONCLUSIONS. The slow movements appear to differ from pursuit and vestibular eye movements and are not fully explained by the various types of abnormal eye movements that can follow saccades, such as gaze-evoked nystagmus or postsaccadic drift. Their origin is uncertain, but they could represent very slow saccades, due to aberrant inhibition of burst cell activity during the saccade. C1 Harvard Univ, Sch Med, Dept Otorhinolaryngol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Johns Hopkins Med Sch, Dept Neurol, Baltimore, MD USA. Johns Hopkins Med Sch, Dept Pediat, Baltimore, MD USA. RP Lewis, RF (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. RI Crawford, Thomas/E-6307-2012 NR 20 TC 6 Z9 6 U1 0 U2 1 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 2002 VL 43 IS 3 BP 686 EP 691 PG 6 WC Ophthalmology SC Ophthalmology GA 526TL UT WOS:000174145700016 PM 11867585 ER PT J AU Duh, EJ Yang, HS Suzuma, I Miyagi, M Youngman, E Mori, K Katai, M Yan, L Suzuma, K West, K Davarya, S Tong, P Gehlbach, P Pearlman, J Crabb, JW Aiello, LP Campochiaro, PA Zack, DJ AF Duh, EJ Yang, HS Suzuma, I Miyagi, M Youngman, E Mori, K Katai, M Yan, L Suzuma, K West, K Davarya, S Tong, P Gehlbach, P Pearlman, J Crabb, JW Aiello, LP Campochiaro, PA Zack, DJ TI Pigment epithelium-derived factor suppresses ischemia-induced retinal neovascularization and VEGF-induced migration and growth SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID PROLIFERATIVE DIABETIC-RETINOPATHY; VASCULAR-PERMEABILITY FACTOR; CEREBELLAR GRANULE CELLS; ENDOTHELIAL-CELLS; FACTOR PEDF; CHOROIDAL NEOVASCULARIZATION; NEUROTROPHIC ACTIVITY; MOTOR-NEURONS; ANGIOGENESIS; INHIBITOR AB PURPOSE. To determine the effect of pigment epithelium-derived factor (PEDF) in a mouse model of ischemia-induced retinal neovascularization and on vascular endothelial growth factor (VEGF)-induced migration and growth of cultured microvascular endothelial cells. METHODS. Human recombinant PEDF was expressed in the human embryonic kidney 293 cell line and purified by ammonium sulfate precipitation and cation exchange chromatography. C57BL/6 mice were exposed to 75% oxygen from postnatal day (P)7 to P12 and then returned to room air. Mice received intravitreal injections of 2 mug PEDF in one eye and vehicle in the contralateral eye on P12 and P14. At P17, mice were killed and eyes enucleated for quantitation of retinal neovascularization. The mitogenic and motogeneic effects of VEGF on cultured bovine retinal and adrenal capillary endothelial cells were examined in the presence or absence of PEDF, using cell counts and migration assays. RESULTS. Two species of human recombinant PEDF, denoted A and B, were purified to apparent homogeneity. PEDF B appeared to comigrate on SDS-PAGE with PEDF from human vitreous samples. Changes in electrophoretic mobility after peptide-N-glycosidase F (PNGase F) digestion suggest that both PEDF forms contain N-linked carbohydrate. Analyses of the intact proteins by liquid chromatography-electrospray mass spectrometry (LC-ESMS) revealed the major molecular weight species for PEDF A (47,705 +/- 4) and B (46,757 +/- 5). LC-ESMS analysis of tryptic peptides indicated that PEDF A and B exhibit differences in glycopeptides containing N-acetylneuraminic acid (NeuAc) and N-acetylhexosamine (HexNAc). Intravitreal administration of either species of PEDF significantly inhibited retinal neovascularization (83% for PEDF A and 55% for PEDF B; P = 0.024 and 0.0026, respectively). PEDF A and B (20 nM) suppressed VEGF-induced retinal microvascular endothelial cell proliferation by 48.8% and 41.4%, respectively, after 5 days (P < 0.001) and VEGF-induced migration by 86.5% +/- 16.7% and 78.1% +/- 22.3%, respectively, after 4 hours (P = 0.004 and P = 0.008, respectively). CONCLUSIONS. These data indicate that elevated concentrations of PEDF inhibit VEGF-induced retinal endothelial cell growth and migration and retinal neovascularization. These findings suggest that localized administration of PEDF may be an effective approach for the treatment of ischemia-induced retinal neovascular disorders. C1 Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21287 USA. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA. RP Zack, DJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Maumenee 809,600 N Wolfe St, Baltimore, MD 21287 USA. RI Youngman, Elaine/E-7072-2013; OI Zack, Don/0000-0002-7966-1973 FU NEI NIH HHS [EY 01765, EY 00398, EY 06603] NR 57 TC 231 Z9 255 U1 1 U2 8 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 2002 VL 43 IS 3 BP 821 EP 829 PG 9 WC Ophthalmology SC Ophthalmology GA 526TL UT WOS:000174145700035 PM 11867604 ER PT J AU Foley, EM AF Foley, EM TI Drug screening and criminal prosecution of pregnant women SO JOGNN-JOURNAL OF OBSTETRIC GYNECOLOGIC AND NEONATAL NURSING LA English DT Editorial Material DE drug testing; drug treatment; ethics; pregnancy; prenatal testing ID COCAINE; EXPOSURE; ABUSE AB According to the U.S. Supreme Court, the Fourth Amendment rights of 10 women were violated by a hospital that provided them prenatal care. The incidence of prenatal drug testing for criminal prosecution with or without a woman's knowledge is increasing. Concurrently, funding and availability of drug treatment programs for pregnant women are declining. Nurses and physicians who act as advocates for the state rather than the patient damage the patient-provider relationship and breach their ethical responsibility to the patient. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Foley, EM (reprint author), 17 Locust St, Woburn, MA 01801 USA. NR 26 TC 6 Z9 6 U1 4 U2 4 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 2002 VL 31 IS 2 BP 133 EP 137 DI 10.1111/j.1552-6909.2002.tb00032.x PG 5 WC Nursing; Obstetrics & Gynecology SC Nursing; Obstetrics & Gynecology GA 606FN UT WOS:000178723800003 PM 11926395 ER PT J AU Kircher, MF Haeusler, M Nickel, R Lamb, JR Renz, H Beyer, K AF Kircher, MF Haeusler, M Nickel, R Lamb, JR Renz, H Beyer, K TI V beta 18.1(+) and V alpha 2.3(+) T-cell subsets are associated with house dust mite allergy in human subjects SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE T-cell receptors; allergy; T lymphocytes; flow cytometry ID RECEPTOR-BETA-CHAIN; PERIPHERAL-BLOOD LYMPHOCYTES; RHEUMATOID-ARTHRITIS; RAGWEED ALLERGEN; RESPONSES; DERMATOPHAGOIDES; SUPERANTIGEN; REPERTOIRE; MICE; ENCEPHALOMYELITIS AB Background: The recognition of allergenic peptides by T cells through their T-cell receptor (TCR) represents a crucial step in the initiation of an allergen-specific immune response. In parallel to the superantigen-driven restricted expansion of Vbeta subsets in autoimmune and infectious diseases, reports in animals and human subjects have shown a similar capacity of classical antigens. Objective: The study was performed to analyze the Valpha/Vbeta expression in house dust mite (HDM) allergy. Methods: The TCR repertoire of 15 subjects with HDM allergy, 22 atopic subjects without HDM allergy, and 19 nonatopic individuals, members of 2 extended and 4 nuclear families, was determined. By using flow cytometry, the expression of 22 Vbeta and 3 Valpha elements was analyzed in vivo and after in vitro allergen stimulation. Results: In comparison with nonatopic and atopic individuals without HDM allergy, freshly isolated PBMCs of individuals with HDM allergy showed a significantly higher frequency of Vbeta18(+) and Valpha2.3(+) T cells. Although members of all 3 groups had a similar lymphocyte proliferation response after in vitro stimulation with Der p 1 or Der p 1 peptide(101-131), a significant expansion of Vbeta18(+) and Va2.3+ T cells in vitro occurred only in individuals with HDM allergy. Moreover, the degree of expansion correlated with the levels of allergen-specific IgE antibodies. No expansion of Vbeta18(+) and Valpha2.3(+) was observed after mitogen stimulation with PHA, indicating allergen specificity of the response. Conclusion: Our results strongly suggest restricted TCR Valpha/Vbeta gene use in HDM allergy and might be a step toward TCR-based immunotherapy. C1 Mt Sinai Sch Med, Div Pediat Allergy & Immunol, New York, NY 10029 USA. Humboldt Univ, Charite, Inst Clin Chem & Biochem, Berlin, Germany. Humboldt Univ, Charite, Dept Pediat Pneumol & Immunol, Berlin, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA 02114 USA. Univ Edinburgh, MRC, Ctr Inflammat Res, Edinburgh EH8 9YL, Midlothian, Scotland. Univ Marburg, Inst Clin Chem & Mol Diagnost, Marburg, Germany. RP Beyer, K (reprint author), Mt Sinai Sch Med, Div Pediat Allergy & Immunol, Box 1198,1 Gustave L Levy Pl, New York, NY 10029 USA. NR 43 TC 14 Z9 16 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAR PY 2002 VL 109 IS 3 BP 517 EP 523 DI 10.1067/mai.2002.121945 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 534KW UT WOS:000174586400021 PM 11898001 ER PT J AU Wechsler, H Lee, JE Kuo, M Sebring, M Nelson, TF Lee, H AF Wechsler, H Lee, JE Kuo, M Sebring, M Nelson, TF Lee, H TI Trends in college binge drinking during a period of increased prevention efforts - Findings from 4 Harvard School of Public Health College Alcohol Study surveys: 1993-2001 SO JOURNAL OF AMERICAN COLLEGE HEALTH LA English DT Article DE alcohol; alcohol-related problems; binge drinking; college students; secondhand effects of alcohol; prevention ID STUDENTS; VALIDITY; IMPACT AB The 2001 Harvard School of Public Health College Alcohol Study surveyed students at 119 4-year colleges that participated in the 1993, 1997, and 1999 studies. Responses in the 4 survey years were compared to determine trends in heavy alcohol use, alcohol-related problems, and encounters with college and community prevention efforts. In 2001, approximately 2 in 5 (44.4%) college students reported binge drinking, a rate almost identical to fates in the previous 3 surveys. Very little change in overall binge drinking occurred at the individual college level. The percentages of abstainers and frequent binge drinkers increased, a polarization of drinking behavior first noted in 1997. A sharp rise in frequent binge drinking was noted among students attending all-women's colleges. Other significant changes included increases in immoderate drinking and harm among drinkers. More students lived in substance-free housing and encountered college educational efforts and sanctions resulting from their alcohol use. C1 Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wechsler, H (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02138 USA. NR 40 TC 833 Z9 838 U1 10 U2 88 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 2002 VL 50 IS 5 BP 203 EP 217 PG 15 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 543HX UT WOS:000175096800002 PM 11990979 ER PT J AU Martinez, M Lopez-Ribot, JL Kirkpatrick, WR Bachmann, SP Perea, S Ruesga, MT Patterson, TF AF Martinez, M Lopez-Ribot, JL Kirkpatrick, WR Bachmann, SP Perea, S Ruesga, MT Patterson, TF TI Heterogeneous mechanisms of azole resistance in Candida albicans clinical isolates from an HIV-infected patient on continuous fluconazole therapy for oropharyngeal candidosis SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; AMINO-ACID SUBSTITUTIONS; ANTIFUNGAL AGENTS; DRUG-RESISTANCE; IN-VITRO; LANOSTEROL 14-ALPHA-DEMETHYLASE; REDUCED AFFINITY; CHROMOGENIC AGAR; SUSCEPTIBILITY; CONTRIBUTE AB Molecular mechanisms of azole resistance in Candida albicans include alterations in the target enzyme and increased efflux of drug, but the impact of specific treatment regimens on resistance has not been established. A patient with advanced AIDS was enrolled in a longitudinal study to receive continuous oral fluconazole (FLU) 200 mg/day for the treatment of oropharyngeal candidosis (OPC). Oral cultures were obtained at time of enrolment, during episodes of OPC and quarterly for surveillance. The patient had five symptomatic relapses on continuous FLU during 43 months. All OPC episodes were successfully treated with increasing doses of FLU although increased FLU MICs were detected for C. albicans isolates with progression of time. DNA-typing techniques demonstrated that resistance developed in a persistent strain of C. albicans. Both FLU-resistant and isogenic isolates with reduced susceptibility were detected in the same clinical samples through multiple episodes. Analysis of molecular mechanisms of resistance revealed overexpression of MDR and CDR genes encoding efflux pumps (but not ERG11) in isolates with decreased FLU susceptibility. In addition, the presence of the G464S amino acid substitution in their lanosterol demethylase, affecting its affinity for FLU, was also detected. However, other isogenic, but FLU-susceptible isolates recovered from the same samples did not harbour the mutation, indicating micro-evolution of yeast populations within the oral cavity. In this patient, the continuous antifungal pressure exerted by FLU resulted in development of resistance of multifactorial nature. Despite their clonal origin, different subpopulations of C. albicans demonstrated distinct resistance mechanisms, including concomitant presence and absence of functional point mutations in ERG11 genes. C1 Univ Texas, Hlth Sci Ctr, S Texas Ctr Biol Med, Dept Med,Div Infect Dis, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX USA. Univ Basque Country, Fac Med & Odontol, Dept Microbiol Immunol & Parasitol, Lejona, Vizcaya, Spain. RP Lopez-Ribot, JL (reprint author), Univ Texas, Hlth Sci Ctr, S Texas Ctr Biol Med, Dept Med,Div Infect Dis, San Antonio, TX 78284 USA. EM ribot@uthsesa.edu RI Lopez-Ribot, Jose/D-2048-2010 FU NCRR NIH HHS [M01 RR 01346]; NIAID NIH HHS [R20 AI 42401]; NIDCR NIH HHS [5R01 DE 11381-04A2] NR 42 TC 29 Z9 39 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD MAR PY 2002 VL 49 IS 3 BP 515 EP 524 DI 10.1093/jac/49.3.515 PG 10 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 530QF UT WOS:000174369900011 PM 11864952 ER PT J AU Levine, S Gregory, C Nguyen, T Shrager, J Kaiser, L Rubinstein, N Dudley, G AF Levine, S Gregory, C Nguyen, T Shrager, J Kaiser, L Rubinstein, N Dudley, G TI Bioenergetic adaptation of individual human diaphragmatic myofibers to severe COPD SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE chronic obstructive pulmonary disease; human diaphragm; succinate dehydrogenase; calcium-activated myosin ATPase; mitochondrial oxidative capacity; diaphragmatic fatigue; muscle fatigue ID OBSTRUCTIVE PULMONARY-DISEASE; ELASTASE-INDUCED EMPHYSEMA; SKELETAL-MUSCLE FIBERS; MYOSIN HEAVY-CHAINS; SPINAL-CORD INJURY; ATPASE ACTIVITY; NORMAL MEN; SUCCINATE-DEHYDROGENASE; MULTIPLE-SCLEROSIS; CRURAL DIAPHRAGM AB To assess the effect of severe chronic obstructive pulmonary disease (COPD) on the ability of human diaphragmatic myofibers to aerobically generate ATP relative to ATP utilization, we obtained biopsy specimens of the costal diaphragm from seven patients with severe COPD (mean +/- SE; age 56 +/- 1 yr; forced expiratory volume in 1 s 23 +/- 2% predicted; residual volume 267 +/- 30% predicted) and seven age-matched control subjects. We categorized all fibers in these biopsies by using standard techniques, and we carried out the following quantitative histochemical measurements by microdensitometry: 1) succinate dehydrogenase (SDH) activity as an indicator of mitochondrial oxidative capacity and 2) calcium-activated myosin ATPase (mATPase) activity, the ATPase that represents a major portion of ATP consumption by contracting muscle. We noted the following: 1) COPD diaphragms had a larger proportion of type I fibers, a lesser proportion of type IIax fibers, and the same proportion of type IIa fibers as controls. 2) SDH activities of each of the fiber types were higher in COPD than control diaphragms (P < 0.0001); the mean increases expressed as percent of control values) in types I, IIa, and IIax were 84, 114, and 130%, respectively. 3) COPD elicited no change in mATPase activity of type I and IIa fibers, but mATPase decreased in type IIax fibers (P = 0.02).4) Mitochondrial oxidative capacity relative to ATP demand (i.e., SDH/ mATPase) was higher (P = 0.03) in each of the fiber types in COPD diaphragms than in controls. These results demonstrate that severe COPD elicits an increase in aerobic ATP generating capacity relative to ATP utilization in all diaphragmatic fiber types as well as the previously described fast-to-slow fiber type transformation (Levine S, Kaiser L, Leferovich J, and Tikunov B, N Engl J Med 337: 1799-1806, 1997). C1 Vet Affairs Med Ctr, Med Serv, Philadelphia, PA 19004 USA. Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA 19004 USA. Vet Affairs Med Ctr, Res Serv, Philadelphia, PA 19004 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. Univ Georgia, Dept Exercise Sci, Athens, GA 30602 USA. RP Levine, S (reprint author), Vet Affairs Med Ctr, Med Serv, Univ & Woodland Ave, Philadelphia, PA 19004 USA. NR 53 TC 82 Z9 87 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAR PY 2002 VL 92 IS 3 BP 1205 EP 1213 DI 10.1152/japplphysiol.00116.2001 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 523NF UT WOS:000173960100042 PM 11842060 ER PT J AU Yu, JL Grinius, L Hooper, DC AF Yu, JL Grinius, L Hooper, DC TI NorA functions as a multidrug efflux protein in both cytoplasmic membrane vesicles and reconstituted proteoliposomes SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; STAPHYLOCOCCUS-AUREUS; FLUOROQUINOLONE RESISTANCE; ANTIBIOTIC-RESISTANCE; QUINOLONE RESISTANCE; TRANSPORTER LMRP; LACTOCOCCUS-LACTIS; TOPOISOMERASE-IV; MAR MUTANTS; DNA GYRASE AB Overexpression of NorA, an endogenous efflux transporter of Staphylococcus aureus, confers resistance to certain fluoroquinolone antimicrobials and diverse other substrates. The norA gene was amplified by PCR and cloned in the expression vector pTrcHis2. Histidine-tagged NorA (NorA-His) was overexpressed in Escherichia coli cells to prepare two experimental systems, everted membrane vesicles enriched with NorA-His and proteoliposomes reconstituted with purified NorA-His. In membrane vesicles, NorA-His actively transported Hoechst 33342, a dye that is strongly fluorescent in the membrane but has low fluorescence in an aqueous environment. Transport was activated by the addition of ATP or lactate and reversed by the addition of nigericin, with the addition of K+-valinomycin having little effect. Transport of Hoechst 33342 was inhibited competitively by verapamil, a known inhibitor of NorA, and by other NorA substrates, including tetraphenyl phosphonium and the fluoroquinolones norfloxacin and ciprofloxacin. In contrast, sparfloxacin, a fluoroquinolone whose antimicrobial activity is not affected by NorA expression, exhibited noncompetitive inhibition. NorA induction and overexpression yielded 0.5 to 1 mg of a largely homogeneous 40- to 43-kDa protein per liter of culture. NorA-His incorporated into proteoliposomes retained the ability to transport Hoechst 33342 in response to an artificial proton gradient, and transport was blocked by nigericin and verapamil. These data provide the first experimental evidence of NorA functioning as a self-sufficient multidrug transporter. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Procter & Gamble Pharmaceut, Hlth Care Res Ctr, Mason, OH 45040 USA. RP Hooper, DC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. FU NIAID NIH HHS [AI 23988, R37 AI023988, R01 AI023988] NR 34 TC 58 Z9 61 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAR PY 2002 VL 184 IS 5 BP 1370 EP 1377 DI 10.1128/JB.184.5.1370-1377.2002 PG 8 WC Microbiology SC Microbiology GA 523BZ UT WOS:000173932600017 PM 11844766 ER PT J AU Pind, S Slominski, E Mauthe, J Pearlman, K Swoboda, KJ Wilkins, JA Sauder, P Natowicz, MR AF Pind, S Slominski, E Mauthe, J Pearlman, K Swoboda, KJ Wilkins, JA Sauder, P Natowicz, MR TI V490M, a common mutation in 3-phosphoglycerate dehydrogenase deficiency, causes enzyme deficiency by decreasing the yield of mature enzyme SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BLOOD-BRAIN-BARRIER; L-SERINE; D-3-PHOSPHOGLYCERATE DEHYDROGENASE; AMINO-ACIDS; D-ASPARTATE; HIPPOCAMPAL-NEURONS; DOMAIN INTERFACE; BIOSYNTHESIS; EXPRESSION; GLYCINE AB A deficiency of 3-phosphoglycerate dehydrogenase (PHGDH) is a disorder of serine biosynthesis identified in children with congenital microcephaly, seizures, and severe psychomotor retardation. We report here the identification of the 1468G-->A (V490M) mutation of this gene in two siblings of an Ashkenazi Jewish family, providing further evidence that the V490M mutation is a common, panethnic cause of this deficiency. Using a novel, DNA-based diagnostic test, the mutation was not detected in 400 non-Jewish controls; one heterozygote was found among 400 persons of Ashkenazi Jewish ethnicity. Extensive biochemical studies were undertaken to characterize the effect of this mutation on enzyme activity, turnover, and stability. The V490M PHGDH yielded less than 35% of the activity observed for the wild-type enzyme when overexpressed by transient transfection or when comparing the endogenous activity in fibroblast cells from the patients with controls. Immunoblotting studies showed a comparable reduction in the level of immunoreactive PHGDH in cells expressing the mutant enzyme. Pulse-chase experiments with metabolically labeled PHGDH indicated that this resulted from an increased rate of degradation of the mutant enzyme following its synthesis. Thermolability analyses of mutant and wild-type enzyme activity revealed no significant differences. While others have proposed that the V490M mutation decreases the V-max of the enzyme, we conclude that this mutation impairs the folding and/or assembly of PHGDH but has minimal effects on the activity or stability of that portion of the V490M mutant that reaches a mature conformation. C1 Univ Manitoba, Dept Biochem & Med Genet, Winnipeg, MB R3E 0W3, Canada. Univ Manitoba, Dept Internal Med, Winnipeg, MB R3E 0W3, Canada. Univ Manitoba, Dept Immunol, Winnipeg, MB R3E 0W3, Canada. Eunice Kennedy Shriver Ctr Mental Retardat Inc, Div Med Genet, Waltham, MA 02452 USA. Univ Utah, Sch Med, Dept Neurol, Salt Lake City, UT 84132 USA. Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT 84132 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Pind, S (reprint author), Univ Manitoba, Dept Biochem & Med Genet, Winnipeg, MB R3E 0W3, Canada. NR 50 TC 22 Z9 23 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 MAR 1 PY 2002 VL 277 IS 9 BP 7136 EP 7143 DI 10.1074/jbc.M111419200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 525ZQ UT WOS:000174104300050 PM 11751922 ER PT J AU Wu, YT Ackerman, JL Kim, HM Rey, C Barroug, A Glimcher, MJ AF Wu, YT Ackerman, JL Kim, HM Rey, C Barroug, A Glimcher, MJ TI Nuclear magnetic resonance spin-spin relaxation of the crystals of bone, dental enamel, and synthetic hydroxyapatites SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE bone mineral; carbonate apatite; bovine; P-31; solid state nuclear magnetic resonance ID TRANSFORM INFRARED-SPECTROSCOPY; CALCIUM PHOSPHATES; NEUTRON-SCATTERING; CAHPO4 MONETITE; NMR; ENVIRONMENT; APATITES; BRUSHITE; PHASES; ION AB Studies of the apatitic crystals of bone and enamel by a variety of spectroscopic techniques have established clearly that their chemical composition, short-range order, and physical chemical reactivity are distinctly different from those of pure hydroxyapatite. Moreover, these characteristics change with aging and maturation of the bone and enamel crystals. Phosphorus-31 solid state nuclear magnetic resonance (NMR) spin-spin relaxation studies were carried out on bovine bone and dental enamel crystals of different ages and the data were compared with those obtained from pure and carbonated hydroxyapatites. By measuring the P-31 Hahn spin echo amplitude as a function of echo time, Van Vleck second moments (expansion coefficients describing the homonuclear dipolar line shape) were obtained and analyzed in terms of the number density of phosphorus nuclei. P-31 magnetization prepared by a 90degrees pulse or by proton-phosphorus cross-polarization (CP) yielded different second moments and experienced different degrees of proton spin-spin coupling, suggesting that these two preparation methods sample different regions, possibly the interior and the surface, respectively, of bone mineral crystals. Distinct differences were found between the biological apatites and the synthetic hydroxyapatites and as a function of the age and maturity of the biological apatites. The data provide evidence that a significant fraction of the protonated phosphates (HPO4-2) are located on the surfaces of the biological crystals, and the concentration of unprotonated phosphates (PO4-3) within the apatitic lattice is elevated with respect to the surface. The total concentration of the surface HPO4-2 groups is higher in the younger, less mature biological crystals. C1 Harvard Univ, Childrens Hosp, Sch Med,Dept Orthopaed Surg, Lab Study Skeletal Disorders & Rehabil, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,NMR Ctr,Biomat Lab, Charlestown, MA 02129 USA. Inst Natl Polytech Toulouse, CNRS, Ctr Interuniv Rech & Ingn, Toulouse, France. RP Ackerman, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,NMR Ctr,Biomat Lab, Room 2301,149 13th St, Charlestown, MA 02129 USA. RI Ackerman, Jerome/E-2646-2015 OI Ackerman, Jerome/0000-0001-5176-7496 FU NCRR NIH HHS [RR03264]; NIA NIH HHS [R01-AG14701]; NIAMS NIH HHS [AR42258] NR 36 TC 82 Z9 82 U1 2 U2 21 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 2002 VL 17 IS 3 BP 472 EP 480 DI 10.1359/jbmr.2002.17.3.472 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 522ZD UT WOS:000173926100013 PM 11874238 ER PT J AU Faulkner, KG Orwoll, E AF Faulkner, KG Orwoll, E TI Implications in the use of T-scores for the diagnosis of osteoporosis in men SO JOURNAL OF CLINICAL DENSITOMETRY LA English DT Article DE T-scores; men; osteoporosis; normative data; WHO criteria ID BONE-DENSITY; FRACTURE RISK; WOMEN AB Osteoporosis is recognized as a disorder of both men and women. However, the World Health Organization's (WHO) definition of osteoporosis (a bone mineral density [BMD] T-score of -2.5 or less) was formulated for use with postmenopausal women only. In the absence of a BMD-based definition for male osteoporosis, the WHO definition is often applied to men as well. Several important questions exist when considering the use of T-scores in men. First, is the WHO definition appropriate for men? What is the impact of using a -2.5 criteria, in terms of the number of men that would be identified as osteoporotic? When calculating T-scores in men, should male or female young normal values be used? Can the same T-score criteria be used for all skeletal sites and technologies? To address these questions, osteoporosis prevalence estimates for men aged 50 yr and over were generated using WHO methods and manufacturer normative data from dual-energy x-ray absorptiometry (DXA), quantitative computed tomography (QCT), and ultrasound. Estimates were determined for several skeletal sites and technologies using both male and female young normal values. Prevalence estimates were compared to published fracture risk estimates. Mean T-scores declined with acre at all measurement sites. Discrepancies were found between the different skeletal sites and techniques, similar to the previously reported differences in women. A -2.5 criterion (based on young normal males or females) appeared to underestimate the prevalence of osteoporosis, except for QCT, which seemed to overestimate risk. Depending on the technique used, 0 to 12.5 million US men 50 yr of age and older would be classified as osteoporotic using or the WHO definition. T-Scores based on male norms were less discordant across skeletal sites than female-based T-scores. Male-based T-scores between -1.8 and -2.3 using DXA and ultrasound and -3.1 for QCT provided osteoporosis prevalence estimates that approximated the likelihood of common fractures in men 50 and over. We conclude that the use of single T-score-based criterion for the diagnosis of osteoporosis in men has many potential difficulties. BMD measurement techniques provide discrepant estimates of prevalence and may underestimate the size of the male population at risk for fracture. Based on available normative data, a -2.5 criterion underestimates osteoporosis prevalence in men, whether based on male or female norms. Prospective studies are needed to further refinement to the BMD definition of osteoporosis in men. C1 Synarc, Portland, OR USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. RP Faulkner, KG (reprint author), 726 Heartland Trail, Madison, WI 53717 USA. OI Orwoll, Eric/0000-0002-8520-7355 NR 15 TC 44 Z9 44 U1 0 U2 2 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1094-6950 J9 J CLIN DENSITOM JI J. Clin. Densitom. PD SPR PY 2002 VL 5 IS 1 BP 87 EP 93 DI 10.1385/JCD:5:1:087 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 542UB UT WOS:000175061700012 PM 11940733 ER PT J AU Palmert, MR Gordon, CM Kartashov, AI Legro, RS Emans, SJ Dunaif, A AF Palmert, MR Gordon, CM Kartashov, AI Legro, RS Emans, SJ Dunaif, A TI Screening for abnormal glucose tolerance in adolescents with polycystic ovary syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INSULIN SENSITIVITY; HOMEOSTASIS MODEL; FASTING GLUCOSE; PREVALENCE; WOMEN; RESISTANCE; HYPERANDROGENISM; PUBERTY; GIRLS; NEUROENDOCRINE AB Insulin resistance is common in adults with polycystic ovary syndrome (PCOS). Although recent data demonstrate that insulin resistance is present in the early stages of PCOS, the prevalence of insulin resistance in adolescents with PCOS has not been determined. Likewise, the prevalence of impaired glucose tolerance (IGT) or type 2 diabetes mellitus (DM) in adolescent cohorts has not been established. In this study we sought to obtain preliminary data regarding the prevalence of IGT and DM in adolescents with PCOS and to assess the ability of screening tests to predict these abnormalities within this population. Twenty-seven adolescents with PCOS underwent oral glucose tolerance tests. Plasma glucose and insulin levels were obtained at baseline, and glucose was measured 2 h after a 75-g glucose challenge. The 2-h plasma glucose level was used to categorize subjects as having IGT or the provisional diagnosis of DM. Eight of our 27 subjects had IGT, and 1 had previously undiagnosed DM. These abnormalities were seen among lean and obese subjects. Fasting plasma glucose levels and simple measures of insulin resistance were suboptimal predictors of IGT and DM within our cohort. As in adults, our results indicate that adolescents with PCOS are at increased risk for IGT and DM and that the 2-h plasma glucose level after an oral glucose challenge appears to be the most reliable screening test for these abnormalities. Our results need to be corroborated by future studies that determine the prevalence of abnormalities in glucose tolerance among large populations of adolescents, both with and without PCOS. However, as DM may be preventable by lifestyle modifications, we would recommend that adolescents with PCOS undergo periodic screening for abnormal glucose tolerance using 2-h postchallenge plasma glucose levels. C1 Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Div Adolescent Med, Boston, MA 02115 USA. Childrens Hosp, Clin Res Prog, Boston, MA 02115 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Penn State Univ, Coll Med, Dept Obstet & Gynecol, Hershey, PA 17003 USA. Brigham & Womens Hosp, Div Womens Hlth, Boston, MA 02115 USA. RP Palmert, MR (reprint author), Rainbow Babies & Childrens Hosp, Div Pediat Endocrinol & Metab, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM mrp13@po.cwru.edu FU NCRR NIH HHS [K23-RR-15544, M01-RR-0265, M01-RR-10732, M01-RR-2172]; NICHD NIH HHS [K24-HD-01476, U54-HD-34449]; NIDDK NIH HHS [R01-DK-40605]; PHS HHS [T71-MC00009-09-S1-RO] NR 40 TC 201 Z9 210 U1 0 U2 6 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 2002 VL 87 IS 3 BP 1017 EP 1023 DI 10.1210/jc.87.3.1017 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 534ZX UT WOS:000174620600012 PM 11889155 ER PT J AU Zhang, X Sun, HP Danila, DC Johnson, SR Zhou, YL Swearingen, B Klibanski, A AF Zhang, X Sun, HP Danila, DC Johnson, SR Zhou, YL Swearingen, B Klibanski, A TI Loss of expression of GADD45 gamma, a growth inhibitory gene, in human pituitary adenomas: Implications for tumorigenesis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID REPRESENTATIONAL DIFFERENCE ANALYSIS; CELL-CYCLE CHECKPOINT; DNA-DAMAGE RESPONSE; ATAXIA-TELANGIECTASIA; TUMOR SUPPRESSION; NUCLEAR ANTIGEN; DIAGNOSIS; PROTEIN; P53; IDENTIFICATION AB The underlying molecular pathogenic mechanisms remain unknown in the majority of human pituitary tumors. GADD45gamma is a member of a growth arrest and DNA damage-inducible gene family that functions in the negative regulation of cell growth. We have found that the mRNA expression of the GADD45gamma gene is significantly different between normal human pituitary tissue and clinically nonfunctioning pituitary adenomas using cDNA-representational difference analysis. Although GADD45gamma mRNA was found in normal human pituitary tissue, it was detectable in only 1 of 18 clinically nonfunctioning pituitary tumors by RT-PCR. Furthermore, this gene was not expressed in the majority of GH- or PRL-secreting pituitary tumors (6 of 8 and 7 of 10, respectively). In colony formation assays, transfection of human GADD45gamma cDNA into the human pituitary tumor-derived cell line, PDFS, results in a dramatic decrease in cell growth by 88%. GADD45gamma also reduces colony formation in other pituitary tumor-derived cell lines, AtT20 and GH4, by approximately 60% and 50%, respectively, confirming its function in controlling cell proliferation in the pituitary. These data indicate that GADD45gamma is a powerful growth suppressor controlling pituitary cell proliferation, and GADD45gamma represents the first identified gene whose expression is lost in the majority of human pituitary tumors. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,BUL 457B, Boston, MA 02114 USA. EM aklibanski@partners.org FU NIDDK NIH HHS [R01-DK-40947]; NIMH NIH HHS [MH/NS 31862] NR 49 TC 102 Z9 104 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2002 VL 87 IS 3 BP 1262 EP 1267 DI 10.1210/jc.87.3.1262 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 534ZX UT WOS:000174620600051 PM 11889197 ER PT J AU Egan, JM Clocquet, AR Elahi, D AF Egan, JM Clocquet, AR Elahi, D TI The insulinotropic effect of acute exendin-4 administered to humans: Comparison of nondiabetic state to type 2 diabetes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GLUCOSE; MICE; MEN AB Exendin-4 is a potent and long-acting agonist of the glucagon-like peptide-1 (GLP-1) receptor. GLP-1 is an insulinotropic gut peptide and is being evaluated for the regulation of plasma glucose in type 2 diabetes. The purpose of the present study was to ascertain whether exendin-4 is insulinotropic and whether it has long-lived biological effects in nondiabetic and type 2 diabetic subjects. Because incretins are glucose dependent with respect to their insulin-releasing capacity, we used the hyperglycemic glucose clamp technique to begin to address these issues in two separate protocols. In one protocol, we infused exendin-4 (0.15 pmol.kg(-1).min(-1)) in seven nondiabetic and seven type 2 diabetic subjects during the second hour of a 5-h hyperglycemic clamp in which fasting plasma glucose was raised by 5.4 mmol/liter. The second protocol was identical to the first except that plasma glucose was allowed to fall to the fasting levels during the fourth hour and again raised by 5.4 mmol/liter during the fifth hour in four nondiabetic and four diabetic subjects. With the initiation of exendin-4 infusion at 60 min, plasma insulin response was potentiated 4- to 5-fold in both groups. Despite termination of exendin-4 at the end of the second hour, the insulin levels remained elevated for several hours and hyperglycemia was maintained. All volunteers ate a meal 5.5 h after inducing hyperglycemia. Postprandial plasma glucose, insulin, and GLP-1 did not rise in any subject, possibly because of delayed gastric emptying by exendin-4 even though its infusion had been terminated 4 h previously. We concluded that exendin-4 is a potent and long-lasting insulinotropic agent in nondiabetic and diabetic subjects. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Geriatr Res Lab, Boston, MA 02114 USA. NIA, Diabet & Metab Sect, Clin Invest Lab, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. RP Elahi, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Geriatr Res Lab, GRBSB-015,55 Fruit St, Boston, MA 02114 USA. EM elahi.dariush@mgh.harvard.edu FU NCRR NIH HHS [M01RR02719] NR 11 TC 178 Z9 185 U1 0 U2 6 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 2002 VL 87 IS 3 BP 1282 EP 1290 DI 10.1210/jc.87.3.1282 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 534ZX UT WOS:000174620600054 PM 11889200 ER PT J AU D'Souza-Li, L Yang, B Canaff, L Bai, M Hanley, DA Bastepe, M Salisbury, SR Brown, EM Cole, DEC Hendy, GN AF D'Souza-Li, L Yang, B Canaff, L Bai, M Hanley, DA Bastepe, M Salisbury, SR Brown, EM Cole, DEC Hendy, GN TI Identification and functional characterization of novel calcium-sensing receptor mutations in familial hypocalciuric hypercalcemia and autosomal dominant hypocalcemia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID NEONATAL SEVERE HYPERPARATHYROIDISM; CA2+-SENSING RECEPTOR; BENIGN HYPERCALCEMIA; EXTRACELLULAR CALCIUM; GENE; EXPRESSION; KINDREDS; CLONING; CASR AB Familial hypocalciuric hypercalcemia (FHH), neonatal severe hyperparathyroidism. (NSHPT), and autosomal dominant hypocalcemia (ADH), in which calcium homeostasis is disordered, are associated with mutations in the calcium-sensing receptor (CASR). Six unrelated kindreds with FHH and/or NSHPT and two unrelated kindreds with ADH were studied. Direct sequence analysis of the exons of the CASR gene identified heterozygous mutations in six of the kindreds with FHH and in one of those with ADH. We performed functional analyses on the novel missense and insertion/frameshift mutants by transiently transfecting wild-type and mutant CASRs tagged with a c-Myc epitope in human embryonic kidney (HEK293) cells. All mutant receptors were expressed at a similar level to that of the wild type; however, whereas mutants R220W and A835T (the ADH mutant) were fully glycosylated and were visualized on the cell surface, glycosylation of mutants G549R and C850<^>851 ins/fs was impaired, resulting in reduced cell surface staining. In fura-2-loaded HEK293 cells expressing the wild-type or mutant receptors, the inactivating R220W mutant produced a significant shift to the right relative to the wild-type CASR in the cytosolic calcium response to increasing extracellular calcium concentrations and the G549R and C850<^>851 ins/fs mutants were without detectable activity. The activating A835T mutation resulted in a shift to the left in the cytosolic calcium response to extracellular calcium concentrations relative to the wild type. Our studies have identified novel CASR mutations that alter the function of the CASR in several different ways. C1 Royal Victoria Hosp, Calcium Res Lab, Montreal, PQ H3A 1A1, Canada. McGill Univ, Dept Med, Montreal, PQ H3A 1A1, Canada. McGill Univ, Dept Human Genet, Montreal, PQ H3A 1A1, Canada. McGill Univ, Dept Physiol, Montreal, PQ H3A 1A1, Canada. Univ Calgary, Dept Med, Calgary, AB T2N 4N1, Canada. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Dalhousie Univ, Dept Pediat, Halifax, NS B3J 3G9, Canada. Dalhousie Univ, Dept Med, Halifax, NS B3J 3G9, Canada. Brigham & Womens Hosp, Div Endocrine Hypertens, Boston, MA 02114 USA. Brigham & Womens Hosp, Membrane Biol Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5G 1L5, Canada. Univ Toronto, Dept Med, Toronto, ON M5G 1L5, Canada. Univ Toronto, Dept Genet, Toronto, ON M5G 1L5, Canada. Banting & Best Inst, Toronto, ON M5G 1L5, Canada. RP Hendy, GN (reprint author), Royal Victoria Hosp, Calcium Res Lab, Room H4-67,687 Pine Ave W, Montreal, PQ H3A 1A1, Canada. EM gnhendy@med.mcgill.ca RI D'Souza-Li, Lilia/A-6973-2013 OI D'Souza-Li, Lilia/0000-0002-8574-7140 NR 32 TC 68 Z9 71 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAR PY 2002 VL 87 IS 3 BP 1309 EP 1318 DI 10.1210/jc.87.3.1309 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 534ZX UT WOS:000174620600057 PM 11889203 ER PT J AU Belke, DD Betuing, S Tuttle, MJ Graveleau, C Young, ME Pham, M Zhang, DF Cooksey, RC McClain, DA Litwin, SE Taegtmeyer, H Severson, D Kahn, CR Abel, ED AF Belke, DD Betuing, S Tuttle, MJ Graveleau, C Young, ME Pham, M Zhang, DF Cooksey, RC McClain, DA Litwin, SE Taegtmeyer, H Severson, D Kahn, CR Abel, ED TI Insulin signaling coordinately regulates cardiac size, metabolism, and contractile protein isoform expression SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID FATTY-ACID OXIDATION; WORKING MOUSE HEART; VIVO GLUCOSE-UPTAKE; NITRIC-OXIDE; GENE-EXPRESSION; TRANSGENIC MICE; SKELETAL-MUSCLE; RAT-HEART; RECEPTOR; GLUT4 AB To investigate the role of insulin signaling, on postnatal cardiac development, physiology, and cardiac metabolism, we generated mice with a cardiomyocyte-selective insulin receptor knockout (CIRKO) using cre/loxP recombination. Hearts of CIRKO mice were reduced in size by 20-30% due to reduced cardiomyocyte size and had persistent expression of the fetal P-myosin heavy chain isoform. In CIRKO hearts, glucose transporter 1 (GLUT1) expression was reduced by about 50%, but there was a twofold increase in GLUT4 expression as well as increased rates of cardiac glucose uptake in vivo and increased glycolysis in isolated working, hearts. Fatty acid oxidation rates were diminished as a result of reduced expression of enzymes that catalyze mitochondrial beta-oxidation. Although basal rates of glucose oxidation were reduced, insulin unexpectedly stimulated glucose oxidation and glycogenolysis in CIRKO hearts. Cardiac performance in vivo and in isolated hearts was mildly impaired. Thus, insulin signaling plays an important developmental role in regulating postnatal cardiac size, myosin isoform expression, and the switching, of cardiac substrate utilization from glucose to fatty acids. Insulin may also modulate cardiac myocyte metabolism through paracrine mechanisms by activating insulin receptors in other cell types within the heart. C1 Univ Utah, Sch Med, Div Endocrinol Metab & Diabet, Salt Lake City, UT 84112 USA. Univ Utah, Sch Med, Program Human Mol Biol & Genet, Salt Lake City, UT 84112 USA. Univ Calgary, Dept Pharmacol & Therapeut, Calgary, AB, Canada. Univ Texas, Sch Med, Div Cardiol, Houston, TX USA. Univ Utah, Div Cardiol, Salt Lake City, UT 84112 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA USA. RP Abel, ED (reprint author), Univ Utah, Sch Med, Div Endocrinol Metab & Diabet, 15 North 2030 East,Bldg 533,Room 3410 B, Salt Lake City, UT 84112 USA. RI Betuing, Sandrine/F-2967-2013 FU NHLBI NIH HHS [R01 HL043133, HL-43133, HL-52338, HL-58073, HL-62886, HL/AG-61483, P50 HL052338, R01 HL061483]; NIDDK NIH HHS [DK-02495, DK-31036, DK-33201, DK-43526, R01 DK031036, R01 DK033201, R01 DK043526, R01 DK092065, R37 DK031036] NR 61 TC 249 Z9 257 U1 1 U2 12 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 2002 VL 109 IS 5 BP 629 EP 639 DI 10.1172/JCI200213946 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 528AW UT WOS:000174222000011 PM 11877471 ER PT J AU Poulaki, V Qin, WY Joussen, AM Hurlbut, P Wiegand, SJ Rudge, J Yancopoulos, GD Adamis, AP AF Poulaki, V Qin, WY Joussen, AM Hurlbut, P Wiegand, SJ Rudge, J Yancopoulos, GD Adamis, AP TI Acute intensive insulin therapy exacerbates diabetic blood-retinal barrier breakdown via hypoxia-inducible factor-l alpha and VEGF SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; ACTIVATED PROTEIN-KINASES; FACTOR MESSENGER-RNA; FACTOR-I; FACTOR EXPRESSION; GLYCEMIC CONTROL; RETINOPATHY; MELLITUS; NEOVASCULARIZATION; INHIBITION AB Acute intensive insulin therapy is an independent risk factor for diabetic retinopathy. Here we demonstrate that acute intensive insulin therapy markedly increases VEGF mRNA and protein levels in the retinae of diabetic rats. Retinal nuclear extracts from insulin-treated rats contain higher hypoxia-inducible factor-1alpha (HIF-1alpha) levels and demonstrate increased HIF-1alpha-dependent binding to hypoxia-responsive elements in the VEGFpromoter. Blood-retinal barrier breakdown is markedly increased with acute intensive insulin therapy but can be reversed by treating animals with a fusion protein containing a soluble form of the VEGF receptor Flt; a control fusion protein has no such protective effect. The insulin-induced retinal HIF-1alpha and VEGF increases and the related blood-retinal barrier breakdown are suppressed by inhibitors of p38 mitogen-activated protein kinase (MAPK) and phosphatidylinositol (PI) 3-kinase, but not inhibitors of p42/p44 MAPK or protein kinase C. Taken together, these findings indicate that acute intensive insulin therapy produces a transient worsening of diabetic blood-retinal barrier breakdown via an HIF-1alpha-mediated increase in retinal VEGF expression. Insulin-induced TGF expression requires p38 MAPK and PI 3-kinase, whereas hyperglycemia-induced VEGF expression is HIF-1alpha-independent and requires PKC and p42/p44 MAPK. To our knowledge, these data are the First to identify a specific mechanism for the transient worsening of diabetic retinopathy, specifically blood-retinal barrier breakdown, that follows the institution of intensive insulin therapy. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Sch Med, Boston, MA 02114 USA. Harvard Univ, Childrens Hosp, Surg Res Lab, Sch Med, Boston, MA 02115 USA. Univ Cologne, Ctr Ophthalmol, Dept Vitreoretinal Surg, Cologne, Germany. Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA. RP Adamis, AP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Sch Med, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY 11627, EY 12611] NR 53 TC 165 Z9 176 U1 1 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2002 VL 109 IS 6 BP 805 EP 815 DI 10.1172/JCI200213776 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 532TF UT WOS:000174490600016 PM 11901189 ER PT J AU Altfeld, M van Lunzen, J Frahm, N Yu, XG Schneider, C Eldridge, RL Feeney, ME Meyer-Olson, D Stellbrink, HJ Walker, BD AF Altfeld, M van Lunzen, J Frahm, N Yu, XG Schneider, C Eldridge, RL Feeney, ME Meyer-Olson, D Stellbrink, HJ Walker, BD TI Expansion of pre-existing, lymph node-localized CD8(+) T cells during supervised treatment interruptions in chronic HIV-1 infection SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; VIRUS-REPLICATION; IMMUNE-RESPONSES; VIRAL-RNA; LYMPHOCYTES; VIREMIA; EFFECTOR; KINETICS; TISSUE; DISCONTINUATION AB To date, most studies have focused on the characterization of HIV-1-specific cellular immune responses in the peripheral blood (PB) of infected individuals. Much less is known about the comparative magnitude and breadth of responses in the lymphoid tissue. This study analyzed HIV-1-specific CD8(+) T cell responses simultaneously in PB and lymph nodes (LNs) of persons with chronic HIV-1 infection and assessed the dynamics of these responses during antiretroviral treatment and supervised treatment interruption (STI). In untreated chronic infection, the magnitude of epitope-specific CD8(+) T cell activity was significantly higher in LNs than in PB. Responses decreased in both compartments during highly active antiretroviral therapy, but this decline was more pronounced in PB. During STI, HIV-1-specific CD8(+) T cell responses in PB increased significantly. Enhancement in breadth and magnitude was largely due to the expansion of pre-existing responses in the LNs, with new epitopes infrequently targeted. Taken together, these data demonstrate that HIV-1-specific CD8(+) T cells are preferentially located in the LNs, with a subset of responses exclusively detectable in this compartment. Furthermore, the enhanced CD8(+) T cell responses observed during STI in chronically infected individuals is largely due to expansion of pre-existing virus-specific CD8(+) T cells, rather than the induction of novel responses. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA USA. Univ Hamburg, Krankenhaus Eppendorf, Chirurg Klin, D-2000 Hamburg, Germany. Univ Hamburg, Krankenhaus Eppendorf, Med Kernklin & Poliklin, D-2000 Hamburg, Germany. RP Walker, BD (reprint author), Massachusetts Gen Hosp E, 5212,149 13th St, Charlestown, MA 02129 USA. FU NIAID NIH HHS [R01 AI-44656, R01 AI-30914, R01 AI040873, R01 AI-40873, R01 AI030914, R01 AI044656, R37 AI-12856-8] NR 45 TC 59 Z9 59 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2002 VL 109 IS 6 BP 837 EP 843 DI 10.1172/JCI14789 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 532TF UT WOS:000174490600019 PM 11901192 ER PT J AU Becker, MR Paster, BJ Leys, EJ Moeschberger, ML Kenyon, SG Galvin, JL Boches, SK Dewhirst, FE Griffen, AL AF Becker, MR Paster, BJ Leys, EJ Moeschberger, ML Kenyon, SG Galvin, JL Boches, SK Dewhirst, FE Griffen, AL TI Molecular analysis of bacterial species associated with childhood caries SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID RIBOSOMAL DATABASE PROJECT; HUMAN ROOT CARIES; DENTAL-CARIES; IN-VITRO; DIVERSITY; LESIONS; IDENTIFICATION; PERIODONTITIS; MICROBIOLOGY; PHYLOGENY AB Although substantial epidemiologic evidence links Streptococcus mutans to caries, the pathobiology of caries may involve more complex communities of bacterial species. Molecular methods for bacterial identification and enumeration now make it possible to more precisely study the microbiota associated with dental caries. The purpose of this study was to compare the bacteria found in early childhood caries (ECC) to those found in caries-free children by using molecular identification methods., Cloning and sequencing of bacterial 16S ribosomal DNAs from a healthy subject and a subject with ECC Were used for identification of novel species or uncultivated phylotypes and species not previously associated with dental caries. Ten novel phylotypes were identified. A number of species or phylotypes that may play, a role in health or disease were identified and warrant further investigation. In addition, quantitative, measurements for 23 previously known bacterial species or species groups were obtained by a reverse capture checkerboard assay for 30 subjects with caries and 30 healthy controls. Significant differences were observed for nine species: S. sanguinis was associated with health and, in order of decreasing cell numbers, Actinomyces gerencseriae, Bifidobacterium, S. mutans, Veillonella, S. salivarius, S. constellatus, S. parasanguinis, and Lactobacillus fermentum were associated with caries. These data suggest that A. gerencseriae and other Actinomyces species may play an important role in caries initiation and that a novel Bifidobacterium may be a major pathogen in deep caries. Further investigation could lead to the identification of targets for biological interventions in the caries process and thereby contribute to improved prevention of and treatment for this significant public health problem. C1 Ohio State Univ, Coll Dent, Dept Pediat Dent, Columbus, OH 43218 USA. Ohio State Univ, Coll Dent, Dept Oral Biol, Columbus, OH 43218 USA. Ohio State Univ, Coll Med & Publ Hlth, Sch Publ Hlth, Div Epidemiol & Biometr, Columbus, OH 43218 USA. Harvard Univ, Sch Dent Med, Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral Biol, Boston, MA 02115 USA. RP Griffen, AL (reprint author), Ohio State Univ, Coll Dent, Dept Pediat Dent, 305 W 12th Ave,POB 182357, Columbus, OH 43218 USA. FU NIDCR NIH HHS [DE10467, DE11443, DE10374, R01 DE010374, R01 DE010467, R01 DE011443] NR 42 TC 314 Z9 337 U1 8 U2 42 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAR PY 2002 VL 40 IS 3 BP 1001 EP 1009 DI 10.1128/JCM.40.3.1001-1009.2002 PG 9 WC Microbiology SC Microbiology GA 528HP UT WOS:000174238600045 PM 11880430 ER PT J AU Willett, CG AF Willett, CG TI Radiation dose escalation in combined-modality therapy for esophageal cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID SQUAMOUS-CELL CANCER; COMBINED CHEMORADIOTHERAPY; UTERINE CERVIX; TREATMENT TIME; RADIOTHERAPY; CHEMOTHERAPY; CARCINOMA; TRIAL; SURGERY; CISPLATIN C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Willett, CG (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 17 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2002 VL 20 IS 5 BP 1151 EP 1153 PG 3 WC Oncology SC Oncology GA 528WZ UT WOS:000174268800001 PM 11870151 ER PT J AU Howard, OM Gribben, JG Neuberg, DS Grossbard, M Poor, C Janicek, MJ Shipp, MA AF Howard, OM Gribben, JG Neuberg, DS Grossbard, M Poor, C Janicek, MJ Shipp, MA TI Rituximab and CHOP induction therapy for newly diagnosed mantle-cell lymphoma: Molecular complete responses are not predictive of progression-free survival SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SMALL LYMPHOCYTIC LYMPHOMA; POLYMERASE CHAIN-REACTION; NON-HODGKINS-LYMPHOMAS; ANTI-CD20 MONOCLONAL-ANTIBODY; MINIMAL RESIDUAL DISEASE; HIGH-DOSE THERAPY; CLINICAL-FEATURES; BONE-MARROW; IN-VIVO; PROGNOSTIC FACTORS AB Purpose: To evaluate the efficacy of rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) induction therapy in patients with newly diagnosed mantle-cell lymphoma (MCL). Patients and Methods: From March 1997 to May 1999, 40 previously untreated patients with stage II through IV MCL were treated with six cycles of rituximab and CHOP chemotherapy in a phase II trial. Pretreatment and interval peripheral-blood (PB) and bone marrow (BM) specimens were also analyzed by polymerase chain reaction (PCR) for tumor-specific BCL-1/immunoglobulin H (IgH) translocations and clonal IgH rearrangements. Study end points included clinical and molecular response rates and long-term progression-free survival (PFS). Results: Forty-eight percent of patients achieved a complete response (CR)/CR unconfirmed (CRu), and 48% of patients obtained a partial response (PR). However, 28 of the 40 patients have already relapsed or developed progressive disease with a median PFS of 16.6 months. Twenty-five patients had PCR-detectable BCL-1/IgH or clonal IgH products in PB or BM at diagnosis. Nine of the 25 informative patients had no evidence of PCR-detectable disease in PB or BM after rituximab and CHOP therapy. However, patients who achieved molecular remissions in PB or BM had PFS similar to patients without molecular remissions (16.5 v 18.8 months, P = .51). Conclusion: Favorable clinical and molecular response rates associated with rituximab and CHOP chemotherapy do not translate into prolonged PFS in MCL. Nevertheless, rituximab and combination chemotherapy may transiently clear PB or BM of detectable tumor cells, prompting additional consideration of antibodybased in vivo purging in subsequent clinical trials. (C) 2002 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Med Oncol, Boston, MA USA. RP Shipp, MA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 48 TC 254 Z9 259 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2002 VL 20 IS 5 BP 1288 EP 1294 DI 10.1200/JCO.20.5.1288 PG 7 WC Oncology SC Oncology GA 528WZ UT WOS:000174268800021 PM 11870171 ER PT J AU Kilbridge, KL Cole, BF Kirkwood, JM Haluska, FG Atkins, MA Ruckdeschel, JC Sock, DE Nease, RF Weeks, JC AF Kilbridge, KL Cole, BF Kirkwood, JM Haluska, FG Atkins, MA Ruckdeschel, JC Sock, DE Nease, RF Weeks, JC TI Quality-of-life-adjusted survival analysis of high-dose adjuvant interferon alfa-2b for high-risk melanoma patients using intergroup clinical trial data SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RESECTED CUTANEOUS MELANOMA; COOPERATIVE-ONCOLOGY-GROUP; AMERICAN JOINT COMMITTEE; OPERABLE BREAST-CANCER; PHASE-I TRIALS; STAGING SYSTEM; THERAPY; CHEMOTHERAPY; PERCEPTIONS; PREFERENCES AB Purpose: High-dose adjuvant interferon alfa-2b (IFNalpha2b) for high-risk melanoma is a 1-year regimen that improves relapse-free and overall survival but has significant toxicity. A quality-of-life-adjusted survival (QAS) analysis analysis of two cooperative group phase III trials, E1684 and E1690/S9111/C9190, was performed, incorporating patient values (utilities) for the toxicity of IFNa2b treatment and melanoma recurrence. Patients and Methods. Quality-Adjusted Time Without Symptoms or Toxicity methodology was used with melanoma patient utilities and trial data to estimate the effect of IFNa2b on QAS. The increase or decrease in QAS that patients could expect from treatment was estimated based on their utilities. Eleven utility predictor questions were tested to identify patients with utilities that result in decreased QAS. Results: Using E1684 data, IFNa2b would result in an increase in QAS for all sets of patient utilities. This benefit was significant (P < .05) for 16% of patients. Using E1690/S9111/C9190 data, 77% of patients would experience a benefit in QAS from IFNa2b and 23% would experience a decrease in QAS; neither of these effects was statistically significant. Using utility predictors and the E1690/S9111/C9190 analysis, a decision rule was formulated that helps identify patients in whom IFNa2b may detract from QAS. Conclusion: Most patients experienced improvement in GAS in both trials, but this benefit was statistically significant in only 16% of patients in E1684. Change in QAS depends more on the utility for IFNa2b toxicity than on the utility for melanoma recurrence. Cancer patients probably have higher utilities for IFNa2b toxicity than members of the general population and will tend to favor IFNa2b treatment as a result. (C) 2002 by American Society of Clinical Oncology. C1 Univ Virginia, Dept Hlth Evaluat Sci, Charlottesville, VA 22908 USA. Washington Univ, St Louis, MO USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Beth Israel Deaconess Med Ctr, Boston, MA 02114 USA. Univ Pittsburgh, Pittsburgh, PA USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. RP Univ Virginia, Dept Hlth Evaluat Sci, HSC POB 800821, Charlottesville, VA 22908 USA. EM kk4h@virginia.edu FU NCI NIH HHS [CA21115, CA12449, CA23318, CA32291, CA39229, CA66636, CA73590, CA80775] NR 29 TC 49 Z9 49 U1 0 U2 0 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 MAR 1 PY 2002 VL 20 IS 5 BP 1311 EP 1318 DI 10.1200/JCO.20.5.1311 PG 8 WC Oncology SC Oncology GA 528WZ UT WOS:000174268800024 PM 11870174 ER PT J AU Socransky, SS Smith, C Haffajee, AD AF Socransky, SS Smith, C Haffajee, AD TI Subgingival microbial profiles in refractory periodontal disease SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE refractory periodontitis; bacteria; periodontal disease; microbiology; etiology ID METRONIDAZOLE; FEATURES AB Background/aim: The purpose of the present investigation was to examine subgingival microbial profiles associated with refractory periodontitis and to seek such profiles in periodontally healthy, periodontally well-maintained elder and untreated periodontitis subjects. Methods: 36 subjects were defined as refractory on the basis of further attachment loss after scaling and root planing, surgery and systemically administered antibiotics. A total of 890 subgingival plaque samples (mean/subject=24.7) were taken from the mesial aspect of each tooth in each subject at baseline and individually processed for their content of 40 subgingival taxa using checker-board DNA-DNA hybridization. Cluster analysis was performed on mean within subject species counts using the chord coefficient and an average unweighted linkage sort. Significant differences among clusters for individual and complexes of species were sought using the Kruskal Wallis test. The microbial profiles of the refractory subjects were compared with those of 27 periodontally healthy subjects (n plaque samples=708), 35 periodontally well-maintained elder subjects (n plaque samples=801) and 115 untreated adult periodontitis subjects (n plaque samples=2871). Results: 28 of 36 refractory subjects fell into 4 clusters with >29% similarity. 10 of 40 species and 4 of 7 complexes differed significantly among clusters. Profile (Cluster) I (n=4) was characterized by high proportions of "yellow" and "green" complex species, profile II (n=3) by low total counts and high proportions of "orange" and "purple" complex species, profile III (n=9) by high total counts and counts of Actinomyces and "purple" complex species, profile IV (n=12) by high proportions of "red" and "orange" complex species. The mean profiles of each cluster were subjected to cluster analysis with microbial data from 4380 (mean 24.7) baseline subgingival plaque samples from 27 periodontally healthy, 35 treated, well-maintained elders and 115 untreated adult periodontitis subjects. 12 clusters were formed with >41% similarity. 3 of the refractory profiles were detected in 3 cluster groups. Profile II in a cluster of 1 healthy, 1 elder and 4 untreated periodontitis subjects; profile III in a cluster of 1 healthy, 2 elder and 12 periodontitis subjects; Profile IV, with 1 healthy and 5 untreated periodontitis subjects. The profile not detected in non refractory subjects was dominated by Streptococcus species. 9 clusters did not harbor refractory profiles. 11.1% of healthy, 8.6% of elder and 18.3% of periodontitis subjects were in clusters exhibiting refractory microbial profiles. Conclusions: 4 subgingival microbial profiles were detected among refractory subjects. "Refractory microbial profiles" could be detected in subjects who had not yet exhibited refractory disease. C1 Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. RP Socransky, SS (reprint author), Forsyth Inst, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE12108, DE12861, DE13232] NR 15 TC 87 Z9 90 U1 0 U2 7 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD MAR PY 2002 VL 29 IS 3 BP 260 EP 268 DI 10.1034/j.1600-051x.2002.290313.x PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 524YP UT WOS:000174040700013 PM 11940147 ER PT J AU McElroy, SL Frye, MA Suppes, T Dhavale, D Keck, PE Leverich, GS Altshuler, L Denicoff, KD Nolen, WA Kupka, R Grunze, H Walden, J Post, RM AF McElroy, SL Frye, MA Suppes, T Dhavale, D Keck, PE Leverich, GS Altshuler, L Denicoff, KD Nolen, WA Kupka, R Grunze, H Walden, J Post, RM TI Correlates of overweight and obesity in 644 patients with bipolar disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID MAJOR DEPRESSIVE DISORDER; BODY-WEIGHT GAIN; EATING DISORDER; PREVALENCE; LITHIUM; MECHANISMS; MANAGEMENT; ENDOCRINE; WOMEN AB Objective: Overweight and obesity are common clinical problems encountered in the treatment of bipolar disorder. We therefore assessed the prevalence and clinical correlates of overweight, obesity, and extreme obesity in 644 bipolar patients. Method: 644 outpatients with DSM-IV bipolar disorder in the Stanley Foundation Bipolar Treatment Outcomes Network were evaluated with structured diagnostic interviews and clinician- and self-administered questionnaires to determine bipolar disorder diagnoses, demographic and historical illness characteristics, comorbid Axis I diagnoses, medical histories, health habits, and body mass indices (BMIs). Results: Fifty-eight percent of the patients with bipolar disorder were overweight, 21% were obese, and 5% were extremely obese. American patients had significantly higher mean (p < .0001) BMIs and significantly higher rates of obesity (p < .001) and extreme obesity (p < .001) than European patients. Significant associations (p:.001) were found between over-weight, obesity, and extreme obesity and gender, age, income level, comorbid binge-eating disorder, hypertension, arthritis, diabetes mellitus, exercise habits, and coffee consumption. Current BMI and weight were each correlated with the number of weight gain-associated psycho-tropics to which patients had been exposed. Multinomial logistic regression (adjusted for site and eating disorder diagnosis and corrected for multiple comparisons) showed that (1) overweight was significantly associated with male gender and hypertension (p < .001), (2) obesity was significantly associated with hypertension (p < .001), and (3) extreme obesity was significantly associated with hypertension and arthritis (p < .001). Conclusion: Overweight, obesity, and extreme obesity were common in this group of bipolar patients, although it was unclear that their prevalence rates were truly elevated, because overweight and obesity are increasingly common public health problems among the general population. Correlates of overweight and obesity in bipolar disorder include patient and treatment variables such as gender, geographical location, comorbid binge-eating disorder, age, income level, degree of exposure to weight gain-associated psychotropics, medical disorders associated with obesity, and health habits. C1 Univ Cincinnati, Coll Med, Biol Psychiat Program, Dept Psychiat,Stanley Fdn Bipolar Treatment Outco, Cincinnati, OH 45267 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. W Los Angeles VA Med Ctr, Los Angeles, CA USA. Univ Texas, SW Med Ctr, Dallas, TX USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Univ Utrecht, Med Ctr, Utrecht, Netherlands. Altrecht Inst Mental Hlth Care, Utrecht, Netherlands. LMU Univ Hosp, Dept Psychiat, Munich, Germany. Univ Hosp, Dept Psychiat, Freiburg, Germany. RP McElroy, SL (reprint author), Univ Cincinnati, Coll Med, Biol Psychiat Program, Dept Psychiat,Stanley Fdn Bipolar Treatment Outco, POB 670559,231 Albert Sabin Way, Cincinnati, OH 45267 USA. RI Nolen, Willem/E-9006-2014 NR 43 TC 213 Z9 217 U1 4 U2 12 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAR PY 2002 VL 63 IS 3 BP 207 EP 213 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 534WU UT WOS:000174613400006 PM 11926719 ER PT J AU Sahani, DV O'Malley, ME Bhat, S Hahn, PF Saini, S AF Sahani, DV O'Malley, ME Bhat, S Hahn, PF Saini, S TI Contrast-enhanced MRI of the liver with mangafodipir trisodium: Imaging technique and results SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE liver tumor; contrast agent; mangafodipir trisodium; magnetic resonance imaging ID MN-DPDP; HEPATOCELLULAR TUMORS; LESIONS; IMAGES AB Magnetic resonance (MR) contrast agents are now routinely used for detecting and characterizing focal liver lesions. Liver specific, hepatobiliary, MRI contrast agent mangafodipir trisodium (Mn-DPDP) is taken up by the functioning hepatocytes and excreted by the biliary system. Contrast uptake leads to persistent elevation of T1-weighted signal of normal liver parenchyma within 10 minutes of injection. Most tumors of non-hepatocellular origin typically are hypointense relative to enhanced liver parenchyma on T1 weighted images and are more conspicuous than on unenhanced images. Whereas, tumors of hepatocellular origin such as focal nodular hyperplasia (FNH). adenoma. and well-differentiated hepatocellular carcinomas (HCC) have been shown to accumulate Mn-DPDP, providing characterization information to discriminate hepatocellular from non-hepatocellular tumors. The purpose of this pictorial essay is to illustrate the appearance of various liver tumors on mangafodipir enhanced liver MR imaging. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. Nycomed Amersham, Clin Res, Wayne, PA USA. Toronto Gen Hosp, Dept Med Imaging, Toronto, ON, Canada. RP Saini, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Ellison 234-E,55 Fruit St, Boston, MA 02114 USA. NR 11 TC 16 Z9 18 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAR-APR PY 2002 VL 26 IS 2 BP 216 EP 222 DI 10.1097/00004728-200203000-00010 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 532CF UT WOS:000174453500011 PM 11884777 ER PT J AU Abukawa, H Kaban, LB Vacanti, JP Troulis, MJ AF Abukawa, H Kaban, LB Vacanti, JP Troulis, MJ TI Effect of interferon on porcine mesenchymal stem cells in culture. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 81 SI SI MA 4040 BP A494 EP A494 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 559KE UT WOS:000176024704006 ER PT J AU Boustany, G Gyurko, R Genco, C Van Dyke, TE Gibson, F AF Boustany, G Gyurko, R Genco, C Van Dyke, TE Gibson, F TI Inducible nitric oxide synthase (iNOS)-deficient mice are impaired in their ablity to clear porphyromonas gingivalis infection. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Boston Univ, Goldman Sch Dent Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 81 SI SI MA 0807 BP A123 EP A123 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 559KE UT WOS:000176024700800 ER PT J AU Chuang, SK Wei, LJ Dodson, TB AF Chuang, SK Wei, LJ Dodson, TB TI Risk factors for dental implant failure: A strategy for the analysis of clustered failure time observations. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Dent Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 2002 VL 81 SI SI MA 4121 BP A503 EP A503 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 559KE UT WOS:000176024704085 ER PT J AU Ding, Y Xue, J Bartlett, JD AF Ding, Y Xue, J Bartlett, JD TI Expression of cathepsin K in the developing porcine molar. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 81 SI SI MA 3598 BP A442 EP A442 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 559KE UT WOS:000176024703566 ER PT J AU Duailibi, SE Duailibi, MT Young, CS Vacanti, JP Yelick, PC Bartlett, JD AF Duailibi, SE Duailibi, MT Young, CS Vacanti, JP Yelick, PC Bartlett, JD TI Tissue engineered teeth grown in rat jaw and omentum. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Fed Sao Paulo, Escola Paulista, Sao Paulo, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 81 SI SI MA 1412 BP A192 EP A192 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 559KE UT WOS:000176024701397 ER PT J AU Eastcott, JW Orr, N Smith, DJ Hayden, TL Taubman, MA AF Eastcott, JW Orr, N Smith, DJ Hayden, TL Taubman, MA TI Expression and delivery of GTF peptides in Salmonella enterica. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 81 SI SI MA 3886 BP A475 EP A475 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 559KE UT WOS:000176024703852 ER PT J AU Ebersole, JL Cappelli, D Holt, SC Pickrum, HM Singer, RE AF Ebersole, JL Cappelli, D Holt, SC Pickrum, HM Singer, RE TI Effects of an H2-receptor antagonist on gingivitis & periodontitis in nonhuman primates (Nhp). SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Univ Kentucky, Lexington, KY 40506 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78284 USA. Forsyth Inst, Boston, MA USA. Procter & Gamble Co, Cincinnati, OH 45202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 81 SI SI MA 4007 BP A490 EP A490 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 559KE UT WOS:000176024703973 ER PT J AU Fowler, CE Li, M Mann, S Margolis, HC AF Fowler, CE Li, M Mann, S Margolis, HC TI Surfactant model system for the growth of tooth enamel. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA USA. Univ Bristol, Bristol BS8 1TH, Avon, England. RI Mann, Stephen/D-1332-2012 OI Mann, Stephen/0000-0003-3012-8964 NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 81 SI SI MA 4011 BP A490 EP A490 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 559KE UT WOS:000176024703977 ER PT J AU Friedlander, AH Garrett, N Norman, D AF Friedlander, AH Garrett, N Norman, D TI Prevalence of atheromas on panographs of patients with type 2 diabetes. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 VA Greater Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 81 SI SI MA 3992 BP A488 EP A488 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 559KE UT WOS:000176024703958 ER PT J AU Inagaki, K Krall, EA Fleet, JC Garcia, RI AF Inagaki, K Krall, EA Fleet, JC Garcia, RI TI Vitamin D receptor alleles, periodontal disease progression and tooth loss in the VA Dental Longitudinal Study. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Aichi Gakuin Univ, Nagoya, Aichi 464, Japan. Boston Univ, Boston, MA 02215 USA. Purdue Univ, W Lafayette, IN 47907 USA. VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 81 SI SI MA 2533 BP A319 EP A319 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 559KE UT WOS:000176024702508 ER PT J AU Jones, JA Garcia, RI Wehler, CJ Rich, SE Miller, DR Rothendler, J Krall, EA Christiansen, CL AF Jones, JA Garcia, RI Wehler, CJ Rich, SE Miller, DR Rothendler, J Krall, EA Christiansen, CL TI Randomization and baseline characteristics: The VA dental diabetes study (VA-DDS). SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 VA Med Ctr, Bedford, MA USA. Boston Univ, Goldman Sch Dent Med & Publ Hlth, Boston, MA 02215 USA. VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Goldman Sch Dent Med, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Boston Univ, Sch Dent Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 2002 VL 81 SI SI MA 2043 BP A264 EP A264 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 559KE UT WOS:000176024702024 ER PT J AU Juvet, LM Kaban, LB Nastri, A Dodson, TB AF Juvet, LM Kaban, LB Nastri, A Dodson, TB TI Variables affecting hospital length of stay in orthognathic surgery patients. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Royal Melbourne Hosp, Melbourne, Vic, Australia. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 81 SI SI MA 3202 BP A397 EP A397 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 559KE UT WOS:000176024703173 ER PT J AU Kutsenko, D Neiderman, R AF Kutsenko, D Neiderman, R TI Determination of high level clinical evidence in oral medicine & radiology. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Cambridge, MA 02138 USA. Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 81 SI SI MA 4057 BP A496 EP A496 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 559KE UT WOS:000176024704023 ER PT J AU McDermott, N Chuang, SK Vehemente, V Daher, S Muftu, A Dodson, TB AF McDermott, N Chuang, SK Vehemente, V Daher, S Muftu, A Dodson, TB TI Dental implant complications: Types, frequency, and associated risk factors. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Dent Med, Cambridge, MA 02138 USA. Boston Univ, Goldman Sch Grad Dent, Boston, MA 02215 USA. Tufts Univ, Sch Dent Med, Medford, MA 02155 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 81 SI SI MA 1028 BP A148 EP A148 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 559KE UT WOS:000176024701018 ER PT J AU Page, RC Krall, EA Martin, JA Mancl, LA Garcia, RI AF Page, RC Krall, EA Martin, JA Mancl, LA Garcia, RI TI Validity and accuracy of a risk calculator for future periodontal disease SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. Boston Univ, Goldman Sch Dent Med, Boston, MA 02215 USA. VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAR PY 2002 VL 81 SI SI MA 0071 BP A38 EP A38 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 559KE UT WOS:000176024700072 ER PT J AU Perciaccante, VJ Carey, JW Dodson, TB AF Perciaccante, VJ Carey, JW Dodson, TB TI Injury location and Women's Abuse Screening Tool scores as markets of intimate partner violence (IPV). SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Emory Univ, Sch Med, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 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 2002 VL 81 SI SI MA 4029 BP A492 EP A492 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 559KE UT WOS:000176024703995 ER PT J AU Wangpichit, K Tanner, ACR Loo, CY Hughes, CV Ganeshkumar, N AF Wangpichit, K Tanner, ACR Loo, CY Hughes, CV Ganeshkumar, N TI Identification of genes coding for immunogenic proteins of Bacteroides forsythus. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Boston Univ, Boston, MA 02215 USA. Forsyth Inst, Boston, MA USA. RI Hughes, Christopher/E-1438-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 81 SI SI MA 4066 BP A497 EP A497 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 559KE UT WOS:000176024704032 ER PT J AU Williams, WB Troulis, MJ AF Williams, WB Troulis, MJ TI Treatment and oral rehabilitation of children with primary jaw tumors. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Dent Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 81 SI SI MA 3921 BP A480 EP A480 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 559KE UT WOS:000176024703887 ER PT J AU Young, CS Vacanti, JP Terad, S Bartletti, JD Yelick, PC AF Young, CS Vacanti, JP Terad, S Bartletti, JD Yelick, PC TI Immunohistochemical analyses of bioengineered tooth tissues. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 7 Z9 7 U1 0 U2 1 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAR PY 2002 VL 81 SI SI MA 1017 BP A147 EP A147 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 559KE UT WOS:000176024701007 ER PT J AU Taneja, A AF Taneja, A TI Treatment of vitiligo SO JOURNAL OF DERMATOLOGICAL TREATMENT LA English DT Article DE excimer laser; NBUVB; PUVA; vitiligo ID STABLE VITILIGO; SPREADING DISEASE; PULSE THERAPY; UV-A; PSORIASIS; PHOTOCHEMOTHERAPY; PHENYLALANINE; GUIDELINES; 8-METHOXYPSORALEN; 5-METHOXYPSORALEN AB Vitiligo, particularly in darker skinned individuals, is a psychosocial disaster. With patient education, proper therapeutic selection and persistence, favorable repigmentation can be achieved in the majority of individuals with vitiligo. Attention to the activity state of the disease, the type, location and extent of the vitiligo must be carefully balanced against the patient's expectations, time commitment and assumption of risks. In this review, Dr Taneja succincly summarizes the wide range of therapeutic options available today for the vitiligo patient. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Dermatol, Gange Photomed Res Ctr,Well Labs Photomed, Boston, MA USA. RP Taneja, A (reprint author), Bar 622 Mgh,55 Fruit St, Boston, MA 02114 USA. NR 59 TC 26 Z9 30 U1 0 U2 1 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 0954-6634 J9 J DERMATOL TREAT JI J. Dermatol. Treat. PD MAR PY 2002 VL 13 IS 1 BP 19 EP 25 DI 10.1080/09546630252775207 PG 7 WC Dermatology SC Dermatology GA 523GV UT WOS:000173946400005 PM 12006134 ER PT J AU Mayfield, JA Caps, MT Boyko, EJ Ahroni, JH Smith, DG AF Mayfield, JA Caps, MT Boyko, EJ Ahroni, JH Smith, DG TI Relationship of medial arterial calcinosis to autonomic neuropathy and adverse outcomes in a diabetic veteran population SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE autonomic neuropathy; medial arterial calcinosis; ulceration; amputation; mortality ID FOOT ULCERATION; FOLLOW-UP; CALCIFICATION; NIDDM; PREDICTORS; DIAGNOSIS; MELLITUS; TESTS; RISK AB Statement of the problem: Medial arterial calcinosis (MAC) is associated with neuropathy, amputation, and mortality through an unknown mechanism. We hypothesized that MAC was a marker of autonomic neuropathy rather than a risk factor and that the outcomes were due to autonomic neuropathy. Methods: All subjects in an ongoing prospective study of diabetic foot conditions in a diabetic veteran cohort who received a foot radiograph between 11/7/90 and 11/5/93 were included. Autonomic neuropathy measured as either heart rate variability with timed respiration or postural hypotension. A logistic model predicted the presence of MAC at baseline and Cox proportional models assessed the relative contribution of autonomic neuropathy and traditional risk factors for the outcomes of ulceration, amputation, and death. Results: MAC was identified in 181 subjects, no MAC in 253 subjects, and 39 were excluded due to disagreement between observers. Both measures of autonomic neuropathy were independent predictors of MAC at baseline, even after adjustment for vibration sensation loss in a logistic model. MAC was associated with an increased risk for ulceration (hazards ratio. HR: 2.1, 95% confidence intervals, CI, 1.4-3.1), amputation (HR 3.3, 95% CI 1.5-7.4), and mortality (HR 1.6, 95% CI 1.1-2.2). The addition of either autonomic measure of neuropathy did not change the MAC HR or significantly improved the fit of the model. Conclusions: Our hypothesis that the excess mortality, amputation, and ulceration in persons with MAC could be explained by autonomic neuropathy measured as postural hypotension or heart rate variability with measured respiration was not supported. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Univ Washington, Seattle ERIC VA Puget Sound, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Res & Dev Serv, Seattle, WA USA. Univ Washington, Dept Vasc Surg, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Surg Serv, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Nursing, Dept Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA. Univ Washington, Dept Orthoped Surg, Seattle, WA 98195 USA. RP Boyko, EJ (reprint author), Univ Washington, Seattle ERIC VA Puget Sound, S-111 GIMC,1660 S Columbian Way, Seattle, WA 98108 USA. NR 30 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD MAR-APR PY 2002 VL 16 IS 2 BP 165 EP 171 AR PII S1056-8727(01)00178-7 DI 10.1016/S1056-8727(01)00178-7 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 537RD UT WOS:000174772500006 PM 12039400 ER PT J AU Reiner, B Siegel, E Scanlon, M AF Reiner, B Siegel, E Scanlon, M TI Changes in technologist productivity with implementation of an enterprisewide PACS SO JOURNAL OF DIGITAL IMAGING LA English DT Article DE picture archival and communications system; technologist productivity ID FILMLESS AB The purpose of this report is to determine what effect filmless operation has on technologist productivity when compared with traditional film-based operation. Retrospective data on technologist productivity was collected from the study institution before and after implementation of PACS using workload reports and payroll records. Departmentwide technologist productivity was defined as the number of examinations per full-time equivalent (exams/FTE) and correlated with local and nationwide standards operating in traditional film-based operations. During film-based operation, technologist productivity was comparable between the study institution and nationwide standards, allowing for the unique examination volumes and modality mix. After implementation of a large-scale PACS, technologist productivity was found to increase 34% above that of national standards and 48% that of the local control site, Implementation of an enterprisewide PACS offers the potential to significantly improve departmentwide technologist productivity when compared with traditional film-based operation. C1 Univ Maryland, Sch Med, Dept Radiol, Baltimore, MD 21201 USA. Vet Affairs Med Ctr, Dept Radiol, Philadelphia, PA USA. RP Reiner, B (reprint author), Dept Diagnost Radiol, 10 N Greene St, Baltimore, MD 21201 USA. NR 18 TC 14 Z9 14 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD MAR PY 2002 VL 15 IS 1 BP 22 EP 26 DI 10.1007/s10278-002-0999-y PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 569YR UT WOS:000176631300004 PM 12134211 ER PT J AU Esnaola, NF Lauwers, GY Mirza, NQ Nagorney, DM Doherty, D Ikai, I Yamaoka, Y Regimbeau, JM Belghiti, J Curley, SA Ellis, LM Vauthey, JN AF Esnaola, NF Lauwers, GY Mirza, NQ Nagorney, DM Doherty, D Ikai, I Yamaoka, Y Regimbeau, JM Belghiti, J Curley, SA Ellis, LM Vauthey, JN TI Predictors of microvascular invasion in patients with hepatocellular carcinoma who are candidates for orthotopic liver transplantation SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 19-23, 2001 CL ATLANTA, GEORGIA SP Soc Surg Alimentary Tract DE hepatocellular carcinoma; liver transplantation; vascular invasion ID HEPATIC RESECTION; NATURAL-HISTORY; INTRAHEPATIC RECURRENCE; COMPLICATING CIRRHOSIS; ARTERIAL PORTOGRAPHY; NEEDLE-BIOPSY; PROGNOSIS; SURVIVAL; CT; METASTASIS AB Microvascular invasion affects survival after orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). We sought to identify preoperative predictors of microvascular invasion in patients with HCC who were candidates for OLT. A cohort of 245 patients who underwent resection for HCC and fulfilled the criteria for OLT (i.e., single tumors : 5 cm or no more than three tumors less than or equal to3 cm) were identified from a multi-institutional database. Thirty-three percent of the patients had pathologic evidence of microvascular invasion. Thirty percent of patients with single tumors and 47% with multiple tumors had microvascular invasion (P = 0.04). Only 25% of patients with tumors smaller than less than or equal to2 cm had microvascular invasion, compared to 31% and 50% with tumors greater than 2 to 4 cm or larger than 4 cm, respectively (P = 0.01). Tumor grade was highly correlated with microvascular invasion: 12% of patients with well-differentiated tumors had microvascular invasion, compared to 29% and 50% with moderately or poorly differentiated tumors, respectively (P < 0.001). The independent predictors of microvascular invasion were tumor size greater than 4 cm (odds ratio [OR], 3.0, 95% confidence interval [0], 1.2 to 7.1), and high tumor grade (OR, 6.3; 95% CI, 2.0 to 19.9). Tumor size and grade are strong predictors of microvascular invasion. A tumor biopsy with pathologic grading at the time of pretransplantation ablative therapy could improve selection of patients with HCC for OLT. C1 Univ Texas, MD Anderson Canc Ctr, Dept Surg, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Mayo Clin, Dept Surg, Rochester, MN USA. Kyoto Univ, Dept Surg, Grad Sch Med, Kyoto, Japan. Hop Beaujon, Dept Surg, Paris, France. RP Vauthey, JN (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Surg, 1515 Holcombe Blvd,Box 444, Houston, TX 77030 USA. FU PHS HHS [T32] NR 49 TC 148 Z9 160 U1 0 U2 9 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 2002 VL 6 IS 2 BP 224 EP 232 AR PII S1091-255X(01)00015-4 DI 10.1016/S1091-255X(01)00015-4 PG 9 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 627EM UT WOS:000179920300023 PM 11992808 ER PT J AU Linder, JA Sim, I AF Linder, JA Sim, I TI Antibiotic treatment of acute bronchitis in smokers - A systematic review SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review DE bronchitis, antibiotics; smoking; systematic review ID CONTROLLED TRIALS; AMBULATORY CARE; ACUTE COUGH; ADULTS; PLACEBO; ERYTHROMYCIN; PHYSICIANS; METAANALYSIS; DOXYCYCLINE; INFECTIONS AB Objective: Community physicians in the United States prescribe antibiotics to 80% to 90% of smokers with acute bronchitis. We performed a systematic review of the literature to determine the efficacy of antibiotics for smokers with acute bronchitis. Design. A MEDLINE search was done using the keywords bronchitis, cough, and antibiotics to identify English language articles published from January 1966 to September 2001. Randomized, placebo-controlled trials of antibiotics in previously healthy smokers and nonsmokers with acute bronchitis were included. Measurements and main results: For each study, we abstracted information on design, size, inclusion criteria, patient characteristics, and outcomes. Of 2,029 articles in the original search, 109 relevant articles were retrieved and reviewed. There have been no studies specifically addressing antibiotic use in smokers with acute bronchitis. Nine randomized, placebo-controlled trials of antibiotics have included 774 patients and over 276 smokers. Lack of subgroup reporting for smokers precluded meta-analysis. In 7 trials, smoking status did not predict or alter patients' response to antibiotics. In one trial, trimethoprim/sulfamethoxazole resulted in less-frequent cough overall, but not among smokers. In another trial, erythromycin reduced symptom scores only among nonsmokers while antibiotic-treated smokers had a trend toward higher symptom scores. Conclusion: Although no trials have specifically addressed antibiotic use in smokers with acute bronchitis, existing data suggest that any benefit of antibiotics is the same or less for smokers than for nonsmokers. C1 Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94143 USA. RP Linder, JA (reprint author), Massachusetts Gen Hosp, Dept Med, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. FU BHP HRSA HHS [5T32PE11001-12] NR 31 TC 19 Z9 19 U1 1 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 2002 VL 17 IS 3 BP 230 EP 234 DI 10.1046/j.1525-1497.2002.10405.x PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 543UH UT WOS:000175119200010 PM 11929510 ER PT J AU Yu, M Wang, EX Liu, YF Cao, DJ Jin, NY Zhang, CWH Bartlam, M Rao, ZH Tien, P Gao, GF AF Yu, M Wang, EX Liu, YF Cao, DJ Jin, NY Zhang, CWH Bartlam, M Rao, ZH Tien, P Gao, GF TI Six-helix bundle assembly and characterization of heptad repeat regions from the F protein of Newcastle disease virus SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID PARAMYXOVIRUS FUSION PROTEIN; SENDAI VIRUS; CELL-FUSION; PEPTIDE INHIBITOR; MEMBRANE-FUSION; CORE TRIMER; GLYCOPROTEINS; REPLICATION; HYPOTHESIS; DOMAIN AB Paramyxoviruses may adopt a similar fusion mechanism to other enveloped viruses, in which an antiparallel six-helix bundle structure is formed post-fusion in the heptad repeat (HR) regions of the envelope fusion protein. In order to understand the fusion mechanism and identify fusion inhibitors of Newcastle disease virus (NDV), a member of the Paramyxoviridae family, we have developed an E. coli system that separately expresses the F protein HR1 and HR2 regions as GST fusion proteins. The purified cleaved HR1 and HR2 have subsequently been assembled into a stable six-helix bundle heterotrimer complex. Furthermore, both the GST fusion protein and the cleaved HR2 show virus-cell fusion inhibition activity (IC50 of 1.07-2.93 muM). The solubility of the GST-HR2 fusion protein is much higher than that of the corresponding peptide. Hence this provides a plausible method for large-scale production of HR peptides as virus fusion inhibitors. C1 Chinese Acad Sci, Inst Microbiol, Dept Mol Virol, Beijing 100080, Peoples R China. Chinese Acad Agr Sci, Harbin Vet Res Inst, Harbin 150001, Peoples R China. Univ Mil Supplies, Dept Virus Res, Changchun 130062, Peoples R China. Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Tsing Hua Univ, Struct Biol Lab, Beijing 100084, Peoples R China. Tsing Hua Univ, MOE Lab Prot Sci, Beijing 100084, Peoples R China. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Childrens Hosp,Lab Mol Med, Boston, MA 02115 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Gao, GF (reprint author), Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Med, Room 7508, Oxford OX3 9DU, England. OI Bartlam, Mark/0000-0001-5173-5080 NR 26 TC 37 Z9 41 U1 0 U2 4 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD MAR PY 2002 VL 83 BP 623 EP 629 PN 3 PG 7 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 523XP UT WOS:000173983100015 PM 11842257 ER PT J AU Vig, EK Brodkin, KI Raugi, GJ Gladstone, H AF Vig, EK Brodkin, KI Raugi, GJ Gladstone, H TI Blue rubber bleb nevus syndrome in a patient with ataxia and dementia SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Geriatrics-Society CY MAY, 2000 CL NASHVILLE, TENNESSEE SP Amer Geriatr Soc ID NATURAL-HISTORY; CAVERNOUS ANGIOMAS; MALFORMATIONS; INVOLVEMENT; KRIT1 AB Blue rubber bleb nevus syndrome (BRBNS), an uncommon disorder characterized by cavernous hemangiomas, most often of the skin and gastrointestinal tract, is usually diagnosed during childhood and young adulthood. We made this diagnosis in an octogenarian referred to a geriatric medicine clinic because of concerns about his ability to live independently. Ataxia, dementia, focal neurologic signs, and bluish/purplish vascular nodules on his lips, buccal mucosa, tongue, chest, and neck were noted on physical examination. Magnetic resonance imaging (MRI) revealed an old left parietal infarction, multiple cavernous hemangiomas most densely concentrated in the subcortical structures and cerebellum, and areas of hemosiderin deposition. Skin biopsy findings were consistent with hemangioma. The physical examination, MRI, and skin biopsy made a diagnosis of BRBNS likely. The patient's ataxia, dementia, and other neurologic signs can be explained by previous hemorrhage from the vascular malformations in his brain. Blue rubber bleb nevus syndrome is an uncommon cause of a relatively common geriatric syndrome presentation. C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Calif Los Angeles, Dept Med, Sch Med, Div Dermatol, Los Angeles, CA USA. Univ Washington, Harborview Med Ctr, Div Gerontol & Geriatric, Seattle, WA 98104 USA. Univ Washington, Harborview Med Ctr, Div Dermatol, Dept Med, Seattle, WA 98104 USA. RP Vig, EK (reprint author), Univ Washington, Harborview Med Ctr, Div Gerontol & Geriatric, 325 9Th Ave,Box 359755, Seattle, WA 98104 USA. NR 19 TC 5 Z9 7 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 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD SPR PY 2002 VL 15 IS 1 BP 7 EP 11 DI 10.1177/089198870201500102 PG 5 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 532GT UT WOS:000174466500002 PM 11936246 ER PT J AU Harwood, DG Sultzer, DL AF Harwood, DG Sultzer, DL TI "Life is not worth living": Hopelessness in Alzheimer's disease SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article ID NEUROBEHAVIORAL RATING-SCALE; MINI-MENTAL-STATE; VASCULAR DEMENTIA; ELDERLY SUBJECTS; MEMORY DEFICIT; CORNELL SCALE; DEPRESSION; DIAGNOSIS; SUICIDE; RELIABILITY AB This study investigated the prevalence and clinical correlates of hopelessness among 91 patients diagnosed with probable Alzheimer's disease (AD) according to National Institute of Neurological Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria. Hopeless ideation was measured with Item 3 on the Hamilton Depression Rating Scale (Suicide), which inquires specifically whether the patient thinks "life is not worth living." The results showed that hopelessness was present in 10% (n = 9) of the sample. Patients with these cognitions evidenced greater psychological symptoms of mood disturbance and more insight into their cognitive and functional impairments. Unrelated factors included age, education, Mini-Mental State Examination score, neurovegetative signs of depression, affective expressions of depression, agitation/disinhibition, and psychosis. Although indifference is frequent in AD, these results indicate that thoughts of hopelessness are also a common phenomenon, occurring in approximately 10% of our probable AD cohort. These thoughts appear to be related to the subjective expressions of depression and anxiety rather than the neurovegetative or affective signs and are more prominent among patients with greater deficit awareness. C1 VA Greater Los Angeles Healthcare Syst, Mental Hlth Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Neuropsychiat Inst & Hosp, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Sultzer, DL (reprint author), W Los Angeles VA Healthcare Ctr, 11301 Wilshire Blvd,3 South,116AF, Los Angeles, CA 90073 USA. FU NIMH NIH HHS [MH00910, MH56031] NR 45 TC 16 Z9 17 U1 2 U2 5 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 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD SPR PY 2002 VL 15 IS 1 BP 38 EP 43 DI 10.1177/089198870201500108 PG 6 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 532GT UT WOS:000174466500008 PM 11936242 ER PT J AU Ring, D Roberge, C Morgan, T Jupiter, JB AF Ring, D Roberge, C Morgan, T Jupiter, JB TI Osteotomy for malunited fractures of the distal radius: A comparison of structural and nonstructural autogenous bone grafts SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE distal radius; fracture; malunion; osteotomy; bone graft ID FIXATION AB Two cohorts of 10 patients who had a corrective osteotomy for a malunited fracture of the distal radius with a pi-shaped plate and screw fixation were compared retrospectively to see whether the outcome was affected by using a nonstructural cancellous bone graft compared with a trapezoidal corticocancellous bone graft. The indications for the osteotomy, surgical techniques, and postoperative rehabilitation were consistent and all surgical procedures were done by the same surgeon. All osteotomies healed without loss of the surgical correction. Follow-up radiographic and functional results were comparable between groups. Use of a nonstructural, cancellous only bone graft-appealing in its relative simplicity-seems safe and efficacious. Copyright (C) 2002 by the American Society for Surgery of the Hand. C1 Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. Clin Chirurg Plast & Esthet Haute Ville, Quebec City, PQ, Canada. RP Ring, D (reprint author), 11 Hancock St,Unit 4, Boston, MA 02114 USA. NR 13 TC 41 Z9 45 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAR PY 2002 VL 27A IS 2 BP 216 EP 222 DI 10.1053/jhsu.2002.32076 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 531VE UT WOS:000174437300004 PM 11901380 ER PT J AU Berfield, AK Abrass, CK AF Berfield, AK Abrass, CK TI IGF-1 induces foam cell formation in rat glomerular mesangial cells SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE mesangial cell; IGF-1; atherosclerosis; lipids; glomerulosclerosis; phagocytosis ID GROWTH-FACTOR-I; LOW-DENSITY-LIPOPROTEIN; SCAVENGER RECEPTOR; INSULIN; CHOLESTEROL; BINDING; CULTURE; ENDOCYTOSIS; NEPHROPATHY; EXPRESSION AB When rat glomerular mesangial cells (MCs) are cultured with IGF-1 they accumulate intracellular lipid and take on foam cell morphology. These changes were characterized by electron microscopy and Nile red staining. To define the mechanism responsible for IGF-1-mediated lipid uptake, MCs were evaluated for endocytosis, scavenger receptor activity, and receptor-mediated uptake by the LDL receptor. Lipid accumulation was markedly increased when MCs were cultured with IGF. The primary route of uptake was through enhanced endocytosis. Lipid-laden MCs have decreased phagocytic capacity and disrupted cytoskeletons. These data show that IGF-1 induces MC to take on a foam cell morphology and that lipid-laden MCs have impaired phagocytic function. C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Abrass, CK (reprint author), Vet Affairs Puget Sound Hlth Care Syst, 111A,1660 S Columbian Way, Seattle, WA 98108 USA. NR 42 TC 13 Z9 14 U1 0 U2 0 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 2002 VL 50 IS 3 BP 395 EP 403 PG 9 WC Cell Biology SC Cell Biology GA 525GR UT WOS:000174061000010 PM 11850441 ER PT J AU Jansson, M Panoutsakopoulou, V Baker, J Klein, L Cantor, H AF Jansson, M Panoutsakopoulou, V Baker, J Klein, L Cantor, H TI Cutting edge: Attenuated experimental autoimmune encephalomyelitis in Eta-1/osteopontin-deficient mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOCYTE-T; TRANSGENIC MICE; IN-VITRO; OSTEOPONTIN; DEFINITION; INDUCTION; GAMMA; ALPHA; MACROPHAGES; MODULATION AB Recent studies indicate that early T lymphocyte activation 1 (Eta-1), also known as osteopontin, is a cytokine contributing to the development of Th1 immunity. In the present report, the role of Eta-1 in experimental autoimmune encephalomyelitis (EAE), a disease associated with Th1 immunity, was examined by analysis of disease progression in Eta-l-deficient (Eta-1(-/-)) mice. Although incidence and onset of peptide-induced EAE were found to be similar in Eta-1(-/-) and Eta-1(+/+) mice, Eta-1(-/-) mice displayed significantly lower mean maximal clinical score and faster recovery without spontaneous relapses. Accordingly, decreased inflammatory infiltration and demyelination were observed in the spinal cords of Eta-1(-/-) mice. Furthermore, in comparison to Eta-1(+/+), Eta-1(-/-) CD4(+) T cells had reduced expression of IFN-gamma and TNF-alpha upon ex vivo restimulation. Taken together, these results suggest that Eta-1 may sustain autoimmune responses by assisting in maintenance of Th1 immunity during EAE. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Cantor, H (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. RI Klein, Ludger/G-8785-2011; OI Panoutsakopoulou, Vily/0000-0002-1569-1508 FU NIAID NIH HHS [AI 12184, AI 37562, AI 48125] NR 24 TC 136 Z9 140 U1 1 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 MAR 1 PY 2002 VL 168 IS 5 BP 2096 EP 2099 PG 4 WC Immunology SC Immunology GA 524AR UT WOS:000173990200004 PM 11859094 ER PT J AU Koido, S Tanaka, Y Chen, DS Kufe, D Gong, JL AF Koido, S Tanaka, Y Chen, DS Kufe, D Gong, JL TI The kinetics of in vivo priming of CD4 and CD8 T cells by dendritic/tumor fusion cells in MUC1-transgenic mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MUC1 TRANSGENIC MICE; IN-VIVO; CROSS-PRESENTATION; CARCINOMA-CELLS; ANTIGEN; DIFFERENTIATION; TOLERANCE; IMMUNITY; GENERATION; VACCINATION AB Previous work has demonstrated that dendritic/tumor fusion cells induce potent antitumor immune responses in vivo and in vitro. However, little is known about the migration and homing of fusion cells after s.c. injection or the kinetics of CD4(+) and CD8(+) T cell activation. In the present study, fluorescence-labeled dendritic/MUC1-positive tumor fusion cells (FC/MUC1) were injected s.c. into MUC1-transgenic mice. The FC/MUC1 migrated to draining lymph nodes and were closely associated with T cells in a pattern comparable with that of unfused dendritic cells. Immunization of MUC1-transgenic mice with FC/MUC1 resulted in proliferation of T cells and induced MUC1-specific CD8(+) CTL. Moreover, CD4+ T cells activated by FC/MUC1 were multifunctional effectors that produced IL-2, IFN-gamma, IL-4, and IL-10. These findings indicate that both CD4(+) and CD8(+) T cells can be primed in vivo by FC/MUC1 immunization. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Gong, JL (reprint author), Beth Israel Deaconess Med Ctr, KS 135,330 Brookline Ave, Boston, MA 02215 USA. FU NCI NIH HHS [R01 CA 87057-01] NR 46 TC 57 Z9 59 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2002 VL 168 IS 5 BP 2111 EP 2117 PG 7 WC Immunology SC Immunology GA 524AR UT WOS:000173990200006 PM 11859096 ER PT J AU Meiler, SE Hung, RR Gerszten, RE Gianetti, J Li, L Matsui, T Gimbrone, MA Rosenzweig, A AF Meiler, SE Hung, RR Gerszten, RE Gianetti, J Li, L Matsui, T Gimbrone, MA Rosenzweig, A TI Endothelial IKK beta signaling is required for monocyte adhesion under laminar flow conditions SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE inflammation; vascular endothelium; adhesion molecules; monocytes; adenoviral gene transfer ID NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; CHRONIC MYELOID-LEUKEMIA; ABL TYROSINE KINASE; CHEMOATTRACTANT PROTEIN-1; VASCULAR ENDOTHELIUM; ATHEROSCLEROTIC LESION; APOLIPOPROTEIN-E; DEFICIENT MICE; GENE-TRANSFER AB S. E. MEILER, R. R. HUNG, R. E. GERSZTEN, J. GIANFTTI, L. LI, T. MATSUI, M. A. GIMBRONE, JR. AND A. ROSENZWEIG, Endothelial IKKbeta Signaling is Required for Monocyte Adhesion under Laminar Flow Conditions. Journal of Molecular and Cellular Cardiology (2002) 34, 349-359. Endothelial activation induces expression of pro-inflammatory molecules that are thought to play an important role in atherogenesis through enhanced vascular monocyte recruitment. Many pro-inflammatory endothelial signals are transcriptionally regulated by members of the NF-kappaB family. The serine-threonine kinase. IKKbeta, can mediate NF-kappaB activation although several alternative pathways exist. To test whether IKKbeta is necessary for cytokine activation of human vascular endothelium and endothelial recruitment of human monocytes under laminar flow, we constructed a recombinant adenoviral vector carrying a dominant negative mutant of IKKbeta (Ad.dnIKKbeta) to transduce human umbilical vein endothelial cells (HUVEC) in vitro. We found that dnIKKbeta expression effectively blocked NF-kappaB activation as assessed by nuclear translocation of NF-kappaB. IkappaB degradation, and NF-kappaB dependent reporter expression, without affecting activation of the other relevant Signaling pathways, SAPK/JNK and p38. Furthermore, overexpression of dnIKKbeta in TNF-alpha-stimulated HUVEC blocked induction of the surface adhesion molecules E-selectin, ICAM-1, and VCAM-1. Under simulated physiologic flow conditions, both firm adhesion and rolling of human peripheral monocytes on dnIKKbeta-transduced endothelial monolayers were markedly inhibited. We conclude that IKKbeta is necessary for the cytokine-induced inflammatory phenotype of human endothelium and endothelial recruitment of human monocytes under flow. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp E, Cardiovasc Res Ctr, Program Cardiovasc Gene Therapy, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Div Vasc Res, Boston, MA 02115 USA. RP Rosenzweig, A (reprint author), Massachusetts Gen Hosp E, Cardiovasc Res Ctr, Program Cardiovasc Gene Therapy, 114 16th St,Rm 2600, Charlestown, MA 02129 USA. EM rosenzweig@helix.mgh.harvard.edu FU NHLBI NIH HHS [HL36028, HL59521, HL65584, HL04250, HL54202, HL67768]; NIAID NIH HHS [AI40970] NR 47 TC 13 Z9 14 U1 0 U2 0 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 2002 VL 34 IS 3 BP 349 EP 359 DI 10.1006/jmcc.2001.1519 PG 11 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 545ED UT WOS:000175202600010 PM 11945026 ER PT J AU Mollica, RF Cui, XJ McInnes, K Massagli, MP AF Mollica, RF Cui, XJ McInnes, K Massagli, MP TI Science-based policy for psychosocial interventions in refugee camps - A Cambodian example SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; HEALTH; TRAUMA; WAR; SYMPTOMATOLOGY; INSTRUMENT; MORTALITY; TORTURE AB No longer are the high rates of psychiatric morbidity associated with mass violence in refugee populations invisible to the humanitarian assistance community. However, identification of mental health risk and protective factors that can be utilized by policy planners is still lacking. The objective of this report is to provide an analytic approach to determining these factors. A description is provided from the first large-scale epidemiological study of Cambodian refugees confined to the Thailand-Cambodian border in the 1980s and 1990s. The original data from this study are reanalyzed to evaluate the mental health impact of psychosocial factors subject to the influence of camp authorities, such as opportunities in the refugee camp environment and personal behaviors, in addition to trauma. The results suggest the extraordinary capacity of refugees to protect themselves against mental illness despite horrific life experiences. The recommendation emerges for refugee policy makers to create programs that support work, indigenous religious practices, and culture-based altruistic behavior among refugees. As refugee mental health policy receives increasing attention from the international community, it must consist of recommendations and practices based on scientific analysis and empirical evidence. C1 Harvard Univ, Massachusetts Gen Hosp, Program Refugee Trauma, Cambridge, MA 02139 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Mollica, RF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Program Refugee Trauma, 22 Putnam St, Cambridge, MA 02139 USA. NR 41 TC 38 Z9 38 U1 2 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 2002 VL 190 IS 3 BP 158 EP 166 DI 10.1097/00005053-200203000-00004 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 535RH UT WOS:000174659400004 PM 11923650 ER PT J AU Kaufman, ML Kimble, MO Kaloupek, DG McTeague, LM Bachrach, P Forti, AM Keane, TM AF Kaufman, ML Kimble, MO Kaloupek, DG McTeague, LM Bachrach, P Forti, AM Keane, TM TI Peritraumatic dissociation and physiological response to trauma-relevant stimuli in Vietnam combat veterans with posttraumatic stress disorder SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID THEATER VETERANS; RELIABILITY; VALIDITY; EVENTS; SAMPLE; FEMALE; SCALE AB A recent study found that female rape victims with acute posttraumatic stress disorder (PTSD) who received a high score on the Peritraumatic Dissociative Experiences Questionnaire exhibited suppression of physiological responses during exposure to trauma-related stimuli. The goal of our present study was to test whether the same relationship holds true for male Vietnam combat veterans with chronic PTSD, using secondary analyses applied to data derived from a Veteran's Affairs Cooperative Study. Vietnam combat veterans (N = 1238) completed measures to establish combat-related PTSD diagnostic status, extent of PTSD-related symptomatic distress, and presence of dissociative symptoms during their most stressful combat-related experiences. Extreme subgroups of veterans with current PTSD were classified as either low dissociators (N = 118) or high dissociators (AT = 256) based on an abbreviated version of the Peritraumatic Dissociative Experiences Questionnaire. Dependent variables reflected subjective distress along with heart rate, skin conductance, electromyographic, and blood pressure data when responding to neutral and trauma-related audiovisual and imagery presentations. Veterans in the current PTSD group had significantly higher dissociation scores than did veterans in the lifetime and never PTSD groups. Among veterans with current PTSD, high dissociators reported greater PTSD-related symptomatic distress than did low dissociators, but the groups did not differ with respect to physiological reactivity to the trauma-related laboratory presentations. Our results replicate the previously reported relationship between peritraumatic dissociation and PTSD status in Vietnam combat veterans. However, we found no association between peritraumatic dissociation and the extent of physiological responding to trauma-relevant cues in male veterans with chronic combat-related PTSD. C1 Natl Ctr Posttraumat Stress Disorder, VA Boston Healthcare Syst, Behav Sci Div, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Kaufman, ML (reprint author), Natl Ctr Posttraumat Stress Disorder, VA Boston Healthcare Syst, Behav Sci Div, Psychol 116B-2,150 S Huntington Ave, Boston, MA 02130 USA. OI Kaloupek, Danny/0000-0002-0795-593X FU NIMH NIH HHS [R29 1MH58215] NR 21 TC 36 Z9 38 U1 0 U2 3 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 2002 VL 190 IS 3 BP 167 EP 174 DI 10.1097/00005053-200203000-00005 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 535RH UT WOS:000174659400005 PM 11923651 ER PT J AU Pless, M Rizzo, JF Shang, JZ AF Pless, M Rizzo, JF Shang, JZ TI Orbital apex syndrome: a rare presentation of extramedullary hematopoiesis - Case report and review of literature SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE polycythemia rubra vera; extramedullary hematopoiesis; optic nerve; visual loss ID SPINAL-CORD COMPRESSION; BETA-THALASSEMIA; MYELOFIBROSIS; MANAGEMENT; MR AB We describe a case of compressive neuropathy in the orbital apex due to extramedullary hematopoiesis (EMH). A 64-year-old man with Polycythemia Rubra Vera developed unilateral visual loss, proptosis, complete ophthalmoplegia, and facial paresis. Bone marrow biopsy showed myelofibrosis. Magnetic resonance imaging demonstrated enhancement at the orbital apex and subtle optic canal narrowing. Decompression of the optic nerve with biopsy of surrounding bone showed EMH. The patient received a course of radiation without benefit. We suggest including the diagnosis of EMH of the orbital apex bones in the differential diagnosis of patients with myeloproliferative disorders who develop an orbital apex syndrome. C1 Univ Pittsburgh, Med Ctr, Div Neuro Ophthalmol, Pittsburgh, PA 15213 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. Univ Pittsburgh, Med Ctr, Dept Neurol, Pittsburgh, PA 15260 USA. RP Pless, M (reprint author), Univ Pittsburgh, Med Ctr, Div Neuro Ophthalmol, 203 Lothrop St, Pittsburgh, PA 15213 USA. NR 22 TC 5 Z9 5 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAR PY 2002 VL 57 IS 1 BP 37 EP 40 DI 10.1023/A:1015789630250 PG 4 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 571TB UT WOS:000176734100005 PM 12125965 ER PT J AU Mann, MB Wu, SJ Rostamkhani, M Tourtellotte, W MacMurray, JP Comings, DE AF Mann, MB Wu, SJ Rostamkhani, M Tourtellotte, W MacMurray, JP Comings, DE TI Association between the phenylethanolamine N-methyltransferase gene and multiple sclerosis SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE multiple sclerosis; PNMT; norepinephrine; epinephrine; SNP ID MULTIVARIATE-ANALYSIS; CONDUCT DISORDER; SUSCEPTIBILITY; SCREEN; TWINS; LOCI; PNMT; ENCEPHALOMYELITIS; DISEASE; LINKAGE AB Phenylethanolamine N-methyltransferase (PNMT), the terminal enzyme of the catecholamine biosynthesis pathway, catalyzes the conversion of norepinephrine (NE) to epinephrine (EPI). PNMT is a candidate gene for multiple sclerosis (MS) for two reasons. PNMT is known to map to a region identified in two genome screens for MS and it directly regulates the amounts of NE and EPI, both of which play a significant role in the modulation of the innate immune response. The frequencies of two promoter polymorphisms of the PNMT gene showed genetic association in a case-control study of 108 patients with MS and 774 ethnically and age-matched control subjects. In subjects with MS, significant differences in the frequency of the GG genotype at the G - 387A marker and the AA genotype at the G - 182A marker were observed. Additionally, when both markers were combined and evaluated, highly significant differences between the polymorphism distributions in patients with MS and control subjects were detected. The data suggest that these promoter polymorphisms of the PNMT gene, both independently and cumulatively, show association with MS. (C) 2002 Elsevier Science B.V. All rights reserved. C1 MGI Appl Genomics, Dept Genomics, Long Beach, CA USA. Los Angeles Vet Affairs Med Ctr, Dept Neurol, Los Angeles, CA USA. Calif State Polytech Univ Pomona, Dept Biol Sci, Pomona, CA 91768 USA. City Hope Natl Med Ctr, Dept Med Genet, Duarte, CA 91010 USA. RP Mann, MB (reprint author), Case Western Reserve Univ, Sch Med, Dept Genet, Cleveland, OH 44106 USA. OI Mann, Michael/0000-0002-7515-6515 NR 31 TC 12 Z9 14 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 2002 VL 124 IS 1-2 BP 101 EP 105 AR PII S0165-5728(02)00009-7 DI 10.1016/S0165-5728(02)00009-7 PG 5 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 536EW UT WOS:000174688600013 PM 11958827 ER PT J AU Kleihues, P Louis, DN Scheithauer, BW Rorke, LB Reifenberger, G Burger, PC Cavenee, WK AF Kleihues, P Louis, DN Scheithauer, BW Rorke, LB Reifenberger, G Burger, PC Cavenee, WK TI The WHO classification of tumors of the nervous system SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Review ID PRIMITIVE NEUROECTODERMAL TUMORS; DISTINCT CLINICOPATHOLOGICAL ENTITY; MOLECULAR-GENETIC-ANALYSIS; FAVORABLE PROGNOSIS; MENINGIOMA PROGRESSION; TANYCYTIC EPENDYMOMA; LIPOMATOUS MEDULLOBLASTOMA; SPORADIC MEDULLOBLASTOMAS; GLIOBLASTOMA-MULTIFORME; GENOMIC ALTERATIONS AB The new World Health Organization (WHO) classification of nervous system tumors. published in 2000, emerged from a 1999 international consensus conference of neuropathologists. New entities include chordoid glioma of the third ventricle. cerebellar liponeurocytoma, atypical teratoid/rhabdoid tumor, and perineurioma, Several histological variants were added, including tanycytic ependymoma. large cell medulloblastoma, and rhabdoid meningioma. The WHO grading scheme was updated and, for meningiomas, extensively revised. In recognition of the emerging role of molecular diagnostic approaches to tumor classification. genetic profiles have been emphasized, as in the distinct subtypes of glioblastoma and the already clinically useful 1p and 19q markers for oligodendroglioma and 22q/INI1 for atypical teratoid/rhabdoid tumors, In accord with the new WHO Blue Book series, the actual classification is accompanied by extensive descriptions and illustrations of clinicopathological characteristics of each tumor type, including molecular genetic features. predictive factors, and separate chapters on inherited tumor syndromes. The 2000 WHO classification of nervous system tumors aims at being used and implemented by the neuro-oncology and biomedical research communities worldwide. C1 Int Agcy Res Canc, F-69372 Lyon, France. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Dusseldorf, Inst Neuropathol, D-4000 Dusseldorf, Germany. Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA. Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. RP Kleihues, P (reprint author), Int Agcy Res Canc, 150 Cours Albert Thomas, F-69372 Lyon, France. NR 75 TC 1156 Z9 1225 U1 6 U2 53 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAR PY 2002 VL 61 IS 3 BP 215 EP 225 PG 11 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 530BK UT WOS:000174335600001 PM 11895036 ER PT J AU Hurley, RA Reneman, L Taber, KH AF Hurley, RA Reneman, L Taber, KH TI Ecstasy in the brain: A model for neuroimaging SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID MDMA ECSTASY; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; SEROTONIN NEUROTOXICITY; EMISSION-TOMOGRAPHY; USERS; TRANSPORTER; INGESTION; NEURONS; MEMORY; DRUG C1 Baylor Coll Med, Dept Radiol, 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, Herbert J Frensley Ctr Imaging Res, Houston, TX 77030 USA. Acad Med Ctr, Sch Neurosci, Amsterdam, Netherlands. RP Taber, KH (reprint author), Baylor Coll Med, Dept Radiol, 1 Baylor Plaza, Houston, TX 77030 USA. NR 31 TC 9 Z9 9 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 2002 VL 14 IS 2 BP 125 EP 129 DI 10.1176/appi.neuropsych.14.2.125 PG 5 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 555JB UT WOS:000175790000001 PM 11983786 ER PT J AU Lim, GT Mendez, MF Bronstein, YL Jouben-Steele, L Vinters, HV AF Lim, GT Mendez, MF Bronstein, YL Jouben-Steele, L Vinters, HV TI Clinicopathologic case report: Akinetic mutism with findings of white matter hyperintensity SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID FRONTAL-SUBCORTICAL CIRCUITS; VASCULAR DEMENTIA; BINSWANGERS-DISEASE; MAGNETIC-RESONANCE; LEUKO-ARAIOSIS; ALZHEIMERS-DISEASE; OXYGEN-METABOLISM; LESIONS; DIAGNOSIS; MRI C1 Univ Calif Los Angeles, Med Ctr, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Med Ctr, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Med Ctr, Brain Res Inst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Med Ctr, Inst Neuropsychiat, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Syst, Neurobehav Unit 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 44 TC 2 Z9 2 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 2002 VL 14 IS 2 BP 214 EP 221 DI 10.1176/appi.neuropsych.14.2.214 PG 8 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 555JB UT WOS:000175790000014 PM 11983799 ER PT J AU Ferrante, RJ Andreassen, OA Dedeoglu, A Ferrante, KL Jenkins, BG Hersch, SM Beal, MF AF Ferrante, RJ Andreassen, OA Dedeoglu, A Ferrante, KL Jenkins, BG Hersch, SM Beal, MF TI Therapeutic effects of coenzyme Q(10) and remacemide in transgenic mouse models of Huntington's disease SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Huntington's disease; excitotoxicity; coenzyme Q(10); remacemide; mitochondria; transgenic ID ENERGY-METABOLISM; MITOCHONDRIAL ENCEPHALOMYOPATHY; INTRANUCLEAR INCLUSIONS; IN-VIVO; LESIONS; MICE; HYDROCHLORIDE; ACID; DYSFUNCTION; IMPAIRMENT AB There is substantial evidence that bioenergetic defects and excitotoxicity may play a role in the pathogenesis of Huntington's disease (HD). Potential therapeutic strategies for neuro-degenerative diseases in which there is reduced energy metabolism and NMDA-mediated excitotoxicity are the administration of the mitochondrial cofactor coenzyme Q(10) and the NMDA antagonist remacemide. We found that oral administration of either coenzyme Q(10) or remacemide significantly extended survival and delayed the development of motor deficits, weight loss, cerebral atrophy, and neuronal intranuclear inclusions in the R6/2 transgenic mouse model of HD. The combined treatment, using coenzyme Q(10) and remacemide together, was more efficacious than either compound alone, resulting in a similar to32 and 17% increase in survival in the R6/2 and N171-82Q mice, respectively. Magnetic resonance imaging showed that combined treatment significantly attenuated ventricular enlargement in vivo. These studies further implicate defective energy metabolism and excitotoxicity in the R6/2 and N171-82Q transgenic mouse models of HD and are of interest in comparison with the outcome of a recent clinical trial examining coenzyme Q(10) and remacemide in HD patients. C1 Bedford Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Bedford, MA 01730 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Massachusetts Gen Hosp, Serv Neurol, Neurochem Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. Massachusetts Gen Hosp, Ctr Aging Genet & Neurodegenerat, Serv Neurol, Boston, MA 02114 USA. RP Beal, MF (reprint author), New York Hosp, Cornell Med Ctr, Dept Neurol, 525 E 68th St, New York, NY 10021 USA. FU NCCIH NIH HHS [AT00613]; NIA NIH HHS [AG13846, AG12992]; NINDS NIH HHS [NS35255, NS37102, NS38180] NR 47 TC 253 Z9 257 U1 0 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 1 PY 2002 VL 22 IS 5 BP 1592 EP 1599 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 527NQ UT WOS:000174192500014 PM 11880489 ER PT J AU Lu, Q Mukhopadhyay, NK Griffin, JD Paredes, M Medina, M Kosik, KS AF Lu, Q Mukhopadhyay, NK Griffin, JD Paredes, M Medina, M Kosik, KS TI Brain Armadillo protein delta-catenin interacts with Abl tyrosine kinase and modulates cellular morphogenesis in response to growth factors SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE neurite extension; phosphorylation; STI571; Abl effector; Abl tyrosine kinase ID SIGNAL-TRANSDUCTION; C-ABL; INHIBITOR STI571; ROLES; CELLS; NEURULATION; MECHANISM; OUTGROWTH; ADHESION; FAMILY AB delta-Catenin associates with adhesive junctions and facilitates cellular morphogenesis (Lu et aL, 1999). Here we show that delta-catenin colocalizes with actin filaments and AN tyrosine kinase in the growth cones of cultured hippocampal neurons. PC12 cells induced to express delta-catenin show accelerated neurite extension upon nerve growth factor (NGF) stimulation. STI571, an AN family kinase inhibitor, further accentuates these stimulatory effects. delta-Catenin is a potent substrate for AN in vitro using an immunocomplex assay and most of the Abl-induced tyrosine phosphorylation within cells is present in the N-terminus of delta-catenin. When delta-catenin-expressing epithelial cells are induced to scatter in response to hepatocyte growth factor (HGF), STI571 leads to the rapid redistribution of delta-catenin and changes in cellular morphology. We suggest that delta-catenin is a possible AN substrate and acts downstream of AN to orchestrate actin-based cellular morphogenesis. (C) 2002 Wiley-Liss, Inc. C1 Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Lu, Q (reprint author), E Carolina Univ, Brody Sch Med, Dept Anat & Cell Biol, 7N 84 Brody Med Sci Bldg,600 Moye Blvd, Greenville, NC 27858 USA. FU NIA NIH HHS [AG06601] NR 28 TC 44 Z9 45 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD MAR 1 PY 2002 VL 67 IS 5 BP 618 EP 624 DI 10.1002/jnr.10151 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 527BV UT WOS:000174166400007 PM 11891774 ER PT J AU Eskandar, EN Borges, LF Budzik, RF Putman, CM Ogilvy, CS AF Eskandar, EN Borges, LF Budzik, RF Putman, CM Ogilvy, CS TI Spinal dural arteriovenous fistulas: experience with endovascular and surgical therapy SO JOURNAL OF NEUROSURGERY LA English DT Article; Proceedings Paper CT 67th Annual Meeting of the American-Association-of-Neurological-Surgeons CY APR 24-29, 1999 CL NEW ORLEANS, LOUISIANA SP Amer Assoc Neurol Surgeons DE spine; dural; arteriovenous fistula ID CLINICAL-FEATURES; VASCULAR MALFORMATIONS; MEDULLARY VEINS; VENOUS DRAINAGE; LONG-TERM; MYELOPATHY; EMBOLIZATION; CORD; MANAGEMENT; INTERRUPTION AB Object. Although the pathophysiology of spinal dural arteriovenous fistulas (AVFs) has recently been elucidated, the optimal treatment strategy for these lesions has yet to be defined. Current management techniques include endovascular embolization or microsurgical obliteration. Methods. The authors reviewed the records and angiograms of all patients with spinal dural AVFs treated at Massachusetts General Hospital over a 6-year period ( 1992-1998). During this period, it was intended initially to treat all patients with ernbolization and to reserve surgery for those in whom endovascular treatment failed or in cases in which pretreatment evaluation suggested that endovascular therapy would be ineffective or unsafe,. A total of 26 patients with spinal dural AVFs ere treated: there were 22 men and 4 women with a mean age of 65 years (range 39-79 years). Lesions were located in the following areas: five in foramen magnum/cervical, 13 in thoracic, Five in lumbar, and three in sacral. Twenty-three (88%) of 26 patient,, underwent embolization and three ( 12%) of 23 patients underwent surgery as the primary mode of treatment. Of the 23 patients in whom embolization was performed or attempted. nine (39%) ultimately required surgery. All patients were stabilized or improved following definitive treatment, as assessed by the Aminoff-Logue scores. There was one death secondary to a myocardial infarction. Conclusions, These data demonstrate that endovascular therapy can be successful as an initial treatment for the majority of patients: however. there is a 39% failure rate, which is not observed following surgical therapy, Once a definitive therapy has been achieved using either technique virtually all patients are either stabilized or improved. C1 Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Intervent Neuroradiol Serv, Boston, MA 02114 USA. RP Ogilvy, CS (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Vincent Burnham Bldg,Room 702, Boston, MA 02114 USA. NR 41 TC 62 Z9 68 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD MAR PY 2002 VL 96 IS 2 SU S BP 162 EP 167 DI 10.3171/spi.2002.96.2.0162 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 527FX UT WOS:000174177000004 PM 12450278 ER PT J AU Wolfe, J Proctor, SP Erickson, DJ Hu, H AF Wolfe, J Proctor, SP Erickson, DJ Hu, H TI Risk factors for multisymptom illness in US army veterans of the Gulf War SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID POPULATION-BASED SURVEY; SELF-REPORTED SYMPTOMS; AIR-POLLUTION; HEALTH; MORTALITY; STRESS; EXPOSURES AB This research study examined the prevalence of symptoms and identified risk factors for reported symptoms among a group of Army Gulf War (GW) veterans. A survey was mailed to all members of the Ft. Devens cohort in 1997, representing the third assessment of a group that consisted of 2949 US Army soldiers deployed to the Gulf, and was studied initially in 1991. A total of 1290 subjects responded to the mailed survey; aggressive follow-up methods to address non-response bias were employed. Subjects were classified as having multisymptom illness if they reported symptoms from at least two of three symptom categories (fatigue, mood cognition, musculoskeletal). Sixty percent of the respondents met criteria for multisymptom illness. Female gender, lower levels of education, psychological symptoms, self-reported use of a medical clinic in the Gulf, ingestion of anti-nerve gas pills (pyridostigmine bromide), anthrax vaccination, tent heaters, exposure to oil fire smoke, and chemical odors were significantly related to multisymptom illness in logistic regression analyses. Analyses in which subjects were stratified by level of psychological symptoms revealed different sets Of GW-service environmental exposures and suggest that subgroups of GW veterans may have different sets of fisk factors. C1 VA Boston Healthcare Syst, Boston Environm Hazards Ctr 116B4, Boston, MA 02130 USA. VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Cambridge, MA 02138 USA. RP Proctor, SP (reprint author), VA Boston Healthcare Syst, Boston Environm Hazards Ctr 116B4, 150 S Huntington Ave, Boston, MA 02130 USA. NR 56 TC 50 Z9 50 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD MAR PY 2002 VL 44 IS 3 BP 271 EP 281 DI 10.1097/00043764-200203000-00015 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 530QQ UT WOS:000174370800014 PM 11911029 ER PT J AU Sullivan, LG Hasan, T Wright, M Mankin, HJ Towle, CA AF Sullivan, LG Hasan, T Wright, M Mankin, HJ Towle, CA TI Photodynamic treatment has chondroprotective effects on articular cartilage SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article ID GROWTH-FACTOR-BETA; LATENT TRANSFORMING GROWTH-FACTOR-BETA-1; MURINE KNEE-JOINT; PROTEOGLYCAN SYNTHESIS; PLATE CHONDROCYTES; ORGAN-CULTURES; IN-VIVO; THERAPY; EXPRESSION; OSTEOARTHRITIS AB Osteoarthritis (OA) is a disabling joint disease for which there is currently no cure. It is characterized by the destruction of articular cartilage. One strategy that is being explored for protecting the cartilage in OA is the administration of transforming growth factor-P, which in vitro antagonizes cartilage degradation initiated by catabolic stimulants such as interleukin-1 (IL-1). The problems associated with selective delivery of the growth factor to chondrocytes, undesirable side-effects on joint tissues, and short biological half-life have led us to explore modalities aimed at activating transforming growth factor-P that is stored in the cartilage as latent complexes. Photodynamic therapy is a two-step protocol of tissue sensitization with a light-activatable chemical called a photosensitizer followed at some interval by irradiation with the appropriate wavelength visible light. Biological effects are typically elicited through oxygen-dependent photochemistry without heat generation. Transforming growth factor-PI can be activated by oxidative mechanism(s), prompting us to explore whether photodynamic technology can be harnessed to modulate cartilage metabolism. Disks of bovine articular cartilage were photosensitized by incubation with a chlorin(c6)-succinylated polylysine conjugate and irradiated with 1-2 J/cm(2) red light (lambda(max) = 671 nm). This two-step regimen dramatically inhibited IL-1-stimulated proteoglycan degradation and concomitantly increased latent and active transforming growth factor-P I in culture medium. This research may lead to the development of minimally invasive photodynamic therapy in which light is delivered to locally activate a chondroprotective program in photosensitized cartilage in the context of OA. (C) 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Orthopaed Res Labs,GRJ 1124, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,Wellman Labs Photomed, Boston, MA 02114 USA. RP Towle, CA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Orthopaed Res Labs,GRJ 1124, 55 Fruit St, Boston, MA 02114 USA. FU NIAMS NIH HHS [R01 AR16265] NR 47 TC 6 Z9 7 U1 1 U2 2 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 2002 VL 20 IS 2 BP 241 EP 248 AR PII S0736-0266(01)00113-9 DI 10.1016/S0736-0266(01)00113-9 PG 8 WC Orthopedics SC Orthopedics GA 531GA UT WOS:000174406600011 PM 11918303 ER PT J AU Misra, M Levitsky, LL Lee, MM AF Misra, M Levitsky, LL Lee, MM TI Transient hyperthyroidism in an adolescent with hydatidiform mole SO JOURNAL OF PEDIATRICS LA English DT Editorial Material ID HUMAN CHORIONIC-GONADOTROPIN; THYROID-FUNCTION; THYROTROPIC ACTIVITY; HYPEREMESIS GRAVIDARUM; TSH RECEPTOR; PREGNANCY; HCG; CHORIOCARCINOMA; DISEASE; HORMONE C1 Duke Univ, Med Ctr, Div Pediat Endocrinol, Durham, NC 27710 USA. Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. RP Lee, MM (reprint author), Duke Univ, Med Ctr, Div Pediat Endocrinol, Box 3080,308 Bell Bldg, Durham, NC 27710 USA. OI Lee, Mary/0000-0002-7204-4884 FU NICHD NIH HHS [K02HD01367] NR 36 TC 4 Z9 4 U1 0 U2 0 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 2002 VL 140 IS 3 BP 362 EP 366 DI 10.1067/mpd.2002.120514 PG 5 WC Pediatrics SC Pediatrics GA 542TZ UT WOS:000175061500017 PM 11953736 ER PT J AU Pitiphat, W Garcia, RI Douglass, CW Joshipura, KJ AF Pitiphat, W Garcia, RI Douglass, CW Joshipura, KJ TI Validation of self-reported oral health measures SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE validity; questionnaires; interviews; epidemiologic methods; periodontitis; dental caries; oral health measures; root canal therapy; dental prosthesis ID CLINICAL EXAMINATION; DENTAL-CARIES; VALIDITY; QUESTIONNAIRE; DISEASE; RATINGS AB Objectives: To assess the validity of self-reported oral disease and health care measures in two populations. Methods: Telephone interviews were conducted among a subsample of participants in the VA Dental Longitudinal Study (VADLS) asking them about periodontal disease status and treatment. Radiographic alveolar bone loss evaluated at all the interproximal sites was used as the standard. A separate study was carried out among first-time patients at the Harvard School of Dental Medicine (HSDM) student clinic. Self-reported measures were obtained by a self-administered questionnaire and compared with clinical and radiograph examinations. The measures used were based on published work that demonstrated good validity of self-reported periodontal measures among health professionals. Results: Among 145 VADLS participants, self-reports of periodontal disease showed a good specificity (59.8%-90.7%), but low sensitivity (17.7%-64.7%). Among 58 HSDM patients, the self-reported numbers of remaining teeth, fillings, root canal therapy, and prosthesis were strongly correlated with clinical records (r=0.74-1.0); self-report was less accurate for measures of periodontal disease (r=0.56) and decayed teeth (r=0.47). Conclusions: Self-reports provide reasonably valid estimates for numbers of remaining teeth, fillings, root canal therapy, and fixed and removable prostheses. However, they appear to be less useful for the assessment of dental caries and periodontal disease in the two populations we have studied. There remains a need and potential to further develop self-report oral health measures that are valid for use in large population studies. Such self-report measures would yield great cost and time savings. C1 Harvard Univ, Sch Dent Med, Dept Oral Hlth Policy & Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Khon Kaen Univ, Fac Dent, Khon Kaen, Thailand. VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, VA Dent Longitudinal Study, Boston, MA USA. Boston Univ, Goldman Sch Dent Med, Dept Hlth Policy & Hlth Serv Res, Boston, MA 02215 USA. RP Joshipura, KJ (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Hlth Policy & Epidemiol, 188 Longwood Ave, Boston, MA 02115 USA. FU NIDCR NIH HHS [K24 DE00419] NR 32 TC 115 Z9 119 U1 0 U2 9 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD SPR PY 2002 VL 62 IS 2 BP 122 EP 128 DI 10.1111/j.1752-7325.2002.tb03432.x PG 7 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 617JY UT WOS:000179359600009 PM 11989207 ER PT J AU Blake, DJ Bodine, C AF Blake, DJ Bodine, C TI An overview of assistive technology for persons with multiple sclerosis SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Review ID DYSFUNCTION AB Multiple sclerosis (MS) is a progressive neurologic disease clinically characterized by episodes of focal disorder of the cranial nerves, spinal cord, and the brain. MS affects a significant number of young adults, and they most often face a future of progressive functional losses as more of their central nervous system and cranial nerves are affected. As the disease progresses, they have new impairments with accompanying limitations in activities, restrictions to their participation in life, and compromised quality of life. Assistive technology includes any item that is used to maintain or improve functional capabilities. The rehabilitation healthcare provider has many opportunities to intervene with assistive technologies to decrease activity limitations and participation restrictions. The purpose of this article is to (1) review the impairments and associated activity limitations and participations restrictions experienced by persons with MS, (2) provide an overview of high- and low-tech assistive technologies appropriate for persons with MS, (3) discuss funding opportunities for assistive technologies, (4) review cur-rent studies of assistive technology used for persons with MS and discuss future research directions, and (5) consider assistive technology as an intervention for disability prevention. C1 Denver Vet Affairs Med Ctr, Phys Med Serv, Denver, CO 80220 USA. Denver Vet Affairs Med Ctr, Rehabil Serv, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Dept Rehabil Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Assist Technol Partners, Denver, CO 80218 USA. RP Blake, DJ (reprint author), Denver Vet Affairs Med Ctr, Phys Med Serv, Denver, CO 80220 USA. NR 28 TC 18 Z9 19 U1 0 U2 6 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 2002 VL 39 IS 2 BP 299 EP 312 PG 14 WC Rehabilitation SC Rehabilitation GA 556RR UT WOS:000175863200014 PM 12051472 ER PT J AU Eroglu, A Nahum, RT Isaacson, K Toth, TL AF Eroglu, A Nahum, RT Isaacson, K Toth, TL TI Laser-assisted intracytoplasmic sperm injection in human oocytes SO JOURNAL OF REPRODUCTIVE MEDICINE LA English DT Article DE intracytoplasmic sperm injections; laser surgery; oocytes ID ZONA-PELLUCIDA; MOUSE OOCYTES; SPERMATOZOA; POLYVINYLPYRROLIDONE; FERTILIZATION; BEAM AB OBJECTIVE: To explore potential applications of a non-contact 1,480-nm diode laser to intracytoplasmic sperm injection (ICSI) of human oocytes. STUDY DESIGN: Human oocytes obtained from in vitro fertilization (IVF) patients and failed to fertilize 24-48 hours after conventional IVF were used for ICSI along with discarded sperm. A noncontact, 1,480-nm diode laser was employed to immobilize sperm, to open a hole in the zona pellucida (ZP) and to perform ICSI through the hole. After ICSI and its simulation, oocytes were examined for formation of pronuclei, cleavage and normality of the cytoskeleton. RESULTS: The 1,480-nm diode laser permitted fast and easy sperm immobilization and microdrilling of ZP to facilitate microinjection. Of the 78 injected oocytes, 53 (68%) survived the procedure, and 13 (25%) of them formed two pronuclei by 18 hours. Further culture of two fertilized eggs resulted in cleavage tip to the eight-cell stage before cease of culture. Four oocytes were fixed after simulation of the procedure without injecting sperm. None of them showed gross abnormalities in cytoskeletal organization. CONCLUSION. A noncontact, 1,480-nm diode laser can be used for the immobilization of sperm and for opening a hole in the ZP to facilitate ICSI, biopsy manipulation toward preimplantation genetic diagnosis and assisted hatching. C1 Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Shriners Burns Hosp, Surg Serv, Boston, MA USA. RP Toth, TL (reprint author), Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. NR 24 TC 4 Z9 5 U1 0 U2 0 PU SCI PRINTERS & PUBL INC PI ST LOUIS PA PO DRAWER 12425 8342 OLIVE BLVD, ST LOUIS, MO 63132 USA SN 0024-7758 J9 J REPROD MED JI J. Reprod. Med. PD MAR PY 2002 VL 47 IS 3 BP 199 EP 203 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 534LH UT WOS:000174587500005 PM 11933684 ER PT J AU Palsson, R Choi, HK Niles, JL AF Palsson, R Choi, HK Niles, JL TI Opportunistic infections are preceded by a rapid fall in Antineutrophil cytoplasmic antibody (ANCA) titer in patients with ANCA associated vasculitis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE opportunistic infection; antineutrophil cytoplasmic antibodies; vasculitis ID PNEUMOCYSTIS-CARINII PNEUMONIA; WEGENERS-GRANULOMATOSIS; SYSTEMIC VASCULITIS; DISEASE-ACTIVITY; IMMUNOSUPPRESSIVE THERAPY; CYCLOPHOSPHAMIDE THERAPY; AUTOANTIBODIES; GLOMERULONEPHRITIS; DIAGNOSIS; NEUTROPHILS AB Objective. To study the clinical course and changes in antineutrophil cytoplasmic antibody (ANCA) titers in patients with ANCA associated vasculitis (AAV) who developed opportunistic infections. Methods. Among the patients with AAV tested in the Immunopathology Laboratory at the Massachusetts General Hospital between 1989 and 1998, all patients who experienced opportunistic infections (n = 16) were included. We retrospectively studied their clinical features and examined the relationship between changes in ANCA titer and the onset of the opportunistic infections. ANCA titers were measured by antigen-specific ELISA. Results. Of the 16 AAV patients with opportunistic infection, 15 had no evidence for active vasculitis at the time of the infection. Among these 15 patients, opportunistic infections were associated with a steep fall in ANCA titers. There was no consistent pattern of change in C-reactive protein levels, In 7 patients, the immunosuppressive regimen was increased for new clinical findings shortly before the diagnosis of an opportunistic infection, despite the absence of histologic documentation of active vasculitis. Three of these 7 patients died. One patient, who did not experience a significant fall in ANCA titer, i.e., less than 4-fold from his prior peak, was simultaneously found to have Pneumocystis carinii pneumonia and biopsy proven active vasculitis. Conclusion. Our data strongly suggest that opportunistic infections in patients with AAV are associated with negative or rapidly failing ANCA titers. Therefore, changes in ANCA titer can help distinguish opportunistic infections from vasculitis flares when patients with AAV present with indeterminate clinical findings. C1 Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Arthrit Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Niles, JL (reprint author), Massachusetts Gen Hosp, Dept Med, Renal Unit, CPZ 701,55 Fruit St, Boston, MA 02114 USA. NR 31 TC 3 Z9 3 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 2002 VL 29 IS 3 BP 505 EP 510 PG 6 WC Rheumatology SC Rheumatology GA 527XW UT WOS:000174214100015 PM 11908563 ER PT J AU Weeks, WB Yano, EM Rubenstein, LV AF Weeks, WB Yano, EM Rubenstein, LV TI Primary care practice management in rural and urban veterans health administration settings SO JOURNAL OF RURAL HEALTH LA English DT Article; Proceedings Paper CT Annual Meeting of the Veterans-Administration-Health-Services-Research-and-Deveolpment-Service (HSR&D) CY FEB, 2001 CL WASHINGTON, D.C. ID ACCESS; VA AB Limited access to specialty care in rural settings may result in more expectations of primary care providers and a higher demand for primary care. The authors used survey and administrative data from 1999 from the Veterans Health Administration (VHA) to compare primary care practice management and performance in 19 rural to 103 urban VHA hospitals nationally. Rural VHA hospitals were smaller, less likely to be academically affiliated, and had fewer integrated specialty care services. Primary care providers in rural settings were more likely to manage specialty care services, provide continuity across patient care settings, and have complete responsibility for a broader range of services. However, rural hospitals had more staff per patient allocated to primary care than did urban hospitals. Patients in rural settings received comparable quality care to those in urban settings, and they appeared to be more satisfied with the care they received. Within the VHA system, primary care providers in rural settings provided a broader range of services than those in urban ones. This increased breadth may be attributable to the lack of availability of integrated specialty care services in rural settings. Because of this broader range of responsibilities, the provision of primary care in rural settings may require higher staffing patterns and may be inherently more costly than in urban settings; therefore, researchers should be cautious when comparing primary care expenditures across rural and urban settings. C1 Vet Adm Med Ctr, White River Jct, VT USA. VA Greater Los Angeles Healthcare Syst, Vet Affairs Greater Los Angeles Hlth Serv Res & D, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA 90406 USA. RP Weeks, WB (reprint author), Vet Adm Med Ctr, 111Q, White River Jct, VT USA. RI Weeks, William/G-7436-2014 NR 16 TC 23 Z9 23 U1 0 U2 0 PU NATL RURAL HEALTH ASSOC PI KANSAS CITY PA ONE WEST ARMOUR BLVD, STE 301, KANSAS CITY, MO 64111 USA SN 0890-765X J9 J RURAL HEALTH JI J. Rural Health PD SPR PY 2002 VL 18 IS 2 BP 298 EP 303 DI 10.1111/j.1748-0361.2002.tb00890.x PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 588GN UT WOS:000177693900005 PM 12135150 ER PT J AU Werner, SL Murray, TA Hawkins, RJ Gill, TJ AF Werner, SL Murray, TA Hawkins, RJ Gill, TJ TI Relationship between throwing mechanics and elbow valgus in professional baseball pitchers SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article AB Valgus elbow stress leads to medial tension and lateral compression injuries in baseball pitchers of all ages. This study was undertaken to investigate the relationship between elbow stress in professional baseball pitchers and the kinematic parameters of pitching mechanics. This was clone in an attempt to understand valgus extension overload better and in an effort to improve preventive and rehabilitative protocols. Highspeed video data were collected on 40 professional pitchers in game situations during the 7 998 and 7 999 Cactus League season in Arizona, as part of Major League Baseball Spring Training. A multiple linear regression analysis was used to relate elbow valgus to kinematic parameters of pitching mechanics. The resulting analysis produced an adjusted multiple R-2 value of 0.974, indicating that nearly 100% of the variance in valgus stress on the elbow was explained by the parameters in the regression equation. This ability to explain over 97% of the variance in valgus stress is significant. The parameters of pitching mechanics related to elbow valgus may be assessed and optimized, if necessary, in order to decrease the magnitude of elbow stress in pitching. C1 Tulane Inst Sports Med, New Orleans, LA 70118 USA. Steadman Hawkins Sports Med Fdn, Orleans, LA USA. Steadman Hawkins Clin, Vail, CO USA. Massachusetts Gen Hosp, Boston, MA USA. RP Werner, SL (reprint author), Tulane Inst Sports Med, 202 McAlister Extens, New Orleans, LA 70118 USA. NR 13 TC 51 Z9 51 U1 4 U2 17 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD MAR-APR PY 2002 VL 11 IS 2 BP 151 EP 155 DI 10.1067/mse.2002.121481 PG 5 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 553FB UT WOS:000175664200008 PM 11988726 ER PT J AU Baer, JS AF Baer, JS TI Student factors: Understanding individual variation in college drinking SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Review ID ALCOHOL-RELATED PROBLEMS; HEAVY DRINKING; OUTCOME EXPECTANCIES; SENSATION SEEKING; SOCIAL-CONTEXT; GAME PARTICIPATION; GENDER DIFFERENCES; ANXIETY DISORDERS; YOUNG ADULTHOOD; BINGE DRINKING AB Objective: Research on individual differences in drinking rates and associated problems among college students is reviewed. Method: Studies are included if completed within U.S, college and university samples and found in published scientific literature as identified by several searches of national databases. Results. The resulting review suggests first that the extant literature is large and varied in quality, as most studies use questionnaire responses from samples of convenience in cross-sectional designs. Evidence from studies of college samples does consistently suggest that alcohol is consumed for several different purposes for different psychological effects in different contexts. A pattern Of impulsivity sensation seeking is strongly related to increased drinking among students. This pattern is supported by research into personality, drinking motives, alcohol expectancies anti drinking contexts. A second pattern of drinking associated with negative emotional states is also documented. Some long-term consequences of this second pattern have been described. Social processes appear especially important for drinking in many college venues and may contribute to individual differences in drinking more than enduring personality differences, Conclusions. Future research efforts should test interactive and mediating models of multiple risk factors and address developmental processes. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. RP Baer, JS (reprint author), VA Puget Sound Hlth Care Syst, S-116-ATC,1660 S Columbian Way, Seattle, WA 98108 USA. NR 105 TC 52 Z9 54 U1 3 U2 15 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD MAR PY 2002 SU 14 BP 40 EP 53 PG 14 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 548KN UT WOS:000175387300005 ER PT J AU Wilens, TE Biederman, J Brown, S Tanguay, S Monuteaux, MC Blake, C Spencer, TJ AF Wilens, TE Biederman, J Brown, S Tanguay, S Monuteaux, MC Blake, C Spencer, TJ TI Psychiatric comorbidity and functioning in clinically referred preschool children and school-age youths with ADHD SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE preschool child; attention-deficit/hyperactivity disorder; comorbidity ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; SEMISTRUCTURED INTERVIEW; BEHAVIOR PROBLEMS; DRUG-USE; ADOLESCENTS; ADJUSTMENT; BOYS; SEVERITY AB Objective: Although the literature documents that attention-deficit/hyperactivity disorder (ADHD) commonly onsets prior to age 6, little is known about the disorder in preschool children. We evaluated the clinical characteristics, psychiatric comorbidity, and functioning of preschool children and school-age youths with ADHD referred to a pediatric psychiatric clinic for evaluation. Method: Structured psychiatric interviews assessing lifetime psychopathology by DSM-III-R criteria were completed with parents about their children. Family, social, and overall functioning were also assessed at intake. Results: We identified 165 children with ADHD aged 4 to 6 years (preschool children) and 381 youths aged 7 to 9 years (school-age) with ADHD, Despite being younger, preschool children had similar rates of comorbid psychopathology compared with school-age youths with ADHD. There was an earlier onset of ADHD and co-occurring psychopathology in the preschool children compared to school-age youths. Both preschool children and school-age youths had substantial impairment in school, social, and overall functioning. Conclusions: The results of this study suggest that despite being significantly younger, clinically referred preschool children with ADHD are reminiscent of school-age youths with ADHD in the quality of ADHD, high rates of comorbid psychopathology, and impaired functioning. Follow-up of these clinically referred preschool children with ADHD to evaluate the stability of their diagnoses, treatment response, and their long-term outcome are necessary. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. RP Wilens, TE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Res Program Pediat Psychopharmacol, ACC 725,15 Parkman St, Boston, MA 02114 USA. NR 41 TC 172 Z9 176 U1 1 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 2002 VL 41 IS 3 BP 262 EP 268 DI 10.1097/00004583-200203000-00005 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 526FD UT WOS:000174118400005 PM 11886020 ER PT J AU Nurcombe, B Drell, MJ Leonard, HL McDermott, JF Mathew AF Nurcombe, B Drell, MJ Leonard, HL McDermott, JF Mathew TI Clinical problem solving: The case of Matthew, part III SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article C1 Univ Queensland, Royal Brisbane Hosp, Mental Hlth Ctr, Herston, Qld, Australia. LSU Hlth Sci Ctr, New Orleans, LA USA. Brown Univ, Sch Med, Providence, RI 02912 USA. Univ Hawaii, Sch Med, Honolulu, HI 96822 USA. RP Nurcombe, B (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Bulfinch 351, Boston, MA 02114 USA. NR 4 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 2002 VL 41 IS 3 BP 344 EP 353 DI 10.1097/00004583-200203000-00015 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 526FD UT WOS:000174118400015 PM 11886030 ER PT J AU Ellis, CN Drake, LA Prendergast, MM Abramovits, W Boguniewicz, M Daniel, CR Lebwohl, M Stevens, SR Whitaker-Worth, DL Cheng, JW Tong, KB AF Ellis, CN Drake, LA Prendergast, MM Abramovits, W Boguniewicz, M Daniel, CR Lebwohl, M Stevens, SR Whitaker-Worth, DL Cheng, JW Tong, KB TI Cost of atopic dermatitis and eczema in the United States SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID CHILDREN AB Background: Atopic dermatitis/eczema (AD/E) is a common disease. Few studies have attempted to quantify the cost to third-party payers. Objective: Our purpose was to identify, the annual cost of medical services and prescription drugs for the treatment of AD/E to private insurance and Medicaid payers in the United States. Methods: We used a retrospective study design employing claims data from 1997 and 1998 from a private insurer and a state Medicaid program to analyze costs incurred. Beneficiaries were considered to have AD/E if they had at least one claim in 1997 with a primary or secondary listing of 1 of 3 diagnosis codes: 691.8, other atopic dermatitis and related conditions; 692.9, contact dermatitis and other eczema when no cause is specified; or 373.3, noninfectious dermatoses of eyelid. Patients who did not meet the diagnosis criteria served as a control group in each payer for comparisons of expenditures with the AD/E group. Results: Disease prevalence was 2.4% (private insurer) to 2.6% (Medicaid) of all eligible beneficiaries, and 3.5% to 4.1% of patients submitted at least one health care claim during the study period. Medicaid-insured patients used outpatient hospital visits and hospitalizations at a greater rate than did privately insured patients; neither used emergency departments extensively. The third-party payer cost of illness for AD/E ranged from $0.9 billion to $3.8 billion when projected across the total number of persons younger than 65 years insured by private insurers and Medicaid in the United States. More than one fourth of all health care costs for patients with AD/E may be attributed to AD/E and co-morbid conditions. Conclusions: Annual costs of AD/E are similar to those of other diseases such as emphysema, psoriasis, and epilepsy Patients incur significant costs associated with AD/E and co-morbid conditions. C1 Univ Michigan, Sch Med, Dept Dermatol, Ann Arbor, MI 48109 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Fujisawa Healthcare Inc, Deerfield, IL USA. Baylor Univ, Med Ctr, Dallas, TX USA. Univ Texas, SW Med Sch, Dallas, TX 75230 USA. Natl Jewish Med & Res Ctr, Denver, CO USA. Univ Mississippi, Jackson, MS 39216 USA. NYU, Mt Sinai Sch Med, New York, NY USA. Case Western Reserve Univ, Univ Hosp Cleveland, Cleveland, OH 44106 USA. Univ Connecticut, Ctr Hlth, Farmington, CT USA. Quorum Consulting Inc, San Francisco, CA USA. RP Ellis, CN (reprint author), Univ Michigan, Sch Med, Dept Dermatol, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. NR 19 TC 106 Z9 109 U1 2 U2 7 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAR PY 2002 VL 46 IS 3 BP 361 EP 370 DI 10.1067/mjd.2002.120528 PG 10 WC Dermatology SC Dermatology GA 528XC UT WOS:000174269200002 PM 11862170 ER PT J AU Best, WR Khuri, SF Phelan, M Hur, K Henderson, WG Demakis, JG Daley, J AF Best, WR Khuri, SF Phelan, M Hur, K Henderson, WG Demakis, JG Daley, J TI Identifying patient preoperative risk factors and postoperative adverse events in administrative databases: Results from the Department of Veterans Affairs National Surgical Quality Improvement Program SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID CLINICAL COMORBIDITY INDEX; PROSPECTIVE-PAYMENT SYSTEM; ARTERY BYPASS-SURGERY; CLAIMS DATA; COMPLICATION RATES; ACCURACY; CARE; ADJUSTMENT; MORTALITY; CLASSIFICATION AB BACKGROUND: The Department of Veterans Affairs (DVA) National Surgical Quality Improvement Program (NSQIP) employs trained nurse data collectors to prospectively gather preoperative patient characteristics and 30-day postoperative outcomes for most major operations in 123 DVA hospitals to provide risk-adjusted outcomes to centers as quality indicators. It has been suggested that routine hospital discharge abstracts contain the same information and would provide accurate and complete data at much lower cost. STUDY DESIGN: With preoperative risks and 30-day outcomes recorded by trained data collectors as criteria standards, ICD-9-CM hospital discharge diagnosis codes in the Patient Treatment File (PTF) were tested for sensitivity and positive predictive value. ICD-9-CM codes for 61 preoperative patient characteristics and 21 postoperative adverse events were identified. RESULTS: Moderately good ICD-9-CM matches of descriptions were found for 37 NSQIP preoperative patient characteristics (61%); good data were available from other automated sources for another 15 (25%). ICD-9-CM coding was available for only 13 (45%) of the top 29 predictor variables. In only three (23%) was sensitivity and in only four (31%) was positive predictive value greater than 0.500. There were ICD-9-CM matches for all 21 NSQIP postoperative adverse events; multiple matches were appropriate for most. Postoperative occurrence was implied in only 41%; same breadth of clinical description in only 23%. In only four (7%) was sensitivity and only two (4%) was positive predictive value greater than 0.500. CONCLUSION: Sensitivity and positive predictive value of administrative data in comparison to NSQIP data were poor. We cannot recommend substitution of administrative data for NSQIP data methods. (J Am Coll Surg 2002;194:257-266. (C) 2002 by the American College of Surgeons). C1 Hines VA Midw Ctr Hlth Serv & Policy Res, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. Vet Affairs Boston Hlth Care Syst, Dept Surg, W Roxbury, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. VA Hosp, Cooperat Studies Program Coordinating Ctr, Hines, IL USA. VHA Cent Off, Hlth Serv Res & Dev Serv, Washington, DC USA. Vet Affairs Boston Hlth Care Syst, Dept Med, W Roxbury, MA USA. Vet Affairs Boston Hlth Care Syst, Hlth Serv Res & Dev Program, W Roxbury, MA USA. Massachusetts Gen Hosp, Partners Healthcare Syst, Inst Hlth Policy, Ctr Hlth Syst Design & Evaluat, Boston, MA 02114 USA. RP Best, WR (reprint author), Hines VA Midw Ctr Hlth Serv & Policy Res, 151H, Hines, IL 60141 USA. NR 39 TC 174 Z9 176 U1 3 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD MAR PY 2002 VL 194 IS 3 BP 257 EP 266 AR PII S1072-7515(01)01183-8 DI 10.1016/S1072-7515(01)01183-8 PG 10 WC Surgery SC Surgery GA 528ER UT WOS:000174231900001 PM 11893128 ER PT J AU Liu, SI Siewert, B Raptopoulos, V Hodin, RA AF Liu, SI Siewert, B Raptopoulos, V Hodin, RA TI Factors associated with conversion to laparotomy in patients undergoing laparoscopic appendectomy SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID RANDOMIZED CONTROLLED TRIALS; ACUTE APPENDICITIS; SUSPECTED APPENDICITIS; CT; CHOLECYSTECTOMY; METAANALYSIS; SURGERY AB BACKGROUND: Laparoscopic appendectomy (LA) has been increasingly adopted for its advantages over the open technique, but there is a possibility of conversion to open appendectomy, (OA) if complications occur or the extent of inflammation prohibits successful dissection. This study, aimed to identify the preoperative predictors for conversion from laparoscopic to open appendectomy. STUDY DESIGN: Medical records of 705 consecutive patients who underwent surgery for suspected appendicitis were reviewed retrospectively. LA was attempted in 595 patients by 25 different Surgeons. Factors evaluated were age, gender, body mass index, previous abdominal surgery, previous appendicitis attack, pain, nausea, vomiting, fever, duration of symptoms, local or diffuse tenderness, leukocyte count and surgeon's experience in LA. RESULTS: Conversion to CIA occurred in 58 patients (9.7%). The most common reason for conversion was dense adhesions due to inflammation, followed by localized perforation and diffuse peritonitis. Based on 261 patients evaluated by CT scan preoperatively, significant factors in the final multivariate analysis associated with conversion to CIA were age greater than or equal to 65 [Odds ratio (OR) = 3.78, 95% CI:1.11-12.84], diffuse tenderness on physical examination (OR = 11.32, 95% CI: 1.32-96.62), and a surgeon with less experience in LA (less than or equal to10 operations, OR = 3.38, 95% Cl: 1.02-11.17). The presence of significant fat stranding associated with fluid accumulation, inflammatory mass or localized abscess in CT scan also significantly, increased the possibility of conversion (OR = 5.60, 95% CI:2.48-12.65). CONCLUSIONS: Identifying the potential factors for conversion preoperatively may assist the surgeons in making decisions concerning the management of patients with appendicitis and in the judicious use of LA. (J Am Coll Surg 2002; 194:298-305. (C) 2002 by the American College of Surgeons). C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. Natl Yang Ming Univ, Vet Gen Hosp Kaohsiung, Dept Surg, Kaohsiung, Taiwan. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA USA. RP Hodin, RA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,Gray 504, Boston, MA 02114 USA. NR 38 TC 36 Z9 40 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD MAR PY 2002 VL 194 IS 3 BP 298 EP 305 AR PII S1072-7515(01)01164-4 DI 10.1016/S1072-7515(01)01164-4 PG 8 WC Surgery SC Surgery GA 528ER UT WOS:000174231900006 PM 11893133 ER PT J AU Lee, WPA AF Lee, WPA TI What's new in plastic surgery SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Plast Surg, Boston, MA 02114 USA. RP Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Plast Surg, WAC-453,15 Parkman St, Boston, MA 02114 USA. NR 60 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 1072-7515 EI 1879-1190 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD MAR PY 2002 VL 194 IS 3 BP 324 EP 334 AR PII S1072-7515(01)01181-4 DI 10.1016/S1072-7515(01)01181-4 PG 11 WC Surgery SC Surgery GA 528ER UT WOS:000174231900009 PM 11894856 ER PT J AU Terpenning, M Shay, K AF Terpenning, M Shay, K TI Oral health is cost-effective to maintain but costly to ignore SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material ID HOME-ACQUIRED PNEUMONIA; GRAM-NEGATIVE BACILLI; ASPIRATION PNEUMONIA; ANTIMICROBIAL AGENTS; DENTAL PLAQUE; COLONIZATION C1 Univ Michigan, Sch Med, Ann Arbor VA Hlth Care Syst, Dept Med,Div Geriatr Med, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med,Ann Arbor GRECC,Dept Periodont, US Dept Vet Affairs,Ann Arbor VA Hlth Care Syst, Geriatr & Extended Care Serv Line,Vet Integrated, Ann Arbor, MI USA. RP Terpenning, M (reprint author), Univ Michigan, Sch Med, Ann Arbor VA Hlth Care Syst, Dept Med,Div Geriatr Med, Ann Arbor, MI 48109 USA. NR 29 TC 24 Z9 24 U1 0 U2 2 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 2002 VL 50 IS 3 BP 584 EP 585 DI 10.1046/j.1532-5415.2002.50131.x PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 528TU UT WOS:000174260000028 PM 11943061 ER PT J AU Mauiyyedi, S Crespo, M Collins, AB Schneeberger, EE Pascual, MA Saidman, SL Tolkoff-Rubin, NE Williams, WW Delmonico, FL Cosimi, AB Colvin, RB AF Mauiyyedi, S Crespo, M Collins, AB Schneeberger, EE Pascual, MA Saidman, SL Tolkoff-Rubin, NE Williams, WW Delmonico, FL Cosimi, AB Colvin, RB TI Acute humoral rejection in kidney transplantation: II. Morphology, immunopathology, and pathologic classification SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 1st Joint Meeting of the American-Society-of-Transplantation/American-Society-of-Transplant-Surge ons CY MAY 13-17, 2000 CL CHICAGO, ILLINOIS SP Amer Soc Transplantat, Amer Transplant Surgeons ID RENAL-ALLOGRAFT REJECTION; MEDIATED REJECTION; VASCULAR REJECTION; GRAFT LOSS; ANTIBODY; DEPOSITION; FRAGMENT; FEATURES; LESIONS AB The incidence of acute humoral rejection (AHR) in renal allograft biopsies has been difficult to determine because widely accepted diagnostic criteria have not been established. C4d deposition in peritubular capillaries (PTC) of renal allografts has been proposed as a useful marker for AHR. This study was designed to test the relative value of C4d staining, histology, and serology in the diagnosis of AHR. Of 232 consecutive kidney transplants performed at a single institution from July 1995 to July 1999, all patients (n = 67) who developed acute rejection within the first 3 mo and had a renal biopsy with available frozen tissue at acute rejection onset, as well as posttransplant sera within 30 d of the biopsy, were included in this study. Hematoxylin and eosin and periodic acid-Schiff stained sections were scored for glomerular, vascular, and tubulointerstitial pathology. C4d staining of cryostat sections was done by a sensitive three-layer immunofluorescence method. Donor-specific antibodies (DSA) were detected in posttransplant recipient sera using antihuman-globulin-enhanced T cell and B cell cytotoxicity assays and/or flow cytometry. Widespread C4d staining in PTC was present in 30% (20 of 67) of all acute rejection biopsies. The initial histologic diagnoses of the C4d(+) acute rejection cases were as follows: AHR only, 30%; acute cellular rejection (ACR) and AHR, 45%; ACR (CCTT types 1 or 2) alone, 15%; and acute tubular injury (ATI), 10%. The distinguishing morphologic features in C4d(+) versus C4d(-) acute rejection cases included the following: neutrophils in PTC, 65% versus 9%; neutrophilic glomerulitis, 55% versus 4%; neutrophilic tubulitis, 55% versus 9%; severe ATI, 75% versus 9%; and fibrinoid necrosis in glomeruli, 20% versus 0%, or arteries, 25% versus 0%; all P < 0.01. Mononuclear cell tubulitis was more common in the C4d(-) group (70% versus 100%; P < 0.01). No significant difference between C4d(+) and C4d(-) acute rejection was noted for endarteritis, 25% versus 32%; interstitial inflammation (mean % cortex), 27.2 +/- 27% versus 38 +/- 21%; interstitial hemorrhage, 25% versus 15%; or infarcts, 5% versus 2%. DSA were present in 90% (18 of 20) of the C4d(+) cases compared with 2% (1 of 47) in the C4d- acute rejection cases (P < 0.001). The pathology of the C4d(+) but DSA(-) cases was not distinguishable from the C4d(+), DSA(+) cases. The C4d(+) DSA(-) cases may be due to non-HLA antibodies or subthreshold levels of DSA. The sensitivity of C4d staining is 95% in the diagnosis of AHR compared with the donor-specific antibody test (90%). Overall, eight grafts were lost to acute rejection in the first year, of which 75% (6 of 8) had AHR. The 1-yr graft failure rate was 27% (4 of 15) for those AHR cases with only capillary neutrophils versus 40% (2 of 5) for those who also had fibrinoid necrosis of arteries. In comparison, the 1-yr graft failure rates were 3% and 7%, respectively, in ACR 1 (Banff/CCTT type 1) and ACR 2 (Banff/CCTT type 2) C4d- groups. A substantial fraction (30%) of biopsy-confirmed acute rejection episodes have a component of AHR as judged by C4d staining; most (90%), but not all, have detectable DSA. AHR may be overlooked in the presence of ACR or ATI by histology or negative serology, arguing for routine C4d staining of renal allograft biopsies. Because AHR has a distinct therapy and prognosis, we propose that it should be classified separately from ACR, with further sub-classification into AHR 1 (neutrophilic capillary involvement) and AHR 2 (arterial fibrinoid necrosis). C1 Massachusetts Gen Hosp, Dept Pathol, Pathol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Immunopathol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mauiyyedi, S (reprint author), Massachusetts Gen Hosp, Dept Pathol, Pathol Serv, 55 Fruit St,Warren 225, Boston, MA 02114 USA. EM shamila.mauiyyedi@uth.tmc.edu FU NHLBI NIH HHS [P01-HL18646] NR 26 TC 340 Z9 369 U1 3 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAR PY 2002 VL 13 IS 3 AR UNSP 1046-6673/1303-0779 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 523PJ UT WOS:000173964000026 PM 11856785 ER PT J AU Ibrahim, JG Chen, MH Gray, RJ AF Ibrahim, JG Chen, MH Gray, RJ TI Bayesian models for gene expression with DNA microarray data SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Bayesian inference; DNA; gene expression; hierarchical prior; L measure; microarray ID PATTERNS AB Two of the critical issues that arise, when examining DNA microarray data are (1) determination of which genes best discriminate among the different types of tissue, and (2) characterization of expression patterns in tumor tissues. For (1 1), there are many genes that characterize DNA expression, and it is of critical importance to try and identify a small set of genes that best discriminate between normal and tumor tissues. For (2), it is critical to be able to characterize the DNA expression of the normal and tumor tissue samples and develop suitable models that explain patterns of DNA expression for these types of tissues. Toward this goal, we propose a novel Bayesian model for analyzing DNA microarray data and propose a model selection methodology for identifying subsets of genes that show different expression levels between normal and cancer tissues. In addition, we propose a novel class of hierarchical priors fur the parameters that allow us to borrow strength across genes for making inference. The properties of the priors are examined in detail. We introduce a Bayesian model selection criterion for assessing the various, models, and develop Markov chain Monte Carlo algorithms for sampling from the posterior distributions of the parameters and for computing the criterion. We present a detailed case study in endometrial cancer to demonstrate our proposed methodology. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. RP Ibrahim, JG (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. NR 18 TC 85 Z9 87 U1 0 U2 0 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 2002 VL 97 IS 457 BP 88 EP 99 DI 10.1198/016214502753479257 PG 12 WC Statistics & Probability SC Mathematics GA 524DU UT WOS:000173997500009 ER PT J AU Torriani, M Etchebehere, M Amstalden, EMI AF Torriani, M Etchebehere, M Amstalden, EMI TI Sonographically guided core needle biopsy of bone and soft tissue tumors SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE sonography; needle biopsy; bone; soft tissue; neoplasms ID MUSCULOSKELETAL NEOPLASMS; PERCUTANEOUS BIOPSY; OSTEOLYTIC LESIONS; ASPIRATION; DIAGNOSIS; CT AB Objective. To determine the value of sonographically guided core needle biopsies of musculoskeletal tumors as a reliable alternative to fluoroscopy and computed tomography. Methods. A prospective study was performed in 74 patients referred for image-guided needle biopsy of primary or recurrent musculoskeletal neoplasms and suspected solitary metastasis. Imaging studies performed before biopsy established the feasibility of sonographic guidance in 65 lesions, of which 38 were soft tissue tumors and 27 were bone lesions with extraosseous masses. The lesions were located mainly in the appendicular skeleton. Tissue samples were obtained with a 14-gauge cutting needle coupled to an automated biopsy device under local anesthesia and sonographic guidance. Statistical analysis was based on 48 biopsies confirmed by successful clinical treatment (10 cases) or surgical resection (38 cases). Results. An accurate diagnosis was obtained in 47 (97%) of 48 biopsies, sensitivity was 96%, and specificity was 100%. The method did not yield sufficient tissue to establish a diagnosis in 1 case. Considering all 65 biopsies, high-quality specimens were obtained in 96%. The procedure was carried out expeditiously, and there were no complications. Conclusions. Sonographically guided core needle biopsy is accurate and safe, obviating open biopsy in most soft tissue masses and bone tumors with extraosseous masses in the appendicular skeleton. In such patients, the sonographically guided procedure is the most prompt and effective method for obtaining tissue samples. C1 Univ Estadual Campinas, Fac Ciencias Med, Hosp Clin, Dept Radiol, Campinas, Brazil. Univ Estadual Campinas, Fac Ciencias Med, Hosp Clin, Dept Orthoped, Campinas, Brazil. Univ Estadual Campinas, Fac Ciencias Med, Hosp Clin, Dept Pathol, Campinas, Brazil. RP Torriani, M (reprint author), Massachusetts Gen Hosp, 15 Parkman St,WACC 515, Boston, MA 02114 USA. RI Etchebehere, Mauricio/C-6785-2013 OI Etchebehere, Mauricio/0000-0002-5176-2369 NR 22 TC 41 Z9 44 U1 1 U2 3 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD MAR PY 2002 VL 21 IS 3 BP 275 EP 281 PG 7 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 526LG UT WOS:000174131500006 PM 11883538 ER PT J AU Collins, MM Meigs, JB Barry, MJ Corkery, EW Giovannucci, E Kawachi, I AF Collins, MM Meigs, JB Barry, MJ Corkery, EW Giovannucci, E Kawachi, I TI Prevalence and correlates of prostatitis in the health professionals follow-up study cohort SO JOURNAL OF UROLOGY LA English DT Article DE prostatitis; epidemiology; cohort studies; risk factors ID CHRONIC ABACTERIAL PROSTATITIS; ASSOCIATION SYMPTOM INDEX; PAIN SYNDROME; HYPERPLASIA; MEN; DIAGNOSIS; QUESTIONNAIRE; UROLOGISTS; VISITS AB Purpose: Prostatitis is an ill-defined condition whose symptoms overlap with benign prostatic hyperplasia (BPH). Little is known about the prevalence and correlates of prostatitis, or factors that distinguish prostatitis from BPH. We examined these issues in a large, nationwide sample of healthy men. Materials and Methods: In 1992, 31,681 United States health professionals without prostate cancer provided information on urological diagnoses, lower urinary tract symptoms, and demographic, clinical and lifestyle factors. We calculated age adjusted odds ratios and 95% confidence intervals for these correlates predicting a history of prostatitis. We also compared characteristics of men with prostatitis to those with BPH. Results: The prevalence of a self-reported history of prostatitis was 16%. Men reporting a history of BPH had 7.7-fold greater odds of a history of prostatitis, those with moderate or severe lower urinary tract symptoms had 1.8 and 2.8-fold greater odds, respectively, those with a history of sexually transmitted disease had 1.8-fold greater odds and those reporting stress at home or work had 1.5- and 1.2-fold greater odds, respectively. The 2,163 men with prostatitis alone were younger and had less severe urinary tract symptoms (but a similar pattern of symptoms) than the 4,575 men with BPH alone. Conclusions: Self-reported prostatitis was common among healthy men of all ages but there was considerable overlap with self-reported BPH. Prostatitis had several identifiable correlates that may aid in its recognition. C1 Harvard Univ, Sch Publ Hlth, Massachusetts Gen Hosp,Channing Lab, Gen Med Div,Med Serv,Dept Hlth & Social Behav, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Collins, MM (reprint author), Harvard Univ, Sch Publ Hlth, Massachusetts Gen Hosp,Channing Lab, Gen Med Div,Med Serv,Dept Hlth & Social Behav, 665 Huntington Ave, Boston, MA 02115 USA. FU AHRQ HHS [HS 08397]; NCI NIH HHS [CA55075]; NIDDK NIH HHS [DK45779, DK53736] NR 25 TC 94 Z9 122 U1 0 U2 3 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 2002 VL 167 IS 3 BP 1363 EP 1366 DI 10.1016/S0022-5347(05)65301-3 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 519YK UT WOS:000173752900043 PM 11832733 ER PT J AU Oh, WK Loda, M Kantoff, PW Janicek, M AF Oh, WK Loda, M Kantoff, PW Janicek, M TI Progressive sclerosis of isolated foot metastasis of prostate cancer SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Adult Oncol & Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Adult Oncol & Radiol, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 3 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAR PY 2002 VL 167 IS 3 BP 1392 EP 1392 DI 10.1016/S0022-5347(05)65312-8 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 519YK UT WOS:000173752900054 PM 11832744 ER PT J AU Arora, S Pomposelli, F LoGerfo, FW Veves, A AF Arora, S Pomposelli, F LoGerfo, FW Veves, A TI Cutaneous microcirculation in the neuropathic diabetic foot improves significantly but not completely after successful lower extremity revascularization SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID SKIN MICROCIRCULATION; DISEASE; PATHOGENESIS; DYSFUNCTION; ULCERATION; MICE AB Objective: The purpose of this study was the examination of the effect of successful large vessel revascularization on the microcirculation of the neuroischemic diabetic foot. Research design and methods: We measured the cutaneous microvascular reactivity in the foot in 13 patients with diabetes with peripheral arterial disease and neuropathy (group DI) before and 4 to 6 weeks after successful lower extremity arterial revascularization. We also compared them with age-matched and sex-matched groups of 15 patients with diabetes and neuropathy, seven patients without neuropathy, and 12 healthy patients for control. We used single-point and laser Doppler scan imaging for the measurement of the foot skin vasodilatation in response to heating to 44degreesC and to iontophoresis of 1% acetylcholine (endothelial-dependent response) and 1% sodium nitroprusside (endothelial-independent response). Results. The group DI response to heat increased from 289% +/- 90% before surgery (percent increase over baseline measured in volts) to 427% +/- 61% (P < .05) after surgery but was still comparable with the response of the patients with diabetes and neuropathy (318% +/- 51%) and lower than the responses of the patients without neuropathy (766% +/- 220%) and the healthy patients for control (891% +/- 121%; P < .0001). The group DI acetylcholine response also improved from 6% +/- 4% before surgery to 26% +/- 8% after surgery (P < .05) and was similar to the responses of patients with diabetes and neuropathy (18% +/- 3%) and patients without neuropathy (38% +/- 8%) but still lower when compared with the response of the patients for control (48% +/- 9%; P < .001). The sodium nitroprusside response for group DI improved from 10% +/- 4% to 29% +/- 9% (P < .05) and was similar to the responses of the neuropathic (25% +/- 9%), nonneuropathic (32% +/- 6%), and control (40% +/- 5%) groups. The group DI neurovascular response, which depends on the healthy function of the C-fiber nociceptors, was similar at baseline (5% +/- 9%) and after surgery (14% +/- %10) and in the neuropathic group (33% +/- 21%), but it was dramatically reduced when compared with the nonneuropathic (110% +/- 40%) and control (198% +/- 54%) groups (P < .001). Conclusion: Impaired vasodilation in the diabetic neuropathic lower extremity leads to functional ischemia, which improves considerably but is not completely corrected with successful bypass grafting surgery. Therefore, patients with diabetes and neuropathy may still be at high risk for the development of foot ulceration or the failure to have an existing ulcer heal despite adequate correction of large vessel blood flow. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg,Microcirculat Lab, Boston, MA 02215 USA. George Washington Univ, Med Ctr, Washington, DC 20037 USA. Vet Affairs Med Ctr, Washington, DC 20422 USA. Harvard Univ, Sch Med, Joslin Beth Israel Deaconess Foot Ctr, Boston, MA 02215 USA. RP Veves, A (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg,Microcirculat Lab, Palmer 317,West Campus,1 Deaconess Rd, Boston, MA 02215 USA. NR 22 TC 44 Z9 48 U1 3 U2 6 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 2002 VL 35 IS 3 BP 501 EP 505 DI 10.1067/mva.2002.121126 PG 5 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 532HJ UT WOS:000174468000013 PM 11877698 ER PT J AU Poggioli, GJ DeBiasi, RL Bickel, R Jotte, R Spalding, A Johnson, GL Tyler, KL AF Poggioli, GJ DeBiasi, RL Bickel, R Jotte, R Spalding, A Johnson, GL Tyler, KL TI Reovirus-induced alterations in gene expression related to cell cycle regulation SO JOURNAL OF VIROLOGY LA English DT Article ID PROTEIN PHOSPHATASE 2A; VIRUS TYPE-1 VPR; SPINDLE CHECKPOINT FUNCTION; POLO-LIKE KINASES; DNA-DAMAGE; RETINOBLASTOMA PROTEIN; ATAXIA-TELANGIECTASIA; NUCLEAR AUTOANTIGEN; INDUCED APOPTOSIS; DEPENDENT KINASE AB Mammalian reovirus infection results in perturbation of host cell cycle progression. Since reovirus infection is known to activate cellular transcription factors, we investigated alterations in cell cycle-retated gene expression following HEK293 cell infection by using the Affymetrix U95A microarray. Serotype 3 reovirus infection results in differential expression of 10 genes classified as encoding proteins that function at the G(1)-to-S transition, 11 genes classified as encoding proteins that function at G(2)-to-M transition, and 4 genes classified as encoding proteins that function at the mitotic spindle checkpoint. Serotype I reovirus infection results in differential expression of four genes classified as encoding proteins that function at the G(1)-to-S transition and three genes classified as encoding proteins that function at G(2)-to-M transition but does not alter any genes classified as encoding proteins that function at the mitotic spindle checkpoint. We have previously shown that serotype 3, but not serotype 1, reovirus infection induces a G(2)-to-M transition arrest resulting from an inhibition of cdc2 kinase activity. Of the differentially expressed genes encoding proteins regulating the G(2)-to-M transition, chk1, wee1, and GADD45 are known to inhibit cdc2 kinase activity. A hypothetical model describing serotype 3 reovirus-induced inhibition of cdc2 kinase is presented, and reovirus-induced perturbations of the G(1)-to-S, G(2)-to-M, and mitotic spindle checkpoints are discussed. C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol B 182, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Hematol & Oncol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Immunol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Neurol Serv, Denver, CO 80220 USA. Natl Jewish Ctr Immunol & Resp Med, Program Mol Signal Transduct, Denver, CO 80206 USA. Natl Jewish Ctr Immunol & Resp Med, Div Basic Sci, Denver, CO 80206 USA. RP Tyler, KL (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol B 182, 4200 E 9th Ave, Denver, CO 80262 USA. OI Tyler, Kenneth/0000-0003-3294-5888 FU NIA NIH HHS [AG14071] NR 87 TC 24 Z9 27 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2002 VL 76 IS 6 BP 2585 EP 2594 DI 10.1128/JVI.76.6.2585-2594.2002 PG 10 WC Virology SC Virology GA 524YA UT WOS:000174039400001 PM 11861824 ER PT J AU Lauer, GM Nguyen, TN Day, CL Robbins, GK Flynn, T McGowan, K Rosenberg, ES Lucas, M Klenerman, P Chung, RT Walker, BD AF Lauer, GM Nguyen, TN Day, CL Robbins, GK Flynn, T McGowan, K Rosenberg, ES Lucas, M Klenerman, P Chung, RT Walker, BD TI Human immunodeficiency virus type 1-hepatitis C virus coinfection: Intraindividual comparison of cellular immune responses against two persistent viruses SO JOURNAL OF VIROLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; CHRONIC HEPATITIS-C; EPSTEIN-BARR-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; HIV-1 INFECTION; QUANTITATIVE-ANALYSIS; PERIPHERAL-BLOOD; NATURAL-HISTORY; VIRAL-INFECTION; CD4(+) AB Both human immunodeficiency virus type I (HIV-1) and hepatitis C virus (HCV) lead to chronic infection in a high percentage of persons, and an expanding epidemic of HIV-1-HCV coinfection has recently been identified. These individuals provide an opportunity for simultaneous assessment of immune responses to two viral infections associated with chronic plasma viremia. In this study we analyzed the breadth and magnitude of the CD8(+)- and CD4(+)-T-lymphocyte responses in 22 individuals infected with both HIV-1 and HCV. A CD8(+)-T-lymphocyte response against HIV-1 was readily detected in all subjects over a broad range of viral loads. In marked contrast, HCV-specific CD8(+)-T-lymphocyte responses were rarely detected, despite viral loads in plasma that were on average 1,000-fold higher. The few HCV-specific responses that were observed were relatively weak and limited in breadth. CD4-proliferative responses against HIV-1 were detected in about half of the coinfected subjects tested, but no proliferative response against any HCV protein was found in these coinfected persons. These data demonstrate a major discordance in immune responses to two persistent RNA viruses. In addition, they show a consistent and profound impairment in cellular immune responses to HCV compared to HIV-1 in HIV-1-HCV-coinfected persons. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Lemuel Shattuck & Faulkner Hosp, Infect Dis Unit, Jamaica Plain, MA 02130 USA. John Radcliffe Hosp, Nuffield Dept Clin Med, Oxford OX3 9DU, England. RP Walker, BD (reprint author), Massachusetts Gen Hosp E, Partners AIDS Res Ctr, 149 13th St, Charlestown, MA 02125 USA. RI Robbins, Gregory/F-7988-2011; Day, Cheryl/J-9844-2012 NR 62 TC 91 Z9 93 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2002 VL 76 IS 6 BP 2817 EP 2826 DI 10.1128/VFI.76.6.2807-2826.2002 PG 10 WC Virology SC Virology GA 524YA UT WOS:000174039400026 PM 11861849 ER PT J AU Franco, RA Singh, B Har-El, G AF Franco, RA Singh, B Har-El, G TI Laryngeal chondroma SO JOURNAL OF VOICE LA English DT Article DE chondroma; chondrosarcoma; laryngeal tumors ID CARTILAGINOUS TUMORS; CHONDROSARCOMA AB Cartilaginous tumors of the larynx represent less than 1% of laryngeal tumors. Chondroma and "low-grade" chondrosarcoma are the most common; 70%-75% of these tumors arise on the endolaryngeal surface of the posterior lamina of the cricoid cartilage. The clinical presentation is varied and directly dependent on the size and location of the tumor; stridor, hoarseness, dyspnea, or a neck mass are common presenting signs. CT scanning in the axial plane is the mainstay of radiographic imaging due to its ability to show size, extent of the tumor, and invasion into surrounding structures. Surgical extirpation is the standard therapy with no role for radiation therapy or chemotherapy. Although significant recurrence rates have been reported, there is not a significant difference between initial conservative therapy followed by salvage therapy versus initial radical therapy. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol,Div Laryngol, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Div Head & Neck Surg, New York, NY 10021 USA. SUNY Brooklyn, Long Isl Coll Hosp, Dept Otolaryngol Head & Neck Surg, Brooklyn, NY USA. RP Franco, RA (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol,Div Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 13 TC 7 Z9 11 U1 0 U2 1 PU SINGULAR PUBLISHING GROUP INC PI CLIFTON PARK PA 5 MAXWELL DR, CLIFTON PARK, NY 12065 USA SN 0892-1997 J9 J VOICE JI J. Voice PD MAR PY 2002 VL 16 IS 1 BP 92 EP 95 DI 10.1016/S0892-1997(02)00077-2 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 651XB UT WOS:000181346700013 PM 12008653 ER PT J AU Reilly, CM Farrelly, LW Viti, D Redmond, ST Hutchison, F Ruiz, P Manning, P Connor, J Gilkeson, GS AF Reilly, CM Farrelly, LW Viti, D Redmond, ST Hutchison, F Ruiz, P Manning, P Connor, J Gilkeson, GS TI Modulation of renal disease in MRL/lpr mice by pharmacologic inhibition of inducible nitric oxide synthase SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT Meeting of the Nephrology-Society-of-Nephrology-Forefronts-in-Nephrology on Nitric Oxide and Renal Inflammation CY AUG 02-05, 2001 CL ST JOHN COLL, CAMBRIDGE, ENGLAND SP Int Soc Nephrol Forefronts Nephrol HO ST JOHN COLL DE lupus; rodent; autoantibody; inflammation; nitric oxide ID MRL-LPR/LPR MICE; MESANGIAL CELLS; L-ARGININE; NEPHROTOXIC NEPHRITIS; AUTOIMMUNE-DISEASE; LUPUS NEPHRITIS; IMMUNE INJURY; MESSENGER-RNA; NO SYNTHASE; GLOMERULONEPHRITIS AB Background. MRL-MPJFas(lpr) (MRL/lpr) mice spontaneously develop lupus-like disease characterized by immune complex glomerulonephritis and overproduction of nitric oxide (NO). Blocking NO production pharmacologically by a non-specific nitric oxide synthase (NOS) inhibitor ameliorated renal disease in MRL/lpr mice while genetically deficient inducible NOS (iNOS) mice developed proliferative glomerulonephritis similar to wild-type controls. Methods. To clarify the role of iNOS in the pathogenesis of nephritis in MRL/lpr mice, we treated mice with two different NOS inhibitors. Either NI-monomethyl-L-arginine (L-NMMA), a nonspecific NOS inhibitor, Or L-N-6-(1-iminoethyl)lysine (L-NIL), an iNOS specific inhibitor, was administered in the drinking water from 10 through 22 weeks of age with disease progression monitored over time. Control mice received water alone. Results. Both L-NMMA and L-NIL blocked NO production effectively in MRL/lpr mice. As expected, neither L-NNMA nor L-NIL had an effect on antibody production, immune complex deposition or complement activation. Although both NOS inhibitors decreased protein excretion, L-NMMA was more effective than L-NIL. Pathologic renal disease was significantly decreased at 19 weeks in both treatment groups. At 22 weeks the L-NIL treated mice, but not the L-NMMA mice, had significantly reduced renal disease scores compared to controls. Conclusion. These results indicate that specific inhibition of iNOS blocks the development of pathologic renal disease in MRL/lpr mice. C1 Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Med Res Ctr, Charleston, SC USA. Univ Miami, Sch Med, Dept Pathol, Miami, FL USA. Pharmacia Corp, St Louis, MO USA. RP Reilly, CM (reprint author), Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, 96 Jonathon Lucas St,Suite 912,POB 250623, Charleston, SC 29425 USA. FU NIAMS NIH HHS [R01 AR 45499] NR 52 TC 46 Z9 47 U1 0 U2 2 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 2002 VL 61 IS 3 BP 839 EP 846 DI 10.1046/j.1523-1755.2002.00230.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 523NB UT WOS:000173959600012 PM 11849435 ER PT J AU Namazie, A Alavi, S Olopade, OI Pauletti, G Aghamohammadi, N Aghamohammadi, M Gornbein, JA Calcaterra, TC Slamon, DJ Wang, MB Srivatsan, ES AF Namazie, A Alavi, S Olopade, OI Pauletti, G Aghamohammadi, N Aghamohammadi, M Gornbein, JA Calcaterra, TC Slamon, DJ Wang, MB Srivatsan, ES TI Cyclin D1 amplification and p16(MTS1/CDK4I) deletion correlate with poor prognosis in head and neck tumors SO LARYNGOSCOPE LA English DT Article DE head and neck tumors; cyclin D1; p16; fluorescence in situ hybridization ID SQUAMOUS-CELL CARCINOMA; IN-SITU HYBRIDIZATION; CHROMOSOME 11Q13 AMPLIFICATION; HUMAN BREAST-CANCER; GENE AMPLIFICATION; IMMUNOHISTOCHEMICAL DETECTION; P16(INK4A) EXPRESSION; P16/CDKN2 GENE; LUNG-CANCER; RB PROTEIN AB Objectives/Hypothesis: Cyclin D1, a cell cycle regulator localized to chromosome 11q13, is amplified in several human tumors including head and neck squamous cell carcinoma (HNSCC). Amplification and/or overexpression of cyclin D1 have been correlated to a poor prognosis. Deletion of the p16 gene, localized to 9p21, has also been observed in a significant proportion of HNSCC. The p16 gene regulates cyclin D1-CDK4 activity and prevents retinoblastoma tumor suppressor gene phosphorylation, thereby downregulating cellular proliferation. Detection of cyclin D1 amplification and p16 deletion using a simple and sensitive method will be valuable for the development of effective treatment modalities for head and neck cancer. Study Design: We have used fluorescence in situ hybridization (FISH) to study cyclin D1 amplification and p16 gene deletion in head and neck tumors. Both single- and dual-color FISH were performed. Methods: Paraffin-embedded tissues from 103 patients with HNSCC were analyzed using genomic DNA probes for cyclin D1 and p16. Dual-color FISH was performed with chromosome 11 or 9 centromeric probes as a control. Twenty-eight of these samples were analyzed for p16 expression by immunohistochemistry. Results: Cyclin D1 amplification was observed in 30% (31/103) of patients, and p16 deletion in 52% (54/103). Lack of p16 expression was observed in 64% (18/28) of patients. There was a good correlation between the deletion of p16 sequences and the loss of p16 expression (P = .008). Amplification of cyclin D1 had a statistically significant association with recurrence, distant metastasis, and survival at 36 months. There was a significant association between p16 deletion and the development of distant metastases. Cyclin D1 amplification and p16 deletion together correlated with recurrence, distant metastasis, and survival. Conclusions: We demonstrate that FISH is a simple and sensitive method for detecting cyclin D1 amplification and p16 deletion in head and neck cancer. Our results suggest that these two genetic aberrations together portend a poorer outcome than either of the abnormalities alone in head and neck cancer. C1 Univ Calif Los Angeles, Sch Med, Div Head & Neck Surg, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Div Hematol Oncol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Div Biomath, Los Angeles, CA 90024 USA. VA Greater Los Angeles Hlth Care Syst, Surg Serv, Dept Surg, Los Angeles, CA 90073 USA. Univ Chicago, Med Ctr, Div Hematol Oncol, Chicago, IL 60637 USA. RP Srivatsan, ES (reprint author), VA Greater Los Angeles Hlth Care Syst, Surg Serv, Dept Surg, 10H2,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 41 TC 90 Z9 104 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAR PY 2002 VL 112 IS 3 BP 472 EP 481 DI 10.1097/00005537-200203000-00013 PG 10 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 530BP UT WOS:000174336000013 PM 12148857 ER PT J AU Spitzer, TR McAfee, S Sackstein, R Dey, B Colby, C Grossberg, H Hope, J Saidman, S Preffer, F Sachs, DH Sykes, M AF Spitzer, TR McAfee, S Sackstein, R Dey, B Colby, C Grossberg, H Hope, J Saidman, S Preffer, F Sachs, DH Sykes, M TI Haploidentical donor BMT for advanced hematologic malignancy (HM) following non-myeloadlative conditioning including in vivo T-cell depletion. SO LEUKEMIA LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 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 2002 VL 16 IS 3 MA 39 BP 415 EP 415 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA 530BR UT WOS:000174336200054 ER PT J AU Semenov, I Akyuz, C Roginskaya, V Chauhan, D Corey, SJ AF Semenov, I Akyuz, C Roginskaya, V Chauhan, D Corey, SJ TI Growth inhibition and apoptosis of myeloma cells by the CDK inhibitor flavopiridol SO LEUKEMIA RESEARCH LA English DT Article DE myeloma; flavopiridol; kinase; signal transduction therapeutics ID CHRONIC LYMPHOCYTIC-LEUKEMIA; DEPENDENT KINASE INHIBITOR; BREAST-CARCINOMA CELLS; MULTIPLE-MYELOMA; AUTOLOGOUS TRANSPLANTATION; ANTITUMOR-ACTIVITY; THERAPY; CANCER; ACTIVATION; SURVIVAL AB Although myeloma shows responsiveness in intensive chemotherapy, overall survival remains less than 40%, at 2 years. Since myeloma appears to be dependent on cytokines, such as IL-6, we hypothesized that targeting signal transduction molecules could effectively treat myeloma. Two myeloma cell lines U266 and RPMI-8226 and CD38(+) myeloma cells were studied by immune complex kinase assay or anti-phosphotyrosine blot for evidence of constitutive activation of tyrosine kinases. Growth arrest and apoptosis were evaluated in these two cell lines following their treatment with specific kinase inhibitors. We found that a variety of Src and Janus kinases were present and constitutively active in U266 and RPMI-8226 cells. Inhibitors of both Src and Janus kinases were inferior to the cyclin-dependent kinase inhibitor, flavopiridol, in inducing both growth arrest with G1(50) of 100 nM and apoptosis in both cell lines and CD38(+) myeloma cells. Although, flavopiridol did not affect cyclin D1 and cyclin A levels, it inhibited Mcl-1 and Bcl-2 protein levels and cyclin-dependent kinase 2 activity. Flavopiridol is a well-tolerated drug, currently in phase I-II trials for a variety of tumors. A clinical trial using flavopiridol should be performed in patients with myeloma. Its mechanism of action may involve targets other than the cyclin-dependent kinases. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Childrens Hosp Pittsburgh, Dept Pediat Hematol Oncol, Pittsburgh, PA 15213 USA. Univ Hacettepe, Fac Med, Dept Pediat Oncol, TR-06100 Ankara, Turkey. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. RP Corey, SJ (reprint author), Childrens Hosp Pittsburgh, Dept Pediat Hematol Oncol, 3705 5th Ave, Pittsburgh, PA 15213 USA. NR 29 TC 39 Z9 40 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD MAR PY 2002 VL 26 IS 3 BP 271 EP 280 AR PII S0145-2126(01)0103-5 DI 10.1016/S0145-2126(01)00103-5 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 536JM UT WOS:000174697000008 PM 11792416 ER PT J AU Gray, RJ Li, Y AF Gray, RJ Li, Y TI Optimal weight functions for marginal proportional hazards analysis of clustered failure time data SO LIFETIME DATA ANALYSIS LA English DT Article DE estimating equations; conditional martingale covariance rate; Archimedean copula ID DISTRIBUTIONS; MODEL; ASSOCIATION; REGRESSION AB The choice of weights in estimating equations for multivariate survival data is considered. Specifically, we consider families of weight functions which are constant on fixed time intervals, including the special case of time-constant weights. For a fixed set of time intervals, the optimal weights are identified as the solution to a system of linear equations. The optimal weights are computed for several scenarios. It is found that for the scenarios examined, the gains in efficiency using the optimal weights are quite small relative to simpler approaches except under extreme dependence, and that a simple estimator of an exchangeable approximation to the weights also performs well. C1 Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Gray, RJ (reprint author), Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. EM gray@jimmy.harvard.edu; yili@jimmy.harvard.edu FU NCI NIH HHS [CA57253] NR 14 TC 10 Z9 11 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD MAR PY 2002 VL 8 IS 1 BP 5 EP 19 DI 10.1023/A:1013568114539 PG 15 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 507LP UT WOS:000173030200001 PM 11878224 ER PT J AU Barry, MJ AF Barry, MJ TI NSAIDs and a lower risk of prostate cancer: Causation or confounding? SO MAYO CLINIC PROCEEDINGS LA English DT Editorial Material ID SUPPLEMENTATION; TRIAL C1 Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Med Practices Evaluat Ctr, 50 Staniford St,9th Floor, Boston, MA 02114 USA. NR 8 TC 2 Z9 2 U1 0 U2 2 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD MAR PY 2002 VL 77 IS 3 BP 217 EP 218 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 526LW UT WOS:000174132800002 PM 11888023 ER PT J AU Kilbourne, AM Andersen, RM Asch, S Nakazono, T Crystal, S Stein, M Gifford, AL Bing, EG Bozzette, SA Shapiro, MF Cunningham, WE AF Kilbourne, AM Andersen, RM Asch, S Nakazono, T Crystal, S Stein, M Gifford, AL Bing, EG Bozzette, SA Shapiro, MF Cunningham, WE TI Response to symptoms among a US national probability sample of adults infected with human immunodeficiency virus SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Article ID QUALITY-OF-LIFE; LOW-PREVALENCE DISEASES; HEALTH-SERVICE USE; HIV-INFECTION; AIDS PATIENTS; UNITED-STATES; MEDICAL-CARE; ACCESS; COST; VALIDITY AB Previous studies concerning disparities in Human Immunodeficiency Virus (HIV) services use among vulnerable groups did not control for specific clinical need for care such as symptom events. Using the Andersen Behavioral Model of Health Services Use, the authors determined whether minorities, women, and the less educated (vulnerable groups) were less likely to receive care for HIV symptoms. Persons enrolled in the HIV Cost and Services Utilization Study were asked whether they received care for their most bothersome symptom. Surprisingly, minorities and women were no more likely to go without care than other groups. Those with Medicaid, Medicare, private health maintenance organization (HMO) insurance, or no insurance were less likely to receive care for symptoms than those with private-non-HMO insurance. Vulnerable groups were no less likely to use services for HIV-related symptoms when need for care was considered. However, disparities may exist for symptom-specific care among HIV infected persons covered by public or HMO insurance. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Rutgers State Univ, Piscataway, NJ 08855 USA. Brown Univ, Providence, RI 02912 USA. VA San Diego Healthcare Syst, San Diego, CA USA. Charles R Drew Univ Med & Sci, Los Angeles, CA 90059 USA. RP Kilbourne, AM (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. FU AHRQ HHS [U01HS08578]; NIAAA NIH HHS [U24AA11899-04]; NIMH NIH HHS [MH-19127] NR 38 TC 13 Z9 13 U1 4 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5587 J9 MED CARE RES REV JI Med. Care Res. Rev. PD MAR PY 2002 VL 59 IS 1 BP 36 EP 58 DI 10.1177/1077558702059001002 PG 23 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 522TW UT WOS:000173913900002 PM 11877878 ER PT J AU Washington, DL Harada, ND Villa, VM Damron-Rodriguez, J Dhanani, S Shon, H Makinodan, T AF Washington, DL Harada, ND Villa, VM Damron-Rodriguez, J Dhanani, S Shon, H Makinodan, T TI Racial variations in Department of Veterans Affairs ambulatory care use and unmet health care needs SO MILITARY MEDICINE LA English DT Article ID MEDICAL-CARE; CARDIOVASCULAR PROCEDURES; ETHNIC-DIFFERENCES; BEHAVIORAL-MODEL; ACCESS; SYSTEM; DISPARITIES; SURVIVAL; SERVICES AB Our objective was to describe racial/ethnic variations in Department of Veterans Affairs (VA) ambulatory care use and its association with the presence of unmet health care needs. Using the 1992 National Survey of Veterans, we examined race/ ethnicity and unmet health care need for ambulatory care users of VA and non-VA facilities. Black and Hispanic veterans were more likely to report any VA use. In unadjusted analyses, American Indian/Eskimo, Hispanic, and black veterans were 4.4, 2.5, and 1.9 times more likely, respectively, than white veterans to report an inability to get needed care. Adjusting for VA ambulatory care use diminished the disparity in inability to get needed care between American Indian/Eskimo or Hispanic veterans and white veterans and eliminated the disparity between black and white veterans. Our findings support the VA's role as a medical safety net provider and suggest that VA ambulatory care use is effective in mitigating health-re ate racial disparities for some veterans. Additional facilitators for reducing unmet need should be explored. C1 VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Publ Policy & Social Res, Los Angeles, CA 90095 USA. RP Washington, DL (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Med, 11301 Wilshire Blvd,111G, Los Angeles, CA 90073 USA. NR 23 TC 29 Z9 29 U1 1 U2 1 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD MAR PY 2002 VL 167 IS 3 BP 235 EP 241 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 653DP UT WOS:000181420200013 PM 11901574 ER PT J AU Hansen, WJ Ohh, M Moslehi, J Kondo, K Kaelin, WG Welch, WJ AF Hansen, WJ Ohh, M Moslehi, J Kondo, K Kaelin, WG Welch, WJ TI Diverse effects of mutations in Exon II of the von Hippel-Lindau (VHL) tumor suppressor gene on the interaction of pVHL with the cytosolic chaperonin and pVHL-dependent ubiquitin ligase activity SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; ELONGIN-C; RENAL-CARCINOMA; MESSENGER-RNAS; BINDING-SITES; BETA-ACTIN; PROTEIN; COMPLEX; PRODUCT; DISEASE AB We examined the biogenesis of the von Hippel-Lindau (VHL) tumor suppressor protein (pVHL) in vitro and in vivo. pVHL formed a complex with the cytosolic chaperonin containing TCP-1 (CCT or TRiC) en route to assembly with elongin B/C and the subsequent formation of the VCB-Cul2 ubiquitin ligase. Blocking the interaction of pVHL with elongin WC resulted in accumulation of pVHL within the CCT complex. pVHL present in purified VHL-CCT complexes, when added to rabbit reticulocyte lysate, proceeded to form VCB and VCB-Cul2. Thus, CCT likely functions, at least in part, by retaining VHL chains pending the availability of elongin B/C for final folding and/or assembly. Tumor-associated mutations within exon 11 of the VHL syndrome had diverse effects upon the stability and/or function of pVHL-containing complexes. First, a pVHL mutant lacking the entire region encoded by exon 11 did not bind to CCT and yet could still assemble into complexes with elongin B/C and elongin B/C-Cul2. Second, a number of tumor-derived missense mutations in exon 11 did not decrease CCT binding, and most had no detectable effect upon VCB-Cul2 assembly. Many exon 11 mutants, however, were found to be defective in the binding to and subsequent ubiquitination of hypoxia-inducible factor 1alpha (HIF-1alpha), a substrate of the VCB-Cul2 ubiquitin ligase. We conclude that the selection pressure to mutate VHL exon 11 during tumorigenesis does not relate to loss of CCT binding but may reflect quantitative or qualitative defects in HIF binding and/or in pVHL-dependent ubiquitin ligase activity. C1 San Francisco Gen Hosp, Surg Res Lab, San Francisco, CA 94110 USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON M5S 1A8, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Welch, WJ (reprint author), San Francisco Gen Hosp, Surg Res Lab, Bldg 1,Rm 210,1001 Potrero Ave, San Francisco, CA 94110 USA. FU NIGMS NIH HHS [GM 27345-20, GM 33551, P50 GM027345, R01 GM033551] NR 63 TC 48 Z9 49 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 2002 VL 22 IS 6 BP 1947 EP 1960 DI 10.1128/MCB.22.6.1947-1960.2002 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 524WH UT WOS:000174035500030 PM 11865071 ER PT J AU Yang, XW Claas, C Kraeft, SK Chen, LB Wang, ZM Kreidberg, JA Hemler, ME AF Yang, XW Claas, C Kraeft, SK Chen, LB Wang, ZM Kreidberg, JA Hemler, ME TI Palmitoylation of tetraspanin proteins: Modulation of CD151 lateral interactions, subcellular distribution, and integrin-dependent cell morphology SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID SUPERFAMILY TM4SF PROTEINS; LEUKEMIA-VIRUS TYPE-1; TRANSMEMBRANE-4 SUPERFAMILY; MONOCLONAL-ANTIBODIES; PLASMA-MEMBRANE; ALPHA-3-BETA-1 INTEGRIN; T-CELLS; METASTASIS SUPPRESSOR; SYNCYTIUM FORMATION; B-LYMPHOCYTES AB Here we demonstrate that multiple tetraspanin (transmembrane 4 superfamily) proteins are palmitoylated, in either the Golgi or a post-Golgi compartment. Using CD151 as a model tetraspanin, we identified and mutated intracellular N-terminal and C-terminal cysteine palmitoylation sites. Simultaneous mutations of C11, C15, C242, and C243 (each to serine) eliminated >90% of CD151 palmitoylation. Notably, palmitoylation had minimal influence on the density of tetraspanin protein complexes, did not promote tetraspanin localization into detergent-resistant microdomains, and was not required for CD151-alpha3beta1 integrin association. However, the CD151 tetra mutant showed markedly diminished associations with other cell surface proteins, including other transmembrane 4 superfamily proteins (CD9, CD63). Thus, palmitoylation may be critical for assembly of the large network of cell surface tetraspanin-protein interactions, sometimes called the "tetraspanin web." Also, compared with wild-type CD151, the tetra mutant was much more diffusely distributed and showed markedly diminished stability during biosynthesis. Finally, expression of the tetra-CD151 mutant profoundly altered alpha3 integrin-deficient kidney epithelial cells, such that they converted from a dispersed, elongated morphology to an epithelium-like cobblestone clustering. These results point to novel biochemical and biological functions for tetraspanin palmitoylation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA-42368, CA-86712, R01 CA042368, R01 CA086712] NR 71 TC 134 Z9 137 U1 4 U2 4 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAR PY 2002 VL 13 IS 3 BP 767 EP 781 DI 10.1091/mbc.01-05-0275 PG 15 WC Cell Biology SC Cell Biology GA 534LC UT WOS:000174587000003 PM 11907260 ER PT J AU Damelin, M Simon, I Moy, TI Wilson, B Komili, S Tempst, P Roth, FP Young, RA Cairns, BR Silver, PA AF Damelin, M Simon, I Moy, TI Wilson, B Komili, S Tempst, P Roth, FP Young, RA Cairns, BR Silver, PA TI The genome-wide localization of Rsc9, a component of the RSC chromatin-remodeling complex, changes in response to stress SO MOLECULAR CELL LA English DT Article ID TOR-SIGNALING PATHWAY; SACCHAROMYCES-CEREVISIAE; TRANSCRIPTION FACTORS; GENE-EXPRESSION; DEAD RINGER; PROTEINS; SWI/SNF; HOMOLOG; FAMILY; SUBSET AB The cellular response to environmental changes includes widespread modifications in gene expression. Here we report the identification and characterization of Rsc9, a member of the RSC chromatin-remodeling complex in yeast. The genome-wide localization of Rsc9 indicated a relationship between genes targeted by Rsc9 and genes regulated by stress; treatment with hydrogen peroxide or rapamycin, which inhibits TOR signaling, resulted in genome-wide changes in Rsc9 occupancy. We further show that Rsc9 is involved in both repression and activation of mRNAs regulated by TOR as well as the synthesis of rRNA. Our results illustrate the response of a chromatin-remodeling factor to signaling cascades and suggest that changes in the activity of chromatin-remodeling factors are reflected in changes in their localization in the genome. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. Univ Utah, Howard Hughes Med Inst, Salt Lake City, UT 84112 USA. Univ Utah, Dept Oncol Sci, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Silver, PA (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 1 Jimmy Fund Way, Boston, MA 02115 USA. RI Young, Richard/F-6495-2012; Roth, Frederick/H-6308-2011; OI Young, Richard/0000-0001-8855-8647; Roth, Frederick/0000-0002-6628-649X FU NIGMS NIH HHS [R01 GM060415] NR 42 TC 96 Z9 99 U1 0 U2 1 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 2002 VL 9 IS 3 BP 563 EP 573 DI 10.1016/S1097-2765(02)00475-6 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 537QA UT WOS:000174769300014 PM 11931764 ER PT J AU Shang, YF Myers, M Brown, M AF Shang, YF Myers, M Brown, M TI Formation of the androgen receptor transcription complex SO MOLECULAR CELL LA English DT Article ID PROSTATE-SPECIFIC ANTIGEN; NUCLEAR-RECEPTOR; HISTONE ACETYLTRANSFERASE; STEROID-RECEPTORS; BINDING DOMAIN; COACTIVATOR; ACTIVATION; CHROMATIN; PROTEIN; GENE AB Androgen receptor (AR) is required for sexual differentiation and is implicated in the development of prostate cancer. Here we describe distinct functions for cofactor proteins and gene regulatory elements in the assembly of AR-mediated transcription complexes. The formation of an activation complex involves AR, coactivators, and RNA polymerase H recruitment to both the enhancer and promoter, whereas the formation of a repression complex involves factors bound only at the promoter and not the enhancer. These results suggest a model for the functional coordination between the promoter and enhancer in which communication between these elements is established through shared coactivators in the AR transcription complex. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Brown, M (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Myles, Brown/B-6906-2008; OI Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [CA57374] NR 63 TC 438 Z9 445 U1 1 U2 11 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 2002 VL 9 IS 3 BP 601 EP 610 DI 10.1016/S1097-2765(02)00471-9 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 537QA UT WOS:000174769300017 PM 11931767 ER PT J AU Fiorini, E Schmitz, I Marissen, WE Osborn, SL Touma, M Sasada, T Reche, PA Tibaldi, EV Hussey, RE Kruisbeek, AM Reinherz, EL Clayton, LK AF Fiorini, E Schmitz, I Marissen, WE Osborn, SL Touma, M Sasada, T Reche, PA Tibaldi, EV Hussey, RE Kruisbeek, AM Reinherz, EL Clayton, LK TI Peptide-induced negative activates transcription of selection of thymocytes an NF-kappa B inhibitor SO MOLECULAR CELL LA English DT Article ID T-CELL-RECEPTOR; ONCOPROTEIN BCL-3; THYMIC SELECTION; NATURAL-KILLER; APOPTOSIS; COMPLEX; DEATH; PROTEIN; REPERTOIRE; ANKYRIN AB Negative selection eliminates thymocytes bearing autoreactive T cell receptors (TOR) via an apoptotic mechanism. We have cloned an inhibitor of NF-kappaB, IkappaBNS, which is rapidly expressed upon TCR-triggered but not dexamethasone- or gamma irradiation-stimulated thymocyte death. The predicted protein contains seven ankyrin repeats and is homologous to IkappaB family members. In class I and class II MHC-restricted TOR transgenic mice, transcription Of IkappaBNS is stimulated by peptides that trigger negative selection but not by those inducing positive selection (i.e., survival) or nonselecting peptides. IkappaBNs blocks transcription from NF-kappaB reporters, alters NF-kappaB electrophoretic mobility shifts, and interacts with NF-kappaB proteins in thymic nuclear lysates following TOR stimulation. Retroviral transduction Of IkappaBNS in fetal thymic organ culture enhances TCR-triggered cell death consistent with its function in selection. 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. Netherlands Canc Inst, Div Immunol, NL-1066 CX Amsterdam, Netherlands. RP Clayton, LK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. RI Schmitz, Ingo/G-2093-2013; Reche, Pedro/B-1881-2013 OI Schmitz, Ingo/0000-0002-5360-0419; Reche, Pedro/0000-0003-3966-5838 FU NIAID NIH HHS [AI19807, AI45022]; Telethon [427/B] NR 55 TC 66 Z9 73 U1 0 U2 3 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 2002 VL 9 IS 3 BP 637 EP 648 DI 10.1016/S1097-2765(02)00469-0 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 537QA UT WOS:000174769300020 PM 11931770 ER PT J AU Luo, H Rose, PE Roberts, TM Dearolf, CR AF Luo, H Rose, PE Roberts, TM Dearolf, CR TI The Hopscotch Jak kinase requires the Raf pathway to promote blood cell activation and differentiation in Drosophila SO MOLECULAR GENETICS AND GENOMICS LA English DT Article DE Drosophila; Jak kinase; Raf; blood cells; signal transduction ID MICE LACKING JAK3; HEMATOPOIETIC-CELLS; PROTEIN-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; LYMPHOPROLIFERATIVE DISEASE; LYMPHOID DEVELOPMENT; SIGNAL-TRANSDUCTION; FACTOR INDEPENDENCE; CYTOKINE RECEPTORS; IFN-ALPHA AB Cytokines regulate the development and differentiated functions of hematopoietic cells by activating multiple signaling pathways, including the Jak-Stat pathway, the PI3-kinase pathway, and the Ras/Raf pathway. While the Jak-Stat interaction has been extensively studied, the relationship between this pathway and other cytokine-induced signaling pathways is not fully understood. In Drosophila melanogaster, mutations that result in hyperactivity of the Jak kinase Hopscotch (Hop) cause an activation of the larval blood cell encapsulation response, including blood cell aggregation and differentiation of plasmatocytes into apparent lamellocytes. Here, we demonstrate that Hop requires the activity of the Raf pathway to promote the activation response of larval plasmatocytes, and provide evidence to suggest that the Hop and D-Raf proteins physically interact. We also show that basal level activity of the Raf pathway is required for the accumulation of circulating blood cells. C1 Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Dearolf, CR (reprint author), Massachusetts Gen Hosp, Dept Pediat, Jackson 1402,55 Fruit St, Boston, MA 02114 USA. NR 57 TC 32 Z9 32 U1 2 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1617-4615 J9 MOL GENET GENOMICS JI Mol. Genet. Genomics PD MAR PY 2002 VL 267 IS 1 BP 57 EP 63 DI 10.1007/s00438-001-0632-7 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 541EE UT WOS:000174971600007 PM 11919715 ER PT J AU Wakimoto, H Ikeda, K Abe, T Ichikawa, T Hochberg, FH Ezekowitz, RAB Pasternack, MS Chiocca, EA AF Wakimoto, H Ikeda, K Abe, T Ichikawa, T Hochberg, FH Ezekowitz, RAB Pasternack, MS Chiocca, EA TI The complement response against an oncolytic virus is species-specific in its activation pathways SO MOLECULAR THERAPY LA English DT Article DE HSV-1; gene therapy; complement; viral infection ID HERPES-SIMPLEX VIRUS; TYPE-1 GLYCOPROTEIN GC; GALACTOSYL NATURAL ANTIBODY; MANNOSE-BINDING LECTIN; HUMAN-SERUM; RIBONUCLEOTIDE REDUCTASE; IMMUNOCOMPETENT MICE; GENE-TRANSFER; DNA-SYNTHESIS; BRAIN-TUMORS AB A variety of oncolytic viruses (OVs) are being tested in clinical trials for different human cancers. Although the innate immune response is critical as the first line of defense in thwarting viral infection of mammalian cells, little is known of this response in the context of OV therapy of tumors. Investigations of activities against a herpes simplex OV demonstrated that HSV-seronegative sera from rats, mice, and humans efficiently neutralize this OV in vitro. Although this neutralization is due to complement, activation of this innate host defense differs in its pathways among species routinely used in preclinical tumor trials. In rats, both natural immunoglobulins and mannan-binding lectin (MBL) activate complement against the OV, while in mice only MBL is relevant to this activation. However, in humans only natural immunoglobulins play a role in complement activity. Quantitative analyses confirm that in vivo complement depletion facilitates the initial infection of tumors by systemic OVs. Therefore, complement activation against oncolytic HSV vectors proceeds through different pathways in different species. These findings are relevant to preclinical rodent studies of OV therapy and their application to human clinical trials. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosurg Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurooncol Labs, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuromed Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Serv Pediat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. RP Chiocca, EA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosurg Serv, Charlestown, MA 02129 USA. FU NCI NIH HHS [P01 CA69246] NR 44 TC 50 Z9 52 U1 2 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAR PY 2002 VL 5 IS 3 BP 275 EP 282 DI 10.1006/mthe.2002.0547 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 527NT UT WOS:000174192700011 PM 11863417 ER PT J AU Richfield, EK Vonsattel, JP MacDonald, ME Sun, ZQ Deng, YPP Reiner, A AF Richfield, EK Vonsattel, JP MacDonald, ME Sun, ZQ Deng, YPP Reiner, A TI Selective loss of striatal preprotachykinin neurons in a phenocopy of Huntington's disease SO MOVEMENT DISORDERS LA English DT Article DE Huntington's disease; PPT neurons; PPE neurons; substance P; striatal lesions ID PALLIDOLUYSIAN ATROPHY DRPLA; SPINOCEREBELLAR ATAXIA; PREFERENTIAL LOSS; QUINOLINIC ACID; FUNCTIONAL-ANATOMY; PROJECTION NEURONS; BASAL GANGLIA; EXPANSION; GENE; DISORDER AB Phenocopies of Huntington's disease (HD) are individuals with a family history, clinical symptoms, and occasionally pathological evidence of HD but without an expanded CAG repeat within the HD gene. We report on an HD phenocopy with selective loss of preprotachykinin (PPT) neurons, dysfunction of surviving PPT neurons, preservation of preproenkephalin (PPE) neurons within the striatum, and greater loss of immunohistochemical staining for substance P in terminals of striatal neurons projecting to the substantia nigra, than in those projecting to the internal pallidal segment. This case demonstrates the existence of one type of striatal lesion that may produce a clinical picture similar to HD, and raises the possibility of a rare hereditary disease that mimics HD. (C) 2002 Movement Disorder Society. C1 Univ Rochester, Sch Med, Dept Pathol & Lab Med, Rochester, NY USA. Univ Rochester, Sch Med, Ctr Aging & Dev Biol, Rochester, NY USA. Massachusetts Gen Hosp, Lab Mol Neuropathol, Charlestown, MA USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Univ Tennessee, Dept Anat & Neurobiol, Memphis, TN USA. RP Richfield, EK (reprint author), Strong Mem Hosp, Dept Pathol & Lab Med, Div Neuropathol, Box 626,601 Elmwood Ave, Rochester, NY 14642 USA. FU NIA NIH HHS [AGO 9016-01]; NIMH NIH HHS [MH 40381, MH/NS 31862]; NINDS NIH HHS [NS16367, NS28721, NS32765] NR 28 TC 15 Z9 15 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAR PY 2002 VL 17 IS 2 BP 327 EP 332 DI 10.1002/mds.10032 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 537CP UT WOS:000174740500014 PM 11921119 ER PT J AU Opal, P Tintner, R Jankovic, J Leung, J Breakefield, XO Friedman, J Ozelius, L AF Opal, P Tintner, R Jankovic, J Leung, J Breakefield, XO Friedman, J Ozelius, L TI Intrafamilial phenotypic variability of the DYT1 dystonia: From asymptomatic TOR1A gene carrier status to dystonic storm SO MOVEMENT DISORDERS LA English DT Article DE dystonia; distonic storm; DYT1; phenotypic variability ID POSTTRAUMATIC MOVEMENT-DISORDERS; IDIOPATHIC TORSION DYSTONIA; RESPONSIVE DYSTONIA; MUTATION; ONSET; EXPRESSION; MANAGEMENT AB When primary torsion dystonia is caused by a GAG deletion in the TORlA gene (DYTI dystonia), it typically presents with an early-onset dystonia involving distal limbs, subsequently spreading to a generalized dystonia. We describe a large family with an unusually broad variability in the clinical features of their dystonia both with regard to severity and age of onset. The proband of this family succumbed in his second decade to malignant generalized dystonia, whereas other family members carrying the same mutation are either asymptomatic or display dystonia that may be focal, segmental, multifocal, or generalized in distribution. One family member had onset of her dystonia at age 64 years, probably the oldest reported in genetically confirmed DYTI dystonia. We conclude that marked phenotypic heterogeneity characterizes some families with DYTI dystonia, suggesting a role for genetic, environmental, or other modifiers. These findings have implications for genetic testing and counseling. (C) 2002 Movement Disorder Society. C1 Baylor Coll Med, Dept Neurol, Parkinsons Dis Ctr, Houston, TX 77030 USA. Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Jankovic, J (reprint author), Baylor Coll Med, Dept Neurol, Parkinsons Dis Ctr, 6550 Fannin,Suite 1801, Houston, TX 77030 USA. NR 26 TC 62 Z9 63 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAR PY 2002 VL 17 IS 2 BP 339 EP 345 DI 10.1002/mds.10096 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 537CP UT WOS:000174740500016 PM 11921121 ER PT J AU Pramstaller, PP Kis, B Eskelson, C Hedrich, K Scherer, M Schwinger, E Breakefield, XO Kramer, PL Ozelius, LJ Klein, C AF Pramstaller, PP Kis, B Eskelson, C Hedrich, K Scherer, M Schwinger, E Breakefield, XO Kramer, PL Ozelius, LJ Klein, C TI Phenotypic variability in a large kindred (Family LA) with deletions in the parkin gene SO MOVEMENT DISORDERS LA English DT Article ID RECESSIVE JUVENILE PARKINSONISM; DISEASE; MUTATIONS; ONSET C1 Reg Gen Hosp, Dept Neurol, I-39100 Bolzano, Italy. Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. Med Univ Lubeck, Inst Human Genet, D-23538 Lubeck, Germany. Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Med Sch, Dept Neurol, Boston, MA USA. Harvard Med Sch, Dept Genet, Boston, MA USA. Harvard Med Sch, Program Neurosci, Boston, MA USA. RP Pramstaller, PP (reprint author), Reg Gen Hosp, Dept Neurol, 5 Lorenz Boehler, I-39100 Bolzano, Italy. RI Kis, Bernhard/A-8731-2008; Pramstaller, Peter/C-2357-2008 OI Kis, Bernhard/0000-0003-3244-9737; FU NINDS NIH HHS [NS38372] NR 9 TC 15 Z9 15 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAR PY 2002 VL 17 IS 2 BP 424 EP 426 DI 10.1002/mds.10071 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 537CP UT WOS:000174740500036 PM 11921141 ER PT J AU Grant, GA Britz, GW Goodkin, R Jarvik, JG Maravilla, K Kliot, M AF Grant, GA Britz, GW Goodkin, R Jarvik, JG Maravilla, K Kliot, M TI The utility of magnetic resonance imaging in evaluating peripheral nerve disorders SO MUSCLE & NERVE LA English DT Review DE magnetic resonance imaging (MRI); neurography; neuropathy; nerve injury; peripheral nerve ID CARPAL-TUNNEL SYNDROME; MEDIAN NERVE; INTRAOPERATIVE FINDINGS; NORMAL ANATOMY; SHEATH TUMORS; MR; NEUROGRAPHY; WRIST; DIAGNOSIS; COMPRESSION AB The evaluation of peripheral nerve injuries has traditionally relied primarily on information gained from the clinical history, physical examination, and electrodiagnostic testing. Taken together, all of this clinical and diagnostic information often allows one to determine the location and severity of the underlying peripheral nerve problem. However, it may not be sufficient in diagnosing a focal entrapment neuropathy superimposed upon a more generalized peripheral neuropathy; localizing a focal lesion along a long segment of nerve which may be difficult to assess accurately with electrodiagnostic studies; distinguishing early between an axonotmetic grade of injury, which can recover through axonal regeneration, and a neurotmetic grade which cannot and therefore may benefit from a surgical exploration and repair procedure; and noninvasively diagnosing and determining the surgical resectability of peripheral nerve mass lesions such as tumors. The goal of this review is to illustrate how standard and evolving magnetic resonance imaging techniques can provide additional information in dealing with some of these problems. (C) 2002 Wiley Periodicals, Inc. C1 Univ Washington, Sch Med, Dept Neurol Surg, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Radiol, Sect Neuroradiol, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Kliot, M (reprint author), Univ Washington, Sch Med, Dept Neurol Surg, 1959 NE Pacific St,Box 356470, Seattle, WA 98195 USA. FU NINDS NIH HHS [T32NS-07144-15] NR 81 TC 95 Z9 98 U1 1 U2 4 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 2002 VL 25 IS 3 BP 314 EP 331 DI 10.1002/mus.10013 PG 18 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 526ZK UT WOS:000174159400002 PM 11870709 ER PT J AU Chiocca, EA AF Chiocca, EA TI Guided genes for tumor warfare SO NATURE BIOTECHNOLOGY LA English DT Editorial Material ID CELLS; ACTIVATION; STRATEGY; THERAPY AB T cells have been recruited to both produce and deliver vectors to specific tumors in an animal model. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Chiocca, EA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 9 TC 4 Z9 4 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAR PY 2002 VL 20 IS 3 BP 235 EP 236 DI 10.1038/nbt0302-235 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 526RE UT WOS:000174142800033 PM 11875420 ER PT J AU Hopyan, S Gokgoz, N Poon, R Gensure, RC Yu, CY Cole, WG Bell, RS Juppner, H Andrulis, IL Wunder, JS Alman, BA AF Hopyan, S Gokgoz, N Poon, R Gensure, RC Yu, CY Cole, WG Bell, RS Juppner, H Andrulis, IL Wunder, JS Alman, BA TI A mutant PTH/PTHrP type I receptor in enchondromatosis SO NATURE GENETICS LA English DT Article ID HORMONE-RELATED PEPTIDE; PARATHYROID-HORMONE; INDIAN HEDGEHOG; METAPHYSEAL CHONDRODYSPLASIA; BLOMSTRAND-CHONDRODYSPLASIA; TRANSGENIC MICE; BONE-GROWTH; GENE; DIFFERENTIATION; CHONDROCYTES AB Enchondromas are common benign cartilage tumors of bone. They can occur as solitary lesions or as multiple lesions in enchondromatosis (Ollier and Maffucci diseases). Clinical problems caused by enchondromas include skeletal deformity and the potential for malignant change to chondrosarcoma(1-3). The extent of skeletal involvement is variable in enchondromatosis and may include dysplasia that is not directly attributable to enchondromas(4). Enchondromatosis is rare, obvious inheritance of the condition is unusual and no candidate loci have been identified. Enchondromas are usually in close proximity to, or in continuity with, growth-plate cartilage. Consequently, they may result from abnormal regulation of proliferation and terminal differentiation of chondrocytes in the adjoining growth plate. In normal growth plates, differentiation of proliferative chondrocytes to post-mitotic hypertrophic chondrocytes is regulated in part by a tightly coupled signaling relay involving parathyroid hormone related protein (PTHrP) and Indian hedgehog (IHH)(5-9). PTHrP delays the hypertrophic differentiation of proliferating chondrocytes, whereas IHH promotes chondrocyte proliferation. We identified a mutant PTH/PTHrP type I receptor (PTHR1) in human enchondromatosis that signals abnormally in vitro and causes enchondroma-like lesions in transgenic mice. The mutant receptor constitutively activates Hedgehog signaling, and excessive Hedgehog signaling is sufficient to cause formation of enchondroma-like lesions. C1 Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Program Mol Biol & Canc, Toronto, ON M5G 1X5, Canada. Hosp Sick Children, Res Inst, Program Dev Biol, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Surg, Div Orthopaed, Toronto, ON, Canada. Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada. Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Pediat Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Hosp Sick Children, Div Orthopaed, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Mol & Med Genet, Toronto, ON, Canada. Mt Sinai Hosp, Univ Musculoskeletal Oncol Unit, Toronto, ON M5G 1X5, Canada. Mt Sinai Hosp, Div Orthopaed, Toronto, ON M5G 1X5, Canada. RP Wunder, JS (reprint author), Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Program Mol Biol & Canc, 600 Univ Ave, Toronto, ON M5G 1X5, Canada. RI Andrulis, Irene/E-7267-2013 NR 29 TC 140 Z9 151 U1 4 U2 5 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 2002 VL 30 IS 3 BP 306 EP 310 DI 10.1038/ng844 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 526YP UT WOS:000174157600016 PM 11850620 ER PT J AU Andre, P Prasad, KSS Denis, CV He, M Papalia, JM Hynes, RO Phillips, DR Wagner, DD AF Andre, P Prasad, KSS Denis, CV He, M Papalia, JM Hynes, RO Phillips, DR Wagner, DD TI CD40L stabilizes arterial thrombi by a beta(3) integrin-dependent mechanism SO NATURE MEDICINE LA English DT Article ID VON-WILLEBRAND-FACTOR; TISSUE FACTOR; ENDOTHELIAL-CELLS; P-SELECTIN; MONOCLONAL-ANTIBODY; GPIIB-IIIA; IIB-IIIA; LIGAND; EXPRESSION; MICE AB CD40L, a member of the tumor necrosis factor family of ligands, plays a major role in immune responses via its receptor, CD40. Recently, CD40L has been detected on the surfaces of activated platelets and shown to activate endothelium. Here we further addressed the function of platelet CD40L. We show that absence of CD40L affects the stability of arterial thrombi and delays arterial occlusion in vivo. Infusion of recombinant soluble (rs) CD40L restored normal thrombosis, whereas rsCD40L lacking the KGD integrin-recognition sequence did not. CD40-deficient mice exhibited normal thrombogenesis. rsCD40L specifically bound to purified integrin alpha(IIb)beta(3) and to activated platelets in a beta(3)-dependent manner and induced platelet spreading. In addition, rsCD40L promoted the aggregation of either human or mouse platelets under high shear rates. Thus, CD40L appears to be an alpha(IIb)beta(3) ligand, a platelet agonist, and necessary for stability of arterial thrombi. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. COR Therapeut, San Francisco, CA USA. MIT, Ctr Canc Res, Howard Hughes Med Inst, Cambridge, MA 02139 USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RI Denis , Cecile/A-7649-2011 OI Denis , Cecile/0000-0001-5152-9156 FU NHLBI NIH HHS [R01 HL041002, P01 HL056949, P01 HL56949, R37 HL41002] NR 36 TC 471 Z9 496 U1 0 U2 6 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 2002 VL 8 IS 3 BP 247 EP 252 DI 10.1038/nm0302-247 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 526PU UT WOS:000174139500029 PM 11875495 ER PT J AU Taub, E Uswatte, G Elbert, T AF Taub, E Uswatte, G Elbert, T TI New treatments in neurorehabilitation founded on basic research SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID INDUCED MOVEMENT THERAPY; BODY-WEIGHT SUPPORT; STROKE PATIENTS; SOMATOSENSORY CORTEX; PHYSICAL-THERAPY; MOTOR RECOVERY; LEARNED NONUSE; REHABILITATION; PLASTICITY; ADULT AB Recent discoveries about how the central nervous system responds to injury and how patients reacquire lost behaviours by training have yielded promising new therapies for neurorehabilitation. Until recently, this field had been largely static, but the current melding of basic behavioural science with neuroscience promises entirely new approaches to improving behavioural, perceptual and cognitive capabilities after neurological damage. Studies of phenomena such as cortical reorganization after a lesion, central nervous system repair, and the substantial enhancement of extremity use and linguistic function by behavioural therapy, support this emerging view. The ongoing changes in rehabilitation strategies might well amount to an impending paradigm shift in this field. C1 Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Birmingham, AL 35294 USA. Univ Alabama Birmingham, Dept Psychol, Birmingham, AL 35294 USA. Univ Konstanz, Dept Psychol, D-78457 Constance, Germany. RP Taub, E (reprint author), Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, CPM 712,1530 3rd Ave S, Birmingham, AL 35294 USA. EM etaub@uab.edu RI Elbert, Thomas/C-8556-2009; Uswatte, Gitendra/C-4913-2009 NR 91 TC 347 Z9 363 U1 4 U2 47 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-003X EI 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD MAR PY 2002 VL 3 IS 3 BP 228 EP 236 DI 10.1038/nrn754 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 527VD UT WOS:000174207900018 PM 11994754 ER PT J AU El-Armouche, A Jaeckel, E Pamminger, T Eschenhagen, T AF El-Armouche, A Jaeckel, E Pamminger, T Eschenhagen, T TI Evidence for phosphatase inhibitor-1 playing a role in beta-adrenergic desensitization observed in heart failure SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract C1 Univ Erlangen Nurnberg, Dept Pharmacol & Toxicol, D-91054 Erlangen, Germany. Dana Faber Inst, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD MAR PY 2002 VL 365 SU 1 MA 339 BP R88 EP R88 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 542EQ UT WOS:000175030900348 ER PT J AU Miura, K Kishino, T Li, E Webber, H Dikkes, P Holmes, GL Wagstaff, J AF Miura, K Kishino, T Li, E Webber, H Dikkes, P Holmes, GL Wagstaff, J TI Neurobehavioral and electroencephalographic abnormalities in Ube3a maternal-deficient mice SO NEUROBIOLOGY OF DISEASE LA English DT Article ID UBIQUITIN-PROTEIN LIGASE; ANGELMAN-SYNDROME GENE; MUTATION; E6-AP; UBE3A/E6-AP; EXPRESSION; P53; FAMILY; BRAIN AB Angelman syndrome (AS), characterized by motor dysfunction, mental retardation, and seizures, is caused by several genetic etiologies involving chromosome 15q11-q13, including mutations of the UBE3A gene. UBE3A encodes UBE3A/E6-AP, a ubiquitin-protein ligase, and shows brain-specific imprinting, with brain expression predominantly from the maternal allelle. Lack of a functional maternal allele of UBE3A causes AS. In order to understand the causal relationship between maternal UBE3A mutations and AS, we have constructed a mouse model with targeted inactivation of Ube3a. The inactive allele contains a lacZ reporter gene for analysis of brain-specific imprinting. Maternal, but not paternal, transmission of the targeted allele leads to beta-galactosidase activity in hippocampal and cerebellar neurons. Maternal inheritance of the Ube3a mutant allele also causes impaired performance in tests of motor function and spatial learning, as well as abnormal hippocampal EEG recordings. As predicted from the dependence of UBE3A-mediated ubliquitination of p53 on HPV E6 protein, our maternal-deficient mice show normal brain p53 levels. (C) 2002 Elsevier Science (USA). C1 Nagasaki Univ, Sch Med, Dept Obstet & Gynecol, Nagasaki 852, Japan. Nagasaki Univ, Sch Med, Dept Human Genet, Nagasaki 852, Japan. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Dartmouth Coll, Program Mol & Cellular Biol, Hanover, NH 03755 USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Virginia, Sch Med, Dept Pediat, Charlottesville, VA 22908 USA. Univ Virginia, Sch Med, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. RP Miura, K (reprint author), Nagasaki Univ, Sch Med, Dept Obstet & Gynecol, Nagasaki 852, Japan. FU NINDS NIH HHS [NS27984] NR 26 TC 121 Z9 121 U1 0 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD MAR PY 2002 VL 9 IS 2 BP 149 EP 159 DI 10.1006/nbdi.2001.0463 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 532PW UT WOS:000174485100004 PM 11895368 ER PT J AU Horner, MD Hamner, MB AF Horner, MD Hamner, MB TI Neurocognitive functioning in posttraumatic stress disorder SO NEUROPSYCHOLOGY REVIEW LA English DT Article DE neuropsychology; cognition; posttraumatic stress disorder ID POSITRON-EMISSION-TOMOGRAPHY; SHORT-TERM-MEMORY; COMBAT VETERANS; HIPPOCAMPAL VOLUME; SEXUAL ABUSE; ADULT SURVIVORS; KOREAN CONFLICT; POW SURVIVORS; DEFICITS; ATTENTION AB This paper reviews the literature on performance on standard neuropsychological tests among individuals with posttraumatic stress disorder (PTSD). Of 19 studies, 16 reported impairment of attention or immediate memory (or both); however, most of these studies included PTSD patients with significant psychiatric comorbidity, so that the extent to which the observed deficits are specifically attributable to PTSD remains unclear. Other potential confounds, including medical illness, substance abuse, and motivational factors, further preclude definitive conclusions at present. Results of structural and functional neuroimaging studies of PTSD are also summarized. Two studies have reported correlations between hippocampal volume and cognitive findings in PTSD patients; functional studies have indicated specific findings in limbic regions, although the relationship of these results to neuropsychological performance remains to be explored. C1 Ralph H Johnson VA Med Ctr, Mental Hlth Serv 116, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. RP Horner, MD (reprint author), Ralph H Johnson VA Med Ctr, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. NR 57 TC 75 Z9 80 U1 4 U2 19 PU CONSULTANTS BUREAU PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1040-7308 J9 NEUROPSYCHOL REV JI Neuropsychol. Rev. PD MAR PY 2002 VL 12 IS 1 BP 15 EP 30 AR UNSP 1040-7308/02/0300-0015/0 DI 10.1023/A:1015439106231 PG 16 WC Psychology, Clinical; Neurosciences SC Psychology; Neurosciences & Neurology GA 566AF UT WOS:000176402700002 PM 12090717 ER PT J AU Chang, EL Rubin, PAD AF Chang, EL Rubin, PAD TI Bilateral multifocal hemangiomas of the orbit in the blue rubber bleb nevus syndrome SO OPHTHALMOLOGY LA English DT Article ID HEREDITARY HEMORRHAGIC TELANGIECTASIA; KLIPPEL-TRENAUNAY SYNDROME; CAVERNOUS HEMANGIOMAS; WEBER SYNDROME; MANIFESTATIONS; MANAGEMENT AB Purpose: To report the clinical findings and surgical treatment of multifocal, bilateral orbital hemangiomas in a patient with the blue rubber bleb nevus syndrome, a rare vascular disorder characterized by distinctive cutaneous and visceral hemangiomas. Design: Interventional case report. Methods: Review of clinical findings, radiologic studies, and treatment of the patient. Results: A 36-year-old female with multifocal, bilateral orbital lesions was seen with severe proptosis and decreased visual acuity of the left eye. Surgical debulking of multiple cavernous hemangiomas of the orbit resulted in decreased proptosis and an improvement in visual acuity. Subsequent histopathologic analysis and the results of a systemic workup revealing multiple, distinctive, cutaneous and visceral lesions were found to be consistent with the blue rubber bleb nevus syndrome. Conclusions: Although hemangiomas of the orbit are relatively common occurrences, multifocal, bilateral lesions may exist in the setting of underlying systemic hemangiomatosis. Bilateral or multifocal hemangiomas associated with cutaneous or visceral lesions should alert the clinician to the possibility of a number of syndromes that may have life-threatening consequences. Ophthalmology 2002;109:537-541 (C) 2002 by the American Academy of Ophthalmology. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ophthalm Plast Orbital & Cosmet Surg Serv, Boston, MA 02114 USA. RP Rubin, PAD (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ophthalm Plast Orbital & Cosmet Surg Serv, 243 Charles St, Boston, MA 02114 USA. NR 32 TC 18 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAR PY 2002 VL 109 IS 3 BP 537 EP 541 AR PII S0161-6420(01)00989-7 DI 10.1016/S0161-6420(01)00989-7 PG 5 WC Ophthalmology SC Ophthalmology GA 525VV UT WOS:000174095500032 PM 11874758 ER PT J AU Ntziachristos, V Ripoll, J Weissleder, R AF Ntziachristos, V Ripoll, J Weissleder, R TI Would near-infrared fluorescence signals propagate through large human organs for clinical studies? SO OPTICS LETTERS LA English DT Article ID OPTICAL TOMOGRAPHY; TURBID MEDIA; LUNG AB We predict the capacity of near-infrared fluorescent signals to propagate through human tissue for non-invasive medical imaging. This analysis employs experimental measurements of a biologically relevant local fluorochrome embedded in tissuelike media and predicts the equivalent photon counts expected from breast, lung, brain, and muscle as a function of diameter by use of an analytical solution of the diffusion equation that can take into account large arbitrary geometries. The findings address feasibility issues for clinical studies and are relevant to recent development of near-infrared fluorescent probes and molecular beacons for in vivo applications. (C) 2002 Optical Society of America. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Fdn Res & Technol Hellas, Inst Elect Struct & Laser, Iraklion 71110, Crete, Greece. RP Ntziachristos, V (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RI Ripoll, Jorge/J-8134-2012 OI Ripoll, Jorge/0000-0001-8856-7738 NR 14 TC 100 Z9 106 U1 1 U2 7 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD MAR 1 PY 2002 VL 27 IS 5 BP 333 EP 335 DI 10.1364/OL.27.000333 PG 3 WC Optics SC Optics GA 526RL UT WOS:000174143400017 PM 18007794 ER PT J AU Hartnick, CJ Giambra, BK Bissell, C Fitton, CM Cotton, RT Parsons, SK AF Hartnick, CJ Giambra, BK Bissell, C Fitton, CM Cotton, RT Parsons, SK TI Final validation of the pediatric tracheotomy health status instrument (PTHSI) SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 09-14, 2001 CL DENVER, COLORADO SP Amer Acad Otolayngol Head Neck Surg ID TRACHEOSTOMY; CHILDREN; CARE AB OBJECTIVE: We sought to describe the development and final testing of an instrument designed to evaluate the impact of tracheotomy on the health-related quality of life of affected families in whom a child has had a tracheotomy (the Pediatric Tracheotomy Health Status Instrument (PTHSI)). STUDY DESIGN: This cross-sectional study designed to analyze a disease-specific health status instrument to establish validity and reliability. RESULTS: The PTHSI was initially pilot tested in 130 families during a 3-month period from September through November 2000. After initial analysis and revision, from January 2001 through July 2001, 154 different families completed the revised instrument. The overall Cronbach's alpha coefficient for the instrument was 0.91, with domain-specific coefficients ranging from 0.66 for physical symptoms to 0.87 for caregiver stress and coping. Specific criterion validity analysis produced a Pearson correlation coefficient of 0.8 (P < 0.0001). Construct validity testing via Wilcoxon matched sum testing suggested statistically significant differences between subpopulations (P < 0.001). CONCLUSION: After initial testing and revision of the PTHSI, final instrument administration and analysis reveal the instrument to be valid and reliable. Future studies are planned to evaluate its responsiveness in longitudinal application. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Childrens Hosp, Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA USA. RP Hartnick, CJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. RI Benneyworth, Brian/A-4667-2009 OI Benneyworth, Brian/0000-0002-4692-5303 NR 10 TC 6 Z9 7 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD MAR PY 2002 VL 126 IS 3 BP 228 EP 233 DI 10.1067/mhn.2002.122634 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 548CM UT WOS:000175371100004 PM 11956529 ER PT J AU Bowling, DM AF Bowling, DM TI Argon beam coagulation for post-tonsillectomy hemostasis SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 26-29, 1999 CL NEW ORLEANS, LOUISIANA SP Amer Acad Otolaryngol Head & Neck Surg AB OBJECTIVE: The study goal was to evaluate the effectiveness of argon beam coagulation (ABC) in the prevention of post-tonsillectomy hemorrhage. ABC provides monopolar coagulation by arcing ionized argon gas to the target tissue; it is not a loser. METHODS: Two consecutive studies were performed as follows. In the first, a retrospective analysis of post-tonsillectomy bleeding in 344 patients was conducted. Final tonsil fossa hemostasis was achieved with ABC (257 patients) or with electrocoagulation (EC) (87 patients). In the second, a prospective, randomized, patient-blind study of post-tonsillectomy bleeding was conducted in 88 patients. Final hemostasis was achieved using ABC in one fossa and EC in the other fossa, with the sides chosen at random. RESULTS: Post-tonsillectomy hemorrhage was defined as the expectoration of fresh blood, as opposed to blood-streaked saliva. The rates of bleeding for the 2 studies were as follows. In study 1 for EC, 20% for adults, 6.5% for children, and 10.3% for total; for ABC, 4.7% for adults, 0.6% for children, and 1.9% for total. In study 2 for EC, 19.2% for adults, 1.6% for children, and 6.8% for total; for ABC, 7.7% for adults, 0.0% for children, and 1.1% for total. The rates of hospital admission for observation or reoperation to treat the bleeding in study 1 for EC were 8% for adults, 6.5% for children, and 6.9% for total; for ABC, 1.2% for adults, 0.6% for children, and 0.7% for total. Corresponding rates for study 2 for EC were 15.4% for adults, 1.6% for children, and 5.7% for total; for ABC, 3.8% for adults, 0.0% for children, and 1.1% for total. CONCLUSION: ABC is more effective than EC for hemostasis after tonsillectomy. The costs of ABC use vs the savings achieved from reduced bleeding are discussed. C1 Massachusetts Eye & Ear Infirm, N Suburban Ctr, Dept Otolaryngol, Stoneham, MA 02180 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. RP Bowling, DM (reprint author), Massachusetts Eye & Ear Infirm, N Suburban Ctr, Dept Otolaryngol, 1 Montvale Ave, Stoneham, MA 02180 USA. NR 4 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 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD MAR PY 2002 VL 126 IS 3 BP 316 EP 320 DI 10.1067/mhn.2002.122386 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 548CM UT WOS:000175371100016 PM 11956541 ER PT J AU El-Sayed, I Busaba, NY Faquin, WC AF El-Sayed, I Busaba, NY Faquin, WC TI Otologic manifestations of amyloidosis SO OTOLOGY & NEUROTOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Triologic-Society CY MAY 15-17, 2000 CL ORLANDO, FLORIDA SP Triol Soc DE amyloidosis; head and neck amyloidosis; otologic manifestations ID HEAD; NECK AB Objective: To describe otologic manifestations of amyloidosis. Study Design: Retrospective case review. Setting: Tertiary referral center. Patients: Case report of a patient with bilateral external auditory meatal stenosis secondary to amyloidosis. Results: The patient is a 60-year-old man who presented with several months' history of bilateral ear blockage and drainage. Physical examination revealed markedly thickened skin in each ear in the area of concha and meatus that was associated with fissuring. The meatus were markedly stenosed. The medial aspect of the external auditory canal and the tympanic membrane were normal. He had partial improvement on medical therapy with topical steroid-containing eardrops and ointment. Past medical history was positive for multiple myeloma. Meatal biopsy was performed. Grossly, the tissue was hypovascular and markedly thickened. Histopathologic examination was consistent with amyloidosis. The patient was continued on topical steroid ointments, frequent car cleaning, and close follow-up. He was subsequently diagnosed with systemic amyloidosis. A review of the literature was done. Head and neck involvement with amyloidosis is reviewed, with emphasis on otologic manifestations. Conclusion: Otologic involvement with amyloidosis is extremely rare. The pathophysiology may be related to the local factors in the external auditory canal. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Otolaryngol, Boston, MA 02118 USA. Boston VA Healthcare Syst, Div Otolaryngol, Boston, MA USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Busaba, NY (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 7 TC 7 Z9 7 U1 0 U2 0 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 2002 VL 23 IS 2 BP 158 EP 159 DI 10.1097/00129492-200203000-00009 PG 2 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 526EB UT WOS:000174115500009 PM 11875343 ER PT J AU Harthorne, JW AF Harthorne, JW TI The grate SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Harthorne, JW (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD MAR PY 2002 VL 25 IS 3 BP 361 EP 361 DI 10.1046/j.1460-9592.2002.00361.x PG 1 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 538RY UT WOS:000174829900015 ER PT J AU Oaklander, AL Cohen, SP Raju, SVY AF Oaklander, AL Cohen, SP Raju, SVY TI Intractable postherpetic itch and cutaneous deafferentation after facial shingles SO PAIN LA English DT Article DE nervous system/physiopathology; human; pruritus/physiopathology; herpes zoster; neuralgia; postherpetic neuralgia ID NOTALGIA-PARESTHETICA; UNILATERAL PRURITUS; NEURALGIA; BRAIN; SKIN AB Some patients develop chronic itch from neurological injuries, and shingles may be a common cause. Neuropathic itch can lead to self-injury from scratching desensate skin. A 39-year-old woman experienced severe postherpetic itch, but no postherpetic neuralgia, after ophthalmic zoster. Within 1 year, she had painlessly scratched through her frontal skull into her brain. Sensory testing and skin biopsies were performed on itchy and normal scalp to generate preliminary hypotheses about mechanisms of neuropathic itch. Quantitation of epidermal neurites in PGP9.5-immunolabeled skin biopsies demonstrated loss of 96% of epidermal innervation in the itchy area. Quantitative sensory testing indicated severe damage to most sensory modalities except itch. These data indicate that in this patient, severe postherpetic itch was associated with loss of peripheral sensory neurons. Possible mechanisms include electrical hyperactivity of hypo-afferented central itch-specific neurons, selective preservation of peripheral itch-fibers from neighboring unaffected dermatomes. and/or imbalance between excitation and inhibition of second-order sensory neurons. (C) 2002 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuropath Pain Study Grp,Dept Anesthesiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neuropathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA USA. MS Ramaiah Med Coll, Bangalore, Karnataka, India. RP Oaklander, AL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuropath Pain Study Grp,Dept Anesthesiol, 55 Fruit St,Clinics 3, Boston, MA 02114 USA. NR 22 TC 65 Z9 67 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD MAR PY 2002 VL 96 IS 1-2 BP 9 EP 12 AR PII S0304-3959(01)00400-6 DI 10.1016/S0304-3959(01)00400-6 PG 4 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 554MD UT WOS:000175738800003 PM 11932056 ER PT J AU Dauber, A Osgood, PF Breslau, AJ Vernon, HL Carr, DB AF Dauber, A Osgood, PF Breslau, AJ Vernon, HL Carr, DB TI Chronic persistent pain after severe burns: A survey of 358 burn survivors SO PAIN MEDICINE LA English DT Article DE chronic pain; burns; burn survivors; pain prevalence; pain treatment; pain characteristics ID MANAGEMENT; CHILDREN; QUESTIONNAIRE AB Objective. To determine the prevalence, characteristics, and effects of chronic persistent pain on burn survivors. Design. Mail survey Setting. Respondents' homes Patients. All members of the Phoenix Society for Burn Survivors Interventions. None Outcome Measures. Twenty-three questions on the prevalence of pain and its characteristics, including the short form of the McGill-Melzack Pain Questionnaire Results. Of 1,500 members who received the survey, 358 (24%) responded. Respondents had burns covering an average of 59% of their bodies. Time between the injury and the survey averaged 12 years. On the survey, 52% of respondents reported ongoing burn-related pain, and 46% were able to characterize their pain with one or more of 15 characteristics, Two-thirds (66%) reported that pain interfered with their rehabilitation, and 55% reported that pain interfered with their daily lives. Asked "what makes the pain worse now?," the most frequent reply (15%) was "the weather" (including "hot" or "cold"). Various physical activities (e.g., walking, bicycling) were also mentioned, along with nerve regrowth, contractures, remembering the accident, and depression. "Things that make your pain better now" included "nothing," a variety of over-the-counter analgesics, "rest," "exercise," "yoga," "acupuncture," "family and friends," and "God." In coping with their pain, most respondents found family the most helpful, although nurse(s) received almost as high a rating. Conclusions. Pain associated with burn trauma continues to be of considerable significance in the lives of burn victims long after the initial injury and hospitalization, Little research has been clone on this population. C1 Tufts Univ New England Med Ctr, Dept Anesthesia, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Anesthesia, Boston, MA 02111 USA. Schwabinger Krankenhaus, Munich, Germany. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Phoenix Soc Burn Survivors, Levittown, PA USA. RP Carr, DB (reprint author), Tufts Univ New England Med Ctr, Dept Anesthesia, Box 298,750 Washington St, Boston, MA 02111 USA. EM daniel.carr@tufts.edu NR 34 TC 59 Z9 60 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD MAR PY 2002 VL 3 IS 1 BP 6 EP 17 DI 10.1046/j.1526-4637.2002.02004.x PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 548EH UT WOS:000175375300003 PM 15102213 ER PT J AU Aslam, N Bernardini, J Fried, L Piraino, B AF Aslam, N Bernardini, J Fried, L Piraino, B TI Large body mass index does not predict short-term survival in peritoneal dialysis patients SO PERITONEAL DIALYSIS INTERNATIONAL LA English DT Article DE body mass index; patient survival; technique survival ID HEMODIALYSIS-PATIENTS; MORTALITY; SIZE AB Objective: Higher than normal body mass index (BMI) is associated with an increased risk of death in the general population. We examined the effect of higher than normal BMI on patient and technique survival in peritoneal dialysis patients (PD), controlling for comorbidity, initial albumin, dialysate-to-plasma ratio of creatinine (D/P-Cr), and initial urea clearance (Kt/V). Design: Registry database. Settings: Four dialysis centers. Patients: Incident PD patients. Methods: All data were collected prospectively. Demographics, BMI, serum albumin, D/P-Cr, and comorbidity using the Charlson Comorbidity Index (CCI) were determined at the start of PD. 104 patients with a high BMI (> 27) were matched to a control group of 104 patients with normal BMI (20 - 27) for age, gender, presence of diabetes, and CCI. Patient and technique survival were compared using Cox proportional hazards model. Main Outcome Measures: Patient and technique survival. Results. The groups were of similar age (56.1 vs 56.7 years), sex (60% males in both groups), race (Caucasian 80% vs 86%), presence of diabetes (40% vs 37%), CCI score (5.4 in both groups), initial albumin (3.6 vs 3.5 g/dL), and D/P-Cr (0.65 in both groups). Kaplan-Meier survival analysis showed similar 2-year patient survival between large BMI (> 27) and control (20 - 27) groups (76.6% vs 76.1%). Two-year technique survival was also similar between the two groups (59.7% vs 66.8%). With Cox proportional hazards analysis, BMI was not a predictor of patient mortality or technique survival when controlling for initial albumin, D/P-Cr, and initial Kt/V. Conclusions: We conclude that a BMI above normal is not associated with any increased or decreased risk of death in patients on PD for 2 years. C1 Univ Pittsburgh, Sch Med, Renal & Elect Div, Pittsburgh, PA 15261 USA. VA Pittsburgh Hlth Care Syst, Renal Div, Pittsburgh, PA USA. RP Aslam, N (reprint author), Univ Pittsburgh, Sch Med, Renal & Elect Div, A907 Scaife Hall 3550 Terrace St, Pittsburgh, PA 15261 USA. OI Piraino, Beth/0000-0001-5061-0841 NR 14 TC 62 Z9 62 U1 0 U2 0 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 0896-8608 J9 PERITON DIALYSIS INT JI Perit. Dial. Int. PD MAR-APR PY 2002 VL 22 IS 2 BP 191 EP 196 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 542ZW UT WOS:000175076700005 PM 11990403 ER PT J AU Gaudette, R Schnitzer, J George, E Briggs, SM AF Gaudette, R Schnitzer, J George, E Briggs, SM TI Lessons learned from the September 11th World Trade Center disaster: Pharmacy preparedness and participation in an international medical and surgical response team SO PHARMACOTHERAPY LA English DT Article C1 Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. RP Gaudette, R (reprint author), Massachusetts Gen Hosp, Dept Pharm, 55 Fruit St, Boston, MA 02114 USA. NR 9 TC 6 Z9 6 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 2002 VL 22 IS 3 BP 271 EP 281 DI 10.1592/phco.22.5.271.33197 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 528KG UT WOS:000174242500001 PM 11898887 ER PT J AU Schultes, G Gaggl, A Karcher, H August, M AF Schultes, G Gaggl, A Karcher, H August, M TI Stability of dental implants in microvascular osseous transplants - Discussion SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Editorial Material ID ADJUNCTIVE HYPERBARIC-OXYGEN; VASCULARIZED BONE FLAPS; OSSEOINTEGRATED IMPLANTS; OROMANDIBULAR RECONSTRUCTION; REHABILITATION; EXPERIENCE C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP August, M (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. NR 15 TC 3 Z9 3 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 2002 VL 109 IS 3 BP 922 EP 924 PG 3 WC Surgery SC Surgery GA 527WX UT WOS:000174211900016 ER PT J AU Servoss, SJ Januzzi, JL Muller, JE AF Servoss, SJ Januzzi, JL Muller, JE TI Triggers of acute coronary syndromes SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review ID ACUTE MYOCARDIAL-INFARCTION; SUDDEN CARDIAC DEATH; CIRCADIAN VARIATION; CARDIOVASCULAR-DISEASE; ANGINA-PECTORIS; ARTERY DISEASE; MENTAL STRESS; PLATELET AGGREGABILITY; PHYSICAL EXERTION; NATIONAL REGISTRY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA 02114 USA. RP Muller, JE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA 02114 USA. NR 74 TC 45 Z9 50 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-0620 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD MAR-APR PY 2002 VL 44 IS 5 BP 369 EP 380 DI 10.1053/pcad.2002.123470 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 555JD UT WOS:000175790200005 PM 12024335 ER PT J AU Ambati, J Adamis, AP AF Ambati, J Adamis, AP TI Transscleral drug delivery to the retina and choroid SO PROGRESS IN RETINAL AND EYE RESEARCH LA English DT Article ID TISSUE-PLASMINOGEN-ACTIVATOR; MOLECULAR-WEIGHT COMPOUNDS; HUMAN SCLERAL PERMEABILITY; RABBIT EYES; TRANSCORNEAL IONTOPHORESIS; OCULAR TOXICITY; HUMAN CORNEAL; COLLAGEN; GENTAMICIN; DIFFUSION AB Rapid advances in the molecular pathogenesis of retinal and choroidal disorders have highlighted the urgent need for innovative drug delivery modalities to the loci of pathology. In vitro and in vivo studies suggest that the transseleral route may offer a means to achieve the goal of sustained, targeted drug delivery to the posterior segment. Potentially therapeutic concentrations of macromolecules with retention of bioactivity can be attained in the choroid and retina via minimally invasive transscleral delivery. (C) 2002 Published by Elsevier Science Ltd. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Univ Kentucky, Dept Ophthalmol, Lexington, KY 40536 USA. Harvard Univ, Childrens Hosp, Sch Med, Surg Res Lab, Boston, MA 02115 USA. RP Adamis, AP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 245 Charles St, Boston, MA 02114 USA. NR 73 TC 60 Z9 63 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1350-9462 J9 PROG RETIN EYE RES JI Prog. Retin. Eye Res. PD MAR PY 2002 VL 21 IS 2 BP 145 EP 151 AR PII S1350-9462(01)00018-0 DI 10.1016/S1350-9462(01)00018-0 PG 7 WC Ophthalmology SC Ophthalmology GA 584EF UT WOS:000177453700001 PM 12062532 ER PT J AU Johnson, WB Huwe, JM AF Johnson, WB Huwe, JM TI Toward a typology of mentorship dysfunction in graduate school SO PSYCHOTHERAPY LA English DT Article ID MENTORING RELATIONSHIPS; PROTEGE RELATIONSHIPS; CLINICAL-PSYCHOLOGY; ETHICAL ISSUES; EDUCATION; PERCEPTIONS; STUDENTS; EXPERIENCES; FACULTY; TEACHER AB Researchers, writers, and practitioners of mentoring relationships have traditionally avoided discussion of the dark and dysfunctional side of mentoring. Student-faculty mentorships in graduate settings are sometimes characterized by dysfunction stemming from such varied sources as faulty matching, boundary violations, incompetence, conflict, and cross-gender or cross-race concerns. In this article, a typology of dysfunctional graduate school mentorships is offered for the purpose of bolstering theory development, research and both departmental and individual prevention efforts. The article concludes with several strategic recommendations for both graduate program administrators and individual faculty members who find themselves in problem mentorships with graduate students. C1 USN Acad, Dept Leadership Eth & Law, Annapolis, MD 21402 USA. Portland Vet Affairs Med Ctr, Dept Psychol, Portland, OR USA. RP Johnson, WB (reprint author), USN Acad, Dept Leadership Eth & Law, Luce Hall,Stop 7B, Annapolis, MD 21402 USA. EM johnsonb@usna.edu NR 45 TC 27 Z9 28 U1 0 U2 4 PU AMER PSYCHOLOGICAL ASSOC, DIV PSYCHOTHERAPY PI CORAL GABLES PA 1390 SOUTH DIXIE HIGHWAY, STE 2222, CORAL GABLES, FL 33146-2946 USA SN 0033-3204 J9 PSYCHOTHERAPY JI Psychotherapy PD SPR PY 2002 VL 39 IS 1 BP 44 EP 55 DI 10.1037//0033-3204.39.1.44 PG 12 WC Psychology, Clinical SC Psychology GA 906OA UT WOS:000227650300005 ER PT J AU Asch, SM Sa'adah, MG Lopez, R Kokkinis, A Richwald, GA Rhew, DC AF Asch, SM Sa'adah, MG Lopez, R Kokkinis, A Richwald, GA Rhew, DC TI Comparing quality of care for sexually transmitted diseases in specialized and general clinics SO PUBLIC HEALTH REPORTS LA English DT Article ID HOSPITAL EXPERIENCE; PHYSICIANS; AIDS; MORTALITY; PERFORMANCE; GUIDELINES; PATIENT AB Objective. The objective of this study was to compare quality of care for patients with sexually transmitted diseases (STDs) in specialized vs. general clinics. Methods. The authors conducted a retrospective chart review evaluating compliance with a set of STD-related process of care quality indicators for adult patients seen in six Los Angeles County clinics (two STD specialized clinics and four general medical clinics). Results. Thirty-two quality indicators were selected using a modified Delphi process. From March 1, 1996, to June 31, 1996, there were 205 STD-related visits to the two specialized STD clinics and 373 STD-related visits to the four general medical clinics. For patients with "classic" STDs (those for which sexual contact is the primary means of transmission), STD clinics achieved greater compliance than general medical clinics on 14 quality indicators, while general medical clinics achieved greater compliance on 4 indicators. Conclusion. STD clinics provide better overall STD care than general medical clinics. Possible explanations include differences in clinician experience with STD patients and greater use of standardized protocol sheets. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Sexually Transmitted Dis Program, Dept Hlth Serv Publ Hlth, Los Angeles, CA USA. Zynx Hlth Inc, Cedars Sinai Dept Med, Beverly Hills, CA USA. Zynx Hlth Inc, Hlth Serv Res, Beverly Hills, CA USA. RP Asch, SM (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd 111G, Los Angeles, CA 90073 USA. NR 17 TC 13 Z9 13 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD MAR-APR PY 2002 VL 117 IS 2 BP 157 EP 163 DI 10.1093/phr/117.2.157 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 605MC UT WOS:000178680800008 PM 12357000 ER PT J AU Shekelle, PG AF Shekelle, PG TI Why don't physicians enthusiastically support quality improvement programmes? SO QUALITY & SAFETY IN HEALTH CARE LA English DT Editorial Material AB Resistance of physicians to clinical governance will continue until they can see how a real programme works operationally and a measurable leap in quality is achieved. In the absence of a role model, the opportunity exists for the NHS to fund primary care groups/trusts to develop a model that can be seen to work. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Shekelle, PG (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 1 TC 25 Z9 25 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1475-3898 J9 QUAL SAF HEALTH CARE JI Qual. Saf. Health Care PD MAR PY 2002 VL 11 IS 1 BP 6 EP 6 DI 10.1136/qhc.11.1.6 PG 1 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 551KM UT WOS:000175560900005 PM 12078372 ER PT J AU Maher, MM Kealey, S McNamara, A O'Laoide, R Gibney, RG Malone, DE AF Maher, MM Kealey, S McNamara, A O'Laoide, R Gibney, RG Malone, DE TI Management of visceral interventional radiology catheters: A troubleshooting guide for interventional radiologists SO RADIOGRAPHICS LA English DT Article DE catheters and catheterization; catheters and catheterization, complications; interventional procedures; interventional procedures, complications AB Visceral interventional radiology catheters can be difficult to exchange or remove for a variety of reasons. These reasons include exit of the guide wire through the side holes of the catheter, blockage of the catheter, difficulty unlocking the pigtail, retention of the string after catheter removal, migration of the string ahead of the guide wire, catheter fracture, and snaring of an adjacent stent by the pigtail. Secure fixation of the catheter to the skin is important. A technique that allows secure fixation without direct puncture and suturing of the catheter to the skin is recommended. If a catheter falls out or is inadvertently removed, access can occasionally be regained and the catheter can be replaced Without repuncture. The timing of catheter removal is based on the clinical condition of the patient and the daily output from the catheter. "Tractography" is a useful study before removal of any catheter that requires a mature tract for removal particularly cholecystostomy catheters and transpleural catheters. In biliary catheter exchange, the most vital issue is the position of the side holes of the catheter. If an abscess cavity remains large after catheter drainage, the catheter can be repositioned or a second catheter can be placed. (C)RSNA 2002. C1 St Vincents Univ Hosp, Dept Radiol, Dublin, Ireland. RP Maher, MM (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. NR 6 TC 10 Z9 10 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD MAR-APR PY 2002 VL 22 IS 2 BP 305 EP 322 PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 529NB UT WOS:000174304600007 PM 11896221 ER PT J AU Bencardino, JT Palmer, WE AF Bencardino, JT Palmer, WE TI Imaging of hip disorders in athletes SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID ACETABULAR LABRAL TEARS; RSNA REFRESHER COURSES; MR ARTHROGRAPHY; OSTEOCHONDRITIS-DISSECANS; ISCHIAL TUBEROSITY; ASYMPTOMATIC HIPS; STRESS-FRACTURES; INJURIES; PAIN; AVULSION AB Normal hip joint function is fundamental in running-, jumping-, and kicking-based sporting activities. Hip disorders do not account for a large portion of exercise-related injuries, but they can pose a clinical dilemma since symptoms tend to be nonspecific. Conventional radiographs may demonstrate some causes of hip pain, such as stress fractures and degenerative joint disease, Magnetic resonance (MR) imaging of the hip has proven valuable in the diagnosis of radiographically occult osseous abnormalities and periarticular soft tissue disorders such as stress fractures, avulsion injuries, musculotendinous abnormalities, and bursitis. Conventional MR imaging has been less useful in the evaluation of intra-articular lesions including acetabular labral tears, intra-articular loose bodies, and cartilage lesions. The visualization of intra-articular structures and their abnormalities can be improved by the injection of diluted Gadolinium, which distends the capsule and leaks into labral tears. This article will focus on the use of conventional radiography and MR imaging in recreational and professional athletes with painful hip joints, and where possible it will compare MR imaging with other diagnostic modalities such as bone scan and CT. C1 Massachusetts Gen Hosp, Div Bone & Joint Radiol, Boston, MA 02114 USA. RP Bencardino, JT (reprint author), Massachusetts Gen Hosp, Div Bone & Joint Radiol, 15 Parkman St,WACC 515, Boston, MA 02114 USA. NR 66 TC 24 Z9 24 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD MAR PY 2002 VL 40 IS 2 BP 267 EP + AR PII S0033-8389(02)00006-4 DI 10.1016/S0033-8389(02)00006-4 PG 23 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 568DZ UT WOS:000176528300008 PM 12118825 ER PT J AU Gervais, DA Hahn, PF O'Neill, MJ Mueller, PR AF Gervais, DA Hahn, PF O'Neill, MJ Mueller, PR TI Percutaneous abscess drainage in Crohn disease: Technical success and short- and long-term outcomes during 14 years SO RADIOLOGY LA English DT Article DE abscess, percutaneous drainage; Crohn disease; interventional procedures ID INTRA-ABDOMINAL ABSCESS; FLUID COLLECTIONS; PELVIC ABSCESS; MANAGEMENT AB PURPOSE: To determine technical success with percutaneous abscess drainage (PAD) in patients with Crohn disease during 14 years. MATERIALS AND METHODS: Medical records of 32 patients with Crohn disease who underwent PAD from 1985 to 1999 were reviewed. Results of abscess drainage and nature of subsequent surgical procedures were recorded. Factors assessed included postoperative or spontaneous nature of the abscess, documentation of a proved fistula, history of occurrence of prior abscesses, duration of Crohn disease, and use of steroid treatment. Technical success was defined as complete abscess drainage. Short-term success was defined as avoidance of surgery within 60 days of drainage. Long-term success was defined as avoidance of surgery beyond the initial 60-day period. Short-term avoidance of surgery was assessed as a predictor of the need for surgery in the long term. Statistical analysis was performed with the chi(2) test to evaluate predictors of short-term success and to assess short-term success as a predictor of long-term success. RESULTS: The technical success rate was 96%. In 16 (50%) of 32 patients, the need for surgery in the short term was avoided, and surgery was more likely to be avoided in patients with postoperative abscesses than in those with spontaneous abscesses (P = .07). At long-term follow-up, short-term avoidance of surgery did not significantly increase the likelihood of need for surgery in the long term, which occurred in nine of 16 short-term successes versus five of 15 short-term failures (P = .55). Recurrent abscesses occurred in seven (22%) patients, a rate comparable to that with surgical abscess drainage; four (44%) of nine cases of redrainage were successful. CONCLUSION: PAD has a high technical success rate of 96%. Half of patients may avoid surgery in the short term. (C) RSNA, 2002. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Gervais, DA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,White 270, Boston, MA 02114 USA. NR 19 TC 64 Z9 67 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAR PY 2002 VL 222 IS 3 BP 645 EP 651 DI 10.1148/radiol.2223010554 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 524TX UT WOS:000174029900010 PM 11867780 ER PT J AU Goldberg, SN Girnan, GD Lukyanov, AN Ahmed, M Monsky, WL Gazelle, GS Huertas, JC Stuart, KE Jacobs, T Torchillin, VP Halpern, EF Kruskal, JB AF Goldberg, SN Girnan, GD Lukyanov, AN Ahmed, M Monsky, WL Gazelle, GS Huertas, JC Stuart, KE Jacobs, T Torchillin, VP Halpern, EF Kruskal, JB TI Percutaneous tumor ablation: Increased necrosis with combined radio-frequency ablation and intravenous liposomal doxorubicin in a rat breast tumor model SO RADIOLOGY LA English DT Article DE animals; breast neoplasms, therapy; chemotherapy; hyperthermia; radiofrequency (RF) ablation ID RADIOFREQUENCY ABLATION; HEPATOCELLULAR-CARCINOMA; HEPATIC METASTASES; THERMAL ABLATION; PHASE-II; HYPERTHERMIA; MALIGNANCIES; ELECTRODE; EFFICACY; CANCER AB PURPOSE: To determine whether a combination of intravenous liposomal doxorubicin and radio-frequency (RF) ablation increases tumor destruction compared with RF alone in an animal tumor model. MATERIALS AND METHODS: R3230 mammary adenocarcinoma 1.4-1.8-cm-diameter nodules were implanted subcutaneously in 132 female Fischer rats. Initially, tumors were treated with (a) conventional, monopolar RF (mean, 250 mA +/- 25 [SD] at 70degreesC +/- 1 for 5 minutes) ablation alone, (b) RF ablation followed by intravenous administration of 1 mg of liposomal doxorubicin, (c) RF ablation followed by intravenous administration of 1 mg of empty liposomes, (d) RF ablation and direct intratumoral administration of liposomal doxorubicin, or (e) no treatment. Subsequently, the dose (0.06-2.00 mg) of liposomal doxorubicin, the timing of administration (3 days before to 3 days after RF ablation), and the time of pathologic examination (0-72 hours after treatment) were varied. RESULTS: Mean coagulation diameter for treated tumors follows: 6.7 mm +/- 0.6, RF ablation alone; 11.1 mm +/- 1.5, RF ablation and intravenous administration of empty liposomes (P < .05, compared with RF ablation alone); and 8.4 mm +/- 1.1, RF ablation with intratumoral administration of liposomal doxorubicin (P < .05, compared with RF ablation alone). Maximal increased mean coagulation diameter (13.1 mm 1.5) was observed with a combination of liposomal doxorubicin and RF ablation (P < .001, for all comparisons). The increased coagulation for combination therapy developed over 48 hours after therapy. Coagulation diameter did not vary with the doxorubicin concentration range and was not dependent on the timing of administration of liposomal doxorubicin from 3 days before to 24 hours after RF ablation. CONCLUSION: Intravenous administration of liposomal doxorubicin can improve RF ablation, since it increases coagulation diameter in solid tumors compared with RF ablation alone or a combination of RF ablation with administration of empty liposomes. (C) RSNA, 2002. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiol, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med Oncol, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Pathol, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Northeastern Univ, Bouve Coll Hlth Sci, Dept Pharmaceut Sci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Goldberg, SN (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA. NR 35 TC 86 Z9 94 U1 0 U2 5 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 2002 VL 222 IS 3 BP 797 EP 804 DI 10.1148/radiol.2223010861 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 524TX UT WOS:000174029900032 PM 11867804 ER PT J AU Bremer, C Tung, CH Bogdanov, A Weissleder, R AF Bremer, C Tung, CH Bogdanov, A Weissleder, R TI Imaging of differential protease expression in breast cancers for detection of aggressive tumor phenotypes SO RADIOLOGY LA English DT Article DE breast neoplasms, experimental studies; infrared and near-infrared spectroscopy; animals ID CATHEPSIN-B; SECRETION; TISSUE; PROTEINASES; INHIBITORS AB PURPOSE: To determine if different expression levels of tumor cathepsin-B activity in well differentiated and undifferentiated breast cancers could be revealed in vivo with optical imaging. MATERIALS AND METHODS: A well differentiated human breast cancer (BT20, n = 8) and a highly invasive metastatic human breast cancer (DU4475, n = 8) were implanted orthotopically in athymic nude mice. Tumor-bearing animals were examined in vivo with near-infrared fluorescence (NIRF) imaging 24 hours after intravenous injection of an enzyme-sensing imaging probe. Immunohistochemistry, Western blotting (on cells and whole tumor samples), and correlative fluorescence microscopy were performed. RESULTS: Both types of breast cancers activated the NIRF probe so that tumors became readily detectable. However, in tumors of equal size, there was a 1.5-fold higher fluorescence signal in the highly invasive breast cancer (861 arbitrary units 88) compared with the well differentiated lesion (566 arbitrary units 36, P < .01). Western blotting confirmed a higher cathepsin-B protein content in the highly invasive breast cancer (DU4475) of about 1.4-fold (whole tumor samples) to 1.7-fold (cells). Immunohistochemistry and fluorescence microscopy findings confirmed the imaging findings. CONCLUSION: Cathepsin-B enzyme activity can be determined in vivo with NIRF optical imaging, while differences in tumoral expression may correlate with tumor aggressiveness. (C) RSNA, 2002. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Bremer, C (reprint author), Univ Munster, Dept Clin Radiol, D-48129 Munster, Germany. OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [P50-CA86355-01]; PHS HHS [N0I-C0M065] NR 31 TC 102 Z9 107 U1 0 U2 14 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 2002 VL 222 IS 3 BP 814 EP 818 DI 10.1148/radiol.2223010812 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 524TX UT WOS:000174029900034 PM 11867806 ER PT J AU Esch, TR Poveromo, JD Aikins, MC Levanos, VA AF Esch, TR Poveromo, JD Aikins, MC Levanos, VA TI A novel lacrimal gland autoantigen in the NOD mouse model of Sjogren's syndrome SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOCYTE POPULATIONS; INDUCED SUPPRESSION; AUTOIMMUNE-DISEASE; EXOCRINE TISSUES; MICE; AUTOANTIBODIES; UTEROGLOBIN; EXPRESSION AB Recent research has demonstrated a crucial role for autoantibodies in the pathogenesis of Sjogren's syndrome (SS)-like disease in the non-obese diabetic (NOD) mouse, but it remains to be determined which antibody species among all those present are directly related to the various aspects of pathology. To identify autoantigens in the NOD mouse system, we have taken the approach of using immunoglobulin (Ig)G purified from sera of NOD mice exhibiting SS-like symptoms to screen cDNA expression libraries derived from exocrine gland mRNA. Here we report the identification of a novel autoantigen, designated LGP10. expressed in lacrimal and submandibular glands. Autoantibodies to this protein are prominent in the sera of NOD mice starting at 11-12 weeks of age, but not in control nonautoimmune mice. LGP10 has no known function. but bears similarities to various other proteins produced by epithelia. Interestingly, all of these similar proteins have been linked to immunosuppression and/or steroid binding, both processes that could have a significant impact on pathological features of SS. C1 Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. Forsyth Inst, Harvard Forsyth Dept Oral Biol, Boston, MA 02115 USA. RP Esch, TR (reprint author), Forsyth Inst, Dept Immunol, 140 Fenway, Boston, MA 02115 USA. FU NIAID NIH HHS [AI-43297] NR 22 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD MAR PY 2002 VL 55 IS 3 BP 304 EP 310 DI 10.1046/j.1365-3083.2002.01042.x PG 7 WC Immunology SC Immunology GA 529PE UT WOS:000174307200013 PM 11940237 ER PT J AU Freedman, R Adler, LE Olincy, A Waldo, MC Ross, RG Stevens, KE Leonard, S AF Freedman, R Adler, LE Olincy, A Waldo, MC Ross, RG Stevens, KE Leonard, S TI Input dysfunction, schizotypy, and genetic models of schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article; Proceedings Paper CT NATO Advanced Research Workshop on Schizophrenia and Schizotypy held in Honor of Peter Venables CY MAR 24-27, 2001 CL TUSCANY, ITALY DE schizophrenia; schizotypy; inhibition; hippocampus; auditory-evoked potential; catecholamines; nicotinic receptors; genetic linkage; human chromosome 15 ID ALPHA-BUNGAROTOXIN-BINDING; P50 SUPPRESSION; SUSCEPTIBILITY LOCUS; NICOTINIC RECEPTORS; GATING DEFICITS; NO EVIDENCE; LINKAGE; SMOKING; CLOZAPINE; BRAIN AB Peter Venables proposed that an input dysfunction. which causes the brain to lose its ability to control the flood of sensors information into its higher level processing areas, might be an important pathophysiological mechanism in schizophrenia. The hypothesis was part of his general belief that even the most severe psychopathology arises from aberrations in normal brain psychophysiology, Neurobiological and genetic investigations based on his initial observations include the demonstration that diminished inhibition of the auditory-evoked response to repeated stimuli is a genetically determined deficit, linked to one of the chromosomal loci that is also responsible for the part of the genetically transmitted risk for schizophrenia. Increasing evidence that schizophrenia is a multigenetic illness prompts reconsideration of the nature of schizotypy. Individual genes that convey part of the risk for schizophrenia may be quite common in the general population and cause relatively subtle changes in psychophysiology, Thus, as predicted by Venables, the substrates of schizotypy and schizophrenia may arise from variants in normal brain function, (C) 2002 Elsevier Science B.V. All rights reserved. C1 Denver Vet Affairs Med Ctr, Dept Psychiat & Pharmacol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. RP Freedman, R (reprint author), Denver Vet Affairs Med Ctr, Dept Psychiat & Pharmacol, Campus Box C-268-71,4200 E 9th Ave, Denver, CO 80262 USA. NR 42 TC 21 Z9 21 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 1 PY 2002 VL 54 IS 1-2 SI SI BP 25 EP 32 AR PII S0920-9964(01)00348-6 DI 10.1016/S0920-9964(01)00348-6 PG 8 WC Psychiatry SC Psychiatry GA 529ND UT WOS:000174304800004 PM 11853975 ER PT J AU Buchsbaum, MS Nenadic, I Hazlett, EA Spiegel-Cohen, J Fleischman, MB Akhavan, A Silverman, JM Siever, LJ AF Buchsbaum, MS Nenadic, I Hazlett, EA Spiegel-Cohen, J Fleischman, MB Akhavan, A Silverman, JM Siever, LJ TI Differential metabolic rates in prefrontal and temporal Brodmann areas in schizophrenia and schizotypal personality disorder SO SCHIZOPHRENIA RESEARCH LA English DT Article; Proceedings Paper CT NATO Advanced Research Workshop on Schizophrenia and Schizotypy held in Honor of Peter Venables CY MAR 24-27, 2001 CL TUSCANY, ITALY DE positron emission tomography (PET); magnetic resonance imaging (MRI); frontal lobe; temporal lobe ID VERBAL-LEARNING TASK; CEREBRAL BLOOD-FLOW; VENTRICULAR VOLUME; MRI; PET; SHAPE; SIZE; ABNORMALITIES; PERFORMANCE; INTERVIEW AB In an exploration of the schizophrenia spectrum, we compared cortical metabolic rates in unmedicated patients with schizophrenia and schizotypal personality disorder (SPD) with findings in age- and sex-matched normal volunteers. Coregistered magnetic resonance imaging (MRI) and positron emission tomography (PET) scans were obtained in 27 schizophrenic, 13 SPD, and 32 normal volunteers who performed a serial verbal learning test during tracer uptake. A template of Brodmann areas derived from a whole brain histological section atlas was used to analyze PET findings. Significantly lower metabolic rates were found in prefrontal areas 44-46 in schizophrenic patients than in normal volunteers. SPD patients did not differ from normal volunteers in most lateral frontal regions, but they had values intermediate between those of normal volunteers and schizophrenic patients in lateral temporal regions. SPD patients showed higher than normal metabolic rates in both medial frontal and medial temporal areas. Metabolic rates in Brodmann area 10 were distinctly higher in SPD patients than in either normal volunteers or schizophrenic patients. (C) 2002 Elsevier Science B.V. All rights reserved. C1 CUNY Mt Sinai Sch Med, Dept Psychiat, Neurosci PET Lab, New York, NY 10029 USA. Klinikum Friedrich Schiller Univ, Hans Berger Kliniken, Psychiat Klin, Jena, Germany. Bronx Vet Affairs Med Ctr, Psychiat Serv, Bronx, NY 10468 USA. RP Buchsbaum, MS (reprint author), CUNY Mt Sinai Sch Med, Dept Psychiat, Neurosci PET Lab, Box 1505,1 Gustave L Levy Pl, New York, NY 10029 USA. FU NIMH NIH HHS [MH 40071, MH 56460, MH 56489, MH 60023] NR 38 TC 71 Z9 71 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 1 PY 2002 VL 54 IS 1-2 SI SI BP 141 EP 150 AR PII S0920-9964(01)00361-9 DI 10.1016/S0920-9964(01)00361-9 PG 10 WC Psychiatry SC Psychiatry GA 529ND UT WOS:000174304800017 PM 11853988 ER PT J AU Tsuang, MT Stone, WS Tarbox, SI Faraone, SV AF Tsuang, MT Stone, WS Tarbox, SI Faraone, SV TI An integration of schizophrenia with schizotypy: identification of schizotaxia and implications for research on treatment and prevention SO SCHIZOPHRENIA RESEARCH LA English DT Article; Proceedings Paper CT NATO Advanced Research Workshop on Schizophrenia and Schizotypy held in Honor of Peter Venables CY MAR 24-27, 2001 CL TUSCANY, ITALY DE schizotypal pcrsonality disorder; negative schizotypy; schizotaxia; schizophrenia ID SPECTRUM PERSONALITY-DISORDERS; NONPSYCHOTIC RELATIVES; INDICATORS; PRONENESS; PSYCHOSIS; SIBLINGS; VALIDITY; MARKERS; FAMILY; RISK AB The liability to schizophrenia (schizotaxia) is associated with deficits in a variety of domains, including negative symptoms and neuropsychological deficits, even in the absence of psychosis or pre-psychotic prodromal symptoms. Conceptually, this view of schizotaxia is similar to negative schizotypy (i.e. schizotypal personality disorder minus the positive symptoms). It is broader than DSM-IV schizotypal personality disorder (SPD), however, in that more relatives of patients with schizophrenia show core symptoms of schizotaxia than meet the diagnostic criteria for SPD. Three lines of evidence support the validity of schizotaxia. First, evidence of concurrent validation was obtained by showing that schizotaxic subjects were more impaired than non-schizotaxic subjects on a variety of independent clinical scales, Second, schizotaxic subjects showed higher levels of negative symptoms on the Structured Interiew for Schizotypy than non-schizotaxic subjects, but did not differ on positive symptoms. Third, subjects who met predetermined criteria for schizotaxia (i.e., negative symptoms and neuropsychological deficits) showed positive effects following treatment with low doses of risperidone (0.25-2.0 mg). Thus, clinical deficits in schizotaxia may be identifiable. and to a significant extent, reversible. Implications for the conception of schizotypy and the prevention of schizophrenia will be discussed, (C) 2002 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Brockton W Roxbury VA Med Ctr, Harvard Med Sch, Dept Psychiat, Brockton, MA 02301 USA. RP Tsuang, MT (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Mental Hlth Ctr, 74 Fenwood Rd, Boston, MA 02115 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [1R01 MH 41879-01, 1R37 MH 43518-01, 5U01 MH 46318-02] NR 43 TC 73 Z9 74 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 1 PY 2002 VL 54 IS 1-2 SI SI BP 169 EP 175 AR PII S0920-9964(01)00364-4 DI 10.1016/S0920-9964(01)00364-4 PG 7 WC Psychiatry SC Psychiatry GA 529ND UT WOS:000174304800020 PM 11853991 ER PT J AU Neumann, HPH Hoegerle, S Manz, T Brenner, K Iliopoulos, O AF Neumann, HPH Hoegerle, S Manz, T Brenner, K Iliopoulos, O TI How many pathways to pheochromocytoma? SO SEMINARS IN NEPHROLOGY LA English DT Review ID HIPPEL-LINDAU-DISEASE; TUMOR-SUPPRESSOR GENE; MULTIPLE ENDOCRINE NEOPLASIA; ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; NEUROFIBROMATOSIS TYPE-1; GERMLINE MUTATIONS; VONRECKLINGHAUSEN NEUROFIBROMATOSIS; RET PROTOONCOGENE; SOMATIC MUTATIONS C1 Univ Freiburg, Nephrol Sect, Dept Med, D-7800 Freiburg, Germany. Univ Freiburg, Dept Nucl Med, D-7800 Freiburg, Germany. Massachusetts Gen Hosp, Canc Ctr, Charlestown, MA USA. RP Neumann, HPH (reprint author), Med Univ Klin, Abt 4, Hugstetterstr 55, D-79106 Freiburg, Germany. NR 102 TC 22 Z9 24 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 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD MAR PY 2002 VL 22 IS 2 BP 89 EP 99 DI 10.1053/snep.2002.30207 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 530RZ UT WOS:000174373900003 PM 11891502 ER PT J AU Nordyke, RJ Peabody, JW AF Nordyke, RJ Peabody, JW TI Market reforms and public incentives: finding a balance in the Republic of Macedonia SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE private care; reform; primary care; Eastern Europe ID HEALTH-CARE; EASTERN-EUROPE; PRIVATIZATION; BULGARIA; STATE AB The Republic of Macedonia is undertaking sweeping reforms of its health sector. Funded by a World Bank credit, the reforms seek to improve the efficiency and quality of primary health care (PHC) by significantly strengthening the role of the market in health care provision. On the supply-side, one of the key reform proposals is to implement a capitation payment system for PHC physicians. By placing individual physicians on productivity-based contracts, these reforms will effectively marketize all PHC provision. In addition, the Ministry of Health is considering the sale or concessions of public PHC clinics to private groups, indicating the government's commitment to marketization of health care provision. Macedonia is in a unique position to develop a new role for the private sector in PHC provision. The private provision of outpatient care was legalized soon after independence in 1991; private physicians now account for nearly 10% of all physicians and 22% of PHC physicians. If the reforms are fully realized, all PHC physicians-over 40% of all physicians-will be financially responsible for their clinical practices. This study draws on Macedonia's experience with limited development of private outpatient care starting in 1991 and the reform proposals for PHC, finding a network of policies and procedures throughout the health sector that negatively impact private and public sector provision, An assessment of the effects that this greater policy environment has on private sector provision identifies opportunities to strategically enhance the reforms. With respect to established market economies, the study finds justification for a greater role for government intervention in private health markets in transition economies. In addition to micro-level payment incentives and administrative controls, marketization in Central and Eastern Europe requires an examination of insurance contracting procedures, quality assurance practices, public clinic ownership, referral practices, hospital privileges, and capital investment policies. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 RAND Corp, Santa Monica, CA 90407 USA. Univ Calif San Francisco, Inst Global Hlth, San Francisco, CA 94105 USA. Univ Calif Los Angeles, Sch Publ Hlth, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Univ So Calif, Sch Policy Planning & Dev, Int Publ Policy & Management Program, Los Angeles, CA 90089 USA. RP Nordyke, RJ (reprint author), RAND Corp, 1700 Main St,MS 14-A, Santa Monica, CA 90407 USA. NR 53 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD MAR PY 2002 VL 54 IS 6 BP 939 EP 953 AR PII S0277-9536(01)00067-3 DI 10.1016/S0277-9536(01)00067-3 PG 15 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 532KC UT WOS:000174473100008 PM 11996027 ER PT J AU Stojanovic, MP Vu, TN Caneris, O Slezak, J Cohen, SP Sang, CN AF Stojanovic, MP Vu, TN Caneris, O Slezak, J Cohen, SP Sang, CN TI The role of fluoroscopy in cervical epidural steroid injections - An analysis of contrast dispersal patterns SO SPINE LA English DT Article DE injection epidural; steroids; fluoroscopy ID CRYOMICROTOME SECTION; CT-EPIDUROGRAPHY; PAIN; ANATOMY; COMPLICATIONS; MANAGEMENT; SPACE AB Study Design. A multicenter, retrospective analysis of cervical epidurograms. Objectives. To determine the effectiveness of the loss of resistance (LOR) technique in identifying the cervical epidural space. To delineate the pattern of epidural contrast spread during cervical epidural steroid injections. Background. Previous studies have shown that if performed without fluoroscopy, the LOR technique can result in inaccurate needle placement in up to 30% of lumbar epidural steroid injections. To date, no study has examined accuracy of LOR technique and pattern of radiographic contrast spread in cervical epidural levels. Methods. Epidurograms of 38 cervical epidural steroid injections in 31 patients were reviewed. The number of LOR attempts and pattern of contrast spread was analyzed. The effects of age, gender, MRI results, previous cervical laminectomy, and the physician's level of training were correlated with results. Results. The authors found a 53% rate of false LOR during the first attempt to enter the epidural space. Unilateral epidural contrast spread was found in 51% and ventral epidural spread was found in 28% of cases. The average number of cervical vertebral levels covered with 2 mL of contrast was 3.14, with significantly wider spread noted in those patients who had not undergone previous cervical laminectomy. Other variables did not influence the accuracy of needle placement and pattern of epidural contrast spread. Conclusions. The loss of resistance technique may not be an adequate method for ensuring accurate needle placement in blindly performed cervical epidural injections. The use of epidurography can improve the accuracy of needle placement and medication delivery to targeted areas of pathology. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, MGH Pain Ctr, Intervent Pain Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Clin Trials Program, MGH Pain Ctr, Boston, MA 02114 USA. NE Rehabil Hosp, Salem, NH USA. NE Pain Consultants, Somersworth, NH USA. RP Stojanovic, MP (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, MGH Pain Ctr, Intervent Pain Program, ACC-324,Fruit St, Boston, MA 02114 USA. NR 30 TC 74 Z9 77 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD MAR 1 PY 2002 VL 27 IS 5 BP 509 EP 514 DI 10.1097/00007632-200203010-00011 PG 6 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 532KE UT WOS:000174473300010 PM 11880836 ER PT J AU Koehler, RH AF Koehler, RH TI Diagnosing the occult contralateral inguinal hernia - Combined use of diagnostic laparoscopy and totally extraperitoneal laparoscopic repair SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article; Proceedings Paper CT Annual Scientific Session of the Society-of-American-Gastrointestinal-Endoscopic-Surgeons (SAGES) CY APR, 2001 CL ST LOUIS, MISSOURI SP Soc Amer Gastrointestinal Endoscop Surg DE hernia; occult; contralateral; laparoscopic surgery ID RANDOMIZED CONTROLLED TRIAL; OPEN MESH REPAIR; GROIN HERNIAS; HERNIOPLASTY; HERNIORRHAPHY; HERNIOGRAPHY; TRANSPERITONEAL; MULTICENTER; SURGERY; ADULTS AB Background: The incidence of bilateral inguinal hernias reported for total extra peritoneal (TEP) laparoscopic hernia repair, which reaches 45%. appears to be higher than that seen in studies of transabdominal laparoscopic and open repair. Given the unique ability of diagnostic laparoscopy to diagnose occult contralateral hernias (OCH) accurately, this study looked at how concurrent transabdominal diagnostic laparoscopy (TADL) would influence planned TEP repairs. Methods: A prospective study of 100 consecutive TEP cases was conducted. All patients had diagnostic laparoscopy via a 5-mm 45degrees scope through an umbilical incision with 15 mmHg of pneumoperitoneum, followed by laparoscopic TEP repair. A contralateral occult hernia was diagnosed and repaired if a true peritoneal eventration through the inguinal region was observed. Results: Among the 100 patients, preoperative diagnosis suggested 31 bilateral hernias (31%). whereas TADL confirmed 25 bilateral hernias (25%). Of these 25 bilateral hernias. TADL confirmed 16 that had been diagnosed preoperatively (64%), but excluded 15 contralateral hernias that were incorrectly diagnosed (37%). Transabdominal diagnostic laparoscopy found nine OCHs, representing 36% of all bilateral hernias and 13% of the 69 preoperatively determined unilateral hernias. The preoperative physician examination false-negative rate for contralateral hernias was 36%. and the false-positive rate was 37%. In 26 cases (26%), TADL changed the operative approach. Conclusions: In this study, patients believed to have unilateral inguinal hernias had OCHs in 13% of cases when examined by TADL. The actual bilateral hernia incidence was 25%. with a 37% false-positive rate for preoperatively diagnosed bilateral hernias. The high rate of bilateral hernias reported by the TEP approach alone suggests that some OCH findings may be an artifact of the TEP dissection. However. Failure to search for an OCH could result in tip to 13% of patients subsequently requiring a second repair. Because some surgeons are concerned about unnecessary TEP dissection of the asymptomatic contralateral side, the approach described Here may offer a solution to accurate diagnosis of the contralateral inguinal region during planned laparoscopic TEP hernia repair. C1 Marthas Vineyard Hosp, Oak Bluffs, MA 02557 USA. Massachusetts Gen Hosp, Boston, MA 02117 USA. RP Koehler, RH (reprint author), Marthas Vineyard Hosp, 1 Hosp Rd, Oak Bluffs, MA 02557 USA. NR 35 TC 22 Z9 24 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD MAR PY 2002 VL 16 IS 3 BP 512 EP 520 DI 10.1007/s00464-001-8166-y PG 9 WC Surgery SC Surgery GA 539WN UT WOS:000174894800030 PM 11928039 ER PT J AU Kuter, DJ AF Kuter, DJ TI Whatever happened to thrombopoietin? SO TRANSFUSION LA English DT Editorial Material ID HUMAN MEGAKARYOCYTE GROWTH; RECOMBINANT HUMAN THROMBOPOIETIN; ACUTE MYELOID-LEUKEMIA; MPL-DEFICIENT MICE; FACTOR PEG-RHUMGDF; C-MPL; PLATELET PRODUCTION; PROGENITOR CELLS; HEMATOPOIETIC RECOVERY; BODY IRRADIATION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hematol Unit, Boston, MA 02114 USA. RP Kuter, DJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hematol Unit, 100 Blossom St, Boston, MA 02114 USA. NR 48 TC 15 Z9 15 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAR PY 2002 VL 42 IS 3 BP 279 EP 283 DI 10.1046/j.1537-2995.2002.00056.x PG 5 WC Hematology SC Hematology GA 540BH UT WOS:000174907900001 PM 11961230 ER PT J AU Wang, JH AF Wang, JH TI Protein recognition by cell surface receptors: physiological receptors versus virus interactions SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Editorial Material ID INTERCELLULAR-ADHESION MOLECULE-1; RHINOVIRUS RECEPTOR; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; MEASLES-VIRUS; IMMUNE-SYSTEM; BINDING; POLIOVIRUS; AFFINITY; DISTINCT AB Protein-protein recognition is a major kind of receptor-ligand interaction: a living cell receives external signals to adapt to the environment through cell surface receptors. On opposing cell surfaces, such recognition bears distinct features: it is a multivalent, reversible and avidity-driven process. The affinity between each individual contacting pair is low. Viruses might take advantage of this low affinity to invade a host cell by evolving a stronger binding affinity to the surface receptors than that associated with physiological ligands. Structural data appear to support this notion. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol CheM & Mol Pharmacol, Boston, MA 02115 USA. RP Wang, JH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, SM-1036B,44 Binney St, Boston, MA 02115 USA. EM jwang@red.dfci.harvard.edu NR 49 TC 47 Z9 51 U1 1 U2 3 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD MAR PY 2002 VL 27 IS 3 BP 122 EP 126 AR PII S0968-0004(01)02038-2 DI 10.1016/S0968-0004(01)02038-2 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 531LK UT WOS:000174416700008 PM 11893508 ER PT J AU Bush, A AF Bush, A TI '...and C is for clioquinol' - the A beta Cs of Alzheimer's disease - Response SO TRENDS IN NEUROSCIENCES LA English DT Article ID HYDROGEN-PEROXIDE; REDUCTION; MICE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Oxidat Biol,Genet & Aging Res Unit, Charlestown, MA 02129 USA. Univ Melbourne, Mental Hlth Res Inst Victoria, Parkville, Vic 3052, Australia. RP Bush, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Oxidat Biol,Genet & Aging Res Unit, Bldg 114,16th St, Charlestown, MA 02129 USA. NR 12 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD MAR PY 2002 VL 25 IS 3 BP 123 EP 124 DI 10.1016/S0166-2236(02)02085-4 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 524GQ UT WOS:000174005200003 ER PT J AU Arshavsky, VY AF Arshavsky, VY TI Rhodopsin phosphorylation: from terminating single photon responses to photoreceptor dark adaptation SO TRENDS IN NEUROSCIENCES LA English DT Article ID MULTIPLE PHOSPHORYLATION; ROD PHOTORECEPTORS; RETINAL RODS; SITES AB Rhodopsin phosphorylation has provided one of the first examples of the ubiquitous regulatory pattern of specific kinases downregulating the activity of G-protein-coupled receptors. However, only recently have studies in living animals allowed us to consider the role of rhodopsin phosphorylation in a broader spectrum of visual functions, ranging from the ability of rods to generate reproducible electrical responses to their ability to adapt to darkness after substantial light exposures. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Arshavsky, VY (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. NR 16 TC 41 Z9 42 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD MAR PY 2002 VL 25 IS 3 BP 124 EP 126 DI 10.1016/S0166-2236(00)02094-4 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 524GQ UT WOS:000174005200004 PM 11852136 ER PT J AU Heerssen, HM Segal, RA AF Heerssen, HM Segal, RA TI Location, location, location: a spatial view of neurotrophin signal transduction SO TRENDS IN NEUROSCIENCES LA English DT Review ID NERVE GROWTH-FACTOR; RETROGRADE AXONAL-TRANSPORT; RAT SYMPATHETIC NEURONS; TRANSCRIPTION FACTOR; RECEPTOR TRAFFICKING; CELL-SURVIVAL; PHOSPHATIDYLINOSITOL 3-KINASE; REGULATED KINASE; PLASMA-MEMBRANE; GENE-EXPRESSION AB Neurotrophins were originally identified as target-derived factors that regulate the survival and differentiation of innervating neurons. However, neurotrophins can also be released by presynaptic cells to stimulate postsynaptic neurons. Recent studies indicate that differences exist between the signaling pathways activated by neurotrophin stimulation of nerve terminals (retrograde signaling) and neurotrophin stimulation of cell bodies. Retrograde signaling relies on the formation of signaling endosomes, vesicles containing activated Trk receptors and their ligands. Signaling endosomes travel from the nerve terminals to remote cell bodies, where they selectively activate a novel MAP kinase, Erk5, as well as P13 kinase, and thereby stimulate neuronal survival. The differences in the signaling pathways activated by neurotrophins, which depends on the location of stimulation, provide a mechanism by which neurons can interpret the 'where' as well as the 'what' of growth factor stimulation. C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Segal, RA (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. FU NINDS NIH HHS [NS35148] NR 60 TC 95 Z9 99 U1 0 U2 4 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD MAR PY 2002 VL 25 IS 3 BP 160 EP 165 AR PII S0166-2236(02)02144-6 DI 10.1016/S0166-2236(02)02144-6 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 524GQ UT WOS:000174005200014 PM 11852149 ER PT J AU Chiarugi, A AF Chiarugi, A TI Poly(ADP-ribose) polymerase: killer or conspirator? The 'suicide hypothesist' revisited SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Editorial Material ID NF-KAPPA-B; ADP-RIBOSE POLYMERASE; DNA-DAMAGE; TRANSCRIPTIONAL ACTIVATION; GENE-EXPRESSION; MICE LACKING; P53 PROTEIN; CELL-DEATH; APOPTOSIS; SYNTHETASE AB Poly(ADP-ribose) polymerase 1 (PARP-1) is an abundant nuclear enzyme involved in DNA repair. The therapeutic efficacy of drugs that inhibit PARP-1 in various disorders underscores the active role of PARP-1 in cell death. Although it is well established that excessive DNA damage causes PARP-1 hyperactivation, which leads to cell death by energy failure, a new mechanistic perspective is emerging following the identification of various PARPs that exhibit different features and subcellular distributions. Studies demonstrating the significant role of PARP-1 in the regulation of gene transcription have further increased the intricacy of poly(ADP-ribosyl)ation in the control of cell homeostasis and challenge the notion that energy collapse is the sole mechanism by which poly(ADP-ribose) formation contributes to cell death. The hypothesis that PARPs might regulate cell fate as essential modulators of death and survival transcriptional programs will be discussed with particular focus on the regulation of transcription factors such as nuclear factor kappaB and p53. (An animation depicting the involvement of PARP-1 in the 'suicide hypothesis' is available at http://archive.bmn.com/supp/tips/tips2303a.htm1). C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosci, Charlestown, MA 02129 USA. RP Chiarugi, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosci, 149 13th St, Charlestown, MA 02129 USA. NR 80 TC 215 Z9 218 U1 0 U2 7 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD MAR PY 2002 VL 23 IS 3 BP 122 EP 129 AR PII S0165-6147(00)01902-7 DI 10.1016/S0165-6147(00)01902-7 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 528VC UT WOS:000174264100009 PM 11879679 ER PT J AU Oyama, T Sano, T Hikino, T Xue, Q Iijima, K Nakajima, T Koerner, F AF Oyama, T Sano, T Hikino, T Xue, Q Iijima, K Nakajima, T Koerner, F TI Microcalcifications of breast cancer and atypical cystic lobules associated with infiltration of foam cells expressing osteopontin SO VIRCHOWS ARCHIV LA English DT Article DE breast cancer; atypical cystic lobules; osteopontin; microcalcification ID CARCINOMA IN-SITU; TERM FOLLOW-UP; BONE SIALOPROTEIN; HYDROXYAPATITE FORMATION; INHIBITION; PHOSPHOPROTEINS; PHOSPHORYLATION; CALCIFICATION; ABNORMALITIES; NUCLEATION AB We studied the pattern of calcification and the expression of osteopontin protein and mRNA by the histiocytes and noninvasive carcinoma cells of 20 breast cancers and the histiocytes and atypical ductal cells of sixteen cases of atypical cystic lobules. Ten breast cancers showed low-grade cribriform carcinoma in situ containing secretory material; the remaining ten cancers displayed high-grade carcinoma in situ with central necrosis characteristic of comedo type carcinoma. Hematoxylin-eosin and Kossa staining revealed calcium hydroxyapatite calcifications in 80% of cribriform type carcinomas, 50% of comedo type carcinomas, and 56% of atypical cystic lobules. Immunohistochemical staining demonstrated osteopontin protein in intraluminal secretory material, necrotic debris, or stroma, and in histiocytes in all the Kossa-positive carcinomas and atypical cystic lobules. In situ hybridization revealed osteopontin mRNA mainly in the histiocytes and especially in those near the calcifications. In two cases, rare carcinoma cells contained osteopontin protein and mRNA. The close relation between hydroxyapatite crystals and osteopontin-producing histiocytes suggests that osteopontin plays a role in the biomineralization that occurs in certain noninvasive breast cancers and atypical cystic lobules. The differences in the morphology of the calcifications and the intraductal contents suggest that the mechanism leading to the osteopontin production might vary depending on the underlying lesion. C1 Gunma Univ, Sch Med, Dept Pathol 2, Maebashi, Gumma 3718511, Japan. Gunma Univ, Sch Med, Dept Surg 2, Gunma, Japan. Harvard Univ, Massachusetts Gen Hosp, James Homer Wright Lab Pathol, Sch Med, Boston, MA 02114 USA. RP Oyama, T (reprint author), Gunma Univ, Sch Med, Dept Pathol 2, Showa Machi 3-39-22, Maebashi, Gumma 3718511, Japan. NR 39 TC 15 Z9 17 U1 2 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. PD MAR PY 2002 VL 440 IS 3 BP 267 EP 273 DI 10.1007/s004280100501 PG 7 WC Pathology SC Pathology GA 539TU UT WOS:000174887800004 PM 11889596 ER PT J AU McMorrow, IM Buhler, L Treter, S Neethling, FA Alwayn, IPJ Comrack, CA Kitamura, H Awwad, M DerSimonian, H Cooper, DKC Sachs, DH LeGuern, C AF McMorrow, IM Buhler, L Treter, S Neethling, FA Alwayn, IPJ Comrack, CA Kitamura, H Awwad, M DerSimonian, H Cooper, DKC Sachs, DH LeGuern, C TI Modulation of the in vivo primate anti-Gal response through administration of anti-idiotypic antibodies SO XENOTRANSPLANTATION LA English DT Article DE anti-idiotype antibody; alpha-galactosyl epitope; anti-Gal antibody; hyperacute rejection; xenotransplantation ID HEMATOPOIETIC-CELL TRANSPLANTATION; TOLERANCE INDUCTION; PIG; SUPPRESSION; EXPRESSION; BABOONS; DEPLETION; IDIOTOPES; EPITOPES; REGIMEN AB Polyclonal anti-idiotypic antibodies (AIA) were generated against human Galalpha1,3Gal antibodies (anti-Gal) isolated from a single donor. Specificity of the AIA was demonstrated by selective binding to anti-Gal antibodies (Ab) and absence of reactivity to non-Gal Ab. The idiotopes identified by AIA were present on anti-Gal Ab from all of the human samples evaluated (n = 59) as well as on pooled samples. demonstrating that a restricted number of dominant idiotopes characterized the human anti-Gal Ab response. Furthermore, the AIA had cross-species reactivity with baboon serum samples (n = 19). suggesting that the overall shape of the anti-Gal Ab combining site is conserved throughout the Old World primates and providing additional evidence of the limited heterogeneity of the anti-Gal Ab repertoire. In order to evaluate the potential effect of AIA in the modulation of the anti-Gal response in vivo, a baboon was injected with repeated doses of the purified AIA. Following AIA treatment, new Ab were generated that reduced Ab-mediated cytotoxicity to porcine cells. Furthermore, administration of the AIA to a baboon prolonged the survival of intravenously infused pig hematopoietic cells when compared with their survival in a control baboon that did not receive prior AIA treatment but underwent a similar conditioning regimen. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. BioTransplant Inc, Charlestown, MA USA. RP McMorrow, IM (reprint author), Massachusetts Gen Hosp East, Transplantat Biol Res Ctr, Bldg 149-9019,13th St, Boston, MA 02129 USA. NR 31 TC 2 Z9 3 U1 0 U2 0 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 2002 VL 9 IS 2 BP 106 EP 114 DI 10.1034/j.1399-3089.2002.1o028.x PG 9 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 538TQ UT WOS:000174831500003 PM 11897003 ER PT J AU Denaro, M Kolber-Simonds, D Schad, V Muthukumar, S Germana, S White-Scharf, ME Banerjee, PT LeGuern, C Andersson, G AF Denaro, M Kolber-Simonds, D Schad, V Muthukumar, S Germana, S White-Scharf, ME Banerjee, PT LeGuern, C Andersson, G TI Expression of xenogeneic MHC class II molecules in HLA-DR+ and -DR- cells: influence of retrovirus vector design and cellular context SO XENOTRANSPLANTATION LA English DT Article DE antigen presentation; gene therapy; MHC; xenotransplantation ID GREEN FLUORESCENT PROTEIN; BONE-MARROW CELLS; HEMATOPOIETIC-CELLS; MINIATURE SWINE; GENE-THERAPY; MONOCLONAL-ANTIBODIES; MIXED CHIMERISM; IMMUNE-RESPONSE; TOLERANCE; LINE AB We recently established that molecular chimeras of major histocompatibility complex (MHC) class II molecules, created via retroviral transfer of allogeneic class II cDNAs into bone marrow cells (BMCs), alleviated complications associated with mixed BMC chimeras while leading to T cell tolerance to renal grafts sharing the transferred class II. Initially demonstrated for allogeneic transplants in miniature swine, this concept was extended to T-dependent antibody (Ab) responses to xenogeneic antigens (Ags) in the pig --> baboon combination. Successful down-regulation of T cell responses appeared, however, to be contingent on a tight lineage-specific expression of transferred class II molecules. The present studies were, therefore, designed to evaluate the influence of construct design and cellular environment on expression of retrovirally transferred xenogeneic class II cDNAs. Proviral genomes for pig class II SLA-DR expression, differing only at the marker neo(r) or enhanced green fluorescent protein (EGFP) gene, showed increased membrane SLA-DR density on HLA-DR fibroblasts as well as HLA-DR+, TF-1 erythroleukemia cells. More importantly, HLA-DR+ human B cell lines, although efficiently transduced with pig DR retroviruses, exhibited unstable surface pig DR. Surface pig DR- B cells, nevertheless, stimulated autologous human T cells pre-sensitized to pig Ags, a proliferation likely occurring through presentation of class II-derived peptides. Collectively, these data suggest that surface expression of transferred class II molecules is not related to the ability of recipient cells to synthesize xenogeneic class II molecules but rather to their Ag processing capacities. C1 BioTransplant Inc, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA USA. RP Andersson, G (reprint author), Swedish Univ Agr Sci, Uppsala Biomed Ctr, Dept Anim Breeding & Genet, Box 597, S-75124 Uppsala, Sweden. FU NIAID NIH HHS [2R01-AI33053] NR 42 TC 3 Z9 3 U1 0 U2 0 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 2002 VL 9 IS 2 BP 115 EP 124 DI 10.1034/j.1399-3089.2002.1o038.x PG 10 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 538TQ UT WOS:000174831500004 PM 11897004 ER PT J AU Teranishi, K Manez, R Awwad, M Cooper, DKC AF Teranishi, K Manez, R Awwad, M Cooper, DKC TI Anti-Gal alpha 1-3Gal IgM and IgG antibody levels in sera of humans and old world non-human primates SO XENOTRANSPLANTATION LA English DT Article DE anti-Gal antibody; human; nonhuman primates; xenotransplantation ID ALPHA-GALACTOSYL EPITOPES; HUMAN NATURAL ANTIBODIES; GAL ANTIBODY; ORGAN XENOTRANSPLANTATION; IMMUNOGLOBULIN-G; PIG ANTIBODIES; CELLS; BABOONS; CYTOTOXICITY; SPECIFICITY AB Organs transplanted from pig to primate are rejected within minutes or hours by an antibody-dependent, complement-mediated mechanism [hyperacute rejection (HAR)]. Even after depletion of anti-Galalpha1-3Gal (Gal) antibody (Ab), for example by extracorporeal immunoadsorption, return of natural Ab is believed to be a major factor in the initiation of acute humoral xenograft rejection. Various non-human primates are used as recipients of pig organs in experimental discordant xenotransplantation (XTx) models. However, anti-Gal IgM and IgG levels in non-human primates may differ from those in humans. Serum levels of anti-Gal IgM and IgG were measured by enzyme-linked immunosorbent assay (ELISA) in humans (n = 14), chimpanzees (n = 8), baboons (n = 214), cynomolgus monkeys (n = 29), rhesus monkeys (n = 23) and Japanese monkeys (n = 6). The mean level of anti-Gal IgM was significantly higher in chimpanzees than in other groups, while in rhesus monkeys it was significantly lower than in other groups, except baboons and Japanese monkeys. The mean human anti-Gal IgG level was higher than in other groups and this difference reached statistical significance except with regard to chimpanzees. The mean anti-Gal IgG level in baboons was significantly lower than that in humans, chimpanzees and cynomolgus monkeys. The measured differences in anti-Gal IgM and IgG levels may affect the kinetics of Ab removal and rate of return in different species, and thus may have relevance for translating work in non-human primate models to the clinical setting. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr,MGH E, Boston, MA 02129 USA. Juan Canalejo Med Ctr, La Coruna, Spain. Univ A Coruna Hlth Inst, La Coruna, Spain. Immerge BioTherapeut, Charlestown, MA USA. RP Cooper, DKC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr,MGH E, Bldg 149-9019,13th St, Boston, MA 02129 USA. EM david.cooper@tbrc.mgh.harvard.edu NR 39 TC 26 Z9 27 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0908-665X EI 1399-3089 J9 XENOTRANSPLANTATION JI Xenotransplantation PD MAR PY 2002 VL 9 IS 2 BP 148 EP 154 DI 10.1034/j.1399-3089.2002.1o058.x PG 7 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 538TQ UT WOS:000174831500007 PM 11897007 ER PT J AU Magnusson, KR Nelson, SE Young, AB AF Magnusson, KR Nelson, SE Young, AB TI Age-related changes in the protein expression of subunits of the NMDA receptor SO MOLECULAR BRAIN RESEARCH LA English DT Article DE NR1; NR2B; NR2A; N-methyl-D-aspartate; cortex; hippocampus ID LONG-TERM POTENTIATION; GLUTAMATE RECEPTORS; RAT-BRAIN; MOLECULAR DIVERSITY; SYNAPTIC PROTEINS; BINDING; PERFORMANCE; HIPPOCAMPUS; ANTAGONISTS; CLONING AB C57B1/6 mice show decreased expression of the mRNA for the epsilon2 and zeta1 subunits of the N-methyl-D-aspartate (NMDA) receptor in subregions of the cerebral cortex and hippocampus with increased age. The purpose of this study was to determine the effects of aging on the protein expression of the three major subunits of the NMDA receptor. Semi-quantitative Western blot techniques were applied with the use of antibodies that recognize either the epsilon1 (NR2A), epsilon2 (NR2B) or zeta1 (NR1) subunits of the NMDA receptor or a synaptic terminal protein, synaptophysin. In the cerebral cortex of 30-month-old mice. the level of protein expression of both the epsilon2 and zeta1 subunits were decreased significantly from levels found in the 3- and 10-month-old mice and the protein expression of the epsilon1 subunit showed a significant decline between 10 and 30 months of age. In the hippocampus, the epsilon2 subunit exhibited a higher protein expression level in the 10-month-old mice as compared to both the young and old mice and the zeta1 subunit showed a significant drop in expression in the old mice from both 3- and 10-month-olds. Synaptophysin showed significant declines in protein expression with increasing age. These results demonstrated that changes in the protein expression of the major subunits of the NMDA receptor occur during the aging process and, in some cases, were greater than changes seen previously in mRNA expression. These subunit alterations may explain some of the changes that are seen in NMDA receptor functions during aging. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Colorado State Univ, Coll Vet Med & Biomed Sci, Dept Anat & Neurobiol, Program Cellular Mol & Integrat Neurosci, Ft Collins, CO 80523 USA. Colorado State Univ, Coll Vet Med & Biomed Sci, Dept Physiol, Ft Collins, CO 80523 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Magnusson, KR (reprint author), Colorado State Univ, Coll Vet Med & Biomed Sci, Dept Anat & Neurobiol, Program Cellular Mol & Integrat Neurosci, Ft Collins, CO 80523 USA. OI Magnusson, Kathy/0000-0002-6108-2519 NR 37 TC 78 Z9 79 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD FEB 28 PY 2002 VL 99 IS 1 BP 40 EP 45 AR PII S0169-328X(01)00344-8 DI 10.1016/S0169-328X(01)00344-8 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 532JY UT WOS:000174472500006 ER PT J AU Asai, T Tena, G Plotnikova, J Willmann, MR Chiu, WL Gomez-Gomez, L Boller, T Ausubel, FM Sheen, J AF Asai, T Tena, G Plotnikova, J Willmann, MR Chiu, WL Gomez-Gomez, L Boller, T Ausubel, FM Sheen, J TI MAP kinase signalling cascade in Arabidopsis innate immunity SO NATURE LA English DT Article ID BACTERIAL ELICITOR FLAGELLIN; ACTIVATED PROTEIN-KINASE; TRANSCRIPTION FACTORS; PATHOGEN DEFENSE; RESISTANCE GENE; RECEPTOR; PLANTS; THALIANA; PERCEPTION; INDUCTION AB There is remarkable conservation in the recognition of pathogen-associated molecular patterns (PAMPs) by innate immune responses of plants, insects and mammals. We developed an Arabidopsis thaliana leaf cell system based on the induction of early-defence gene transcription by flagellin, a highly conserved component of bacterial flagella that functions as a PAMP in plants and mammals. Here we identify a complete plant MAP kinase cascade (MEKK1, MKK4/MKK5 and MPK3/MPK6) and WRKY22/WRKY29 transcription factors that function downstream of the flagellin receptor FLS2, a leucine-rich-repeat (LRR) receptor kinase. Activation of this MAPK cascade confers resistance to both bacterial and fungal pathogens, suggesting that signalling events initiated by diverse pathogens converge into a conserved MAPK cascade. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Inst Desarrollo Reg, Secc Biotecnol, E-02071 Albacete, Spain. Friedrich Miescher Inst, CH-4002 Basel, Switzerland. RP Sheen, J (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RI Boller, Thomas/G-3500-2012; OI Tena, Guillaume/0000-0001-8652-905X; Gomez-Gomez, Lourdes/0000-0003-2586-4457 NR 46 TC 1223 Z9 1339 U1 34 U2 241 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 28 PY 2002 VL 415 IS 6875 BP 977 EP 983 DI 10.1038/415977a PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 525MF UT WOS:000174075000031 PM 11875555 ER PT J AU Kollias, N Zonios, G Stamatas, GN AF Kollias, N Zonios, G Stamatas, GN TI Fluorescence spectroscopy of skin SO VIBRATIONAL SPECTROSCOPY LA English DT Article; Proceedings Paper CT Conference on Shedding New Light on Disease - Optical Diagnostics for the New Millennium CY JUN 25-30, 2000 CL WINNIPEG, CANADA DE aging; photoaging; collagen; tryptophan ID IN-VIVO FLUORESCENCE; PROLIFERATION; PHOTOGRAPHY; EXPOSURE; MARKER AB The fluorescence properties of skin both human and of an animal model are reviewed in this article. Fluorescence spectroscopy is a valuable tool for the investigation of the optical properties of the skin in the ultraviolet range of the spectrum because the absorption bands are confluent. Epidermal and dermal fluorescence signals are each produced in distinct spectral regions. Biological processes modulate the fluorescence signals in predictable ways. Such cases include aging, epidermal proliferation, and photoaging as well as diseases such as psoriasis, acne and non-melanoma skin cancer. Fluorescence excitation spectroscopy has proved a valuable approach in the study of the structure and function of human skin. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Johnson & Johnson Consumer Prod Worldwide, Skillman, NJ 08558 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Kollias, N (reprint author), Johnson & Johnson Consumer Prod Worldwide, 199 Grandview Rd, Skillman, NJ 08558 USA. NR 20 TC 79 Z9 80 U1 0 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-2031 J9 VIB SPECTROSC JI Vib. Spectrosc. PD FEB 28 PY 2002 VL 28 IS 1 BP 17 EP 23 AR PII S0924-2031(01)00142-4 DI 10.1016/S0924-2031(01)00142-4 PG 7 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 547BQ UT WOS:000175313100003 ER PT J AU Erdag, G Morgan, JR AF Erdag, G Morgan, JR TI Survival of fetal skin grafts is prolonged on the human peripheral blood lymphocyte reconstituted-severe combined immunodeficient mouse/skin allograft model SO TRANSPLANTATION LA English DT Article ID T-CELLS; ANTIGEN PRESENTATION; ENDOTHELIAL-CELLS; CLASS-I; EXPRESSION; REJECTION; MICE; TRANSPLANTATION; PROLIFERATION; PANCREAS AB Background. Fetal tissue is considered to be immune privileged and is under extensive investigation as a source of tissue for transplantation. In this paper, we analyzed the immune properties of human fetal and neonatal skin before and after transplantation to severe combined immunodeficient (SCID) mice. Using a human peripheral blood mononuclear cell reconstituted SCID (huPBMC-SCID) mouse model of allograft rejection, we compared the immune response to transplanted fetal and neonatal skin. Methods. We analyzed human fetal (55-122 days of gestation) and neonatal skin samples by routine histology and immunohistochemistry for the expression of (MHC class I and II antigens before and after transplantation to SCID mice. After transplantation, we injected the mice with huPBMCs and analyzed the survival of neonatal and fetal skin grafts both visually and microscopically. Results. We detected no class II expression in fetal skin of all gestational ages and only weak class I expression after 89 days compared with abundant class I and II expression in neonatal skin before transplantation. When transplanted to SCID mice, fetal skin grafts differentiated and expressed class I and II, but the levels were lower than neonatal grafts. In mice injected with huPBMCs, rejection of neonatal grafts started on day 5, and by day 9 all grafts were rejected. In contrast, rejection of fetal skin grafts was significantly delayed. Rejection started on day 13 and was complete by day 23 (P < 0.00005). Histology sections from the rejected grafts showed marked CD3(+) T cell infiltration in the human skin with a sharp demarcation between the human and mouse skin, with no T-cell infiltration in the mouse skin. CD4(+) and CD8(+) T cells were present in the rejected sites in similar densities. Conclusions. Our results show that fetal skin differentiates and expresses increased amounts of MHC class I and class II antigens when transplanted to SCID mice. However, these levels are much lower than the levels found in neonatal skin. We demonstrate that the survival of human fetal skin allografts is markedly prolonged compared with that of neonatal skin grafts in the huPBMC-SCID mouse model. Our results support the hypothesis that low levels of MHC antigen expression lead to a delay in the rejection of fetal skin and further demonstrate the utility of the huPBMC-SCID mouse model to investigate the molecular and cellular mechanisms of the immune response to human fetal tissues. C1 Harvard Univ, Sch Med, Shriner Burns Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. RP Morgan, JR (reprint author), Harvard Univ, Sch Med, Shriner Burns Hosp, 51 Blossom St, Boston, MA 02114 USA. OI Morgan, Jeffrey/0000-0002-7546-3443 FU NICHD NIH HHS [HD-28528] NR 30 TC 9 Z9 11 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 27 PY 2002 VL 73 IS 4 BP 519 EP 528 DI 10.1097/00007890-200202270-00005 PG 10 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 528VB UT WOS:000174263900005 PM 11889422 ER PT J AU Borges, E Ferry, JA Friedmann, AM AF Borges, E Ferry, JA Friedmann, AM TI Epstein-Barr virus-negative precursor B cell lymphoblastic lymphoma after liver transplantation: A unique form of posttransplant lymphoproliferative disease SO TRANSPLANTATION LA English DT Article ID DISTINCT ENTITY; DISORDERS; MALIGNANCIES; RECIPIENTS; EBV AB Background. We report a liver transplant patient with Epstein-Barr virus-negative, precursor B cell lymphoblastic lymphoma diagnosed 6 months after transplantation. Patient. The patient was a 13-year-old boy with acute, fulminant hepatic failure of unknown etiology who underwent cadaveric liver transplantation. Results. Six months after the transplant, the patient developed non-tender cervical lymphadenopathy 2 days after a reduction in prednisone dosage. The adenopathy worsened despite withdrawal of immunosuppression, and a biopsy showed precursor B cell lymphoblastic lymphoma. All investigations for Epstein-Barr virus were negative. The patient responded well to chemotherapy and is currently in complete remission 24 months after diagnosis. Conclusions. Precursor B cell lymphoblastic lymphoma has not been previously reported as a form of posttransplant lymphoproliferative disease. We discuss this unique form of posttransplant lymphoproliferative disease and briefly review the clinical and pathological spectrum of posttransplant lymphoproliferative disease. C1 Massachusetts Gen Hosp, Dept Pediat, Div Pediat Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Friedmann, AM (reprint author), Massachusetts Gen Hosp, Dept Pediat, Div Pediat Hematol Oncol, Blake 255,55 Fruit St, Boston, MA 02114 USA. NR 17 TC 6 Z9 7 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 27 PY 2002 VL 73 IS 4 BP 541 EP 543 DI 10.1097/00007890-200202270-00008 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 528VB UT WOS:000174263900008 PM 11889425 ER PT J AU Kauffman, HM McBride, MA Cherikh, WS Spain, PC Delmonico, FL AF Kauffman, HM McBride, MA Cherikh, WS Spain, PC Delmonico, FL TI Transplant tumor registry: Donors with central nervous system tumors SO TRANSPLANTATION LA English DT Article ID GLIOBLASTOMA-MULTIFORME; MALIGNANT-TUMOR; TRANSMISSION; RECIPIENTS; MEDULLOBLASTOMA; METASTASES AB Background. Despite 13,000 central nervous system (CNS) tumor deaths per year in the United States, CNS tumor donors comprise only 1% of cadaveric donors recovered per year. Concern about tumor transmission may be a possible reason for this very small percentage. Both the size of the candidate waiting list and the number of deaths on the waiting list are progressively increasing because of the donor shortage. Methods. During a 96-month period, the United Network for Organ Sharing recorded 42,340 cadaver donors of whom 397 had a past history of a CNS tumor or the cause of death listed as a CNS tumor. A total of 1,220 organs were transplanted from these 397 donors. All recipients who reported a posttransplant malignancy during a mean follow-up of 36 months were identified. Results. There was no difference in patient survival of organs from CNS tumor donors when compared to donors with no CNS tumors. CNS tumor donors were not used more often for either urgent or older recipients. A total of 39 patients reported posttransplant malignancies but none of these tumors were donor-derived. There is a wide variation in the number of CNS tumor donors utilized by individual organ procurement organizations. Conclusions. The risk of tumor transmission from donors with CNS malignancies seems to be small. Certain tumors, such as glioblastoma multiforme and medulloblastoma, carry a high risk of transmission and should be avoided. The risk of tumor transmission should be weighed against the risk of the patient dying on the waiting list without a transplant. C1 UNOS, United Network Organ Sharing, Dept Res, Richmond, VA 23225 USA. Massachusetts Gen Hosp, Kidney Transplant Program, Boston, MA 02114 USA. RP Kauffman, HM (reprint author), UNOS, United Network Organ Sharing, Dept Res, 1100 Boulders Pkwy,Suite 500,Box 13770, Richmond, VA 23225 USA. NR 20 TC 62 Z9 66 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 2002 VL 73 IS 4 BP 579 EP 582 DI 10.1097/00007890-200202270-00017 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 528VB UT WOS:000174263900017 PM 11889434 ER PT J AU Ross, AS Graeme-Cook, F Cosimi, AB Chung, RT AF Ross, AS Graeme-Cook, F Cosimi, AB Chung, RT TI Combined liver and kidney transplantation in a patient with sickle cell disease SO TRANSPLANTATION LA English DT Article ID INTRAHEPATIC CHOLESTASIS; FAILURE; ANEMIA AB Sickle cell intrahepatic cholestasis is a potentially fatal end-organ complication of sickle cell anemia. Renal involvement in sickle cell anemia is common, and in some cases, can present as acute renal failure. Although renal transplants have been performed in patients with sickle cell anemia since the late 1960s and a number of liver transplants have been recently performed for these complications, there has not been experience with dual organ transplantation for sickle cell anemia-related complications. We describe the case of a patient with sickle cell anemia who underwent successful combined liver and kidney transplantation after the development of acute sickle cell intrahepatic cholestasis and renal failure requiring continuous venovenous hemodialysis. The patient underwent a successful combined liver and kidney transplant with limited perioperative complications and preserved allograft function. At 22 months posttransplant, the patient expired as a result of an acute pulmonary embolus in the setting of bilateral hip fractures. Autopsy revealed no evidence of liver or kidney allograft rejection and evidence of chronic sickle cell nephropathy in the native kidney. Combined liver and kidney transplantation is a viable therapeutic option in patients with severe end-organ effects of sickle cell anemia. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Med Serv, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Transplantat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Pathol Serv, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, GRJ-825, Boston, MA 02114 USA. NR 11 TC 15 Z9 15 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 27 PY 2002 VL 73 IS 4 BP 605 EP 608 DI 10.1097/00007890-200202270-00022 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 528VB UT WOS:000174263900022 PM 11889439 ER PT J AU del Monte, F Harding, SE Dec, GW Gwathmey, JK Hajjar, RJ AF del Monte, F Harding, SE Dec, GW Gwathmey, JK Hajjar, RJ TI Targeting phospholamban by gene transfer in human heart failure SO CIRCULATION LA English DT Article DE calcium; heart failure; gene therapy ID FAILING HUMAN MYOCARDIUM; SARCOPLASMIC-RETICULUM; DILATED CARDIOMYOPATHY; CA2+-ATPASE ACTIVITY; PROTEIN-LEVELS; PHOSPHORYLATION; CONTRACTILITY; STIMULATION; SPARE AB Background-Myocardial cells from failing human hearts are characterized by abnormal calcium handling, a negative force-frequency relationship, and decreased sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) activity. In this study, we tested whether contractile function can be improved by decreasing the inhibitory effects of phospholamban on SERCA2a with adenoviral gene transfer of antisense phospholamban (asPL). Methods and Results-Myocardial cells isolated from 9 patients with end-stage heart failure and 18 donor nonfailing hearts were infected with adenoviruses encoding for either the antisense of phospholamban (Ad.asPL), the SERCA2a gene (Ad.SERCA2a), or the reporter genes beta-galactosidase and green fluorescent protein (Ad.betagal-GFP). Adenoviral gene transfer with Ad.asPL decreased phospholamban expression over 48 hours, increasing the velocity of both contraction and relaxation. Compared with cardiomyocytes infected with Ad.asPL (n=13), human myocytes infected with Ad.betagal-GFP (n=8) had enhanced contraction velocity (20.3+/-3.9% versus 8.7+/-2.6% shortening/second; P<0.01) and relaxation velocity (26.0+/-6.2% versus 8.6+/-4.3% shortening/second; P<0.01). The improvement in contraction and relaxation velocities was comparable to cardiomyocytes infected with Ad.SERCA2a. Failing human cardiomyocytes had decreased contraction and Ca2+ release with increasing frequency (0.1 to 2 Hz). Phospholamban ablation restored the frequency response in the failing cardiomyocytes to normal; increasing frequency resulted in enhanced sarcoplasmic reticulum Ca2+ release and contraction. Conclusion-These results show that gene transfer of asPL can improve the contractile function in failing human myocardium. Targeting phospholamban may provide therapeutic benefits in human heart failure. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Heart Failure & Cardiac Transplantat Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. RP Hajjar, RJ (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Heart Failure & Cardiac Transplantat Ctr, 149 13th St,CNY-4,4215, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL 57623, R01 HL049574-05S1, R01 HL049574-06, R01 HL049574-08, R01 HL049574-06S1, HL 49574, R01 HL049574-05, R01 HL049574-07] NR 16 TC 160 Z9 161 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 26 PY 2002 VL 105 IS 8 BP 904 EP 907 DI 10.1161/hc0802.105564 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 526QP UT WOS:000174141400011 PM 11864915 ER PT J AU Moreno, PR Lodder, RA Purushothaman, KR Charash, WE O'Connor, WN Muller, JE AF Moreno, PR Lodder, RA Purushothaman, KR Charash, WE O'Connor, WN Muller, JE TI Detection of lipid pool, thin fibrous cap, and inflammatory cells in human aortic atherosclerotic plaques by near-infrared spectroscopy SO CIRCULATION LA English DT Article DE atherosclerosis; plaque; tissue; spectroscopy ID ACUTE CORONARY SYNDROMES; INTRAVASCULAR ULTRASOUND; RISK-FACTORS; IN-VIVO; TISSUE; SPECTROMETRY; MORPHOLOGY; DISRUPTION; ARTERIES; DISEASE AB Background-A method is needed to identify nonstenotic, lipid-rich coronary plaques that are likely to cause acute coronary events. Near-infrared (NIR) spectroscopy can provide information on the chemical composition of tissue. We tested the hypothesis that NIR spectroscopy can identify plaque composition and features associated with plaque vulnerability in human aortic atherosclerotic plaques obtained at the time of autopsy. Methods and Results-A total of 199 samples from 5 human aortic specimens were analyzed by NIR spectroscopy. Features of plaque vulnerability were defined by histology as presence of lipid pool, thin fibrous cap (<65 mum by ocular micrometry), and inflammatory cell infiltration. An InfraAlyzer 500 spectrophotometer was used. Spectral absorbance values were obtained as log (1/R) data from 1100 to 2200 nm at 10-nm intervals. Principal component regression was used for analysis. An algorithm was constructed with 50% of the samples used as a reference set; blinded predictions of plaque composition were then performed on the remaining samples. NIR spectroscopy sensitivity and specificity for histological features of plaque vulnerability were 90% and 93% for lipid pool, 77% and 93% for thin cap, and 84% and 89% for inflammatory cells, respectively. Conclusions-NIR spectroscopy can identify plaque composition and features associated with plaque vulnerability in postmortem human aortic specimens. These results support efforts to develop an NIR spectroscopy catheter system to detect vulnerable coronary plaques in living patients. C1 Univ Kentucky, Linda & Jack Gill Heart Inst, Lexington, KY USA. Boston Univ, Sch Med, Dept Surg, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Unit, Boston, MA USA. InfraReDx, Cambridge, MA USA. RP Moreno, PR (reprint author), Vet Adm Med Ctr, 111B-CDD,2250 Leestown Rd, Lexington, KY 40511 USA. NR 31 TC 177 Z9 196 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD FEB 26 PY 2002 VL 105 IS 8 BP 923 EP 927 DI 10.1161/hc0802.104291 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 526QP UT WOS:000174141400015 PM 11864919 ER EF