FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Sonnenberg, A Lieberman, DA AF Sonnenberg, A Lieberman, DA TI Calculating the benefit of a negative endoscopy SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material ID COST-EFFECTIVENESS; RENAL-FAILURE; DYSPEPSIA; CANCER C1 Oregon Hlth Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Oregon Hlth Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. NR 17 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 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD NOV PY 2003 VL 58 IS 5 BP 752 EP 754 AR PII S0016-5107(03)02022-4 DI 10.1016/S0016-5107(03)02022-4 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 739GY UT WOS:000186337800017 PM 14595313 ER PT J AU Huffman, JC Popkin, MK Stern, TA AF Huffman, JC Popkin, MK Stern, TA TI Psychiatric considerations in the patient receiving organ transplantation: a clinical case conference SO GENERAL HOSPITAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-of-Medicine-and-Psychiatry CY NOV 20, 2002 CL TUCSON, AZ SP Assoc Med & Psychiat ID BORDERLINE PERSONALITY-DISORDER; LIVER-TRANSPLANTATION; DELIRIUM; CYCLOSPORINE; OLANZAPINE AB Psychiatric consultations to evaluate a patient's suitability to receive organ transplantation can require the integration of multiple types and sources of information. A patient's social support network, history of treatment compliance, ongoing Axis I and Axis 11 disorders, and understanding of the procedure and follow-up required must all be evaluated during such a consultation. This article presents the case of a woman with borderline personality disorder who developed hepatic failure following a drug overdose, and discusses her evaluation for liver transplantation. The discussion frames the pertinent issues in the transplant evaluation and describes the perioperative (transplant) management of the borderline patient. (C) 2003 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. McLean Hosp, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. RP Huffman, JC (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM jhuffman@partners.org NR 17 TC 13 Z9 14 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0163-8343 EI 1873-7714 J9 GEN HOSP PSYCHIAT JI Gen. Hosp. Psych. PD NOV-DEC PY 2003 VL 25 IS 6 BP 484 EP 491 DI 10.1016/S0163-8343(03)00090-2 PG 8 WC Psychiatry SC Psychiatry GA 761FH UT WOS:000187890100003 PM 14706415 ER PT J AU Meisenhelder, JB AF Meisenhelder, JB TI Gender differences in religiosity and functional health in the elderly SO GERIATRIC NURSING LA English DT Article ID OLDER ADULTS; DEPRESSION; PRAYER; ATTENDANCE; MORTALITY; SERVICES; SYMPTOMS; OUTCOMES C1 Massachusetts Gen Hosp, MGH Inst Hlth Profess, Boston, MA 02114 USA. RP Meisenhelder, JB (reprint author), Massachusetts Gen Hosp, MGH Inst Hlth Profess, Boston, MA 02114 USA. NR 35 TC 8 Z9 8 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0197-4572 J9 GERIATR NURS JI Geriatr. Nurs. PD NOV-DEC PY 2003 VL 24 IS 6 BP 343 EP + DI 10.1016/j.gerinurse.2003.09.055 PG 6 WC Geriatrics & Gerontology; Gerontology; Nursing SC Geriatrics & Gerontology; Nursing GA 759QZ UT WOS:000187749500018 PM 14694322 ER PT J AU Wu, ZL Rosenberg, RD AF Wu, ZL Rosenberg, RD TI Determining the structures on heparan sulfate in the vicinity of specific sulfotransferase recognition sites by stable isotope incorporation and mass spectrometry SO GLYCOBIOLOGY LA English DT Meeting Abstract CT 8th Annual Conference of the Society-for-Glycobiology CY DEC 03-06, 2003 CL SAN DIEGO, CALIFORNIA SP Soc Glycobiol C1 MIT, Dept Biol, Cambridge, MA USA. Harvard Univ, Sch Med, Dept Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2003 VL 13 IS 11 MA 232 BP 887 EP 887 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 735WU UT WOS:000186138200232 ER PT J AU Matulonis, U Campos, S Duska, L Fuller, A Berkowitz, R Gore, S Roche, M Colella, T Lee, H Seiden, MV AF Matulonis, U Campos, S Duska, L Fuller, A Berkowitz, R Gore, S Roche, M Colella, T Lee, H Seiden, MV CA Gynecologic Oncology Res Program D Dana Farber-Harvard Canc Ctr TI A phase II trial of three sequential doublets for the treatment of advanced mullerian malignancies SO GYNECOLOGIC ONCOLOGY LA English DT Article DE ovarian cancer; topotecan; gemcitabine; adriamycin; paclitaxel; cisplatin; Neupogen treatment ID EPITHELIAL OVARIAN-CANCER; GYNECOLOGIC-ONCOLOGY-GROUP; RANDOMIZED TRIAL; STAGE-III; CISPLATIN; CYCLOPHOSPHAMIDE; GEMCITABINE; CARCINOMA; PACLITAXEL; CHEMOTHERAPY AB Objective. In an effort to improve the results of primary chemotherapy for mullerian malignancies a novel chemotherapy program was piloted that delivered three sequential chemotherapy doublets. The primary endpoints were surgically defined response rates and evaluation of toxicity. Methods. After primary cytoreductive surgery patients were treated with three sequential doublets including three initial cycles of carboplatin and paclitaxel (doublet 1) and then two cycles of cisplatin (day 1) and gemcitabine (days I and 8; doublet 2), and finally two cycles of doxorubicin (day 1) and topotecan (days 3,4, and 5; doublet 3). Cycles 4 through 7 were given with G-CSF (Neupogen) support at a dose of 5 mcg/kg/day. After therapy, all women were clinically staged and evaluated by second-look laparoscopy/laparotomy (SLO) if clinical staging was negative for residual disease. Results. A total of 49 eligible patients were enrolled with a median age of 52 (SD 9). Forty-four women had either ovarian cancer or primary peritoneal carcinoma with 3 women diagnosed with fallopian tube carcinoma and 2 with papillary serous carcinoma of the uterus. Eighty-four percent of patients had stage lIIc/IV tumors, with 29% having > I cm residual disease after primary cytoreductive surgery. Thirty-nine of 49 (80%) patients completed therapy. A total of 283 cycles of chemotherapy were delivered with acceptable toxicities. There were no toxic deaths. Five women were withdrawn from trial (3 for Taxol hypersensitivity, I for gemcitabine pulmonary hypersensitivity, and I for serious line infection). Neutropenia, typically without fever, was relatively frequent in the first doublet. Nausea and thrombocytopenia were the predominant toxicities in doublet 2. Thirty-nine women completed all cycles of treatment. Thirty-six women had restaging results consistent with a clinical complete response (CR) and underwent SLO. The pathologic CR rate of the patients undergoing SLO was 38%. Conclusions. Treatment with this sequential doublet regimen is feasible with a 38% pathologic CR rate. (C) 2003 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Gynecol Oncol, Boston, MA 02115 USA. RP Seiden, MV (reprint author), Massachusetts Gen Hosp, Div Med Oncol, Cox 640,100 Blossom St, Boston, MA 02114 USA. NR 24 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD NOV PY 2003 VL 91 IS 2 BP 293 EP 298 DI 10.1016/S0090-8258(03)00496-7 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 744GP UT WOS:000186619800004 PM 14599858 ER PT J AU Faden, RR Dawson, L Bateman-House, AS Agnew, DM Bok, H Brock, DW Chakravarti, A Gao, XJ Greene, M Hansen, JA King, PA O'Brien, SJ Sachs, DH Schill, KE Siegel, A Solter, D Suter, SM Verfaillie, CM Walters, LB Gearhart, JD AF Faden, RR Dawson, L Bateman-House, AS Agnew, DM Bok, H Brock, DW Chakravarti, A Gao, XJ Greene, M Hansen, JA King, PA O'Brien, SJ Sachs, DH Schill, KE Siegel, A Solter, D Suter, SM Verfaillie, CM Walters, LB Gearhart, JD TI Public stem cell banks: Considerations of justice in stem cell research and therapy SO HASTINGS CENTER REPORT LA English DT Article ID TRANSPLANTATION TOLERANCE; UNRELATED MARROW; MIXED CHIMERISM; HLA-A; DIVERSITY; PROBABILITY; DONORS; PLURIPOTENCY; POLYMORPHISM; RECIPIENTS C1 Johns Hopkins Univ, Phoebe R Berman Bioeth Inst, Dept Philosophy, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Dev Genet Lab, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, MckUsick Nathans Inst Genet Med, Baltimore, MD 21218 USA. NCI, Frederick, MD 21701 USA. Johns Hopkins Univ, Greenwall Fellowship Program Bioeth & Hlth Policy, Baltimore, MD 21218 USA. Georgetown Univ, Ctr Law, Washington, DC 20057 USA. Amer Genet Assoc, Buckeystown, MD USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res ctr, Boston, MA 02129 USA. Johns Hopkins Univ, Sch Med, Dept Obstet & Gynecol, Baltimore, MD 21205 USA. Max Planck Inst Immunbiol, Dept Dev Biol, D-7800 Freiburg, Germany. George Washington Univ, Sch Law, Washington, DC 20052 USA. Univ Minnesota, Stem cell Inst, Minneapolis, MN 55455 USA. Georgetown Univ, Kennedy Inst Eth, Washington, DC 20057 USA. Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21218 USA. RP Faden, RR (reprint author), Johns Hopkins Univ, Phoebe R Berman Bioeth Inst, Dept Philosophy, Baltimore, MD 21218 USA. OI Verfaillie, Catherine/0000-0001-7564-4079; Bateman-House, Alison/0000-0001-6921-9666 NR 35 TC 43 Z9 44 U1 1 U2 3 PU HASTINGS CENTER PI BRIARCLIFF MANOR PA 255 ELM ROAD, BRIARCLIFF MANOR, NY 10510 USA SN 0093-0334 J9 HASTINGS CENT REP JI Hastings Cent. Rep. PD NOV-DEC PY 2003 VL 33 IS 6 BP 13 EP 27 DI 10.2307/3527822 PG 15 WC Ethics; Health Care Sciences & Services; Medical Ethics; Social Sciences, Biomedical SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical Ethics; Biomedical Social Sciences GA 766TC UT WOS:000188390800016 PM 14983554 ER PT J AU Epstein, JB Feldman, R Dolor, RJ Porter, SR AF Epstein, JB Feldman, R Dolor, RJ Porter, SR TI The utility of tolonium chloride rinse in the diagnosis of recurrent or second primary cancers in patients with prior upper aerodigestive tract cancer SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article DE diagnostic sensitivity; oropharyngeal cancer; tolonium chloride ID TOLUIDINE BLUE APPLICATION; SQUAMOUS-CELL CARCINOMAS; ORAL-CANCER; EPITHELIAL DYSPLASIA; STAINING TEST; RISK; TOBACCO; LESIONS; LEUKOPLAKIA; SENSITIVITY AB Background. The clinical utility of tolonium chloride rinse was compared with unaided visual examination alone in the diagnosis of oral carcinoma in patients previously treated for carcinoma of the upper aerodigestive tract. Methods. A total of 668 patients were enrolled in this multicenter study. At each site, an oral clinical visual examination was completed by one investigator followed by tolonium chloride rinse and examination by a second investigator blinded to the examination findings of the first investigator. If a lesion was considered suspicious (urgent biopsy required at the first visit), the lesion was biopsied after tolonium chloride rinsing. Patients with lesions characterized at the first visit as not suspicious (biopsy not urgent) or that stained with tolonium chloride were asked to return for a second visit. At the second visit, any residual lesion or lesions that retained tolonium chloride were biopsied. Results. A total of 96 biopsies was performed in 81 of the 668 patients (12.1%), of which 30 (31.3%) were diagnosed histologically as carcinoma/carcinoma in situ (CIS) and the remainder as inflammation (31.3%), keratosis (26.6%), dysplasia (21.9%), ulcer (2.1%), other (3.1%), or no abnormality (1.0%). Of the 30 lesions with the diagnosis of carcinoma/CIS, 12 (sensitivity 40.0%) were considered to be clinically suspicious (CS+), whereas 29 (sensitivity 96.7%) retained tolonium chloride (p = .0002). The predictive values of a positive test for clinical examination and tolonium chloride staining were similar (36.4% vs 32.6%; p = .5871), indicating that the greater sensitivity of tolonium chloride was not associated with an excessive number of unnecessary biopsies (false positives). Conclusions. Tolonium chloride rinse is more sensitive than clinical examination alone in detecting lesions that might be found on biopsy to be carcinoma or CIS. The increased sensitivity is largely attributed to lesions that stain but were not detected clinically on visual examination. (C) 2003 Wiley Periodicals, Inc. C1 British Columbia Canc Agcy, Div Dent, Vancouver, BC V5Z 4E6, Canada. Univ & Woodland Ave, Dent Serv, Vet Affairs Med Ctr, Philadelphia, PA USA. Vet Affairs Med Ctr, Durham, NC USA. UCL Eastman Dent Inst, London, England. RP Epstein, JB (reprint author), British Columbia Canc Agcy, Div Dent, 600 W 10th Ave, Vancouver, BC V5Z 4E6, Canada. EM jepstein@uic.edu NR 46 TC 52 Z9 53 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD NOV PY 2003 VL 25 IS 11 BP 911 EP 921 DI 10.1002/hed.10309 PG 11 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 736FJ UT WOS:000186160500004 PM 14603451 ER PT J AU Koenig, L Dobson, A Ho, S Siegel, JM Blumenthal, D Weissman, JS AF Koenig, L Dobson, A Ho, S Siegel, JM Blumenthal, D Weissman, JS TI Estimating the mission-related costs of teaching hospitals SO HEALTH AFFAIRS LA English DT Article AB Academic health centers and other teaching hospitals face higher patient care costs than nonteaching community hospitals face, because of their missions of graduate medical education (GME), biomedical research, and the maintenance of standby capacity for medically complex patients. We estimate that total mission-related costs were $27 billion in 2002 for all teaching hospitals, with GME (including indirect and direct GME) and standby capacity accounting for roughly 60 and 35 percent of these costs, respectively. To assure their continued ability to perform important social missions in a competitive environment, it may be necessary to reassess the way in which these activities are financed. C1 Lewin Grp, Falls Church, VA USA. Massachusetts Gen Hosp, Partners Healthcare Syst, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Koenig, L (reprint author), Lewin Grp, Falls Church, VA USA. NR 10 TC 20 Z9 20 U1 0 U2 1 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 2003 VL 22 IS 6 BP 112 EP 122 DI 10.1377/hlthaff.22.6.112 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 744LN UT WOS:000186632200015 PM 14649437 ER PT J AU Weissman, JS Moy, E Campbell, EG Gokhale, M Yucel, R Causino, N Blumenthal, D AF Weissman, JS Moy, E Campbell, EG Gokhale, M Yucel, R Causino, N Blumenthal, D TI Limits to the safety net: Teaching hospital faculty report on their patients' access to care SO HEALTH AFFAIRS LA English DT Article ID HIDDEN CURRICULUM; MEDICAL-EDUCATION; MARKET FORCES; MANAGED CARE; INSURANCE; CENTERS AB Many major teaching hospitals might not be able to offer adequate access to specialty care for uninsured patients. This study found that medical school faculty were more likely to have difficulty obtaining specialty services for uninsured than for privately insured patients. These gaps in access were similar in magnitude for public and private institutions. Initial treatment of uninsured patients at academic health centers (AHCs) does not guarantee access to specialty and other referral services, which suggests that there are limits to relying on a health care safety net for uninsured patients. AHCs and affiliated group practices should examine policies that limit access for uninsured patients. C1 Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Agcy Healthcare Res & Qual, Rockville, MD USA. RP Weissman, JS (reprint author), Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. NR 31 TC 20 Z9 20 U1 0 U2 1 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 2003 VL 22 IS 6 BP 156 EP 166 DI 10.1377/hlthaff.22.6.156 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 744LN UT WOS:000186632200021 PM 14649442 ER PT J AU Stankovic, KM Corfas, G AF Stankovic, KM Corfas, G TI Real-time quantitative RT-PCR for low-abundance transcripts in the inner ear: analysis of neurotrophic factor expression SO HEARING RESEARCH LA English DT Article DE real-time quantitative reverse transcription-polymerase chain reaction; neurotrophin 3; brain-derived neurotrophic factor; glial cell-line-derived neurotrophic factor; postnatal inner ear ID POLYMERASE CHAIN-REACTION; MATURE RAT COCHLEA; AUDITORY-NERVE; FACTOR GDNF; STRESS; CELL; HYPERGRAVITY; PROTECTION; RECEPTORS; MICE AB Real-time quantitative reverse transcription-PCR is a highly sensitive technology that allows high throughput quantification of gene expression. Application of this technique to the inner ear is potentially very important, but is not straightforward because tissue harvesting can be challenging, RNA yield from individual inner ears is low, and cDNA synthesis from scant RNA can be inefficient. To overcome these challenges, we tested many parameters and reagents, and developed an approach to reliably quantitate small changes in low-abundance transcripts. Using this technique we demonstrate the presence and quantify amounts of the neurotrophic factors neurotrophin 3 (NT-3), brain-derived neurotrophic factor (BDNF) and glial cell-line-derived neurotrophic factor (GDNF),. in the cochlea and vestibular end organs of postnatal murine inner ear (P26). We show that out of the factors tested, BDNF is the only one differentially expressed between the cochlea and vestibular end organs, being 23.4 +/- 0.3 times more abundant in the vestibular end organs. Within the cochlea, GDNF gene expression is 4.9 +/- 0.2 times greater than NT-3 expression. Within the combined vestibular end organs, BDNF expression is 43.0 +/- 1.5 times greater than NT-3 expression. Our results suggest that neurotrophic factors continue to play a role in the postnatal inner ear, in addition to their previously shown essential role during development. (C) 2003 Elsevier B.V. All rights reserved. C1 Childrens Hosp, Div Neurosci, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Corfas, G (reprint author), Childrens Hosp, Div Neurosci, 300 Longwood Ave, Boston, MA 02115 USA. FU NICHD NIH HHS [P30-HD 18655]; NIDCD NIH HHS [R01 DC04820] NR 24 TC 32 Z9 32 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD NOV PY 2003 VL 185 IS 1-2 BP 97 EP 108 DI 10.1016/S0378-5955(03)00298-3 PG 12 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 743FR UT WOS:000186562200011 PM 14599697 ER PT J AU Wu, J Haugk, K Plymate, SR AF Wu, J Haugk, K Plymate, SR TI Activation of pro-apoptotic p38-MAPK pathway in the prostate cancer cell line M12 expressing a truncated IGF-IR SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE pAkt; PI3K; ERK; 486/STOP; insulin-like growth factor I (IGF-I) ID DOMINANT-NEGATIVE MUTANT; GROWTH-FACTOR RECEPTOR; SIGNAL-TRANSDUCTION; TUMOR-GROWTH; IN-VIVO; INSULIN; PHOSPHORYLATION; TUMORIGENESIS; INHIBITION; SURVIVAL AB The type I insulin-like growth factor receptor (IGF-IR) plays a critical role in signaling survival and proliferation in many cell types. Activation of IGF-IR by its ligands promotes cell proliferation via mitogen-activated protein kinase (MAPK) cascade and cell survival via phosphoinositide 3-kinase (PI3K) cascade. The IGF-IR emerges as a powerful growth factor for many tumor cells. A truncated IGF-IR 486/STOP, described as a dominant negative IGF-IR mutant, was shown to induce apoptosis and inhibit tumor growth in vivo while endogenous IGF-IR was activated. To investigate the mechanism(s) of the action of 486/STOP, we have introduced 486/STOP into the prostate tumor model cell line M12 and its derivative M12lisn that expresses high levels of wild type IGF-IR. We have found that 486/STOP induces apoptosis in M12 and M12lisn cells in culture and that 486/STOP acts through activation of the pro-apoptotic p38-MAPK without interfering with wild type IGF-IR activation. In addition, our results have indicated that 486/STOP induced activation of p38-MAPK increases through activation of endogenous IGF-IR. These data suggest that activation of the IGF-IR by 486/STOP can selectively enhance the previously reported IGF-IR pro-apoptotic signaling pathways. C1 Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98104 USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. RP Plymate, SR (reprint author), Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Box 359755,325 9th Ave, Seattle, WA 98104 USA. EM splymate@u.washington.edu FU NCI NIH HHS [P01 CA85859]; NIDDK NIH HHS [R01DK52683] NR 27 TC 12 Z9 13 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD NOV-DEC PY 2003 VL 35 IS 11-12 BP 751 EP 757 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 761UB UT WOS:000187932900014 PM 14710354 ER PT J AU Butts, BD Linseman, DA Le, SS Laessig, TA Heidenreich, KA AF Butts, BD Linseman, DA Le, SS Laessig, TA Heidenreich, KA TI Insulin-like growth factor-I suppresses degradation of the pro-survival transcription factor myocyte enhancer factor 2D (MEF2D) during neuronal apoptosis SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE cerebellar granule neurons; neurodegeneration; programmed cell death; caspases; signal transduction ID CEREBELLAR GRANULE NEURONS; FACTOR 2A; IGF-I; BINDING-PROTEINS; GENE-EXPRESSION; CELL-SURVIVAL; CANCER CELLS; PHOSPHORYLATION; ACTIVATION; DEATH AB Cultured rat cerebellar granule neurons (CGNs) require depolarization-mediated calcium influx for survival. Calcium regulates the activity of the pro-survival transcription factor, myocyte enhancer factor 2D (MEF2D). MEF2D is hyperphosphorylated and degraded in CGNs undergoing apoptosis induced by lowering the extracellular potassium concentration from 25 mM to 5 mM. Since insulin-like growth factor-I (IGF-I) is known to protect CGNs from apoptotic cell death, we investigated the effects of IGF-I on MEF2D processing during apoptosis. IGF-I administered during the apoptotic insult did not prevent the hyperphosphorylation of MEF2D and consequential loss of DNA binding. However, IGF-I significantly blocked the degradation of MEF2D. Furthermore, IGF-I had no effect on the initial loss of MEF2 transcriptional activity following hyperphosphorylation, but the recovery of MEF2 activity following restoration of intracellular calcium was significantly increased by IGF-I. We conclude that IGF-I blocks the degradation of MEF2D and enhances recovery of MEF2 activity by protecting MEF2D from caspase-dependent cleavage during apoptosis. These results suggest that IGF-I can prolong the time of commitment to irreversible cell death and enhance the recovery of neurons subjected to an acute apoptotic stimulus by preserving the activity of the pro-survival factor MEF2D. C1 Denver VAMC, Denver, CO 80220 USA. Univ Colorado, Ctr Hlth Sci, Dept Pharmacol, Denver, CO 80202 USA. RP Heidenreich, KA (reprint author), Denver VAMC, 111H,1055 Clermont St, Denver, CO 80220 USA. EM kim.heidenreich@uchsc.edu FU NINDS NIH HHS [NS38619-01A1] NR 52 TC 10 Z9 10 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD NOV-DEC PY 2003 VL 35 IS 11-12 BP 763 EP 770 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 761UB UT WOS:000187932900016 PM 14710356 ER PT J AU Harms, MP Melcher, JR AF Harms, MP Melcher, JR TI Detection and quantification of a wide range of fMRI temporal responses using a physiologically-motivated basis set SO HUMAN BRAIN MAPPING LA English DT Article DE fMRI; general linear model; temporal dynamics; auditory cortex ID TIME-SERIES ANALYSIS; PRIMARY VISUAL-CORTEX; CEREBRAL BLOOD-FLOW; FUNCTIONAL MRI; STATISTICAL-METHODS; STIMULUS RATE; RESAMPLING METHODS; WAVELET ANALYSIS; STRIATE CORTEX; BRAIN ACTIVITY AB The temporal dynamics of fMRI responses can span a broad range, indicating a rich underlying physiology, but also posing a significant challenge for detection. For instance, in human auditory cortex, prolonged sound stimuli (similar to30 sec) can evoke responses ranging from sustained to highly phasic (i.e., characterized by prominent peaks just after sound onset and offset). In the present study, we developed a method capable of detecting a wide variety of responses, while simultaneously extracting information about individual response components, which may have different neurophysiological underpinnings. Specifically, we implemented the general linear model using a novel set of basis functions chosen to reflect temporal features of cortical fMRI responses. This physiologically-motivated basis set (the "OSORU" basis set) was tested against (1) the commonly employed "sustained-only" basis "set" (i.e., a single smoothed "boxcar" function), and (2) a sinusoidal basis set, which is capable of detecting a broad range of responses, but lacks a direct relationship to individual response components. On data that included many different temporal responses, the OSORU basis set performed far better overall than the sustained-only set, and as well or better than the sinusoidal basis set. The OSORU basis set also proved effective in exploring brain physiology. As an example, we demonstrate that the OSORU basis functions can be used to spatially map the relative amount of transient vs. sustained activity within auditory cortex. The OSORU basis set provides a powerful means for response detection and quantification that should be broadly applicable to any brain system and to both human and non-human species. (C) 2003 Wiley-Liss, Inc. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Harms, MP (reprint author), Pfizer Inc, 700 Chesterfield Pkwy W, Chesterfield, MO 63017 USA. OI Harms, Michael/0000-0001-7945-036X FU NCRR NIH HHS [P41 RR014075]; NIDCD NIH HHS [P01 DC000119, P01 DC000119-260023, T32 DC000038] NR 54 TC 37 Z9 37 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD NOV PY 2003 VL 20 IS 3 BP 168 EP 183 DI 10.1002/hbm.10136 PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 741WT UT WOS:000186483900005 PM 14601143 ER PT J AU Sharma, S Batra, RK Yang, SC Hillinger, S Zhu, L Atianzar, K Strieter, RM Riedl, K Huang, M Dubinett, SM AF Sharma, S Batra, RK Yang, SC Hillinger, S Zhu, L Atianzar, K Strieter, RM Riedl, K Huang, M Dubinett, SM TI Interleukin-7 gene-modified dendritic cells reduce pulmonary tumor burden in spontaneous murine bronchoalveolar cell carcinoma SO HUMAN GENE THERAPY LA English DT Article ID GROWTH-FACTOR-BETA; COLONY-STIMULATING FACTOR; ANGIOGENESIS IN-VIVO; MHC CLASS-I; T-CELL; LUNG-CANCER; ANTITUMOR IMMUNITY; INTERFERON-GAMMA; DOWN-REGULATION; INTRATUMORAL INJECTION AB The antitumor efficiency of dendritic cells transduced with an adenovirus vector expressing interleukin (IL)-7 (DC-AdIL-7) was evaluated in a murine model of spontaneous bronchoalveolar cell carcinoma. These transgenic mice (CC-10 TAg), expressing the SV40 large T antigen under the Clara cell promoter, develop bilateral multifocal pulmonary adenocarcinomas and die at 4 months as a result of progressive pulmonary tumor burden. Injection of DC-AdIL-7 in the axillary lymph node region (ALNR) weekly for 3 weeks led to a marked reduction in tumor burden with extensive lymphocytic infiltration of the tumors and enhanced survival. The antitumor responses were accompanied by the enhanced elaboration of interferon (IFN)-gamma and IL-12 as well as an increase in the antiangiogenic chemokines, IFN-gamma-inducible protein 10 (IP-10/CXCL10) and monokine induced by IFN-gamma (MIG/CXCL9). In contrast, production of the immunosuppressive mediators IL-10, transforming growth factor (TGF)-beta, prostaglandin E-2 (PGE(2)), and the proangiogenic modulator vascular endothelial growth factor ( VEGF) decreased in response to DC-AdIL-7 treatment. Significant reduction in tumor burden in a model in which tumors develop in an organ-specific manner provides a strong rationale for further evaluation of DC-AdIL-7 in regulation of tumor immunity and its use in lung cancer genetic immunotherapy. C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med,Dept Med, Ctr Hlth Sci 37 131,Lung Canc Res Program, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Mol Gene Med Lab, Los Angeles, CA 90073 USA. RP Sharma, S (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med,Dept Med, Ctr Hlth Sci 37 131,Lung Canc Res Program, 0833 LeConte Ave, Los Angeles, CA 90095 USA. FU NCI NIH HHS [P50 CA090388, R01 CA 78654, R01 CA078654, P50 CA 90388, R01 CA085686, CA 85686] NR 76 TC 22 Z9 23 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD NOV PY 2003 VL 14 IS 16 BP 1511 EP 1524 DI 10.1089/104303403322495025 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 736MX UT WOS:000186175500002 PM 14577913 ER PT J AU Saunders, AJ Bertram, L Mullin, K Sampson, AJ Latifzai, K Basu, S Jones, J Kinney, D MacKenzie-Ingano, L Yu, S Albert, MS Moscarillo, TJ Go, RCP Bassett, SS Daly, MJ Laird, NM Wang, X Velicelebi, G Wagner, SL Becker, DK Tanzi, RE Blacker, D AF Saunders, AJ Bertram, L Mullin, K Sampson, AJ Latifzai, K Basu, S Jones, J Kinney, D MacKenzie-Ingano, L Yu, S Albert, MS Moscarillo, TJ Go, RCP Bassett, SS Daly, MJ Laird, NM Wang, X Velicelebi, G Wagner, SL Becker, DK Tanzi, RE Blacker, D TI Genetic association of Alzheimer's disease with multiple polymorphisms in alpha-2-macroglobulin SO HUMAN MOLECULAR GENETICS LA English DT Article ID RECEPTOR-RELATED PROTEIN; FAMILY-BASED TESTS; BETA-AMYLOID PEPTIDE; LINKAGE DISEQUILIBRIUM; DELETION POLYMORPHISM; I1000V POLYMORPHISM; APOLIPOPROTEIN-E; NO ASSOCIATION; ALPHA(2)-MACROGLOBULIN POLYMORPHISMS; FIBRIL FORMATION AB Alpha-2-Macroglobulin (A2M) is a highly plausible candidate gene for Alzheimer's disease (AD) in a region of chromosome 12 that has numerous independent reports of genetic linkage. We previously reported that a 5 bp deletion in A2M was associated with AD in a subset of the National Institute of Health (NIMH) Genetics Initiative AD family sample. Efforts to replicate this association finding in case - control samples have been largely negative, while those in family samples have been more positive. We hypothesized that variable findings regarding this deletion, along with variable reports of association with V1000I, another polymorphism in the gene, result from linkage disequilibrium in the area as well as ascertainment differences between family-based and case-control studies. Thus, we resequenced the A2M locus to identify novel polymorphisms to test for genetic association with AD. We identified seven novel polymorphisms and tested them in the full NIMH sample of 1439 individuals in 437 families. We found significant genetic association of the 5 bp deletion and two novel polymorphisms with AD. Substantial linkage disequilibrium was detected across the gene as a whole, and haplotype analysis also showed significant association between AD and groups of A2M polymorphisms. Several of these polymorphisms and haplotypes remain significantly associated with AD even after correction for multiple testing. Taken together, these findings, and the positive reports in other family-based studies, continue to support a potential role for A2M or a nearby gene in AD. However, the negative case - control studies suggest that any underlying pathogenic polymorphisms have a modest effect, and may operate primarily among individuals with a family history of AD. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Genet & Aging Res Unit, Dept Neurol,Ctr Aging Genet & Neurodegenerat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Gerontol Res Unit, Charlestown, MA USA. Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA. Johns Hopkins Univ, Inst Med, Dept Psychiat & Behav Sci, Baltimore, MD USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Neurogenet Inc, La Jolla, CA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Tanzi, RE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Genet & Aging Res Unit, Dept Neurol,Ctr Aging Genet & Neurodegenerat, C3809,114 16th St, Charlestown, MA 02129 USA. RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X NR 81 TC 50 Z9 55 U1 0 U2 3 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 NOV 1 PY 2003 VL 12 IS 21 BP 2765 EP 2776 DI 10.1093/hmg/ddg310 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 738WH UT WOS:000186310500004 PM 12966032 ER PT J AU Crowson, AN Nuovo, GJ Mihm, MC Magro, C AF Crowson, AN Nuovo, GJ Mihm, MC Magro, C TI Cutaneous manifestations of Crohn's disease, its spectrum, and its pathogenesis: Intracellular consensus bacterial 16S rRNA is associated with the gastrointestinal but not the cutaneous manifestations of Crohn's disease SO HUMAN PATHOLOGY LA English DT Article DE Crohn's disease; 16S rRNA; cutaneous manifestations ID INFLAMMATORY-BOWEL-DISEASE; POLYMERASE-CHAIN-REACTION; POLYARTERITIS-NODOSA; MEASLES-VIRUS; VASCULITIS; LESIONS; CELLS; INFECTION; CYTOKINES; BIOPSIES AB The classic pathology of skin disease discontinuous from the inflamed gastrointestinal (GI) tract in patients with Crohn's disease (CD) includes pyoderma gangrenosum (PG), erythema nodosum (EN), and so-called metastatic Crohn's disease. The purpose of this study was two-fold: First, we explored the full spectrum of cutaneous lesions associated with Crohn's disease, and second, we sought to explore a potential molecular basis of the skin lesions in patients with CD. In this regard, we analyzed skin and GI tract biopsies from affected patients for the consensus bacterial SrRNA to determine whether direct bacterial infection was associated with either condition. Formalin-fixed, paraffin-embedded sections were studied and correlated to clinical presentation and histories from 33 patients with CD. Consensus bacterial RNA sequences were analyzed using an RT in situ PCR assay on both skin biopsy and GI biopsy material. The GI tract material included biopsies from 3 patients who had skin lesions and from 7 patients in whom there were no known skin manifestations. There were 8 cases of neutrophilic dominant dermal infiltrates, including pyoderma gangrenosum, 6 cases of granuloma annulare/necrobiosis lipoidica-like lesions, 5 cases of sterile neutrophilic folliculitis, 5 cases of parmiculitis, 4 cases of vasculitis, 2 cases of psoriasis, 2 cases of lichenoid and granulomatous inflammation, and I case of classic metastatic CD. Intracellular bacterial 16S rRNA was detected in 8 of 10 tissues of active CD in the GI tract, of which 3 of the cases tested were from patients who also developed skin lesions at some point in their clinical course; in contrast, none of the skin biopsies had detectable bacterial RNA. The dermatopathological manifestations of CD discontiguous from the involved GI tract mucosa have in common a vascular injury syndrome, typically with a prominent extravascular neutrophilic and/or histiocytic dermal infiltrate. In addition, this study, the first to document in situ intracellular consensus bacterial SrRNA in the GI tract in CD, suggests that hematogenous dissemination of viable microbes is not associated with the cutaneous manifestations of this disease. Bacteria do, however, appear to play a role in bowel lesions of patients with CD. (C) 2003 Elsevier Inc. All rights reserved. C1 Ohio State Univ, Med Ctr, Dept Pathol, Columbus, OH 43210 USA. Ohio State Univ, Div Dermatopathol, Columbus, OH 43210 USA. Ohio State Univ, Div Mol Diagnost, Columbus, OH 43210 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Reg Med Lab, Tulsa, OK USA. Univ Oklahoma, Dept Dermatol, Norman, OK 73019 USA. Univ Oklahoma, Dept Pathol, Norman, OK 73019 USA. Cent Med Labs, Winnipeg, MB, Canada. RP Nuovo, GJ (reprint author), Ohio State Univ, Med Ctr, Dept Pathol, E305 Doan Hall,410 W 10th Ave, Columbus, OH 43210 USA. NR 53 TC 30 Z9 30 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD NOV PY 2003 VL 34 IS 11 BP 1185 EP 1192 DI 10.1016/S0046-8177(03)00428-3 PG 8 WC Pathology SC Pathology GA 746FC UT WOS:000186735500016 PM 14652821 ER PT J AU Orkin, SH AF Orkin, SH TI Priming the hematopoietic pump SO IMMUNITY LA English DT Editorial Material ID PRECEDES COMMITMENT; LINEAGE COMMITMENT; STEM-CELLS; PROGENITORS; REGION; BETA C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 9 TC 22 Z9 22 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 2003 VL 19 IS 5 BP 633 EP 634 DI 10.1016/S1074-7613(03)00302-9 PG 2 WC Immunology SC Immunology GA 745CY UT WOS:000186672200001 PM 14614848 ER PT J AU Ye, M Iwasaki, H Laiosa, CV Stadtfeld, M Xie, HF Heck, S Clausen, BE Akashi, K Graf, T AF Ye, M Iwasaki, H Laiosa, CV Stadtfeld, M Xie, HF Heck, S Clausen, BE Akashi, K Graf, T TI Hematopoietic stem cells expressing the myeloid lysozyme gene retain long-term, multilineage repopulation potential SO IMMUNITY LA English DT Article ID LINEAGE COMMITMENT; MICE; DIFFERENTIATION; GRANULOCYTES; PROGENITORS; MACROPHAGES; PLASTICITY; LEUKEMIA; PROTEIN; SYSTEM AB Single cell PCR studies showed that hematopoietic stem cells (HSCs) express a variety of lineage-affiliated genes. However, it remains unclear whether these cells exhibiting "lineage priming" represent bona fide stem cells or a subpopulation earmarked for differentiation. Here we have used a Cre-Lox approach to follow the fate of cells expressing a lineage-affiliated marker. We crossed lysozyme Cre mice with yellow fluorescent protein (EYFP) reporter mice and found EYFP gene expression not only in myelomonocytic cells but also in a fraction of HSCs as well as B cells and T cells. Transplantation of EYFP(+) HSCs into primary and secondary recipients generated mice in which all hematopoietic cells were EYFP(+). In contrast, crosses between CD19 Cre and lck Cre mice with reporter mice showed no EYFP expression in HSCs or intermediate progenitors. Our results demonstrate that lysozyme expression does not mark myeloid commitment and that longterm repopulation potential is maintained in primed HSCs. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Graf, T (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Dev & Mol Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM graf@aecom.yu.edu RI CLAUSEN, Bjorn/A-8229-2010; Graf, Thomas/B-4252-2015 OI CLAUSEN, Bjorn/0000-0002-2484-7842; Graf, Thomas/0000-0003-2774-4117 FU NCI NIH HHS [CA072009, R01 CA89590-01]; NIDDK NIH HHS [DK050654, DK061320]; NINDS NIH HHS [R01 NS43881-01] NR 31 TC 115 Z9 116 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 2003 VL 19 IS 5 BP 689 EP 699 DI 10.1016/S1074-7613(03)00299-1 PG 11 WC Immunology SC Immunology GA 745CY UT WOS:000186672200009 PM 14614856 ER PT J AU Rosenkranz, KA Sheridan, RL AF Rosenkranz, KA Sheridan, RL TI Trauma to adult bicyclists: a growing problem in the urban environment SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article ID SAFETY HELMETS AB The proportion of adults involved in serious bicycle accidents has increased in the last two decades. The majority of the bicycle injury prevention efforts, however, are directed toward child riders. The authors performed a retrospective review of injury statistics from the Massachusetts Hospital Discharge Data Set, 1994-1999, the Massachusetts Emergency Department Injury Surveillance System, 1999, and the trauma registry of an Urban Level I Trauma Centre, 1993-2000. Massachusetts's state-wide injury data reveals a 30% increase in hospital charges between 1994 and 1999 for adults following bicycle falls and collisions with concomitant stability in the charges for children. In the years 1993-2000, 60% of patients requiring inpatient care at the Study Centre for Bicycle Related Injuries were over 16 years of age. Fifty-one percent of patients were without a helmet. Positive blood alcohol tests were present in 35 (16%) of the 222 patients. Forty-six (75%) of patients suffering closed head injury were not helmeted. Adult bicycle trauma is a significant health and financial problem in the urban state of Massachusetts. Bicycle education and legislation emphasising safe bicycling practice, the protective effects of helmets, and the danger of cycling under the influence of alcohol may help alleviate this problem. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Surg, Div Trauma & Burns, Clin 108, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Dartmouth Hitchcock Med Ctr, Dept Surg, Boston, MA 02114 USA. RP Sheridan, RL (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Trauma & Burns, Clin 108, Boston, MA 02114 USA. NR 6 TC 24 Z9 25 U1 0 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 J9 INJURY JI Injury-Int. J. Care Inj. PD NOV PY 2003 VL 34 IS 11 BP 825 EP 829 AR PII S0020-1383(02)00389-3 DI 10.1016/S0020-1383(02)00389-3 PG 5 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA 745DJ UT WOS:000186673400004 PM 14580814 ER PT J AU Huang, TT Zong, YM Dalwadi, H Chung, C Miceli, MC Spicher, K Birnbaumer, L Braun, J Aranda, R AF Huang, TT Zong, YM Dalwadi, H Chung, C Miceli, MC Spicher, K Birnbaumer, L Braun, J Aranda, R TI TCR-mediated hyper-responsiveness of autoimmune G alpha i2(-/-) mice is an intrinsic naive CD4(+) T cell disorder selective for the G alpha i2 subunit SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE autoimmunity; mucosa; signal transduction; T lymphocytes; TCR ID PERTUSSIS TOXIN; G-PROTEINS; ALPHA-SUBUNITS; MEMORY CELLS; LYMPHOCYTES; RECEPTOR; EXPRESSION; ACTIVATION; CHANNELS; ANTIGEN AB Heterotrimeric Gi signaling regulates immune homeostasis, since autoimmunity occurs upon disruption of this pathway. However, the role of the lymphocyte-expressed Galphai subunits (Galphai2 and 3) on T cell activation and cytokine production is poorly understood. To examine this role, we studied T lymphocytes from mice deficient in the Galphai2 or Galphai3 subunits. Galphai2(-/-) but not Galphai3(-/-) splenocytes were hyper-responsive for IFN-gamma and IL-4 production following activation through the TCR. Galphai2(-/-) T cells had a relaxed costimulatory requirement for IL-2 secretion and proliferation compared to wild-type cells. Purified naive Galphai2(-/-) T cells produced more IL-2 than naive wild-type T cells following TCR activation, indicating that the hyper-responsive cytokine profile was not due to the expanded Galphai2(-/-), memory T cells, but involved an intrinsic T cell alteration. Cytokine hyper-responsiveness was not seen when purified Galphai2(-/-) T cells were stimulated with phorbol myristic acetate/ionomycin, localizing the alteration to a proximal TCR-specific signaling pathway. Galphai2(-/-) CD4(+) T cells were distinguished from wild-type or Galphai3(-/-) T cells by a globally augmented TCR-induced calcium response. These findings indicate that Galphai2(-/-) mice have an intrinsic CD4(+) T cell abnormality in TCR signaling which may be one cause of augmented T cell effector function and Galphai2(-/-) autoimmune susceptibility. C1 Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. VA GReater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Braun, J (reprint author), Univ Calif Los Angeles, Inst Mol Biol, Box 951732,CHS 13-222, Los Angeles, CA 90095 USA. FU NCI NIH HHS [CA 16042, R01 CA 65979]; NIAID NIH HHS [AI 28697, 5T32 AI 07325, AI 07126-23]; NIDDK NIH HHS [DK 43026, DK 46763] NR 45 TC 43 Z9 45 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD NOV PY 2003 VL 15 IS 11 BP 1359 EP 1367 DI 10.1093/intimm/dxg135 PG 9 WC Immunology SC Immunology GA 739CX UT WOS:000186325600010 PM 14565934 ER PT J AU Santillan, AA Camargo, CA AF Santillan, AA Camargo, CA TI Body mass index and asthma among Mexican adults: the effect of using self-reported vs measured weight and height SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE asthma; bias; body mass index; Mexico ID OBESITY; POPULATION; PREVALENCE; WOMEN AB Several recent studies have demonstrated a positive association between obesity and asthma among women but not men. The present study examines the effect of misclassification of body mass indes (BMI) in the association between obesity and asthma by gender. This cross-sectional analysis included a total sample of 961 Mexican adults. Use of measured BMI revealed that obesity (BMI >30 kg/m(2)) was a risk factor for asthma diagnosis in both men (OR, 2.5; 95% CI, 1.1 - 5.9) and women (OR, 2.3; 95% CI, 1.5 - 3.8). In contrast, use of self-reported BMI showed that only women (OR, 1.7; 95% CI, 1.1 - 2.7) and not men (OR, 1.3; 95% CI, 0.6 - 2.9) were at increased risk of asthma diagnosis. Use of self-reported BMI substantially underestimated the prevalence of obesity; this bias was not related to asthma per se but was mainly due to obesity. Therefore, misclassification of BMI obscured the relationship between obesity and asthma to a greater extent among men than among women since obesity prevalence in the general population was higher among men. Measurement bias merits greater attention in future research on obesity and asthma. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. RP Camargo, CA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-63841] NR 16 TC 35 Z9 37 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD NOV PY 2003 VL 27 IS 11 BP 1430 EP 1433 DI 10.1038/sj.ijo.0802395 PG 4 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 735KE UT WOS:000186111900022 PM 14574357 ER PT J AU McDermott, NE Chaung, SK Woo, VV Dodson, TB AF McDermott, NE Chaung, SK Woo, VV Dodson, TB TI Complications of dental implants: Identification, frequency, and associatied risk factors SO INTERNATIONAL JOURNAL OF ORAL & MAXILLOFACIAL IMPLANTS LA English DT Article; Proceedings Paper CT Meeting of the International-Association-for-Dental-Research/American-Association-for-D ental-Research CY MAR 06-09, 2002 CL SAN DIEGO, CALIFORNIA SP Int Assoc Dent Res, Amer Assoc Dent Res DE complications; dental implants; proportional hazards models; retrospective cohort study; risk factors ID COMPLETE FIXED PROSTHESES; MARGINAL BONE LOSS; OSSEOINTEGRATED IMPLANTS; ENDOSSEOUS IMPLANTS; PERIODONTAL ASPECTS; 15-YEAR; SUCCESS; TISSUE; TEETH AB Purpose: This study sought to identify the types, frequencies, and risk factors associated with complications following placement of dental implants. It was hypothesized that one or more factors could be identified that are associated with an increased risk for complications and may be modified by the clinician to enhance outcome. Materials and Methods: A retrospective cohort study design was used that included patients who received Bicon implants (Bicon, Boston, MA) between 1992 and 2000. Predictor variables were grouped into demographic, medical history, implant-specific, anatomic, prosthetic, and reconstructive categories. Complications were grouped into inflammatory, prosthetic, operative, and major or minor categories. Cox proportional hazards regression models were developed to identify risk factors for complications. Results: The sample was composed of 677 patients. The overall frequency of implant complications was 13.9% (10.2% inflammatory, 2.7% prosthetic, 1.0% operative), of which 53% were minor. The multivariate Cox model revealed that smoking, use of 1-stage implants, and reconstructive procedures were statistically associated with an increased risk for overall complications (P less than or equal to .05). The median duration of follow-up was 13.1 months (range 0 to 85.6 months). Discussion: A lower frequency of complications was found compared to mean frequencies calculated from past reports. Investigations examining the influence of smoking and reconstructive procedures on implant complications are recommended. Conclusion: Of the 3 factors associated with an increased risk for complications, tobacco use and implant staging may be modified by the clinician to enhance outcome. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. Childrens Hosp, Dept Dent, Boston, MA 02115 USA. RP McDermott, NE (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. FU NIDCR NIH HHS [K24 DE000448, K16 DE000275] NR 45 TC 58 Z9 64 U1 1 U2 5 PU QUINTESSENCE PUBL CO INC PI CAROL STREAM PA 551 NORTH KIMBERLY DR, CAROL STREAM, IL 60188-1881 USA SN 0882-2786 J9 INT J ORAL MAX IMPL JI Int. J. Oral Maxillofac. Implants PD NOV-DEC PY 2003 VL 18 IS 6 BP 848 EP 855 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 752LJ UT WOS:000187161800008 PM 14696660 ER PT J AU Coen, JJ Chung, CS Shipley, WU Zietman, AL AF Coen, JJ Chung, CS Shipley, WU Zietman, AL TI Influence of follow-up bias on PSA failure after external beam radiotherapy for localized prostate cancer: Results from a 10-year cohort analysis SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE PSA; prostate cancer; follow-up; bias ID BIOCHEMICAL FAILURE; RADIATION AB Purpose: To estimate the biases inherent in prostate cancer outcome that arise from different failure end points and variations in follow-up time and intensity using a cohort of men with long follow-up. Methods and Materials: The study cohort consisted of 205 men with T1-T2N0-Nx prostate cancer treated with conventional radiotherapy between 1991 and 1993. The median follow-up was 103 months. Outcome was assessed using different definitions of biochemical failure, including the American Society for Therapeutic Radiology and Oncology (ASTRO) consensus criteria and the "nadir plus two" criteria (any rise of 2 ng/mL greater than the current nadir). Patient subgroups were created according to where patients had received their last 2 years of follow-up. Patients were also stratified according to whether they were initially present in the departmental database (under regular surveillance) or were uncovered after more vigorous investigation (previously "lost to follow-up"). Results: In this series with maximized follow-up, the 10-year biochemical disease-free survival rate did not change significantly with varying definitions of failure, 49% and 45% for ASTRO and "nadir plus two" criteria, respectively. Patients followed by outside physicians (n = 99) were faring better at 10 years than those followed at the treating institution by either their radiation oncologist (n = 50) or their medical oncologist or urologist (n = 52). This was by all measures of outcome, including overall survival, and metastasis-free survival. Patients previously lost to follow-up (n = 43) who were tracked down also appeared to be doing better than those on our database for whom information had been readily available (n = 161). This, however, may have been an artifact of the ASTRO criteria, which underestimates failure when insufficient prostate-specific antigen values are available. Conclusion: The ASTRO definition of failure underestimates late failure. This bias may be compensated for by the use of cohorts with long follow-up or the use of the "nadir plus two" definition of failure. The use of institutional prostate cancer databases may overestimate failure rates because patients followed outside of the treating institution fared better with respect to both survival and biochemical recurrence. Vigorous attempts to obtain follow-up beyond the hospital walls may correct this bias. (C) 2003 Elsevier Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Coen, JJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. NR 10 TC 18 Z9 19 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 NOV 1 PY 2003 VL 57 IS 3 BP 621 EP 628 DI 10.1016/S0360-3016(03)00722-3 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 730GQ UT WOS:000185821200003 PM 14529765 ER PT J AU Hagan, MP Winter, KA Kaufman, DS Wajsman, Z Zietman, AL Heney, NM Toonkel, LM Jones, CU Roberts, JD Shipley, WU AF Hagan, MP Winter, KA Kaufman, DS Wajsman, Z Zietman, AL Heney, NM Toonkel, LM Jones, CU Roberts, JD Shipley, WU TI RTOG 97-06: Initial report of a phase I-II trial of selective bladder conservation using TURBT, twice-daily accelerated irradiation sensitized with cisplatin, and adjuvant MCV combination chemotherapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY NOV 04-08, 2001 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Therapeut Radiol & Oncol DE bladder conservation; radiotherapy; chemotherapy; bladder cancer ID TRANSITIONAL-CELL-CARCINOMA; COMBINED-MODALITY PROGRAM; RADIATION-THERAPY; TRANSURETHRAL SURGERY; CONCURRENT CISPLATIN; ORGAN PRESERVATION; RADICAL CYSTECTOMY; TUMOR-MARKERS; CANCER; RADIOTHERAPY AB Purpose: To examine combination cisplatin and twice-daily accelerated irradiation (RT) after aggressive transurethral resection of bladder tumor (TURBT) in an attempt to preserve the bladder and to determine the likelihood that patients who complete this regimen could then complete three cycles of methotrexate, cisplatin, vinblastine (MCV) chemotherapy. Methods and Materials: Between 1998 and 2000, 52 patients with Stage T2-T4aN0M0 disease, from 17 institutions, were entered into the trial. Forty-seven patients were deemed eligible; the planned accrual was 40. Of the 46 patients, 68% were >60 years old, 70% were men, and 96% had a Karnofsky score greater than or equal to90. The clinical T stage was T2 in 66%, T3a in 25%, and T3b in 9%. The median follow-up at the time of analysis was 26 months. The protocol required TURBT within 6 weeks of the initiation of induction therapy. Induction treatment involved 13 days of concomitant boost RT, 1.8 Gy to the pelvis in the morning followed by 1.6 Gy to the tumor 4-6 h later. For sensitization, cisplatin (20 mg/m(2)) was given on the first 3 days of each treatment week. Three to four weeks after induction, patients were evaluated cystoscopically for residual disease. Patients whose biopsies and cytologic evaluations showed no disease completed consolidation chemoirradiation. Patients with residual tumor went on to cystectomy. After either consolidation or cystectomy, patients were to complete three cycles of MCV chemotherapy. Results: Of the 47 patients, 45% completed all phases of the protocol treatment with minor, or no, deviations. Five patients refused either the postinduction evaluation or cystectomy and 6 refused adjuvant chemotherapy. The CR rate after induction therapy was 74%. For 2 patients, residual disease after induction was limited to positive cytologic findings, and for 8 patients, biopsy of the primary site revealed persistence. Of the 8 cystectomy patients, 2 had no evidence of disease in the bladder at pathologic review of the surgery specimen. Grade 3 toxicity related to chemotherapy was observed in 11% of patients during both induction and consolidation, and in 41% during adjuvant chemotherapy. A total of 8 patients (36% of those receiving adjuvant chemotherapy) went on to develop Grade 4 neutropenia or thrombocytopenia during additional adjuvant chemotherapy. Grade 3 toxicity due to RT was seen in 4% and 0% of patients during induction and consolidation., respectively. One patient developed Grade 4 hydronephrosis during consolidation. The projected 36-month value for locoregional failure, distant metastasis, overall survival, and bladder-intact survival was 27%, 29%.. 61%, and 48%, respectively. Conclusion: After aggressive TURBT, twice-daily accelerated RT initiated in concomitant-boost format is well tolerated and results in a rate of complete response (74%) similar to that in previous bladder-sparing trials. The projected 2-year values for locoregional control, bladder-intact survival, and overall survival were also consistent with previously reported trials of bladder-sparing treatment. With only 45% of patients completing three cycles of MCV, this form of adjuvant chemotherapy appears to be poorly tolerated by most patients. (C) 2003 Elsevier Inc. C1 Med Coll Virginia Hosp, Richmond, VA USA. Radiat Therapy Oncol Grp Headquarters, Philadelphia, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Florida, Gainesville, FL USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Radiol Associates Sacramento, Sacramento, CA USA. RP Hagan, MP (reprint author), Virginia Commonwealth Univ Med Coll Virginia, Dept Radiat Oncol, 401 Coll St, Richmond, VA 23298 USA. NR 26 TC 102 Z9 105 U1 0 U2 2 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 NOV 1 PY 2003 VL 57 IS 3 BP 665 EP 672 DI 10.1016/S0360-3016(03)00718-1 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 730GQ UT WOS:000185821200008 PM 14529770 ER PT J AU Roof, KS Fidias, P Lynch, TJ Ancukiewicz, M Choi, NC AF Roof, KS Fidias, P Lynch, TJ Ancukiewicz, M Choi, NC TI Radiation dose escalation in limited-stage small-cell lung cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 18-21, 2002 CL ORLANDO, FLORIDA SP Amer Soc Clin Oncol DE small-cell carcinoma; radiation dose escalation; dose intensification ID THORACIC RADIOTHERAPY; POSTOPERATIVE RADIOTHERAPY; RANDOMIZED TRIAL; BREAST-CANCER; PHASE-III; CHEMOTHERAPY; THERAPY; CARCINOMA; CONCURRENT; ETOPOSIDE AB Purpose: To review the treatment outcomes of limited-stage small-cell lung cancer (LS-SCLC) patients treated with greater than or equal to50 Gy of radiation at Massachusetts General Hospital (MGH) between 1987 and 2000 and to assess for evidence of a continuation of a radiation dose response. Methods and Materials: The NIGH cancer registry was searched for SCLC patients treated with radiotherapy between 1987 and 2000. Records of LS-SCLC patients treated with curative intent and radiation doses greater than or equal to50 Gy at NIGH were reviewed. Surgical patients were excluded. Results: Eighty-four LS-SCLC patients were treated with radiotherapy at NIGH between 1987 and 2000. Of the 84 patients, 54 (64%) met the inclusion criteria; 30 patients (56%) in this study died, and 4 (7%) were lost to follow-up. The median follow-up of the surviving patients was 42 months. The median overall survival was 29 months. The 2- and 5-year survival rate was 64% and 47%, respectively. The local control rate at 3 years was 78%. Conclusion: The overall survival, local control, and disease-free survival rates for LS-SCLC patients treated with greater than or equal to50 Gy of radiation compare favorably with historical data. These findings suggest a continuation of the radiation dose-response curve in LS-SCLC. This further supports the need for appropriately powered, Phase III, prospective randomized trials in radiation dose escalation or radiation dose intensification for LS-SCLC. (C) 2003 Elsevier Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med Oncol, Boston, MA USA. RP Roof, KS (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Cox 3, Boston, MA 02116 USA. NR 25 TC 35 Z9 38 U1 0 U2 4 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 NOV 1 PY 2003 VL 57 IS 3 BP 701 EP 708 DI 10.1016/S0360-3016(03)00715-6 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 730GQ UT WOS:000185821200012 PM 14529774 ER PT J AU Maiden, MFJ Cohee, P Tanner, ACR AF Maiden, MFJ Cohee, P Tanner, ACR TI Proposal to conserve the adjectival form of the specific epithet in the reclassification of Bacteroides forsythus Tanner et al. 1986 to the genus Tannerella Sakamoto et al. 2002 as Tannerella forsythia corrig., gen. nov., comb. nov. Request for an Opinion SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article AB With reference to the first Principle of the International Code of Nomenclature of Bacteria, which emphasizes stability of names, it is proposed that the original adjectival form of the specific epithet be conserved in the reclassification of Bacteroides forsythus to the new genus Tannerella. Thus, Tannerella forsythensis Sakamoto et al. 2002 should be Tannerella forsythia Sakamoto et al. 2002 corrig., gen. nov., comb. nov., and we put forward a Request for an Opinion to the Judicial Commission regarding this correction. C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Boston Latin Sch, Dept Class, Boston, MA 02115 USA. RP Maiden, MFJ (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. NR 4 TC 15 Z9 21 U1 1 U2 2 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 NOV PY 2003 VL 53 BP 2111 EP 2112 DI 10.1099/ijs.0.02641-0 PN 6 PG 2 WC Microbiology SC Microbiology GA 749KF UT WOS:000186918500059 PM 14657155 ER PT J AU Chen, F Ng, PS Faull, KF Lee, RH AF Chen, F Ng, PS Faull, KF Lee, RH TI Cone photoreceptor beta gamma-transducin: Posttranslational modification and interaction with phosducin SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID RETINAL ROD; CRYSTAL-STRUCTURE; PROTEIN-BINDING; ALPHA-SUBUNIT; CELLS; IDENTIFICATION; COMPLEX; ISOPRENYLATION/METHYLATION; PHOSPHODIESTERASE; PHOSPHORYLATION AB PURPOSE. To characterize the structure of cone betagamma-transducin (Tbeta3gamma8) and its interaction with phosducin (pdc). METHODS. The Tgamma8 subunit of Tbeta3gamma8 was isolated by column chromatography for peptide mapping with mass spectrometry. Tbeta3gamma8 was compared with rod betagamma-transducin (Tbeta1gamma1) in terms of the electrophoretic mobility, pdc binding affinity, and the effects of phosphorylation and methylation, and then the correlation to the crystal structures and functional domains of Tbeta1gamma1 was determined. RESULTS. The mature Tgamma8 is a 65-amino-acid peptide encoded by the Ggamma8 gene with an acetylated and a farnesylated-methylated N- and C-terminus, respectively. Purified Tbeta3gamma8 is similar to Tbeta1gamma1 in that (1) both are heterogeneous, containing methylated and demethylated Tgamma subunits; (2) each demethylated dimer migrates faster than its methylated counterpart during native gel electrophoresis, and the methylation-associated mobility differential is masked by pdc binding; and (3) both dimers bind pdc with the same affinity, and the affinity is reduced threefold by PKA phosphorylation of pdc and twofold by demethylation at the C-terminus of Tgamma. Tbeta3gamma8 differs from Tbeta1gamma1 in. exhibiting lower intrinsic electrophoretic mobility, and the difference is unaffected by either pdc binding or the status of Tgamma methylation. CONCLUSIONS. Tbeta3gamma8 is identical with Tbeta1gamma1 in Tgamma isoprenylation, the spatial organization, and the mode of pdc binding, indicating that its interaction with pdc does not play an important role in the specialization of cones. Changes in Tbetagamma characteristics by Tgamma methylation reveal conformational changes on a surface domain that is essential for Tbetagamma functions and support a regulatory role for reversible methylation. C1 VA Greater LA Healthcare Syst Sepulveda, Mol Neurol Lab, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Pasaraw Mass Spectormetry Lab, Dept Chem Biochem Psychiat & Behav Sci, Los Angeles, CA USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. RP Lee, RH (reprint author), VA Greater LA Healthcare Syst Sepulveda, Mol Neurol Lab, Mail Code 151B9,16111 Plummer St, Sepulveda, CA 91343 USA. EM rlee@ucla.edu FU NEI NIH HHS [EY09936] NR 41 TC 5 Z9 5 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2003 VL 44 IS 11 BP 4622 EP 4629 DI 10.1167/iovs.03-0420 PG 8 WC Ophthalmology SC Ophthalmology GA 737LL UT WOS:000186231800004 PM 14578377 ER PT J AU Neuzil, KM Coffey, CS Mitchel, EF Griffin, MR AF Neuzil, KM Coffey, CS Mitchel, EF Griffin, MR TI Cardiopulmonary hospitalizations during influenza season in adults and adolescents with advanced HIV infection SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE influenza; HIV infection; AIDS ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; VACCINATION; MORTALITY; MORBIDITY; VIRUS AB The etiologic role of influenza in hospitalizations and deaths among persons infected with HIV since the introduction of highly active antiretroviral therapy (HAART) is not known. A retrospective cohort study was performed of all persons aged 15 to 50 years with AIDS or advanced HIV infection enrolled in the Tennessee Medicaid program from 1995 through 1999, representing 7368 person-years of follow-up. The influenza season was defined based on local virus surveillance, and hospitalizations were measured for acute cardiopulmonary causes and deaths from any cause throughout the year. From 1995 through 1999, cardiopulmonary hospitalization rates in HIV-infected patients declined by 53% and death rates declined by 77%. The influenza-attributable hospitalization rate was 48 (95% confidence interval [CI]: 16-91) per 1000 persons in 1995 and 5 (95% CI: -0.5-11) per 1000 persons per year during 1996 through 1999, after the introduction of HAART. Influenza-associated hospitalizations have declined in patients with HIV infection in the post-HAART era. Rates remain comparable to rates in other high-risk groups for which annual influenza vaccination is recommended, however. C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. Vanderbilt Univ, Sch Med, Dept Prevent Med, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. Tennessee Valley Healthcare Syst, Ctr Geriatr Res Educ & Clin, Nashville, TN USA. RP Neuzil, KM (reprint author), 1660 S Columbian Way,Med Serv 111, Seattle, WA 98108 USA. FU ODCDC CDC HHS [UR6 CCU417579] NR 11 TC 50 Z9 50 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD NOV 1 PY 2003 VL 34 IS 3 BP 304 EP 307 DI 10.1097/00126334-200311010-00008 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 740YW UT WOS:000186431700008 PM 14600576 ER PT J AU Narr, KL Green, MF Capetillo-Cunliffe, L Toga, AW Zaidel, E AF Narr, KL Green, MF Capetillo-Cunliffe, L Toga, AW Zaidel, E TI Lateralized lexical decision in schizophrenia: Hemispheric specialization and interhemispheric lexicality priming SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID BILATERAL TRANSFER DEFICIT; ERROR-CORRECTING BEHAVIOR; CORPUS-CALLOSUM SIZE; THOUGHT-DISORDER; WORD PRONUNCIATION; DYSFUNCTION; ASYMMETRIES; PERFORMANCE; PEOPLE; GENDER AB Reports of left-hemisphere dysfunction and abnormal interhemispheric transfer in schizophrenia are mixed. The authors used a unified paradigm, the lateralized lexical decision task, to assess hemispheric specialization in word recognition, hemispheric error monitoring, and interhemispheric transfer in male, right-handed participants with schizophrenia (n = 34) compared with controls (n = 20). Overall, performance and error monitoring were worse in patients. However, patients like controls showed left-hemisphere superiority for lexical processing and right-hemisphere superiority for error monitoring. Only patients showed selective-interhemispheric lexicality priming for accuracy, in which performance improved when the lexical status of target and distractor stimuli presented to each hemifield was congruent. Results suggest that schizophrenia is associated with impaired monitoring and with increased interhemispheric automatic information transfer rather than with changed hemispheric specialization for language or error monitoring. C1 Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. RP Narr, KL (reprint author), Univ Calif Los Angeles, Dept Neurol, 710 Westwood Plaza,Room 4238, Los Angeles, CA 90095 USA. FU NIMH NIH HHS [MH-43292]; NINDS NIH HHS [NS-20187, NS38253]; NLM NIH HHS [LM/MH05639] NR 81 TC 9 Z9 10 U1 2 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD NOV PY 2003 VL 112 IS 4 BP 623 EP 632 DI 10.1037/0021-843X.112.4.623 PG 10 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 750QK UT WOS:000187008100008 PM 14674874 ER PT J AU Allen, TM Altfeld, M AF Allen, TM Altfeld, M TI HIV-1 superinfection SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE HIV-1; superinfection; recombination; cytotoxic T lymphocyte; viral evolution ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-LYMPHOCYTES; CROSS-CLADE; TYPE-1 INFECTION; DUAL INFECTION; CELL RECOGNITION; RHESUS-MONKEYS; WEST-AFRICA; SUBTYPE-B; RECOMBINATION AB During the past year, a number of reports have described HIV-1 superinfection in human subjects, defined as the reinfection of an individual with a second heterologous strain of HIV-1. These reports have challenged the assumption that HIV-1-specific immune responses generated during primary infection are protective against subsequent infection and have raised concern, not only with respect to HIV-1-positive individuals engaging in unsafe sex but also from the standpoint of developing effective vaccines. Herein we review the published reports of HIV-1 superinfection and highlight studies providing additional insight into the potential for HIV-1 superinfections to affect the global epidemic. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Bldg 149,13th St,5th Floor, Charlestown, MA 02129 USA. RI Allen, Todd/F-5473-2011 NR 75 TC 32 Z9 33 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 NOV PY 2003 VL 112 IS 5 BP 829 EP 835 DI 10.1067/mai.2003.1821 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 743BV UT WOS:000186553300002 PM 14610465 ER PT J AU Shearer, WT Rosenblatt, HM Gelman, RS Oymopito, R Plaeger, S Stiehm, ER Wara, DW Douglas, SD Luzuriaga, K McFarland, EJ Yogev, R Rathore, MH Levy, W Graham, BL Spector, SA AF Shearer, WT Rosenblatt, HM Gelman, RS Oymopito, R Plaeger, S Stiehm, ER Wara, DW Douglas, SD Luzuriaga, K McFarland, EJ Yogev, R Rathore, MH Levy, W Graham, BL Spector, SA TI Lymphocyte subsets in healthy children from birth through 18 years of age: The pediatric AIDS clinical trials group P1009 study SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE lymphocyte subsets; 3-colorflow cytometry; infants; children; adolescents; healthy control subjects ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED CHILDREN; PERIPHERAL-BLOOD; FLOW-CYTOMETRY; T-LYMPHOCYTES; UNINFECTED CHILDREN; REFERENCE VALUES; CELL MARKERS; WHOLE-BLOOD; SUBPOPULATIONS AB Background: Peripheral blood lymphocyte subsets need to be determined in a large, urban, minority-predominant cohort of healthy children to serve as suitable control subjects for the interpretation of the appearance of these cells in several disease conditions, notably pediatric HIV-1 infection. Objective: We sought to determine the distribution of lymphocyte subsets in healthy urban-dwelling infants, children, and adolescents in the United States. Methods: Lymphocyte subsets were determined by means of 3-color flow cytometry in a cross-sectional study of 807 HIV-unexposed children from birth through 18 years of age. Results: Cell-surface marker analysis demonstrated that age was an extremely important variable in 24 lymphocyte subset distributions measured as percentages or absolute counts-eg, the CD4 (helper) T cell, CD8 (cytotoxic) T cell, CD19 B cell, CD4CD45RACD62L (naive helper) T cell, CD3CD4CD45RO (memory helper) T cell, CD8HLA-DRCD38 (activated cytotoxic) T cell, and CD8CD28 (activation primed cytotoxic) T cell. The testing laboratory proved to be an important variable, indicating the need for using the same laboratory or group of laboratories to assay an individual's blood over time and to assay control and ill or treated populations. Sex and race-ethnicity were much less important. Conclusion: The results of this study provide a control population for assessment of the effects of HIV infection on the normal development and distribution of lymphocyte subsets in children of both sexes, all races, and all ethnic backgrounds from birth through 18 years of age in an urban population. This study's findings will also prove invaluable in interpreting the immune changes in children with many other chronic diseases, such as primary immunodeficiency, malignancy, rheumatoid arthritis, and asthma. C1 Baylor Coll Med, Houston, TX 77030 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NIAID, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Massachusetts, Worcester, MA 01003 USA. Univ Colorado, Ctr Hlth Sci, Denver, CO 80202 USA. Childrens Mem Hosp, Chicago, IL 60614 USA. Univ Florida, Ctr Hlth Sci, Jacksonville, FL USA. Univ Calif San Diego, San Diego, CA 92103 USA. RP Shearer, WT (reprint author), Texas Childrens Hosp, 6621 Fannin St,MC FC330-01, Houston, TX 77030 USA. FU NCRR NIH HHS [M01 RR-00188, M01 RR-00865, M01 RR-01271, M01 RR-02240]; NIAID NIH HHS [U01 AI32921, P30 AI36211, R01 AI94029, U01 AI27541, U01 AI27551, U01 AI27559, U01 AI27750, U01 AI32907, U01 AI41089, U01 AI41110]; NICHD NIH HHS [N01 HD33162] NR 55 TC 349 Z9 362 U1 2 U2 16 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 NOV PY 2003 VL 112 IS 5 BP 973 EP 980 DI 10.1067/mai.2003.1778 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 743BV UT WOS:000186553300022 PM 14610491 ER PT J AU Laouini, D Kawamoto, S Yalcindag, A Bryce, P Mizoguchi, E Oettgen, H Geha, RS AF Laouini, D Kawamoto, S Yalcindag, A Bryce, P Mizoguchi, E Oettgen, H Geha, RS TI Epicutaneous sensitization with superantigen induces allergic skin inflammation SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE atopic dermatitis; superantigens; skin inflammation; cytokines; staphylococcal enterotoxin B; in vivo animal models ID STAPHYLOCOCCAL-ENTEROTOXIN-B; T-CELL-RECEPTOR; ATOPIC-DERMATITIS; MURINE MODEL; IFN-GAMMA; EXPRESSION; MICE; HYPERRESPONSIVENESS; EOSINOPHILIA; STIMULATION AB Background: Atopic dermatitis (AD) is characterized by skin infiltration with eosinophils and lymphocytes and expression of Th-2 cytokines in acute skin lesions. The skin of patients with AD is frequently colonized with enterotoxin-secreting strains of Staphylococcus aureus. Staphylococcal enterotoxins have been implicated in the exacerbations of the inflammatory skin lesions in patients with AD. Objective: We sought to determine whether epicutaneous (EC) sensitization of mice with staphylococcal enterotoxin B (SEB) results in allergic skin inflammation. Methods: BALB/c mice were EC-sensitized with SEB. Their skin was examined for allergic inflammation and cytokine expression, and their splenocytes were examined for cylokine secretion in response to SEB. Results: EC sensitization with SEB elicited a local, cutaneous, inflammatory response characterized by dermal infiltration with eosinophils and mononuclear cells and increased mRNA expression of the Th-2 cytokine IL-4 but not of the Th-1 cytokine IFN-gamma. EC-sensitized mice mounted a systemic Th-2 response to SEB evidenced by elevated total and SEB-specific IgG1 and IgE. Although EC sensitization with SEB resulted in selective depletion of SEB-specific T-cell receptor Vbeta8+ cells from the spleen and sensitized skin, splenoeytes from SEB-sensitized mice secreted relatively more IL-4 and less IFN-gamma than did saline-sensitized controls, consistent with Th-2 skewing of the systemic immune response to the superantigen. Conclusion: These results suggest that EC exposure to super-antigens skews the immune response toward Th-2 cells, leading to allergic skin inflammation and increased IgE synthesis that are characteristic of AD. C1 Childrens Hosp, Div Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,Immunopathol Unit, Cambridge, MA 02138 USA. RP Geha, RS (reprint author), Childrens Hosp, Div Immunol, 300 Longwood Ave,Enders 8, Boston, MA 02115 USA. RI Kawamoto, Seiji/F-3423-2015 FU NIAMS NIH HHS [AR 47417] NR 30 TC 69 Z9 73 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 NOV PY 2003 VL 112 IS 5 BP 981 EP 987 DI 10.1067/mai.2003.1789 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 743BV UT WOS:000186553300023 PM 14610492 ER PT J AU Kelly, TLJ Li, E Trasler, JM AF Kelly, TLJ Li, E Trasler, JM TI 5-aza-2 '-deoxycytidine induces alterations in murine spermatogenesis and pregnancy outcome SO JOURNAL OF ANDROLOGY LA English DT Article DE DNA methylation; 5-azacytidine; DNMT; DNMT1; mouse; fertility; DNA methyltransferase 1 ID MALE GERM-CELLS; DNA METHYLTRANSFERASE; HISTONE DEACETYLASE; MOUSE EMBRYO; MYELODYSPLASTIC SYNDROME; SEMINIFEROUS EPITHELIUM; MAMMALIAN DEVELOPMENT; METHYLATION; GENE; 5-AZACYTIDINE AB Because of the ability of cytidine analogues, such as 5-aza-2'-deoxycytidine, to incorporate into DNA and lead to decreases in DNA methylation, there has recently been renewed interest in using these drugs in anticancer therapy. To determine the effects of paternal 5-aza-2'-deoxycytidine treatment on spermatogenesis and progeny outcome in the mouse and whether effects are modulated by decreased levels of the predominant DNA methyltransferase, DNMT1, adult Dnmt1(+/+) and Dnmtl-deficient (Dnmtl(c/+)) male mice were treated with 5-aza-2'-deoxycytidine for 7 weeks, which resulted in dose-dependent decreases in testicular weight, an increase in histological abnormalities, and a decline in sperm counts, with no apparent effect on androgen status. Testes of Dnmt1(c/+) mice, however, were less severely affected by 5-aza-2'-deoxycytidine than were those of wild-type mice. The exposure of Dnmt1(+/+) male mice to even low doses of 5-aza-2'-deoxycytidine followed by mating elicited significantly reduced pregnancy rates and elevated preimplantation loss in females. Dnmt1 deficiency, however, protected against such drug-induced decreases in pregnancy rate but not preimplantation loss. Altered DNA methylation or DNMT1 activity may explain such adverse effects, because treatment resulted in dose-dependent decreases in the global methylation of sperm DNA. Thus, in the mouse, paternal administration of 5-aza-2'-deoxycytidine interferes with normal male germ cell development and results in reduced fertility, whereas lowering DNMT1 levels appears to partially protect the seminiferous epithelium from deleterious drug effects. C1 McGill Univ, Ctr Hlth, Montreal Childrens Hosp, Res Inst, Montreal, PQ H3H 1P3, Canada. McGill Univ, Dept Pediat, Montreal, PQ H3A 2T5, Canada. McGill Univ, Dept Human Genet, Montreal, PQ H3A 2T5, Canada. McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H3A 2T5, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiovasc Res Ctr, Charlestown, MA USA. RP Trasler, JM (reprint author), McGill Univ, Ctr Hlth, Montreal Childrens Hosp, Res Inst, 2300 Tupper St, Montreal, PQ H3H 1P3, Canada. NR 41 TC 49 Z9 55 U1 0 U2 2 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD NOV-DEC PY 2003 VL 24 IS 6 BP 822 EP 830 PG 9 WC Andrology SC Endocrinology & Metabolism GA 740LJ UT WOS:000186403600011 PM 14581508 ER PT J AU Mairbaurl, H Schwobel, F Hoschele, S Maggiorini, M Gibbs, S Swenson, ER Bartsch, P AF Mairbaurl, H Schwobel, F Hoschele, S Maggiorini, M Gibbs, S Swenson, ER Bartsch, P TI Altered ion transporter expression in bronchial epithelium in mountaineers with high-altitude pulmonary edema SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE nasal potential; alveolar fluid clearance; airway Na-K-ATPase; epithelial Na channels ID BETA-ADRENERGIC AGONIST; POTENTIAL DIFFERENCE; FLUID TRANSPORT; SODIUM-CHANNEL; A549 CELLS; HYPOXIA; LUNG; NA,K-ATPASE AB Hypoxia inhibits activity and expression of transport proteins of cultured lung alveolar epithelial cells. Here we tested whether hypoxia at high altitude affected the expression of ion transport proteins in tissues obtained from controls and mountaineers with high-altitude pulmonary edema (HAPE) at the Capanna Margherita (4,559 m). Expression was determined by RT-PCR and Western blots from brush biopsies of bronchial epithelium and from leukocytes obtained before and during the stay at high altitude. At low altitude, amounts of mRNAs were not different between control and HAPE-susceptible subjects. At high altitude, the amount of mRNA of Na-K-ATPase, CFTR, and beta-actin of brush biopsies did not change in controls but decreased significantly (-60%) in HAPE-susceptible subjects. There was no change in Na channel mRNAs at high altitude in controls and HAPE. No statistically significant correlation was found between the expression of Na transporters and PO2 and O-2 saturation. In leukocytes, 28S-rRNA and Na-K-ATPase decreased at altitude in control and HAPE-susceptible subjects, but no significant change in Na-K-ATPase protein was found. Hypoxia-inducible factor-1alpha mRNA and GAPDH mRNA tended to increase in leukocytes obtained from HAPE-susceptible subjects at high altitude but did not change in controls. These results show that hypoxia induces differences in mRNA expression of ion transport-related proteins between HAPE-susceptible and control subjects but that these changes may not necessarily predict differences in protein concentration or activity. It is therefore unclear whether these differences are related to the pathophysiology of HAPE. C1 Univ Heidelberg, Dept Med, Div Sports Med, D-69115 Heidelberg, Germany. Univ Hosp, Dept Internal Med, Intens Care Unit, Zurich, Switzerland. Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Med & Res Serv, Seattle, WA 98195 USA. RP Mairbaurl, H (reprint author), Univ Heidelberg, Dept Med, Div Sports Med, Luisenstr 5,Geb 4100, D-69115 Heidelberg, Germany. NR 26 TC 21 Z9 21 U1 0 U2 3 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 NOV 01 PY 2003 VL 95 IS 5 BP 1843 EP 1850 DI 10.1152/japplphysiol.01156.2002 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 730VF UT WOS:000185850300012 PM 14555664 ER PT J AU Cassidy, C Jupiter, JB Cohen, M Delli-Santi, M Fennell, C Leinberry, C Husband, J Ladd, A Seitz, WR Constanz, B AF Cassidy, C Jupiter, JB Cohen, M Delli-Santi, M Fennell, C Leinberry, C Husband, J Ladd, A Seitz, WR Constanz, B TI Norian SRS cement compared with conventional fixation in distal radial fractures - A randomized study SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID COLLES FRACTURE; BONE-CEMENT; INTRAARTICULAR FRACTURES; CALCIUM-PHOSPHATE; INTERNAL-FIXATION; CLOSED TREATMENT; YOUNG-ADULTS; END; STABILIZATION; COMPLICATIONS AB Background: A prospective, randomized multicenter study was conducted to evaluate closed reduction and immobilization with and without Norian SRS (Skeletal Repair System) cement in the management of distal radial fractures. Norian SRS is a calcium-phosphate bone cement that is injectable, hardens in situ, and cures by a crystallization reaction to form dahllite, a carbonated apatite equivalent to bone mineral. Methods: A total of 323 patients with a distal radial fracture were randomized to treatment with or without Norian SRS cement. Stratification factors included fracture type (intra-articular or extra-articular), hand dominance, bone density, and the surgeon's preferred conventional treatment (cast or external fixator). The subjects receiving Norian SRS underwent a closed reduction followed by injection of the cement percutaneously or through a limited open approach. Wrist motion, beginning two weeks postoperatively, was encouraged. Control subjects, who had not received a Norian SRS injection, underwent closed reduction and application of a cast or external fixator for six to eight weeks. Supplemental Kirschner wires were used in specific instances in both groups. Patients were followed clinically and radiographically at one, two, four, and between six and eight weeks and at three, six, and twelve months. Patients rated pain and the function of the hand with use of a visual analog scale. Quality of life was assessed with use of the Short Form-36 (SF-36) health status questionnaire. Complications were recorded. Results: Significant clinical differences were seen at six to eight weeks postoperatively, with better grip strength, wrist range of motion, digital motion, use of the hand, and social and emotional function, and less swelling in the patients treated with Norian SRS than in the control group (p < 0.05). By three months, these differences had normalized except for digital motion, which remained significantly better in the group treated with Norian SRS (p = 0.015). At one year, no clinical differences were detected. Radiographically, the average change in uInar variance was greater in the patients treated with Norian SRS (+2.0 mm) than in the control group (+1.4 mm) (p < 0.02). No differences were seen in the total number of complications, including loss of reduction. The infection rate, however, was significantly higher (p < 0.001) in the control group (16.7%) than in the group treated with Norian SRS (2.5%) and the infections were always related to external fixator pins or Kirschner wires. Four patients with intra-articular extravasation of cement were identified; no sequelae were observed at twenty-four months. Cement was seen in extraosseous locations in 112 (70%) of the SRS-treated patients; loss of reduction was highest in this subgroup (37%). The extraosseous material had disappeared in eighty-three of the 112 patients by twelve months. Conclusions: Our results indicate that fixation of a distal radial fracture with Norian SRS cement may allow for accelerated rehabilitation. A limited open approach and supplemental fixation with Kirschner wires are recommended. Additional or alternate fixation is necessary for complex articular fractures. Level of Evidence: Therapeutic study, Level I-1a (randomized controlled trial [significant difference]). See Instructions to Authors for a complete description of levels of evidence. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Midw Orthopaed, Chicago, IL 60612 USA. Riverview Orthoped Clin, Crookston, MN 56716 USA. Philadelphia Hand Ctr, Bryn Mawr, PA 19010 USA. Pk Nicollet Clin, St Louis Pk, MN 55426 USA. Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA. Cleveland Orthopaed & Spine Hosp Lutheran, Cleveland, OH 44113 USA. Corazon, Menlo Pk, CA 94025 USA. RP Cassidy, C (reprint author), 750 Washington St,Box 26, Boston, MA 02111 USA. NR 59 TC 101 Z9 106 U1 1 U2 7 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD NOV PY 2003 VL 85A IS 11 BP 2127 EP 2137 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 740VX UT WOS:000186423600010 PM 14630841 ER PT J AU Tingart, MJ Apreleva, M Zurakowski, D Warner, JP AF Tingart, MJ Apreleva, M Zurakowski, D Warner, JP TI Pullout strength of suture anchors used in rotator cuff repair SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID MECHANICAL STRENGTH; FIXATION; TEARS; FRACTURES; HUMERUS AB Background: Surgical treatment of rotator cuff tears may be complicated by osteoporosis of the proximal part of the humerus. The purpose of this study was to determine whether pullout strength of suture anchors is affected by the location of the anchor placement and by bone mineral density. We hypothesized that higher bone mineral density is associated with higher pullout strength of suture anchors. Methods: Peripheral quantitative computed tomography was used to measure total, trabecular, and cortical bone mineral density in different regions of the lesser and greater tuberosities in seventeen cadaveric humeri. Suture anchors were inserted into individual regions and subjected to cyclic loading. Repeated-measures analysis of variance was used to assess differences in bone mineral density and load to failure between regions of interest. Pearson correlation was used to determine the association between bone mineral density and pullout strength of suture anchors. Results: Total, trabecular, and cortical bone mineral densities were an average of 50%, 50%, and 10% higher, respectively, in the proximal part of the tuberosities compared with the distal part (p < 0.01). Within the proximal part of the greater tuberosity, trabecular bone mineral density of the posterior region and cortical bone mineral density of the middle region were, on the average, 25% and 16% higher, respectively, than the densities in the other regions (p < 0.01). Load to failure in the proximal part of the tuberosities was an average of 53% higher than that in the distal part (p < 0.01). The lesser tuberosity showed, on the average, a 32% higher load to failure than did the greater tuberosity (p < 0.01). Within the proximal part of the greater tuberosity, loads to failure in the anterior and middle regions were, on the average, 62% higher than the load to failure in the posterior region (p less than or equal to 0.01). Overall positive correlations were found between bone mineral density and load to failure (0.65 less than or equal to r less than or equal to 0.74, p < 0.01). Conclusions: We found that pullout strength of suture anchors correlates well with bone mineral density of the tuberosities. Higher loads to failure were found in regions in the proximal part of the tuberosities. Placement of anchors in these regions may prevent anchor loosening, formation of a tendon-bone gap, and failure of the rotator cuff repair. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med,Massachusetts Gen Hosp, Orthopaed Biomech Lab, Boston, MA 02215 USA. Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. Childrens Hosp, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Tingart, MJ (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Orthopaed Biomech Lab, 330 Brookline Ave,RN 115, Boston, MA 02215 USA. NR 31 TC 72 Z9 74 U1 1 U2 3 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD NOV PY 2003 VL 85A IS 11 BP 2190 EP 2198 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 740VX UT WOS:000186423600021 PM 14630852 ER PT J AU Sheridan, RL Keaney, T Stoddard, F Enfanto, R Kadillack, P Breault, L AF Sheridan, RL Keaney, T Stoddard, F Enfanto, R Kadillack, P Breault, L TI Short-term propofol infusion as an adjunct to extubation in burned children SO JOURNAL OF BURN CARE & REHABILITATION LA English DT Article ID PEDIATRIC INTENSIVE-CARE; CRITICALLY-ILL PATIENTS; METABOLIC-ACIDOSIS; SEDATION; MIDAZOLAM; UNIT; PATIENT; CONTAMINATION; TOLERANCE; TRIAL AB Children who require intubation as a component of their burn management generally need heavy sedation, usually with a combination of opiate and benzodiazepine infusions with a target sensorium of fight sleep. When extubation approaches, the need for sedation to prevent uncontrolled extubation can conflict with the desire to lighten sedation enough to ensure that airway protective reflexes are strong. The several hours' half-life of these medications can make this period of weaning challenging. Therefore, the hours preceding extubation are among the most difficult in which to ensure safe adequate sedation. The pharmacokinetics of propofol allow for the rapid emergence of a patient from deep sedation. We have had success with an extubation strategy using short-term propofol infusions in critically ill children. In this work, children were maintained on morphine and midazolam infusions per our unit protocol, escalating doses as required to maintain comfort. Approximately 8 hours before planned extubation, these infusions were decreased by approximately half and propofol infusion added to maintain a state of fight sleep. Extubation was planned approximately 8 hours later to allow ample time for the chronically infused opiates and benzodiazepines to be metabolized down to the new steady-state level. Thirty minutes before planned extubation, propofol was stopped while morphine and midazolam infusions were maintained at the reduced level. When the children awakened from the propofol-induced state of fight sleep, they were extubated while the reduced infusions of morphine and midazolam were maintained. These were subsequently weaned slowly, depending on the child's need for ongoing pain and anxiety medication, per our unit protocol to minimize the incidence of withdrawal symptoms. Data are shown in the text as mean standard deviation. These 11 children (eight boys and three girls) had an average age of 6.6 +/- 5.6 years (range, 1.2-13 years), average weight of 36.9 +/- 28.7 kg (range, 9.3-95 kg), and burn size of 43 +/- 21.4% (range, 10-85%). Three children had sustained scald burns and eight had flame injuries with associated inhalation injury. They had been intubated for an average of 12.7 +/- 10.9 (range, 2-33 days). Morphine infusions immediately before the initiation of propofol averaged 0.26 +/- 0.31 mg/kg/hour (range, 0.04-1.29 mg/kg/hr) and midazolam averaged 0.15 +/- 0.16 mg/kg/hr (range, 0.06-0.65 mg/kg/hr). Morphine infusions after beginning propofol and at extubation averaged 0.16 0.16 (range, 0.04-0.65 mg/kg/hr) and midazolam averaged 0.09 +/- 0.08 mg/kg/hr (range, 0.02-0.32 mg/kg/hr). Propofol doses after initial titration during the first hour of infusion averaged 3.6 +/- 2.9 mg/kg/hr (range, 0.4-8.1 mg/kg/hr). Nine of the 11 children (82%) were successfully extubated on the first attempt. Two required reintubation for postextubation stridor 2 to 6 hours after extubation but were successfully extubated the next day after a short course of steroids, again using the same propofol technique. All were awake at extubation and went on to survive. Morphine and midazolam infusions were gradually weaned, and there were no withdrawal symptoms noted. Although prolonged (days) infusions of propofol have been associated with adverse cardiovascular complications in critically ill young children and should probably be avoided, short-term (in hours) use of the drug can facilitate smooth extubation. C1 Shriners Burns Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Div Burns & Trauma, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Sheridan, RL (reprint author), Shriners Burns Hosp, 51 Blossom St, Boston, MA 02114 USA. NR 42 TC 16 Z9 17 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0273-8481 J9 J BURN CARE REHABIL JI J. Burn Care Rehabil. PD NOV-DEC PY 2003 VL 24 IS 6 BP 356 EP 360 DI 10.1097/01.BCR.0000095505.56021.27 PG 5 WC Emergency Medicine; Rehabilitation; Surgery SC Emergency Medicine; Rehabilitation; Surgery GA 745JH UT WOS:000186685200002 PM 14610418 ER PT J AU Sheridan, RL Wilson, NC O'Connell, MF Fabri, JA AF Sheridan, RL Wilson, NC O'Connell, MF Fabri, JA TI Noncontact electrosurgical grounding is useful in burn surgery SO JOURNAL OF BURN CARE & REHABILITATION LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the American-Burn-Association CY APR 24-27, 2002 CL CHICAGO, ILLINOIS SP Amer Burn Assoc AB Grounding patients with large burns to facilitate the use of electrocautery devices during surgery is commonly difficult because of the paucity of available grounding sites. The Mega 2000 Patient Return Electrode System (Megadyne Medical Products, Draper, UT) is an electrode designed to provide electrical return to facilitate function of electrocautery devices without direct patient contact. It accomplishes this by having a very large surface area (720 square inches) in the form of a reusable pad placed on the operating table that is covered by an impermeable drape and clean sheet beneath the patient. We used this noncontact device in 25 operations of 17 children with large burns and limited availability of traditional grounding sites. The patients had an average age of 8.8 +/- 4.6 years (range, 14 months-14 years), average burn size of 55 +/- 33% of the body surface (range, 10-95%), and average weight of 33.0 +/- 17.9 kg (range, 9-75 kg). Operations included 22 excision and grafting operations, an axillary release, a neck release, and bilateral groin releases. The device functioned well in all cases. There were no cutaneous burns observed. No additional traditional devices required placement. We found the device useful in burn surgery in those cases where there is a paucity of traditional grounding sites available. C1 Shriners Burns Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Div Burns & Trauma, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Sheridan, RL (reprint author), Shriners Burns Hosp, 51 Blossom St, Boston, MA 02114 USA. NR 1 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0273-8481 J9 J BURN CARE REHABIL JI J. Burn Care Rehabil. PD NOV-DEC PY 2003 VL 24 IS 6 BP 400 EP 401 DI 10.1097/01.BCR.0000095514.65067.15 PG 2 WC Emergency Medicine; Rehabilitation; Surgery SC Emergency Medicine; Rehabilitation; Surgery GA 745JH UT WOS:000186685200011 PM 14610427 ER PT J AU Torchiana, DF AF Torchiana, DF TI Symposium on tissue sealants - Introduction SO JOURNAL OF CARDIAC SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Torchiana, DF (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 0886-0440 J9 J CARDIAC SURG JI J. Card. Surg. PD NOV-DEC PY 2003 VL 18 IS 6 BP 479 EP 479 DI 10.1046/j.0886-0440.2003.00301.x PG 1 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 748BP UT WOS:000186842200001 ER PT J AU MacGillivray, TE AF MacGillivray, TE TI Fibrin sealants and glues SO JOURNAL OF CARDIAC SURGERY LA English DT Article ID CARDIAC OPERATIONS; CARDIOVASCULAR OPERATIONS; SPRAY APPLICATION; SURGERY; BLOOD; EXPERIENCE; ANTIBODIES; REDUCTION; THROMBIN; DEFECTS AB Fibrin sealants and fibrin glues have become effective instruments in the care of surgical patients. They have been used as an adjunct to hemostasis, wound healing, tissue adhesion, and drug delivery. In cardiac surgery, fibrin glues have emerged as valuable tools to improve hemostasis, decreased blood transfusions, improve tissue handling, and pretreat vascular grafts. Fibrin glues and sealants are now available commercially in the United States. This article will review the history, pharmacology, uses, and toxicity of fibrin sealants and fibrin glues. C1 Massachusetts Gen Hosp, Cardiac Surg Unit EDR121, Boston, MA 02114 USA. RP MacGillivray, TE (reprint author), Massachusetts Gen Hosp, Cardiac Surg Unit EDR121, 55 Fruit St, Boston, MA 02114 USA. NR 31 TC 55 Z9 58 U1 0 U2 4 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 0886-0440 J9 J CARDIAC SURG JI J. Card. Surg. PD NOV-DEC PY 2003 VL 18 IS 6 BP 480 EP 485 DI 10.1046/j.0886-0440.2003.02073.x PG 6 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 748BP UT WOS:000186842200002 PM 14992096 ER PT J AU Bennett, SL Melanson, DA Torchiana, DF Wiseman, DM Sawhney, AS AF Bennett, SL Melanson, DA Torchiana, DF Wiseman, DM Sawhney, AS TI Next-generation HydroGel films as tissue sealants and adhesion barriers SO JOURNAL OF CARDIAC SURGERY LA English DT Article ID PERICARDIAL ADHESIONS; MORBIDITY; MORTALITY; SURGERY AB Background. The development of conveniently sprayed, tissue-adherent, inert hydrogel films has made possible the creation of novel products that can serve a dual function, as a surgical sealant to achieve immediate hemostasis, and as a barrier to prevent adhesion formation over time. Methods: A sprayable, in situ formed absorbable hydrogel film was evaluated as a tissue sealant in a heparinized canine carotid artery graft model. PTFE grafts with leaking end-to-side anastomoses were treated with the synthetic sealant, and hemostasis was evaluated upon restoration of blood flow. Also, the hydrogel films were evaluated as an adhesion barrier in a rabbit pericardial abrasion model. Results: The sprayable, in situ forming hydrogel film was shown to immediately seal carotid-PTFE anastomoses in six of six applications. Hydrogel application in a rabbit pericardial abrasion model resulted in a statistically significant reduction in the number and tenacity of adhesions. Conclusions: This novel in situ formed sprayable hydrogel film has demonstrated a dual function as an effective tissue sealant and as an adhesion barrier in cardiovascular preclinical models. These next generation synthetic biomaterials are currently undergoing clinical investigations. C1 Confluent Surg Inc, Waltham, MA 02451 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Sawhney, AS (reprint author), Confluent Surg Inc, 101 A 1st Ave, Waltham, MA 02451 USA. NR 12 TC 38 Z9 38 U1 2 U2 14 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 0886-0440 J9 J CARDIAC SURG JI J. Card. Surg. PD NOV-DEC PY 2003 VL 18 IS 6 BP 494 EP 499 DI 10.1046/j.0886-0440.2003.00303.x PG 6 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 748BP UT WOS:000186842200004 PM 14992098 ER PT J AU Chao, HH Torchiana, DF AF Chao, HH Torchiana, DF TI BioGlue: Alburnin/glutaraldehyde sealant in cardiac surgery SO JOURNAL OF CARDIAC SURGERY LA English DT Article ID RESORCINOL-FORMALIN GLUE AB BioGlue is a commercially available sealant manufactured by Cryolife (Atlanta, GA) as a hemostatic adjunct for cardiac and vascular surgery. This type of sealant has evolved conceptually from the gelatin resorcinol formalin glue (GRF or "French Glue") in the sense that it is devised not only to act a sealant but also as an agent to strengthen friable tissues, particularly in acute aortic dissection. In fact, the initial availability of BioGlue in the United States was under an FDA humanitarian device exemption for use in acute aortic dissection. This novel regulatory strategy expedited clinical use of BioGlue in acute aortic dissection and was permissible because of the small number of patients (less than 4000 per annum) in the potential treatment population. In this article, we will discuss the mechanism of action and composition of this agent, preclinical experience, the results of a prospective randomized trial as well as the results of our initial experience with BioGlue at MGH. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Torchiana, DF (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 11 TC 63 Z9 65 U1 1 U2 5 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 0886-0440 J9 J CARDIAC SURG JI J. Card. Surg. PD NOV-DEC PY 2003 VL 18 IS 6 BP 500 EP 503 DI 10.1046/j.0886-0440.2003.00304.x PG 4 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 748BP UT WOS:000186842200005 PM 14992099 ER PT J AU Torchiana, DF AF Torchiana, DF TI Polyethylene glycol based synthetic sealants: Potential uses in cardiac surgery SO JOURNAL OF CARDIAC SURGERY LA English DT Article ID TISSUE SEALANT; AIR LEAKS; HYDROGEL AB Focalseal is a polyethylene glycol based synthetic hydrogel. It is FDA approved as a sealant to limit airleak following pulmonary resection. In preclinical use, this type of sealant has also been shown to be effective as a hemostatic adjunct to prevent anastomotic bleeding and to seal other types of closure such as the dura, pancreatic stump, or open wounds.(1-4) The sealant has two components, a primer and a sealant, and is applied in two steps and then polymerized by the application of a blue-green light (Fig. 1)(Genzyme Biosurgery, Inc. Cambridge, MA). The sealant does not bond covalently to tissue and is degraded by hydrolysis. This kind of sealant is flexible and nontoxic and has many intriguing possible applications as well as some mechanical properties that are essential to understand for safe use. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Torchiana, DF (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. NR 9 TC 25 Z9 26 U1 2 U2 11 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 0886-0440 J9 J CARDIAC SURG JI J. Card. Surg. PD NOV-DEC PY 2003 VL 18 IS 6 BP 504 EP 506 DI 10.1046/j.0886-0440.2003.00305.x PG 3 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 748BP UT WOS:000186842200006 PM 14992100 ER PT J AU Perez, VL Colby, KA Azar, DT AF Perez, VL Colby, KA Azar, DT TI Epithelial ingrowth in the flap-graft interface after microkeratome-assisted posterior penetrating keratoplasty SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID LAMELLAR ENDOTHELIAL KERATOPLASTY; SURGICAL TECHNIQUE AB A 79-year-old woman with pseudophakic bullous keratopathy had microkeratome-assisted posterior keratoplasty for the treatment of clinically significant corneal edema. An island of epithelial ingrowth was noted in the flap-graft interface that was not communicating with the flap periphery. Partial lifting of the anterior corneal flap and removal and irrigation of the epithelial cells were successfully performed. A review of reports of microkeratome-assisted posterior penetrating keratoplasty shows epithelial ingrowth is common after this procedure. The presence of posterior sutures, a central location of the epithelial cells, communication with the periphery, and evidence of stromal melting should prompt immediate surgical intervention. (C) 2003 ASCRS and ESCRS. C1 Harvard Univ, Massachusetts Eye & Ear Infirm,Sch Med, Corneal & Refract Surg Serv, Dept Ophthalmol, Boston, MA 02114 USA. RP Azar, DT (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm,Sch Med, Corneal & Refract Surg Serv, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 12 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 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD NOV PY 2003 VL 29 IS 11 BP 2225 EP 2228 DI 10.1016/j.jcrs.2002.10.002 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 753CY UT WOS:000187215400038 PM 14670436 ER PT J AU Devroe, E Engelman, A Silver, PA AF Devroe, E Engelman, A Silver, PA TI Intracellular transport of human immunodeficiency virus type 1 integrase SO JOURNAL OF CELL SCIENCE LA English DT Article DE HIV-1; integrase; nuclear transport; preintegration complex ID DNA-BINDING DOMAIN; TARGET SITE SELECTION; PHOTO-CROSS-LINKING; HIV-1 INTEGRASE; NUCLEAR IMPORT; HUMAN-CELLS; PREINTEGRATION COMPLEXES; RETROVIRAL INTEGRASE; PROVIRAL DNA; PROTEIN AB The human immunodeficiency virus type 1 integrase protein has karyophilic properties; that is, it localizes to the cell nucleus according to a range of assays. As an essential component of the preintegration complex, it has been suggested that the karyophilic properties of integrase might facilitate transport of the preintegration complex through the nuclear pore complexes of nondividing cells. However, no experiments have satisfactorily identified a nuclear localization signal within integrase. In this work, we investigated the karyophilic properties of integrase in intact cells with hopes of identifying a genuine transferable nuclear localization signal. Our results confirm that integrase tightly binds chromosomal DNA in vivo. However, our analysis determined that large integrase fusion proteins are unable to access the nucleus, indicating that integrase might lack a transferable nuclear localization signal. In addition, we present several lines of evidence to indicate that DNA binding might facilitate integrase nuclear accumulation. Furthermore, our data indicate integrase is degraded in the cytoplasm by a proteasome-dependent process, an event that probably contributes to the apparent nuclear accumulation of integrase. These results provide new insight into human immunodeficiency virus type 1 integrase intracellular dynamics. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Silver, PA (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. FU NIAID NIH HHS [AI39394, AI52014] NR 33 TC 42 Z9 43 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 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD NOV 1 PY 2003 VL 116 IS 21 BP 4401 EP 4408 DI 10.1242/jcs.00747 PG 8 WC Cell Biology SC Cell Biology GA 755GN UT WOS:000187395300013 PM 13130095 ER PT J AU Lan, J Li, WJ Zhang, F Sun, FY Nagayama, T O'Horo, C Chen, J AF Lan, J Li, WJ Zhang, F Sun, FY Nagayama, T O'Horo, C Chen, J TI Inducible repair of oxidative DNA lesions in the rat brain after transient focal ischemia and reperfusion SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE DNA damage; base excision repair; 8-hydroxyl-2 '; deoxyguanosine-; AP site; stroke ID BASE-EXCISION-REPAIR; COLI ENDONUCLEASE-III; POLYMERASE-BETA; CEREBRAL-ISCHEMIA; ABASIC SITES; MAMMALIAN-CELLS; APURINIC/APYRIMIDINIC ENDONUCLEASE; STRAND BREAKS; POLY(ADP-RIBOSE) POLYMERASE; INDUCED CYTOTOXICITY AB To determine the role of oxidative DNA damage and repair in brain injury after focal ischemia and reperfusion, the authors investigated DNA base damage and DNA base excision repair (BER) capacity, the predominant repair mechanism for oxidative DNA lesions, in the rat model of temporary middle cerebral artery occlusion. Contents of 8-hydroxyl-2'-deoxyguanosine (8-oxodG) and apurinic/apyrimidinic abasic site (AP site), hallmarks of oxidative DNA damage, were quantitatively measured in nuclear DNA extracts from brains 0.25 to 72 hours after I hour of middle cerebral artery occlusion. In parallel to the detection of DNA lesions, the capacity for 8-oxodG- or AP site-dependent DNA repair synthesis was measured in nuclear protein extracts using specific in vitro DNA repair assays. After postischemic reperfusion, the levels of 8-oxodG and AP sites were markedly increased in ischemic tissues. In frontal/parietal cortex, regions that survived ischemia, 8-oxodG and AP sites were efficiently repaired during reperfusion. However, in the caudate, a region that was destined to infarct, the DNA lesions were poorly repaired. In consistent with the patterns of endogenous lesion repair, a markedly induced and long-lasting (at least 72 hours) BER activity was detected in the cortex but not in the caudate after ischemia. The induced BER activity in ischemic cortex was attributed to the upregulation of gene expression and activation of selective BER enzymes, particularly DNA polymerase-beta and OGG1. These results strongly suggest that inducible DNA BER constitutes an important endogenous mechanism that protects brain against ischemia-induced oxidative neuronal injury. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Pittsburgh Inst Neurodegenerat Disorders, Pittsburgh, PA USA. Fudan Univ, Sch Med, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, S-507,Biomed Sci Tower, Pittsburgh, PA 15213 USA. FU NINDS NIH HHS [NS35965, NS36736, NS38560] NR 71 TC 41 Z9 42 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD NOV PY 2003 VL 23 IS 11 BP 1324 EP 1339 DI 10.1097/01.WCB.0000091540.60196.F2 PG 16 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 741TY UT WOS:000186477500009 PM 14600440 ER PT J AU Zhang, X Zhou, YL Mehta, KR Danila, DC Scolavino, S Johnson, SR Klibanski, A AF Zhang, X Zhou, YL Mehta, KR Danila, DC Scolavino, S Johnson, SR Klibanski, A TI A pituitary-derived MEG3 isoform functions as a growth suppressor in tumor cells SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID TRANSFORMING GENE PTTG; MENINGIOMA PROGRESSION; IMPRINTED GENES; CHROMOSOME 14Q; HUMAN HOMOLOG; DELTA-LIKE; ADENOMAS; EXPRESSION; GTL2; DIFFERENTIATION AB Human pituitary adenomas are the most common intracranial neoplasm. Typically monoclonal in origin, a somatic mutation is a prerequisite event in tumor development. To identify underlying pathogenetic mechanisms in tumor formation, we compared the difference in gene expression between normal human pituitary tissue and clinically nonfunctioning pituitary adenomas by cDNA-representational difference analysis. We cloned a cDNA, the expression of which was absent in these tumors, that represents a novel transcript from the previously described MEG3, a maternal imprinting gene with unknown function. It was expressed in normal human gonadotrophs, from which clinically nonfunctioning pituitary adenomas are derived. Additional investigation by Northern blot and RT-PCR demonstrated that this gene was also not expressed in functioning pituitary tumors as well as many human cancer cell lines. Moreover, ectopic expression of this gene inhibits growth in human cancer cells including HeLa, MCF-7, and H4. Genomic analysis revealed that MEG3 is located on chromosome 14q32.3, a site that has been predicted to contain a tumor suppressor gene involved in the pathogenesis of meningiomas. Taken together, our data suggest that MEG3 may represent a novel growth suppressor, which may play an important role in the development of human pituitary adenomas. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, 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] NR 41 TC 159 Z9 183 U1 2 U2 21 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 NOV 1 PY 2003 VL 88 IS 11 BP 5119 EP 5126 DI 10.1210/jc.2003-030222 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 740GD UT WOS:000186393900010 PM 14602737 ER PT J AU Poulaki, V Mitsiades, CS McMullan, C Sykoutri, D Fanourakis, G Kotoula, V Tseleni-Balafouta, S Koutras, DA Mitsiades, N AF Poulaki, V Mitsiades, CS McMullan, C Sykoutri, D Fanourakis, G Kotoula, V Tseleni-Balafouta, S Koutras, DA Mitsiades, N TI Regulation of vascular endothelial growth factor expression by insulin-like growth factor I in thyroid carcinomas SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID MULTIPLE-MYELOMA CELLS; BREAST-CANCER CELLS; THERAPEUTIC IMPLICATIONS; UP-REGULATION; KAPPA-B; ANGIOGENESIS; HYPOXIA; VIVO; ACTIVATION; TUMORS AB Vascular endothelial growth factor (VEGF) produced by tumor cells potently stimulates endothelial cell proliferation and angiogenesis and plays a key role in the pathophysiology of several neoplasias. Hypoxia activates the VEGF promoter via response elements that bind the transcription factors hypoxia-inducible factor-1alpha (HIF-1alpha) and activator protein-1 (AP-1). Yet, the paracrine signaling pathways regulating VEGF production and angiogenesis in thyroid cancer have not been fully elucidated. In this study, we, therefore, investigated the regulation of VEGF production by the thyroid carcinoma cell line SW579. We found that IGF-I up-regulated VEGF mRNA expression and protein secretion. Furthermore, transfection of SW579 cells with vector expressing a constitutively active form of Akt, a major mediator of IGF-I signaling, also stimulated VEGF expression. The IGF-I-induced up-regulation of VEGF production was associated with activation of AP-1 and HIF-1alpha and was abrogated by phosphatidylinositol 3-kinase inhibitors (wortmannin and LY294002); Jun kinase inhibitor (SP600125); HIF-1alpha antisense oligonucleotide; or geldanamycin, an inhibitor of the heat shock protein 90 molecular chaperone, which regulates the three-dimensional conformation and function of IGF-I-receptor and Akt. These data indicate that IGF-I stimulates VEGF synthesis in thyroid carcinomas in an Akt-dependent pathway via AP-1 and HIF-1alpha and provide the framework for clinical use of small-molecule inhibitors, including geldanamycin analogs, to abrogate proangiogenic cascades in thyroid cancer. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Angiogenesis Lab, Boston, MA 02114 USA. Aristotle Univ Thessaloniki, Sch Med, Dept Pathol, Thessaloniki 54621, Greece. Evgenid Hosp, Endocrine Unit, Athens 11527, Greece. RP Mitsiades, CS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Mayer Bldg,M555, Boston, MA 02115 USA. EM mitsiades@netscape.net NR 36 TC 72 Z9 78 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV 1 PY 2003 VL 88 IS 11 BP 5392 EP 5398 DI 10.1210/jc.2003-030389 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 740GD UT WOS:000186393900052 PM 14602779 ER PT J AU Katznelson, L Fairfield, WP Zeizafoun, N Sands, BE Peppercorn, MA Rosenthal, DI Klibanski, A AF Katznelson, L Fairfield, WP Zeizafoun, N Sands, BE Peppercorn, MA Rosenthal, DI Klibanski, A TI Effects of growth hormone secretion on body composition in patients with Crohn's disease SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; ADIPOSE-TISSUE; OBESE MEN; FAT; METABOLISM; CHILDREN AB Crohn's disease is a multisystem disorder characterized by chronic intestinal inflammation. Accumulation of mesenteric fat occurs in patients with Crohn's disease, although the mechanisms underlying site-specific changes in adipose deposition are unclear. To investigate whether there are alterations in site-specific adipose deposition in patients with Crohn's disease and to determine hormonal influences that mayunderlie such changes, weinvestigated body composition and serum hormone levels in 20 men with Crohn's disease ( mean age, 45 +/- 2 yr) and 20 age-, gender-, and body mass index-matched normal controls ( mean age, 43 +/- 3 yr). None of the Crohn's patients was receiving glucocorticoid therapy. Subjects underwent hourly GH sampling for 12 h beginning at 2000 h and fasting serum IGF-I and testosterone measurements. Body composition was assessed by quantitative computed tomography of the abdomen and bioelectrical impedance analysis. In the Crohn's disease and control subjects, mean serum GH levels were 1.07 +/- 0.2 and 1.7 +/- 0.2 ng/ml (P = 0.06), serum IGF-I levels were 162.7 +/- 10.5 and 194.8 +/- 15.7 ng/ml ( P = 0.1), and serum testosterone levels were 489 +/- 33 and 514 +/- 38 ng/ml (P = NS), respectively. Percentage body fat was significantly higher in the Crohn's patients ( 21 +/- 0.8% vs. 17.7 +/- 0.9%, respectively; P = 0.013). Intraabdominal fat (IAF) was significantly higher in the Crohn's subjects vs. controls ( 115 +/- 11 vs. 69 +/- 7 cm(2), respectively; P = 0.001). The ratio of intraabdominal to total body fat was higher in the Crohn's subjects than in the controls (0.4 +/- 0.1 vs. 0.3 +/- 0.1, respectively; P = 0.025). Subcutaneous fat area was similar in the two groups. IAF was higher in Crohn's patients even when controlling for testosterone and mean serum GH. Mean serumGH contributed independently to the differences in IAF ( P = 0.001). The ratio of IAF to total body fat remained higher in the Crohn's subjects when controlling for serum testosterone, but was no longer significant in a model that also included IGF-I and mean serum GH. GH levels contributed independently to the differences in the intraabdominal to total body fat ratio ( P = 0.02). In the Crohn's patients, serum GH correlated negatively with intraabdominal and total body fat and the ratio of intraabdominal to total body fat. Crohn's disease is associated with an increase in central fat accumulation, with more IAF and a higher ratio of intraabdominal to total body fat compared with controls. Although serum GH levels were similar in the two groups, GH contributed significantly to the abdominal fat measurements. These data show that GH has an important role in modulating visceral fat distribution in patients with Crohn's disease. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Gastroenterol, Boston, MA 02215 USA. RP Katznelson, L (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,Bulfinch 457, Boston, MA 02114 USA. EM lkatznelson1@partners.org FU NCRR NIH HHS [M01-RR-01066] NR 17 TC 18 Z9 18 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 NOV 1 PY 2003 VL 88 IS 11 BP 5468 EP 5472 DI 10.1210/jc.2003-030608 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 740GD UT WOS:000186393900064 PM 14602791 ER PT J AU Hayden, KM Khachaturian, AS Tschanz, JT Corcoran, C Nortond, M Breitner, JCS AF Hayden, KM Khachaturian, AS Tschanz, JT Corcoran, C Nortond, M Breitner, JCS CA Cache Cty Study Grp TI Characteristics of a two-stage screen for incident dementia SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE receiver-operating characteristic analysis; sensitivity; specificity; dementia; mass screening; validation sample ID ALZHEIMERS-DISEASE; CACHE COUNTY; RELIABILITY; POPULATION; PREVALENCE; DECLINE; AD AB Background and Objectives: To avoid costly evaluation of healthy individuals, efficient methods of screening for incident dementia must combine adequate sensitivity and high specificity. Two-stage screening may offer improvements over single-stage methods. We therefore investigated a two-stage screening protocol for incident dementia among 3,308 elderly. Methods: We administered the Modified Mini-Mental-State (3MS) or, rarely, Jorm's IQCODE, to a validation sample of 441 high-risk respondents. Informants then completed the Dementia Questionnaire (DQ). Finally, all 441 sample members underwent physical, neurologic, and neuropsychologic assessment. We studied the sensitivity and specificity of the 3MS/IQCODE and DQ using Receiver-Operating Characteristic analyses. Results: A 3MS cut point of 82/83 (of 100) yielded sensitivity and specificity of 91.5 and 90.1%. With 3MS scores of less than or equal to82, a DQ cut point of 2/3 (of five) yielded conditional sensitivity and specificity of 90.2 and 55.3%. Combining these instruments yielded sensitivity and specificity of 82.5 and 95.6%. Age stratification and use of longitudinal decline score criteria did not materially improve these figures. Conclusions: The improved specificity of the two-stage approach offers economies that are attractive, particularly if sensitivity can be enhanced, for example, by examination of a high-risk validation sample. (C) 2003 Elsevier Inc. All rights reserved. C1 Johns Hopkins Univ, Sch Publ Hlth, Dept Mental Hyg, Baltimore, MD 21205 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA. Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Utah State Univ, Dept Family Consumer & Human Dev, Logan, UT 84322 USA. Utah State Univ, Ctr Epidemiol Studies, Logan, UT 84322 USA. Utah State Univ, Dept Math & Stat, Logan, UT 84322 USA. Utah State Univ, Dept Psychol, Logan, UT 84322 USA. RP Breitner, JCS (reprint author), Johns Hopkins Univ, Sch Publ Hlth, Dept Mental Hyg, 624 N Broadway, Baltimore, MD 21205 USA. RI Corcoran, Chris/F-2155-2010; Tschanz, JoAnn/E-5986-2010; Norton, Maria/E-6994-2013; Hayden, Kathleen/B-6442-2012 OI Hayden, Kathleen/0000-0002-7745-3513 FU NIA NIH HHS [R01AG11380]; NIMH NIH HHS [T32MH14592] NR 17 TC 34 Z9 34 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD NOV PY 2003 VL 56 IS 11 BP 1038 EP 1045 DI 10.1016/S0895-4356(03)00247-6 PG 8 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 745ND UT WOS:000186694000003 PM 14614994 ER PT J AU Hennige, AM Burks, DJ Ozcan, U Kulkarni, RN Ye, J Park, SM Schubert, M Fisher, TL Dow, MA Leshan, R Zakaria, M Mossa-Basha, M White, MF AF Hennige, AM Burks, DJ Ozcan, U Kulkarni, RN Ye, J Park, SM Schubert, M Fisher, TL Dow, MA Leshan, R Zakaria, M Mossa-Basha, M White, MF TI Upregulation of insulin receptor substrate-2 in pancreatic beta cells prevents diabetes SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; HOMEOBOX FACTOR; KNOCKOUT MICE; RESISTANCE; GENE; GROWTH; APOPTOSIS; IRS-2; RAT; GLUCOSE AB The insulin receptor substrate-2 (Irs2) branch of the insulin/IGF signaling system coordinates peripheral insulin action and pancreatic beta cell function, so mice lacking Irs2 display similarities to humans with type 2 diabetes. Here we show that beta cell-specific expression of Irs2 at a low or a high level delivered a graded physiologic response that promoted beta cell growth, survival, and insulin secretion that prevented diabetes in Irs2(-/-) mice, obese mice, and streptozotocin-treated mice; and that upon transplantation, the transgenic islets cured diabetes more effectively than WT islets. Thus, pharmacological approaches that promote Irs2 expression in beta cells, especially specific cAMP agonists, could be rational treatments for beta cell failure and diabetes. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP White, MF (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, 1 Joslin Pl, Boston, MA 02215 USA. RI Schubert, Markus/F-5150-2010 FU NIDDK NIH HHS [R01 DK055326, R01 DK55326-04] NR 55 TC 173 Z9 180 U1 1 U2 10 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 NOV PY 2003 VL 112 IS 10 BP 1521 EP 1532 DI 10.1172/JCI200318581 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 743NU UT WOS:000186580400010 PM 14617753 ER PT J AU Cambien, B Bergmeier, W Saffaripour, S Mitchell, HA Wagner, DD AF Cambien, B Bergmeier, W Saffaripour, S Mitchell, HA Wagner, DD TI Antithrombotic activity of TNF-alpha SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NITRIC-OXIDE SYNTHASE; VON-WILLEBRAND-FACTOR; SMOOTH-MUSCLE CELLS; DEFICIENT MICE; MESSENGER-RNA; P-SELECTIN; THROMBOSIS; EXPRESSION; ACTIVATION; PLATELETS AB Basic and clinical observations suggest that thrombosis and inflammation are closely related. Here we addressed the role played by TNF-alpha in thrombus formation and growth in an in vivo mouse model. Using intravital microscopy, we show that systemic administration of TNF-alpha at doses found in sepsis transiently inhibits thrombus formation and delays arterial occlusion upon vascular injury. These results were reflected in a prolonged bleeding time. Platelets isolated from the TNF-alpha-treated mice showed a marked decrease in fibrinogen binding and P-selectin expression as well as reduced platelet aggregation in response to various agonists. In contrast, in vitro treatment of platelets with TNF-alpha did not affect their function. TNF receptor 1- and 2-deficient mice exhibited normal thrombogenesis in the presence of TNF-alpha. Additionally, the inhibitory effect of TNF-a was lost either after treatment with N-G-monomethyl-L-arginine, an inhibitor of NO production, or in mice deficient for iNOS. These results indicate that under inflammatory conditions, when leukocytes need free passage to transmigrate into tissues, TNF-alpha decreases platelet activation and inhibits thrombi formation. This effect is not exerted directly on platelets but mediated through the rapid generation of NO in the vessel wall. C1 CBR Inst Biomed Res Inc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wagner, DD (reprint author), CBR Inst Biomed Res Inc, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [R37 HL041002, R01 HL053756, R01-HL-53756, R37-HL-41002, P01 HL056949] NR 42 TC 60 Z9 62 U1 1 U2 1 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 NOV PY 2003 VL 112 IS 10 BP 1589 EP 1596 DI 10.1172/JCI200319284 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 743NU UT WOS:000186580400017 PM 14617760 ER PT J AU Barron, MA Sutton, DA Veve, R Guarro, J Rinaldi, M Thompson, E Cagnoni, PJ Moultney, K Madingerl, NE AF Barron, MA Sutton, DA Veve, R Guarro, J Rinaldi, M Thompson, E Cagnoni, PJ Moultney, K Madingerl, NE TI Invasive mycotic infections caused by Chaetomium perlucidum, a new agent of cerebral phaeohyphomycosis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID TRANSPLANT RECIPIENT; DACTYLARIA-GALLOPAVA; SUCCESSFUL THERAPY; PATIENT; GLOBOSUM; SUSCEPTIBILITY; CLADOSPORIUM; LEUKEMIA AB We report the first two cases of invasive human mycoses caused by the phaeoid ascomycete, Chaetomium perlucidum, and review the English literature regarding invasive Chaetomium infections. Fatal disseminated disease involving the brain, heart, lungs, and spleen is described in an acute myelogenous leukemia patient. A second patient with a history of asthma and chronic bronchiectasis experiencing right-middle-lobe syndrome grew C. perlucidum from lung tissue. This study adds C. perlucidum to the list of other known neurotropic Chaetomium species, C. atrobrunneum and C. strumarium, and also documents this organism's ability to disseminate beyond the central nervous system. C1 Univ Colorado, Hlth Sci Ctr, Div Infect Dis, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Bone Marrow Transplant Program, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. Univ Colorado Hosp, Clin Microbiol Lab, Denver, CO 80262 USA. Univ Rovira & Virgili, Fac Med, Unitat Microbiol, Tarragona 43201, Spain. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Lab Serv, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX USA. RP Barron, MA (reprint author), Univ Colorado, Hlth Sci Ctr, Div Infect Dis, 4200 E 9th Ave,Box B168, Denver, CO 80262 USA. OI Guarro, Josep/0000-0002-7839-7568 NR 21 TC 29 Z9 32 U1 0 U2 0 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 NOV PY 2003 VL 41 IS 11 BP 5302 EP 5307 DI 10.1128/JCM.41.11.5302-5307.2003 PG 6 WC Microbiology SC Microbiology GA 745AR UT WOS:000186665500073 PM 14605190 ER PT J AU Marty, FM Barouch, DH Coakley, EP Baden, LR AF Marty, FM Barouch, DH Coakley, EP Baden, LR TI Disseminated trichosporonosis caused by Trichosporon loubieri SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID AMPHOTERICIN-B; EXPERIMENTAL-THERAPY; FUNGAL-INFECTIONS; MOLECULAR PROBES; ASAHII INFECTION; DIMORPHIC FUNGI; PATHOGENS; IDENTIFICATION; VORICONAZOLE; COMBINATION AB Trichosporonosis is an emerging invasive fungal infection in immunosuppressed patients; a case of disseminated infection caused by Trichosporon loubieri presented confirms its role as a human pathogen. C1 Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Marty, FM (reprint author), Brigham & Womens Hosp, Div Infect Dis, 75 Francis St,PBB-A4, Boston, MA 02115 USA. NR 29 TC 34 Z9 36 U1 0 U2 0 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 NOV PY 2003 VL 41 IS 11 BP 5317 EP 5320 DI 10.1128/TCM.41.11.5317-5320.2003 PG 4 WC Microbiology SC Microbiology GA 745AR UT WOS:000186665500077 PM 14605194 ER PT J AU Hanks, GE Pajak, TF Porter, A Grignon, D Brereton, H Venkatesan, V Horwitz, EM Lawton, C Rosenthal, SA Sandler, HM Shipley, WU AF Hanks, GE Pajak, TF Porter, A Grignon, D Brereton, H Venkatesan, V Horwitz, EM Lawton, C Rosenthal, SA Sandler, HM Shipley, WU TI Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate: The Radiation Therapy Oncology Group Protocol 92-02 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) CY OCT 21-26, 2000 CL BOSTON, MA SP Amer Soc Therapeut Radiol & Oncol ID DOSE-RESPONSE; CANCER; SURVIVAL; STRATIFICATION; SUPPRESSION; GOSERELIN AB (Purpose) under bar: Radiation Therapy Ontology Group (RTOG) Protocol 92-02 was a randomized trial testing long-term (LT) adjuvant androgen deprivation (AD) after initial AD with external-beam radiotherapy (RT) in patients with locally advanced prostate cancer (PC; T2c-4) and with prostate-specific antigen level less than 150 ng/mL. (Patients and Methods) under bar: Patients received a total of 4 months of goserelin and flutamide, 2 months before and 2 months during FIT. A radiation dose of 65 to 70 Gy was given to the prostate and a dose of 44 to 50 Gy to the pelvic lymph nodes. Patients were randomly assigned to receive no additional therapy (short-term [ST]AD-RT) or 24 months of goserelin (LTAD-RT),- 1,554 patients were entered onto the study. (Results) under bar: The LTAD-RT arm showed significant improvement in all efficacy end points except overall survival (OS, 80.0% v 78.5% at 5 years, P = .73), compared with the STAD-RT arm. In a subset of patients not part of the original study design, with tumors assigned Gleason scares of 8 to 10 by the contributing institutions, the LTAD-RT arm had significantly better OS (81.0% v 70.7%, P = .044). There was a small but significant increase in the frequency of late radiation grades 3, 4, and 5 gastrointestinal toxicity ascribed to the LTAD-RT arm (2.6% v 1.2% at 5 years, P = .037), the cause of which is not clear. (Conclusion) under bar: The RTOG 92-02 trial supports the addition of LT adjuvant AD to STAD with RT for T2c-4 PC. In the exploratory subset analysis of patients with Gleason scares 8 to 10, LT adjuvant AD resulted in a survival advantage. (C) 2003 by American Society of Clinical Oncology. C1 Radiat Therapy Oncol Grp, Dept Stat, Philadelphia, PA 19107 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Mercy Hosp, Scranton, PA USA. Wayne State Univ, Harper Hosp, Detroit, MI 48202 USA. Univ Western Ontario, London, ON, Canada. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Radiol Associates Sacramento, Sacramento, CA USA. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Radiat Therapy Oncol Grp, Dept Stat, 1101 Mkt St, Philadelphia, PA 19107 USA. EM tpajak@phila.acr.org FU NCI NIH HHS [CA-21661, CA-32115] NR 18 TC 466 Z9 491 U1 0 U2 8 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 NOV 1 PY 2003 VL 21 IS 21 BP 3972 EP 3978 DI 10.1200/JCO.2003.11.023 PG 7 WC Oncology SC Oncology GA 738NV UT WOS:000186295500014 PM 14581419 ER PT J AU Talcott, JA Manola, J Clark, JA Kaplan, I Beard, CJ Mitchell, SP Chen, RC O'Leary, MP Kantoff, PW D'Amico, AV AF Talcott, JA Manola, J Clark, JA Kaplan, I Beard, CJ Mitchell, SP Chen, RC O'Leary, MP Kantoff, PW D'Amico, AV TI Time course and predictors of symptoms after primary prostate cancer therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; BEAM RADIATION-THERAPY; RADICAL PROSTATECTOMY; SEXUAL FUNCTION; OUTCOMES; COMPLICATIONS; MEN; URINARY; BOTHER AB (Purpose) under bar :Understanding the distinctive patterns of treatment-related dysfunction after alternative initial treatments for early prostate cancer (PC) may improve patients' choice of treatment and later help them adjust to its consequences. We characterized the time course of treatment complications while adjusting for potentially confounding pretreatment factors hindering other observational studies. (Patients and Methods) under bar: In a prospective cohort study of 417 men we assessed urinary, bowel, and sexual function from before primary treatment to 24 months after. To control for potential confounding, we measured sociodemogrophic and PC prognostic factors, medical comorbidity, and pretreatment function commonly affected by PC and its treatment. (Results) under bar: Patients who underwent external beam radiotherapy (EBRT), radical prostatectomy (RP), and brachytherapy (BT) differed significantly in sociodemographic factors, cancer prognostic factors, and pretreatment symptom status, especially sexual function. Urinary incontinence increased sharply after RP, while bowel problems and urinary irritation/obstruction rose after EBRT and BT. Sexual dysfunction increased in all patients, particularly after radical prostatectomy, and nerve-sparing surgical technique had little apparent benefit. There was no change in urinary function and little change in overall bowel function after 12 months, but the time course of sexual dysfunction varied by treatment and, for bowel function, by symptom. Multiple regression modeling confirmed that treatment influences all 24-month outcomes, but residual confounding persisted. (Conclusion) under bar: Pretreatment function and the primary treatment modality for early stage PC strongly predict the affected organ systems and time course of dysfunction. With this information, patients and their physicians may refine their choice of treatment and better anticipate its consequences. (C) 2003 by American Society of Clinical Oncology. C1 Massachusetts Gen Hosp, Ctr Canc, Ctr Outcomes Ctr, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Edith Nourse Rogers Mem Vet Adm Hosp, Ctr High Qual Outcomes & Econ Res, Bedford, MA 01730 USA. RP Talcott, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Outcomes Ctr, B75 230,55 Fruit St, Boston, MA 02114 USA. OI Clark, Jack/0000-0002-7424-1670 FU AHRQ HHS [HS08208] NR 22 TC 146 Z9 147 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 1 PY 2003 VL 21 IS 21 BP 3979 EP 3986 DI 10.1200/JCO.2003.01.199 PG 8 WC Oncology SC Oncology GA 738NV UT WOS:000186295500015 PM 14581420 ER PT J AU Ramberg, P Sekino, S Uzel, NG Socransky, S Lindhe, J AF Ramberg, P Sekino, S Uzel, NG Socransky, S Lindhe, J TI Bacterial colonization during de novo plaque formation SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE checkerboard DNA-DNA hybridization technique; microorganisms; plaque formation ID NON-SURGICAL TREATMENT; STREPTOCOCCUS-SANGUIS; SUPRAGINGIVAL PLAQUE; PERIODONTAL-DISEASE; DENTAL PLAQUE; SUBGINGIVAL PLAQUE; APATITIC SURFACES; BARRIER MATERIAL; AMYLASE-BINDING; ACTINOMYCES AB Objective: To determine microbial changes that occur during plaque formation in a dentition free of gingival inflammation. Material and Methods: Ten subjects were recruited. The study included one preparatory period (2 weeks) and a plaque accumulation period (4 days). The volunteers exercised proper tooth cleaning methods, were scaled and received repeated professional mechanical tooth cleaning during the preparatory period. During the plaque accumulation period, the participants abstained from plaque control measures. Plaque was scored on the approximal surfaces of maxillary and mandibular premolars on Days 0, 1, 2 and 4 using a scale from 0 to 5 and according to the criteria of the Quigley and Hein Plaque Index (QHI). Supragingival plaque samples were obtained from the same intervals and surfaces and evaluated using a checkerboard DNA-DNA hybridization technique. Results: The mean QHI increased from 0 to 1.6 (Day 4). The total number of organisms on Day 0 averaged 140x10(5) and increased to about 210x10(5) after 4 days without oral hygiene. The most dominant species on Day 0 were members of the genus Actinomyces. These organisms comprised almost 50% of the microbiota evaluated. None of the Actinomyces species increased significantly during the 4 days. Some Streptococcus species increased significantly over time as well as species of the genera Capnocytophaga, Campylobacter, Fusobacteria and Actinomyces actinomycetemcomitans. Conclusion: In the present investigation, the preparatory phase established a situation with minimal gingival inflammation and close to zero amounts of dental plaque. The Day 0 plaque samples exhibited high proportions of Actinomyces species. During the 4 days of no oral hygiene, there was a small increase in total numbers of organisms as well as a modest increase in the proportion of "disease-associated" taxa such as species of the "orange complex" species. C1 Univ Gothenburg, Inst Odontol, Dept Periodontol, SE-40530 Gothenburg, Sweden. Forsyth Inst, Dept Periodontol, Boston, MA USA. RP Ramberg, P (reprint author), Univ Gothenburg, Inst Odontol, Dept Periodontol, Box 450, SE-40530 Gothenburg, Sweden. NR 45 TC 27 Z9 32 U1 0 U2 4 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 NOV PY 2003 VL 30 IS 11 BP 990 EP 995 DI 10.1034/j.1600-051X.2003.00419.x PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 736MN UT WOS:000186174700010 PM 14761122 ER PT J AU Torresyap, G Haffajee, AD Uzel, NG Socransky, SS AF Torresyap, G Haffajee, AD Uzel, NG Socransky, SS TI Relationship between periodontal pocket sulfide levels and subgingival species SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE periodontal diseases; sulfide; periodontitis; pocket depth; dental plaque; biofilms; microbial ecology ID SULFATE-REDUCING BACTERIA; HYDROGEN-SULFIDE; METHYL MERCAPTAN; ORAL MALODOR; DISEASE; PLAQUE AB Background: Many species implicated in the pathogenesis of periodontal disease produce volatile sulfur compounds (VSC). This investigation examined the relationship between levels of sulfide and subgingival bacterial species in the same periodontal pockets. Material and Methods: Twenty chronic periodontitis subjects were measured clinically at six sites per tooth for plaque, gingivitis, bleeding on probing, suppuration, pocket depth and attachment level. Subgingival plaque samples, taken from the mesial aspect of each tooth, were individually analyzed for their content of 40 bacterial species using checkerboard DNA-DNA hybridization. Sulfide levels were measured at the same sites using a Diamond Probe/Perio 2000 system. Clinical and microbiological data were averaged for sulfide-positive and -negative sites separately in each subject and then averaged across subjects. Significance differences in clinical and microbial parameters between sulfide-positive and -negative sites were sought using the Wilcoxon signed ranks test. Results: Mean total DNA probe counts (x10(5), +/-SEM) at sulfide-negative and -positive sites were 44.0+/-9.9 and 65.0+/-13.3, respectively (p<0.01). Seventeen species were found at significantly higher levels in sulfide-positive than -negative sites. These included abundant producers of VSC such as members of the genera Fusobacterium, Campylobacter, Prevotella, Treponema and Eubacterium, and Bacteriodes forsythus, Selenomonas noxia and Propionibacterium acnes. Prevotella intermedia, Bacteriodes forsythus, Prevotella nigrescens, Fusobacterium nucleatum ss vincentii and Treponema denticola exhibited the greatest difference in mean counts between sulfide-negative and -positive sites. Orange and red complex species were at higher counts at shallow (<4 mm) sulfide-positive than shallow sulfide-negative sites. Although not statistically significant, mean clinical parameters were somewhat higher at sulfide-positive than sulfide-negative sites. Conclusions: Intra-pocket sulfide levels reflect the levels of sulfide-producing species and may provide useful diagnostic information. C1 Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. RP Torresyap, G (reprint author), Forsyth Inst, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-10977, DE-12108, DE-12861, DE-13232] NR 22 TC 21 Z9 25 U1 0 U2 2 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 NOV PY 2003 VL 30 IS 11 BP 1003 EP 1010 DI 10.1034/j.1600-051X.2003.00377.x PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 736MN UT WOS:000186174700012 PM 14761124 ER PT J AU Papakostas, GI Petersen, TJ Farabaugh, AH Murakami, JL Pava, JA Alpert, JE Fava, M Nierenberg, AA AF Papakostas, GI Petersen, TJ Farabaugh, AH Murakami, JL Pava, JA Alpert, JE Fava, M Nierenberg, AA TI Psychiatric Comorbidity as a predictor of clinical response to nortriptyline in treatment-resistant major depressive disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID TRIDIMENSIONAL PERSONALITY QUESTIONNAIRE; AXIS-II; FLUOXETINE; OUTPATIENTS; IMIPRAMINE; PATHOLOGY; BEHAVIOR; ONSET AB Background. A number of studies of major depressive disorder suggest that psychiatric comorbidity may contribute to treatment resistance. The purpose of this study was to test whether the presence of comorbid Axis I and Axis II disorders predicts clinical response to an open trial of nortriptyline among patients with treatment-resistant depression. Method. Ninety-two outpatients with treatment-resistant DSM-III-R major depressive disorder were enrolled in a 6-week open trial of nortriptyline (Nov. 1992-Jan. 1999). The presence of comorbid Axis I and Axis II disorders was established at baseline with the use of the Structured Clinical Interview for DSM-III-R. Chi-square analyses were used to test Axis I or Axis II comorbid conditions as a predictor of clinical response to nortriptyline. Results: Thirty-nine patients (42.4%) responded to nortriptyline. The presence of avoidant personality disorder (p < .01) predicted poorer response to nortriptyline. The response rate was 16.7% for patients with and 48.6% for patients without comorbid avoidant personality disorder. No other comorbid diagnoses were found to predict clinical response in a statistically significant manner. Conclusion: The presence of avoidant personality disorder conferred a poorer prognosis in treatment-resistant depression patients treated with nortriptyline. C1 Harvard Univ, Depress Clin & Res Program, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Papakostas, GI (reprint author), Harvard Univ, Depress Clin & Res Program, Sch Med, Massachusetts Gen Hosp, 15 Parkman St,WAC 812, Boston, MA 02114 USA. RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [R29 MH46952] NR 33 TC 14 Z9 15 U1 0 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD NOV PY 2003 VL 64 IS 11 BP 1357 EP 1361 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 747RX UT WOS:000186819700012 PM 14658951 ER PT J AU Nagurney, JT Brown, DFM Chang, YC Sane, S Wang, AC Weiner, JB AF Nagurney, JT Brown, DFM Chang, YC Sane, S Wang, AC Weiner, JB TI Use of diagnostic testing in the emergency department for patients presenting with non-traumatic abdominal pain SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE diagnostic testing; technology; abdominal pain; decision making; CT scan ID RIGHT LOWER QUADRANT; CT; MANAGEMENT; ABDOMEN; IMPACT AB The objective of the study was to measure the utilization and diagnostic value of tests used in the Emergency Department (ED) on patients with undifferentiated non-traumatic abdominal or flank pain. Specific goals were to measure how often these tests led to changes in diagnosis or disposition, which tests were most commonly used, and which tests providers considered most helpful. We conducted a pilot single-center, prospective descriptive study, enrolling all eligible adult patients who presented to our ED with non-traumatic abdominal or flank pain during defined hours of our intake period. Based on serial provider interviews pre- and post-testing, we measured the frequency of change of most likely diagnosis and disposition, which tests were performed, and the provider-perceived value of tests. We enrolled 124 subjects with a mean age of 44 years; 27% were admitted. Testing led to a change in most likely diagnosis in 37% of subjects, and in disposition in 41%. Frequency of diagnostic test use varied from a high of 93% for CBC to 6% for a blood or urine culture. Overall, 65% of patients had at least one imaging study performed, and 39% had an abdominal/pelvic computed tomography (CT) scan. Over all subjects, providers identified the most useful tests as the CT scan (31%) and urinalysis (17%). In conclusion, among ED patients who presented with non-traumatic abdominal or flank pain to one academic center, the pre-test most likely diagnosis and disposition were changed based on the ED evaluation in over one-third of subjects. Almost all received blood tests and two-thirds received one or more imaging studies. Based on providers' subjective opinions, the most valuable tests were the abdomino/pelvic CT scan and the urinalysis. (C) 2003 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Gen Med, Dept Internal Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Internal Med, Boston, MA USA. Princeton Univ, Princeton, NJ 08544 USA. Univ Michigan, Sch Med, Ann Arbor, MI 48104 USA. RP Nagurney, JT (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Clin 115,55 Fruit St, Boston, MA 02115 USA. NR 17 TC 31 Z9 31 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD NOV PY 2003 VL 25 IS 4 BP 363 EP 371 DI 10.1016/S0736-4679(03)00237-3 PG 9 WC Emergency Medicine SC Emergency Medicine GA 748VC UT WOS:000186880900003 PM 14654174 ER PT J AU Huffman, JC Stern, TA AF Huffman, JC Stern, TA TI The use of benzodiazepines in the treatment of chest pain: A review of the literature SO JOURNAL OF EMERGENCY MEDICINE LA English DT Review DE benzodiazepines; chest pain; myocardial infarction; myocardial ischemia; angina ID CORONARY-ARTERY DISEASE; ACUTE MYOCARDIAL-INFARCTION; DOUBLE-BLIND; PANIC DISORDER; POSTHERPETIC NEURALGIA; INTRAVENOUS DIAZEPAM; PLASMA-CATECHOLAMINE; CARDIAC ARRHYTHMIAS; BINDING-SITES; HEART-DISEASE AB Benzodiazepines, although not listed in the American Heart Association's guidelines for the treatment of chest pain, are often used to provide symptomatic relief to patients who experience chest pain. To investigate the utility of benzodiazepines in the treatment of chest pain, the pharmacologic actions and cardiovascular effects of benzodiazepines were reviewed. In addition, a literature search regarding the use of benzodiazepines to treat patients with chest pain was conducted. The results indicated that benzodiazepines reduce anxiety, pain, and cardiovascular activation. Benzodiazepines amplify gamma-aminobutyric acid (GABA) throughout the central nervous system, and act more peripherally to reduce catecholamines. In addition, preliminary evidence indicates that benzodiazepines may cause coronary vasodilatation, prevent dysrhythmias, and block platelet aggregation, though further study is needed. Both non-cardiac chest pain (associated with musculoskeletal, esophageal, neurologic, and psychiatric conditions) and cardiac chest pain (associated with acute and chronic myocardial ischemia) seem to be effectively treated with benzodiazepines. Benzodiazepines are safe and well tolerated when administered alone or in combination with other medications. Moreover, the risk of dependence is minimal when benzodiazepines are prescribed on a short-term basis. Further study of benzodiazepines in the treatment of acute chest pain is needed to confirm these favorable actions and better define their use in the acute medical setting. (C) 2003 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Psychiat Consultat Serv, Boston, MA 02114 USA. RP Stern, TA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Warren 605,55 Fruit St, Boston, MA 02114 USA. NR 106 TC 24 Z9 25 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD NOV PY 2003 VL 25 IS 4 BP 427 EP 437 DI 10.1016/j.jemermed.2003.01.001 PG 11 WC Emergency Medicine SC Emergency Medicine GA 748VC UT WOS:000186880900014 PM 14654185 ER PT J AU Brown, DFM Benzer, TI Nadel, ES AF Brown, DFM Benzer, TI Nadel, ES TI An unusual cause of acute myocardial infarction SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID ABDOMINAL AORTIC-ANEURYSM; ULTRASOUND; REPAIR C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St,Bullfinch 105, Boston, MA 02114 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD NOV PY 2003 VL 25 IS 4 BP 439 EP 444 DI 10.1016/j.jemermed.2003.07.001 PG 6 WC Emergency Medicine SC Emergency Medicine GA 748VC UT WOS:000186880900015 PM 14654186 ER PT J AU Lisi, S Chiovato, L Pinchera, A Marcocci, C Menconi, F Morabito, E Altea, MA McCluskey, RT Marino, M AF Lisi, S Chiovato, L Pinchera, A Marcocci, C Menconi, F Morabito, E Altea, MA McCluskey, RT Marino, M TI Impaired thyroglobulin (Tg) secretion by FRTL-5 cells transfected with soluble receptor associated protein (RAP): Evidence for a role of RAP in the Tg biosynthetic pathway SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Article DE thyroglobulin; thyroid; RAP; LDL receptor; megalin ID MEGALIN-MEDIATED TRANSCYTOSIS; RETICULUM STORAGE DISEASE; THYROID-HORMONE RELEASE; ENDOPLASMIC-RETICULUM; MOLECULAR CHAPERONE; SPECIALIZED CHAPERONE; LIPOPROTEIN RECEPTORS; ENDOCYTIC RECEPTORS; CONGENITAL GOITER; HYPOTHYROIDISM AB Secretion of thyroglobulin (Tg) by thyrocytes requires several endoplasmic reticulum (ER)-resident molecular chaperones. The receptor-associated protein (RAP), a known molecular chaperone, binds to Tg in thyroid cells shortly after biosynthesis. Here we investigated whether RAP is involved in Tg secretion by FRTL-5 cells. For this purpose, we studied Tg secretion by FRTL-5 cells transfected with a soluble RAP chimera, as a mean for interfering with endogenous RAP. We used a RAP-human IgG Fc (RAP-Ig) chimeric cDNA, which was designed in order to exclude the ER retention sequence of RAP and to allow generation of a secreted form of RAP. FRTL-5 cells were transiently transfected with the RAP-Ig cDNA or, as control, with a CD8-Ig cDNA. Media were collected at 24, 48 and 72 h after transfection. Secretion of fusion proteins and of Tg in the media was measured by ELISA. As expected, under standard culture conditions, RAP was not secreted into the media by FRTL-5 cells, even though it could be detected by Western blotting in cell extracts. In transfection experiments, fusion proteins were present in the media of FRTL-5 cells transfected with either RAP-Ig or CD8-Ig, indicating that transfection was successful. Although Tg was found in the media of FRTL-5 cells transfected with either CD8-19 or RAP-Ig, a lower amount was found in cells transfected with RAP-Ig. Therefore, we concluded that RAP is involved in Tg secretion by FRTL-5 cells suggesting that RAP may function as a Tg molecular chaperone. (C) 2003, Editrice Kurtis. C1 Univ Pisa, Dipartimento Endocrinol, I-56124 Pisa, Italy. Univ Pavia, IRCCS, Salvatore Maugeri Fdn, Endocrine Unit, Pavia, Italy. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. RP Marino, M (reprint author), Univ Pisa, Dipartimento Endocrinol, Via Paradisa 2, I-56124 Pisa, Italy. EM m.marino@endoc.med.unipi.it NR 31 TC 5 Z9 5 U1 0 U2 0 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD NOV PY 2003 VL 26 IS 11 BP 1105 EP 1110 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 770MT UT WOS:000188735100010 PM 15008249 ER PT J AU Hirashima, Y Tsuruzoe, K Kodama, S Igata, M Toyonaga, T Ueki, K Kahn, CR Araki, E AF Hirashima, Y Tsuruzoe, K Kodama, S Igata, M Toyonaga, T Ueki, K Kahn, CR Araki, E TI Insulin down-regulates insulin receptor substrate-2 expression through the phosphatidylinositol 3-kinase/Akt pathway SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID PROTEIN-KINASE-B; RNA-POLYMERASE-II; RESPONSE SEQUENCE; GLUCOSE-TRANSPORT; SKELETAL-MUSCLE; GENE-EXPRESSION; GLYCOGEN-SYNTHESIS; 3T3-L1 ADIPOCYTES; PROMOTER ACTIVITY; IRS-2 GENE AB Insulin receptor substrate (IRS)-1 and IRS-2 are the major substrates that mediate insulin action. Insulin itself regulates the expression of the IRS protein in the liver, but the underlying mechanisms of IRS-1 and IRS-2 regulation are not fully understood. Here we report that insulin suppressed the expression of both IRS-1 and IRS-2 proteins in Fao hepatoma cells. The decrease in IRS-1 protein occur-red via proteasomal degradation without any change in IRS-1 mRNA, whereas the insulin-induced suppression of IRS-2 protein was associated with a parallel decrease in IRS-2 mRNA without changing IRS-2 mRNA half-life. The insulin-induced suppression of IRS-2 mRNA and protein was blocked by the phosphatidylinositol (PI) 3-kinase inhibitor, LY294002, but not by the MAP kinase-ERK kinase (MEK) inhibitor, PD098059. Inhibition of Akt by overexpression of dominant-negative Akt also caused complete attenuation of the insulin-induced decrease in IRS-2 protein and partial attenuation of its mRNA down-regulation. Some nuclear proteins bound to the insulin response element (IRE) sequence on the IRS-2 gene in an insulin-dependent manner in vitro, and the binding was also blocked by the PI 3-kinase inhibitor. Reporter gene assay showed that insulin suppressed the activity of both human and rat IRS-2 gene promoters through the IRE in a PI 3-kinase-dependent manner. Our results indicate that insulin regulates IRS-1 and IRS-2 through different mechanisms and that insulin represses IRS-2 gene expression via a PI 3-kinase/Akt pathway. C1 Kumamoto Univ, Dept Metab Med, Grad Sch Med Sci, Kumamoto 8608556, Japan. Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr,Dept Med, Boston, MA 02215 USA. RP Kumamoto Univ, Dept Metab Med, Grad Sch Med Sci, 1-1-1 Honjo, Kumamoto 8608556, Japan. EM earaki@kaiju.medic.kumamoto-u.ac.jp NR 59 TC 48 Z9 52 U1 2 U2 6 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 EI 1479-6805 J9 J ENDOCRINOL JI J. Endocrinol. PD NOV PY 2003 VL 179 IS 2 BP 253 EP 266 DI 10.1677/joe.0.1790253 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 745RZ UT WOS:000186703000013 PM 14596677 ER PT J AU Vacanti, JP AF Vacanti, JP TI Tissue and organ engineering: Can we build intestine and vital organs? SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 18-22, 2003 CL ORLANDO, FLORIDA SP Soc Surg Alimentary Tract ID BIODEGRADABLE POLYMERS; CELL TRANSPLANTATION; CARTILAGE; CHONDROCYTES; BONE C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, 55 Fruit St,WRN 1157, Boston, MA 02114 USA. NR 21 TC 26 Z9 27 U1 0 U2 1 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 NOV PY 2003 VL 7 IS 7 BP 831 EP 835 DI 10.1016/S1091-255X(03)00135-5 PG 5 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 742KL UT WOS:000186515900002 PM 14592654 ER PT J AU Lewis, JH Andersen, RM Gelberg, L AF Lewis, JH Andersen, RM Gelberg, L TI Health care for homeless women - Unmet needs and barriers to care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE barriers; homeless; unmet need; vulnerable population; women ID MEDICAL-CARE; LOS-ANGELES; URBAN HOMELESS; HOUSED POOR; ADULTS; SERVICES; FAMILIES; OUTCOMES; CHILDREN; HISTORY AB Objective: Homelessness is a significant and growing problem in the United States. Women and families are the fastest growing segments of the homeless population. Homelessness increases the risk of having health problems and encountering barriers to care. This study determines how much perceived unmet need for medical care there is among homeless women, what homeless women perceive to be barriers to health care, and how barriers and other factors are associated with unmet needs. Design: Cross-sectional study of homeless women, utilizing structured interviews. Setting and Participants: Community-based probability sample of 974 homeless women aged 15 to 44 years. Main Outcome Measures: Perceived unmet need for medical care in the past 60 days. Relationship between unmet need and demographic variables, place of stay, source of health care, insurance, and perceived barriers to care. Results: Of the 974 women, 37% reported unmet need for medical care. Controlling for other factors, the odds of unmet need were lower among those with a regular source of care (odds ratio [OR] to .35, 95% confidence interval [CI], .21 to 58), while having health insurance was not significantly associated. The odds of unmet need were higher among those who experienced the barriers: not knowing where to go (OR 2.27, 95% CI, 1.40 to 3.69), long office waiting times (OR 1.89, 95% CI 1.27 to 2.83) and being too sick to seek care (OR 2.03, 95% CI, 1.14 to 3.62). Conclusions: There is significant unmet need for medical care among homeless women. Having a regular source of care was more important than health insurance in lowering the odds of unmet need. Homeless women must be educated regarding sources of care, and clinics serving the homeless must decrease waiting times. C1 Univ Calif Los Angeles, Los Angeles, CA USA. W Los Angeles VA Med Ctr, Los Angeles, CA USA. RP Lewis, JH (reprint author), POB 1765, Wilson, WY 83014 USA. FU AHRQ HHS [R01 HS08323, R01 HS008323]; NIAAA NIH HHS [R21 AA013398, R21 AA 13398]; NIDA NIH HHS [R01 DA14835, R01 DA014835] NR 43 TC 53 Z9 53 U1 2 U2 7 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 NOV PY 2003 VL 18 IS 11 BP 921 EP 928 DI 10.1046/j.1525-1497.2003.20909.x PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 743FW UT WOS:000186562600007 PM 14687278 ER PT J AU O'Toole, TP Conde-Martel, A Gibbon, JL Hanusa, BH Fine, MJ AF O'Toole, TP Conde-Martel, A Gibbon, JL Hanusa, BH Fine, MJ TI Health care of homeless veterans - Why are some individuals falling through the safety net? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE homelessness; mental health; needs assessment; substance abuse; veterans ID URBAN HOMELESS; MENTAL-ILLNESS; HOUSED POOR; SERVICE USE; OUTCOMES; MODEL AB It is important to understand the needs of those veterans who are homeless. We describe characteristics of homeless male veterans and factors associated with needing VA benefits from a two-city, community survey of 531 homeless adults. Overall, 425 were male, of whom 127 were veterans (29.9%). Significantly more veterans had a chronic medical condition and two or more mental health conditions. Only 35.1% identified a community clinic for care compared with 66.8% of non-veterans (P<.01); 47.7% identified a shelter-based clinic and 59.1% reported needing VA benefits. Those reporting this need were less likely to report a medical comorbidity (58.7% vs 76.9%; P=.04), although 66.7% had a mental health comorbidity and 82.7% met Diagnosic Screening Manual (DSM)-IIIR criteria for substance abuse/dependence. They were also significantly more likely to access shelter clinics compared with veterans without this need. Homeless veterans continue to have substantial health issues. Active outreach is needed for those lacking access to VA services. C1 Johns Hopkins Univ, Welch Ctr, Sch Med, Baltimore, MD 21205 USA. Hosp Univ Gran Canaria, Las Palmas Gran Canaria, Spain. Maricopa Cty Dept Publ Hlth, Phoenix, AZ USA. Univ Pittsburgh, Div Gen Internal Med, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. VA Pittsburgh Hlth Care Syst, VA Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP O'Toole, TP (reprint author), Johns Hopkins Univ, Welch Ctr, Sch Med, Rm 2-513,2024 E Monument St, Baltimore, MD 21205 USA. FU NIDA NIH HHS [K23 DA013988, K23DA13988-01] NR 19 TC 45 Z9 45 U1 0 U2 3 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 NOV PY 2003 VL 18 IS 11 BP 929 EP 933 DI 10.1046/j.1525-1497.2003.21209.x PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 743FW UT WOS:000186562600008 PM 14687279 ER PT J AU Braithwaite, RS Chlebowski, RT Lau, J George, S Hess, R Col, NF AF Braithwaite, RS Chlebowski, RT Lau, J George, S Hess, R Col, NF TI Meta-analysis of vascular and neoplastic events associated with tamoxifen SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the Society-for-Medical-Decision-Making CY SEP 25-26, 2000 CL CINCINNATI, OHIO SP Soc Med Decis Making DE tamoxifen; adverse events; selective estrogen receptor modulators; chemoprevention ID POSITIVE BREAST-CANCER; SURGICAL-ADJUVANT-BREAST; CARDIOVASCULAR RISK-FACTORS; RANDOMIZED CONTROLLED-TRIAL; POSTMENOPAUSAL WOMEN; PLUS TAMOXIFEN; HYSTERECTOMIZED WOMEN; PREMENOPAUSAL WOMEN; METASTATIC MELANOMA; CORONARY-ARTERIES AB Objective: Tamoxifen reduces the risk of developing breast cancer but also affects the risks of certain vascular and neoplastic events. Our purpose was to estimate the effects of tamoxifen on potentially life-threatening vascular and neoplastic outcomes. Design: Random effects meta-analysis of published randomized controlled trials. Patients: Participants in all trials in which a treatment arm that included tamoxifen was compared to a similar control arm. Breast cancer risk reduction and treatment trials were included. Interventions: Tamoxifen at variable dose and duration. Measurements and Main Results: Thirty-two trials (52,929 patients) reported one or more outcomes of interest. Tamoxifen was associated with significantly increased risks of endometrial cancer (relative risk [RR] 2.70; 95% CI, 1.94 to 3.75), gastrointestinal cancers (RR 1.31; 95% CI, 1.01 to 1.69), strokes (RR 1.49; 95% CI, 1.16 to 1.90), and pulmonary emboli (RR 1.88; 95% CI, 1.77 to 3.01). Tamoxifen had no effect on secondary malignancies other than endometrial and gastrointestinal cancers (RR 0.96; 95% CI, 0.81 to 1.13). In contrast, tamoxifen significantly decreased myocardial infarction deaths (RR 0.62; 95% CI, 0.41 to 0.93) and was associated with a statistically insignificant decrease in myocardial infarction incidence (RR 0.90; 95% CI, 0.66 to 1.23). Postmenopausal women had greater risk increases for neoplastic outcomes. Conclusions: This meta-analysis of randomized trials found tamoxifen use to be significantly associated with several neoplastic and vascular outcomes. Consideration of tamoxifen use requires balance of potential benefits and risks. C1 Univ Pittsburgh, Dept Med, Div Gen Internal Med, Sect Clin Syst Modeling, Pittsburgh, PA 15213 USA. Harbor UCLA Res & Educ Inst, Torrance, CA USA. Tufts New England Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Gen Med, Boston, MA 02115 USA. RP Braithwaite, RS (reprint author), Univ Pittsburgh, Dept Med, Div Gen Internal Med, Sect Clin Syst Modeling, 933 W MUH,200 Lothrop St, Pittsburgh, PA 15213 USA. FU AHRQ HHS [R25 HS009796, R25-HS09796]; NLM NIH HHS [T15 LM007092, T15-LM07092-09] NR 62 TC 189 Z9 193 U1 0 U2 5 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 NOV PY 2003 VL 18 IS 11 BP 937 EP 947 DI 10.1046/j.1525-1497.2003.20724.x PG 11 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 743FW UT WOS:000186562600010 PM 14687281 ER PT J AU Kobza, PE Budoff, JE Yeh, ML Luo, ZP AF Kobza, PE Budoff, JE Yeh, ML Luo, ZP TI Management of the scaphoid during four-corner fusion - A cadaveric study SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE midcarpal fusion; partial wrist arthrodesis ID PROXIMAL ROW CARPECTOMY; WRIST; ARTHRODESIS; MOTION; JOINT AB Purpose: To examine the effects of scaphoid retention, inclusion, and excision on wrist motion and radiolunate contact characteristics in a cadaveric model after simulated 4-corner fusion with rigid, internal fixation. Methods: Seven. fresh-frozen cadaveric upper extremities were examined. For all surgical manipulations the motion was measured and contact characteristics were assessed using ultra-low prescale pressure-sensitive film. Results: Compared with the intact specimen, simple 4-corner fusion with scaphoid retention led to a significant decrease in extension, radial deviation, and ulnar deviation, but no change in radiolunate contact characteristics. After 4-corner fusion there was no significant difference in motion or radiolunate contact characteristics between scaphoid retention and scaphoid inclusion. After, 4-corner fusion scaphoid excision allowed significantly greater radial deviation compared with scaphoid retention and scaphoid inclusion. Compared with the intact specimen 4-corner fusion with-scaphoid excision also led to a significant increase in radiolunate contact area and mean contact pressure. Conclusions:. When performing 4-corner arthrodesis in the absence of radioscaphoid arthritis; scaphoid excision may improve motion at the cost of increased mean radiolunate contact pressure Copyright (C) 2003 by the American Society for Surgery of the Hand. C1 Baylor Coll Med, Dept Orthopaed Surg, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Houston, TX USA. RP Budoff, JE (reprint author), 6550 Fannin 2525, Houston, TX 77030 USA. NR 14 TC 10 Z9 13 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 NOV PY 2003 VL 28A IS 6 BP 904 EP 909 DI 10.1016/S0363-5023(03)00372-1 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 745VE UT WOS:000186710500004 PM 14642504 ER PT J AU Moreland, ME AF Moreland, ME TI Practitioner application SO JOURNAL OF HEALTHCARE MANAGEMENT LA English DT Editorial Material C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Moreland, ME (reprint author), VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL HEALTHCARE EXEC HEALTH ADMINISTRATION PRESS PI CHICAGO PA ONE NORTH FRANKLIN ST SUITE 1700, CHICAGO, IL 60606 USA SN 1096-9012 J9 J HEALTHC MANAG JI J. Healthc. Manag. PD NOV-DEC PY 2003 VL 48 IS 6 BP 406 EP 407 PG 2 WC Health Policy & Services SC Health Care Sciences & Services GA 746RZ UT WOS:000186762600010 ER PT J AU Cai, SH Davis, AE AF Cai, SH Davis, AE TI Complement regulatory protein C1 inhibitor binds to selectins and interferes with endothelial-leukocyte adhesion SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HEREDITARY ANGIONEUROTIC-EDEMA; INFLAMMATION-INDUCED EXPRESSION; CUTANEOUS LYMPHOCYTE ANTIGEN; SIALYL LEWIS(X); P-SELECTIN; ALPHA(1)-ACID GLYCOPROTEIN; C1-ESTERASE INHIBITOR; C1BAR INHIBITOR; CELLS; LIGAND AB C1 inhibitor (C1INH), a member of the serine proteinase inhibitor (serpin) family, is an inhibitor of proteases in the complement system, the contact system of kinin generation, and the intrinsic coagulation pathway. It is the most heavily glycosylated plasma protein, containing 13 definitively identified glycosylation sites as well as an additional 7 potential glycosylation sites. C1INH consists of two distinct domains: a serpin domain and an amino-terminal domain. The serpin domain retains all the protease-inhibitory function, while the amino-terminal domain bears most of the glycosylation sites. The present studies test the hypothesis that plasma C1INH bears sialyl Lewis(x)-related moieties and therefore binds to selectin adhesion molecules. We demonstrated that plasma C1INH does express sialyl Lewis(x)-related moieties on its N-glycan as detected using mAb HECA-452 and CSLEX1. The data also show that plasma C1INH can bind to P- and E-selectins by FACS and immunoprecipitation experiments. In a tissue culture model of endothelial-leukocyte adhesion, C1INH showed inhibition in a dose-dependent manner. Significant inhibition (>50%) was achieved at a concentration of 250 mug/ml or higher. This discovery may suggest that C1INH plays a role in the endothelial-leukocyte interaction during inflammation. It may also provide another example of the multifaceted anti-inflammatory effects of C1INH in various animal models and human diseases. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Davis, AE (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NICHD NIH HHS [HD33727, HD22082] NR 48 TC 57 Z9 59 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2003 VL 171 IS 9 BP 4786 EP 4791 PG 6 WC Immunology SC Immunology GA 735WD UT WOS:000186136800038 PM 14568956 ER PT J AU Rao, AR Quinones, MP Garavito, E Kalkonde, Y Jimenez, F Gibbons, C Perez, J Melby, P Kuziel, W Reddick, RL Ahuja, SK Ahuja, SS AF Rao, AR Quinones, MP Garavito, E Kalkonde, Y Jimenez, F Gibbons, C Perez, J Melby, P Kuziel, W Reddick, RL Ahuja, SK Ahuja, SS TI CC chemokine receptor 2 expression in donor cells serves an essential role in graft-versus-host-disease SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; ALLOREACTIVE T-CELLS; INTERFERON-GAMMA; ALLOGRAFT TOLERANCE; APLASTIC-ANEMIA; DENDRITIC CELLS; IFN-GAMMA; IN-VIVO; MICE AB The complete repertoire of cellular and molecular determinants that influence graft-vs-host disease (GVHD) is not known. Using a well-established murine model of GVHD (B6-->bm12 mice), we sought to elucidate the role of the donor non-T cell compartment and molecular determinants therein in the pathogenesis of GVHD. In this model the acute GVHD-inducing effects of purified B6 wild-type (wt) CD4(+) T cells was inhibited by wt non-T cells in a dose-dependent manner. Paradoxically, unlike the chronic GVHD phenotype observed in bm12 mice transplanted with B6wt unfractionated splenocytes, bm12 recipients of B6ccr2-null unfractionated splenocytes developed acute GVHD and died of IFN-gamma-mediated bone marrow aplasia. This switch from chronic to acute GVHD was associated with increased target organ infiltration of activated CD4(+) T cells as well as enhanced expression of Th1/Th2 cytokines, chemokines, and the antiapoptotic factor bfl1. In vitro, ccr2(-/-) CD4(+) T cells in unfractionated splenocytes underwent significantly less activation-induced cell death than B6wt CD4(+) T cells, providing another potential mechanistic basis along with enhanced expression of bfl1 for the increased numbers of activated T cells in target organs of B6ccr2(-/-) splenocyte-->bm12 mice. Collectively, these findings have important clinical implications, as they implicate the donor non-T cell compartment as a critical regulator of GVHD and suggest that ccr2 expression in this cellular compartment may be an important molecular determinant of activation-induced cell death and GVHD pathogenesis. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78284 USA. Vet Adm Ctr, Res AIDS & HIV Infect 1, San Antonio, TX 78229 USA. Univ Texas, Dept Mol Genet & Microbiol, Austin, TX 78712 USA. Univ Texas, Inst Mol & Cellular Biol, Austin, TX 78712 USA. RP Ahuja, SS (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr,MC 7870, San Antonio, TX 78229 USA. FU PHS HHS [A148644, 5K12C801723] NR 58 TC 27 Z9 28 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 NOV 1 PY 2003 VL 171 IS 9 BP 4875 EP 4885 PG 11 WC Immunology SC Immunology GA 735WD UT WOS:000186136800050 PM 14568968 ER PT J AU Atkins, M McDermott, D Mier, J Stanbridge, E Youmans, A Polivy, A Regan, M Connolly, C Signoretti, S AF Atkins, M McDermott, D Mier, J Stanbridge, E Youmans, A Polivy, A Regan, M Connolly, C Signoretti, S TI High carbonic anhydrase IX expression predicts for renal cancer response to IL-2 therapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 18th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2003 CL BETHESDA, MARYLAND C1 Harvard Univ, Dana Farber Canc Inst, Renal Canc Program Dev, Boston, MA 02115 USA. Univ Calif Irvine, Coll Med, Dept Microbiol, Irvine, CA 92717 USA. Univ Calif Irvine, Coll Med, Dept Mol Genet, Irvine, CA 92717 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2003 VL 26 IS 6 BP S39 EP S39 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 736UG UT WOS:000186191100123 ER PT J AU Warren, HS Matyal, R Allaire, JE Yarmush, D Loiselle, P Hellman, J Paton, BG Fink, MP AF Warren, HS Matyal, R Allaire, JE Yarmush, D Loiselle, P Hellman, J Paton, BG Fink, MP TI Protective efficacy of CAP18(106-138)-immunoglobulin G in sepsis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID GRAM-NEGATIVE BACTERIA; PERMEABILITY-INCREASING PROTEIN; POLYMYXIN-B; ESCHERICHIA-COLI; ANTILIPOPOLYSACCHARIDE FACTOR; MONOCLONAL-ANTIBODIES; NEUTRALIZING ACTIVITY; BIOLOGICAL-ACTIVITIES; HUMAN-NEUTROPHILS; IMMUNOGLOBULIN-G AB Naturally present antibacterial proteins play an important role in innate host defense. A synthetic peptide mimicking the C-terminal lipopolysaccharide (LPS)-binding domain of rabbit cathelicidin CAP18 was coupled to immunoglobulin (Ig) G to create CAP18(106-138)-IgG, a construct that, in concentrations equimolar to those of peptide alone, binds and neutralizes LPS and kills multiple gram-negative bacterial strains. The protective efficacy of CAP18(106-138)-IgG was evaluated in a model of cecal ligation and puncture in mice. A single intravenous administration of 20 mg/kg CAP18(106-138)-IgG protected against mortality, compared with sham-coupled IgG (P < .03). There was no protection offered by administration of equimolar peptide alone (P = .96). There was a trend toward protection in C3H/HeJ mice that are minimally sensitive to LPS (P = .06), suggesting that direct detoxification of LPS was not the only mechanism of protection. Chemical or genetic coupling of antimicrobial peptides to IgG may be a means of using these peptides to treat infections. C1 Massachusetts Gen Hosp, Dept Pediat & Med, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Shriners Burns Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. Massachusetts Eye & Ear Infirm, Microbiol Lab, Boston, MA 02114 USA. RP Warren, HS (reprint author), Massachusetts Gen Hosp E, Infect Dis Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIGMS NIH HHS [R01-GM59694] NR 44 TC 12 Z9 12 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2003 VL 188 IS 9 BP 1382 EP 1393 DI 10.1086/379081 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 739JM UT WOS:000186341400016 PM 14593598 ER PT J AU Soma, T Dohrmann, CE Hibino, T Raftery, LA AF Soma, T Dohrmann, CE Hibino, T Raftery, LA TI Profile of transforming growth factor-beta responses during the murine hair cycle SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE Smad; TSC-22; apoptosis; morphogenesis ID FOLLICLE REGRESSION CATAGEN; RECEPTOR TYROSINE KINASE; GLAND CANCER-CELLS; STIMULATED CLONE-22; SIGNAL-TRANSDUCTION; MOUSE DEVELOPMENT; IN-VIVO; TSC-22; EXPRESSION; APOPTOSIS AB Transforming growth factor-beta (TGF-beta) appears to promote the regression phase of the mammalian hair cycle, in vivo in mice and in organ culture of human hair follicles. To assess the relationship between TGF-beta activity and apoptosis of epithelial cells during the murine hair cycle, we identified active TGF-beta responses using phospho-Smad2/3-specific antibodies (PS2). Strong, nuclear PS2 staining was observed in the outer root sheath throughout the anagen growth phase. Some bulb matrix cells were positive for PS2 during late anagen. Extensive, but weak, staining was observed in this region at the anagen-catagen transition. We also examined expression of TGF-beta-stimulated clone-22 (TSC-22), which is associated with TGF-beta-induced apoptosis of some cell lines. Recombinant rat TSC-22 was used to generate a rabbit anti-TSC-22 antibody useful for immunohistochemistry. TSC-22 RNA accumulation and immunoreactivity were observed in follicles throughout the murine hair cycle, including the dermal papilla and lower epithelial strand of late-catagen hair follicles. Neither the expression pattern nor the presence of nuclear TSC-22 correlated with the sites of apoptosis, suggesting that TSC-22 is not an effector of apoptosis in mouse catagen hair follicles. These studies support a complex role for TGF-beta in regulating the regression phase of the cycle, with potential for indirect promotion of apoptosis during the anagen-catagen transition. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Shiseido Life Sci Res Ctr, Yokohama, Kanagawa, Japan. RP Raftery, LA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RI Raftery, Laurel/H-1406-2012 OI Raftery, Laurel/0000-0003-4797-4163 FU NIGMS NIH HHS [GM60501] NR 33 TC 23 Z9 23 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD NOV PY 2003 VL 121 IS 5 BP 969 EP 975 DI 10.1046/j.1523-1747.2003.12516.x PG 7 WC Dermatology SC Dermatology GA 739VM UT WOS:000186367200012 PM 14708594 ER PT J AU Egan, BM Basile, JN AF Egan, BM Basile, JN TI Controlling blood pressure in 50% of all hypertensive patients: An achievable goal in the healthy people 2010 report? SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article DE Healthy People 2010; hypertension; high blood pressure ID CORONARY HEART-DISEASE; AFRICAN-AMERICAN WOMEN; CARDIOVASCULAR-DISEASE; RESISTANT HYPERTENSION; SYSTOLIC HYPERTENSION; UNCONTROLLED HYPERTENSION; TIME-PREFERENCES; CONTROLLED TRIAL; OLDER PATIENTS; SELF-EFFICACY AB Background: One important objective defined in the Healthy People 2010 report was to improve blood pressure (BP) control to < 140/90 mm Hg in 50% of all hypertensive patients. Because the US population is becoming older, more obese, and ethnically diverse, the health and economic benefits of reaching this goal become more valuable each year. Hypertension control rates are currently at similar to31% of all hypertensives and have risen slowly and erratically since 1988. In the absence of a coordinated strategic plan, achieving this critically important goal for BP control is highly unlikely. Methods: A selected literature review was undertaken to briefly assess the cardiovascular benefits of controlling hypertension. Greater focus was placed on variables that impact hypertension awareness, treatment, and control. The impact on hypertension control rates of theoretic changes in awareness, treatment, and control individually and collectively was examined. Four categories of potential barriers to optimizing BP control are discussed: systems, provider, patient, and treatment factors. Results: Raising awareness to 80% of all hypertensives, ensuring treatment of 90% of aware hypertensives, and controlling BP to < 140/90 mm Hg in 70% of treated patients would achieve control rates of 50%. Conclusions: The barriers to achieving the Healthy People 2010 goal of controlling hypertension in 50% of all patients are formidable but appear to be resolvable with a coordinated strategic plan. Given projected demographic changes in the United States, the health and economic benefits of attaining the national goal for hypertension control would seem to merit a serious integrated effort. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Div Gen Internal Med Geriatr & Hypertens, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Primary Care Serv Line, Charleston, SC USA. RP Egan, BM (reprint author), Med Univ S Carolina, Dept Med, 96 Jonathan Lucas St, Charleston, SC 29425 USA. FU AHRQ HHS [P01HS1087-03]; NHLBI NIH HHS [HL04290]; NIMHD NIH HHS [P60-MD00267] NR 100 TC 16 Z9 18 U1 2 U2 3 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD NOV PY 2003 VL 51 IS 6 BP 373 EP 385 DI 10.2310/6650.2003.8979 PG 13 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 751XN UT WOS:000187115500017 PM 14686641 ER PT J AU Toledo, SE Toledo-Pereyra, LH AF Toledo, SE Toledo-Pereyra, LH TI Early American medicine SO JOURNAL OF INVESTIGATIVE SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Michigan State Univ, Kalamazoo Ctr Med Studies, Borgess Res Inst, Kalamazoo, MI USA. Michigan State Univ, Dept Surg, E Lansing, MI 48824 USA. RP Toledo, SE (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0894-1939 J9 J INVEST SURG JI J. Invest. Surg. PD NOV-DEC PY 2003 VL 16 IS 6 BP 311 EP 314 DI 10.1080/08941930390253275 PG 4 WC Surgery SC Surgery GA 753RU UT WOS:000187245000002 PM 14660329 ER PT J AU Paracchini, S Pearce, CL Kolonel, LN Altshuler, D Henderson, BE Tyler-Smith, C AF Paracchini, S Pearce, CL Kolonel, LN Altshuler, D Henderson, BE Tyler-Smith, C TI A Y chromosomal influence on prostate cancer risk: the multi-ethnic cohort study SO JOURNAL OF MEDICAL GENETICS LA English DT Article AB Background: A Y chromosomal role in prostate cancer has previously been suggested by both cytogenetic findings and patterns of Y chromosomal gene expression. We took advantage of the well established and stable phylogeny of the non- recombining segment of the Y chromosome to investigate the association between Y chromosomal DNA variation and prostate cancer risk. Methods: We examined the distribution of 116 Y lineages in 930 prostate cancer cases and 1208 controls from four ethnic groups from a cohort study in Hawaii and California. Results: One lineage, found only among the Japanese group in our study, was associated with a statistically significant predisposition to prostate cancer ( odds ratio ( OR) = 1.63; 95% confidence interval ( CI) 1.07 to 2.47), and, in particular, to high severity disease in younger individuals ( OR = 3.89; 95% CI 1.34 to 11.31). Conclusions: This finding suggests that a Y chromosomal factor contributes significantly to the development of prostate cancer in Japanese men. C1 Univ Oxford, Dept Biochem, Oxford OX1 3QU, England. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Zilkha Neurogenet Inst, Los Angeles, CA USA. Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Whitehead MIT Ctr Genome Res, Program Med & Populat Genet, Cambridge, MA 02139 USA. RP Tyler-Smith, C (reprint author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton CB10 1SA, Cambs, England. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 FU NCI NIH HHS [R01 CA63464, R01 CA54281] NR 17 TC 15 Z9 15 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1468-6244 J9 J MED GENET JI J. Med. Genet. PD NOV 1 PY 2003 VL 40 IS 11 BP 815 EP 819 DI 10.1136/jmg.40.11.815 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 745GY UT WOS:000186682000005 PM 14627670 ER PT J AU Del Monte, F AF Del Monte, F TI SR Ca2+ ATPase. Therapeutic target in diseased myocardium SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract CT Fetzer-Institute Conference on Religiosity and Substance Use CY MAY, 2002 CL KALAMAZOO, MI SP Fetzer Inst C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 NOV PY 2003 VL 35 IS 11 BP A14 EP A14 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 748DT UT WOS:000186847400043 ER PT J AU Matsui, T Nagoshi, T Rosenzweig, A AF Matsui, T Nagoshi, T Rosenzweig, A TI The multiple effects of Akt (PKB) in the heart SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract CT Fetzer-Institute Conference on Religiosity and Substance Use CY MAY, 2002 CL KALAMAZOO, MI SP Fetzer Inst C1 Massachusetts Gen Hosp, Program Cardiovasc Gene Therapy, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD NOV PY 2003 VL 35 IS 11 BP A14 EP A14 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 748DT UT WOS:000186847400045 ER PT J AU Mick, E Biederman, J Santangelo, S Wypij, D AF Mick, E Biederman, J Santangelo, S Wypij, D TI The influence of gender in the familial association between ADHD and major depression SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE ADHD; major depression; gender; family study ID ATTENTION-DEFICIT HYPERACTIVITY; CONDUCT DISORDER; BIPOLAR DISORDER; GENETIC-FACTORS; NORMAL PARENTS; RISK-FACTORS; COMORBIDITY; CHILDREN; GIRLS; RELATIVES AB This study estimated the impact of gender on the familial associations between attention-deficit/hyperactivity disorder (ADHD) and major depression (MD). The risk for ADHD and MD in first degree relatives was stratified by the presence of MD in boy and girl ADHD probands. In families ascertained via boy probands, the risk for MID was greater in the relatives of both the depressed ADHD and nondepressed ADHD probands. In families ascertained via girl probands, there was cosegregation and the risk of MD was greater only for those relatives of depressed ADHD probands. The results indicate that there may be two mechanisms underlying MD in ADHD families: 1) an etiologically distinct familial subtype of ADHD and MD that is more evident in females, and 2) a familial, gender-specific susceptibility to nonfamilial risk factors that mediate the onset of either ADHD or MD in males and females. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Charlestown, MA USA. RP Mick, E (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, 15 Parkman St,WACC 725, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145 FU NIMH NIH HHS [MH41314-08, MH-50657-04, 5T32MH17119] NR 44 TC 15 Z9 15 U1 1 U2 2 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 NOV PY 2003 VL 191 IS 11 BP 699 EP 705 DI 10.1097/01.nmd.0000095121.16728.26 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 748AD UT WOS:000186838600001 PM 14614336 ER PT J AU Ramdya, P Skoch, J Bacskai, BJ Hyman, BT Berezovska, O AF Ramdya, P Skoch, J Bacskai, BJ Hyman, BT Berezovska, O TI Activated Notch1 associates with a presenilin-1/gamma-secretase docking site SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE docking site; fluorescence lifetime imaging microscopy assay; fluorescence resonance energy transfer; gamma-secretase inhibitor; Notch1; presenilin-1 ID GAMMA-SECRETASE INHIBITORS; AMYLOID PRECURSOR PROTEIN; INTRACELLULAR DOMAIN; NUCLEAR-LOCALIZATION; PHYSICAL INTERACTION; SIGNAL-TRANSDUCTION; BETA-APP; PRESENILIN; CLEAVAGE; NICASTRIN AB Presenilin-1 (PS1), implicated as the active component of the gamma-secretase enzymatic complex, is known to cleave the cell surface receptor Notch1 after ligand binding. Here we directly visualize Notch1-PS1 interactions using a novel fluorescence lifetime imaging microscopy assay to monitor fluorescence resonance energy transfer. We demonstrate that endogenous Notch1 and PS1 move into close proximity at the cell surface after activation of Notch1 by the Delta1 ligand. A constitutively active N-terminally truncated form of Notch1, an immediate substrate of the gamma-secretase complex, similarly is found in close proximity to PS1. Interestingly, this interaction remains in the presence of a potent gamma-secretase active site inhibitor. Thus ligand binding to Notch1 appears to result in access of truncated Notch1 to a putative docking site on the PS1-gamma-secretase complex. These results suggest a novel mechanism of ligand binding-mediated signal transduction of Notch1. C1 Massachusetts Gen Hosp, Alzheimers Res Unit, Charlestown, MA 02129 USA. RP Berezovska, O (reprint author), Massachusetts Gen Hosp, Alzheimers Res Unit, Room 2750,114-16th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG15379] NR 35 TC 17 Z9 17 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2003 VL 87 IS 4 BP 843 EP 850 DI 10.1046/j.1471-4159.2003.02030.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 737QJ UT WOS:000186243000005 PM 14622115 ER PT J AU Montanez, S Daws, LC Gould, GG Frazer, A AF Montanez, S Daws, LC Gould, GG Frazer, A TI Serotonin (5-HT) transporter (SERT) function after graded destruction of serotonergic neurons SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE 5; 7-DHT; CA3 region of hippocampus; chronoamperometry; degeneration; rat; serotonin transporter ID IN-VIVO; RAT-BRAIN; EXTRACELLULAR DOPAMINE; ANIMAL-MODEL; CLEARANCE; STRIATUM; ANTIDEPRESSANTS; AUTORADIOGRAPHY; HIPPOCAMPUS; CITALOPRAM AB The degree of occupancy of the serotonin transporter (SERT) by selective serotonin reuptake inhibitors (SSRIs) appears to be critical in determining therapeutic response. To gain insight into the extent of occupancy required to alter serotonergic neurotransmission we used high-speed chronoamperometry to determine the extent of serotonergic destruction required to reduce the clearance of exogenously administered serotonin from extracellular fluid in the CA3 region of the hippocampus. Rats were pretreated with various doses of 5,7-dihydroxytryptamine to produce either a low, intermediate or high loss of SERTs. Clearance of 5-HT was reduced only in rats with > 90% loss of SERT. In these rats, there was also a trend for peak signal amplitudes to be greater. There was no significant difference in these parameters between the sham group and those with low or intermediate loss of SERTs. The SSRI, fluvoxamine, prolonged clearance of 5-HT in sham, low and intermediate groups, whereas there was no effect of fluvoxamine in those rats with > 90% loss of SERT. Functional loss of SERT activity occurs when destruction of serotonergic innervation is greater than 90% but serotonin clearance and efficacy of fluvoxamine is maintained with as few as one fifth of a full complement of SERTs. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Montanez, S (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, 7703 Floyd Curl Dr,MS 7792, San Antonio, TX 78229 USA. OI Gould, Georgianna/0000-0002-5470-8763 FU NIMH NIH HHS [MH57001, MH64489] NR 35 TC 16 Z9 17 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2003 VL 87 IS 4 BP 861 EP 867 DI 10.1046/j.1471-4159.2003.02032.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 737QJ UT WOS:000186243000007 PM 14622117 ER PT J AU Ahmadi, FA Linseman, DA Grammatopoulos, TN Jones, SM Bouchard, RJ Freed, CR Heidenreich, KA Zawada, WM AF Ahmadi, FA Linseman, DA Grammatopoulos, TN Jones, SM Bouchard, RJ Freed, CR Heidenreich, KA Zawada, WM TI The pesticide rotenone induces caspase-3-mediated apoptosis in ventral mesencephalic dopaminergic neurons SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE DEVD; dopamine neurons; midbrain; neurotoxin; Parkinson's disease; tyrosine hydroxylase ID CALCIUM-BINDING PROTEINS; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; BASAL GANGLIA; INHIBITION; CALBINDIN-D28K; DAMAGE; BRAIN; DEATH; MPTP AB In vivo, the pesticide rotenone induces degeneration of dopamine neurons and parkinsonian-like pathology in adult rats. In the current study, we utilized primary ventral mesencephalic (VM) cultures from E15 rats as an in vitro model to examine the mechanism underlying rotenone-induced death of dopamine neurons. After 11 h of exposure to 30 nm rotenone, the number of dopamine neurons identified by tyrosine hydroxylase (TH) immunostaining declined rapidly with only 23% of the neurons surviving. By contrast, 73% of total cells survived rotenone treatment, indicating that TH+ neurons are more sensitive to rotenone. Examination of the role of apoptosis in TH+ neuron death, revealed that 10 and 30 nm rotenone significantly increased the number of apoptotic TH+ neurons from 7% under control conditions to 38 and 55%, respectively. The increase in apoptotic TH+ neurons correlated with an increase in immunoreactivity for active caspase-3 in TH+ neurons. The caspase-3 inhibitor, DEVD, rescued a significant number of TH+ neurons from rotenone-induced death. Furthermore, this protective effect lasted for at least 32 h post-rotenone and DEVD exposure, indicating lasting neuroprotection achieved with an intervention prior to the death commitment point. Our results show for the first time in primary dopamine neurons that, at low nanomolar concentrations, rotenone induces caspase-3-mediated apoptosis. Understanding the mechanism of rotenone-induced apoptosis in dopamine neurons may contribute to the development of new neuroprotective strategies against Parkinson's disease. C1 Denver Vet Affairs Med Ctr, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Div Clin Pharmacol & Toxicol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Neurosci Program, Denver, CO 80262 USA. RP Zawada, WM (reprint author), Univ Colorado, Hlth Sci Ctr, Div Clin Pharmacol, 4200 E 9th Ave,C-237, Denver, CO 80262 USA. OI Grammatopoulos, Tom/0000-0001-7175-051X FU NIAAA NIH HHS [AA13473]; NINDS NIH HHS [NS 38619] NR 39 TC 66 Z9 69 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2003 VL 87 IS 4 BP 914 EP 921 DI 10.1046/j.1471-4159.2003.02068.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 737QJ UT WOS:000186243000012 PM 14622122 ER PT J AU Dudman, JT Eaton, ME Rajadhyaksha, A Macias, W Taher, M Barczak, A Kameyama, K Huganir, R Konradi, C AF Dudman, JT Eaton, ME Rajadhyaksha, A Macias, W Taher, M Barczak, A Kameyama, K Huganir, R Konradi, C TI Dopamine D1 receptors mediate CREB phosphorylation via phosphorylation of the NMDA receptor at Ser897-NR1 SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE calcium/calmodulin kinase; CREB; cyclic AMP; dopamine D1 receptor; NMDA; protein kinase A ID ELEMENT-BINDING PROTEIN; D-ASPARTATE RECEPTORS; EXCITATORY AMINO-ACIDS; RAT PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; BEHAVIORAL SENSITIZATION; GENE-EXPRESSION; CYCLIC-AMP; KINASE-A; STRIATAL NEURONS AB Addictive drugs such as amphetamine and cocaine stimulate the dopaminergic system, activate dopamine receptors and induce gene expression throughout the striatum. The signal transduction pathway leading from dopamine receptor stimulation at the synapse to gene expression in the nucleus has not been fully elucidated. Here, we present evidence that D1 receptor stimulation leads to phosphorylation of the transcription factor Ca2+ and cyclic AMP response element binding protein (CREB) in the nucleus by means of NMDA receptor-mediated Ca2+ signaling. Stimulation of D1 receptors induces the phosphorylation of Ser897 on the NR1 subunit by protein kinase A (PKA). This phosphorylation event is crucial for D1 receptor-mediated CREB phosphorylation. Dopamine cannot induce CRE-mediated gene expression in neurons transfected with a phosphorylation-deficient NR1 construct. Moreover, stimulation of D1 receptors or increase in cyclic AMP levels leads to an increase in cytosolic Ca2+ in the presence of glutamate, but not in the absence of glutamate, indicating the ability of dopamine and cyclic AMP to facilitate NMDA channel activity. The recruitment of the NMDA receptor signal transduction pathway by D1 receptors may provide a general mechanism for gene regulation that is fundamental for mechanisms of drug addiction and long-term memory. C1 McLean Hosp, Mailman Res Ctr, Lab Neuroplast, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Mol & Dev Neurosci Lab, Charlestown, MA USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Howard Hughes Med Inst, Baltimore, MD 21205 USA. RP Konradi, C (reprint author), McLean Hosp, Mailman Res Ctr, Lab Neuroplast, 115 Mill St, Belmont, MA 02478 USA. OI Dudman, Joshua/0000-0002-4436-1057 FU NIDA NIH HHS [DA07134, R01 DA007134, R01 DA007134-14] NR 84 TC 104 Z9 105 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2003 VL 87 IS 4 BP 922 EP 934 DI 10.1046/j.1471-4159.2003.02067.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 737QJ UT WOS:000186243000013 PM 14622123 ER PT J AU Maison, SF Emeson, RB Adams, JC Luebke, AE Liberman, MC AF Maison, SF Emeson, RB Adams, JC Luebke, AE Liberman, MC TI Loss of alpha CGRP reduces sound-evoked activity in the cochlear nerve SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID GENE-RELATED PEPTIDE; LATERAL-LINE ORGAN; NICOTINIC ACETYLCHOLINE-RECEPTOR; CROSSED OLIVOCOCHLEAR BUNDLE; SPIRAL MODIOLAR ARTERY; RAT CHROMAFFIN CELLS; CALCITONIN-GENE; GUINEA-PIG; HAIR CELL; ACOUSTIC INJURY AB alpha-Calcitonin gene-related peptide (alphaCGRP) is one of several neurotransmitters immunolocalized in the unmyelinated component of the cochlear efferent innervation, the lateral olivocochlear (OC) system, which makes axo-dendritic synapses with cochlear sensory neurons. In rodents, CGRP is also immunocolocalized in the myelinated medial OC system, which contacts cochlear outer hair cells (OHCs). To understand the role(s) of this neuropeptide in the OC system, we characterized the auditory phenotype of alphaCGRP-null mice. Cochlear threshold sensitivity was normal in mutant mice, both via a neural metric, the auditory brain stem response (ABR), and an OHC-based metric, distortion product otoacoustic emissions (DPOAEs). Medial OC function and resistance to acoustic injury were also unaffected by alphaCGRP deletion: the former was assessed by measuring cochlear response suppression with electrical stimulation of the OC bundle, the latter by measuring temporary threshold shifts after exposure to high level sound. However, significant abnormality in alphaCGRP-null mice was seen in the growth of cochlear neural responses with increasing stimulus level. This observation, contrasted with normal amplitude-versus-level functions for DPOAEs, is consistent with a selective, postsynaptic effect on cochlear neurons via alphaCGRP release from lateral OC terminals. This constitutes the most direct evidence to date for a functional role of the lateral OC system in the auditory periphery. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. Univ Miami, Sch Med, Dept Otolaryngol, Miami, FL 33136 USA. Univ Miami, Sch Med, Neurosci Program, Miami, FL 33136 USA. RP Maison, SF (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [P30 DC005209, R01 DC003086, R01 DC-0188] NR 68 TC 33 Z9 34 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV 1 PY 2003 VL 90 IS 5 BP 2941 EP 2949 DI 10.1152/jn.00596.2003 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 742ZH UT WOS:000186547600012 PM 12904337 ER PT J AU Groff, JA Liberman, MC AF Groff, JA Liberman, MC TI Modulation of cochlear afferent response by the lateral olivocochlear system: Activation via electrical stimulation of the inferior colliculus SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID GUINEA-PIG COCHLEA; SUPERIOR OLIVARY COMPLEX; AUDITORY-NERVE RESPONSE; HAIR CELL RESPONSES; EFFERENT INNERVATION; CAT COCHLEA; BLOOD-FLOW; ADRENERGIC INNERVATION; DE-EFFERENTATION; SERIAL SECTIONS AB The olivocochlear (OC) efferent innervation of the mammalian inner ear consists of two subdivisions, medial (MOC) and lateral (LOC), with different peripheral terminations on outer hair cells and cochlear afferent terminals, respectively. The cochlear effects of electrically activating MOC efferents are well known, i.e., response suppression effected by reducing outer hair cells' contribution to cochlear amplification. LOC peripheral effects are unknown, because their unmyelinated axons are difficult to electrically stimulate. Here, stimulating electrodes are placed in the inferior colliculus (IC) to indirectly activate the LOC system, while recording cochlear responses bilaterally from anesthetized guinea pigs. Shocks at some IC sites produced novel cochlear effects attributable to activation of the LOC system: long-lasting (5-20 min) enhancement or suppression of cochlear neural responses (compound action potentials and round window noise), without changes in cochlear responses dominated by outer hair cells (oto-acoustic emissions and cochlear microphonics). These novel effects also differed from classic MOC effects in their lack of dependence on the level and frequency of the acoustic stimulus. These effects disappeared on sectioning the entire OC bundle, but not after selective lesioning of the MOC tracts or the cochlea's autonomic innervation. We conclude that the LOC pathway comprises two functional subdivisions, capable of inducing slow increases or decreases in response magnitudes in the auditory nerve. Such a system may be useful in maintaining accurate binaural comparisons necessary for sound localization in the face of slow changes in interaural sensitivity. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Harvard MIT, Div Hlth Sci & Technol, Program Speech & Hearing Biosci & Technol, Cambridge, MA 02139 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, T32 DC-00038] NR 78 TC 75 Z9 80 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV 1 PY 2003 VL 90 IS 5 BP 3178 EP 3200 DI 10.1152/jn.00537.2003 PG 23 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 742ZH UT WOS:000186547600033 PM 14615429 ER PT J AU Nishida, S Sasaki, Y Murakami, I Watanabe, T Tootell, RBH AF Nishida, S Sasaki, Y Murakami, I Watanabe, T Tootell, RBH TI Neuroimaging of direction-selective mechanisms for second-order motion SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Review ID HUMAN VISUAL-CORTEX; NON-FOURIER MOTION; LATERAL OCCIPITAL COMPLEX; RAT FOREPAW STIMULATION; RESONANCE-IMAGING FMRI; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; HUMAN BRAIN ACTIVITY; AREA MT; FUNCTIONAL-ANALYSIS AB Psychophysical findings have revealed a functional segregation of processing for 1st-order motion (movement of luminance modulation) and 2nd-order motion (e.g., movement of contrast modulation). However neural correlates of this psychophysical distinction remain controversial. To test for a corresponding anatomical segregation, we conducted a new functional magnetic resonance imaging (fMRI) study to localize direction-selective cortical mechanisms for 1st- and 2nd-order motion stimuli, by measuring direction-contingent response changes induced by motion adaptation, with deliberate control of attention. The 2nd-order motion stimulus generated direction-selective adaptation in a wide range of visual cortical areas, including areas V1, V2, V3, VP, V3A, V4v, and MT+. Moreover, the pattern of activity was similar to that obtained with 1st- order motion stimuli. Contrary to expectations from psychophysics, these results suggest that in the human visual cortex, the direction of 2nd-order motion is represented as early as V1. In addition, we found no obvious anatomical segregation in the neural substrates for 1st- and 2nd-order motion processing that can be resolved using standard fMRI. C1 NTT Corp, NTT Commun Sci Labs, Kanagawa 2430198, Japan. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. RP Nishida, S (reprint author), NTT Corp, NTT Commun Sci Labs, 3-1 Morinosato Wakamiya, Kanagawa 2430198, Japan. EM nishida@brl.ntt.co.jp NR 108 TC 60 Z9 61 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 EI 1522-1598 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV 1 PY 2003 VL 90 IS 5 BP 3242 EP 3254 DI 10.1152/jn.00693.2003 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 742ZH UT WOS:000186547600038 PM 12917391 ER PT J AU D'Sa, C Klocke, BJ Cecconi, F Lindsten, T Thompson, CB Korsmeyer, SJ Flavell, RA Roth, KA AF D'Sa, C Klocke, BJ Cecconi, F Lindsten, T Thompson, CB Korsmeyer, SJ Flavell, RA Roth, KA TI Caspase regulation of genotoxin-induced neural precursor cell death SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE apoptosis; programmed cell death; Bcl-2; Bax; p53 ID CYTOCHROME-C RELEASE; CENTRAL-NERVOUS-SYSTEM; DEFICIENT MICE; BCL-2 FAMILY; STEM-CELLS; DNA-DAMAGE; P53-DEPENDENT APOPTOSIS; HIPPOCAMPAL-NEURONS; IN-VIVO; P53 AB Neural precursor cells (NPCs) critically regulate brain morphogenesis and recent studies have revealed an unexpectedly high frequency of NPC chromosomal abnormalities and apoptosis in the developing brain. We have shown previously that the apoptotic response of NPCs to genotoxic agents is dependent on p53 and caspase-9, but not Bax or caspase-3 expression. In this study, we found that NPCs deficient in Apaf-1, or both the pro-apoptotic multidomain Bcl-2 family members Bax and Bak, were resistant to cytosine arabinoside and gamma-irradiation-induced apoptosis. Inhibitors of gene transcription, protein translation, and caspase activity also blocked genotoxin-induced NPC apoptosis. Although caspase-3 and caspase-6 were both cleaved in response to DNA damage, neither of these effector caspases was critical for apoptosis. Genotoxin-induced NPC death was accompanied by the generation of reactive oxygen species and could be inhibited by several known antioxidants. Conversely, DNA damage-induced reactive oxygen species generation was inhibited significantly by gene disruption of p53, Apaf-1, or caspase-9, and combined deficiency of Bax and Bak, but not by caspase-3 or caspase-6 deficiency. These studies suggest that caspase-9 activation is both necessary and sufficient for genotoxin-induced neural precursor cell reactive oxygen species generation and death. (C) 2003 Wiley-Liss, Inc. C1 Univ Alabama, Sch Med, Div Neuropathol, Dept Pathol, Birmingham, AL 35294 USA. Univ Roma Tor Vergata, Dept Biol, Dulbecco Telethon Inst, Rome, Italy. Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. Univ Penn, Lab Med, Philadelphia, PA 19104 USA. Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. Univ Penn, Dept Canc Biol, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06510 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA. RP Roth, KA (reprint author), Univ Alabama, Sch Med, Div Neuropathol, Dept Pathol, 1530 3rd Ave S,SC961, Birmingham, AL 35294 USA. OI Cecconi, Francesco/0000-0002-5614-4359; Roth, Kevin/0000-0002-0643-995X FU NIDDK NIH HHS [DK07296]; NINDS NIH HHS [NS35107, NS41962]; Telethon [TCP99038] NR 76 TC 29 Z9 31 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD NOV 1 PY 2003 VL 74 IS 3 BP 435 EP 445 DI 10.1002/jnr.10738 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 739DD UT WOS:000186326200012 PM 14598320 ER PT J AU Jhawar, BS Fuchs, CS Colditz, GA Stampfer, MJ AF Jhawar, BS Fuchs, CS Colditz, GA Stampfer, MJ TI Sex steroid hormone exposures and risk for meningioma SO JOURNAL OF NEUROSURGERY LA English DT Article DE patient cohort; estrogen; meningioma; progesterone; prospective study; sex steroid; brain tumor ID NERVOUS-SYSTEM NEOPLASMS; LOS-ANGELES-COUNTY; BREAST-CANCER; INTRACRANIAL MENINGIOMAS; REPRODUCTIVE FACTORS; COLORECTAL-CANCER; MENOPAUSAL STATUS; BRAIN-TUMORS; US WOMEN; EPIDEMIOLOGY AB Object. The goal of this study was to investigate the risk of meningioma in relation to exogenous and endogenous sex hormones. Methods. The study participants were female registered nurses from I I US states who were between 30 and 55 years of age when they enrolled in the Nurses' Health Study cohort. These women completed biennial questionnaires between 1976 and 1996. All participants were free from cancer and other major medical illness at the onset of the study. The primary endpoint was meningioma as self-reported in biennial and supplemental questionnaires. During 1,213,522 person-years of follow-up review, 125 cases of meningioma were confirmed. After adjusting for age and body mass index (BMI), compared with postmenopausal women who had never used postmenopausal hormones, the relative risk (RR) for premenopausal women was 2.48 (95% confidence interval [CI] 1.29-4.77; p = 0.01) and the RR for postmenopausal women who received hormone therapy was 1.86 (95% CI 1.07-3.24; p = 0.03). The authors found no excess risk associated with past hormone use. In models that additionally controlled for hormone use and menopausal status, the authors found that, compared with women whose menarche occurred before they were 12 years of age, the RR for women whose menarche occurred at ages 12 through 14 years was 1.29 (95% CI 0.86-1.92; p = 0.21) and the RR for women whose menarche occurred after age 14 years was 1.97 (95% Cl 1.06-3.66; p = 0.03). The authors also observed a tendency, albeit nonsignificant, for increased risk of meningioma in parous as opposed to nulliparous women (multivariate RR = 2.39, 95% Cl 0.76-7.53; p = 0.14). A trend toward an increasing risk of meningioma with increasing BMI was also noted (p for trend = 0.06). No association was found for past or current use of oral contraceptives. Conclusions. The risk for meningiomas was increased among women exposed to either endogenous or exogenous sex hormones. An unexpected relationship with increasing age at menarche was also noted; this remains unexplained. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Jhawar, BS (reprint author), Univ Western Ontario, London Hlth Sci Ctr, Dept Neurosurg, London, ON N6A 5A5, Canada. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA 87969] NR 42 TC 72 Z9 76 U1 1 U2 2 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 NOV PY 2003 VL 99 IS 5 BP 848 EP 853 DI 10.3171/jns.2003.99.5.0848 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 737MY UT WOS:000186237400011 PM 14609164 ER PT J AU Eskandar, EN Flaherty, A Cosgrove, GR Shinobu, LA Barker, FG AF Eskandar, EN Flaherty, A Cosgrove, GR Shinobu, LA Barker, FG TI Surgery for Parkinson disease in the United States, 1996 to 2000: practice patterns, short-term outcomes, and hospital charges in a nationwide sample SO JOURNAL OF NEUROSURGERY LA English DT Article DE Parkinson disease; pallidotomy; deep brain stimulation; hospital case volume; outcome ID DEEP-BRAIN-STIMULATION; HIGH-FREQUENCY STIMULATION; SUBTHALAMIC NUCLEUS STIMULATION; POSTEROVENTRAL PALLIDOTOMY; GLOBUS-PALLIDUS; FOLLOW-UP; STEREOTAXIC PALLIDOTOMY; UNILATERAL PALLIDOTOMY; SUBARACHNOID HEMORRHAGE; CAROTID-ENDARTERECTOMY AB Object. The surgical treatment of Parkinson disease (PD) has undergone a dramatic shift, from stereotactic ablative procedures toward deep brain stimulaion (DBS). The authors studied this process by investigating practice patterns, mortality and morbidity rates, and hospital charges as reflected in the records of a representative sample of US hospitals between 1996 and 2000. Methods. The authors conducted a retrospective cohort study by using the Nationwide Inpatient Sample database; 1761 operations at 71 hospitals were studied. Projected to the US population, there were 1650 inpatient procedures performed for PD per year (pallidotomies, thalamotomies, and DBS), with no significant change in the annual number of procedures during the study period. The in-hospital mortality rate was 0.2%, discharge other than to home was 8.1%, and the rate of neurological complications was 1.8%, with no significant differences between procedures. In multivariate analyses, hospitals with larger annual caseloads had lower mortality rates (p = 0.002) and better outcomes at hospital discharge (p = 0.007). Placement of deep brain stimulators comprised 0% of operations in 1996 and 88% in 2000. Factors predicting placement of these devices in analyses adjusted for year of surgery included younger age, Caucasian race, private insurance, residence in higher-income areas, hospital teaching status, and smaller annual hospital caseload. In multivariate analysis, total hospital charges were 2.2 times higher for DBS (median $36,000 compared with $12,000, p < 0.001), whereas charges were lower at higher-volume hospitals (p < 0.001). Conclusions. Surgical treatment of PD in the US changed significantly between 1996 and 2000. Larger-volume hospitals had superior short-term outcomes and lower charges. Future studies should address long-term functional end points, cost/benefit comparisons, and inequities in access to care. C1 Harvard Univ, Brain Tumor Ctr, Massachusetts Gen Hosp, Sch Med,Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Brain Tumor Ctr, Massachusetts Gen Hosp, Sch Med,Dept Neurol, Boston, MA 02114 USA. RP Barker, FG (reprint author), Harvard Univ, Brain Tumor Ctr, Massachusetts Gen Hosp, Sch Med,Dept Neurosurg, Cox 315,Fruit St, Boston, MA 02114 USA. NR 71 TC 46 Z9 46 U1 0 U2 2 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 NOV PY 2003 VL 99 IS 5 BP 863 EP 871 DI 10.3171/jns.2003.99.5.0863 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 737MY UT WOS:000186237400013 PM 14609166 ER PT J AU Ponte, PR Branowicki, P Somerville, J Anderson, D Erickson, JI Kruger, N Sporing, E Connaughton, M Conlin, G AF Ponte, PR Branowicki, P Somerville, J Anderson, D Erickson, JI Kruger, N Sporing, E Connaughton, M Conlin, G TI Collaboration among nurse executives in complex environments - Fostering administrative best practice SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article C1 Dana Farber Canc Inst, Patient Care Serv, Boston, MA 02115 USA. Brigham & Womens Hosp, Patient Care Serv, Boston, MA 02115 USA. Childrens Hosp, Med Patient Serv, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Med Ctr, Patient Care Serv, New York, NY 10003 USA. Connaughton Consulting, Newton, MA USA. RP Ponte, PR (reprint author), Dana Farber Canc Inst, Patient Care Serv, 44 Binney St, Boston, MA 02115 USA. NR 10 TC 1 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD NOV PY 2003 VL 33 IS 11 BP 596 EP 602 DI 10.1097/00005110-200311000-00009 PG 7 WC Nursing SC Nursing GA 745VP UT WOS:000186711400009 PM 14608218 ER PT J AU Rhodes, D Spiro, A Aro, A Hu, H AF Rhodes, D Spiro, A Aro, A Hu, H TI Relationship to bone and blood lead levels to psychiatric symptoms: The normative aging study SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID X-RAY-FLUORESCENCE; PHEOCHROMOCYTOMA PC12 CELLS; TYROSINE-HYDROXYLASE; INORGANIC LEAD; CYCLIC-AMP; EXPOSURE; WORKERS; BURDEN; SYNAPTOSOMES; PREVALENCE AB Blood and bone. lead levels were used to investigate lead's potential effect on psychiatric symptoms among middle-aged to elderly men from the Normative Aging Study. Symptoms were assessed using the Brief Symptom Inventory (BSI) and analyzed as individual outcomes as well as a measure that combined anxiety, depression, and phobic anxiety. Blood and bone lead averaged 6.3 mug/dL (standard deviation [SD] = 4.16), 21.9 mug/g (SD = 13.5), and 32.1 mug/g (SD = 19.8) for blood, tibia, and patella lead, respectively. In logistic regression models that adjusted for age, alcohol intake, employment status, and education status, we found that patella bone lead was significantly associated with an increased risk of phobic anxiety and the combined outcome measure at the P less than or equal to 0.05 level. Tibia and blood lead hod similar associations. We conclude that cumulative lead exposure, which bone lead levels reflect, could be a risk factor for psychiatric symptoms even at modest levels of exposure. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. VA Boston Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. RP Rhodes, D (reprint author), 255 Broadway,2, Cambridge, MA 02139 USA. FU NCRR NIH HHS [M01RR02635]; NIEHS NIH HHS [2 P30 ES00002, 5 P42 ES05947, ES03918-02, ES 05257] NR 34 TC 33 Z9 33 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD NOV PY 2003 VL 45 IS 11 BP 1144 EP 1151 DI 10.1097/01.jom.0000094995.23808.7b PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 743CY UT WOS:000186555900004 PM 14610395 ER PT J AU Chou, R Clark, E Helfand, M AF Chou, R Clark, E Helfand, M TI Comparative efficacy and safety of long-acting oral Opioids for chronic non-cancer pain: A systematic review SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Review DE analgesics; opioid; pain; meta-analysis; fentanyl; morphine; oxycodone; codeine ID CHRONIC NONMALIGNANT PAIN; PLACEBO-CONTROLLED-TRIAL; CONTROLLED-RELEASE OXYCODONE; TRANSDERMAL FENTANYL; NEUROPATHIC PAIN; DOUBLE-BLIND; POSTHERPETIC NEURALGIA; RANDOMIZED TRIAL; SUBSTANCE-ABUSE; CANCER PAIN AB Opioids have been endorsed as appropriate treatment for refractory chronic non-cancer pain when used according to published guidelines. They are widely used for this indication. However, there appear to be gaps in our understanding of the efficacy and safety of individual long acting opioids compared to each other or as a class compared to short-acting opioids. This systematic review summarizes and assesses the evidence for the comparative efficacy and safety of long acting opioids in the management of chronic non,efficacy and adverse events) and cancer pain. Randomized trials (for comparative observational studies (for adverse events only) that included non-parenteral long-acting opioids were sought using electronic databases, handsearching reference lists, and soliciting pharmaceutical company submissions. Searches were performed through October 2002. The validity of each included study was assessed using a data abstraction form and predefined criteria. An overall grade was allocated for the body of evidence for each key question. A total of 16 randomized trials (comparative efficacy and adverse events), enrolling 1427 patients, and 8 observational studies (adverse events) of 1190 patients were included in this review. No randomized trial was rated good quality; observational studies were generally of poorer quality than the trials. There was insufficient evidence to prove that different long-acting opioids are associated with different efficacy or safety profiles. There was also insufficient evidence to determine whether long-acting opioids as a class are more effective or safer than short-acting opioids. A subgroup of three studies on long acting versus short-acting oxycodone was more homogeneous and provided fair evidence that these formulations are equally effective for pain control. (C) 2003 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved. C1 Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Family Med, Portland, OR 97201 USA. Oregon Evidence Based Practice Ctr, Portland, OR USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Chou, R (reprint author), 9721 SW Morrison St, Portland, OR 97225 USA. NR 42 TC 114 Z9 117 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD NOV PY 2003 VL 26 IS 5 BP 1026 EP 1048 DI 10.1016/j.jpainsymman.2003.03.003 PG 23 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 740WZ UT WOS:000186426400006 PM 14585554 ER PT J AU Kearns, GL Winter, TS AF Kearns, GL Winter, TS TI Proton pump inhibitors in pediatrics: Relevant pharmacokinetics and pharmacodynamics SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article; Proceedings Paper CT Conference on Treatment of Pediatric Gastroesophageal Reflux Disease CY DEC 06-08, 2000 CL WASHINGTON, D.C. DE cytochrome P450; genetic polymorphism; pediatries; pharmacodynamics; pharmacokinetics; proton pump inhibitors ID INTRAGASTRIC ACIDITY; S-MEPHENYTOIN; OMEPRAZOLE; CHILDREN; PANTOPRAZOLE; LANSOPRAZOLE; METABOLISM; CYTOCHROME-P450; RABEPRAZOLE; EFFICACY AB A marked discordance between the disposition of proton pump inhibitors (PPIs) in plasma and the kinetics of effect suggests the need for new approaches to characterize the clinical pharmacology of PPIs in infants and children. An assessment of pharmacokinetics and pharmacodynamics must take into account the genetic polymorphism of CYP2C19 and the impact of ontogeny on the activity of this and other enzymes (e.g., CYP3A4) which affect the biotransformation of the PPIs and, thus, their plasma clearance. In addition, the potential effects of extemporaneous formulations of the drugs on their rate and extent of absorption must be considered. Because of the apparent safety of PPIs and a well-demonstrated dose-response-effect relationship in adults, pediatric pharmacokinetic data and an exposure correlate, such as the dose-area-under-the-plasma-concentration-versus-time-curve relationship, can be used as a bridge to determine pediatric dosing. C1 Childrens Mercy Hosp & Clin, Div Pediat Pharmacol & Med Toxicol, Kansas City, MO 64108 USA. Univ Missouri, Missouri Chair Pediat Pharmacol, Kansas City, MO 65211 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. MassGen Hosp Children, Boston, MA USA. RP Kearns, GL (reprint author), Childrens Mercy Hosp & Clin, Div Pediat Pharmacol & Med Toxicol, 2401 Gillham Rd, Kansas City, MO 64108 USA. NR 24 TC 27 Z9 28 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD NOV-DEC PY 2003 VL 37 SU 1 BP S52 EP S59 DI 10.1097/00005176-200311001-00011 PG 8 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 739YW UT WOS:000186368100011 PM 14685079 ER PT J AU Koski, G AF Koski, G TI Changing the paradigm: New directions in federal oversight of human research SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article; Proceedings Paper CT Conference on Treatment of Pediatric Gastroesophageal Reflux Disease CY DEC 06-08, 2000 CL WASHINGTON, D.C. DE research ethics; clinical research oversight; office for human research protections; protection of human subjects in research AB The system of institutional review boards (IRBs) was established about 30 years ago for the protection of human subjects and as a mechanism for assuring an independent peer review of research activities. To keep pace with an evolving environment, a new model for human research oversight is needed that focuses less on achieving regulatory compliance and more on applying our conscience to the responsible conduct of research. The recent implementation of a unified federal registration system for IRBs and a new assurance system point the way to a more effective structure for the oversight of clinical trials. C1 Off Human Res Protect, Dept Hlth, Washington, DC USA. Off Human Res Protect, Human Serv, Washington, DC USA. RP Koski, G (reprint author), Massachusetts Gen Hosp, 32 Fruit St, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD NOV-DEC PY 2003 VL 37 SU 1 BP S2 EP S6 DI 10.1097/00005176-200311001-00002 PG 5 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 739YW UT WOS:000186368100002 PM 14685070 ER PT J AU Binstadt, BA Caldas, AMC Turvey, SE Weinstein, HJ Jackson, J Fuhlbrigge, RC Sundel, RP AF Binstadt, BA Caldas, AMC Turvey, SE Weinstein, HJ Jackson, J Fuhlbrigge, RC Sundel, RP TI Rituximab therapy for multisystem autoimmune diseases in pediatric patients SO JOURNAL OF PEDIATRICS LA English DT Article ID ANTI-CD20 MONOCLONAL-ANTIBODY; SYSTEMIC-LUPUS-ERYTHEMATOSUS; COLD AGGLUTININ DISEASE; NON-HODGKINS-LYMPHOMA; HEMOLYTIC-ANEMIA; ANTIPHOSPHOLIPID-SYNDROME; B-CELLS; CHOREA; IDEC-C2B8; CHILDHOOD AB Objective: To evaluate the effects of rituximab (anti-CD20 monoclonal antibody) on the disease course in pediatric patients with multisystem autoimmune diseases. Methods: Four patients with multisystem autoimmune diseases refractory to conventional immunosuppressive medications, each with central nervous system (CNS) involvement, were treated with four weekly infusions of rituximab. Their clinical and laboratory responses were evaluated. Results: Each of the patients had improvement in clinical symptoms and laboratory parameters. One patient with autoimmune cytopenias and autoimmune CNS and peripheral nervous system disease had resolution of the cytopenias and marked improvement in neurologic symptoms; he currently receives no immunosuppressive medications. Two half-siblings with lymphoplasmacytic colitis, pulmonary nodules, and CNS disease had improvement of their symptoms. A fourth patient with chorea and seizures secondary to primary antiphospholipid antibody syndrome had improvement in fine and gross motor function and reduced seizure frequency. There were no serious adverse events. Conclusions: The biologic response modifier rituximab, designed to eliminate B lymphocytes, was safe and effective in four pediatric patients with multisystem autoimmune disorders. It appears to be beneficial in autoimmune conditions presumably mediated by a variety of B-cell-related mechanisms, and may decrease or eliminate the need for other immunosuppressive medications. C1 Childrens Hosp, Div Immunol, Rheumatol Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Pediat Hematol Oncol Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Rheumatol, Boston, MA 02115 USA. Univ Fed Sao Paulo, Escola Paulista Med, Div Allergy Immunol & Rheumatol, Sao Paulo, Brazil. RP Sundel, RP (reprint author), Childrens Hosp, Div Immunol, Rheumatol Program, 300 Longwood Ave, Boston, MA 02115 USA. EM robert.sundel@tch.harvard.edu RI Binstadt, Bryce/N-1305-2013; OI Binstadt, Bryce/0000-0003-3127-3856; Sundel, Robert/0000-0002-0083-5695; Turvey, Stuart/0000-0003-1599-1065 NR 29 TC 26 Z9 30 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 NOV PY 2003 VL 143 IS 5 BP 598 EP 604 DI 10.1067/S0022-3476(03)00382-2 PG 7 WC Pediatrics SC Pediatrics GA 745VR UT WOS:000186711700014 PM 14615729 ER PT J AU Chae, JH Nahas, Z Lomarev, M Denslow, S Lorberbaum, JP Bohning, DE George, MS AF Chae, JH Nahas, Z Lomarev, M Denslow, S Lorberbaum, JP Bohning, DE George, MS TI A review of functional neuroimaging studies of vagus nerve stimulation (VNS) SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Review DE vagus nerve stimulation (VNS); functional neuroimaging; positron emission tomography (PET); single-photon emission computed tomography (SPECT); functional magnetic resonance imaging (fMRI) ID CEREBRAL BLOOD-FLOW; RESISTANT DEPRESSION; REFRACTORY EPILEPSY; SLEEP-DEPRIVATION; NEURONAL-ACTIVITY; MAJOR DEPRESSION; BRAIN; ACTIVATION; CORTEX; SPECT AB Vagus nerve stimulation (VNS) is a new method for preventing and treating seizures, and shows promise as a potential new antidepressant. The mechanisms of action of VNS are still unknown, although the afferent direct and secondary connections of the vagus nerve are well established and are the most likely route of VNS brain effects. Over the past several years, many groups have used functional brain imaging to better understand VNS effects on the brain. Since these studies differ somewhat in their methodologies, findings and conclusions, at first glance, this literature may appear inconsistent. Although disagreement exists regarding the specific locations and the direction of brain activation, the differences across studies are largely due to different methods, and the results are not entirely inconsistent. We provide an overview of these functional imaging studies of VNS. PET (positron emission tomography) and SPECT (single photon emission computed tomography) studies have implicated several brain areas affected by VNS, without being able to define the key structures consistently and immediately activated by VNS. BOLD (blood oxygen level dependent) fMRI (functional magnetic resonance imaging), with its relatively high spatio-temporal resolution, performed during VNS, can reveal the location and level of the brain's immediate response to VNS. As a whole, these studies demonstrate that VNS causes immediate and longer-term changes in brain regions with vagus innervations and which have been implicated in neuropsychiatric disorders. These include the thalamus, cerebellum, orbitofrontal cortex, limbic system, hypothalamus, and medulla. Functional neuroimaging studies have the potential to provide greater insight into the brain circuitry behind the activity of VNS. (C) 2003 Elsevier Ltd. All rights reserved. C1 Med Univ S Carolina, Ctr Adv Imaging Res, Charleston, SC 29425 USA. Med Univ S Carolina, Brain Stimulat Lab, Charleston, SC 29425 USA. Catholic Univ Korea, Dept Psychiat, Seoul, South Korea. Inst Human Brain, St Petersburg, Russia. Ralph H Johnson Vet Hosp, Charleston, SC USA. RP George, MS (reprint author), Inst Psychiat, Brain Stimulat Lab, 67 President St,Room 502 N, Charleston, SC 29425 USA. NR 64 TC 90 Z9 91 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD NOV-DEC PY 2003 VL 37 IS 6 BP 443 EP 455 DI 10.1016/S0022-3956(03)00074-8 PG 13 WC Psychiatry SC Psychiatry GA 737NY UT WOS:000186239700001 PM 14563375 ER PT J AU Robinson-Whelen, S Rintala, DH AF Robinson-Whelen, S Rintala, DH TI Informal care providers for veterans with SCI: Who are they and how are they doing? SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE caregivers; long-term care; spinal cord injuries ID SPINAL-CORD-INJURY; LIFE SATISFACTION; DISABILITY; OUTCOMES; MODEL AB Veterans with spinal cord injury (SCI) who received care at the Houston Department of Veterans Affairs Medical Center were interviewed about their use of formal and informal assistance to meet their daily physical needs. Informal caregivers were found to play an important role in the daily care of veterans with SCI, with 37% receiving some informal, unpaid assistance with personal care. Primary informal caregivers were mostly women, had a mean age of 53, and provided an average of almost 12 hours of care a day. Nearly one-third of participants rated their primary caregiver as being only in fair or poor health, and one-fourth thought their caregiver was unlikely to be able to provide the same level of care 5 years from now. Of particular concern, more than half reported that they did not have anyone else willing and able to provide assistance if their primary family caregiver became permanently unable to care for them. C1 VA Med Ctr, Dept Vet Affairs, VA Rehabil Res & Dev Serv, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP Robinson-Whelen, S (reprint author), Houston VAMC 153, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 19 TC 10 Z9 10 U1 1 U2 1 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD NOV-DEC PY 2003 VL 40 IS 6 BP 511 EP 516 DI 10.1682/JRRD.2003.11.0511 PG 6 WC Rehabilitation SC Rehabilitation GA 753JD UT WOS:000187227500012 PM 15077663 ER PT J AU Ang, HTS Helfgott, S AF Ang, HTS Helfgott, S TI Do the clinical responses and complications following etanercept or infliximab therapy predict similar outcomes with the other tumor necrosis factor-alpha antagonists in patients with rheumatoid arthritis? SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE rheumatoid arthritis; etanercept; infliximab; class effect ID METHOTREXATE; TRIAL AB Objective. To study a group of 29 patients with rheumatoid arthritis (RA) who have been treated with both tumor necrosis factor (TNF)-alpha antagonists, etanercept and infliximab and to determine the correlation of responses and complications seen in these patients. Methods. Patients' responses to and complications from either treatment were reviewed retrospectively by determining the joint counts, acute phase reactants, as well as occurrences of infection, hypersensitivity, and cytopenia. The correlation of responses and complications was determined using phi coefficients and exact p values. Results. There was no correlation between the joint count responses (exact p value for correlation coefficient, 0.70) and acute phase reactant responses (exact p value 0.14) with the use of etanercept and infliximab in the same patient. There was no correlation between the occurrences of drug hypersensitivity reactions (exact p value 0.20) or infectious complications (exact p value 1.00). However, the occurrence of anemia with the use of one TNF-alpha antagonist was correlated with a similar occurrence with the use of the other antagonist (exact p value 0.007). Conclusion. Our study indicates that patients who fail to respond to one TNF-alpha antagonist can respond to the other antagonist. Furthermore, there appears to be no contraindication to using one TNF-alpha antagonist for patients who have developed hypersensitivity reactions to the other. The infections observed in our study were generally mild and did not necessarily recur with the use of the second antagonist. In contrast, anemia, when present with the use of one agent, was likely to occur with the use of the second agent. C1 Brigham & Womens Hosp, Dept Med, Div Rheumatol, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Div Allergy & Immunol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Ang, HTS (reprint author), Brigham & Womens Hosp, Dept Med, Div Rheumatol, 133 Brookline Ave, Boston, MA 02215 USA. FU NIAMS NIH HHS [AR 07258-24] NR 15 TC 63 Z9 65 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD NOV PY 2003 VL 30 IS 11 BP 2315 EP 2318 PG 4 WC Rheumatology SC Rheumatology GA 743BX UT WOS:000186553500006 PM 14677170 ER PT J AU Bertagnolli, MM AF Bertagnolli, MM TI Guest editorial - The potential of non-steroidal anti-inflammatory drugs (NSAIDs) for colorectal cancer prevention SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Editorial Material ID FAMILIAL ADENOMATOUS POLYPOSIS; CYCLOOXYGENASE-2 INHIBITORS; INTESTINAL POLYPOSIS; ENDOTHELIAL-CELLS; INDUCED APOPTOSIS; COLON-CANCER; SULINDAC; PROSTAGLANDINS; TUMORIGENESIS; TARGET C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bertagnolli, MM (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. NR 53 TC 9 Z9 9 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 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD NOV PY 2003 VL 84 IS 3 BP 113 EP 119 DI 10.1002/jso.10279 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 739EP UT WOS:000186330300002 PM 14598353 ER PT J AU Tsao, H Mihm, MC Sheehan, C AF Tsao, H Mihm, MC Sheehan, C TI PTEN expression in normal skin, acquired melanocytic nevi, and cutaneous melanoma SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID TUMOR-SUPPRESSOR GENE; MALIGNANT-MELANOMA; PTEN/MMAC1 ALTERATIONS; PHOSPHATASE-ACTIVITY; GERMLINE MUTATIONS; COWDEN-DISEASE; BREAST-CANCER; CELL-LINES; PROGRESSION; PROTEIN AB Background: Although various studies have shown mutations of the tumor suppressor gene, PTEN/MMAC1, in primary, metastatic, and cultured cutaneous melanoma specimens, little is known about the pattern of PTEN protein expression in early melanocytic tumor progression. Objective: To further investigate the role of PTEN in melanocytic tumor development. Methods: We assessed the level and distribution of PTEN in normal skin, 39 acquired melanocytic nevi, and 30 primary cutaneous melanomas, including lentigo malignas, by immunostaining. Results: We found high levels of PTEN expression in cutaneous muscles, nerves, and muscular arteries, and moderate-to-high amounts of PTEN in the epidermis, follicular epithelium, and sebaceous and eccrine glands. PTEN staining in cutaneous lymphatics, dermal and periadnexal adventitial fibroblasts, and chondrocytes were variably absent. junctional melanocytes and chondrocytes frequently exhibited preferential nuclear staining. We found uniformly strong PTEN expression in the cytoplasm of almost all benign and dysplastic nevi. However, there was some evidence of nuclear PTEN loss even in the benign melanocytic proliferations in addition, Out of 30 primary cutaneous melanomas and lentigo malignas, we detected diffuse expression of PTEN in 11 (37%) tumors, widespread loss of PTEN in 11 (37%) tumors and mixed PTEN expression in 8 (27%) lesions. In the primary cutaneous melanomas, PTEN was largely localized to the cytoplasm. Conclusions: The presence of PTEN in benign melanocytic tumors and the absence of PTEN in a significant proportion of primary cutaneous melanomas support a role for PTEN loss in the pathogenesis of melanoma. C1 Harvard Univ, Dept Dermatol, Massachusetts Gen Hosp, Sch Med,Wellman Lab Photomed, Boston, MA 02114 USA. Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02114 USA. Albany Med Ctr, Dept Pathol, Albany, NY USA. RP Tsao, H (reprint author), Harvard Univ, Dept Dermatol, Massachusetts Gen Hosp, Sch Med,Wellman Lab Photomed, Bartlett 622,48 Blossom St, Boston, MA 02114 USA. NR 26 TC 65 Z9 66 U1 0 U2 4 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 NOV PY 2003 VL 49 IS 5 BP 865 EP 872 DI 10.1067/S0190-9622(03)02473-3 PG 8 WC Dermatology SC Dermatology GA 737NE UT WOS:000186238000010 PM 14576666 ER PT J AU Bevona, C Tannous, M Tsao, H AF Bevona, C Tannous, M Tsao, H TI Dermal melanocytic proliferation with features of a plaque-type blue nevus and neurocristic hamartoma SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID MELANOMA AB Blue nevi (BN) and neurocristic hamartomas (NCH) are pigmented lesions that originate from the aberrant development of cells derived from the neural crest. BN are composed of dermal melanocytes, whereas NCH have a broader histology and show Schwann cell differentiation as well. In addition, BN and NCH might differ in their potential to develop into a malignancy. We describe a patient with a lesion showing features of both a plaque-type BN and NCH. C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Labs, Boston, MA 02114 USA. Boston Univ, Dept Dermatol, Boston, MA 02215 USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Bartlett 622,48 Blossom St, Boston, MA 02114 USA. NR 17 TC 24 Z9 24 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD NOV PY 2003 VL 49 IS 5 BP 924 EP 929 DI 10.1067/S0190-9622(03)00477-8 PG 6 WC Dermatology SC Dermatology GA 737NE UT WOS:000186238000026 PM 14576682 ER PT J AU Vig, EK Pearlman, RA AF Vig, EK Pearlman, RA TI Quality of life while dying: A qualitative study of terminally ill older men SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE quality of life; attitude to death; terminal care; patient-centered care; qualitative research ID ADVANCE DIRECTIVES; FAMILY MEMBERS; PATIENTS PERSPECTIVES; CONTROLLED-TRIAL; CARE; END; DEATH; PERCEPTIONS; PREFERENCES; CANCER AB OBJECTIVES: To characterize the experience of quality of life while dying from the perspective of terminally ill men. DESIGN: Descriptive study involving semistructured interviews. SETTING: Patients attending clinics at two university-affiliated medical centers were interviewed in a private conference room or in their homes. PARTICIPANTS: Twenty-six men identified by their physicians as having terminal heart disease or cancer. Eligible participants acknowledged that they had serious illness. MEASUREMENTS: The interview contained open-ended questions such as: "What are the most important things in your life right now?" The interview also contained closed-ended questions about symptom intensity, presence of depressed mood, and other items related to overall quality of life. The open-ended questions were tape-recorded, transcribed, and analyzed using grounded theory methods. The closed-ended questions were analyzed using descriptive statistics. RESULTS: Participants believed that death was near. Participants saw engaging in hobbies and other enjoyable activities as an alternative to moving into the final stage of illness, in which they saw themselves as actively dying. They admitted to occasionally ignoring prescribed diets; these actions improved their overall quality of life but worsened symptoms. New symptoms brought concerns about progression to active dying. They anticipated what their dying would be like and how it would affect others. Participants believed that their actions in the present could improve the quality of their dying and lessen the burden of their deaths on others. Many participants therefore were preparing for death by engaging in such tasks as putting their finances in order and planning their funerals, to relieve anticipated burden on loved ones. CONCLUSION: To help terminally ill patients plan for the end of life, clinicians are encouraged to become familiar with their patients' experiences of living with terminal illness, to identify each patient's unique priorities, and to incorporate that information into care plans aimed at maximizing quality of life at the end of life. C1 VAPSHCS, GEC S182, Seattle, WA 98108 USA. Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. RP Vig, EK (reprint author), VAPSHCS, GEC S182, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 43 TC 36 Z9 37 U1 5 U2 14 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 NOV PY 2003 VL 51 IS 11 BP 1595 EP 1601 DI 10.1046/j.1532-5415.2003.51505.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 736KE UT WOS:000186169300011 PM 14687389 ER PT J AU Wu, JC Nasseri, BA Bloch, KD Picard, MH Scherrer-Crosbie, M AF Wu, JC Nasseri, BA Bloch, KD Picard, MH Scherrer-Crosbie, M TI Influence of sex on ventricular remodeling after myocardial infarction in mice SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID WALL-MOTION ABNORMALITIES; GENDER-DIFFERENCES; PRESSURE-OVERLOAD; HEART-FAILURE; RATS; CARDIOMYOPATHY; ENLARGEMENT; SIZE AB Murine models are increasingly used to elucidate the molecular mechanisms contributing to left ventricular (LV) remodeling. Epidemiologic and animal studies have suggested that women undergo differing patterns of LV remodeling than men after myocardial infarction (MI). We, therefore, sought to compare LV remodeling after MI in male and female mice. Echocardiography was performed in male and female C57BL6 mice before and serially after MI. Two days after MI, end-diastolic LV internal diameter and shortening fraction were similar in males and females. Between days 2 and 28 after MI, LV internal diameter increased in male mice but remained unchanged in female mice. During this time period, shortening fraction declined in males, but not in females. Posterior wall thickness increased more in females than in males. The size of the MI and the LV mass/body weight were similar between the 2 sexes after MI. Echocardiography showed that after MI, female mice undergo less extensive LV remodeling than males, with less dilation and better preserved LV systolic function 28 days after MI. These sex differences should be taken into account when studying murine cardiac adaptation to MI. C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Scherrer-Crosbie, M (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, 55 Fruit St, Boston, MA 02114 USA. OI Picard, Michael/0000-0002-9264-3243 FU NHLBI NIH HHS [HL-70896] NR 26 TC 21 Z9 22 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD NOV PY 2003 VL 16 IS 11 BP 1158 EP 1162 DI 10.1067/S0894-7317(03)00648-5 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 740KN UT WOS:000186401700008 PM 14608287 ER PT J AU Williams, ME Bolton, WK Degenhardt, TP Schotzinger, R AF Williams, ME Bolton, WK Degenhardt, TP Schotzinger, R TI A phase 2 clinical trial of pyridoxamine (Pyridorin (TM)) in type 1 and type 2 diabetic patients with overt nephropathy (PYR-206) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Joslin Diabet Ctr, Renal Unit, Boston, MA 02215 USA. Univ Virginia, Med Ctr, Charlottesville, VA USA. BioStratum Inc, Durham, NC USA. NR 0 TC 6 Z9 6 U1 0 U2 0 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 NOV PY 2003 VL 14 SU S BP 7A EP 7A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100030 ER PT J AU Yuan, XL Clarkson, MR Schmitt, I Salama, AD Auchincloss, H Glimcher, LH Sayegh, MH AF Yuan, XL Clarkson, MR Schmitt, I Salama, AD Auchincloss, H Glimcher, LH Sayegh, MH TI The role of the novel gene, T-bet, in allograft rejection and tolerance. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Brigham & Womens Hosp, Div Renal, Lab Immunogenet & Transplantat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RI Salama, Alan/B-5183-2010 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 13A EP 13A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100057 ER PT J AU Gooch, JL Guler, RL Vanden Heuvel, GB AF Gooch, JL Guler, RL Vanden Heuvel, GB TI Defects in nephrogenic zone development and mesangial cell proliferation in calcineurin A alpha knockout mice. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX USA. Univ Kansas, Med Ctr, Dept Anat & Cell Biol, Kansas City, KS 66103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 18A EP 18A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100081 ER PT J AU Thadhani, R Mutter, W Wolf, M Levine, R Ecker, J Karumanchi, A AF Thadhani, R Mutter, W Wolf, M Levine, R Ecker, J Karumanchi, A TI First trimester angiogenic growth factor (PIGF) and inhibitor (sFlt-1) and risk for precclampsia. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. NICHD, NIH, Bethesda, MD USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Vincent Obstet Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 21A EP 21A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100094 ER PT J AU Miller, RL Zhang, P Brown, D Breton, S Nelson, RD AF Miller, RL Zhang, P Brown, D Breton, S Nelson, RD TI Two methods for isolation of collecting duct cells from EGFP transgenic mice. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Utah, Salt Lake City, UT USA. Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA USA. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 24A EP 24A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100108 ER PT J AU Lu, HAJ Sun, TX Yi, XF Bouley, R Sever, S McLaughlin, M Brown, D AF Lu, HAJ Sun, TX Yi, XF Bouley, R Sever, S McLaughlin, M Brown, D TI Heat shock protein 70 interacts with AQP2 and regulates its trafficking. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Program Membrance Biol, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 31A EP 31A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100143 ER PT J AU Gooch, JL Guler, RL Toro, JJ AF Gooch, JL Guler, RL Toro, JJ TI Calcineurin A alpha is required for normal AQP2 trafficking and function. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 32A EP 32A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100145 ER PT J AU Procino, G Carmosino, M Tamma, G Gouraud, S Laera, A Svelto, M Valenti, G AF Procino, G Carmosino, M Tamma, G Gouraud, S Laera, A Svelto, M Valenti, G TI Calcium-sensing receptors signaling counteracts forskolin-induced aquaporin-2 trafficking in kidney collecting duct contributing to hypercalciuria-induced polyuria SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Texas, Ctr Hlth Sci, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX USA. RI Carmosino, Monica/O-2594-2014; Tamma, Grazia/F-8823-2016 OI Carmosino, Monica/0000-0001-7600-8816; NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 32A EP 32A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100146 ER PT J AU Knight, EL Verhave, JC Spiegelman, D Hillege, HL De Zeeuw, D Curhan, GC De Jong, PE AF Knight, EL Verhave, JC Spiegelman, D Hillege, HL De Zeeuw, D Curhan, GC De Jong, PE TI Serum cystatin C is not only dependent on renal function but also on age, sex and weight. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Brigham & Womens Hosp, Channing Lab, Boston, MA USA. Brigham & Womens Hosp, Renal Unit, Boston, MA USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Univ Groningen, Ctr Med, Div Nephrol, Groningen, Netherlands. Univ Groningen, Ctr Med, Div Cardiol, Groningen, Netherlands. Univ Groningen, Ctr Med, Div Clin Pharmacol, Groningen, Netherlands. RI Verhave, Jacobien/F-6786-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 34A EP 34A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100154 ER PT J AU Ali, S Chandraker, A DeCaprio, J AF Ali, S Chandraker, A DeCaprio, J TI Inhibition of polyoma helicase activity by quinolones SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Brigham & Womens Hosp, Lab Immunogenet & Transplantat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 43A EP 43A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100196 ER PT J AU Rincon-Choles, H Vasylyeva, TL Bhandari, K Barnes, JL Bhandari, B Simon, M Pergola, PE Gorin, Y Abboud, HE AF Rincon-Choles, H Vasylyeva, TL Bhandari, K Barnes, JL Bhandari, B Simon, M Pergola, PE Gorin, Y Abboud, HE TI Regulation of ZO-1 expression and phosphorylation in experimental diabetes SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 NOV PY 2003 VL 14 SU S BP 47A EP 47A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100216 ER PT J AU Otto, EA Schermer, B Obara, T O'Toole, JF Landau, D Goodship, JA Strachan, T Antignac, C Walz, G Drummond, LA Benzing, T Hildebrandt, F AF Otto, EA Schermer, B Obara, T O'Toole, JF Landau, D Goodship, JA Strachan, T Antignac, C Walz, G Drummond, LA Benzing, T Hildebrandt, F TI Inversin mutations cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Michigan, Dept Pediat & Commun Dis, Ann Arbor, MI 48109 USA. Univ Freiburg Klinikum, Div Renal, Freiburg, Germany. Univ Freiburg Klinikum, Clin Res Ctr, Freiburg, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Charlestown, MA USA. Soroka Med Ctr, Dept Pediat, IL-84101 Beer Sheva, Israel. Univ Newcastle Upon Tyne, Inst Human Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Univ Paris 05, Dept Genet, F-75270 Paris 06, France. Univ Paris 05, Hop Necker Enfants Malad, INSERM, U574, F-75270 Paris 06, France. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. RI Schermer, Bernhard/E-9972-2014 OI Schermer, Bernhard/0000-0002-5194-9000 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 49A EP 49A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100226 ER PT J AU Chen, Y Polci, R Litchfield, P Gaczynska, M Riley, DJ AF Chen, Y Polci, R Litchfield, P Gaczynska, M Riley, DJ TI Nek1 regulates renal epithelial cell apoptosis through phosphorylation of the mitochondrial transition pore channel VDAC. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Texas, Hlth Sci Ctr, Inst Biotechnol, San Antonio, TX USA. Univ Roma La Sapienza, Policlin Umberto I, Div Nephrol, Rome, Italy. S Texas Vet Hlth Care Syst, Div Res, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 50A EP 50A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100231 ER PT J AU Kramer-Zucker, AG Haycraft, CJ Yoder, BK Drummond, LA AF Kramer-Zucker, AG Haycraft, CJ Yoder, BK Drummond, LA TI A novel protein causing cystic kidney disease in zebrafish. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA USA. Univ Alabama, Med Ctr, Dept Cell Biol, Birmingham, AL 35294 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2003 VL 14 SU S BP 50A EP 50A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100227 ER PT J AU Nagami, GT Warech, EM AF Nagami, GT Warech, EM TI Metabolic acidosis enhances the stimulatory effects of angiotensin II on ammonia production and secretion by mouse S3 proximal tubule segments. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 VA Greater Los Angeles Healthcare Syst, Nephrol Sect, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 69A EP 69A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100318 ER PT J AU Nagami, GT Patel, S Warech, EM AF Nagami, GT Patel, S Warech, EM TI High pH increases cell surface expression of type 2 angiotensin II receptors in cultured proximal tubule cells. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 VA Greater Los Angeles Healthcare Syst, Nephrol Sect, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 70A EP 70A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100323 ER PT J AU Muckova, K Held, KD Bonventre, JV Sheridan, AM AF Muckova, K Held, KD Bonventre, JV Sheridan, AM TI Tip60 splice variants localize to different cellular compartments in response to ionizing irradiation and H2O2. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 84A EP 85A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100397 ER PT J AU Ercolani, L Wane, JF Chen, T AF Ercolani, L Wane, JF Chen, T TI G alpha i-2 and RACKI protein interactions required for renal tubule mitogenesis: RACK1 is a GTPase inhibitor. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 87A EP 87A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100409 ER PT J AU Mariappan, M Duraisamy, S Choudhury, GG Kasinath, BS AF Mariappan, M Duraisamy, S Choudhury, GG Kasinath, BS TI Novel role of SRC and PLC in regulation of VEGF-induced ERK activation in proximal tubular epithelial cells and its role in protein synthesis. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 87A EP 87A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100410 ER PT J AU Gloy, J Schmitt, A Hikasa, H Waz, G Sokol, S AF Gloy, J Schmitt, A Hikasa, H Waz, G Sokol, S TI Signaling mechanisms of Frodo, a novel player in the Wnt pathway. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Clin Freiburg, Div Nephrol, Freiburg, Germany. Harvard Univ, Sch Med, Mol Med Unit, BIDMC, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 91A EP 91A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100428 ER PT J AU Gorin, Y Ricono, JM Kim, NH Bhandari, B Choudhury, GG Abboud, HE AF Gorin, Y Ricono, JM Kim, NH Bhandari, B Choudhury, GG Abboud, HE TI Nox4 mediates angiotensin II-induced mesangial cell hypertrophy via activation of Akt/protein kinase B. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Audie L Murphy Mem Hosp Div, S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 91A EP 91A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100430 ER PT J AU Achinger, SG Polci, R Litchfield, P Riley, DJ Chen, Y AF Achinger, SG Polci, R Litchfield, P Riley, DJ Chen, Y TI Dynamic association between Nek1 protein kinase and VDAC1 in renal tubular epithelial cells after reversible or lethal DNA damage. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 93A EP 93A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100438 ER PT J AU Boyle, S Shioda, T de Caestecker, MP AF Boyle, S Shioda, T de Caestecker, MP TI Cited1 specifies diverse cell fates within the developing kidney. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Vanderbilt Univ, Div Nephrol, Nashville, TN USA. Massachusetts Gen Hosp, Lab Tumor Biol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 101A EP 101A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100481 ER PT J AU Zhang, SL Moini, B Ingelfinger, JR AF Zhang, SL Moini, B Ingelfinger, JR TI Angiotensin II interacts with Pax-2 in renal cells: Implications for development. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 101A EP 101A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100480 ER PT J AU Manotham, K Tanaka, T Matsumoto, M Ohse, T Inagi, R Miyata, T Kurokawa, K Fujita, T Ingelfinger, JR Nangaku, M AF Manotham, K Tanaka, T Matsumoto, M Ohse, T Inagi, R Miyata, T Kurokawa, K Fujita, T Ingelfinger, JR Nangaku, M TI Transdifferentiation of tubular cells induced by hypoxia. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Massachusetts Gen Hosp, Div Pediat Nephrol, Boston, MA 02114 USA. Tokai Univ, Sch Med, Dept Med, Kanagawa 2591100, Japan. Tokai Univ, Sch Med, Inst Med Sci, Kanagawa 2591100, Japan. Univ Tokyo, Sch Med, Div Nephrol & Endocrinol, Tokyo 113, Japan. RI Nangaku, Masaomi/A-5300-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 121A EP 121A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100570 ER PT J AU Isshiki, K He, ZH Yasuda, Y Lock, J Patti, ME Shoelson, SE Weir, GC Stanton, RC King, GL AF Isshiki, K He, ZH Yasuda, Y Lock, J Patti, ME Shoelson, SE Weir, GC Stanton, RC King, GL TI Identification of SOCS2 and STAT5a's novel roles on IGF1R signaling and effects in diabetic nephropathy by DNA microarray. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 126A EP 127A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100595 ER PT J AU Hsieh, TJ Fantus, IG Tang, SS Ingelfinger, JR Hamet, P Chan, JSD AF Hsieh, TJ Fantus, IG Tang, SS Ingelfinger, JR Hamet, P Chan, JSD TI Antioxidants and inhibitors of hexosamine biosynthetic pathway (HBP) prevent high glucose induction of insulin resistance on inhibition of angiotensinogen (ANG) gene expression in rat immortalized renal proximal tubular cells (IRPTCs). SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Massachusetts Gen Hosp, Ped Nephrol Unit, Boston, MA 02114 USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Hop Hotel Dieu, CHUM, Res Ctr, Montreal, PQ H2W 1T8, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 130A EP 130A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100613 ER PT J AU Bochenski, JP Poznik, GD Wolkow, PP Canani, LE Mlynarski, WM Placha, G Ficociello, L James, W Krolewski, AS AF Bochenski, JP Poznik, GD Wolkow, PP Canani, LE Mlynarski, WM Placha, G Ficociello, L James, W Krolewski, AS TI Haplotype of ectonucleotide pyrophosphatase/phosphodiesterase gene (ENPP-1) is associated with the early renal function decline (ERFD) in the course of microalbuminuria in type 1 diabetics (T1DM) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Joslin Diabet Ctr, Boston, MA 02215 USA. RI Canani, Luis/G-9686-2012 OI Canani, Luis/0000-0002-1813-4491 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 132A EP 132A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100623 ER PT J AU Placha, GP Canani, LE Bochenski, JP Poznik, DG Ficociello, LH Wolkow, PP Mlynarski, WM Smiles, AM Rogus, JJ Warram, JH AF Placha, GP Canani, LE Bochenski, JP Poznik, DG Ficociello, LH Wolkow, PP Mlynarski, WM Smiles, AM Rogus, JJ Warram, JH TI Polymorphism in promoter region of cyclin-dependent kinase inhibitor 1A gene (p21) reduces the progression of proteinuria to end stage renal disease (ESRD) in type 1 diabetes (T1DM) SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Joslin Diabet Ctr, Boston, MA 02215 USA. RI Canani, Luis/G-9686-2012 OI Canani, Luis/0000-0002-1813-4491 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 133A EP 133A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100625 ER PT J AU Smirnakis, KV Wolf, MS Ecker, J Thadhani, RI AF Smirnakis, KV Wolf, MS Ecker, J Thadhani, RI TI Interleukin-6 as an early marker for gestational diabetes mellitus SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 135A EP 135A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100637 ER PT J AU Smirnakis, KV Wolf, MS Shah, A Sauk, J Jiminez-Kimble, R Ecker, J Thadhani, R AF Smirnakis, KV Wolf, MS Shah, A Sauk, J Jiminez-Kimble, R Ecker, J Thadhani, R TI Post-partum diabetes screening among women with a history of gestational diabetes mellitus SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 135A EP 135A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100635 ER PT J AU Racusen, LC Colvin, R Solez, K AF Racusen, LC Colvin, R Solez, K TI Standardization of scoring of C4d staining in renal allograft biopsies: Consensus from the seventh Banff Conference on allograft pathology SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Johns Hopkins Univ, Int Consensus Grp, Baltimore, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Alberta, Edmonton, AB, Canada. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 146A EP 147A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100690 ER PT J AU Salama, AD Yamada, A Forman, J Kewalramani, R Najafian, N Ito, T Sandner, SE Sho, M Harada, H Mandelbrot, D Sharpe, AH Oshima, H Chalasani, G Lakkis, F Yagita, H Auchincloss, H Sayegh, MH AF Salama, AD Yamada, A Forman, J Kewalramani, R Najafian, N Ito, T Sandner, SE Sho, M Harada, H Mandelbrot, D Sharpe, AH Oshima, H Chalasani, G Lakkis, F Yagita, H Auchincloss, H Sayegh, MH TI CD70-CD27 is a critical CD28-independent costimulatory pathway for alloimmune CD8+T cell responses SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Yale Univ, Sch Med, New Haven, CT USA. Juntendo Univ, Sch Med, Tokyo 113, Japan. Childrens Hosp, Boston, MA 02115 USA. RI Salama, Alan/B-5183-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 178A EP 178A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100840 ER PT J AU Wong, WC Tolkoff-Rubin, N Delmonico, FL Farrell, ML Shih, V Cosimi, AB Pascual, M AF Wong, WC Tolkoff-Rubin, N Delmonico, FL Farrell, ML Shih, V Cosimi, AB Pascual, M TI A Randomized clinical trial to analyze the effect of 50% cyclosporine reduction on the cardiovascular risk profile in stable kidney transplant recipients SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. CHUV, Transplant Ctr, Lausanne, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 186A EP 186A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100880 ER PT J AU Zomlefer, K McCluskey, RT Wong, WC Pascual, M Zhang, H Cosimi, AB Tolkoff-Rubin, N AF Zomlefer, K McCluskey, RT Wong, WC Pascual, M Zhang, H Cosimi, AB Tolkoff-Rubin, N TI Risk factors for severe, early recurrence of IgA nephropathy SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Massachusetts Gen Hosp, Renal Transplant Unit, Boston, MA 02114 USA. CHU Vaudois, Transplant Ctr, CH-1011 Lausanne, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 189A EP 189A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100892 ER PT J AU Schaeffner, ES Kurth, T de Jong, PE Glynn, RJ Buring, JE Gaziano, MJ AF Schaeffner, ES Kurth, T de Jong, PE Glynn, RJ Buring, JE Gaziano, MJ TI Alcohol and the risk of renal dysfunction in apparently healthy men. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Freiburg, Dept Nephrol, Freiburg, Germany. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02115 USA. Univ Groningen Hosp, Dept Med, Groningen, Netherlands. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. Boston VA Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. RI Kurth, Tobias/A-9243-2012 OI Kurth, Tobias/0000-0001-7169-2620 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 196A EP 196A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219100921 ER PT J AU Kaufman, JS Stefanik, K Zhang, Y Scharfstein, D Cotter, DJ AF Kaufman, JS Stefanik, K Zhang, Y Scharfstein, D Cotter, DJ TI Reaching target hematocrits with epoetin: Is the inference of a survival benefit valid? SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 VA Boston Healthcare Syst, Renal Sect, Boston, MA USA. Med Technol & Practice Patterns Inst Inc, Bethesda, MD USA. Johns Hopkins Sch Hyg & Publ Hlth, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 268A EP 268A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219101240 ER PT J AU Rabito, CA Modell, M AF Rabito, CA Modell, M TI Non invasive, real-time monitoring of glomerular filtration rate using time-resolved fluorometry SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. DiametRx Inc, Natick, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 278A EP 278A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219101287 ER PT J AU Weisbord, SD Kip, KE Saul, MI Palevsky, PM AF Weisbord, SD Kip, KE Saul, MI Palevsky, PM TI Defining clinically significant radiocontrast nephropathy SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 280A EP 281A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219101300 ER PT J AU Beaulieu, V Pastor-Soler, N Da Silva, N Brown, C Smith, P Kwiatkowski, D Brown, D Breton, S AF Beaulieu, V Pastor-Soler, N Da Silva, N Brown, C Smith, P Kwiatkowski, D Brown, D Breton, S TI Role of the actin cytoskeleton, gelsolin, and calcium in the regulation of pH-dependent V-ATPase recycling in the epididymis SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Massachusetts Gen Hosp, Renal Unit, Program Membrane Biol, Charlestown, MA USA. BioCurrents Res Ctr, Biol Marine Lab, Woods Hole, MA USA. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 302A EP 302A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219101392 ER PT J AU Silberstein, C Brown, D Van Hoek, AN AF Silberstein, C Brown, D Van Hoek, AN TI Appearance and disappearance of aquaporin-4 orthogonal arrays SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 1 Z9 2 U1 0 U2 0 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 NOV PY 2003 VL 14 SU S BP 311A EP 311A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219101437 ER PT J AU Arystarkhova, E Wetzell, RK Sweadner, KJ AF Arystarkhova, E Wetzell, RK Sweadner, KJ TI Regulation of renal Na,K-ATPase by the gamma subunit (FXYD2): plasticity and control SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Massachusetts Gen Hosp, Lab Membrane Biol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 316A EP 316A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219101459 ER PT J AU Tanaka, T Hanafusa, N Ingelfinger, JR Ohse, T Fujita, T Nangaku, M AF Tanaka, T Hanafusa, N Ingelfinger, JR Ohse, T Fujita, T Nangaku, M TI Hypoxia induces apoptosis in SV40-immortalized rat proximal tubular cells through the mitochondrial pathways, devoid of HIF-1-mediated upregulation of Bax. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Tokyo, Sch Med, Div Nephrol & Endocrinol, Tokyo 113, Japan. Massachusetts Gen Hosp, Div Pediat Nephrol, Boston, MA 02114 USA. RI Nangaku, Masaomi/A-5300-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 338A EP 339A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219101568 ER PT J AU Balkovetz, DF Gerrard, ER Li, SX AF Balkovetz, DF Gerrard, ER Li, SX TI Cell contact dependent regulation of ERK 1/2 and cyclin D1 controls Madin Darby canine kidney epithelial cell proliferation. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Dept Med, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 342A EP 342A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219101584 ER PT J AU Bukanov, NO Obara, T Roberts, BL Klinger, KW Drummond, IA Ibraghimov-Beskrovnaya, O AF Bukanov, NO Obara, T Roberts, BL Klinger, KW Drummond, IA Ibraghimov-Beskrovnaya, O TI Proteome analysis of the zebrafish double bubble mutant suggests a role for cathepsins in pronephric cystogenesis. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Genzyme Corp, Appl Genom, Framingham, MA 01701 USA. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 365A EP 365A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219101699 ER PT J AU Riley, DJ Achinger, SG Chen, YM AF Riley, DJ Achinger, SG Chen, YM TI Expression of Nek1 protein kinase during kidney development and after ischemic tubular injury. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 366A EP 366A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219101700 ER PT J AU Xu, YZ Osborne, B Stanton, RC AF Xu, YZ Osborne, B Stanton, RC TI Pathogenesis of diabetic nephropathy: The role of glucose-6-phosphate dehydrogenase and oxidative stress. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 384A EP 384A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219101786 ER PT J AU Chan, JSD Hsieh, TJ Fantus, G Tang, SS Ingelfinger, JR Carriere, S Hamet, P AF Chan, JSD Hsieh, TJ Fantus, G Tang, SS Ingelfinger, JR Carriere, S Hamet, P TI Inhibitors of NADPH oxidase and repin-angiotensin system prevent reactive oxygen species (ROS) generation, glutamine: fructose-6-phosphate (GFAT) and angiotensinogen (ANG) gene expression in rat immortalized renal proximal tubular cells (IRPTCs) in high glucose. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 CHUM, Res Ctr, Hotel Dieu Hosp, Montreal, PQ, Canada. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Massachusetts Gen Hosp, Pediat Nephrol Univ, Boston, MA 02114 USA. Servier Canada, R&D, Laval, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 385A EP 385A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219101790 ER PT J AU Ficociello, LH Perkins, BA Palecek, BE Warram, JH Krolewski, AS AF Ficociello, LH Perkins, BA Palecek, BE Warram, JH Krolewski, AS TI Determinants of early declining renal function in a cohort of patients with type 1 diabetes and microalbuminuria. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 397A EP 397A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219101845 ER PT J AU Feliers, D Senthil, D Ghosh-Choudhury, G Barnes, J Kasinath, BS AF Feliers, D Senthil, D Ghosh-Choudhury, G Barnes, J Kasinath, BS TI Selective translational regulation of vascular endothelial growth factor (VEGF) expression in proximal tubular cells (MCT) by angiotensin II (AII). SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU 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 NOV PY 2003 VL 14 SU S BP 402A EP 402A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219101871 ER PT J AU Nestoridi, E Kushak, RI Grabowski, EF Ingelfinger, JR AF Nestoridi, E Kushak, RI Grabowski, EF Ingelfinger, JR TI Enhancement of tissue factor activity in human proximal tubular epithelial cells in response to shiga toxin. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Massachusetts Gen Hosp, Dept Pediat, Div Pediat Nephrol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Div Pediat Hematol Oncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 415A EP 415A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219101929 ER PT J AU Wong, WC Hirsch, H Pascual, M Doran, MT DelVecchio, AM Cosimi, AB Tolkoff-Rubin, N AF Wong, WC Hirsch, H Pascual, M Doran, MT DelVecchio, AM Cosimi, AB Tolkoff-Rubin, N TI BK virus replication in kidney transplant recipients who received thymoglobulin induction. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Univ Basel Hosp, Div Infect Dis, CH-4031 Basel, Switzerland. CHU Vaudois, Transplant Ctr, CH-1011 Lausanne, Switzerland. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 426A EP 426A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219101977 ER PT J AU Forman, JP Tolkoff-Rubin, N Pascual, M Lin, J AF Forman, JP Tolkoff-Rubin, N Pascual, M Lin, J TI Impact of recipient hepatitis C virus infection on acute rejection and allograft, survival after kidney transplantation. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Brigham & Womens Hosp, Div Nephrol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 429A EP 430A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219101994 ER PT J AU Wong, WC Tolkoff-Rubin, N Pascual, M Baid, S Walters, MF Cosimi, AB Mason, RP AF Wong, WC Tolkoff-Rubin, N Pascual, M Baid, S Walters, MF Cosimi, AB Mason, RP TI Conversion of kidney transplant recipients from cyclosporine and tacrolimus correlates with reduced LDL oxidation: A potential direct drug effect. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplant Unit, Boston, MA 02114 USA. CHUV, Transplant Ctr, Lausanne, Switzerland. Elucida Res, Beverly, MA USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 436A EP 437A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219102025 ER PT J AU Wong, WC Agrawal, N Pascual, M DelVecchio, AM Doran, MT Anderson, D Hirsh, H Delmonico, FL Cosimi, AB Tolkoff-Rubin, N AF Wong, WC Agrawal, N Pascual, M DelVecchio, AM Doran, MT Anderson, D Hirsh, H Delmonico, FL Cosimi, AB Tolkoff-Rubin, N TI Use of thymoglobulin for induction immunosuppression in living unrelated kidney transplant recipients. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. CHUV, Transplant Ctr, Lausanne, Switzerland. Univ Basel Hosp, Div Infect Dis, CH-4031 Basel, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 442A EP 442A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219102047 ER PT J AU Han, WK Alinani, A Wu, CL Thadhani, RI McGovern, FJ Moses, MA Bonventre, JV AF Han, WK Alinani, A Wu, CL Thadhani, RI McGovern, FJ Moses, MA Bonventre, JV TI Kidney injury molecule-1 (KIM-1) is a urinary tumor marker for renal cell carcinoma. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Renal Unit, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 454A EP 454A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219102101 ER PT J AU Palevsky, PM O'Connor, TZ Zhang, JH Star, R AF Palevsky, PM O'Connor, TZ Zhang, JH Star, R CA VA NIH Acute Renal Failure Trial N TI VA/NIH acute renal failure trial network: Study design. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. CSPCC, VA Connecticut Healthcare Syst, West Haven, CT USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 512A EP 512A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219102359 ER PT J AU Wolf, M Shah, A Thadhani, R AF Wolf, M Shah, A Thadhani, R TI Cardiovascular Disease risk factors in women with prior preeclampsia. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Massachusetts Gen Hosp, Renal Unit, Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 515A EP 515A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219102372 ER PT J AU Wolf, M Shah, A Sauk, J Jiminez-Kimble, R Ecker, J Thadhani, R AF Wolf, M Shah, A Sauk, J Jiminez-Kimble, R Ecker, J Thadhani, R TI Differential risk of hypertensive disorders of pregnancy among Hispanic women. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA USA. Massachusetts Gen Hosp, Dept Obstet & Gynaecol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 517A EP 518A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219102383 ER PT J AU Eslami, P Corry, DB Nyby, MD Tuck, ML AF Eslami, P Corry, DB Nyby, MD Tuck, ML TI Angiotensin II AT1 receptor Blockers and antioxidants reverse the inhibition of nitric oxide production by uric acid in vascular smooth muscle cells. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CA SP Amer Soc Nephrol C1 Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Univ Calif Los Angeles, SFVP, Sylmar, CA USA. VA Greater Los Angeles Healthcare, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 523A EP 523A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219102406 ER PT J AU Mahimainathan, L Ghosh-Choudhury, G AF Mahimainathan, L Ghosh-Choudhury, G TI TGF beta and high glucose downregulate the tumor suppressor protein PTEN (Phosphatase and tensin homolog deleted on chromosome 10) to regulate mesangial cell hypertrophy SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 551A EP 551A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219102539 ER PT J AU Chen, XY Feliers, D Akis, N Choudhury, GG Madaio, MS Kasinath, BS AF Chen, XY Feliers, D Akis, N Choudhury, GG Madaio, MS Kasinath, BS TI Vascular endothelial growth factor (VEGF) regulation of eNOS in glomerular endothelial (G Endo) cells. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 553A EP 553A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219102549 ER PT J AU Bouley, R Lin, HY Brown, D Ausiello, DA AF Bouley, R Lin, HY Brown, D Ausiello, DA TI Downregulation of the vasopressin type 2 receptor (V2R) after agonist-induced internalization: Involvement of a lysosomal degradation pathway SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 560A EP 560A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219102582 ER PT J AU Thadhani, R Wolf, M Smirnakas, K Karumanchi, A Ecker, J AF Thadhani, R Wolf, M Smirnakas, K Karumanchi, A Ecker, J TI Early pregnancy urine proteomic arrays in the prediction of preeclampsia. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Massachusetts Gen Hosp, Renal & Obstet Unit, Boston, MA 02114 USA. Beth Israel Deaconess Hosp, Div Renal, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 583A EP 584A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219102701 ER PT J AU Faulkner, JL Barnes, JL AF Faulkner, JL Barnes, JL TI TGF beta-1 and angiotensin II (AII) have distinct effects on renal fibroblast phenotype, hypertrophy and fibronectin synthesis. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 S Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 590A EP 590A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219102730 ER PT J AU Tofovic, SP Mady, H Jackson, EK AF Tofovic, SP Mady, H Jackson, EK TI Estradiol metabolites attenuate renal and cardiovascular injury induced by chronic angiotensin II administration. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Pittsburgh, Sch Med, Dept Med, Ctr Clin Pharmacol, Pittsburgh, PA USA. Sch Med, Dept Pathol, Pittsburgh, PA USA. VA Pittsburgh Hlth Syst, Pittsburgh, PA USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 620A EP 620A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219102872 ER PT J AU Wong, W Pascual, M Hirsch, H Goggins, W Bae, J Farrell, ML Delmonico, FL Cosimi, AB Tolkoff-Rubin, N AF Wong, W Pascual, M Hirsch, H Goggins, W Bae, J Farrell, ML Delmonico, FL Cosimi, AB Tolkoff-Rubin, N TI Safety and efficacy of thymoglobulin induction in cadaveric kidney transplant recipients with tacrolimus, steroids and mycophenolate mofetil. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Basel Hosp, Div Infect Dis, CH-4031 Basel, Switzerland. CHU Vaudois, Transplant Ctr, CH-1011 Lausanne, Switzerland. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 651A EP 651A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219103017 ER PT J AU Wong, WC Pascual, M Agrawal, N Anderson, D Cardarelli, F Delmonico, FL Cosimi, AB Tolkoff-Rubin, N AF Wong, WC Pascual, M Agrawal, N Anderson, D Cardarelli, F Delmonico, FL Cosimi, AB Tolkoff-Rubin, N TI Determination of the optimal dose of thymoglobulin when used as a three-day induction course for T-Cell clearance in kidney transplant recipients. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 CHU Vaudois, Transplant Ctr, CH-1011 Lausanne, Switzerland. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 651A EP 651A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219103016 ER PT J AU Sierra, JA Ramos, FJM Montanez, JL Gutierrez, R Chung, RT Celis, AJ Vivas, C Ruelas, S Navarro, BG Navarro, AMC AF Sierra, JA Ramos, FJM Montanez, JL Gutierrez, R Chung, RT Celis, AJ Vivas, C Ruelas, S Navarro, BG Navarro, AMC TI Risk factors associated with posttransplantation diabetes mellitus in kidney recipients. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 IMSS, Ctr Med Nacl Occidente, Collaborat Grp Study Hepatitis Kidney Dis, Guadalajara, Jalisco, Mexico. Massachusetts Gen Hosp, Boston, MA 02114 USA. IMSS, Ctr Med Nacl Occidente, Guadalajara, Jalisco, Mexico. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 658A EP 658A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219103046 ER PT J AU Knight, EL Rimm, EB Pai, JK Rexrode, KM Cannuscio, CC Manson, JE Stampfer, MJ Curhan, GC AF Knight, EL Rimm, EB Pai, JK Rexrode, KM Cannuscio, CC Manson, JE Stampfer, MJ Curhan, GC TI Renal function, inflammation and coronary events: A prospective study. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA USA. Merck & Co Inc, Whitehouse Stn, NJ USA. RI Cannuscio, Carolyn/A-1123-2007 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 677A EP 677A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219103129 ER PT J AU O'Hare, AM Feinglass, J Reiber, GE Rodriguez, RA Daley, J Khuri, S Henderson, WG Johansen, KL AF O'Hare, AM Feinglass, J Reiber, GE Rodriguez, RA Daley, J Khuri, S Henderson, WG Johansen, KL TI Post-operative mortality after non-traumatic lower extremity amputation in patients with renal insufficiency SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 San Francisco VA Med Ctr, San Francisco, CA USA. UCSF, San Francisco, CA USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Washington, Seattle, WA 98195 USA. VA Puget Sound HCS, Hlth Serv Epidemiol, Seattle, WA 98195 USA. San Francisco Gen Hosp, San Francisco, CA 94110 USA. Tenet Hlth & Harvard Univ, Dallas, TX USA. VA Boston HCS, Boston, MA USA. Harvard Univ, Boston, MA 02115 USA. Univ Colorado, Denver, CO 80202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 679A EP 679A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219103139 ER PT J AU Kestenbaum, B Seliger, SL Gillen, DL Wasse, H Young, B Sherrard, DJ Weiss, NS Stehman-Breen, CO AF Kestenbaum, B Seliger, SL Gillen, DL Wasse, H Young, B Sherrard, DJ Weiss, NS Stehman-Breen, CO TI Parathyroidectomy rates among US dialysis patients: 1990-1999. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Washington, Div Nephrol, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Div Gen Internal Med, Seattle, WA 98195 USA. Univ Washington, VA Puget Sound Healthcare Syst, Div Nephrol, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RI Wasse, Haimanot/A-5726-2013 OI Wasse, Haimanot/0000-0001-5756-0242 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 684A EP 684A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219103162 ER PT J AU Curhan, GC Willett, WC Knight, EL Stampfer, MJ AF Curhan, GC Willett, WC Knight, EL Stampfer, MJ TI Dietary factors and the risk of incident kidney stones in younger women (Nurses health study II). SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 698A EP 699A PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219103222 ER PT J AU Palevsky, PM Zgibor, JC Stevenson, JA Rohay, JM Perry, SB Dyer, NJ Freed, B AF Palevsky, PM Zgibor, JC Stevenson, JA Rohay, JM Perry, SB Dyer, NJ Freed, B TI Influenza immunization in ESRD patients: Comparison between medicare billing and facility data. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. ESRD Network 4, Pittsburgh, PA USA. Pinney Associates, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 719A EP 719A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219103316 ER PT J AU Humphreys, BD Sharman, JP Clark, JEW Marks, PW Zhu, AX Magee, CC AF Humphreys, BD Sharman, JP Clark, JEW Marks, PW Zhu, AX Magee, CC TI Nine cases of gemcitabine-associated thrombotic microangiopathy: Characteristics, cumulative incidence and outcome. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Massachusetts Gen Hosp, Div Renal, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 744A EP 744A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219103425 ER PT J AU Aaronson, ML Charytan, C Cornell, LD Rachlin, P Spinowitz, B Fang, M AF Aaronson, ML Charytan, C Cornell, LD Rachlin, P Spinowitz, B Fang, M TI The safety of high dose, 500mg over 4 hours, iron sucrose therapy. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Avera Hlth, N Cent Kidney Inst, Sioux Falls, SD USA. Cornell Univ, Coll Med, New York Hosp, Queens Med Ctr, Flushing, NY USA. Massachusetts Gen Hosp, Cambridge, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 772A EP 772A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219103554 ER PT J AU Young, BA Boyko, EJ McDonell, M Fihn, SS AF Young, BA Boyko, EJ McDonell, M Fihn, SS TI Risk of cardiovascular events with renal insufficiency: Results from the ambulatory care quality improvement project SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 VA Puget Sound Hlth Care Syst, HSR&D, Seattle, WA USA. VA Puget Sound Hlth Care Syst, ERIC, Seattle, WA USA. Univ Washington, Div Gen Internal Med, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 816A EP 816A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219103760 ER PT J AU Watnick, SG Angelo, D Paul, K John, C AF Watnick, SG Angelo, D Paul, K John, C TI Depression as a potential barrier to renal transplantation. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Portland VA Med Ctr, Portland, OR USA. Yale Univ, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 830A EP 830A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219103822 ER PT J AU Arar, M Ye, P Barnes, J Abboud, H AF Arar, M Ye, P Barnes, J Abboud, H TI Mesangial cell development: Role of PDGF. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 873A EP 873A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219104021 ER PT J AU Razzaque, MS Ghinelli, E Gallazzi, A Taguchi, T AF Razzaque, MS Ghinelli, E Gallazzi, A Taguchi, T TI Neurotrophins and their receptors in adult normal and diseased rat kidneys. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. Schepens Eye Res Inst, Dept Ophthalmol, Boston, MA USA. Massachusetts Gen Hosp, Dept AIDS Res, Boston, MA 02114 USA. Nagasaki Univ, Dept Pathol, Grad Sch Biomed Sci, Nagasaki 852, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2003 VL 14 SU S BP 883A EP 883A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219104067 ER PT J AU Mittalhenkle, A Meligro, CM Sherrard, DJ AF Mittalhenkle, A Meligro, CM Sherrard, DJ TI The changing relationship between intact parathyroid hormone (iPTH) and bone histology in dialysis patients. SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CALIFORNIA SP Amer Soc Nephrol C1 Univ Washington, Div Nephrol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 1 U1 0 U2 0 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 NOV PY 2003 VL 14 SU S BP 894A EP 894A PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 737FE UT WOS:000186219104115 ER PT J AU Kaelin, WG AF Kaelin, WG TI The von Hippel-Lindau gene, kidney cancer, and oxygen sensing SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID TUMOR-SUPPRESSOR PROTEIN; ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; HYPOXIA-INDUCIBLE FACTOR; NUCLEAR-CYTOPLASMIC TRAFFICKING; BIOLOGICALLY-ACTIVE PRODUCT; TYROSINE KINASE INHIBITOR; UBIQUITIN LIGASE COMPLEX; REQUIRES DIRECT BINDING; CLEAR-CELL AB Recent studies of a relatively rare hereditary cancer syndrome, von Hippel-Lindau (VHL) disease, have shed new light on the molecular pathogenesis of kidney cancer and, perhaps more important, on how mammalian cells sense and respond to changes in oxygen availability. This knowledge is already translating into new therapeutic targets for kidney cancer as well as for multiple conditions, such as myocardial infarction and stroke, in which ischemia plays a pathogenic role. This review summarizes the current knowledge of the molecular pathogenesis of von Hippel-Lindau disease and the role of the VHL gene product (pVHL) in kidney cancer and the mammalian oxygen sensing pathway. C1 Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Howard Hughes Med Inst, 44 Binney St,Mayer 457, Boston, MA 02115 USA. NR 135 TC 67 Z9 70 U1 0 U2 0 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 NOV PY 2003 VL 14 IS 11 BP 2703 EP 2711 DI 10.1097/01.ASN.0000092803.69761.41 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 734TF UT WOS:000186073500003 PM 14569079 ER PT J AU Zietman, AL Sacco, D Skowronski, U Gomery, P Kaufman, DS Clark, JA Talcott, JA Shipley, WU AF Zietman, AL Sacco, D Skowronski, U Gomery, P Kaufman, DS Clark, JA Talcott, JA Shipley, WU TI Organ conservation in invasive bladder cancer by transurethral resection, chemotherapy and radiation: Results of a urodynamic and quality of life study on long-term survivors SO JOURNAL OF UROLOGY LA English DT Article DE bladder neoplasms; drug therapy; radiation; quality of life; urodynamics ID RADICAL CYSTECTOMY; PRESERVATION; TRIAL; RADIOTHERAPY; THERAPY; SURGERY; 5-FLUOROURACIL; IRRADIATION; CARCINOMA; SYMPTOMS AB Purpose: Transurethral resection, chemotherapy and radiation with salvage cystectomy may be used as alternatives to immediate radical cystectomy in the management of invasive bladder cancer. Concern exists about the function of the retained bladder after such therapy. Materials and Methods: Of 221 patients with clinical T2-4a bladder cancer treated at Massachusetts General Hospital from 1986 to 2000 with trimodality therapy, 71 were alive with native bladders and disease-free in 2001. These patients were asked to undergo a urodynamic study and to complete a quality of life questionnaire. A total of 69% participated in some component of this study with a median time from trimodality therapy of 6.3 years (range 1.6 to 14.9). Results: Of 32 patients 24 had normally functioning bladders by urodynamic study. Decreased bladder compliance was seen in 7. Bladder hypersensitivity, involuntary detrusor contractions and incontinence were present in 2 women. The questionnaire showed that flow symptoms occurred in 6%, urgency in 15% and control problems in 19%. Of all women 11% wore pads. Distress from urinary symptoms was half as common as prevalence. Bowel symptoms occurred in 22% with 14% recording any level of distress. The majority of men retained sexual function. Global health related quality of life was high. Conclusions: The majority of patients treated with trimodality therapy retain good bladder function. A fifth have evidence of bowel dysfunction. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med Oncol, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, Dept Hlth Serv, Boston, MA USA. RP Zietman, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St,Cox 302, Boston, MA 02114 USA. OI Clark, Jack/0000-0002-7424-1670 NR 20 TC 121 Z9 124 U1 1 U2 4 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 NOV PY 2003 VL 170 IS 5 BP 1772 EP 1776 DI 10.1097/01.ju.0000093721.23249.c3 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 730YU UT WOS:000185858400015 PM 14532773 ER PT J AU Myers, DD Hawley, AE Farris, DM Wrobleski, SK Thanaporn, P Schaub, RG Wagner, DD Kumar, A Wakefield, TW AF Myers, DD Hawley, AE Farris, DM Wrobleski, SK Thanaporn, P Schaub, RG Wagner, DD Kumar, A Wakefield, TW TI P-selectin and leukocyte microparticles are associated with venous thrombogenesis SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 15th Annual Meeting of the American-Venous-Forum CY FEB 20-23, 2003 CL CANCUN, MEXICO SP Amer Venous Forum ID TISSUE FACTOR; PLATELET MICROPARTICLES; PROCOAGULANT ACTIVITY; ADHERENT PLATELETS; FIBRIN DEPOSITION; UNSTABLE ANGINA; FLOW-CYTOMETRY; IN-VIVO; THROMBOSIS; INHIBITION AB Objectives: P-selectin inhibition has been found to limit venous thrombosis. We hypothesize that elevated levels of P-selectin will amplify thrombosis, mediated by procoagulant microparticles (MPs). Methods: Male mice (Mus musculus, n659), 20 to 25 grams, underwent IVC ligation to induce thrombosis. Groups consisted of wild type (WT) C57BL/6 controls, mice with high circulating levels of soluble P-selectin (<^>CT), P-selectin gene-interrupted knockout mice (PKO), and E- and P-selectin gene-interrupted mice (EPKO). Additional groups were used to evaluate the ability of a P-sel antagonist (rPSGL-Ig) and an antibody directed against PSGL-1 to downregulate the effects of P-sel in ACT mice and WT mice administered soluble P-sel at time of thrombosis. Animals were sacrificed on days 2 and 6 after IVC ligation. Thrombus mass (TM), vein wall morphometrics, and serum leukocyte/platelet microparticles (MPs) were evaluated by means of double-stained fluorescence-activated cell scanning analysis, and soluble P- and E-sel protein determination by ELISA. Results: At days 2 and 6 in phase I of the experiment, significant differences (P <.01) in TM were noted between groups, with <^>CT animals having the largest thrombi (50% and 57% increase in TM compared to WT at days 2 and 6) while EPKO mice had the smallest thrombi. Statistically, greater levels of neutrophils and total inflammatory cells were noted in the vein walls of <^>CT animals at day 2 compared with WT and PKO animals. A significant difference was noted between <^>CT and EPKO for neutrophils, monocytes, and total inflammatory cells, also at day 2. At day 6, the only statistically significant difference was found for monocytes, with a higher number in the <^>CT animals than in WT animals. The evaluation of MPs revealed that the <^>CT mice had a mixed leukocyte (MAC-1) and platelet (CD41) MP population that was also present in WT and PKO mice on day 2 and day 6. EPKO mice revealed a primarily platelet-derived MP population. Of interest, the <^>CT mice with the highest TM showed a high amount of mean channel fluorescence for MAC-1 (phycoerythrin) antibody, indicative of leukocyte MPs. <^>CT mice revealed statistically higher levels of soluble P-selectin at days 2 and 6. In phase 2, an antibody directed against PSGL-1 was more effective than rPSGL-Ig in decreasing TM and limiting leukocyte-derived MP fluorescence. Conclusions: This study demonstrates that high circulating levels of P-selectin are associated with increased thrombosis, whereas a lack of P-selectin and E-selectin is associated with a lessening of thrombosis. Additionally, leukocyte MPs are associated with venous thrombus formation. These data suggest the importance of selectins to venous thrombogenesis and show that P-selectin and leukocyte-derived MPs should be good targets to limit venous thrombus formation. C1 Univ Michigan, Unit Lab Anim Med, Ann Arbor, MI 48109 USA. Univ Michigan, Jobst Vasc Lab, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Surg, Vasc Surg Sect, Ann Arbor, MI 48109 USA. Wyeth Res, Cambridge, MA USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Myers, DD (reprint author), 1150 W Med Ctr Dr,Dock 6,MSRB 2 A570D, Ann Arbor, MI 48109 USA. FU NHLBI NIH HHS [R01 HL 70766, R01 HL53756, R01 HL 63148, R01 HL053756] NR 41 TC 128 Z9 143 U1 0 U2 8 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 NOV PY 2003 VL 38 IS 5 BP 1075 EP 1089 DI 10.1016/S0741-5214(03)01033-4 PG 15 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 740VU UT WOS:000186423300034 PM 14603220 ER PT J AU Ohagen, A Devitt, A Kunstman, KJ Gorry, PR Rose, PP Korber, B Taylor, J Levy, R Murphy, RL Wolinsky, SM Gabuzda, D AF Ohagen, A Devitt, A Kunstman, KJ Gorry, PR Rose, PP Korber, B Taylor, J Levy, R Murphy, RL Wolinsky, SM Gabuzda, D TI Genetic and functional analysis of full-length human immunodeficiency virus type 1 env genes derived from brain and blood of patients with AIDS SO JOURNAL OF VIROLOGY LA English DT Article ID GP120 ENVELOPE GLYCOPROTEIN; HUMAN MONOCLONAL-ANTIBODY; CHEMOKINE RECEPTOR UTILIZATION; CYTOPLASMIC DOMAIN; SMALL-MOLECULE; HIV-1; NEUTRALIZATION; INFECTION; CORECEPTOR; CCR5 AB The genetic evolution of human immunodeficiency virus type 1 (HIV-1) in the brain is distinct from that in lymphoid tissues, indicating tissue-specific compartmentalization of the virus. Few primary HIV-1 envelope glycoproteins (Envs) from uncultured brain tissues have been biologically well characterized. In this study, we analyzed 37 full-length env genes from uncultured brain biopsy and blood samples from four patients with AIDS. Phylogenetic analysis of intrapatient sequence sets showed distinct clustering of brain relative to blood env sequences. However, no brain-specific signature sequence was identified. Furthermore, there was no significant difference in the number or positions of N-linked glycosylation sites between brain and blood env sequences. The patterns of coreceptor usage were heterogeneous, with no clear distinction between brain and blood env clones. Nine Envs used CCR5 as a coreceptor, one used CXCR4, and two used both CCR5 and CXCR4 in cell-to-cell fusion assays. Eight Envs could also use CCR3, CCR8, GPR15, STRL33, Apj, and/or GPR1, but these coreceptors did not play a major role in virus entry into microglia. Recognition of epitopes by the 2F5, T30, AG10H9, F105, 17b, and C11 monoclonal antibodies varied among env clones, reflecting genetic and conformational heterogeneity. Envs from two patients contained 28 to 32 N-glycosylation sites in gp120, compared to around 25 in lab strains and well-characterized primary isolates. These results suggest that HIV-1 Envs in brain cannot be distinguished from those in blood on the basis of coreceptor usage or the number or positions of N-glycosylation sites, indicating that other properties underlie neurotropism. The study also demonstrates characteristics of primary HIV-1 Envs from uncultured tissues and implies that Env variants that are glycosylated more extensively than lab strains and well-characterized primary isolates should be considered during development of vaccines and neutralizing antibodies. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Depr Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Depr Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Neurosurg, Chicago, IL 60611 USA. Los Alamos Natl Lab, Los Alamos, NM USA. Santa Fe Inst, Santa Fe, NM 87501 USA. RP Gabuzda, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Depr Canc Immunol & AIDS, JFB816,44 Binney St, Boston, MA 02115 USA. RI Wolinsky, Steven/B-2893-2012; OI Wolinsky, Steven/0000-0002-9625-6697; Murphy, Robert/0000-0003-3936-2052; Korber, Bette/0000-0002-2026-5757 FU NCI NIH HHS [CA79458]; NIAID NIH HHS [AI28691, P30 AI028691]; NIMHD NIH HHS [L60 MD003100]; NINDS NIH HHS [NS35734, NS37277, R01 NS035734, R01 NS037277] NR 49 TC 121 Z9 124 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 NOV PY 2003 VL 77 IS 22 BP 12336 EP 12345 DI 10.1128/JVI.77.22.12336-12345.2003 PG 10 WC Virology SC Virology GA 738NG UT WOS:000186294300048 PM 14581570 ER PT J AU Mroczek, DK Spiro, A AF Mroczek, DK Spiro, A TI Personality structure and process, variance between and within: Integration by means of a developmental framework SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Editorial Material ID TRAITS AB Hooker and McAdams (2003) offer a six-foci model of personality organized around the concepts of structure and process. The structure and process distinction is essentially one of emphasizing within- or between-person variance, yet both types of variance are valuable, especially in personality development. Cattell (1966) understood the distinction and incorporated it into his concept of the data box. Hooker and McAdams's model shares aspects of Cattell's scheme but is more explicitly developmental. We argue that the concept of the developmental trajectory fits neatly into both the Cattell and Hooker-McAdams models and affords a data analytic framework for understanding both within- and between-person variance, allowing greater integration of process and structure approaches. C1 Fordham Univ, Dept Psychol, Bronx, NY 10458 USA. VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. RP Mroczek, DK (reprint author), Fordham Univ, Dept Psychol, Bronx, NY 10458 USA. FU NIA NIH HHS [R01 AG018436] NR 11 TC 2 Z9 2 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD NOV PY 2003 VL 58 IS 6 BP P305 EP P306 PG 2 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA 745WC UT WOS:000186712900002 PM 14614111 ER PT J AU Santamaria, R Almaden, Y Felsenfeld, A Martin-Malo, A Gao, P Cantor, T Aljama, P Rodriguez, M AF Santamaria, R Almaden, Y Felsenfeld, A Martin-Malo, A Gao, P Cantor, T Aljama, P Rodriguez, M TI Dynamics of PTH secretion in hemodialysis patients as determined by the intact and whole PTH assays SO KIDNEY INTERNATIONAL LA English DT Article DE calcium; hemodialysis; PTH; PTH fragments; secondary hyperparathyroidism ID IONIZED CALCIUM-CONCENTRATION; CARBOXYL-TERMINAL FRAGMENTS; PARATHYROID-HORMONE RELEASE; CHRONIC-RENAL-FAILURE; SECONDARY HYPERPARATHYROIDISM; BONE TURNOVER; SET-POINT; METABOLISM; DIAGNOSIS; RECEPTOR AB Background. Renal hyperparathyroidism is assessed by measurement of parathyroid hormone (PTH) levels. The intact PTH assay (I-PTH) not only reacts with 1-84 PTH but also with large, truncated fragments of non-1-84 PTH. Because the whole PTH assay (W-PTH) is specific for 1-84 PTH, non-1-84 PTH is determined by subtracting W-PTH from I-PTH values. These large circulating PTH fragments may exert a hypocalcemic effect by contributing to skeletal resistance to 1-84 PTH. Methods. The dynamic secretion of both 1-84 PTH and non-1-84 PTH was evaluated during the induction of hypo- and hypercalcemia in eight hemodialysis patients. Results. The basal ionized calcium concentration was 1.23 +/- 0.03 mmol/L at which time I-PTH, W-PTH, and non-1-84 PTH values were 276 +/- 78 pg/mL, 164 +/- 48 pg/mL, and 102 +/- 28 pg/mL, respectively. The induction of hypo- and hypercalcemic changes resulted in a sigmoidal response for all three PTH moieties, I-PTH, W-PTH, and non-1-84 PTH. During hypocalcemia, maximal values of W-PTH were greater than those of non-1-84 PTH. But during hypercalcemia, minimal values of W-PTH and non-1-84 PTH were similar. Neither the set points nor the basal/maximal ratios for W-PTH, I-PTH, and non-1-84 PTH were different. At the baseline ionized calcium concentration, the W-PTH (1-84 PTH)/non-1-84 PTH ratio was 1.53 +/- 0.15. Changes in ionized calcium resulted in a sigmoidal relationship with hypocalcemia, increasing this ratio to a maximum of 2.01 +/- 0.30 and hypercalcemia decreasing this ratio to a minimum of 1.18 +/- 0.15 (P < 0.01 vs baseline for both hypo- and hypercalcemia). Conclusion. Although acute changes in serum calcium produce similar secretory responses in 1-84 PTH and non-1-84 PTH, the secretory responses are not proportional for these PTH moieties. Changes in the serum calcium concentration modulate the ratio of 1-84 PTH/non-1-84 PTH in a sigmoidal pattern with hypocalcemia maximizing this ratio. Whether changes in the 1-84 PTH/non-1-84 PTH ratio specifically modulate the calcemic action and other biologic effects of 1-84 PTH remain to be determined. C1 Reina Sofia Univ Hosp, Serv Nephrol, Cordoba 14004, Spain. Reina Sofia Univ Hosp, Res Unit, Cordoba, Spain. W Los Angeles VA Med Ctr, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Scantibodies Lab Inc, Dept R&D & Diagnost, Santee, CA USA. RP Santamaria, R (reprint author), Reina Sofia Univ Hosp, Serv Nephrol, Avda Menendez Pidal S-N, Cordoba 14004, Spain. RI Rodriguez, teresa/H-5452-2011 NR 28 TC 14 Z9 14 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2003 VL 64 IS 5 BP 1867 EP 1873 DI 10.1046/j.1523-1755.2003.00262.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 730HH UT WOS:000185824300036 PM 14531822 ER PT J AU Coburn, JW AF Coburn, JW TI An update on vitamin D as related to nephrology practice: 2003 SO KIDNEY INTERNATIONAL LA English DT Article DE renal osteodystrophy; vitamin D; calcitriol ID CHRONIC-RENAL-FAILURE; DOXERCALCIFEROL 1-ALPHA-HYDROXYVITAMIN D-2; INTERMITTENT CALCITRIOL THERAPY; PARATHYROID-HORMONE SECRETION; SECONDARY HYPERPARATHYROIDISM; DOUBLE-BLIND; D-DEFICIENCY; HEMODIALYSIS-PATIENTS; CALCIUM HOMEOSTASIS; DIALYSIS PATIENTS AB In this article, an up-to-date consideration of vitamin D therapeutics in nephrology is reviewed. The condition of vitamin D insufficiency is defined as the level of serum 25(OH)vitamin D at which vitamin D-2 or D-3 supplementation leads to a reduction of levels of parathyroid hormone (PTH). The risks of such vitamin D insufficiency in the normal population and likely risks in individuals with chronic kidney disease (CKD) stages 3 and 4 are reviewed. The potential for its safe treatment and prevention using moderate supplements of vitamin D-2 or vitamin D-3 are outlined. The role of altered "vitamin D nutrition" in leading to the observed greater incidence of secondary hyperparathyroidism in African Americans with ESRD compared to other racial groups is considered. The actions of active vitamin D sterols to augment intestinal absorption of both calcium and phosphorus, the effect to reduce levels of PTH, and to be a factor contributing to the rising incidence of low bone turnover (adynamic bone) are discussed. Growing evidence for contributions of elevated levels of serum calcium, serum phosphorus, and the calcium x phosphorus product as factors contributing to vascular and cardiac calcification in ESRD patients are cited. Questions are raised about whether the current practice of vitamin D usage in ESRD patients might be a contributing factor to such vascular abnormalities. The economic factors that likely affect the usage of intravenous vitamin D sterols in the United States are reviewed. It is recommended that potential adverse vascular effects of vitamin D sterols related to the increments of serum Ca and P be carefully evaluated. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Med Serv, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. RP Coburn, JW (reprint author), W Los Angeles Vet Affairs Med Ctr, Nephrol Sect, 111L,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 56 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2003 VL 64 SU 87 BP S125 EP S130 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 730CQ UT WOS:000185812000020 ER PT J AU Goldfine, AB Kahn, CR AF Goldfine, AB Kahn, CR TI Adiponectin: linking the fat cell to insulin sensitivity SO LANCET LA English DT Editorial Material ID ACTIVATED PROTEIN-KINASE; SKELETAL-MUSCLE; RESISTANCE; OXIDATION; ACTION/; GENE C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. NR 19 TC 74 Z9 79 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD NOV 1 PY 2003 VL 362 IS 9394 BP 1431 EP 1432 DI 10.1016/S0140-6736(03)14727-7 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 739PX UT WOS:000186356600005 PM 14602433 ER PT J AU Gribben, JG AF Gribben, JG TI Indolent B-cell malignancies: Immune recognition and antiself SO LEUKEMIA & LYMPHOMA LA English DT Article; Proceedings Paper CT 1st International Workshop on Non-Hodgkins Lymphoma CY NOV, 2002 CL CHANTILLY, FRANCE DE B lymphocytes; immunology; bone marrow transplantation; leukemia; B-cell malignancies; chemotherapy; immunotherapeutics ID NON-HODGKINS-LYMPHOMA; ANTI-CD20 MONOCLONAL-ANTIBODY; CHRONIC LYMPHOCYTIC-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; IODINE I-131 TOSITUMOMAB; REFRACTORY LOW-GRADE; T-CELLS; FOLLICULAR LYMPHOMA; PHASE-II; SURFACE-IMMUNOGLOBULIN AB B-cell malignancies appear to be ideal candidates for treatment with immunotherapeutic approaches. Monoclonal antibodies that target cell-surface determinants have been used as single agents in B-cell malignancies, in combination with chemotherapy, and coupled to other agents to create radioimmunoconjugates and immunotoxins. Another approach is to take advantage of the graft-vs.-lymphoma effect seen following allogeneic bone marrow transplantation. To exploit this effect without inducing the complication of graft-vs.-host disease, it is necessary to understand the mechanisms whereby lymphoma cells escape T-cell-mediated responses. CD40 activation may offer a means of increasing the immunogenicity of lymphoma cells and of stimulating allogeneic T-cell proliferation and cytokine production. Vaccination using tumor-specific antigens shows promise as a therapeutic strategy. Pre-clinical studies with immunoglobulin idiotype peptides have shown that humoral and cellular immune responses can be stimulated by antibodies to these peptides, but better tumor antigens need to be identified that can reliably generate cytotoxic T-cell responses. Candidate antigens include heteroclitic peptides from the immunoglobulin V region and newly identified antigens including the cytochrome P450 1B1. Clinical trials are ongoing in all these fields. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gribben, JG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM john_gribben@dfci.harvard.edu NR 55 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD NOV PY 2003 VL 44 SU 3 BP S77 EP S83 DI 10.1080/10428190310001623739 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 763YL UT WOS:000188128000012 PM 15202529 ER PT J AU Liu, WH Makrigiorgos, GM AF Liu, WH Makrigiorgos, GM TI Sensitive and quantitative detection of mutations associated with clinical resistance to STI-571 SO LEUKEMIA RESEARCH LA English DT Article DE mutation detection; known mutation detection; PCR-RFLP; STI-571; chronic myeloid leukemia ID CHRONIC MYELOID-LEUKEMIA; POINT MUTATIONS; BCR-ABL; SITE; PCR; DIAGNOSIS; CANCER; STI571; DNA AB Resistance to chronic myeloid leukemia (CML) drug STI571 has been associated with point mutations in the kinase domain of BCR-ABL. For example, the mutation T315I (g. 68721C>T) and, to a lesser extent, Y253F (g. 58796A>T) appear in a significant proportion of patients resistant to treatment. Mutations appear intimately related to the development of resistance, and they may pre-exist in a small percentage (<1%) of tumor cells at the time of treatment initiation. Most mutation detection methods, including sequencing, are unable to detect such a small percentage of mutations in a background of wild type sequences. We describe the simplification and modification of a recently developed enhanced PCR-RFLP method, and its application to the detection of T315I and Y253F mutations. The method is quantitative, can be used in agarose gel or real time PCR formats, and reliably detects 1 mutation-containing cell in a background of almost 1000 non-mutated cells. The increased sensitivity offered by this assay will allow detection of these mutations at an early stage during treatment and will be useful in rational treatment modification and in studies which address the association between these mutations and drug resistance. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. RP Makrigiorgos, GM (reprint author), Dana Farber Canc Ctr, Level L2,75 Francis St, Boston, MA 02115 USA. FU NCI NIH HHS [5 T32 CA09078] NR 15 TC 16 Z9 17 U1 1 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 NOV PY 2003 VL 27 IS 11 BP 979 EP 982 DI 10.1016/S0145-2126(03000066-3 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 715JQ UT WOS:000184968700002 PM 12859990 ER PT J AU Stone, ME AF Stone, ME TI Handbook of chronic fatigue syndrome. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD NOV 1 PY 2003 VL 128 IS 18 BP 70 EP 70 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 736UY UT WOS:000186192600050 ER PT J AU Rosen, HR AF Rosen, HR TI Hepatitis C pathogenesis: Mechanisms of viral clearance and liver injury SO LIVER TRANSPLANTATION LA English DT Article ID VIRUS ENVELOPE PROTEIN; CD8(+) T-CELLS; HYPERVARIABLE REGION 1; NATURAL-KILLER-CELLS; DENDRITIC CELLS; IMMUNE-RESPONSES; INFECTION; CD4(+); INTERFERON; PERSISTENCE AB 1. The development of hepatitis C virus (HCV) quasispecies has a number of biological consequences, including the development of escape mutants to humoral or cellular immunity, the generation of "defective" viral particles, variable cell tropism, and the development of drug resistance. 2. Accumulating evidence shows that HCV affects the early innate immune response mediated by natural killer and dendritic cells. 3. Recent data suggest that clearance of HCV bestows antibody to HCV immunity that affords partial protection against persistent infection. However, after spontaneous recovery from HCV infection, titers of HCV-specific antibodies decline and disappear in a subset of patients, whereas viral-specific CD4(+) and CD8(+) T-cell responses persist for decades. 4. HCV-specific CD8(+) T-cell responses are phenotypically and functionally diverse and may be associated with either viral eradication or chronic hepatic immunopathologic states. 5. Novel HCV genome-wide screening approaches have shown that the breadth of the immune response is considerably greater than was initially appreciated using more conventional assays, but why the majority of patients remain chronically infected despite the presence of vital-specific immune responses remains undefined. C1 Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol, Portland, OR 97207 USA. RP Rosen, HR (reprint author), Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol, SW US Vet Hosp 371 0, P3-G1, Portland, OR 97207 USA. FU NIDDK NIH HHS [U01-DK60342-01, R01 DK60590-1] NR 57 TC 32 Z9 32 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 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD NOV PY 2003 VL 9 IS 11 SU 3 BP S35 EP S43 DI 10.1053/jlts.2003.50253 PG 9 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 738DC UT WOS:000186270600006 PM 14586893 ER PT J AU Lin, FH Kwong, KK Huang, IJ Belliveau, JW Wald, LL AF Lin, FH Kwong, KK Huang, IJ Belliveau, JW Wald, LL TI Degenerate mode birdcage volume coil for sensitivity-encoded imaging SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE parallel MRI; SENSE; birdcage; RF coil; brain ID MR; RECONSTRUCTION; INHOMOGENEITY; ACQUISITION; SENSE; BRAIN; SMASH AB A volume birdcage coil for accelerated image encoding with parallel acquisition methods such as SENSE is demonstrated. The coil is degenerately tuned with both the standard homogeneous mode and the first gradient mode of the birdcage coil resonant at the Larmor frequency. Conventional and antisymmetric coupling structures allow imaging from each of these modes simultaneously. The coil for SENSE-type reconstruction with acceleration factors of up to 2-fold is demonstrated. The spatial distribution of the added noise from the SENSE reconstruction (g-factor map) due to geometrical arrangement of the two-channel system is estimated. The spatially averaged g-factors were found to be 1.21, 1.36, and 1.55 for 1.3, 1.6, and 2-fold accelerations, respectively. The system was demonstrated in vivo using accelerated and nonaccelerated anatomical brain images at 1.5 T. The maximal 2-fold acceleration in this dual-mode degenerate birdcage coil offers the potential to extend SENSE-type image reconstruction methods to applications demanding uniform whole brain coverage. Magn Reson Med 50:1107-1111, 2003. (C) 2003 Wiley-Liss, Inc. C1 MGH, HMS, MIT, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Harvard MIT Div Hlth Sci & Technol, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Natl Taiwan Univ, Dept Elect Engn, Taipei 10764, Taiwan. RP Wald, LL (reprint author), MGH, HMS, MIT, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149 13th St,Mailcode 149-2301, Charlestown, MA 02129 USA. RI Lin, Fa-Hsuan/G-6988-2012; Wald, Lawrence/D-4151-2009 OI Lin, Fa-Hsuan/0000-0002-9539-1731; FU NCRR NIH HHS [P41RR14075] NR 12 TC 11 Z9 11 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD NOV PY 2003 VL 50 IS 5 BP 1107 EP 1111 DI 10.1002/mrm.10632 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 739DF UT WOS:000186326400026 PM 14587023 ER PT J AU Epstein, AM Weissman, JS Schneider, EC Gatsonis, C Leape, LL Piana, RN AF Epstein, AM Weissman, JS Schneider, EC Gatsonis, C Leape, LL Piana, RN TI Race and gender disparities in rates of cardiac revascularization - Do they reflect appropriate use of procedures or problems in quality of care? SO MEDICAL CARE LA English DT Article DE access to care; quality of care; racial disparities; gender disparities; underuse; overuse; disparities in care ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY DISEASE; INVASIVE CARDIOVASCULAR PROCEDURES; BYPASS GRAFT-SURGERY; RACIAL-DIFFERENCES; SEX-DIFFERENCES; HEART-DISEASE; MEDICAL-CARE; RENAL-TRANSPLANTATION; AMERICAN-COLLEGE AB BACKGROUND. Numerous studies have documented substantial differences by race and gender in the use of coronary artery bypass graft surgery and percutaneous coronary angioplasty. However, few studies have examined whether these differences reflect problems in quality of care. METHOD. We selected a random sample stratified by gender, race, and income of 5026 Medicare beneficiaries aged 65 to 75 who underwent inpatient coronary angiography during 1991 to 1992 in 1 of 5 states. We compared the frequency of 2 problems in quality by race and gender underuse or the failure to receive a clinically indicated revascularization procedure and receipt of revascularization when it was not clinically indicated. We used 2 independent sets of criteria developed by the RAND Corporation and the American College of Cardiology/American Hospital Association (ACC/ AHA). We also examined survival of the cohort through March 31, 1994. RESULTS. Revascularization procedures were clinically indicated more frequently among whites than blacks and among men than women. Failure to receive revascularization when it was indicated was more common among blacks than among whites (40% vs. 23-24%, depending on the criteria, both P < 0.001) but similar among men and women (25% vs. 22-24%, P >0.05). Racial disparities remained similar after adjusting for patient and hospital characteristics. Among patients rated inappropriate, use of procedures was greater for whites than blacks using RAND criteria (10.5% vs. 5.8%, P < 0.01) and greater for men than for women (14.2% vs. 5.3% by RAND criteria, P = 0.001; 8.2% vs. 4.0%% by ACC/AHA criteria, P = 0.04). After multivariate adjustment, the disparities for race and gender remained similar and were statistically significant using RAND criteria. Mortality rates tended to validate our appropriateness criteria for underuse. CONCLUSIONS. Racial differences in procedure use reflect higher rates of clinical appropriateness among whites, greater underuse among blacks, and more frequent revascularization when it was not clinically indicated among whites. Underuse is associated with higher mortality. In contrast, men had higher rates of clinical appropriateness and were more likely to receive revascularization when it was not clinically indicated. There was no evidence of greater underuse among women. C1 Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gen Med, Sect Hlth Serv & Policy Res, Boston, MA 02115 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Vanderbilt Univ, Ctr Med, Div Cardiol, Nashville, TN 37232 USA. Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Epstein, AM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. OI Schneider, Eric/0000-0002-1132-5084 FU AHRQ HHS [5 R0 HS07098-02S1] NR 57 TC 92 Z9 92 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD NOV PY 2003 VL 41 IS 11 BP 1240 EP 1255 DI 10.1097/01.MLR.0000093423.38746.8C PG 16 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 738DB UT WOS:000186270500004 PM 14583687 ER PT J AU Friebely, JS Regestein, QR Shifren, JL AF Friebely, JS Regestein, QR Shifren, JL TI Cognitive test performance between users and non-users of postmenopausal estrogens SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 14th Annual Meeting of the North-American-Menopause-Society CY SEP 17-20, 2003 CL MIAMI, FLORIDA SP N Amer Menopause Soc C1 Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV-DEC PY 2003 VL 10 IS 6 BP 599 EP 599 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 743TE UT WOS:000186589000173 ER PT J AU Drenkard, E AF Drenkard, E TI Antimicrobial resistance of Pseudomonas aeruginosa biofilms SO MICROBES AND INFECTION LA English DT Review DE Pseudomonas aeruginosa; biolilms; antimicrobial resistance ID ESCHERICHIA-COLI BIOFILMS; ANTIBIOTIC-RESISTANCE; GROWTH-RATE; TWITCHING MOTILITY; HYDROGEN-PEROXIDE; GENE-EXPRESSION; SIGMA-FACTOR; EFFLUX PUMP; CIPROFLOXACIN; PENETRATION AB Resistance to antimicrobial agents is the most important feature of biofilm infections. As a result, infections caused by bacterial biofilms are persistent and very difficult to eradicate. Although several mechanisms have been postulated to explain reduced susceptibility to antimicrobials in bacterial biofilms, it is becoming evident that biofilm resistance is multifactorial. The contribution of each of the different mechanisms involved in biofilm resistance is now beginning to emerge. (C) 2003 Editions scientitiques et medicales Elsevier SAS. All rights reserved. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Drenkard, E (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RI Hori, Katsutoshi/K-5289-2012 NR 51 TC 207 Z9 234 U1 5 U2 39 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD NOV PY 2003 VL 5 IS 13 BP 1213 EP 1219 DI 10.1016/j.micinf.2003.08.009 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 745PD UT WOS:000186696300007 PM 14623017 ER PT J AU Roose, T Netti, PA Munn, LL Boucher, Y Jain, RK AF Roose, T Netti, PA Munn, LL Boucher, Y Jain, RK TI Solid stress generated by spheroid growth estimated using a linear poroelasticity model SO MICROVASCULAR RESEARCH LA English DT Article DE solid stress; tumor spheroid; mathematical model ID MULTICELLULAR TUMOR SPHEROIDS; ARTICULAR-CARTILAGE; TENSEGRITY MODEL; LYMPHATICS; ABSENCE; ADULT AB The unchecked growth of a solid tumor produces solid stress, causing deformation of the surrounding tissue. This stress can result in clinical complications, especially in confined environments such as the brain, and may also be responsible for pathophysiological anomalies such as the collapse of blood and lymphatic vessels. High stress levels may also inhibit further cell division within tumors. Unfortunately, little is known about the dynamics of stress accumulation in tumors or its effects on cell biology. We present a mathematical model for tumor growth in a confined, elastic environment such as living tissue. The model, developed from theories of thermal expansion using the current configuration of the material element, allows the stresses within the growing tumor and the surrounding medium to be calculated. The experimental observation that confining environments limit the growth of tumor spheroids to less than the limit imposed by nutrient diffusion is incorporated into the model using a stress dependent rate for tumor growth. The model is validated against experiments for MU89 tumor spheroid growth in Type VII agarose gel. Using the mathematical model and the experimental evidence we show that the tumor cell size is reduced by solid stress inside the tumor spheroid. This leads to the interesting possibility that cell size could be a direct indicator of solid stress level inside the tumors in clinical setting. (C) 2003 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Steele Lab Tumor Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Cambridge, MA 02138 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 7, Boston, MA 02114 USA. RI Roose, Tiina/A-6352-2010; Munn, Lance/L-3950-2016; OI Roose, Tiina/0000-0001-8710-1063; Munn, Lance/0000-0003-0698-7232; NETTI, PAOLO/0000-0002-2435-7181 FU NCI NIH HHS [R24-CA-85146] NR 30 TC 120 Z9 124 U1 1 U2 21 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD NOV PY 2003 VL 66 IS 3 BP 204 EP 212 DI 10.1016/S0026-2862(03)00057-8 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 744TM UT WOS:000186649000005 PM 14609526 ER PT J AU Chatterjee, B AF Chatterjee, B TI The role of the androgen receptor in the development of prostatic hyperplasia and prostate cancer SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE androgen receptor; prostate; prostate cancer; androgen; antiandrogen; growth factor; apoptosis; signal cross talk ID LIGAND-BINDING DOMAIN; CARCINOMA-CELLS; TRANSACTIVATION FUNCTION; HORMONE-RECEPTOR; INTERFERING RNAS; TUMOR-SUPPRESSOR; MAMMALIAN-CELLS; GENE-EXPRESSION; PROTEIN; KINASE AB The androgen receptor (AR) is an androgen-inducible transcription factor characterized by a modular primary structure, with each module representing a distinct functional unit. After its interaction with androgens, the cytoplasmic AR is activated and translocated to the nucleus where it binds to target genes at the androgen responsive element(s) and recruits coregulators to form a multiprotein complex that interacts with transcriptional mediators and the basal transcription machinery to regulate gene transcription. Androgens play an essential role in the morphogenesis and physiology of the normal prostate. The etiology of benign prostatic hyperplasia (BPH) and prostatic neoplasia, which can progress to adenocarcinoma, is androgen-dependent, and reduction/obliteration of androgen action in the prostate has been the therapy of choice for BPH and prostate cancer. After androgen withdrawal and antiandrogen treatment, the androgen responsive prostate cancer cells cease to proliferate and undergo apoptosis, causing tumor regression. However, relapses are seen invariably, when tumors emerge as androgen-independent and apoptosis-resistant. Gene amplification and amino acid substitutions in the AR are detected at a high frequency in recurrent tumors. These changes confer growth advantage to the tumor cells due to either hypersensitivity of AR to low, castrate-level androgens or a realignment of the receptor conformation, leading to altered ligand specificity that enables antiandrogens, adrenal androgens and non-androgen steroids act agonistically to increase AR activity. Persistence of signaling by the wildtype AR in therapy-resistant tumors is due to the increased receptor activity caused by cross talk of AR with multiple intracellular signaling cascades, especially the growth factor activated MAP kinase/ERK and PI3 kinase/Akt pathways. Ablation of AR function using antisense oligodeoxynucleotides, ribozymes or small interference RNAs (RNAi) holds promise as future approaches to the successful treatment of hormone-refractory, apoptosis-resistant prostate tumors. C1 Univ Texas, Hlth Sci Ctr, Dept Mol Med, Inst Biotechnol, San Antonio, TX 78245 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Chatterjee, B (reprint author), Univ Texas, Hlth Sci Ctr, Dept Mol Med, Inst Biotechnol, 15355 Lambda Dr, San Antonio, TX 78245 USA. FU NIA NIH HHS [R01 AG19660] NR 81 TC 85 Z9 89 U1 0 U2 5 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD NOV PY 2003 VL 253 IS 1-2 BP 89 EP 101 DI 10.1023/A:1026057402945 PG 13 WC Cell Biology SC Cell Biology GA 727LN UT WOS:000185660200011 PM 14619959 ER PT J AU Meriin, AB Zhang, XQ Miliaras, NB Kazantsev, A Chernoff, YO McCaffery, JM Wendland, B Sherman, MY AF Meriin, AB Zhang, XQ Miliaras, NB Kazantsev, A Chernoff, YO McCaffery, JM Wendland, B Sherman, MY TI Aggregation of expanded polyglutamine domain in yeast leads to defects in endocytosis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CORTICAL ACTIN CYTOSKELETON; SACCHAROMYCES-CEREVISIAE; PROTEIN AGGREGATION; CHOREA-ACANTHOCYTOSIS; LOCALIZATION SIGNALS; HUNTINGTONS-DISEASE; CELLULAR TOXICITY; LINKS HUNTINGTIN; BINDING-PROTEIN; MUTANT AB The role of aggregation of abnormal proteins in cellular toxicity is of general importance for understanding many neurological disorders. Here, using a yeast model, we demonstrate that mutations in many proteins involved in endocytosis and actin function dramatically enhance the toxic effect of polypeptides with an expanded polyglutamine (polyQ) domain. This enhanced cytotoxicity required polyQ aggregation and was dependent on the yeast protein Rnq1 in its prion form. In wild-type cells, expression of expanded polyQ followed by its aggregation led to specific and acute inhibition of endocytosis, which preceded growth inhibition. Some components of the endocytic machinery were efficiently recruited into the polyQ aggregates. Furthermore, in cells with polyQ aggregates, cortical actin patches were delocalized and actin was recruited into the polyQ aggregates. Aggregation of polyQ in mammalian HEK293 cells also led to defects in endocytosis. Therefore, it appears that inhibition of endocytosis is a direct consequence of polyQ aggregation and could significantly contribute to cytotoxicity. C1 Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. Johns Hopkins Univ, Integrated Imaging Ctr, Baltimore, MD 21218 USA. Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. Georgia Inst Technol, Inst Bioengn & Biosci, Atlanta, GA 30332 USA. RP Sherman, MY (reprint author), Boston Univ, Sch Med, Dept Biochem, K323,715 Albany St, Boston, MA 02118 USA. RI Chernoff, Yury/J-2833-2014; OI Chernoff, Yury/0000-0002-8934-9051 FU NIGMS NIH HHS [R01 GM60979, R01 GM060979] NR 63 TC 73 Z9 76 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2003 VL 23 IS 21 BP 7554 EP 7565 DI 10.1128/MCB.23.21.7554-7565.2003 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 734KQ UT WOS:000186055400011 PM 14560003 ER PT J AU Hestermann, EV Brown, M AF Hestermann, EV Brown, M TI Agonist and chemopreventative ligands induce differential transcriptional cofactor recruitment by aryl hydrocarbon receptor SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN BREAST-CANCER; CYTOCHROME P4501A1; IN-VIVO; DIOXIN RECEPTOR; AH RECEPTOR; COMPLEX; COACTIVATOR; MECHANISM; 2,3,7,8-TETRACHLORODIBENZO-PARA-DIOXIN; ASSOCIATION AB Aryl hydrocarbon receptor (AHR) is a transcription factor whose activity is regulated by environmental agents, including several carcinogenic agonists. We measured recruitment of AHR and associated proteins to the human cytochrome P4501A1 gene promoter in vivo. Upon treatment with the agonist beta-naphthoflavone, AHR is rapidly associated with the promoter and recruits the three members of the p160 family of coactivators as well as the p300 histone acetyltransferase, leading to recruitment of RNA polymerase 11 (Pol 11) and induction of gene transcription. AHR, coactivators, and Pol 11 cycle on and off the promoter, with a period of similar to60 min. In contrast, the chemopreventative AHR ligand 3,3'-diindolylmethane promotes AHR nuclear translocation and p160 coactivator recruitment but, remarkably, fails to recruit Pol II or cause histone acetylation. This novel mechanism of receptor antagonism may account for the antitumor properties of chemopreventative compounds targeting the AHR. C1 Dana Farber Canc Inst, Dept Mol 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), 44 Binney St,D730, Boston, MA 02115 USA. RI Myles, Brown/B-6906-2008; OI Brown, Myles/0000-0002-8213-1658 NR 35 TC 97 Z9 100 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2003 VL 23 IS 21 BP 7920 EP 7925 DI 10.1128/MCB.23.21.7920-7925.2003 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 734KQ UT WOS:000186055400042 PM 14560034 ER PT J AU Baba, H Ji, RR Kohno, T Moore, KA Ataka, T Wakai, A Okamoto, M Woolf, CJ AF Baba, H Ji, RR Kohno, T Moore, KA Ataka, T Wakai, A Okamoto, M Woolf, CJ TI Removal of GABAergic inhibition facilitates polysynaptic A fiber-mediated excitatory transmission to the superficial spinal dorsal horn SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID SUBSTANTIA-GELATINOSA NEURONS; RECEPTOR ANTAGONIST KETAMINE; PERIPHERAL-NERVE INJURY; NEUROPATHIC PAIN; MAP KINASE; C-FIBERS; RAT; CORD; GABA; GLYCINE AB Primary afferent A-fiber stimulation normally evokes fast mono- or polysynaptic EPSCs of short duration. However, in the presence of the GABA(A) receptor antagonist bicuculline, repetitive, long lasting, polysynaptic EPSCs can be observed following the initial, fast response. A-fiber-induced ERK activation is also facilitated in the presence of bicuculline. The frequency of miniature EPSCs and the amplitude of the monosynaptic A-fiber-evoked EPSCs are not affected by bicuculline or the GABA(A) receptor agonist muscimol, suggesting that GABA(A) receptors located on somatodendritic sites of excitatory interneurons are critical for this action. Bicuculline-enhanced polysynaptic EPSCs are completely eliminated by NMDA receptor antagonists APV and ketamine, as was the augmented ERK activation. This NMDA receptor-dependent phenomenon may contribute to bicuculline-induced allodynia or hyperalgesia, as well as the hypersensitivity observed in neuropathic pain patients. (C) 2003 Elsevier Inc. All rights reserved. C1 Niigata Univ, Sch Med, Dept Anesthesiol, Niigata 9518510, Japan. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Baba, H (reprint author), Niigata Univ, Sch Med, Dept Anesthesiol, 1-757 Asahimachi, Niigata 9518510, Japan. OI Ji, Ru-Rong/0000-0002-9355-3688 FU NINDS NIH HHS [NS38253-01] NR 35 TC 135 Z9 139 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD NOV PY 2003 VL 24 IS 3 BP 818 EP 830 DI 10.1016/S1044-7431(03)00236-7 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 751YH UT WOS:000187117700024 PM 14664828 ER PT J AU Shen, YH Godlewski, J Bronisz, A Zhu, J Comb, MJ Avruch, J Tzivion, G AF Shen, YH Godlewski, J Bronisz, A Zhu, J Comb, MJ Avruch, J Tzivion, G TI Significance of 14-3-3 self-dimerization for phosphorylation-dependent target binding SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID EXOENZYME-S; CRYSTAL-STRUCTURE; KINASE-ACTIVITY; PROTEIN-KINASE; LIGAND-BINDING; RAF-1 KINASE; IDENTIFICATION; 14-3-3-PROTEINS; SITE; PATHWAYS AB 14-3-3 proteins via binding serine/threonine-phosphorylated proteins regulate diverse intracellular processes in all eukaryotic organisms. Here, we examine the role of 14-3-3 self-dimerization in target binding, and in the susceptibility of 14-3-3 to undergo phosphorylation. Using a phospho-specific antibody developed against a degenerated mode-1 14-3-3 binding motif (RSxpSxP), we demonstrate that most of the 14-3-3-associated proteins in COS-7 cells are phosphorylated on sites that react with this antibody. The binding of these phosphoproteins depends on 14-3-3 dimerization, inasmuch as proteins associated in vivo with a monomeric 14-3-3 form are not recognized by the phospho-specific antibody. The role of 14-3-3 dimerization in the phosphorylation-dependent target binding is further exemplified with two well-defined 14-3-3 targets, Raf and DAF-16. Raf and DAF-16 can bind both monomeric and dimeric 14-3-3; however, whereas phosphorylation of specific Raf and DAF-16 sites is required for binding to dimeric 14-3-3, binding to monomeric 14-3-3 forms is entirely independent of Raf and DAF-16 phosphorylation. We also find that dimerization diminishes 14-3-3 susceptibility to phosphorylation. These findings establish a significant role of 14-3-3 dimerization in its ability to bind targets in a phosphorylation-dependent manner and point to a mechanism in which 14-3-3 phosphorylation and dimerization counterregulate each other. C1 Texas A&M Univ, Cardiovasc Res Inst, Div Mol Cardiol, Hlth Sci Ctr,Coll Med, Temple, TX 76504 USA. Massachusetts Gen Hosp, Dept Mol Biol, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Cell Signaling Technol, Beverly, MA 01915 USA. RP Tzivion, G (reprint author), Texas A&M Univ, Cardiovasc Res Inst, Div Mol Cardiol, Hlth Sci Ctr,Coll Med, Temple, TX 76504 USA. RI Tzivion, Guri/D-8954-2011 FU NIGMS NIH HHS [R01GM-067134, R01 GM067134] NR 46 TC 74 Z9 75 U1 1 U2 7 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2003 VL 14 IS 11 BP 4721 EP 4733 DI 10.1091/mbc.E02-12-0821 PG 13 WC Cell Biology SC Cell Biology GA 746GH UT WOS:000186738300033 PM 14551260 ER PT J AU Shi, Y Blackwell, TK AF Shi, Y Blackwell, TK TI A two-tiered transcription regulation mechanism that protects germ cell identity SO MOLECULAR CELL LA English DT Article ID C-ELEGANS; GENE-EXPRESSION; REPRESSION; EMBRYOS; LINEAGE AB In the November issue of Developmental Cell, Schaner and colleagues (2003) describe remarkable versatility in how the embryonic germ lineage blocks differentiation: in early C. elegans germ cell precursors transcription is silenced but chromatin remains open, and then after lineage restriction a conserved inhibitory chromatin architecture appears. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. CBR Inst Biomed Res, Boston, MA 02115 USA. RP Shi, Y (reprint author), Harvard Univ, Sch Med, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. FU NIGMS NIH HHS [R01 GM062891] NR 10 TC 1 Z9 5 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD NOV PY 2003 VL 12 IS 5 BP 1062 EP 1064 DI 10.1016/S1097-2765(03)00447-7 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 746TX UT WOS:000186764700003 PM 14636565 ER PT J AU Wallberg, AE Yamamura, S Malik, S Spiegelman, BM Roeder, RG AF Wallberg, AE Yamamura, S Malik, S Spiegelman, BM Roeder, RG TI Coordination of p300-mediated chromatin remodeling and TRAP/mediator function through coactivator PGC-1 alpha SO MOLECULAR CELL LA English DT Article ID ACTIVATED RECEPTOR-GAMMA; RETINOID-X-RECEPTOR; NUCLEAR RECEPTORS; TRANSCRIPTIONAL ACTIVATION; DEPENDENT TRANSCRIPTION; TRAP220 COMPONENT; IN-VITRO; COMPLEX; BINDING; LIGAND AB Transcriptional coactivators; showing physical and functional interactions with PPARgamma include the protein acetyl transferase p300, the TRAP/Mediator complex that interacts with the general transcription machinery, and the highly regulated PGC-1alpha. We show that PGC-1alpha directly interacts with TRAP/Mediator, through the PPARgamma-interacting subunit TRAP220, and stimulates TRAP/Mediator-dependent function on DNA templates. Further, while ineffective by itself, PGC-1alpha stimulates p300-dependent histone acetylation and transcription on chromatin templates in response to PPARgamma. These functions are mediated by largely independent PPARgamma, p300, and TRAP220 interaction domains in PGC-1alpha, whereas p300 and TRAP220 show ligand-dependent interactions with a common region of PPARgamma. Apart from showing PGC-1alpha functions both in chromatin remodeling and in preinitiation complex formation or function (transcription), these results suggest a key role for PGC-1alpha, through concerted but dynamic interactions, in coordinating these steps. C1 Rockefeller Univ, Lab Biochem & Mol Biol, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Roeder, RG (reprint author), Rockefeller Univ, Lab Biochem & Mol Biol, 1230 York Ave, New York, NY 10021 USA. FU NCI NIH HHS [CA42567] NR 37 TC 144 Z9 153 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 NOV PY 2003 VL 12 IS 5 BP 1137 EP 1149 DI 10.1016/S1097-2765(03)00391-5 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 746TX UT WOS:000186764700011 PM 14636573 ER PT J AU Schmidt, C Peng, BL Li, ZK Sclabas, GM Fujioka, S Niu, JG Schmidt-Supprian, M Evans, DB Abbruzzese, JL Chiao, PJ AF Schmidt, C Peng, BL Li, ZK Sclabas, GM Fujioka, S Niu, JG Schmidt-Supprian, M Evans, DB Abbruzzese, JL Chiao, PJ TI Mechanisms of proinflammatory cytokine-induced biphasic NF-kappa B activation SO MOLECULAR CELL LA English DT Article ID DEFICIENT MICE; IKK-BETA; LIVER DEGENERATION; PROTEIN-KINASE; C-REL; ALPHA; PHOSPHORYLATION; COMPLEX; DEGRADATION; PATHWAY AB The transcription factor NF-kappaB regulates genes involved in innate and adaptive immune response, inflammation, apoptosis, and oncogenesis. Proinflammatory cytokines induce the activation of NF-kappaB in both transient and persistent phases. We investigated the mechanism for this biphasic NF-kappaB activation. Our results show that MEKK3 is essential in the regulation of rapid activation of NF-kappaB, whereas MEKK2 is important in controlling the delayed activation of NF-kappaB in response to stimulation with the cytokines TNF-alpha and IL-1alpha. MEKK3 is involved in the formation of the IkappaBalpha:NF-kappaB/IKK complex, whereas MEKK2 participates in assembling the IkappaBbeta:NF-kappaB/IKK complex; these two distinct complexes regulate the proinflammatory cytokine-induced biphasic NF-kappaB activation. Thus, our study reveals a novel mechanism in which different MAP3K and IkappaB isoforms are involved in specific complex formation with IKK and NF-kappaB for regulating the biphasic NF-kappaB activation. These findings provide further insight into the regulation of cytokine-induced specific and temporal gene expression. C1 Univ Texas, MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. Univ Texas, Grad Sch Biomed Sci, Program Canc Biol, Houston, TX 77030 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Chiao, PJ (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA. RI Schmidt-Supprian, Marc/F-5893-2011; OI Schmidt-Supprian, Marc/0000-0002-8543-6166; Schmidt, Christian/0000-0002-1260-9732 FU NCI NIH HHS [CA73675-01, CA78778-01]; PHS HHS [R21PA-98-029] NR 44 TC 104 Z9 116 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD NOV PY 2003 VL 12 IS 5 BP 1287 EP 1300 DI 10.1016/S1097-2765(03)00390-3 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 746TX UT WOS:000186764700023 PM 14636585 ER PT J AU Kocks, C Maehr, R Overkleeft, HS Wang, EW Iyer, LK Lennon-Dumenil, AM Ploegh, HL Kessler, BM AF Kocks, C Maehr, R Overkleeft, HS Wang, EW Iyer, LK Lennon-Dumenil, AM Ploegh, HL Kessler, BM TI Functional proteomics of the active cysteine protease content in drosophila S2 cells SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID COMPLEMENT-LIKE PROTEIN; GENOME-WIDE ANALYSIS; ANTIGEN PRESENTATION; CATHEPSIN-L; SCAVENGER RECEPTOR; ANOPHELES-GAMBIAE; MELANOGASTER; PHAGOCYTOSIS; INHIBITORS; MECHANISM AB The fruit fly genome is characterized by an evolutionary expansion of proteases and immunity-related genes. In order to characterize the proteases that are active in a phagocytic Drosophila model cell line ( S2 cells), we have applied a functional proteomics approach that allows simultaneous detection and identification of multiple protease species. DCG-04, a biotinylated, mechanism-based probe that covalently targets mammalian cysteine proteases of the papain family was found to detect Drosophila polypeptides in an activity-dependent manner. Chemical tagging combined with tandem mass spectrometry permitted retrieval and identification of these polypeptides. Among them was thiol-ester motif-containing protein (TEP) 4 which is involved in insect innate immunity and shares structural and functional similarities with the mammalian complement system factor C3 and the pan-protease inhibitor alpha2-macroglobulin. We also found four cysteine proteases with homologies to lysosomal cathepsin (CTS) L, K, B, and F, which have been implicated in mammalian adaptive immunity. The Drosophila CTS equivalents were most active at a pH of 4.5. This suggests that Drosophila CTS are, similar to their mammalian counterparts, predominantly active in lysosomal compartments. In support of this concept, we found CTS activity in phagosomes of Drosophila S2 cells. These results underscore the utility of activity profiling to address the functional role of insect proteases in immunity. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp,Lab Dev Immunol, Boston, MA 02114 USA. Leiden Univ, Leiden Inst Chem, Gorlaeus Labs, NL-2300 RA Leiden, Netherlands. Surface Logix Inc, Brighton, MA 02135 USA. Bauer Lab, Bauer Ctr Genom, Cambridge, MA 02138 USA. Inst Curie, INSERM, F-75248 Paris, France. RP Kessler, BM (reprint author), Harvard Univ, Sch Med, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. RI Lennon-Dumenil, Ana-Maria/I-6716-2016; OI Kessler, Benedikt/0000-0002-8160-2446 FU NIAID NIH HHS [5P01 AI 44220-05]; PHS HHS [1R01 62502] NR 52 TC 31 Z9 34 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD NOV PY 2003 VL 2 IS 11 BP 1188 EP 1197 DI 10.1074/mcp.M300067-MCP200 PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 744MH UT WOS:000186635900005 PM 13130081 ER PT J AU Mahon, MJ Cole, JA Lederer, ED Segre, GV AF Mahon, MJ Cole, JA Lederer, ED Segre, GV TI Na+/H+ exchanger-regulatory factor 1 mediates inhibition of phosphate transport by parathyroid hormone and second messengers by acting at multiple sites in opossum kidney cells SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PROTEIN-KINASE-C; NA/P-I COTRANSPORTER; OK CELLS; NITRIC-OXIDE; PDZ DOMAINS; STIMULATION; RECEPTOR; MOUSE; COMPLEXES; MEMBRANE AB The opossum kidney (OK) line displays PTH-mediated activation of adenylyl cyclase and phospholipase C and inhibition of phosphate (P-i) uptake via regulation of the type IIa sodium-phosphate cotransporter, consistent with effects in vivo. OKH cells, a subclone of the OK cell line, robustly activates PTH-mediated activation of adenylyl cyclase, but is defective in PTH-mediated inhibition of sodium-phosphate cotransport and signaling via phospholipase C. Compared with wild-type OK cells, OKH cells express low levels of the Na+/ H+ exchanger regulatory factor 1 (NHERF-1). Stable expression of NHERF-1 in OKH cells (OKH-N1) rescues the PTH-mediated inhibition of sodium-phosphate cotransport. NHERF-1 also restores the capacity of 8-bromo-cAMP and forskolin to inhibit P-i uptake, but the PTH dose-response for cAMP accumulation and inhibition of P-i uptake differ by 2 orders of magnitude. NHERF-1, in addition, modestly restores phorbol ester-mediated inhibition of P-i uptake, which is much weaker than that elicited by PTH. A poor correlation exists between the inhibition of P-i uptake mediated by PTH (similar to60%) and the inhibition mediated by phorbol 12-myristate 13-acetate (similar to30%) and the ability of these molecules to activate the protein kinase C-responsive reporter gene. Furthermore, we show that NHERF-1 directly interacts with type IIa cotransporter in OK cells. Although, PTH-mediated inhibition of P-i uptake in OK cells is largely NHERF-1 dependent, the signaling pathway(s) by which this occurs is still unclear. These pathways may involve cooperativity between cAMP- and protein kinase C-dependent pathways or activation/inhibition of an unrecognized NHERF-1-dependent pathway(s). C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Univ Louisville, Kidney Dis Program, Louisville, KY 40202 USA. Univ Missouri, Sch Med, Dept Pharmacol, Columbia, MO 65212 USA. RP Segre, GV (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Wellman 501,50 Blossom St, Boston, MA 02114 USA. FU NIDDK NIH HHS [K01 DK59900-01A1, R01 DK062285-01] NR 39 TC 60 Z9 60 U1 1 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD NOV 1 PY 2003 VL 17 IS 11 BP 2355 EP 2364 DI 10.1210/me.2003-0043 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 738EL UT WOS:000186273700019 PM 12881509 ER PT J AU Asakawa, R Komatsuzawa, H Kawai, T Yamada, S Goncalves, RB Izumi, S Fujiwara, T Nakano, Y Suzuki, N Uchida, Y Ouhara, K Shiba, H Taubman, MA Kurihara, H Sugai, M AF Asakawa, R Komatsuzawa, H Kawai, T Yamada, S Goncalves, RB Izumi, S Fujiwara, T Nakano, Y Suzuki, N Uchida, Y Ouhara, K Shiba, H Taubman, MA Kurihara, H Sugai, M TI Outer membrane protein 100, a versatile virulence factor of Actinobacillus actinomycetemcomitans SO MOLECULAR MICROBIOLOGY LA English DT Article ID MICROVASCULAR ENDOTHELIAL-CELLS; GINGIVAL EPITHELIAL-CELLS; ESCHERICHIA-COLI; SEROTYPE-B; SERUM RESISTANCE; PORPHYROMONAS-GINGIVALIS; POLYSACCHARIDE ANTIGEN; MORAXELLA-CATARRHALIS; PERIODONTAL-DISEASE; INVASION AB Actinobacillus actinomycetemcomitans (Aa) is one of the pathogenic bacteria involved in periodontal diseases. We have previously identified six major outer membrane proteins (Omps) of Aa Y4. Among them is an Omp with high molecular mass, designated Omp100, which has homology to a variety of virulence factors. Electron microscopic observation indicated that Omp100 is randomly localized on the cell surface of Aa. Aa Y4 has been shown to adhere and invade KB or normal human gingival keratinocytes. Anti-Omp100 antibody inhibited 50% of adhesion and 70% of invasion of Aa Y4 to KB cells. An Omp100 knock-out mutant had a decreased adhesion and invasion efficiency of 60%, compared with that of the wild type. Escherichia coli HB101 expressing Omp100 adhered twofold and invaded 10-fold more than the wild-type E. coli HB101. HB101 expressing Omp100 showed resistance to serum by trapping factor H, an inhibitor for C3b, with Omp100. Omp100 induced inflammatory cytokine responses of interleukin (IL)-8, IL-6 and tumour necrosis factor (TNF)alpha in epithelial cells, and induced IL-1beta and TNFalpha production in mouse macrophages. These results indicate that Omp100 is a versatile virulence factor that may demonstrate potential significance in the onset of periodontal diseases related to Aa. C1 Hiroshima Univ, Grad Sch Biomed Sci, Dept Bacteriol, Minami Ku, Hiroshima 7348553, Japan. Hiroshima Univ, Grad Sch Biomed Sci, Dept Periodontal Med, Minami Ku, Hiroshima 7348553, Japan. Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. Kawasaki Med Univ, Dept Microbiol, Okayama 7010192, Japan. Hiroshima Univ, Grad Sch Sci, Dept Math & Life Sci, Higashihiroshima 7398526, Japan. Kyushu Univ, Fac Dent Sci, Dept Prevent Dent, Fukuoka 8128582, Japan. RP Komatsuzawa, H (reprint author), Hiroshima Univ, Grad Sch Biomed Sci, Dept Bacteriol, Minami Ku, Kasumi 1-2-3, Hiroshima 7348553, Japan. RI Nakano, Yoshio/J-3182-2013 OI Nakano, Yoshio/0000-0001-9848-3124 FU NIDCR NIH HHS [DE14551, DE3420] NR 47 TC 71 Z9 73 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 2003 VL 50 IS 4 BP 1125 EP 1139 DI 10.1046/j.1365-2958.2003.03748.x PG 15 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 740YJ UT WOS:000186430500007 PM 14622404 ER PT J AU Sabatos, CA Chakravarti, S Cha, E Schubart, A Sanchez-Fueyo, A Zheng, XX Coyle, AJ Strom, TB Freeman, GJ Kuchroo, VK AF Sabatos, CA Chakravarti, S Cha, E Schubart, A Sanchez-Fueyo, A Zheng, XX Coyle, AJ Strom, TB Freeman, GJ Kuchroo, VK TI Interaction of Tim-3 and Tim-3 ligand regulates T helper type 1 responses and induction of peripheral tolerance SO NATURE IMMUNOLOGY LA English DT Article ID HEPATITIS-A VIRUS; CHEMOKINE RECEPTOR EXPRESSION; AUTOIMMUNE-DISEASE; IN-VIVO; CUTTING EDGE; CYTOCHROME-C; RICH REGION; GENE FAMILY; CELLS; LYMPHOCYTES AB T helper type 1 (T(H)1) immune responses are central in cell-mediated immunity, and a T(H)1-specific cell surface molecule called Tim-3 (T cell immunoglobulin domain, mucin domain) has been identified. Here we report the identification of a secreted form of Tim-3 that contains only the immunoglobulin (Ig) variable (V) domain of the full-length molecule. Fusion proteins (Tim-3-Ig) of both Tim-3 isoforms specifically bound CD4(+) T cells, indicating that a Tim-3 ligand is expressed on CD4(+) T cells. Administration of Tim-3-Ig to immunized mice caused hyperproliferation of T(H)1 cells and T(H)1 cytokine release. Tim-3-Ig also abrogated tolerance induction in T(H)1 cells, and Tim-3-deficient mice were refractory to the induction of high-dose tolerance. These data indicate that interaction of Tim-3 with Tim-3 ligand may serve to inhibit effector T(H)1 cells during a normal immune response and may be crucial for the induction of peripheral tolerance. C1 Brigham & Womens Hosp, Dept Neurol, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Immunol, Boston, MA 02215 USA. Millennium Pharmaceut, Inflammat Dept, Div Expt Med, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Kuchroo, VK (reprint author), Brigham & Womens Hosp, Dept Neurol, Ctr Neurol Dis, 75 Francis St, Boston, MA 02115 USA. OI Cha, Eugene/0000-0002-8807-2353 FU NIAID NIH HHS [1R01AI44880-03, 2P01AI39671-07]; NIGMS NIH HHS [1F31GM20927-01]; NINDS NIH HHS [2R37NS30843-11, 1PO1NS38037-04, 1R01NS045937-01, 2R01NS35685-06] NR 36 TC 290 Z9 333 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD NOV PY 2003 VL 4 IS 11 BP 1102 EP 1110 DI 10.1038/ni988 PG 9 WC Immunology SC Immunology GA 737PN UT WOS:000186241100014 PM 14556006 ER PT J AU Brander, C Walker, BD AF Brander, C Walker, BD TI Gradual adaptation of HIV to human host populations: good or bad news? SO NATURE MEDICINE LA English DT Article ID T-CELL RESPONSES; SIMIAN IMMUNODEFICIENCY VIRUS; LYMPHOCYTE RESPONSES; PRIMARY INFECTION; ESCAPE MUTATIONS; VIRAL LOAD; HLA; SELECTION; IMMUNODOMINANT; EVOLUTION AB The continuous evolution and adaptation of HIV to its host has produced extensive global viral diversity. Understanding the kinetics and directions of this continuing adaptation and its impact on viral fitness, immunogenicity and pathogenicity will be crucial to the successful design of effective HIV vaccines. Here we discuss some potential scenarios of viral and host coevolution. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA 02114 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Brander, C (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. OI Brander, Christian/0000-0002-0548-5778 NR 38 TC 51 Z9 52 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 2003 VL 9 IS 11 BP 1359 EP 1362 DI 10.1038/nm941 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 739AH UT WOS:000186319700024 PM 14595431 ER PT J AU Ambati, J Anand, A Fernandez, S Sakurai, E Lynn, BC Kuziel, WA Rollins, BJ Ambati, BK AF Ambati, J Anand, A Fernandez, S Sakurai, E Lynn, BC Kuziel, WA Rollins, BJ Ambati, BK TI An animal model of age-related macular degeneration in senescent Ccl-2-or Ccr-2-deficient mice SO NATURE MEDICINE LA English DT Article ID RETINAL-PIGMENT EPITHELIUM; ENDOTHELIAL GROWTH-FACTOR; GLYCATION END-PRODUCTS; CHLAMYDIA-PNEUMONIAE INFECTION; HIGH-FAT DIET; CHOROIDAL NEOVASCULARIZATION; BRUCHS MEMBRANE; COMPLEMENT ACTIVATION; TARGETED DISRUPTION; DEPOSIT FORMATION AB The study and treatment of age-related macular degeneration (AMD), a leading cause of blindness, has been hampered by a lack of animal models. Here we report that mice deficient either in monocyte chemoattractant protein-1 (Ccl-2; also known as MCP-1) or its cognate C-C chemokine receptor-2 (Ccr-2) develop cardinal features of AMD, including accumulation of lipofuscin in and drusen beneath the retinal pigmented epithelium (RPE), photoreceptor atrophy and choroidal neovascularization (CNV). Complement and IgG deposition in RPE and choroid accompanies senescence in this model, as in human AMD. RPE or choroidal endothelial production of Ccl-2 induced by complement C5a and IgG may mediate choroidal macrophage infiltration into aged wild-type choroids. Wild-type choroidal macrophages degrade C5 and IgG in eye sections of Ccl2(-/-) or Ccr2(-/-) mice. Impaired macrophage recruitment may allow accumulation of C5a and IgG, which induces vascular endothelial growth factor (VEGF) production by RPE, possibly mediating development of CNV. These models implicate macrophage dysfunction in AMD pathogenesis and may be useful as a platform for validating therapies. C1 Univ Kentucky, Dept Ophthalmol, Lexington, KY 40536 USA. Univ Kentucky, Dept Microbiol & Immunol, Lexington, KY 40506 USA. Univ Kentucky, Dept Chem, Lexington, KY 40506 USA. Univ Texas, Inst Mol & Cellular Biol, Austin, TX 78712 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Med Coll Georgia, Dept Ophthalmol, Augusta, GA 30907 USA. RP Ambati, J (reprint author), Univ Kentucky, Dept Ophthalmol, 740 S Limestone St, Lexington, KY 40536 USA. NR 47 TC 399 Z9 418 U1 2 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 2003 VL 9 IS 11 BP 1390 EP 1397 DI 10.1038/nm950 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 739AH UT WOS:000186319700029 PM 14566334 ER PT J AU Chen, SZ Rio, C Ji, RR Dikkes, P Coggeshall, RE Woolf, CJ Corfas, G AF Chen, SZ Rio, C Ji, RR Dikkes, P Coggeshall, RE Woolf, CJ Corfas, G TI Disruption of ErbB receptor signaling in adult non-myelinating Schwann cells causes progressive sensory loss SO NATURE NEUROSCIENCE LA English DT Article ID NEUROTROPHIC FACTOR GDNF; SPINAL-CORD; SCIATIC-NERVE; PAIN HYPERSENSITIVITY; NEURON SURVIVAL; TRANSGENIC MICE; UP-REGULATION; EXPRESSION; NEUREGULIN; PROTEIN AB Here we studied the role of signaling through ErbB-family receptors in interactions between unmyelinated axons and non-myelinating Schwann cells in adult nerves. We generated transgenic mice that postnatally express a dominant-negative ErbB receptor in non-myelinating but not in myelinating Schwann cells. These mutant mice present a progressive peripheral neuropathy characterized by extensive Schwann cell proliferation and death, loss of unmyelinated axons and marked heat and cold pain insensitivity. At later stages, C-fiber sensory neurons die by apoptosis, a process that may result from reduced GDNF (glial cell line-derived neurotrophic factor) expression in the sciatic nerve. Neuregulin 1 (NRG1)-ErbB signaling mediates, therefore, reciprocal interactions between non-myelinating Schwann cells and unmyelinated sensory neuron axons that are critical for Schwann cell and C-fiber sensory neuron survival. This study provides new insights into ErbB signaling in adult Schwann cells, the contribution of non-myelinating Schwann cells in maintaining trophic support of sensory neurons, and the possible role of disrupted ErbB signaling in peripheral sensory neuropathies. C1 Harvard Univ, Sch Med, Childrens Hosp, Div Neurosci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Univ Texas, Med Branch, Dept Anat & Neurosci, Galveston, TX 77555 USA. RP Corfas, G (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Div Neurosci, 300 Longwood Ave, Boston, MA 02115 USA. OI Ji, Ru-Rong/0000-0002-9355-3688 FU NICHD NIH HHS [P30-HD 18655]; NIDCD NIH HHS [R01 DC04820]; NINDS NIH HHS [NS38253, NS39518, NS40698, R01 NS35884] NR 49 TC 111 Z9 112 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2003 VL 6 IS 11 BP 1186 EP 1193 DI 10.1038/nn1139 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 737KH UT WOS:000186229200018 PM 14555954 ER PT J AU Nelson, PS Montgomery, B AF Nelson, PS Montgomery, B TI Unconventional therapy for prostate cancer: Good, bad or questionable? SO NATURE REVIEWS CANCER LA English DT Review ID RANDOMIZED CLINICAL-TRIAL; CELL-CYCLE PROGRESSION; PC-SPES; VITAMIN-E; GREEN TEA; ALPHA-TOCOPHEROL; BETA-CAROTENE; UNITED-STATES; SAW PALMETTO; IN-VITRO AB Complementary and alternative medicine (CAM) encompasses a wide range of interventions that are often used for the prevention and treatment of malignant disease. As prostate cancer is characterized by strong dietary influences, a long disease latency period and limited treatment strategies for advanced disease, many patients turn to CAM with the belief that they represent a viable therapeutic option that is free of adverse side effects. Although the efficacy of many CAM therapies seems compelling, definitive studies are underway and the potentially harmful effects of these 'natural' interventions need to be recognized. C1 Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98105 USA. Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98105 USA. Univ Washington, Dept Med, Seattle, WA 98108 USA. VA Puget Sound HCS, Seattle, WA 98108 USA. RP Nelson, PS (reprint author), Fred Hutchinson Canc Res Ctr, Div Human Biol, 1100 Fairview Ave, Seattle, WA 98105 USA. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 106 TC 32 Z9 33 U1 3 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD NOV PY 2003 VL 3 IS 11 BP 845 EP 858 DI 10.1038/nrc1210 PG 14 WC Oncology SC Oncology GA 739AJ UT WOS:000186319800015 PM 14668815 ER PT J AU Liang, P Pardee, AB AF Liang, P Pardee, AB TI Timeline - Analysing differential gene expression in cancer SO NATURE REVIEWS CANCER LA English DT Editorial Material ID DNA MICROARRAYS; MESSENGER-RNA; P53-DEPENDENT APOPTOSIS; P53-INDUCED APOPTOSIS; POTENTIAL MEDIATOR; RAS ONCOGENES; TARGET GENE; CELL-LINE; P53; DISPLAY C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Vanderbilt Univ, Sch Med, Dept Canc Biol, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA. RP Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. EM peng.liang@vanderbilt.edu; Arthur_Pardee@dfci.harvard.edu NR 88 TC 69 Z9 71 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X EI 1474-1768 J9 NAT REV CANCER JI Nat. Rev. Cancer PD NOV PY 2003 VL 3 IS 11 BP 869 EP 876 DI 10.1038/nrc1214 PG 8 WC Oncology SC Oncology GA 739AJ UT WOS:000186319800017 PM 14668817 ER PT J AU McClatchey, AI AF McClatchey, AI TI Opinion - Merlin and ERM proteins: Unappreciated roles in cancer development? SO NATURE REVIEWS CANCER LA English DT Editorial Material ID NF2 TUMOR-SUPPRESSOR; EPIDERMAL-GROWTH-FACTOR; EZRIN/RADIXIN/MOESIN PROTEINS; NEUROFIBROMATOSIS TYPE-2; FACTOR RECEPTOR; GENE-PRODUCT; FERM DOMAIN; CONTACT INHIBITION; EPITHELIAL-CELLS; RHO-GTPASES C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Dept Pathol, Charlestown, MA 02129 USA. RP McClatchey, AI (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Dept Pathol, 149 13th St, Charlestown, MA 02129 USA. NR 85 TC 131 Z9 139 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD NOV PY 2003 VL 3 IS 11 BP 877 EP 883 DI 10.1038/nrc1213 PG 7 WC Oncology SC Oncology GA 739AJ UT WOS:000186319800018 PM 14668818 ER PT J AU von Andrian, UH Mempel, TR AF von Andrian, UH Mempel, TR TI Homing and cellular traffic in lymph nodes SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID HIGH ENDOTHELIAL VENULES; CXC CHEMOKINE RECEPTOR-5; STEADY-STATE CONDITIONS; NAIVE T-CELLS; DENDRITIC CELLS; L-SELECTIN; IN-VIVO; VASCULAR ADDRESSIN; SPHINGOSINE 1-PHOSPHATE; LANGERHANS CELLS AB Lymph nodes (LNs) are the organs where innate immune responses lead to acquired immunity, where some of our most devastating pathogens evade immunity, and where autoreactive lymphocytes first encounter tissue-specific self-antigens and are either tolerized or activated. The many roles of LNs depend on the coordinated migration of its cellular constituents. This article covers new insights into the organization and microvascular specialization of LNs, the guidance mechanisms that allow lymphocytes and antigen-presenting cells to find their correct place in the nodal parenchyma; and the role of afferent lymph flow in LN function. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. RI von Andrian, Ulrich/A-5775-2008 NR 148 TC 672 Z9 682 U1 8 U2 47 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD NOV PY 2003 VL 3 IS 11 BP 867 EP 878 DI 10.1038/nri1222 PG 12 WC Immunology SC Immunology GA 743EC UT WOS:000186558600013 PM 14668803 ER PT J AU Hogemann-Savellano, D Bos, E Blondet, C Sato, F Abe, T Josephson, L Weissleder, R Gaudet, J Sgroi, D Peters, PJ Basilion, JP AF Hogemann-Savellano, D Bos, E Blondet, C Sato, F Abe, T Josephson, L Weissleder, R Gaudet, J Sgroi, D Peters, PJ Basilion, JP TI The transferrin receptor: A potential molecular Imaging marker for human cancer SO NEOPLASIA LA English DT Article DE transferrin receptor; molecular imaging; CLIO; breast cancer; electron microscopy ID CELL-SURFACE GLYCOPROTEIN; GENE-EXPRESSION; IN-VIVO; GA-67; TISSUE; INTERNALIZATION; MACROMOLECULES; PROLIFERATION; EFFICIENCY; MECHANISM AB Noninvasive imaging of differences between the molecular properties of cancer and normal tissue has the potential to enhance the detection of tumors. Because overexpression of endogenous transferrin receptor (TfR) has been qualitatively described for various cancers and is presumably due to malignant transformation of cells, TfR may represent a suitable target for application of molecular imaging technologies to increase detection of smaller tumors. In the work reported here, investigation into the biology of this receptor using electron microscopy has demonstrated that iron oxide particles targeted to TfR are internalized and accumulate in lysosomal vesicles within cells. Biochemical analysis of the interaction of imaging probes with cells overexpressing the TfR demonstrated that the extent of accumulation, and therefore probe efficacy, is dependent on the nature of the chemical cross-link between transferrin and the iron oxide particle. These data were utilized to design and synthesize an improved imaging probe. Experiments demonstrate that the novel magnetic resonance imaging (MRI) probe is sensitive enough to detect small differences in endogenous TfR expression in human cancer cell lines. Quantitative measurement of TfR overexpression in a panel of 27 human breast cancer patients demonstrated that 74% of patient cancer tissues overexpressed the TfR and that the sensitivity of the new imaging agent was suitable to detect TfR overexpression in greater than 40% of these cases. Based on a biochemical and cell biological approach, these studies have resulted in the synthesis and development of an improved MRI probe with the best in vitro and in vivo imaging properties reported to date. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Netherlands Canc Inst, Antoni Van Leeuwenhoek Hosp, NL-1066 CX Amsterdam, Netherlands. Massachusetts Gen Hosp, NFCR, Ctr Mol Anal & Imaging, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. RP Basilion, JP (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St 5406, Charlestown, MA 02129 USA. EM basilion@helix.mgh.harvard.edu FU NCI NIH HHS [R01 CA085240, R01 CA85240] NR 38 TC 106 Z9 109 U1 1 U2 17 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD NOV-DEC PY 2003 VL 5 IS 6 BP 495 EP 506 PG 12 WC Oncology SC Oncology GA 760MX UT WOS:000187838900004 PM 14965443 ER PT J AU Klucken, J McLean, PJ Gomez-Tortosa, E Ingelsson, M Hyman, BT AF Klucken, J McLean, PJ Gomez-Tortosa, E Ingelsson, M Hyman, BT TI Neuritic alterations and neural system dysfunction in Alzheimer's disease and dementia with Lewy bodies SO NEUROCHEMICAL RESEARCH LA English DT Review DE AD; DLB; neurodegeneration; synaptic plasticity ID AMYLOID PRECURSOR PROTEIN; CENTRAL-NERVOUS-SYSTEM; A-BETA COMPONENT; ALPHA-SYNUCLEIN IMMUNOREACTIVITY; LONG-TERM POTENTIATION; PARKINSONS-DISEASE; SYNAPTIC PLASTICITY; TRANSGENIC MICE; BODY DISEASE; SENILE PLAQUES AB Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are neurodegenerative disorders that share progressive dementia as the common major clinical symptom. Damages to memory-related brain structures are the likely pathological correlate, and in both illnesses deposition of amyloidogenic proteins are present mainly within these limbic structures. Amyloid-beta-positive plaques and phospho-tau-positive neurofibrillary tangles are the main feature of AD and alpha-synuclein-positive Lewy bodies and Lewy neurites are found in DLB. Interestingly the associated proteins also interfere with synaptic function and synaptic plasticity. Here, we propose that the same neuronal circuits are disturbed within the hippocampal formation in AD and DLB and that in both diseases the associated proteins might lead to changes in synaptic plasticity and function. Thus both classic neuropathological changes and cellular dysfunctions might contribute to the cognitive impairments in AD and DLB. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. Fdn Jimenez Diaz, Serv Neurol, E-28040 Madrid, Spain. RP Hyman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS 38372] NR 121 TC 16 Z9 17 U1 1 U2 3 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD NOV PY 2003 VL 28 IS 11 BP 1683 EP 1691 DI 10.1023/A:1026061021946 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 730JK UT WOS:000185827500011 PM 14584822 ER PT J AU Leergaard, TB Bjaalie, JG Devor, A Wald, LL Dale, AM AF Leergaard, TB Bjaalie, JG Devor, A Wald, LL Dale, AM TI In vivo tracing of major rat brain pathways using manganese-enhanced magnetic resonance imaging and three-dimensional digital atlasing SO NEUROIMAGE LA English DT Article DE brain atlas; corticocortical; cortico-subcortical; corticothalamic; neural tracing; T-1-weighted MRI; topography ID PRIMARY SOMATOSENSORY CORTEX; FAST AXONAL-TRANSPORT; CORTICOTHALAMIC PROJECTIONS; NEURONAL CONNECTIONS; BARREL CORTEX; ORGANIZATION; VALIDATION; URETHANE; SYSTEM; MOUSE AB The magnetic resonance imaging (MRI)-detectable T-1 contrast agent manganese (Mn2+) has recently been introduced as a neural tracer in rodents, birds, and monkeys. We have tested to what extent this in vivo method is useful for three-dimensional (3-D) survey of connectivity patterns in the rat somatosensory system. A commonly available 3 T human clinical MRI scanner was used to trace neural pathways following focal injection of manganese chloride (MnCl2) in the somatosensory cortex. Six to 10 h after MnCl2 injection, we found significant signal enhancement in major projection systems, including corticocortical, corticostriatal, corticothalamic, corticotectal, corticopontine, and corticospinal pathways. To facilitate the assignment of anatomic localization to the observed Mn2+ signal enhancement, we registered the MRI data with a 3-D digital reconstruction of a stereotaxic rat brain atlas. Across-animal comparison using the digital model allowed demonstration of a corticothalamic 3-D topographic organization in agreement with previously published two-dimensional topographic schemes based on classical neural tracing data. We conclude that anterograde MnCl2/MRI tracing allows rapid analysis of topographic organization across multiple brain regions. The method allows a higher data throughput for 3-D studies of large-scale brain connectivity than conventional methods based on tissue sectioning. (C) 2003 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Boston, MA 02129 USA. Univ Oslo, Inst Basic Med Sci, Dept Anat, N-0317 Oslo, Norway. Univ Oslo, Ctr Mol Biol & Neurosci, Neural Syst & Graph Comp Lab, N-0317 Oslo, Norway. RP Dale, AM (reprint author), Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Bldg 149,13th St, Boston, MA 02129 USA. RI Dale, Anders/A-5180-2010; Wald, Lawrence/D-4151-2009 FU NIBIB NIH HHS [R01 EB000790, R01-EB00307, R01-EB00790]; NINDS NIH HHS [R01-NS39581] NR 44 TC 73 Z9 79 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD NOV PY 2003 VL 20 IS 3 BP 1591 EP 1600 DI 10.1016/S1053-8119(03)00459-2 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 746AK UT WOS:000186723800014 PM 14642470 ER PT J AU Manoach, DS Greve, DN Lindgren, KA Dale, AM AF Manoach, DS Greve, DN Lindgren, KA Dale, AM TI Identifying regional activity associated with temporally separated components of working memory using event-related functional MRI SO NEUROIMAGE LA English DT Article ID DORSOLATERAL PREFRONTAL CORTEX; DELAYED-RESPONSE; EXPERIMENTAL-DESIGN; COORDINATE SYSTEM; EXECUTIVE CONTROL; CORTICAL SURFACE; BRAIN-REGIONS; BASAL GANGLIA; FMRI EVIDENCE; MAINTENANCE AB This study describes the neural circuitry underlying temporally separated components of working memory (WM) performance-stimulus encoding, maintenance of information during a delay, and the response to a probe. While other studies have applied event-related fMRI to separate epochs of WM tasks, this study differs in that it employs a methodology that does not make any a priori assumptions about the shape of the hemodynamic response (HDR). This is important because no one model of the HDR is valid across the range of activated brain regions and stimulus types. Systematic modeling inaccuracies may lead to the misattribution of activity to adjacent events. Twelve healthy subjects performed a numerical version of the Sternberg Item Recognition Paradigm adapted for rapid presentation event-related fMRI. This paradigm emphasized maintenance rather than manipulative WM processes and used a subcapacity WM load. WM trials with different delay lengths were compared to fixation. The HDR of the entire WM trial for each trial type was estimated using a finite impulse response (FIR). Regional activity associated with the Encode, Delay, and Probe epochs was identified using contrasts that were based on the FIR estimates and by examining the HDRs. Each epoch was associated with a distinct but overlapping pattern of regional activity. Activation of the dorsolateral prefrontal cortex, thalamus, and basal ganglia was exclusively associated with the probe. This suggests that frontostriatal neural circuitry participates in selecting an appropriate response based on the contents of WM. (C) 2003 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA. Athinoula A Martinos Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Manoach, DS (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Charlestown Navy Yard,36 1st Ave,Room 420, Boston, MA 02129 USA. RI Dale, Anders/A-5180-2010 FU NCRR NIH HHS [P41RR14075]; NIMH NIH HHS [K23MH01829] NR 63 TC 78 Z9 79 U1 1 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD NOV PY 2003 VL 20 IS 3 BP 1670 EP 1684 DI 10.1016/j.neuroimage.2003.08.002 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 746AK UT WOS:000186723800021 PM 14642477 ER PT J AU Wilkinson, DT Halligan, PW AF Wilkinson, DT Halligan, PW TI Stimulus symmetry affects the bisection of figures but not lines: evidence from event-related fMRI SO NEUROIMAGE LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; MIRROR SYMMETRY; VISUOSPATIAL ATTENTION; UNILATERAL NEGLECT; FUNCTIONAL-ANATOMY; VISUAL NEGLECT; JUDGMENTS; PERCEPTION; ACTIVATION; PARIETAL AB Many geometric shapes retain their symmetry when bisected, but appear asymmetrical when misbisected. We have previously shown that this correspondence can guide the accuracy and speed of perceptual bisection (Landmark) judgments. Using event-related fMRI, here we examined whether the behavioural effects of symmetry are also evident at the neural level. The data showed that the presence/absence of symmetry modulates the activity of right anterior cingulate gyrus, an area associated with a variety of higher level attentional functions. A previous visual half-field study also showed that bisected lines are apprehended more quickly and accurately than misbisected lines in right, but not left, visual field. We were able to localise this advantage to right superior temporal gyrus. Significantly, we found no evidence that symmetry played a role in apprehending the midpoint of the line stimuli traditionally used to assess visual neglect. The data clarify the effects of visual symmetry on bisection behaviour, and highlight novel dissociations within the neural systems thought to underline Landmark performance. (C) 2003 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Boston, MA 02130 USA. Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. Univ Wales Coll Cardiff, Sch Psychol, Cardiff CF10 3YG, S Glam, Wales. RP Wilkinson, DT (reprint author), VA Boston Healthcare Syst, CRECC 182 JP, 150 S Huntington Ave, Boston, MA 02130 USA. RI Halligan, Peter/A-1669-2010 OI Halligan, Peter/0000-0003-2784-6690 NR 39 TC 10 Z9 10 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD NOV PY 2003 VL 20 IS 3 BP 1756 EP 1764 DI 10.1016/S1053-8119(03)00448-8 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 746AK UT WOS:000186723800029 PM 14642485 ER PT J AU Klunk, WE Engler, H Nordberg, A Bacskai, BJ Wang, YM Price, JC Bergstrom, M Hyman, BT Langstrom, B Mathis, CA AF Klunk, WE Engler, H Nordberg, A Bacskai, BJ Wang, YM Price, JC Bergstrom, M Hyman, BT Langstrom, B Mathis, CA TI Imaging the pathology of Alzheimer's disease: amyloid-imaging with positron emission tomography SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; PRECURSOR PROTEIN; BETA-SECRETASE; MONOCLONAL-ANTIBODY; HUMAN BRAIN; PLAQUES; PEPTIDE; NEURODEGENERATION; PURIFICATION; DERIVATIVES AB The steep rise in the incidence of Alzheimer's disease (AD) has further added to the considerable public health burden caused by aging of the United States population. Among the most characteristic pathologic hallmarks of AD are neuritic plaques and neurofibrillary tangles. The capability to use positron emission tomography and selective markers for amyloid protein deposition promises to substantially alter the way we diagnosis and manage patients who have AD. C1 Univ Pittsburgh, Sch Med, Dept Psychiat, Lab Mol Neuropharmacol, Pittsburgh, PA 15213 USA. Univ Uppsala, Positron Emiss Tomog Ctr, Uppsala Res Imaging Solut AB, Akad Sjukhuset, S-75185 Uppsala, Sweden. Huddinge Univ Hosp, Karolinska Inst, Dept Geriatr Med, Neurotec Dept, S-14186 Stockholm, Sweden. Massachusetts Gen Hosp, Alzheimers Res Unit, Dept Neurol, Charlestown, MA 02139 USA. Univ Pittsburgh, Sch Med, Dept Radiol, Positron Emiss Tomog Facil, Pittsburgh, PA 15213 USA. RP Klunk, WE (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, Lab Mol Neuropharmacol, 705 Parran Hall, Pittsburgh, PA 15213 USA. RI Mathis, Chester/A-8607-2009; OI Klunk, William/0000-0001-5512-0251 FU NIA NIH HHS [AG01039, AG08487, AG18402, AG20226] NR 61 TC 57 Z9 60 U1 1 U2 11 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD NOV PY 2003 VL 13 IS 4 BP 781 EP + DI 10.1016/S1052-5149(03)00092-3 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 745FE UT WOS:000186678000012 PM 15024961 ER PT J AU Grunwald, ME Kaplan, JM AF Grunwald, ME Kaplan, JM TI Mutations in the ligand-binding and pore domains control exit of glutamate receptors from the endoplasmic reticulum in C-elegans SO NEUROPHARMACOLOGY LA English DT Article DE glutamate receptor; endoplasmic reticulum (ER); ligand binding site; permeation; trafficking; C. elegans ID ER RETENTION SIGNAL; AMPA RECEPTOR; PHARMACOLOGICAL CHAPERONES; SYNAPTIC-TRANSMISSION; CAENORHABDITIS-ELEGANS; SURFACE EXPRESSION; QUALITY-CONTROL; GOLGI-COMPLEX; CHANNELS; TRAFFICKING AB The abundance of ion channels and neurotransmitter receptors in the plasma membrane is limited by the efficiency of protein folding and subunit assembly in the endoplasmic reticulum (ER). The ER has a quality-control system for monitoring nascent proteins, which prevents incompletely folded and assembled proteins from being transported from the ER. Chaperone proteins identify Unfolded and misassembled proteins in the ER via retention motifs that are normally buried at intersubunit contacts or via carbohydrate residues that are attached to misfolded domains. Here, we examined the trafficking of a C. elegalls non-NMDA glutamate receptor (GLR-1). We show that Mutations in the pore domain (predicted to block ion permeation) and mutations in the ligand-binding domain (predicted to block glutamate binding) both caused a dramatic reduction in the synaptic abundance of GLR1 and increased retention of GLR-1 in the ER. These results suggest that the structural integrity of the ligand-binding site and the pore domain of GLR-1 are monitored in the ER during the process of quality control. (C) 2003 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Kaplan, JM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, 50 Blossom St,Wellman 8, Boston, MA 02114 USA. FU NINDS NIH HHS [NS 32196] NR 67 TC 28 Z9 33 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD NOV PY 2003 VL 45 IS 6 BP 768 EP 776 DI 10.1016/S0028-3908(03)00274-0 PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 738PR UT WOS:000186297500007 PM 14529715 ER PT J AU Caballero, AE AF Caballero, AE TI Endothelial dysfunction in obesity and insulin resistance: A road to diabetes and heart disease SO OBESITY RESEARCH LA English DT Review DE insulin resistance; endothelium; diabetes; inflammation; prediabetes ID SOLUBLE ADHESION MOLECULES; OXIDE SYNTHASE GENE; SMOOTH-MUSCLE-CELLS; C-REACTIVE PROTEIN; WEIGHT-LOSS; CARDIOVASCULAR-DISEASES; ESSENTIAL-HYPERTENSION; MEDIATED VASODILATION; VASCULAR ENDOTHELIUM; BRACHIAL-ARTERY AB Obesity, insulin resistance, and endothelial dysfunction closely coexist throughout the natural history of type 2 diabetes. They all can be identified not only in people with type 2 diabetes, but also in various groups at risk for the disease, such as individuals with impaired glucose tolerance, family history of type 2 diabetes, hypertension, dyslipidemia, prior gestational diabetes, or polycystic ovary syndrome. Whereas their evident association cannot fully establish a cause-effect relationship, fascinating mechanisms that bring them closer together than ever before are rapidly emerging. Central or abdominal obesity leads to insulin resistance and endothelial dysfunction through fat-derived metabolic products, hormones, and cytokines., Insulin resistance leads to endothelial dysfunction through the frequent association with traditional cardiovascular risk factors and through some more direct novel mechanisms. Some specific and shared insulin signaling abnormalities in muscle, fat, and endothelial cells, as well as some new genetic and nontraditional factors, may contribute to this interesting association. Some recent clinical studies demonstrate that nonpharmacological and pharmacological strategies targeting obesity and/or insulin resistance ameliorate endothelial function and low-grade inflammation. All these findings have added a new dimension to the association of obesity, insulin resistance, and endothelial dysfunction that may become a key target in the prevention of type 2 diabetes and cardiovascular disease. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Caballero, AE (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. NR 90 TC 199 Z9 218 U1 2 U2 12 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD NOV PY 2003 VL 11 IS 11 BP 1278 EP 1289 DI 10.1038/oby.2003.174 PG 12 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 745ZL UT WOS:000186721400002 PM 14627747 ER PT J AU Culver, JP Siegel, AM Stott, JJ Boas, DA AF Culver, JP Siegel, AM Stott, JJ Boas, DA TI Volumetric diffuse optical tomography of brain activity SO OPTICS LETTERS LA English DT Article ID CALIBRATION; RAT AB We present three-dimensional diffuse optical tomography of the hemodynamic response to somatosensory stimulation in a rat. These images show the feasibility of volumetrically imaging the functional response to brain activity with diffuse light. A combination of positional optode calibration and contrast-to-noise ratio weighting was found to improve imaging performance. (C) 2003 Optical Society of America. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Culver, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. FU NCRR NIH HHS [P41-RR14075]; NINDS NIH HHS [K25-NS44339, R29-NS38842] NR 13 TC 110 Z9 112 U1 0 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 NOV 1 PY 2003 VL 28 IS 21 BP 2061 EP 2063 DI 10.1364/OL.28.002061 PG 3 WC Optics SC Optics GA 733XC UT WOS:000186025100017 PM 14587815 ER PT J AU de Boer, JF Cense, B Park, BH Pierce, MC Tearney, GJ Bouma, BE AF de Boer, JF Cense, B Park, BH Pierce, MC Tearney, GJ Bouma, BE TI Improved signal-to-noise ratio in spectral-domain compared with time-domain optical coherence tomography SO OPTICS LETTERS LA English DT Article AB A signal-to-noise ratio (SNR) analysis is presented for optical coherence tomography (OCT) signals in which time-domain performance is compared with that of the spectral domain. A significant SNR gain of several hundredfold is found for acquisition in the spectral domain. The SNR benefit is demonstrated experimentally in a hybrid time-domain-spectral-domain OCT system. (C) 2003 Optical Society of America. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Harvard Univ, Sch Med, 50 Blossom St,BAR 724, Boston, MA 02114 USA. EM deboer@helix.mgh.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU NEI NIH HHS [1R24 EY12877] NR 12 TC 814 Z9 821 U1 11 U2 93 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 EI 1539-4794 J9 OPT LETT JI Opt. Lett. PD NOV 1 PY 2003 VL 28 IS 21 BP 2067 EP 2069 DI 10.1364/OL.28.002067 PG 3 WC Optics SC Optics GA 733XC UT WOS:000186025100019 PM 14587817 ER PT J AU Hartig, GK Connor, NP Heisey, DM Conforti, ML AF Hartig, GK Connor, NP Heisey, DM Conforti, ML TI Comparing a mechanical device with medicinal leeches for treating venous congestion SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT 106th Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 22-25, 2002 CL SAN DIEGO, CALIFORNIA SP Amer Acad Otolaryngol Head & Neck Surg ID SURGERY AB OBJECTIVE. To compare mechanical device therapy to medicinal leech therapy for treating venous congestion. STUDY DESIGN. Fasciocutaneous flaps of 9 x 7-cm (porcine model, n = 11) were elevated and the associated veins clamped for 15 hours. Device-treated flaps (n = 6) were treated with up to 3 devices/flap. Leech-treated flaps (n = 5) were treated with 75 leeches/flap (5 leeches/hour). Treatment evaluation parameters included: blood volume removed, skin color, surface perfusion, tissue oxygen tension, and endpoint histology. RESULTS: No significant differences were seen in blood volume removed, surface perfusion, and oxygen tension. However, significant differences were seen in skin color change over time. Histological assessment showed mild congestion in 5/5 leech-treated flaps and 2/6 device-treated flaps. CONCLUSION: Device therapy was comparable to leech therapy for decongesting a 9 x 7-cm flap over a 15-hour period. However, digital images and significant differences in skin color change over time demonstrate that device therapy promotes more global decongestion versus leech therapy. C1 Univ Wisconsin, Sch Med, Clin Sci Ctr K4720, Dept Surg,Div Otolaryngol, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Dept Res, Dept Vet Affairs, Madison, WI USA. RP Hartig, GK (reprint author), Univ Wisconsin, Sch Med, Clin Sci Ctr K4720, Dept Surg,Div Otolaryngol, Madison, WI 53792 USA. NR 11 TC 9 Z9 9 U1 0 U2 3 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 NOV PY 2003 VL 129 IS 5 BP 556 EP 564 DI 10.1016/S0194-5998(03)01587-0 PG 9 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 741CA UT WOS:000186440100013 PM 14595279 ER PT J AU Pandol, SJ Gukovsky, I Satoh, A Lugea, A Gukovskaya, AS AF Pandol, SJ Gukovsky, I Satoh, A Lugea, A Gukovskaya, AS TI Animal and in vitro models of alcoholic pancreatitis: Role of cholecystokinin SO PANCREAS LA English DT Article DE alcohol; cholecystokinin; pancreatitis; nuclear factor kappa B; activator protein 1; protein kinase C ID NF-KAPPA-B; ACINAR-CELLS; GENE-EXPRESSION; ACTIVATION; INJURY; CURCUMIN; ETHANOL; KINASE; RATS; TRANSCRIPTION AB Although ethanol abuse is the major etiologic factor in the development of acute and chronic pancreatitis, the mechanisms of ethanol effects to cause pancreatitis are poorly understood. The major reason for the lack of progress is the relative lack of animal models that reproduce the deleterious effects of ethanol on the pancreas that are observed in human disease. We propose that the effect of ethanol on the pancreas is due to its ability to sensitize animals and humans to the potentially injurious effects of other stimuli. We have developed models of ethanol-induced acute and chronic pancreatitis in rats as well as pancreatic acinar cells in primary culture demonstrating that ethanol sensitizes the pancreas to the inflammatory, cell death, and fibrosing responses caused by cholecystokinin (CCK). Our results indicate that the ethanol-sensitized inflammatory response is the key or trigger event for the development of the other pathologic responses in both acute and chronic pancreatitis, such as cell death, intracellular digestive enzyme activation, and fibrosis. These findings suggest that experimental strategies designed to reveal the modulating effects of ethanol on the mechanisms underlying the inflammatory, cell death, and fibrosing responses stimulated by CCK will provide the key information needed to understand how ethanol abuse causes pancreatitis. C1 VA Greater Los Angeles Healthcare Syst, Dept Med, W Los Angeles Healthcare Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. USC UCLA, Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA USA. RP Pandol, SJ (reprint author), VA Greater Los Angeles Healthcare Syst, Dept Med, W Los Angeles Healthcare Ctr, Bldg 258,Room 340,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIAAA NIH HHS [P50-AA11999]; NIDDK NIH HHS [DK59508] NR 40 TC 28 Z9 29 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2003 VL 27 IS 4 BP 297 EP 300 DI 10.1097/00006676-200311000-00004 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 737GV UT WOS:000186222800004 PM 14576490 ER PT J AU Whitcomb, DC AF Whitcomb, DC TI Genetic predisposition to alcoholic chronic pancreatitis SO PANCREAS LA English DT Article DE pancreatitis; pancreatic secretory trypsin inhibitor; alcohol; cystic fibrosis transmembrane conductance regulator; trypsinogen; trypsin ID CYSTIC-FIBROSIS GENE; IDIOPATHIC CHRONIC-PANCREATITIS; CATIONIC TRYPSINOGEN GENE; SERINE-PROTEASE INHIBITOR; HEREDITARY PANCREATITIS; KAZAL TYPE-1; MUTATIONS; RISK; SPINK1; POLYMORPHISMS AB The mechanisms leading to alcoholic chronic pancreatitis in humans have remained elusive. Numerous questions surround the apparent random nature of the disease in which 1 person is hit with alcoholic chronic pancreatitis while the next is spared. Why do fewer than 10% of chronic, heavy alcohol users ever develop pancreatitis, while others develop alcoholic liver disease, neuropathy, or other alcohol-associated problems? Why do laboratory animals, fed large amounts of alcohol for prolonged periods of time, fail to develop typical chronic pancreatitis? Why are heavy alcohol users from a black African background more likely to develop pancreatic diseases than Caucasians, whereas the opposite is true for the development of liver disease? The answers underlying these questions appear to reflect the differences in underlying genetic susceptibility, environmental exposure, and the interaction between these factors. Thus, even cases of "typical" alcoholic chronic pancreatitis or other forms of pancreatitis appear to be complex diseases. Recently, several genetic mutations have been identified that increase the susceptibility to pancreatitis. However, the major common gene mutations in CFTR, PRSS1, and SPINK1 only slightly increase the risk of alcoholic chronic pancreatitis. New genetic, environmental, and triggering factors must be considered to gain further insight into the mechanisms leading to alcoholic chronic pancreatitis so that strategies for treatment and prevention can be developed. C1 Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. RP Whitcomb, DC (reprint author), UPMC Presbyterian Hosp, Mezzanine Level,C Wing,200 Lothrop St, Pittsburgh, PA 15213 USA. NR 35 TC 26 Z9 26 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2003 VL 27 IS 4 BP 321 EP 326 DI 10.1097/00006676-200311000-00009 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 737GV UT WOS:000186222800009 PM 14576495 ER PT J AU Levy, O Teixeira-Pinto, A White, ML Carroll, SF Lehmann, L Wypij, D Guinan, E AF Levy, O Teixeira-Pinto, A White, ML Carroll, SF Lehmann, L Wypij, D Guinan, E TI Endotoxemia and elevation of lipopolysaccharide-binding protein after hematopoietic stem cell transplantation SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE lipopolysaccharide; endotoxin; lipopolysaccharide-binding protein; hematopoietic stem cell transplantation; bone marrow transplantation; graft vs. host disease ID BONE-MARROW TRANSPLANTATION; VERSUS-HOST-DISEASE; BACTERICIDAL/PERMEABILITY-INCREASING PROTEIN; C-REACTIVE PROTEIN; SEPSIS AB Background. Hematopoietic stem cell transplantation (SCT) carries a significant risk of severe therapy-associated complications chief among which is acute graft vs. host disease (aGVHD). Animal models indicate that myeloablative chemotherapy compromises the mucosal barrier, thereby allowing translocation of intestinal flora-derived lipopolysaccharides (or endotoxin) that subsequently trigger aGVHD, but there are no comparable data in humans. Our aim was to gain insight into the potential role of endotoxin and endotoxin-induced acute phase proteins in children undergoing SCT. Methods. Plasma concentrations of C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP) were measured in 57 pediatric patients undergoing SCT. In addition plasma endotoxin levels were measured in 25 patients. Results. The previously described rise in CRP was confirmed, and a marked elevation of LBP was observed that peaked at Day 7 (median value, 6.6 mug/ml; P < 0.03 for all pairwise comparisons). CRP and LBP values were significantly correlated (r = 0.77, P < 0.001). A significant but complex relationship was noted between LBP concentrations at Day 0 and severity of subsequent aGVHD (P = 0.02). Of the 25 patients assayed, 11 (44%) had detectable endotoxemia, including 4 who were endotoxin-positive at Day 0. Conclusions. The detection of endotoxemia coupled with marked elevations in LBP at Day 7 raises the possibility that inflammatory responses early after SCT may be driven in part by the entry of lipopolysaccharide into the bloodstream. C1 Harvard Univ, Sch Med, Childrens Hosp, Clin Res Program,Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Res Inst, Boston, MA 02115 USA. Xoma Corp, Berkeley, CA 94710 USA. RP Levy, O (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Clin Res Program,Div Infect Dis, 300 Longwood Ave, Boston, MA 02115 USA. RI Teixeira-Pinto, Armando/H-7947-2013 OI Teixeira-Pinto, Armando/0000-0002-9389-2516 FU NCRR NIH HHS [M01 RR 02172] NR 13 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD NOV PY 2003 VL 22 IS 11 BP 978 EP 981 DI 10.1097/01.inf.0000095196.19606.d2 PG 4 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 744HM UT WOS:000186622200009 PM 14614371 ER PT J AU Kleinman, RE Barness, LA Finberg, L AF Kleinman, RE Barness, LA Finberg, L TI History of pediatric nutrition and fluid therapy SO PEDIATRIC RESEARCH LA English DT Review ID IRON-DEFICIENCY ANEMIA; ACRODERMATITIS ENTEROPATHICA; INTRAVENOUS ALIMENTATION; PROTEIN-REQUIREMENTS; DEVELOPING-COUNTRIES; ENERGY-EXPENDITURE; BODY-COMPOSITION; BIRTH-WEIGHT; INFANTS; ZINC C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Univ S Florida, Dept Pediat, Sch Med, Tampa, FL 33606 USA. Stanford Univ, Sch Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. RP Finberg, L (reprint author), 152 Lombard St,602, San Francisco, CA 94111 USA. NR 106 TC 6 Z9 8 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 NOV PY 2003 VL 54 IS 5 BP 762 EP 772 DI 10.1203/01.PDR.0000088018.17598.C5 PG 11 WC Pediatrics SC Pediatrics GA 736GJ UT WOS:000186162800021 PM 12930922 ER PT J AU Winickoff, JP Buckley, VJ Palfrey, JS Perrin, JM Rigotti, NA AF Winickoff, JP Buckley, VJ Palfrey, JS Perrin, JM Rigotti, NA TI Intervention with parental smokers in an outpatient pediatric clinic using counseling and nicotine replacement SO PEDIATRICS LA English DT Article DE parent; smoking; tobacco; smoking cessation; tobacco control; proactive; telephone counseling; nicotine replacement therapy; pediatrics; outpatient; clinic; environmental tobacco smoke; secondhand smoke; respiratory illness; asthma ID ENVIRONMENTAL TOBACCO-SMOKE; RANDOMIZED CONTROLLED-TRIAL; PASSIVE SMOKING; ASTHMATIC-CHILDREN; MATERNAL SMOKING; CESSATION INTERVENTION; RESPIRATORY ILLNESS; HOSPITAL PATIENTS; YOUNG-CHILDREN; EXPOSURE AB Objective. To evaluate the feasibility of implementing a smoking cessation intervention for parents at the time of the pediatric visit. Methods. A prospective cohort of smoking parents whose child was seen in an outpatient pediatric practice was offered the Stop Tobacco Outreach Program, which includes 3 brief counseling sessions, written materials, free nicotine replacement therapy (NRT), proactive referral to a free state telephone quitline, and fax referral to the parents' primary clinician. The primary outcome was completion of all three counseling sessions. Other outcomes were quit attempts, cessation, NRT use, state quitline use, and household smoking assessed at 2-month follow-up. Results. One hundred fifty-eight smoking parents met eligibility criteria and 100 (63%) enrolled in the study. Of the 100 enrollees, 81% completed all three counseling sessions and 78% accepted free NRT at the time of enrollment. At 2-month follow-up, of the 100 enrollees, 56% reported making a quit attempt of >24 hours, 18% reported 7-day tobacco abstinence, 34% used NRT, and 42% received additional counseling from the state telephone quitline. The mean number of cigarettes smoked inside the home and car declined over 2 months (home, 5.1 vs 1.4; and car, 2.5 vs 1.4). Conclusions. This study demonstrates the feasibility of engaging parents in a smoking cessation intervention at the time of a child's clinic visit. This approach may be an effective way to reach smokers who otherwise are unlikely to access smoking cessation interventions. High rates of program enrollment, use of NRT, and completion of telephone counseling in this study support the hypothesis that a child's clinic visit is a teachable moment to address parental smoking cessation. C1 Massachusetts Gen Hosp Children, MGH Ctr Child & Adolescent Hlth Policy, Div Gen Pediat, Boston, MA USA. Massachusetts Gen Hosp, Div Gen Med, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. Childrens Hosp, Div Gen Pediat, Boston, MA 02115 USA. RP Winickoff, JP (reprint author), MGH Ctr Child & Adolescent Hlth Policy, 50 Staniford St,Suite 901, Boston, MA 02114 USA. FU AHRQ HHS [T32-HS00063]; NHLBI NIH HHS [K24-HL04440] NR 61 TC 58 Z9 59 U1 2 U2 8 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV 1 PY 2003 VL 112 IS 5 BP 1127 EP 1133 DI 10.1542/peds.112.5.1127 PG 7 WC Pediatrics SC Pediatrics GA 738XA UT WOS:000186312100019 PM 14595057 ER PT J AU Fried, L Bernardini, J Piraino, B AF Fried, L Bernardini, J Piraino, B TI Comparison of the Charlson Comorbidity Index and the Davies score as a predictor of outcomes in PD patients SO PERITONEAL DIALYSIS INTERNATIONAL LA English DT Article; Proceedings Paper CT 9th Congress of the International-Society-of-Peritoneal-Dialysis CY JUN 26-29, 2001 CL MONTREAL, CANADA SP Int Soc Peritonial Dialysis DE comorbidity; hospitalization; mortality ID PERITONEAL-DIALYSIS PATIENTS; HOSPITAL UTILIZATION; COEXISTENT DISEASE; CLINICAL-OUTCOMES; SURVIVAL; MORBIDITY; HEMODIALYSIS; ADEQUACY; ILLNESS; CANCER AB Background: Comorbidity is a strong predictor and confounds many studies of outcomes. Previous studies have shown that the Charlson Comorbidity Index (CCI) and the Davies score predict mortality in peritoneal dialysis (PD) patients. However, there are few data on the comparison of comorbidity scores. Objective: To compare the CCI (combines comorbidity and age) and Davies score (comorbidity score without age) to see if one score was superior to the other in predicting outcomes. Design: Prospective database study. Setting: Seven dialysis centers in Western Pennsylvania. Participants: 415 incident PD patients, starting PD from 1/1/90 to 2/1/00. Measurements: The CCI and Davies score calculated at the start of PD; serum albumin levels and demographics at the start of PD; total hospitalizations and mortality, collected prospectively. Results: The correlation between CCI and Davies was 0.80, p < 0.0001. The CCI was inversely correlated with serum albumin (-0.31, p < 0.0001). Davies was significantly correlated with age (0.32, p < 0.0001) and inversely correlated with albumin (-0.27, p < 0.0001). The CCI alone was a stronger predictor than Davies alone (score by best subsets regression 49.6 vs 42.0, p = 0.0058). The CCI and Davies with age appeared to be equivalent models of survival (49.61 vs; 49.64). The best predictive models were CCI and initial albumin, or Davies, age, and initial albumin. Both CCI and Davies were predictors of hospitalization rates, but the model with the Davies score was better (Akaike information criterion 799.2 vs; 850.2). The best predictive model was Davies, albumin, age, and race. Conclusions: Both comorbidity scores were significant predictors of outcomes, with CCI the stronger predictor for mortality, but the Davies was a stronger predictor of hospitalizations. One or both should be done at the start of dialysis to predict outcome. C1 Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Renal Sect,VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Med, Sch Med, Pittsburgh, PA 15261 USA. RP Fried, L (reprint author), Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Renal Sect,VA Pittsburgh Healthcare Syst, A919 Scaife Hall, Pittsburgh, PA 15261 USA. NR 22 TC 26 Z9 26 U1 0 U2 1 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 NOV-DEC PY 2003 VL 23 IS 6 BP 568 EP 573 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 752MQ UT WOS:000187165000007 PM 14703198 ER PT J AU Chen, ZY AF Chen, ZY TI Applications of genomics in the inner ear SO PHARMACOGENOMICS LA English DT Review DE auditory system; deafness; development; functional genomics; hair cell; microarray; utricle ID GENE-EXPRESSION; HAIR-CELLS; IN-VIVO; MICROARRAY DATA; SENSORY ORGANS; HEARING; DEAFNESS; MICE; DIFFERENTIATION; IDENTIFICATION AB Understanding the development and function of the inner ear requires knowledge of the genes expressed and the pathways involved. Such knowledge is also essential for the development of therapeutic approaches for a wide range of inner ear diseases affecting millions of people. The completion of the Human Genome Project and emergence of genomics-based technologies have made it possible to analyze the expression patterns of the inner ear genes at the whole genome level, generating an unprecedented amount of information on gene expression patterns. This review will discuss the current status of work using genomics, in particular the functional genomics approach, to study different aspects of inner ear genes. It will also illustrate how the approach can help to identify and characterize deafness genes, as well as contributing to work related to hair cell regeneration. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Chen, ZY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Serv, Wellman 425,55 Fruit St, Boston, MA 02114 USA. NR 44 TC 2 Z9 2 U1 1 U2 1 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD NOV PY 2003 VL 4 IS 6 BP 735 EP 745 DI 10.1517/phgs.4.6.735.22814 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 743NB UT WOS:000186578200011 PM 14596637 ER PT J AU Fungaloi, P Waterman, P Nigri, G Statius-van Eps, R Sluiter, W van Urk, H LaMuraglia, G AF Fungaloi, P Waterman, P Nigri, G Statius-van Eps, R Sluiter, W van Urk, H LaMuraglia, G TI Photochemically modulated endothelial cell thrombogenicity via the thrombomodulin-tissue factor pathway SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID PHOTODYNAMIC THERAPY; VASCULAR ENDOTHELIUM; NATURAL ANTICOAGULANT; PROCOAGULANT ACTIVITY; MICROPARTICLES; THROMBOSIS; APOPTOSIS; INVITRO; SURFACE; PHOSPHATIDYLSERINE AB Photodynamic therapy (PDT) is based on a photochemical reaction using a photosensitizer and light to produce reactive oxygen species that have biological effects. Although its application in some fields is largely based on thrombosis, in the vascular setting thrombosis must be prevented. In this study we examined the effects of PDT on the changes in activity of thrombomodulin (TM) and tissue factor (TF) as important regulators of the coagulation process of endothelial cells. Human umbilical vein endotheliall cells were treated with PDT (chloro-aluminum-sulfonated phthalocyanine, lambda = 630 nm) at different light-energy doses, and TM and TF levels were measured using fluorescence spectroscopy. Microparticles (MP) were analyzed using flow cytometry analysis. PDT alters the thrombogenic state of endothelial cells by causing decreased expression of TNI and increased expression of functional TF in a light-energy dose-dependent way. PDTtreated endothelial cells shed large numbers of NIP containing high levels of TF. TF functionality of PDT-treated cells, measured by a Factor Xa-generating assay, was high. TF was located mosths, intracellularly and in MP. The disturbed anticoagulant balance described in this study may explain the occurrence of thrombosis induced by PDT and, if not contained, dispute the suitability of PDT as an adjuvant modality to treat vascular restenosis. C1 Atrium Med Ctr, Div Vasc Surg, NL-6419 PC Heerlen, Netherlands. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Vasc Surg, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02115 USA. Erasmus Med Ctr, Dept Biochem, Rotterdam, Netherlands. RP Fungaloi, P (reprint author), Atrium Med Ctr, Div Surg, Henri Dunantstr 5, NL-6419 PC Heerlen, Netherlands. NR 37 TC 12 Z9 12 U1 0 U2 1 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 NOV PY 2003 VL 78 IS 5 BP 475 EP 480 DI 10.1562/0031-8655(2003)078<0475:PMECTV>2.0.CO;2 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 744RV UT WOS:000186646900009 PM 14653579 ER PT J AU Ritsher, JB Otilingam, PG Grajales, M AF Ritsher, JB Otilingam, PG Grajales, M TI Internalized stigma of mental illness: psychometric properties of a new measure SO PSYCHIATRY RESEARCH LA English DT Article DE stereotyping; social alienation; risk factors; mental disorders; questionnaires; psychometrics ID PERCEIVED STIGMA; HEALTH-SERVICES; CONSEQUENCES; EMPOWERMENT; CONSUMERS; CONSTRUCT; RECOVERY; VALIDITY AB The study evaluated the Internalized Stigma of Mental Illness (ISMI) scale, designed to measure the subjective experience of stigma, with subscales measuring Alienation, Stereotype Endorsement, Perceived Discrimination, Social Withdrawal and Stigma Resistance. The ISMI was developed in collaboration with people with mental illnesses and contains 29 Likert items. The validation sample included 127 mental health outpatients. Results showed that the ISMI had high internal consistency and test-retest reliability. Construct validity was supported by comparisons against scales measuring related constructs with the same methodology. As expected, the ISMI had positive correlations with measures of stigma beliefs and depressive symptoms, and it had negative correlations with measures of self-esteem, empowerment and recovery orientation. Factor analyses of the joint set of items from the ISMI and each scale supported the distinction between constructs. Having a validated measure of internalized stigma may encourage clinicians to include stigma reduction as a verifiable treatment goal in addition to symptom reduction. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 US Dept Vet Affairs, Ctr Hlth Care Evaluat, Menlo Park, CA USA. Stanford Univ, Sch Med, Menlo Park, CA USA. Univ Calif San Francisco, Dept Psychiat 116A, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, San Francisco, CA 94121 USA. Univ So Calif, Dept Psychol, Los Angeles, CA USA. San Francisco State Univ, Dept Social Psychol, San Francisco, CA 94132 USA. RP Ritsher, JB (reprint author), US Dept Vet Affairs, Ctr Hlth Care Evaluat, Menlo Park, CA USA. NR 28 TC 335 Z9 356 U1 6 U2 55 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD NOV 1 PY 2003 VL 121 IS 1 BP 31 EP 49 DI 10.1016/j.physchres.2003.08.008 PG 19 WC Psychiatry SC Psychiatry GA 736LG UT WOS:000186171800004 PM 14572622 ER PT J AU Kahkonen, S Ahveninen, J Jaaskelainen, IP Pennanen, S Liesivuori, J Nikulin, VV AF Kahkonen, S Ahveninen, J Jaaskelainen, IP Pennanen, S Liesivuori, J Nikulin, VV TI Acute tryptophan depletion does not change somatosensory evoked magnetic fields SO PSYCHOPHARMACOLOGY LA English DT Article DE magnetoencephalography; serotonin; somatosensory; evoked magnetic fields; tryptophan ID INTENSITY DEPENDENCE; SEROTONIN; POTENTIALS; MALES AB Rationale: Serotonin is shown to regulate the activity of primary auditory cortex, but little is known about serotonin modulation of other sensory cortices. Methods: We investigated somatosensory evoked magnetic fields (SEF) to left median nerve stimulation in eight healthy subjects in a double-blind, controlled, cross-over design study after acute tryptophan depletion (ATD) and control mixture. SEFs were recorded with the whole-head magnetoencephalography 6 h after ingestion of mixtures. The SEF sources and strength were estimated by a least-squares fit of a single equivalent current dipole. Results: ATD decreased the total and free TPR levels by 75 and 48% and control mixture increased them by 98% and 44%. ATD had no effect on the amplitudes or latencies of SEF components. The source locations of the responses were not significantly affected by ATD. Conclusion: Serotonin does not affect stimuli processing in the primary somatosensory cortex. C1 Univ Helsinki, Cent Hosp, BioMag Lab, FIN-00290 Helsinki, Finland. Univ Helsinki, Cognit Brain Res Unit, Helsinki, Finland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA USA. Helsinki Univ Technol, Lab Computat Engn, Helsinki, Finland. Univ Helsinki, Dept Psychol, FIN-00014 Helsinki, Finland. Kuopio Reg Inst Occupat Hlth, Occupat Hyg & Toxicol Sect, FIN-70701 Kuopio, Finland. Univ Kuopio, Dept Pharmacol & Toxicol, FIN-70211 Kuopio, Finland. Karolinska Hosp, Dept Clin Neurophysiol, S-10401 Stockholm, Sweden. RP Kahkonen, S (reprint author), Univ Helsinki, Cent Hosp, BioMag Lab, POB 340, FIN-00290 Helsinki, Finland. RI Jaaskelainen, Iiro/C-7392-2012; Liesivuori, Jyrki/O-2519-2013; Nikulin, Vadim/A-6050-2014 OI Jaaskelainen, Iiro/0000-0001-6001-6950; Nikulin, Vadim/0000-0001-6082-3859 NR 10 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 2003 VL 170 IS 3 BP 332 EP 333 DI 10.1007/s00213-003-1560-5 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 754QD UT WOS:000187341200013 PM 12845404 ER PT J AU Oslin, DW Sayers, S Ross, J Kane, V Ten Have, T Conigliaro, J Cornelius, J AF Oslin, DW Sayers, S Ross, J Kane, V Ten Have, T Conigliaro, J Cornelius, J TI Disease management for depression and at-risk drinking via telephone in an older population of veterans SO PSYCHOSOMATIC MEDICINE LA English DT Article DE telephone; depression; at-risk drinking; primary care ID RANDOMIZED CONTROLLED-TRIAL; PRIMARY-CARE PATIENTS; LATE-LIFE; FAMILY PHYSICIANS; MENTAL-DISORDERS; MAJOR DEPRESSION; VALIDATION; ALCOHOLISM; ATTITUDES; KNOWLEDGE AB Objectives: The purpose of this study was to explore the efficacy in a primary care setting of a telephone-based disease management program for the acute management of depression and/or at-risk drinking. Materials and Methods: Veterans (N = 97) with depression and/or at-risk drinking were identified by systematic screening and assessment. Eligible subjects received either telephone disease management (TDM) program or usual care based on random assignment of their clinician. The TDM program consisted of regular contacts with each subject by a behavioral health specialist (BHS) to assist in assessment, education, support, and treatment planning. Symptomatic outcomes were assessed at 4 months. Results: Overall response rates favored those assigned to TDM compared with those assigned to usual care (39.1% responded vs. 17.6%,p = 0.022). Response rates within the separate diagnostic groups also favored TDM, but this was only significant for depressive disorders. Conclusions: Although the sample size was modest and the sample was limited to veterans, findings strongly suggest that a telephone-based disease management program can improve outcomes for patients with a behavioral health problem. Findings also suggest that a health specialist can focus and manage patients with different diagnoses, thus expanding the role beyond just depression care. TDM may be a viable, low-cost, model for primary care clinicians to deliver manual guideline-adherent behavioral health care, especially in a VA clinical setting. C1 Univ Penn, Sect Geriatr Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychiat, Philadelphia, PA USA. Univ Penn, Ctr Study Addict, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. VISN 4 MIRECC, Philadelphia, PA USA. Univ Penn, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. RP Oslin, DW (reprint author), Univ Penn, Sect Geriatr Psychiat, 3535 Market St,Room 3002, Philadelphia, PA 19104 USA. FU NIMH NIH HHS [1K08 MH01599-01] NR 49 TC 53 Z9 53 U1 6 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD NOV-DEC PY 2003 VL 65 IS 6 BP 931 EP 937 DI 10.1097/01.PSY.0000097335.35776.FB PG 7 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 748QK UT WOS:000186872400002 PM 14645769 ER PT J AU Schettino, G Folkard, M Prise, KM Vojnovic, B Held, KD Michael, BD AF Schettino, G Folkard, M Prise, KM Vojnovic, B Held, KD Michael, BD TI Low-dose studies of bystander cell killing with targeted soft X rays SO RADIATION RESEARCH LA English DT Article ID CHARGED-PARTICLE MICROBEAM; HUMAN FIBROBLASTS; HAMSTER-CELLS; RADIATION; V79; SYSTEM AB The Gray Cancer Institute ultrasoft X-ray microprobe was used to quantify the bystander response of individual V79 cells exposed to a focused carbon K-shell (278 eV) X-ray beam. The ultrasoft X-ray microprobe is designed to precisely assess the biological response of individual cells irradiated in vitro with a very fine beam of low-energy photons. Characteristic C-K X rays are generated by a focused beam of 10 keV electrons striking a graphite target. Circular diffraction gratings (i.e. zone plates) are then employed to focus the X-ray beam into a spot with a radius of 0.25 mum at the sample position. Using this microbeam technology, the correlation between the irradiated cells and their nonirradiated neighbors can be examined critically. The survival response of V79 cells irradiated with a C-K X-ray beam was measured in the 0-2-Gy dose range. The response when all cells were irradiated was compared to that obtained when only a single cell was exposed. The cell survival data exhibit a linear-quadratic response when all cells were targeted (with evidence for hyper-sensitivity at low doses). When only a single cell was targeted within the population, 10% cell killing was measured. In contrast to the binary bystander behavior reported by many other investigations, the effect detected was initially dependent on dose (<200 mGy) and then reached a plateau (>200 mGy). In the low-dose region (<200 mGy), the response after irradiation of a single cell was not significantly different from that when all cells were exposed to radiation. Damaged cells were distributed uniformly over the area of the dish scanned (similar to25 mm(2)). However, critical analysis of the distance of the damaged, unirradiated cells from other damaged cells revealed the presence of clusters of damaged cells produced under bystander conditions. (C) 2003 by Radiation Research Society. C1 Mt Vernon Hosp, Gray Canc Inst, Northwood HA6 2JR, Middx, England. Harvard Univ, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA USA. RP Schettino, G (reprint author), Mt Vernon Hosp, Gray Canc Inst, POB 100, Northwood HA6 2JR, Middx, England. RI Prise, Kevin/N-7872-2015; OI Prise, Kevin/0000-0001-6134-7946; Vojnovic, Borivoj/0000-0001-9013-3816; Schettino, Giuseppe/0000-0003-3284-3953 NR 16 TC 96 Z9 98 U1 0 U2 3 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD NOV PY 2003 VL 160 IS 5 BP 505 EP 511 DI 10.1667/RR3060 PG 7 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 736NC UT WOS:000186176000002 PM 14565833 ER PT J AU Federle, MP Megibow, AF Laing, FC Curtin, HD Klein, FS Towbin, RB AF Federle, MP Megibow, AF Laing, FC Curtin, HD Klein, FS Towbin, RB TI Image interpretation session SO RADIOGRAPHICS LA English DT Article DE image, interpretation; radiological society of north America, 89th scientific assembly and annual meeting C1 Univ Pittsburgh, Presbyterian Univ Hosp, Med Ctr, Dept Radiol, Pittsburgh, PA 15213 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NYU, Med Ctr, New York, NY 10016 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Univ Vermont, Med Ctr, Burlington, VT USA. Fletcher Allen Hlth Care, Burlington, VT USA. RP Federle, MP (reprint author), Univ Pittsburgh, Presbyterian Univ Hosp, Med Ctr, Dept Radiol, 200 Lothrop St, Pittsburgh, PA 15213 USA. NR 0 TC 0 Z9 0 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 NOV-DEC PY 2003 VL 23 IS 6 BP 1703 EP 1713 DI 10.1148/rg.236035942 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 741FG UT WOS:000186447600034 ER PT J AU Ferrucci, JT Mueller, PR AF Ferrucci, JT Mueller, PR TI Interventional approach to pancreatic fluid collections SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID ABSCESS; DRAINAGE; PSEUDOCYSTS; RADIOLOGY AB Interventional radiologic catheter drainage may be an effective therapeutic approach to fluid collections complicating acute pancreatitis. Pancreatic pseudocysts and abscess are the most common conditions requiring radiologic intervention. Imaging guidance is best performed under CT control allowing precise definition of access route, catheter placement, and response. Access routes are chosen to avoid traversing vital intervening structures, especially the pleural space, colon, and small bowel. Optimal results are achieved with the use of large-bore multihole catheters, prolonged duration of drainage, and careful collaboration with the surgical team. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Mueller, PR (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, White 270,55 Fruit St, Boston, MA 02114 USA. NR 14 TC 16 Z9 17 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD NOV PY 2003 VL 41 IS 6 BP 1217 EP + DI 10.1016/S0033-8389(03)00123-4 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 746RX UT WOS:000186762400010 PM 14661667 ER PT J AU Kopans, DB Monsees, B Feig, SA AF Kopans, DB Monsees, B Feig, SA TI Screening for cancer: When is it valid? - Lessons from the mammography experience SO RADIOLOGY LA English DT Editorial Material DE breast radiography, utilization; cancer screening; opinions ID RANDOMIZED CONTROLLED TRIALS; BREAST-CARCINOMA MORTALITY; POSITIVE PREDICTIVE-VALUE; WOMEN 40-49 YEARS; DUCTAL CARCINOMA; QUANTITATIVE INTERPRETATION; STATISTICAL POWER; SAMPLE-SIZE; IN-SITU; AGE AB There is increasing interest in the development of imaging tests to screen for diseases such as cancer. Mammographic screening for breast cancer has undergone greater scrutiny than any other test. Many important lessons have been learned from the issues that have been raised with regard to mammographic screening. Those interested in developing new screening tests can learn from the mammography experience. (C) RSNA, 2003. C1 Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Avon Fdn Comprehens Breast Evaluat Ctr, Wang Ambulatory Care Ctr, Dept Radiol, Boston, MA 02114 USA. Washington Univ, Med Ctr, Dept Radiol, St Louis, MO USA. Mt Sinai Sch Med, Dept Radiol, New York, NY USA. RP Kopans, DB (reprint author), Harvard Univ, Sch Med, Dept Radiol, Suite 240,15 Parkman St, Boston, MA 02114 USA. EM kopans.daniel@mgh.harvard.edu NR 43 TC 32 Z9 33 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 NOV PY 2003 VL 229 IS 2 BP 319 EP 327 DI 10.1148/radiol.2292021272 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 736KJ UT WOS:000186169700007 PM 14595137 ER PT J AU Grant, EG Benson, CB Moneta, GL Alexandrov, AV Baker, JD Bluth, EI Carroll, BA Eliasziw, M Gocke, J Hertzberg, BS Katanick, S Needleman, L Pellerito, J Polak, JF Rholl, KS Wooster, DL Zierler, E AF Grant, EG Benson, CB Moneta, GL Alexandrov, AV Baker, JD Bluth, EI Carroll, BA Eliasziw, M Gocke, J Hertzberg, BS Katanick, S Needleman, L Pellerito, J Polak, JF Rholl, KS Wooster, DL Zierler, E TI Carotid artery stenosis: Gray-scale and Doppler US diagnosis - Society of Radiologists in Ultrasound consensus conference SO RADIOLOGY LA English DT Article DE carotid arteries, flow dynamics; carotid arteries, stenosis or obstruction; carotid arteries, US; Special Reports ID MAGNETIC-RESONANCE ANGIOGRAPHY; DUPLEX CRITERIA; ENDARTERECTOMY TRIAL; SYMPTOMATIC PATIENTS; SYSTOLIC VELOCITY; SURGERY-TRIAL; ULTRASONOGRAPHY; 70-PERCENT; STANDARDIZATION; 60-PERCENT AB The Society of Radiologists in Ultrasound convened a multidisciplinary panel of experts in the field of vascular ultrasonography (US) to come to a consensus regarding Doppler US for assistance in the diagnosis of carotid artery stenosis. The panel's consensus statement is believed to represent a reasonable position on the basis of analysis of available literature and panelists' experience. Key elements of the statement include the following: (a) All internal carotid artery (ICA) examinations should be performed with gray-scale, color Doppler, and spectral Doppler US. (b) The degree of stenosis determined at gray-scale and Doppler US should be stratified into the categories of normal (no stenosis), <50% stenosis, 50%-69% stenosis, greater than or equal to70% stenosis to near occlusion, near occlusion, and total occlusion. (c) ICA peak systolic velocity (PSV) and presence of plaque on gray-scale and/or color Doppler images are primarily used in diagnosis and grading of ICA stenosis; two additional parameters, ICA-to-common carotid artery PSV ratio and ICA end-diastolic velocity may also be used when clinical or technical factors raise concern that ICA PSV may not be representative of the extent of disease. (d) ICA should be diagnosed as (i) normal when ICA PSV is less than 125 cm/sec and no plaque or intimal thickening is visible; (ii) <50% stenosis when ICA PSV is less than 125 cm/sec and plaque or intimal thickening is visible; (iii) 50%-69% stenosis when ICA PSV is 125-230 cm/sec and plaque is visible; (iv) greater than or equal to70% stenosis to near occlusion when ICA PSV is greater than 230 cm/sec and visible plaque and lumen narrowing are seen; (v) near occlusion when there is a markedly narrowed lumen at color Doppler US; and (vi) total occlusion when there is no detectable patent lumen at gray-scale US and no flow at spectral, power, and color Doppler US. (e) The final report should discuss velocity measurements and gray-scale and color Doppler findings. Study limitations should be noted when they exist. The conclusion should state an estimated degree of ICA stenosis as reflected in the above categories. The panel also considered various technical aspects of carotid US and methods for quality assessment and identified several important unanswered questions meriting future research. (C) RSNA, 2003. C1 Univ So Calif, Keck Sch Med, Dept Radiol, Los Angeles, CA 90033 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. Oregon Hlth Sci Univ, Dept Surg, Portland, OR 97201 USA. Univ Texas, Houston Med Sch, Cerebrovasc Ultrasound & Stroke Treatment Team, Houston, TX USA. W Los Angeles Vet Affairs Med Ctr, Dept Surg, Los Angeles, CA USA. Alton Ochsner Med Fdn & Ochsner Clin, Dept Radiol, New Orleans, LA 70121 USA. Duke Univ, Sch Med, Dept Radiol, Durham, NC 27706 USA. Univ Calgary, Dept Biostat, Calgary, AB T2N 1N4, Canada. Midw Heart Specialists Vasc Lab, Downers Grove, IL USA. La Grange Mem Vasc Lab, Downers Grove, IL USA. Intersocietal Accreditat Commiss, Columbia, MD USA. Thomas Jefferson Univ, Dept Radiol, Philadelphia, PA 19107 USA. NYU, N Shore Univ Hosp, Sch Med, Dept Radiol, New York, NY USA. Inova Alexandria Hosp, Dept Radiol, Alexandria, VA USA. Univ Toronto, Dept Surg, Toronto, ON, Canada. Univ Washington, Sch Med, Dept Surg, Seattle, WA 98195 USA. RP Grant, EG (reprint author), Univ So Calif, Keck Sch Med, Dept Radiol, 1500 San Pablo St, Los Angeles, CA 90033 USA. RI Bluth, Edward/A-8613-2011; OI Alexandrov, Andrei V/0000-0001-8871-1023 NR 40 TC 574 Z9 593 U1 2 U2 18 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 2003 VL 229 IS 2 BP 340 EP 346 DI 10.1148/radiol.2292030516 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 736KJ UT WOS:000186169700009 PM 14500855 ER PT J AU Hoffmann, U Kwait, DC Handwerker, J Chan, R Lamuraglia, G Brady, TJ AF Hoffmann, U Kwait, DC Handwerker, J Chan, R Lamuraglia, G Brady, TJ TI Vascular calcification in ex vivo carotid specimens: Precision and accuracy of measurements with multi-detector row CT SO RADIOLOGY LA English DT Article DE arteries, calcification; carotid arteries, CT; carotid arteries, stenosis or obstruction; computed tomography (CT), multidetector row ID BEAM COMPUTED-TOMOGRAPHY; CORONARY-ARTERY CALCIUM; X-RAY ABSORPTIOMETRY; ELECTRON-BEAM; ATHEROSCLEROTIC PLAQUE; INTRAVASCULAR ULTRASOUND; HELICAL CT; BONE MASS; DISEASE; QUANTIFICATION AB PURPOSE: To test the accuracy and precision of multi-detector row computed tomography (CT)-derived measurements of vascular calcification in ex vivo human carotid endarterectomy (CEA) specimens. MATERIALS AND METHODS: Sixteen ex vivo CEA specimens were imaged with multi-detector row CT. Multi-detector row CT-derived calcium scoring algorithms (ie, mineral mass and volume score) were compared with the mass and volume of ashed remnants of the CEA specimens. Bland-Altman analysis was performed to assess the mean (ie, bias) and SD (ie, precision) of differences between multi-detector rove CT- and ashing-derived measurements. In addition, conventional Agatston score, volume score, mineral mass, and modified Agatston score were calculated for each specimen by using a number of scanning protocols. Images were obtained at a section thickness of 1.25 mm by using different tube energy settings and tube currents. Specimens were also imaged at different section thicknesses with fixed combinations of tube energy and tube current. To compare measurement variability of scoring methods, coefficients of variation for all protocols were calculated. RESULTS: Both mean multi-detector row CT-derived mineral mass and mean ashing-derived mineral mass were 0.129 g +/- 0.173 (r = 0.99, P < .001). Mean multi-detector row CT- and ashing-derived volumes were 339.94 mm(3) +/- 395.4 and 39.48 mm(3) +/- 55.76, respectively (r = 0.95, P < .001). Measurement bias relative to the reference ashing values was high (2,800.0%) for volume score and low (2.58%) for mineral mass. Measurement precision was 0.6% for volume score and greater than 0.0005% for mineral mass. Mean coefficients of variation for all CT protocols were 5.0% +/- 4.2 and 4.9% +/- 4.2 for mineral mass and modified Agatston score, respectively, and 16.0% +/- 9.2 and 14.5% +/- 3.9 for conventional Agatston and volume scores, respectively (P < .001). CONCLUSION: Compared with the conventional volume score, multi-detector row CT-derived mineral mass is a less biased and more precise measurement of the mineral content of nonmoving ex vivo CEA specimens. Mineral mass and modified Agatston score are more reproducible than conventional volume and Agatston scores. (C) RSNA, 2003. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Vasc Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Dept Radiol, 100 Charles River Plaza,Suite 400, Boston, MA 02114 USA. NR 31 TC 35 Z9 36 U1 1 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 2003 VL 229 IS 2 BP 375 EP 381 DI 10.1148/radiol.2292021016 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 736KJ UT WOS:000186169700014 PM 14526093 ER PT J AU Buchsbaum, MS Shihabuddin, L Brickman, AM Miozzo, R Prikryl, R Shaw, R Davis, K AF Buchsbaum, MS Shihabuddin, L Brickman, AM Miozzo, R Prikryl, R Shaw, R Davis, K TI Caudate and putamen volumes in good and poor outcome patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE caudate; putamen; Kraepelinian subtype ID GLUCOSE METABOLIC-RATE; BASAL GANGLIA VOLUMES; VENTRICULAR ENLARGEMENT; EPISODE SCHIZOPHRENIA; STRIATAL SIZE; MRI; SYMPTOMS; CLOZAPINE; DISORDER AB Magnetic resonance images of 37 patients with schizophrenia and 37 age- and sex-matched volunteers were acquired. The caudate nucleus and putamen were traced on axial slices from the most superior extent of the caudate to the most inferior point where the caudate and putamen merge. Two subtypes of schizophrenia were compared, the Kraepelinian subtype (n = 13), characterized by an unremitting and severe course, and the non-Kraepelinian subtype (n = 24), characterized by a remitting course and some periods of self-care. Patients with good outcome schizophrenia had larger relative mean putamen size (0.0129) than poor outcome patients (0.0123) or normal controls (0.0121), but not caudate size. This enlargement was most marked for the dorsal putamen and right hemisphere. Striatal size was not related to whether patients were currently being treated with atypical or typical neuroleptics or whether they had been predominantly treated with typical or atypical neuroleptics over the past 3 years. This suggests the possibility that the expansion of putamen size may be a physiological correlate of neuroleptic responsiveness or that small putamen size at disease onset may be a predictor of outcome. (C) 2003 Elsevier Science B.V. All rights reserved. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. Fac Hosp Brno, Dept Psychiat, Brno, Czech Republic. RP Buchsbaum, MS (reprint author), Mt Sinai Sch Med, Dept Psychiat, Box 1505,1 Gustave L Levy Pl, New York, NY 10029 USA. FU NIMH NIH HHS [MH60023, MH56489] NR 31 TC 53 Z9 54 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 NOV 1 PY 2003 VL 64 IS 1 BP 53 EP 62 DI 10.1016/S0920-9964(02)00526-1 PG 10 WC Psychiatry SC Psychiatry GA 729ZK UT WOS:000185804600006 PM 14511801 ER PT J AU Rosenberg, AE AF Rosenberg, AE TI Malignant fibrous histiocytoma: past, present, and future SO SKELETAL RADIOLOGY LA English DT Review DE malignant fibrous histiocytoma; history; fibrosarcoma ID SOFT-TISSUE SARCOMAS; PROGNOSTIC FACTORS; GENE-EXPRESSION; TUMORS; DIFFERENTIATION; FIBROXANTHOSARCOMA; LEIOMYOSARCOMAS; FIBROSARCOMA; DIAGNOSIS; XANTHOMAS C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,James Homer Wright Labs, Boston, MA 02114 USA. RP Rosenberg, AE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,James Homer Wright Labs, Boston, MA 02114 USA. NR 48 TC 12 Z9 18 U1 1 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD NOV PY 2003 VL 32 IS 11 BP 613 EP 618 DI 10.1007/s00256-003-0686-1 PG 6 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 736ZK UT WOS:000186203000001 PM 14517697 ER PT J AU Carden, K AF Carden, K TI The debate about gender differences in obstructive sleep apnea SO SLEEP MEDICINE LA English DT Editorial Material ID UPPER AIRWAY-RESISTANCE; POLYCYSTIC-OVARY-SYNDROME; HEALTHY-MEN; MUSCLE-ACTIVITY; NREM SLEEP; WOMEN; VENTILATION; PREVALENCE; AGE; MECHANICS C1 BIDMC, Brigham Sleep Disorders Program, Boston, MA USA. RP Carden, K (reprint author), BIDMC, Brigham Sleep Disorders Program, 75 Francis St, Boston, MA USA. EM amalhotra1@partners.org NR 34 TC 5 Z9 5 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1389-9457 J9 SLEEP MED JI Sleep Med. PD NOV PY 2003 VL 4 IS 6 BP 485 EP 487 DI 10.1016/S1389-9457(03)00167-9 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 772JW UT WOS:000188839700002 PM 14607341 ER PT J AU Ryan, L AF Ryan, L TI Epidemiologically based environmental risk assessment SO STATISTICAL SCIENCE LA English DT Article DE quantitative risk assessment; arsenic; carcinogenicity; dose response ID MAXIMUM-LIKELIHOOD METHODS; DRINKING-WATER; LOGISTIC-REGRESSION; ENDEMIC AREA; LUNG-CANCER; AIR TOXICS; MODELS; DISEASE; ISSUES; EXPOSURE AB Environmental health research aims to discover and understand the links between environmental exposure and disease and to inform the regulatory community so that society can be protected against cancer, birth defects and other adverse health effects associated with chemical, industrial and other exposures. Statistical science has a critical role to play in terms of providing the appropriate tools to design and analyze the studies needed to address the questions of interest, as well as quantifying risks and characterizing uncertainty. Recent years have seen some dramatic changes in the way that environmental risk assessment is accomplished. One such change is a move away from a traditional reliance on toxicological studies in animals to incorporate more epidemiological data. This shift has been facilitated by scientific advances that now allow researchers to accurately characterize human exposures in a variety of settings, as well as to measure genetic and other biomarkers that reflect subtle health effects and variations in susceptibility. This article will use a high profile case study to highlight some of the challenging statistical issues arising from this shifting emphasis from animal based toxicology to environmental epidemiology in the risk assessment world. Among the topics to be discussed are the uses of biologically based models and biomarkers, as well as the role of Bayesian methods to characterize uncertainty due to population heterogeneity, unmeasured confounders, exposure measurement error and model uncertainty. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ryan, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 4th Floor,Room 409,655 Huntington Ave, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 62 TC 4 Z9 4 U1 1 U2 5 PU INST MATHEMATICAL STATISTICS PI BEACHWOOD PA PO BOX 22718, BEACHWOOD, OH 44122 USA SN 0883-4237 J9 STAT SCI JI Stat. Sci. PD NOV PY 2003 VL 18 IS 4 BP 466 EP 480 DI 10.1214/ss/1081443230 PG 15 WC Statistics & Probability SC Mathematics GA 815MQ UT WOS:000221046800007 ER PT J AU Wada, K Sugimori, H Bhide, PG Moskowitz, MA Finklestein, SP AF Wada, K Sugimori, H Bhide, PG Moskowitz, MA Finklestein, SP TI Effect of basic fibroblast growth factor treatment on brain progenitor cells after permanent focal ischemia in rats SO STROKE LA English DT Article DE cerebral ischemia; dentate gyrus; fibroblast growth factor 2; progenitor cells ID ADULT MAMMALIAN FOREBRAIN; CEREBRAL-ARTERY OCCLUSION; SUBVENTRICULAR ZONE; SUBEPENDYMAL LAYER; DENTATE GYRUS; NEUROGENESIS; PROLIFERATION; HIPPOCAMPUS; RECOVERY; PROTEIN AB Background and Purpose-Intracisternal basic fibroblast growth factor (bFGF) enhances sensorimotor recovery after focal cerebral infarction in rats. One possible mechanism is stimulation of endogenous progenitor cells in brain. We investigated the effects of intracisternal bFGF on brain progenitor cells after stroke. Methods-Proliferating brain cells were labeled with bromodeoxyuridine (BrdU) before middle cerebral artery (MCA) occlusion or sham surgery in rats. bFGF (0.5 mug) or vehicle was administered intracisternally at 24 and 48 hours after MCA occlusion, and rats were killed at 7, 14, or 21 days after stroke. Immunohistochemistry for BrdU and neuron- or astrocyte-specific markers was used to characterize progenitor cells and their progeny in the subventricular zone and dentate gyrus of the hippocampus. Results-Infarct size did not differ among rats with or without bFGF treatment. MCA occlusion alone increased the number of BrdU-labeled cells in the ipsilateral subventricular zone at days 7 to 21, and there was a trend toward increased cell proliferation with bFGF treatment. In the dentate gyrus, the number of BrdU-labeled cells was increased bilaterally after MCA occlusion (peak at day 7). This increase was greater after bFGF treatment. In the subventricular zone, 30% of BrdU-labeled cells were immunopositive for the immature neuron- specific marker doublecortin at day 7, and their number declined to 2% at day 21. In the dentate gyrus, the majority of BrdU-labeled cells colabeled with doublecortin at day 7, becoming NeuN positive at day 21. Conclusions-Stroke produces significant changes in progenitor cells in brain that are augmented by bFGF treatment. C1 ViaCell Inc, ViaCell Neurosci, Worcester, MA 01605 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab, Boston, MA USA. RP Finklestein, SP (reprint author), ViaCell Inc, ViaCell Neurosci, 1 Innnovat Dr, Worcester, MA 01605 USA. FU NINDS NIH HHS [NS10828] NR 25 TC 46 Z9 54 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2003 VL 34 IS 11 BP 2722 EP 2728 DI 10.1161/01.STR.0000094421.61917.71 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 740JG UT WOS:000186398800039 PM 14576381 ER PT J AU Warshaw, AL AF Warshaw, AL TI The challenge of faculty retention: A personal reflection 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, 55 Fruit St,Suite 506, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD NOV PY 2003 VL 134 IS 5 BP 743 EP 744 DI 10.1016/S0039-60609(03)00323-4 PG 2 WC Surgery SC Surgery GA 751EM UT WOS:000187039900004 PM 14639350 ER PT J AU Sims, C Stylopoulos, N Clavijo, J Barlow, C AF Sims, C Stylopoulos, N Clavijo, J Barlow, C TI Histologic characteristics of laparoscopic saline-enhanced electrosurgery of liver and splenic injuries SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article DE electrocautery; hemostasis; liver injury; splenic injury; laparoscopic ID ARGON BEAM COAGULATION; FORCEPS AB Background: Hemostasis is crucial during laparoscopic surgery. Unlike conventional electrosurgery, saline-enhanced electrosurgery (SEE) improves the electrode-to-tissue interface. This study investigated SEE as a means of achieving hemostasis in liver and splenic injuries and assessed the associated histologic changes. Methods: Nine anesthetized pigs underwent laparoscopic liver tip and splenic wedge amputations. Injuries were treated with SEE (25-35 and 35-45 W, respectively). Animals were sacrificed postprocedure and at 1 and 4 weeks. Depth of necrosis was analyzed using a mixed model analysis of variance. Results: Liver mean depth of necrosis was 5.3 mm (acute), 6.0 mm (1 week), and 5.3 mm (4 weeks) (p = not significant). Splenic mean depth of necrosis was 7.0 mm (acute), 7.0 mm (1 week), and 2.7 mm (4 weeks). (p < 0.01) Acute injuries demonstrated thermal coagulation necrosis that healed with well-defined bands of collagen at 1 and 4 weeks. Conclusions: SEE provides effective hemostasis and results in an acceptable depth of necrosis with satisfactory wound healing in a porcine model of solid organ injury. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02214 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. Harvard Univ, Ctr Minimally Invas Surg, Boston, MA 02115 USA. RP Sims, C (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,Hurlbut Room, Boston, MA 02214 USA. NR 10 TC 4 Z9 4 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 NOV PY 2003 VL 17 IS 11 BP 1739 EP 1743 DI 10.1007/s00464-002-8638-8 PG 5 WC Surgery SC Surgery GA 765AB UT WOS:000188243300008 PM 12739124 ER PT J AU Lowe, HC Jang, IK Khachigian, LM AF Lowe, HC Jang, IK Khachigian, LM TI Animal models of vulnerable plaque - Clinical context and current status SO THROMBOSIS AND HAEMOSTASIS LA English DT Review DE animal models; atherosclerosis; ischaemic heart disease ID CORONARY-ARTERY DISEASE; HUMAN ATHEROSCLEROTIC PLAQUES; UNSTABLE ANGINA-PECTORIS; SMOOTH-MUSCLE CELLS; MYOCARDIAL-INFARCTION; TISSUE FACTOR; IN-VIVO; MATRIX METALLOPROTEINASES; INTRAVASCULAR ULTRASOUND; ANGIOGRAPHIC MORPHOLOGY AB There is increasing recognition of the importance of vulnerable plaque and acute plaque rupture leading to thrombosis, in the pathogenesis of acute coronary syndromes. This is fueling a number of developments, including novel imaging modalities and potential plaque stabilization therapies. However, to date, no animal model of vulnerable plaque or plaque rupture has been established. Recent developments, particularly using Apo E knockout mice, appear set to provide key breakthroughs. The present status of our understanding of plaque vulnerability is therefore discussed, with a discussion of these current advances in animal models. C1 Univ New S Wales, Ctr Vasc Res, Sydney, NSW 2139, Australia. Univ Sydney, Concord Repatriat Gen Hosp, Dept Cardiol, Sydney, NSW 2006, Australia. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lowe, HC (reprint author), Univ New S Wales, Ctr Vasc Res, Sydney, NSW 2139, Australia. NR 79 TC 6 Z9 7 U1 0 U2 1 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD NOV PY 2003 VL 90 IS 5 BP 774 EP 780 DI 10.1160/TH03-06-0374 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 742EU UT WOS:000186504500006 PM 14597970 ER PT J AU Da Costa, RT Franca, JC Mayrink, W Nascimento, E Genaro, O Campos-Neto, A AF Da Costa, Roberto Teodoro Franca, Joao Carlos Mayrink, Wilson Nascimento, Evaldo Genaro, Odair Campos-Neto, Antonio TI Standardization of a rapid immunochromatographic test with the recombinant antigens K39 and K26 for the diagnosis of canine visceral leishmaniasis SO TRANSACTIONS OF THE ROYAL SOCIETY OF TROPICAL MEDICINE AND HYGIENE LA English DT Article DE canine visceral leishmaniasis; Leishmania chagasi; rapid immunochromatographic test; recombinant antigens; Brazil AB The serological diagnosis of canine visceral leishmaniasis (CVL) remains problematic because there are no reliable commercially available tests. Most laboratories use domestically prepared tests such as the enzyme-linked immunosorbent assay (ELISA) or the indirect immunofluorescent antibody test (IFAT). We evaluated rapid immunochromatographic (RICH) test kits for the diagnosis of CVL. The tests were assembled with either Leishmania chagasi recombinant antigens K39 or K26 and with either gold-labelled Staphylococcus aureus protein A or Streptococcus pyogenes protein G. Fifty sera from dogs with CVL, 14 sera from dogs with Chagas disease, and 50 sera from normal healthy dogs were tested. The results show that the RICH test using recombinant antigen K39 has a sensitivity of 96% and 100% specificity for the diagnosis of CVL. No significant differences were observed in the tests assembled with either protein A or protein G. The RICH tests using recombinant antigen K26 were equally specific but less sensitive than those using K39. However, the 2 antigens complemented each other and increased the overall sensitivity of the test. Because of its simplicity and performance the RICH test is a quick and reliable alternative for the diagnosis of CVL either in conventional laboratories or for remote areas where laboratories are not readily accessible for conventional assays. C1 Univ Fed Minas Gerais, Inst Biol Sci, Dept Parasitol, Lab Leishmaniasis & Vaccines, Belo Horizonte, MG, Brazil. Infect Dis Res Inst, Seattle, WA USA. Sch Med, Itajuba, MG, Brazil. RP Campos-Neto, A (reprint author), Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. EM acampos@forsyth.org NR 41 TC 21 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0035-9203 J9 T ROY SOC TROP MED H JI Trans. Roy. Soc. Trop. Med. Hyg. PD NOV-DEC PY 2003 VL 97 IS 6 BP 678 EP 682 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA V43WB UT WOS:000202964100059 PM 16117962 ER PT J AU Jimenez, RE Castillo, CF Rattner, DW Warshaw, AL AF Jimenez, RE Castillo, CF Rattner, DW Warshaw, AL TI Pylorus-preserving pancreaticoduodenectomy in the treatment of chronic pancreatitis SO WORLD JOURNAL OF SURGERY LA English DT Article ID WHIPPLE PROCEDURE; TOTAL PANCREATECTOMY; HEAD RESECTION; PRESERVATION; PANCREATODUODENECTOMY; COMPLICATIONS; ANTRECTOMY; CANCER; 1990S AB The pylorus-preserving pancreaticoduodenectomy (PPPD) is an alternative to the standard Whipple resection in the treatment of chronic pancreatitis. The operation is safe and can be performed with a low mortality rate. The most common early complication is delayed gastric emptying, which occurs in 25% to 30% of patients, and generally results in longer hospital stays than the standard Whipple procedure. Follow-up studies show that both operations are equally effective in relieving pain in approximately 75% of selected patients. In the long term, the PPPD successfully preserves physiologic gastric emptying, but at the cost of a higher marginal ulceration rate. The purported nutritional advantages of the PPPD over the classic Whipple resection have not been clearly established. At present, the PPPD is the procedure of choice for patients with chronic pancreatitis requiring panceraticoduodenectomy. Based on available information, this recommendation appears to arise form the fact that the PPPD is less radical than the regular Whipple procedure, and some surgeons find it technically easier. Our experience fails to show a distinct superiority of the PPPD over the Whipple operation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Univ Connecticut, Sch Med, Hartford Hosp, Dept Surg, Hartford, CT 06102 USA. RP Warshaw, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 55 Fruit St,WHT506, Boston, MA 02114 USA. NR 32 TC 36 Z9 38 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD NOV PY 2003 VL 27 IS 11 BP 1211 EP 1216 DI 10.1007/s00268-003-7240-0 PG 6 WC Surgery SC Surgery GA 746YG UT WOS:000186776000008 PM 14508610 ER PT J AU Gollackner, B Knosalla, C Houser, S Mauiyyedi, S Buhler, L Kawai, T Duggan, M Sachs, DH Awwad, M Cooper, DKC AF Gollackner, B Knosalla, C Houser, S Mauiyyedi, S Buhler, L Kawai, T Duggan, M Sachs, DH Awwad, M Cooper, DKC TI Pig kidney transplantation in baboons treated intravenously with a bovine serum albumin-Gal alpha 1-3Gal conjugate SO XENOTRANSPLANTATION LA English DT Article DE baboon; bovine serum albumin; Gal alpha 1-3Gal; glycoconjugate; kidney transplantation; pig ID HEMATOPOIETIC-CELL TRANSPLANTATION; HUMORAL XENOGRAFT REJECTION; ANTI-GAL ANTIBODY; IMMUNOAFFINITY COLUMN; HYPERACUTE REJECTION; NATURAL ANTIBODIES; NONHUMAN-PRIMATES; IN-VIVO; XENOTRANSPLANTATION; COAGULATION AB The maintenance of depletion of antibody (Ab) reactive with Galalpha1-3Gal (Gal) on pig vascular endothelial cells by the intravenous (i.v.) infusion of a synthetic Gal conjugate has been proposed as a means of delaying Ab-mediated rejection of transplanted pig organs in primates. We have therefore studied the effect of the continuous i.v. infusion of bovine serum albumin conjugated to multiple synthetic Gal type 6 oligosaccharides (BSA-Gal) on anti-Gal Ab levels and on graft survival in baboons undergoing pig kidney transplantation. Group 1 baboons (n = 3) underwent extracorporeal immunoadsorption of anti-Gal Ab, a cyclophosphamide (CPP)-based immunosuppressive regimen, and a non-transgenic pig kidney transplant. Group 2 (n = 2) were treated identically to Group 1 but, in addition, received a continuous i.v. infusion of BSA-Gal. Group 3 (n = 2) were treated identically to Group 2, but without CPP. A single baboon (Group 4) underwent extracorporeal immunoadsorption, a CPP-based regimen, and continuous i.v. BSA-Gal therapy for 28 days, but did not receive a pig kidney transplant. Two of the transplanted pig kidneys in Group 1 were excised on post-transplant days 7 and 13 for a rejected ureter, and disseminated intravascular coagulation (DIC), respectively. The third baboon died of sepsis on day 6. All transplanted ureters and kidneys showed some histopathologic features of acute humoral xenograft rejection. Group 2 baboons were euthanized on days 8 and 11, respectively, for liver failure. At autopsy, there were histopathological features of widespread liver necrosis, but the pig kidneys and ureters showed no features of rejection. The pig kidneys in Group 3 baboons were excised for renal vein thrombosis (day 9) and DIC (day 12); there were no histological signs of rejection in the pig kidneys or ureters, although there were focal areas of modest liver injury in one baboon on biopsy. The single Group 4 baboon showed no biochemical or histological features of liver injury. Anti-Gal Ab levels returned in Group 1, but were maintained at negligible levels in the baboons in Groups 2 to 4 that received BSA-Gal therapy. Continuous i.v. therapy with BSA-Gal is largely successful in maintaining depletion of circulating anti-Gal antibodies and in preventing or delaying Ab deposition and acute humoral xenograft rejection in porcine grafts, but may be associated with liver injury when administered in the presence of a pig kidney transplant and CPP therapy. The mechanism of the hepatic injury remains uncertain. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplantat Unit, Boston, MA 02129 USA. Immerge BioTherapeut, Cambridge, MA USA. Univ Texas, Texas Med Ctr, Dept Pathol, Houston, TX USA. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH-E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU PHS HHS [1PO1 A145897] NR 25 TC 12 Z9 12 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 NOV PY 2003 VL 10 IS 6 BP 606 EP 614 DI 10.1034/j.1399-3089.2003.00065.x PG 9 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 730HG UT WOS:000185824100009 PM 14708529 ER PT J AU McKenzie, IFC Li, YQ Xing, PX Dinatale, I Koulmanda, M Loveland, BE Sandrin, MS AF McKenzie, IFC Li, YQ Xing, PX Dinatale, I Koulmanda, M Loveland, BE Sandrin, MS TI CD46 protects pig islets from antibody but not cell-mediated destruction in the mouse SO XENOTRANSPLANTATION LA English DT Article DE complement regulators; human CD46; hyperacute rejection; porcine fetal islets; xenotransplantation ID MEMBRANE COFACTOR PROTEIN; DECAY-ACCELERATING FACTOR; TRANSGENIC PIGS; HUMAN CD59; TRANSPLANTATION; COMPLEMENT; EXPRESSION; XENOGRAFTS; ANTIGEN; MODEL AB We have previously reported that islets present in cultured fetal pig pancreas (FPP) are resistant to destruction by Galalpha(1,3)Gal antibodies and complement, but are susceptible to the 'secondary' antibody response which occurs on transplanting pig islet tissue to Galo/o murine recipients. In a model of antibody-mediated graft rejection, we tested the resistance of porcine islets to antibody. Using FPP from human CD46 transgenic pigs, we now report that the complement regulator, CD46, affords protection from antibody-mediated rejection when mouse anti-pig serum (MAPS) was administered to scid mice bearing FPP grafts from either CD46 transgenic or normal pigs. Indeed, whereas normal pig islets were destroyed by an intraperitoneal (i.p.) injection of 0.1 to 0.2 ml of MAPS antibody, destruction of CD46-expressing transgenic islets required 0.5 ml, i.e. up to five times the amount. In contrast, there was no prolongation of the survival of CD46 transgenic mouse skin or heart major histocompatibility complex-compatible or -incompatible allografts - rejected by predominantly cellular immune mechanisms, as opposed to xenograft rejection. Although complement regulators have been examined for their protective role in hyperacute rejection of vascularized xenografts, it is clear that they also have protective effects in the later, antibody-mediated responses, but are unlikely to effect the inflammatory response in cell-mediated rejection. C1 Austin Res Inst, Heidelberg, Vic 3084, Australia. Massachusetts Gen Hosp, Dept Surg, Islet Transplantat Lab, Boston, MA 02114 USA. RP McKenzie, IFC (reprint author), Austin Res Inst, Studley Rd, Heidelberg, Vic 3084, Australia. NR 26 TC 7 Z9 7 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 NOV PY 2003 VL 10 IS 6 BP 615 EP 621 DI 10.1034/j.1399-3089.2003.00066.x PG 7 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 730HG UT WOS:000185824100010 PM 14708531 ER PT J AU Achenbach, S Schmermund, A Erbel, R Silber, S Haberl, R Moshage, W Daniel, WG AF Achenbach, S Schmermund, A Erbel, R Silber, S Haberl, R Moshage, W Daniel, WG TI Detection of coronary calcifications by electron beam tomography and multislice spiral CT: clinical relevance SO ZEITSCHRIFT FUR KARDIOLOGIE LA German DT Review DE coronary calcification; electron beam tomography; multislice spiral CT; computed tomography; atherosclerosis; coronary artery disease ID ACUTE MYOCARDIAL-INFARCTION; ULTRAFAST COMPUTED-TOMOGRAPHY; PRACTICE GUIDELINES COMMITTEE; ASSOCIATION TASK-FORCE; CARDIAC RISK-FACTORS; ARTERY CALCIUM; PROGNOSTIC VALUE; FOLLOW-UP; ASYMPTOMATIC SUBJECTS; AMERICAN-COLLEGE AB Coronary calcifications can be detected and quantified using electron beam tomography (EBT) or newer generation multi-slice spiral CT (MSCT) scanners. An abundance of data has been acquired by EBT. It could be shown that the amount of coronary calcium correlates to the coronary plaque burden. The detection of coronary calcium with CT imaging methods therefore provides a unique opportunity to detect and quantify coronary atherosclerosis in a subclinical stage. Consequently, the presence and amount of coronary calicum has been shown to be indicative for an increased coronary event risk in symptomatic and asymptomatic individuals. Serveral clinical studies found a predictive value that was superior to conventional risk factors. Clinically, the use of coronary calcification assessment may therefore be beneficial in patients who, based on traditional risk factors, seem to be at,intermediate risk" for coronary events (10-year event risk 10-20%) in order to decide on the aggressiveness of risk factor modification. The role of coronary calcium quantification to monitor the progression of disease has not been clarified yet. Large, ongoing trials will provide further data as to the relative merit of coronary calcium assessment for risk stratification and will help to more clearly define its clinical role. The relationship between coronary calcium and coronary stenoses is more complex. While the absence of coronary calcifications makes significant coronary stenoses unlikely, even large amounts of coronary calicum do not necessarily indicate the presence of coronary artery stenoses. Pronounced coronary calcifications as an isolated finding should therefore not be the motivation for invasive diagnostic procedures in the absence of other evidence of ischemic heart disease. C1 Univ Erlangen Nurnberg, Med Klin 2 & Poliklin, Erlangen, Germany. Univ Essen Gesamthsch, Med Klin & Poliklin, Kardiol Klin, D-45147 Essen, Germany. Herzdiagnostikzentrum, Kardiol Gemeinschaftspraxis, Munich, Germany. RP Achenbach, S (reprint author), Massachusetts Gen Hosp, CIMIT, 100 Charles River Plaza,Suite 400, Boston, MA 02114 USA. NR 82 TC 14 Z9 15 U1 1 U2 4 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0300-5860 J9 Z KARDIOL JI Z. Kardiol. PD NOV PY 2003 VL 92 IS 11 BP 899 EP 907 DI 10.1007/s00392-003-0993-5 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 749TV UT WOS:000186945700001 PM 14634759 ER PT J AU Hsieh, JJD Cheng, EHY Korsmeyer, SJ AF Hsieh, JJD Cheng, EHY Korsmeyer, SJ TI Taspase1: A threonine aspartase required for cleavage of MLL and proper HOX gene expression SO CELL LA English DT Article ID 11Q23 CHROMOSOMAL TRANSLOCATIONS; DROSOPHILA-TRITHORAX; PROTEOLYTIC CLEAVAGE; BITHORAX COMPLEX; ACUTE LEUKEMIAS; HOMEOBOX GENES; PROTEIN; ACTIVATION; MECHANISM; PROTEASOME AB The Mixed-Lineage Leukemia gene (MLL/HRX/ALL1) encodes a large nuclear protein homologous to Drosophila trithorax that is required for the maintenance of HOX gene expression. MLL is cleaved at two conserved sites generating N320 and C180 fragments, which heterodimerize to stabilize the complex and confer its subnuclear destination. Here, we purify and clone the protease responsible for cleaving MLL. We entitle it Taspase1 as it initiates a class of endopeptidases that utilize an N-terminal threonine as the active site nucleophile to proteolyze polypeptide substrates following aspartate. Taspase1 proenzyme is intramolecularly proteolyzed generating an active 28 kDa alpha/22 kDa beta heterodimer. RNAi-mediated knockdown of Taspase1 results in the appearance of unprocessed MLL and the loss of proper HOX gene expression. Taspase1 coevolved with MLL/trithorax as Arthropoda and Chordata emerged from Metazoa suggesting that Taspase1 originated to regulate complex segmental body plans in higher organisms. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Korsmeyer, SJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA102594, CA68484] NR 49 TC 152 Z9 155 U1 1 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 31 PY 2003 VL 115 IS 3 BP 293 EP 303 DI 10.1016/S0092-8674(03)00816-X PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 740RH UT WOS:000186415000009 PM 14636557 ER PT J AU Fukumura, D Ushiyama, A Duda, DG Xu, L Tam, J Chatterjee, VKK Garkavtsev, I Jain, RK AF Fukumura, D Ushiyama, A Duda, DG Xu, L Tam, J Chatterjee, VKK Garkavtsev, I Jain, RK TI Paracrine regulation of angiogenesis and adipocyte differentiation during in vivo adipogenesis SO CIRCULATION RESEARCH LA English DT Article DE obesity; adipogenesis; angiogenesis; vascular endothelial growth factor; peroxisome proliferator-activated receptor gamma ID ENDOTHELIAL GROWTH-FACTOR; ACTIVATED RECEPTOR-GAMMA; ADIPOSE-TISSUE; PPAR-GAMMA; GENE-EXPRESSION; MESSENGER-RNA; PREADIPOCYTE DIFFERENTIATION; STIMULATES ANGIOGENESIS; MOLECULAR REGULATION; VEGF RECEPTOR-2 AB With an increasing incidence of obesity worldwide, rational strategies are needed to control adipogenesis. Growth of any tissue requires the formation of a functional and mature vasculature. To gain mechanistic insight into the link between active adipogenesis and angiogenesis, we developed a model to visualize noninvasively and in real time both angiogenesis and adipogenesis using intravital microscopy. Implanted murine preadipocytes induced vigorous angiogenesis and formed fat pads in a mouse dorsal skin-fold chamber. The newly formed vessels subsequently remodeled into a mature network consisting of arterioles, capillaries, and venules, whereas the preadipocytes differentiated into adipocytes as confirmed by increased aP2 expression. Inhibition of adipocyte differentiation by transfection of preadipocytes with a peroxisome proliferator-activated receptor gamma dominant-negative construct not only abrogated fat tissue formation but also reduced angiogenesis. Surprisingly, inhibition of angiogenesis by vascular endothelial growth factor receptor-2 (VEGFR2) blocking antibody not only reduced angiogenesis and tissue growth but also inhibited preadipocyte differentiation. We found that part of this inhibition stems from the paracrine interaction between endothelial cells and preadipocytes and that VEGF-VEGFR2 signaling in endothelial cells, but not preadipocytes, mediates this process. These findings reveal a reciprocal regulation of adipogenesis and angiogenesis, and suggest that blockade of VEGF signaling can inhibit in vivo adipose tissue formation. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steel Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Cambridge, Dept Med, Cambridge CB2 2QQ, England. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steel Lab, 100 Blossom St,COX-7, Boston, MA 02114 USA. FU NCI NIH HHS [R24 CA085140, R01 CA085140-06, R24-CA85140, T32 CA073479, P01-CA80124, T32-CA73479, R01 CA085140, T32 CA073479-11, P01 CA080124, P01 CA080124-08]; Wellcome Trust NR 67 TC 148 Z9 153 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD OCT 31 PY 2003 VL 93 IS 9 BP E88 EP E97 DI 10.1161/01.RES.0000099243.20096.FA PG 10 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 738EM UT WOS:000186273800016 PM 14525808 ER PT J AU Madras, BK Fahey, MA Miller, GM De La Garza, R Goulet, M Spealman, RD Meltzer, PC George, SR O'Dowd, BF Bonab, AA Livni, E Fischman, AJ AF Madras, BK Fahey, MA Miller, GM De La Garza, R Goulet, M Spealman, RD Meltzer, PC George, SR O'Dowd, BF Bonab, AA Livni, E Fischman, AJ TI Non-amine-based dopamine transporter (reuptake) inhibitors retain properties of amine-based progenitors SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE dopamine transporter (DAT); cocaine; attention deficit hyperactivity disorder (ADHD); anti-depressant; serotonin transporter (SERT); addiction ID COCAINE RECOGNITION SITES; BETA-ADRENERGIC-RECEPTOR; SEROTONIN TRANSPORTER; NONHUMAN-PRIMATES; BINDING-SITES; MONKEY BRAIN; RAT-BRAIN; MONOAMINE TRANSPORTERS; DIFFERENTIALLY ALTER; NUCLEUS-ACCUMBENS AB Without exception, therapeutic and addictive drugs that produce their primary effects by blocking monoamine transporters in brain contain an amine nitrogen in their structure. This fundamental canon of drug design was based on a prevailing premise that an amine nitrogen is required to mimic the structures of monoamine neurotransmitters and other natural products. Non-amines, a novel class of compounds that contain no amine nitrogen, block monoamine transporters in the nM range and display markedly high selectivity for monoamine transporters, but not for receptors. Non-amines retain the spectrum of biochemical and pharmacological properties characteristic of amine-bearing counterparts. These novel drugs compel a revision of current concepts of drug-monoamine transporter complex formation and open avenues for discovery of a new generation of therapeutic drugs. (C) 2003 Elsevier B.V. All rights reserved. C1 Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Dept Psychiat, Southborough, MA 01772 USA. Organix Inc, Woburn, MA 01801 USA. Univ Toronto, Dept Pharmacol, Toronto, ON M5S 1A8, Canada. Massachusetts Gen Hosp, Dept Nucl Med, Boston, MA 02114 USA. RP Madras, BK (reprint author), Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Dept Psychiat, 1 Pine Hill Dr, Southborough, MA 01772 USA. RI De La Garza, Richard/B-2489-2014 OI De La Garza, Richard/0000-0003-1943-4469 FU NCRR NIH HHS [RR00168]; NIDA NIH HHS [DA 4-8309, DA-7-8825, DA00304, DA06303, DA09462, DA11305, DA11542, DA11558]; NIMH NIH HHS [N01 MH80005] NR 49 TC 14 Z9 14 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD OCT 31 PY 2003 VL 479 IS 1-3 BP 41 EP 51 DI 10.1016/j.ejphar.2003.08.055 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 745NG UT WOS:000186694300005 PM 14612136 ER PT J AU Lee, EDH Pappalardo, E Scafidi, J Davis, AE AF Lee, EDH Pappalardo, E Scafidi, J Davis, AE TI Approaches toward reversal of increased vascular permeability in C1 inhibitor deficient mice SO IMMUNOLOGY LETTERS LA English DT Article DE C1 inhibitor; hereditary angioedema; complement; contact system ID ACTING BRADYKININ-ANTAGONIST; HEREDITARY ANGIOEDEMA; FUNCTIONAL-ANALYSIS; COMPLEMENT; C1-INHIBITOR; ACTIVATION; KALLIKREIN; HOE-140; POTENT; RATS AB C1 inhibitor (C1INH) deficient mice have increased vascular permeability that can be demonstrated by the extravasation of Evans Blue dye. This vascular leak is reversed with protease inhibitors, such as C1INH itself, DX88 (a recombinant variant Kunitz domain plasma kallikrein inhibitor), and the bradykinin receptor type 2 antagonist, Hoe 140. The studies described here were undertaken for the following reasons: (1) To provide a more quantitative analysis of the effects of these interventions; (2) to provide data to further test the hypothesis that increased vascular permeability results from contact system activation with kallikrein-mediated release of bradykinin; (3) to test the hypothesis that the amino terminal non-serpin domain of C1INH modulates access to complex proteases, such as kallikrein complexed with high molecular weight kininogen (HK); and (4) to determine whether attenuated androgens or estrogens exert a direct effect on C1INH synthesis. To characterize the differences in these reagents, the dose-response and the rate of reappearance of increased vascular permeability in C1INH(-/-) mice were determined for the following agents: human plasma-derived C1INH, a recombinant Kunitz domain plasma kallikrein inhibitor (DX88), a bradykinin receptor antagonist (Hoe 140), and a recombinant C1INH with an amino terminal truncation at amino acid 98 and substitution of the P2 Ala with a Val (Cserp98,A443V). C1INH and Cserp98,A443V were equivalent in activity, which provides further support for the hypothesis that the vascular leak is mediated by bradykinin and suggests that the amino terminal domain neither enhances nor interferes with access to kallikrein within the kallikrein-HK complex. DX88 was effective at very low doses, as was Hoe140. The duration of action of Hoe140 was quite prolonged. The data indicate that, in the mouse, neither danazol nor estrogens have a significant effect on C1INH synthesis. (C) 2003 Elsevier B.V. All rights reserved. C1 Ctr Blood Res, Boston, MA 02115 USA. Univ Milan, IRCCS, Osped Maggiore, Dept Internal Med, I-20122 Milan, Italy. RP Davis, AE (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. EM aldavis@cbr.med.harvard.edu NR 17 TC 14 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 EI 1879-0542 J9 IMMUNOL LETT JI Immunol. Lett. PD OCT 31 PY 2003 VL 89 IS 2-3 BP 155 EP 160 DI 10.1016/S0165-2478(03)00130-5 PG 6 WC Immunology SC Immunology GA 733WG UT WOS:000186023200010 ER PT J AU Vergnes, L Phan, J Strauss, M Tafuri, S Reue, K AF Vergnes, L Phan, J Strauss, M Tafuri, S Reue, K TI Cholesterol and cholate components of an atherogenic diet induce distinct stages of hepatic inflammatory gene expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DENSITY-LIPOPROTEIN LEVELS; HIGH-FAT DIETS; TRANSGENIC MICE; STELLATE CELLS; ATHEROSCLEROSIS; MOUSE; FIBROSIS; SUSCEPTIBILITY; IV; HYPERCHOLESTEROLEMIA AB Atherosclerosis in inbred mouse strains has been widely studied by using an atherogenic (Ath) diet containing cholesterol, cholic acid, and fat, but the effect of these components on gene expression has not been systematically examined. We employed DNA microarrays to interrogate gene expression levels in liver of C57BL/6J mice fed the following five diets: mouse chow, the Ath diet, or modified versions of the Ath diet in which either cholesterol, cholate, or fat were omitted. Dietary cholesterol and cholate produced discrete gene expression patterns. Cholesterol was required for induction of genes involved in acute inflammation, including three genes of the serum amyloid A family, three major histocompatibility class II antigen genes, and various cytokine-related genes. In contrast, cholate induced expression of genes involved in extracellular matrix deposition in hepatic fibrosis, including five collagen family members, collagen-interacting proteins, and connective tissue growth factor. The gene expression findings were confirmed by biochemical measurements showing that cholesterol was required for elevation of circulating serum amyloid A, and cholate was required for accumulation of collagen in the liver. The possibility that these gene expression changes are relevant to atherogenesis in C57BL/6J mice was supported by the observation that the closely related, yet atherosclerosis-resistant, C57BL/ 6ByJ strain was largely resistant to dietary induction of the inflammatory and fibrotic response genes. These results establish that cholesterol and cholate components of the Ath diet have distinct proatherogenic effects on gene expression and suggest a strategy to study the contribution of acute inflammatory response and fibrogenesis independently through dietary manipulation. C1 Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Pfizer Global Res & Dev, Ann Arbor Labs, Ann Arbor, MI 48105 USA. RP Reue, K (reprint author), 11301 Wilshire Blvd,Bldg 113,Rm 312, Los Angeles, CA 90073 USA. FU NHLBI NIH HHS [HL28481, HL58627] NR 35 TC 106 Z9 109 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 OCT 31 PY 2003 VL 278 IS 44 BP 42774 EP 42784 DI 10.1074/jbc.M306022200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 736EA UT WOS:000186157000008 PM 12923166 ER PT J AU Shimizu, S Ugi, S Maegawa, H Egawa, K Nishio, Y Yoshizaki, T Shi, K Nagai, Y Morino, K Nemoto, K Nakamura, T Bryer-Ash, M Kashiwagi, A AF Shimizu, S Ugi, S Maegawa, H Egawa, K Nishio, Y Yoshizaki, T Shi, K Nagai, Y Morino, K Nemoto, K Nakamura, T Bryer-Ash, M Kashiwagi, A TI Protein-tyrosine phosphatase 1B as new activator for hepatic lipogenesis via sterol regulatory element-binding protein-1 gene expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INSULIN SENSITIVITY; RESISTANCE; MICE; PATHWAY; GLUCOSE; LIVERS; SP1; 2A; PHOSPHORYLATION; OVEREXPRESSION AB Like hyperglycemia, postprandial (diet-induced) hypertriglyceridemia is thought to play crucial roles in the pathogenesis of insulin resistant/metabolic syndrome. Sterol regulatory element-binding protein-1 (SREBP-1) is a key transcription factor to induce postprandial hypertriglyceridemia. We found that insulin-resistant rats fed a diet high in fructose showed an increased protein-tyrosine phosphatase 1B (PTP1B) content with strong expression of SREBP-1 mRNA in the liver. To clarify the association of PTP1B with SREBP-1 gene expression, we overexpressed PTP1B in rat hepatocytes, which led to increased mRNA content and promoter activity of SREBP-1a and -1c, resulting in the increased mRNA expression of fatty-acid synthase, one of the SREBP-1-responsive lipogenic genes. Because PTP1B overexpression increased phosphatase 2A (PP2A) activity, we inhibited PP2A activity by expression of its selective inhibitor, SV40 small t antigen and found that this normalized the PTP1B-enhanced SREBP-1a and -1c mRNA expressions through activation of the Sp1 site. These results indicate that PTP1B may regulate gene expression of SREBP-1 via enhancement of PP2A activity, thus mediating hepatic lipogenesis and postprandial hypertriglyceridemia. We demonstrate here a unique serial activation of the PTP1B-PP2A axis as a novel mechanism for the regulation of gene expression in the biosynthesis of triglyceride. C1 Shiga Univ Med Sci, Dept Med, Div Endocrinol & Metab, Shiga 5202192, Japan. Shiga Univ Med Sci, Dept Anat, Shiga 5202192, Japan. Univ Calif Los Angeles, Dept Med, Div Endocrinol Diabet & Hypertens, Gonda Goldschmied Diabet Ctr, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90095 USA. RP Maegawa, H (reprint author), Shiga Univ Med Sci, Dept Med, Div Endocrinol & Metab, Shiga 5202192, Japan. NR 32 TC 54 Z9 59 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 OCT 31 PY 2003 VL 278 IS 44 BP 43095 EP 43101 DI 10.1074/jbc.M306880200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 736EA UT WOS:000186157000048 PM 12941932 ER PT J AU Sneddon, WB Syme, CA Bisello, A Magyar, CE Rochdi, MD Parent, JL Weinman, EJ Abou-Samra, AB Friedman, PA AF Sneddon, WB Syme, CA Bisello, A Magyar, CE Rochdi, MD Parent, JL Weinman, EJ Abou-Samra, AB Friedman, PA TI Activation-independent parathyroid hormone receptor internalization is regulated by NHERF1 (EBP50) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; CHRONIC-RENAL-FAILURE; PTH-RELATED PROTEIN; PDZ-DOMAIN; KINASE-A; SIGNAL-TRANSDUCTION; BINDING PROTEIN; PLASMA-MEMBRANE; PHOSPHOLIPASE-C; EZRIN AB Parathyroid hormone (PTH) regulates extracellular calcium homeostasis through the type 1 PTH receptor (PTH1R) expressed in kidney and bone. The PTH1R undergoes beta-arrestin/dynamin-mediated endocytosis in response to the biologically active forms of PTH, PTH-(1 34), and PTH-( 1 - 84). We now show that amino-truncated forms of PTH that do not activate the PTH1R nonetheless induce PTH1R internalization in a cell-specific pattern. Activation-independent PTH1R endocytosis proceeds through a distinct arrestin-independent mechanism that is operative in cells lacking the adaptor protein Na/H exchange regulatory factor 1 (NHERF1) (ezrin-binding protein 50). Using a combination of radioligand binding experiments and quantitative, live cell confocal microscopy of fluorescently tagged PTH1Rs, we show that in kidney distal tubule cells and rat osteosarcoma cells, which lack NHERF1, the synthetic antagonist PTH-( 7 - 34) and naturally circulating PTH-( 7 - 84) induce internalization of PTH1R in a beta-arrestin-independent but dynamin-dependent manner. Expression of NHERF1 in these cells inhibited antagonist-induced endocytosis. Conversely, expression of dominant-negative forms of NHERF1 conferred internalization sensitivity to PTH-( 7 - 34) in cells expressing NHERF1. Mutation of the PTH1R PDZ-binding motif abrogated interaction of the receptor with NHERF1. These mutated receptors were fully functional but were now internalized in response to PTH-( 7 - 34) even in NHERF1-expressing cells. Removing the NHERF1 ERM domain or inhibiting actin polymerization allowed otherwise inactive ligands to internalize the PTH1R. These results demonstrate that NHERF1 acts as a molecular switch that legislates the conditional efficacy of PTH fragments. Distinct endocytic pathways are determined by NHERF1 that are operative for the PTH1R in kidney and bone cells. C1 Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Med, Div Endocrinol, Pittsburgh, PA 15261 USA. Univ Sherbrooke, Fac Med, Div Rheumatol, Sherbrooke, PQ J1H 5N4, Canada. Univ Sherbrooke, Clin Res Ctr, Sherbrooke, PQ J1H 5N4, Canada. Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA. Dept Vet Affairs Med Ctr, Baltimore, MD 21201 USA. Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Pittsburgh, Sch Med, Dept Med, Div Renal, Pittsburgh, PA 15261 USA. RP Friedman, PA (reprint author), Univ Pittsburgh, Sch Med, Dept Pharmacol, E-1347 Biomed Sci Tower, Pittsburgh, PA 15261 USA. OI Abou-Samra, Abdul/0000-0001-8735-1142 FU NIDDK NIH HHS [DK-54171, DK-62078] NR 62 TC 118 Z9 118 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 OCT 31 PY 2003 VL 278 IS 44 BP 43787 EP 43796 DI 10.1074/jbc.M306019200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 736EA UT WOS:000186157000129 PM 12920119 ER PT J AU Stiles, CD AF Stiles, CD TI Lost in space: Misregulated positional cues create tripotent neural progenitors in cell culture SO NEURON LA English DT Editorial Material ID STEM-CELLS; SPECIFICATION; CNS AB In a widely held view of vertebrate CNS development, neurons, astrocytes, and oligodendrocytes arise from a common tripotent progenitor cell. However, tripotent progenitors have never been detected in developing embryos. In this issue of Neuron, Gabay et al. show that tripotent progenitors can be created in vitro by deregulation of normal dorsoventral positional cues. C1 Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Program Neurooncol,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Stiles, CD (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Program Neurooncol,Dana Farber Canc Inst, Boston, MA 02115 USA. NR 12 TC 10 Z9 10 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD OCT 30 PY 2003 VL 40 IS 3 BP 447 EP 449 DI 10.1016/S0896-6273(03)00683-4 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 740AQ UT WOS:000186379000001 PM 14642266 ER PT J AU Shattuck, TM Valimaki, S Obara, T Gaz, RD Clark, OH Shoback, D Wierman, ME Tojo, K Robbins, CM Carpten, JD Farnebo, LO Larsson, C Arnold, A AF Shattuck, TM Valimaki, S Obara, T Gaz, RD Clark, OH Shoback, D Wierman, ME Tojo, K Robbins, CM Carpten, JD Farnebo, LO Larsson, C Arnold, A TI Somatic and germ-line mutations of the HRPT2 gene in sporadic parathyroid carcinoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID JAW TUMOR SYNDROME; HEREDITARY HYPERPARATHYROIDISM; SUPPRESSOR GENES; RETINOBLASTOMA; DIAGNOSIS; MANAGEMENT; HISTORY; CANCER; BRCA2 AB BACKGROUND: We looked for mutations of the HRPT2 gene, which encodes the parafibromin protein, in sporadic parathyroid carcinoma because germ-line inactivating HRPT2 mutations have been found in a type of familial hyperparathyroidism -- hyperparathyroidism-jaw tumor (HPT-JT) syndrome -- that carries an increased risk of parathyroid cancer. METHODS: We directly sequenced the full coding and flanking splice-junctional regions of the HRPT2 gene in 21 parathyroid carcinomas from 15 patients who had no known family history of primary hyperparathyroidism or the HPT-JT syndrome at presentation. We also sought to confirm the somatic nature of the identified mutations and tested the carcinomas for tumor-specific loss of heterozygosity at HRPT2. RESULTS: Parathyroid carcinomas from 10 of the 15 patients had HRPT2 mutations, all of which were predicted to inactivate the encoded parafibromin protein. Two distinct HRPT2 mutations were found in tumors from five patients, and biallelic inactivation as a result of a mutation and loss of heterozygosity was found in one tumor. At least one HRPT2 mutation was demonstrably somatic in carcinomas from six patients. Unexpectedly, HRPT2 mutations in the parathyroid carcinomas of three patients were identified as germ-line mutations. CONCLUSIONS: Sporadic parathyroid carcinomas frequently have HRPT2 mutations that are likely to be of pathogenetic importance. Certain patients with apparently sporadic parathyroid carcinoma carry germ-line mutations in HRPT2 and may have the HPT-JT syndrome or a phenotypic variant. C1 Univ Connecticut, Sch Med, Ctr Mol Med, Farmington, CT 06030 USA. Univ Connecticut, Sch Med, Div Endocrinol & Metab, Farmington, CT 06030 USA. Karolinska Hosp, Dept Mol Med, S-10401 Stockholm, Sweden. Karolinska Hosp, Dept Surg Sci, S-10401 Stockholm, Sweden. Tokyo Womens Med Univ, Dept Endocrine Surg, Sinjuku Ku, Tokyo, Japan. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Univ Calif San Francisco, Mt Zion Med Ctr, Dept Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Vet Affairs Med Ctr, Endocrine Res Unit, San Francisco, CA 94143 USA. Univ Colorado, Vet Affairs Med Ctr, Div Endocrinol, Denver, CO 80202 USA. Jikei Univ, Sch Med, Dept Internal Med, Div Diabet & Endocrinol, Tokyo, Japan. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Arnold, A (reprint author), Univ Connecticut, Sch Med, Ctr Mol Med, 263 Farmington Ave, Farmington, CT 06030 USA. NR 34 TC 266 Z9 278 U1 1 U2 5 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 OCT 30 PY 2003 VL 349 IS 18 BP 1722 EP 1729 DI 10.1056/NEJMoa031237 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 737FJ UT WOS:000186219500006 PM 14585940 ER PT J AU Chung, DC Mino, M Shannon, KM Isselbacher, KJ Harris, NL AF Chung, DC Mino, M Shannon, KM Isselbacher, KJ Harris, NL TI Case 34-2003: A 45-year-old woman with a family history of colonic polyps and cancer - Attenuated familial adenomatous polyposis syndrome with a germ-line truncating mutation of the APC gene at codon 169 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID NONPOLYPOSIS COLORECTAL-CANCER; CYCLOOXYGENASE-2 INHIBITOR; SULINDAC; EXPRESSION; DIAGNOSIS; CELECOXIB; ALLELES; COLI; AFAP C1 Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc Risk Anal, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Chung, DC (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. NR 34 TC 7 Z9 8 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 30 PY 2003 VL 349 IS 18 BP 1750 EP 1760 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 737FJ UT WOS:000186219500011 PM 14585944 ER PT J AU DeArmond, D Brattain, MG Jessup, JM Kreisberg, J Malik, S Zhao, SJ Freeman, JW AF DeArmond, D Brattain, MG Jessup, JM Kreisberg, J Malik, S Zhao, SJ Freeman, JW TI Autocrine-mediated ErbB-2 kinase activation of STAT3 is required for growth factor independence of pancreatic cancer cell lines SO ONCOGENE LA English DT Article DE growth factors; ErbB-2; cell signaling; pancreatic cancer ID CYCLIN D1; FACTOR-ALPHA; CONSTITUTIVE ACTIVATION; BREAST-CANCER; SIGNAL TRANSDUCERS; TYROSINE KINASES; CDK INHIBITORS; ABERRANT REGULATION; DEPENDENT KINASE; FACTOR RECEPTORS AB Pancreatic ductal adenocarcinoma (PDAC) cell lines, MIA PaCa-2, and UK Pan-1, were used to investigate the role of ErbB2 in PDAC oncogenesis. Both these cell lines exhibit exogenous growth factor-independent proliferation that was attributed to the production of autocrine growth factors and/or overexpression of growth factor receptors. The exogenous growth factor-independent phenotype displayed by these PDAC cell lines was dependent on ErbB2 kinase activity since treatment of cells with tyrphostin AG879 prevented serum-free media (SFM) induction of cell proliferation. We determined that ErbB2 kinase contributed to aberrant cell cycle regulation in PDAC through the induction of cyclin D1 levels and the suppression of p21(Cip1) and p27(Kip1). Inhibition of ErbB2 kinase led to cell cycle arrest marked by an increased association of p27(Kip1) with cdk2 and reduced levels of phosphorylated pRb. We further observed constitutive STAT3 activation in the PDAC cell lines and an increase in STAT3 activation upon stimulating quiescent cells with SFM. Inhibitors of ErbB2 kinase blocked STAT3 activation, whereas inhibition of EGFR kinase led to a slight reduction of STAT3 activation. STAT3 was coimmunoprecipitated with ErbB2. SFM stimulation caused an increase in the association of ErbB2 and STAT3, which was blocked by inhibition of ErbB2 kinase. Expression of a STAT3 dominant negative prevented SFM-stimulated cell proliferation of MIA PaCa-2 cells, suggesting that activation of STAT3 by ErbB2 is required for a growth factor-independent phenotype of these cells. Consistent with this observation in PDAC cell lines, we found that most PDAC tumor specimens ( 10 of 11) showed constitutive activation of STAT3 and that ErbB2 was readily detected in most of these tumors ( nine of 11). We believe that these findings indicate a novel mechanism of oncogenesis in PDAC and may suggest future therapeutic strategies in the treatment of PDAC. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Med Oncol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Surg, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, Res & Dev, San Antonio, TX 78229 USA. Roswell Pk Canc Inst, Dept Pharmacol & Therapeut, Buffalo, NY 14263 USA. Georgetown Univ, Med Ctr, Dept Surg, Washington, DC 20007 USA. RP Freeman, JW (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Med Oncol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NCI NIH HHS [R01 CA69122, P30 CA 54174] NR 70 TC 41 Z9 42 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 OCT 30 PY 2003 VL 22 IS 49 BP 7781 EP 7795 DI 10.1038/sj.onc.1206966 PG 15 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 737PD UT WOS:000186240200008 PM 14586404 ER PT J AU Ancukiewicz, M Finkelstein, DM Schoenfeld, DA AF Ancukiewicz, M Finkelstein, DM Schoenfeld, DA TI Modelling the relationship between continuous covariates and clinical events using isotonic regression SO STATISTICS IN MEDICINE LA English DT Article DE survival; isotonic; non-parametric; longitudinal; CD4; HIV ID INFECTION AB In a medical study we are often interested in graphically displaying the relationship between continuous variables and clinical events indicating disease progression. Often, it is reasonable to make the minimal assumption that the risk of progression is an arbitrary monotone function of the continuous variable. Sometimes the continuous variable is a disease marker which is recorded longitudinally, and so the goal is to provide a graphical display of the relationship between the hazard for progression and the most recent measurement of the longitudinal marker. For example, we know that for a patient with HIV infection, declining CD4 Count is associated with an increased risk of opportunistic infection. The goal of this paper is to extend isotonic regression techniques to failure time data with a continuous covariate, to obtain a non-parametric estimate for the hazard of disease progression as a monotonic function of the continuous variable. We propose two methods for modelling the relationship of the hazard and covariate: the first assumes that the hazard is constant over time, and the second allows the hazard to be an arbitrary function of time. These methods will be applied to graphically display the risk for an AIDS patient of an Opportunistic infection as a function of CD4 Count. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA USA. RP Finkelstein, DM (reprint author), Massachusetts Gen Hosp, Ctr Biostat, 50 Staniford St,Suite 560, Boston, MA 02114 USA. FU NCI NIH HHS [CA 74302]; NIAID NIH HHS [AI 38855] NR 12 TC 1 Z9 1 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD OCT 30 PY 2003 VL 22 IS 20 BP 3151 EP 3159 DI 10.1002/sim.1561 PG 9 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 727JV UT WOS:000185655600003 PM 14518020 ER PT J AU Gagnon, DR Glickman, ME Myers, RH Cupples, LA AF Gagnon, DR Glickman, ME Myers, RH Cupples, LA TI The analysis of survival data with a non-susceptible fraction and dual censoring mechanisms SO STATISTICS IN MEDICINE LA English DT Article DE survival analysis; Bayesian; Weibull distribution; censoring; missing data ID CURE RATE MODELS; AGE-OF-ONSET; HUNTINGTONS-DISEASE; ALZHEIMERS-DISEASE; REPEAT LENGTH; RISK; HETEROGENEITY; INSTABILITY AB It is known that the ages of onset of many diseases are determined by both a genetic predisposition to disease as well as environmental risk factors that are capable of either triggering or hastening the onset of disease. Difficulties in modelling onset ages arise when a large fraction fail to inherit the disease-causing gene, and multiple reasons for censoring result in unobserved onset ages. We present a parametric Bayesian model that includes subjects with missing age information, non-susceptible subjects and allows for regression on risk factor information. The model is fit using Markov chain Monte Carlo simulation from the posterior distribution, and allows the simultaneous estimation of the proportion of the population at risk of disease, the mean onset age of disease, survival after disease onset, and the association of risk factors with susceptibility, onset age and survival after onset. An example employing Huntington's disease data is presented. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA 02130 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Boston Univ, Dept Neurol, Boston, MA 02118 USA. RP Gagnon, DR (reprint author), Boston Univ, Sch Med, Dept Epidemiol & Biostat, 715 Albany St,Talbot E 4, Boston, MA 02118 USA. OI Glickman, Mark/0000-0003-3993-2801; Gagnon, David/0000-0002-6367-3179; Cupples, L. Adrienne/0000-0003-0273-7965; Myers, Richard/0000-0002-8365-2674 NR 23 TC 2 Z9 2 U1 1 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD OCT 30 PY 2003 VL 22 IS 20 BP 3249 EP 3262 DI 10.1002/sim.1568 PG 14 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 727JV UT WOS:000185655600009 PM 14518026 ER PT J AU Arnett, HA Wang, Y Matsushima, GK Suzuki, K Ting, JPY AF Arnett, HA Wang, Y Matsushima, GK Suzuki, K Ting, JPY TI Functional genomic analysis of remyelination reveals importance of inflammation in oligodendrocyte regeneration SO JOURNAL OF NEUROSCIENCE LA English DT Article DE oligodendrocytes; glia; neuroinflammation; regeneration; major histocompatibility complex; gene array; multiple sclerosis; remyelination; demyelination; TNF ID CENTRAL-NERVOUS-SYSTEM; CUPRIZONE-INDUCED DEMYELINATION; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; FACTOR-DEFICIENT MICE; MULTIPLE-SCLEROSIS; GENE-EXPRESSION; IMMUNE FUNCTION; T-CELLS; TNF; ABSENCE AB Tumor necrosis factor alpha (TNFalpha), a proinflammatory cytokine, was shown previously to promote remyelination and oligodendrocyte precursor proliferation in a murine model for demyelination and remyelination. We used Affymetrix microarrays in this study to identify ( 1) changes in gene expression that accompany demyelination versus remyelination and ( 2) changes in gene expression during the successful remyelination of wild-type mice versus the unsuccessful attempts in mice lacking TNFalpha. Alterations in inflammatory genes represented the most prominent changes, with major histocompatibility complex (MHC) genes dramatically enhanced in microglia and astrocytes during demyelination, remyelination, and as a consequence of TNFalpha stimulation. Studies to examine the roles of these genes in remyelination were then performed using mice lacking specific genes identified by the microarray. Analysis of MHC-II- null mice showed delayed remyelination and regeneration of oligodendrocytes, whereas removal of MHC-I had little effect. These data point to the induction of MHC-II by TNFalpha as an important regulatory event in remyelination and emphasize the active inflammatory response in regeneration after pathology in the brain. C1 Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Ctr Neurosci, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Immunol Microbiol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. RP Arnett, HA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Smith Bldg 1070,1 Jimmy Fund Way, Boston, MA 02115 USA. FU NINDS NIH HHS [NS24453, NS34190] NR 40 TC 120 Z9 123 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 29 PY 2003 VL 23 IS 30 BP 9824 EP 9832 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 737PZ UT WOS:000186242100016 PM 14586011 ER PT J AU Huq, F Liao, R Hajjar, RJ AF Huq, F Liao, R Hajjar, RJ TI Parvalbumin reverses diastolic dysfunction in senescent myocytes SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 18 BP 4 EP 4 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600081 ER PT J AU Mansour, M Hajjar, R Ruskin, J AF Mansour, M Hajjar, R Ruskin, J TI Atrial action potential duration prolongation by inhibition of Kv4.3 using adenoviral gene transfer in goats SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Cardiovasc Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 23 BP 5 EP 5 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600086 ER PT J AU Shin, JT Pomerantsev, EV Bloch, KD MacRae, CA AF Shin, JT Pomerantsev, EV Bloch, KD MacRae, CA TI Quantitative cardiovascular physiology reveals a role for soluble guanylate cyclase in the developing zebrafish SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 58 BP 12 EP 13 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600121 ER PT J AU He, HM Musi, N Arad, M Fujii, N Hirshman, MF Goodyear, LJ Seidman, JG Seidman, CE Ingwall, JS Rong, T AF He, HM Musi, N Arad, M Fujii, N Hirshman, MF Goodyear, LJ Seidman, JG Seidman, CE Ingwall, JS Rong, T TI Cardiac-specific overexpression of mutant gamma 2 AMPK subunit causes abnormal glucose metabolism and cardiomyopathy in mouse SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 79 BP 17 EP 17 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600142 ER PT J AU Chen, HC Feener, EP AF Chen, HC Feener, EP TI Sp1 and AP-1 co-activation is required for MEK1,2-induced PAI-1 expression SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 88 BP 18 EP 19 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600151 ER PT J AU Cook, SA Morissette, M Matsui, T Nagoshi, T Molkentin, JD Rosenzweig, A AF Cook, SA Morissette, M Matsui, T Nagoshi, T Molkentin, JD Rosenzweig, A TI Myostatin regulates cardiomyocyte growth in vitro and in vivo SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. Cincinnati Childrens Hosp, Med Ctr, Div Mol Cardiovasc Biol, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 158 BP 33 EP 33 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600220 ER PT J AU Ellinor, PT Shin, JT Yoerger, DM Moore, RK MacRae, CA AF Ellinor, PT Shin, JT Yoerger, DM Moore, RK MacRae, CA TI A locus for atrial fibrillation on chromosome 6 SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 162 BP 33 EP 34 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600224 ER PT J AU Shaw, SY Peterson, TA Milan, DJ Zhong, TP MacRae, CA Schreiber, SL Fishman, MC Peterson, RT AF Shaw, SY Peterson, TA Milan, DJ Zhong, TP MacRae, CA Schreiber, SL Fishman, MC Peterson, RT TI Discovery of a novel pro-vasculogenic small molecule via a chemical genetic screen for suppressors of zebrafish gridlock mutants SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Novartis Inst BioMed Res, Cambridge, MA USA. Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 161 BP 33 EP 33 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600223 ER PT J AU Kuhlencordt, PJ Chen, JQ Han, F Astern, J Riehl, G Sykes, M Ertl, G Huang, PL AF Kuhlencordt, PJ Chen, JQ Han, F Astern, J Riehl, G Sykes, M Ertl, G Huang, PL TI The effects of cell type specific iNOS deletion on atherosclerosis development in apoE knockout mice SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Wurzburg, Wurzburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 185 BP 39 EP 39 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600247 ER PT J AU Hoetten, S Kai, H Widder, J Riehl, G Marx, A Huang, PL Ertl, G Kuhlencordt, PJ AF Hoetten, S Kai, H Widder, J Riehl, G Marx, A Huang, PL Ertl, G Kuhlencordt, PJ TI Atheroprotective effects of neuronal nitric oxide synthase (nNOS) in Apolipoprotein E knockout (apoE ko) mice SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Univ Wurzburg, Wurzburg, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 188 BP 40 EP 40 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600250 ER PT J AU O'Donnell, JM Alpert, N Zampino, M Geenen, D Lewandowski, ED AF O'Donnell, JM Alpert, N Zampino, M Geenen, D Lewandowski, ED TI Myocardial triglyceride pool kinetics from C-13 NMR of intact diabetic rat heart demonstrate faster turnover rates and altered Compartmentation versus healthy controls SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Univ Illinois, Coll Med, Program Integrat Cardiac Metab, Dept Physiol & Biophys, Chicago, IL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Illinois, Coll Med, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 283 BP 61 EP 61 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600344 ER PT J AU Friedrich, EB Tager, AM Liu, E Bromley, L Luster, AD Gerszten, RE AF Friedrich, EB Tager, AM Liu, E Bromley, L Luster, AD Gerszten, RE TI Leukotriene B-4 is as potent as MCP-1 in triggering monocyte adhesion yet signals via different pathways SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Ctr Immunol & Inflammat Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 301 BP 65 EP 65 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600362 ER PT J AU Fitzgerald, ML Morris, AL Chroni, A Zannis, VI Freeman, MW AF Fitzgerald, ML Morris, AL Chroni, A Zannis, VI Freeman, MW TI Amphipathic helices are required for acceptor Apolipoproteins to directly interact with ABCA1 and stimulate its facilitation of cholesterol efflux SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 329 BP 71 EP 71 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600390 ER PT J AU Liu, E Brothag, A Bromley, L Sinha, S Friedrich, EB Gerszten, RE AF Liu, E Brothag, A Bromley, L Sinha, S Friedrich, EB Gerszten, RE TI Stimulated neutrophils secrete an inhibitor of thrombolysis SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 490 BP 105 EP 105 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600551 ER PT J AU He, ZH Opland, DM Way, KJ Ueki, K Kulkarni, RN Liau, R King, GL AF He, ZH Opland, DM Way, KJ Ueki, K Kulkarni, RN Liau, R King, GL TI Direct demonstration of insulin's effect on vascular endothelial growth factor expression and vascularization in the myocardium at basal and insulin resistant states SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Boston Univ, Ctr Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 534 BP 113 EP 114 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600595 ER PT J AU Han, YC Liu, ZL Izumo, S Kang, PM AF Han, YC Liu, ZL Izumo, S Kang, PM TI HAX-1 is antiapoptotic in adult rat cardiac myocytes SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 537 BP 114 EP 114 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600598 ER PT J AU Shiraishi, I Melendez, J Youngkeun, A Vondriska, TM Wang, GW Welch, S Schaefer, E Walsh, K Rosenzweig, A Sussman, MA AF Shiraishi, I Melendez, J Youngkeun, A Vondriska, TM Wang, GW Welch, S Schaefer, E Walsh, K Rosenzweig, A Sussman, MA TI Nuclear targeting of Akt enhances kinase activity and survival of cardiomyocytes SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Childrens Hosp Res Fdn, Cincinnati, OH 45229 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Biosource Int, Hopkinton, MA USA. Boston Univ, Sch Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 543 BP 115 EP 115 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600604 ER PT J AU Ahmad, F Arad, M He, HM Musi, N Branco, D Xing, YQ Fujii, N Rong, T Goodyear, LJ Berul, CI Ingwall, JS Seidman, CE Seidman, JG AF Ahmad, F Arad, M He, HM Musi, N Branco, D Xing, YQ Fujii, N Rong, T Goodyear, LJ Berul, CI Ingwall, JS Seidman, CE Seidman, JG TI PRKAG2 cardiomyopathy mice demonstrate preserved resting cardiac energy levels and are able to increase cardiac contractility with exercise SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Metab, Boston, MA 02115 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 559 BP 118 EP 119 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600620 ER PT J AU Choe, EY Liu, HL Schulze, C Bloch, KD Lee, RT AF Choe, EY Liu, HL Schulze, C Bloch, KD Lee, RT TI Nitric oxide increases thioredoxin activity while regulating expression of vitamin D3-upregulated protein 1 and thioredoxin reductase in rat pulmonary artery smooth muscle cells SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. Brigham & Womens Hosp, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 576 BP 122 EP 122 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600637 ER PT J AU Liu, HL Choe, EY Ichinose, F Busch, CJ Panella, SM Bloch, KD AF Liu, HL Choe, EY Ichinose, F Busch, CJ Panella, SM Bloch, KD TI Nitric oxide stimulates inducible cAMP early repressor (ICER) gene expression in rat pulmonary artery smooth muscle cells SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 575 BP 122 EP 122 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600636 ER PT J AU Quinn, DA Mascarenhas, MM Ochoa, CD Hales, CA AF Quinn, DA Mascarenhas, MM Ochoa, CD Hales, CA TI Pulmonary artery endothelial cell control of pulmonary artery smooth muscle cell growth SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 577 BP 122 EP 122 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600638 ER PT J AU Pathak, A Wen, Z Hahn, H Carr, A Bodi, I Fan, GC Lin, P Colbert, M DePaoli-Roach, AA del Monte, F Hajjar, R Kranias, EG AF Pathak, A Wen, Z Hahn, H Carr, A Bodi, I Fan, GC Lin, P Colbert, M DePaoli-Roach, AA del Monte, F Hajjar, R Kranias, EG TI Targeted inhibition of protein phosphatase 1 via expression of the constitutively active inhibitor-1 protein: A novel "Molecular inotrope" SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Univ Cincinnati, Cincinnati, OH USA. Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. Indiana Univ, Indianapolis, IN 46204 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 587 BP 124 EP 124 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600648 ER PT J AU Uzui, H Asotra, K Chen, S Doherty, T Xu, J Tung, CH Rajavashisth, TB AF Uzui, H Asotra, K Chen, S Doherty, T Xu, J Tung, CH Rajavashisth, TB TI Colocalization of membrane type-matrix metalloproteinases in vascular endothelial cells SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Cedars Sinai Med Ctr, Atherosclerosis Rsch Cntr, Los Angeles, CA USA. Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 786 BP 166 EP 167 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600847 ER PT J AU Sinha, S Liu, E Friedrich, EB Force, T Dedhar, S Gerszten, RE AF Sinha, S Liu, E Friedrich, EB Force, T Dedhar, S Gerszten, RE TI Conditional deletion of ILK reveals an important role in T cell chemotaxis SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Tufts Univ, Sch Med, Boston, MA 02111 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 797 BP 169 EP 169 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600858 ER PT J AU Schulze, PC Yoshioka, J Takahashi, T He, ZH King, GL Lee, RT AF Schulze, PC Yoshioka, J Takahashi, T He, ZH King, GL Lee, RT TI Hyperglycemia inhibits thioredoxin antioxidative function and promotes oxidative stress through induction of vitamin D3 up-regulated protein-1 SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 820 BP 173 EP 173 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600881 ER PT J AU Ellinor, PT Moore, RK Patton, KK Ruskin, JN MacRae, CA AF Ellinor, PT Moore, RK Patton, KK Ruskin, JN MacRae, CA TI Mutations in KCNQ1 are an uncommon cause of atrial fibrillation SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Patton, Kristen/A-5626-2008; OI Patton, Kristen K./0000-0002-9034-6966 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 863 BP 182 EP 183 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600924 ER PT J AU del Monte, F Tsuji, T Supple, G Guerrero, L Gwathmey, J AF del Monte, F Tsuji, T Supple, G Guerrero, L Gwathmey, J TI Abrogation of ventricular arrhythmias & contractile dysfunction in ischemia-reperfusion by gene transfer of SERCA2a SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. Gwathmey Inc, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 892 BP 188 EP 188 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600953 ER PT J AU Nagoshi, T Matsui, T Li, L Rosenzweig, A AF Nagoshi, T Matsui, T Li, L Rosenzweig, A TI Chronic cardiac Akt activation in-vivo inhibits PI 3-kinase and worsens the response to ischemia-reperfusion injury SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 971 BP 205 EP 205 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360601031 ER PT J AU Feinberg, MW Lebedeva, MA Haspel, R Sen, S Gray, S Segre, JA Miyamoto, T Akashi, K Jain, MK AF Feinberg, MW Lebedeva, MA Haspel, R Sen, S Gray, S Segre, JA Miyamoto, T Akashi, K Jain, MK TI The Kruppel-like factor KLF4 is a novel regulator of monocytic differentiation SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Brigham & Womens Hosp, Boston, MA 02115 USA. NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 990 BP 209 EP 209 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360601050 ER PT J AU Friedrich, EB Liu, E Sinha, S Cook, SA Hess, C St Arnaud, R Force, T Rosenzweig, A Dedhar, S Gerszten, RE AF Friedrich, EB Liu, E Sinha, S Cook, SA Hess, C St Arnaud, R Force, T Rosenzweig, A Dedhar, S Gerszten, RE TI Targeted deletion of Integrin-Linked Kinase reveals an essential role in endothelial cell survival SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Program Cardiovasc Gene Therapy, Cardiovasc Res Ctr, Boston, MA 02114 USA. Shriners Hosp Children, Montreal, PQ, Canada. McGill Univ, Montreal, PQ, Canada. Tufts Univ, Sch Med, New England Med Ctr, Mol Cardiol Res Inst, Boston, MA 02111 USA. Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V5Z 1M9, Canada. Vancouver Gen Hosp & Hlth Serv Ctr, Jack Bell Canc Ctr, Vancouver, BC, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 1175 BP 249 EP 249 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360601235 ER PT J AU Hiroi, Y Huang, ZH Simoncini, T Limbourg, FP Gannon, J Moskowitz, MA Liao, JK AF Hiroi, Y Huang, ZH Simoncini, T Limbourg, FP Gannon, J Moskowitz, MA Liao, JK TI Stroke protection mediated by rapid, nongenomic actions of thyroid hormone SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Chelsea, MA USA. Univ Pisa, I-56100 Pisa, Italy. Brigham & Womens Hosp, Cambridge, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 1195 BP 253 EP 253 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360601254 ER PT J AU Wolfrum, S Dendorfer, A Rikitake, Y Scalia, R Huang, ZH Stalker, TJ Moskowitz, MA Dominiak, P Liao, JK AF Wolfrum, S Dendorfer, A Rikitake, Y Scalia, R Huang, ZH Stalker, TJ Moskowitz, MA Dominiak, P Liao, JK TI A novel mechanism of cardiovascular protection mediated by Rho-kinase inhibition and Akt activation SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Schleswig Holstein, Inst Pharmacol, Lubeck, Germany. Thomas Jefferson Univ, Jefferson Med Coll, Dept Physiol, Philadelphia, PA 19107 USA. Massachusetts Gen Hosp, Lab Stroke & Neurovasc Regulat, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 1203 BP 255 EP 255 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360601262 ER PT J AU Aoyama, T Matsui, T Gerszten, RE Rosenzweig, A AF Aoyama, T Matsui, T Gerszten, RE Rosenzweig, A TI ILK is dynamically regulated during pressure overload in the heart and acts to enhance IGF-I-induced cardiomyocyte hypertrophy SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 1227 BP 260 EP 260 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360601286 ER PT J AU Pokreisz, P Vermeersch, P Szelid, Z Gillijns, H Pellens, M Collen, D Bloch, K Janssens, S AF Pokreisz, P Vermeersch, P Szelid, Z Gillijns, H Pellens, M Collen, D Bloch, K Janssens, S TI Cardiomyocyte-restricted endothelial nitric oxide synthase overexpression impairs right ventricular remodeling in transgenic mice exposed to chronic hypoxia SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Katholieke Univ Leuven, Ctr Transgene Technol & Gene Therapy, Louvain, Belgium. Thromb X, Louvain, Belgium. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02115 USA. Katholieke Univ Leuven, Cardiac Unit, Louvain, Belgium. RI Vermeersch, Pieter/M-8352-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 1276 BP 269 EP 270 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360601335 ER PT J AU Rudd, MA Daumerie, G Maitland, K Bridges, L Yancey, S Cloutier, T Toolan, G Davis, W Huang, P Loscalzo, J AF Rudd, MA Daumerie, G Maitland, K Bridges, L Yancey, S Cloutier, T Toolan, G Davis, W Huang, P Loscalzo, J TI Increased glomerular damage during high salt diet in eNOS deficient mice SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 N Carolina Cent Univ, Durham, NC USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Univ New Hampshire, Durham, NH 03824 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 1272 BP 269 EP 269 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360601331 ER PT J AU Matsui, T Hartil, K Nagoshi, T Gorovits, N Luptak, I Li, L Tian, R Charron, MJ Rosenzweig, A AF Matsui, T Hartil, K Nagoshi, T Gorovits, N Luptak, I Li, L Tian, R Charron, MJ Rosenzweig, A TI Chronic Akt activation increases basal glucose uptake and GLUT-12 expression in the heart SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 1405 BP 296 EP 296 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360601463 ER PT J AU Sugita, I Sugita, H Kaneki, M AF Sugita, I Sugita, H Kaneki, M TI Farnesyltransferase inhibitor, manumycin a prevents the development of mature atherosclerosis in ApoE knock out mice SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 1430 BP 301 EP 301 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360601488 ER PT J AU Fox, CS Evans, JC Larson, MG Sorlie, PD Manolio, TA Lloyd-Jones, DM Kannel, W O'Donnell, CJ Levy, D AF Fox, CS Evans, JC Larson, MG Sorlie, PD Manolio, TA Lloyd-Jones, DM Kannel, W O'Donnell, CJ Levy, D TI Death certificate out-of-hospital cardiac death overestimates sudden cardiac death SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NHLBI, Rockville, MD USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RI Lloyd-Jones, Donald/C-5899-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 1501 BP 318 EP 318 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360601559 ER PT J AU Tawakol, A Migrino, RQ Aziz, KS Fischman, AJ Gewirtz, H AF Tawakol, A Migrino, RQ Aziz, KS Fischman, AJ Gewirtz, H TI Very high-dose folic acid acutely improves myocardial blood flow in humans with coronary artery disease SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 1563 BP 333 EP 333 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360601621 ER PT J AU Greenberg, BH Banish, D Goldman, S Thomas, I Havranek, E Bijou, R O'Leary, M Zhu, Y Ticho, B Massie, B Abraham, W AF Greenberg, BH Banish, D Goldman, S Thomas, I Havranek, E Bijou, R O'Leary, M Zhu, Y Ticho, B Massie, B Abraham, W TI BG9928, an oral adenosine antagonist, preserves renal function, improves sodium excretion and is well tolerated in heart failure patients SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Univ Calif San Diego, San Diego, CA 92103 USA. New Orleans Clin Trial Management, New Orleans, LA USA. VA Healthcare Syst, Tucson, AZ USA. Med Res Inst, Slidell, LA USA. Denver Hlth Med Ctr, Denver, CO USA. Columbia Univ, Coll Phys & Surg, New York, NY 10027 USA. Biogen Inc, Cambridge, MA 02142 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Ohio State Univ, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 1602 BP 342 EP 342 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360601660 ER PT J AU Contreras, JM Westlake, RM Fleming, CM Systrom, DM AF Contreras, JM Westlake, RM Fleming, CM Systrom, DM TI Hemoglobin concentration and exercise performance in COPD SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Brown Univ, Providence, RI 02912 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 1646 BP 351 EP 352 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360601704 ER PT J AU Gibson, CM Murphy, SA McCabe, CH Giugliano, RP Cannon, CP Antman, E Braunwald, E AF Gibson, CM Murphy, SA McCabe, CH Giugliano, RP Cannon, CP Antman, E Braunwald, E TI Time is muscle: Delays in time from symptom onset to fibrinolytic administration in ST elevation MI are associated with poorer myocardial perfusion SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 TIMI Study Grp, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 1685 BP 360 EP 360 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360601742 ER PT J AU Wong, GC Murphy, SA Wiviott, SD Giugliano, RP Antman, EM Marble, SJ Dumaine, R McCabe, CH Gibson, CM AF Wong, GC Murphy, SA Wiviott, SD Giugliano, RP Antman, EM Marble, SJ Dumaine, R McCabe, CH Gibson, CM TI Statin therapy within 2 weeks prior to admission is associated with improved myocardial perfusion in ST elevation myocardial infarction: A Thrombolysis In Myocardial Infarction angiographic study SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 TIMI Study Grp, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 1686 BP 360 EP 361 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360601743 ER PT J AU Jang, IK Bouma, B MacNeill, B Takano, M Shishkov, M Iftima, N Tearney, GJ AF Jang, IK Bouma, B MacNeill, B Takano, M Shishkov, M Iftima, N Tearney, GJ TI In-vivo coronary plaque characteristics in patients with various clinical presentations using Optical Coherence Tomography SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 1738 BP 373 EP 373 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360601795 ER PT J AU MacNeill, BD Jang, IK Bouma, BE Takano, M Iftimia, NV Houser, SL Tearney, GJ AF MacNeill, BD Jang, IK Bouma, BE Takano, M Iftimia, NV Houser, SL Tearney, GJ TI Coronary plaque macrophage imaging in living patients SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Wellman Labs Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 1737 BP 373 EP 373 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360601794 ER PT J AU Gibson, CM Pinto, DS Murphy, SA Morrow, DA Hobbach, HP Dumaine, R Wiviott, SD Giugliano, RP Cannon, CP Braunwald, E AF Gibson, CM Pinto, DS Murphy, SA Morrow, DA Hobbach, HP Dumaine, R Wiviott, SD Giugliano, RP Cannon, CP Braunwald, E TI Association of creatinine and creatinine clearance on presentation in acute myocardial infarction with subsequent mortality SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 TIMI Study Grp, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA. St Marien Hosp, Siegen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 1755 BP 378 EP 378 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360601812 ER PT J AU Sadanandan, S Cannon, CP Murphy, SA Chelkuri, K Partin, M DiBattiste, PM Morrow, DA de Lemos, JA McCabe, CH Braunwald, E Gibson, M AF Sadanandan, S Cannon, CP Murphy, SA Chelkuri, K Partin, M DiBattiste, PM Morrow, DA de Lemos, JA McCabe, CH Braunwald, E Gibson, M TI Association of B-type natriuretic peptide with angiographic findings in non-ST elevation acute coronary syndromes: A TACTICS-TIM 18 substudy SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Univ Oklahoma, Oklahoma City, OK USA. Brigham & Womens Hosp, Boston, MA 02115 USA. TIMI Study Grp, Boston, MA USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 1759 BP 379 EP 379 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360601816 ER PT J AU Ferguson, TB Shroyer, LA Coombs, LP DeLong, ER Grover, FL Peterson, ED AF Ferguson, TB Shroyer, LA Coombs, LP DeLong, ER Grover, FL Peterson, ED TI Risk-adjusted mortality, revascularization completeness and the learning curve effect in off-pump CABG SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 LSU, HSC, New Orleans, LA USA. Denver VA Med Ctr, Denver, CO USA. Duke Clin Res Inst, Durham, NC USA. Univ Colorado, HSC, Denver, CO 80202 USA. Duke Clin Rsch Inst, Durham, NC USA. RI Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 1810 BP 391 EP 391 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360601867 ER PT J AU Lewis, GD Bloch, KD Semigran, MJ AF Lewis, GD Bloch, KD Semigran, MJ TI Pulmonary thromboembolism superimposed on congenital ventricular septal defect in a 50 year old man: Inhaled nitric oxide and sildenafil to the rescue SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 1824 BP 394 EP 394 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360601881 ER PT J AU Wood, MJ Yoerger, DM Lawlor, DF Scherrer-Crosie, M Marshall, JE Appleton, CP Johansson, AC Douglas, PS Picard, MH AF Wood, MJ Yoerger, DM Lawlor, DF Scherrer-Crosie, M Marshall, JE Appleton, CP Johansson, AC Douglas, PS Picard, MH TI Left ventricular systolic and diastolic dysfunction following prolonged strenuous exercise SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin Scottsdale, Scottsdale, AZ USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Wisconsin, Madison, WI 53706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 1822 BP 394 EP 394 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360601879 ER PT J AU Yabushita, H Bouma, BE Houser, SL Aretz, HT Jang, IK Schlendorf, KH Kauffman, CR Shishkov, M Halpern, EF Tearney, GJ AF Yabushita, H Bouma, BE Houser, SL Aretz, HT Jang, IK Schlendorf, KH Kauffman, CR Shishkov, M Halpern, EF Tearney, GJ TI Monitoring atherosclerotic plaque evolution in vivo by optical coherence tomography SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Kinki Univ, Sch Med, Dept Cardiol, Osakasayama, Japan. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 1919 BP 416 EP 416 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360601976 ER PT J AU Zhang, H Otsuji, Y Uemura, T Kumanohoso, T Yu, B Zhou, XY Levine, RA Kisanuki, A AF Zhang, H Otsuji, Y Uemura, T Kumanohoso, T Yu, B Zhou, XY Levine, RA Kisanuki, A TI Different mechanisms of ischemic mitral regurgitation in patients with anterior and inferior myocardial infarction SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Kagoshima Univ, Fac Med, Kagoshima 890, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 1991 BP 432 EP 432 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360602048 ER PT J AU Howard, G Hobson, RW Brott, TG Howard, VJ Cohen, SN Petrossian, G Levy, D Mishkel, G Barnwell, SL AF Howard, G Hobson, RW Brott, TG Howard, VJ Cohen, SN Petrossian, G Levy, D Mishkel, G Barnwell, SL TI Does the stroke risk of stenting increase at older ages? Thirty-day stroke - Death rates in the CREST lead-in phase SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Univ Alabama, Birmingham, AL USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. St Francis Hosp, Port Washington, NY USA. Kaiser Permanente Med Ctr, San Diego, CA USA. Prairie Cardiol St Johns Hosp & Mem Med Ctr, Springfield, IL USA. Oregon Hlth Sci Cntr, Portland, OR USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 2116 BP 461 EP 461 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360602173 ER PT J AU Hung, J Papakostas, L Tahta, SA Hardy, BG Bollen, BA Duran, CM Levine, RA AF Hung, J Papakostas, L Tahta, SA Hardy, BG Bollen, BA Duran, CM Levine, RA TI Mechanism of recurrent ischemic mitral regurgitation post-annuloplasty: Continued LV remodeling as a moving target SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Int Inst Montana, Missoula, MT USA. Int Heart Inst Montana, Missoula, MT USA. Univ Montana, Missoula, MT 59812 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 2181 BP 476 EP 476 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360602238 ER PT J AU Otsuji, Y Yuge, K Yotsumoto, G Ueno, T Nakashiki, K Mizukami, N Zhou, XY Hasegawa, W Kisanuki, A Minagoe, S Sakata, R Levine, RA Tei, C AF Otsuji, Y Yuge, K Yotsumoto, G Ueno, T Nakashiki, K Mizukami, N Zhou, XY Hasegawa, W Kisanuki, A Minagoe, S Sakata, R Levine, RA Tei, C TI Excessive left ventricular volume reduction can lead to late onset ischemic mitral regurgitation following Dor's procedure SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Kagoshima Univ, Kagoshima 890, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. Kagoshima Univ, Kagoshima 890, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 2183 BP 476 EP 476 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360602240 ER PT J AU Collins, JS Evagelista, A Nienaber, CA Bossone, E Cooper, JV Issellbacher, EM Penn, M Mehta, RH AF Collins, JS Evagelista, A Nienaber, CA Bossone, E Cooper, JV Issellbacher, EM Penn, M Mehta, RH TI Differences in clinical features, management and outcomes of acute aortic dissection in patients with and without prior cardiac surgery SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Univ Michigan, Hlth Syst, Ann Arbor, MI 48109 USA. Hosp Gen Univ Valle Hebron, Barcelona, Spain. Univ Rostock, Rostock, Germany. CNR, Lecce, Italy. Massachusetts Gen Hosp, Boston, MA 02114 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 2202 BP 480 EP 481 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360602259 ER PT J AU Bossone, E Isselbacher, EM Nienaber, CA Gilon, D Cooper, JV Evangelista, A Suzuki, T Mehta, RH AF Bossone, E Isselbacher, EM Nienaber, CA Gilon, D Cooper, JV Evangelista, A Suzuki, T Mehta, RH TI Simple decision rule for risk stratification of elderly with acute type B aortic dissection SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 CNR, Lecce, Italy. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Rostock, Rostock, Germany. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. Univ Michigan, Hlth Syst, Ann Arbor, MI 48109 USA. Hosp Gen Univ Valle Hebron, Barcelona, Spain. Univ Tokyo, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 2204 BP 481 EP 481 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360602261 ER PT J AU Ropers, D Baum, U Anders, K Schmid, M Pohle, K Bautz, W Daniel, WG Achenbach, S AF Ropers, D Baum, U Anders, K Schmid, M Pohle, K Bautz, W Daniel, WG Achenbach, S TI Contrast-enhanced multi-detector row CT with submillimeter collimation for the investigation of coronary artery bypass patients SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Univ Erlangen Nurnberg, Dept Cardiol, Erlangen, Germany. Univ Erlangen Nurnberg, Dept Radiol, Erlangen, Germany. Massachusetts Gen Hosp, Dept Radiol & Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 2243 BP 490 EP 490 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360602300 ER PT J AU Corvera-Tindel, T Doering, LV Casimiro, L Dracup, K Khan, S AF Corvera-Tindel, T Doering, LV Casimiro, L Dracup, K Khan, S TI Estimating daily activity in heart failure patients: What do exercise tests mean? SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 2291 BP 502 EP 502 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360602348 ER PT J AU Corvera-Tindel, T Doering, LV Aquino, C Roper, J Dracup, K AF Corvera-Tindel, T Doering, LV Aquino, C Roper, J Dracup, K TI Quality of life in heart failure: Feelings or performance? SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 2295 BP 503 EP 503 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360602352 ER PT J AU Ferencik, M Achenbach, S Houser, S Tearney, GJ Bouma, BE Hoffmann, U Brady, TJ Chan, RC AF Ferencik, M Achenbach, S Houser, S Tearney, GJ Bouma, BE Hoffmann, U Brady, TJ Chan, RC TI Performance of 16-slice MDCT for measurement of arterial morphology and composition relative to IVUS and OCT in ex vivo coronary arteries SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 2413 BP 528 EP 528 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360602469 ER PT J AU Achenbach, S Ropers, D Hoffmann, U Pohle, K MacNeill, B Ferencik, M Chan, R Pomerantsev, E Schmid, M Brady, TJ AF Achenbach, S Ropers, D Hoffmann, U Pohle, K MacNeill, B Ferencik, M Chan, R Pomerantsev, E Schmid, M Brady, TJ TI Measurement of cross-sectional coronary atherosclerotic plaque and vessel areas by 16-slice multi-detector CT: Comparison to IVUS SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Erlangen Nurnberg, Erlangen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 2414 BP 529 EP 529 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360602470 ER PT J AU Hoffmann, U Bull-Stewart, A Achenbach, S Ferencik, M Brady, TJ O'Donnell, C AF Hoffmann, U Bull-Stewart, A Achenbach, S Ferencik, M Brady, TJ O'Donnell, C TI Interscan and Interobserver variability of coronary artery calcium measurements in prospectively triggered multislice computed tomography SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Massachusetts Gen Hosp, Div Cardiol, NHLBI, Framingham Heart Study, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 2416 BP 529 EP 529 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360602472 ER PT J AU Sebag, IA Handschumacher, MD Morgan, JG Ichinose, F Derumeaux, G Weyman, AE Picard, MH Scherrer-Crosbie, M AF Sebag, IA Handschumacher, MD Morgan, JG Ichinose, F Derumeaux, G Weyman, AE Picard, MH Scherrer-Crosbie, M TI Systolic strain rate is a strong noninvasive index of cardiac function in mice SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Ctr Univ Rouen, Rouen, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 2524 BP 553 EP 553 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360602579 ER PT J AU Sebag, IA Morgan, JG Nesta, F Handschumacher, MD Marshall, JE Hung, J Picard, MH Levine, RA AF Sebag, IA Morgan, JG Nesta, F Handschumacher, MD Marshall, JE Hung, J Picard, MH Levine, RA TI Three-dimensionally guided rapid, reproducible assessment of mitral stenosis using matrix-array technology SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 2529 BP 554 EP 555 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360602584 ER PT J AU Latini, R Wong, M Masson, S Barlera, S Staszewsky, L Salio, M Maggioni, AP Anand, IS Tognoni, G Cohn, JN AF Latini, R Wong, M Masson, S Barlera, S Staszewsky, L Salio, M Maggioni, AP Anand, IS Tognoni, G Cohn, JN CA Val HeFT Investigators TI Predicting outcomes in chronic heart failure from short-term change in BNP as a surrogate end-point: Val-HeFT data SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Ist Mario Negri, Milan, Italy. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. ANMCO Res Ctr, Florence, Italy. VA Med Ctr, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 2542 BP 557 EP 558 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360602597 ER PT J AU Sheppard, RJ Bedi, MS McTiernan, CF Semigran, M Dec, GW Kubota, T McNamara, DM AF Sheppard, RJ Bedi, MS McTiernan, CF Semigran, M Dec, GW Kubota, T McNamara, DM TI Myocardial fas expression in patients with recent onset cardiomyopathy: Results from the IMAC trial SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Univ Pittsburgh, Pittsburgh, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Kyushu Univ, Fukuoka 812, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 2719 BP 597 EP 598 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360602772 ER PT J AU Carroll, DL Rankin, SH Hamilton, GA AF Carroll, DL Rankin, SH Hamilton, GA TI Effects of gender on symptoms and health status in unpartnered cardiac surgical elders SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Oslo, N-0316 Oslo, Norway. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 2779 BP 611 EP 611 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360602831 ER PT J AU Albert, CM Rich, DQ Wang, PJ Ruskin, JN Tofler, GH Muller, JE Mittleman, MA AF Albert, CM Rich, DQ Wang, PJ Ruskin, JN Tofler, GH Muller, JE Mittleman, MA TI Driving and ICD discharge for VT/VF: The TOVA study SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Royal N Shore Hosp, Sydney, NSW, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 2799 BP 616 EP 616 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360602851 ER PT J AU Mittleman, MA Rich, DQ Wang, PJ Tofler, GH Ruskin, JN Muller, JE Albert, CM AF Mittleman, MA Rich, DQ Wang, PJ Tofler, GH Ruskin, JN Muller, JE Albert, CM TI Moderate exertion as a trigger of ICD discharge for VT/VF SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. Royal N Shore Hosp, Sydney, NSW, Australia. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 2804 BP 617 EP 617 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360602856 ER PT J AU Shah, A Sauk, J Jimenez-Kimble, R Ecker, JL Thadhani, R Wolf, M AF Shah, A Sauk, J Jimenez-Kimble, R Ecker, JL Thadhani, R Wolf, M TI Differential risk of hypertensive disorders of pregnancy among hispanic women SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 2863 BP 630 EP 630 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360602914 ER PT J AU Jang, IK MacNeill, BD Tearney, G Bouma, B Takano, M AF Jang, IK MacNeill, BD Tearney, G Bouma, B Takano, M TI Prevalence of lipid-rich coronary plaques is not higher in patients with acute coronary syndromes compared to those with stable angina pectoris SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 3074 BP 676 EP 676 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360603124 ER PT J AU Turakhia, MP Karmpaliotis, D Morrow, DA Murphy, SA Kirtane, AJ Kosmidou, I Marble, SJ Giugliano, RP McCabe, CH Braunwald, E Gibson, CM AF Turakhia, MP Karmpaliotis, D Morrow, DA Murphy, SA Kirtane, AJ Kosmidou, I Marble, SJ Giugliano, RP McCabe, CH Braunwald, E Gibson, CM TI Sequential risk stratification using the TIMI risk score and the TIMI flow grade among patients treated with fibrinolytic therapy for acute ST segment elevation myocardial infarction (STEMI) SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Brigham & Womens Hosp, TMI Study Grp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. TIMI Study Grp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 3089 BP 679 EP 679 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360603139 ER PT J AU Kaneda, H Ako, J Honda, Y Sakurai, R Terashima, M Morino, Y Sonoda, S Brown, C Simonton, C Fitzgerald, PJ AF Kaneda, H Ako, J Honda, Y Sakurai, R Terashima, M Morino, Y Sonoda, S Brown, C Simonton, C Fitzgerald, PJ TI Sirolimus-eluting stent: Effect on instent and edge neointimal proliferation in small vessels SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Stanford Univ, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Piedmont Hosp, Fuqua Heart Cntr, Atlanta, GA USA. Sanger Clin PA, Charlotte, NC USA. RI Honda, Yasuhiro/J-6227-2013 OI Honda, Yasuhiro/0000-0002-0102-7841 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 3188 BP 702 EP 702 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360603238 ER PT J AU Fonarow, GC Bonow, RO Tyler, P Hong, YL Skea, W Emond, JA Smith, SC LaBresh, KA AF Fonarow, GC Bonow, RO Tyler, P Hong, YL Skea, W Emond, JA Smith, SC LaBresh, KA CA GWTG Steering Committee Investiga TI Does the AHA get with the guidelines program improve the quality of care in hospitalized patients with coronary artery disease at both teaching and non-teaching hospitals? SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. Amer Heart Assoc, Dallas, TX USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. MassPro, Waltham, MA USA. RI LaBresh, Kenneth/A-6995-2017 OI LaBresh, Kenneth/0000-0001-9040-1956 NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 3269 BP 721 EP 722 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360603319 ER PT J AU LaBresh, KA Fonarow, GC Ellrodt, G Borrow, RO Smaha, LA Tyler, PA Skea, W Hong, YL Emond, J Smith, SC AF LaBresh, KA Fonarow, GC Ellrodt, G Borrow, RO Smaha, LA Tyler, PA Skea, W Hong, YL Emond, J Smith, SC TI Get with the guidelines improves cardiovascular care in hospitalized patients with CAD SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 MassPRO, Waltham, MA USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. Berkshire Med Ctr, Pittsfield, MA USA. Northwestern Univ, Sch Med, Chicago, IL USA. Guthrie Clin, Sayre, PA USA. Amer Heart Assoc, Irvine, CA USA. Amer Heart Assoc, Dallas, TX USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. RI LaBresh, Kenneth/A-6995-2017 OI LaBresh, Kenneth/0000-0001-9040-1956 NR 0 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 3270 BP 722 EP 722 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360603320 ER PT J AU Varo, N Vicent, D Libby, P Nuzzo, R Calle-Pascual, A Bernal, MR Veves, A Jarolim, P Varo, JJ Goldfine, A Horton, E AF Varo, N Vicent, D Libby, P Nuzzo, R Calle-Pascual, A Bernal, MR Veves, A Jarolim, P Varo, JJ Goldfine, A Horton, E TI Elevated plasma levels of the atherogenic mediator sCD40L in diabetic patients: A novel target of thiazolidinediones (TZD) SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Hosp Carlos III, Madrid, Spain. Hosp Univ San Carlos, Madrid, Spain. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Navarra, E-31080 Pamplona, Spain. Joslin Diabet Ctr, Boston, MA 02215 USA. RI Bernal-Lopez, Rosa/F-3548-2011; Vicent, David/O-2255-2014 OI Vicent, David/0000-0002-6663-0350 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 3384 BP 749 EP 749 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360603433 ER PT J AU Huon, N D'Agostino, RB Massaro, J Muller, JE Mittleman, MA Levy, D Lipinska, I Sutherland, PA Tofler, G AF Huon, N D'Agostino, RB Massaro, J Muller, JE Mittleman, MA Levy, D Lipinska, I Sutherland, PA Tofler, G TI Seasonal variation in haemostatic factors in Framingham study: Link to cardiovascular events SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Royal N Shore Hosp, Sydney, NSW, Australia. Boston Univ, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Hosp, Boston, MA USA. Framingham Heart Dis Epidemiol Study, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 3418 BP 757 EP 757 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360603467 ER PT J AU Fang, MC Go, AS Chang, YC Jensvold, NG Selby, JV Singer, DE AF Fang, MC Go, AS Chang, YC Jensvold, NG Selby, JV Singer, DE TI The impact of age on intracranial hemorrhage and 30-day mortality patients with atrial fibrillation: The anticoagulation and risk factors atrial fibrillation (ATRIA) study SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Kaiser Permanente No Calif, Oakland, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 3461 BP 766 EP 767 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360603510 ER PT J AU O'Donnell, CJ Yang, Q Lochner, A Larson, MG Kathiresan, S Tofler, GH Gabriel, SB AF O'Donnell, CJ Yang, Q Lochner, A Larson, MG Kathiresan, S Tofler, GH Gabriel, SB TI Associations of haplotypes of fibrinogen beta, alpha and gamma chain genes on chromosome 4 with circulating fibrinogen levels in men and women SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, NHLBI Framingham Heart Study, Framingham, MA USA. Massachusetts Gen Hosp, Div Cardiol, Framingham, MA USA. NHLBI, Framingham Heart Study, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. MIT, Whitehead Inst Biomed Res, Ctr Genome Res, Cambridge, MA 02142 USA. Royal N Shore Hosp, Sydney, NSW, Australia. RI Yang, Qiong/G-5438-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 3479 BP 771 EP 772 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360603528 ER PT J AU Erkkila, AT Lichtenstein, AH MAyer, J Mozaffarian, D Herrington, DM AF Erkkila, AT Lichtenstein, AH MAyer, J Mozaffarian, D Herrington, DM TI Fish intake is associated with reduced progression of coronary-artery atherosclerosis in diabetic women with coronary artery disease SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. RI Mozaffarian, Dariush/B-2276-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 3543 BP 785 EP 785 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360603592 ER PT J AU Fang, MC Go, AS Chang, YC Jensvold, NG Selby, JV Singer, DE Hylek, EM AF Fang, MC Go, AS Chang, YC Jensvold, NG Selby, JV Singer, DE Hylek, EM TI Age-specific rates and predictors of major extracranial hemorrhage in patients with atrial fibrillation: The anticoagulation and risk factors in atrial fibrillation (ATRIA) study SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Kaiser Permanente No Calif, Oakland, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S MA 3548 BP 786 EP 786 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360603597 ER PT J AU Murakami, K Enkhbaatar, P Hecox, S Westphal, M Cox, RA Hawkins, HK Yu, YM Young, VR Tompkins, RG Traber, LD Traber, DL AF Murakami, K Enkhbaatar, P Hecox, S Westphal, M Cox, RA Hawkins, HK Yu, YM Young, VR Tompkins, RG Traber, LD Traber, DL TI L-arginine attenuates ovine model of acute lung injury following smoke inhalation and SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Univ Texas, Med Branch, Galveston, TX 77555 USA. Shriners Hosp Children, Galveston, TX 77550 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Shriners Burns Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S BP A1041 EP A1042 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360603668 ER PT J AU Fang, MC Go, AS Chang, YC Jensvold, NG Selby, JV Singer, DE Hylek, EM AF Fang, MC Go, AS Chang, YC Jensvold, NG Selby, JV Singer, DE Hylek, EM TI The impact of age on intracranial Hemorrhage and 30-day mortality in patients with atrial fibrillation; The anticoagulation and risk factors in atrial fibrillation (ATRIA) study SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Kaiser Permanente No Calif, Oakland, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S BP S EP S PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600048 ER PT J AU Lewis, GD Bloch, KD Semigran, MJ AF Lewis, GD Bloch, KD Semigran, MJ TI Pulmonary thromboembolism superimposed on congenital ventricular septal defect in a 50-year-old man inhaled nitric oxide and sildenafil to the rescue SO CIRCULATION LA English DT Meeting Abstract CT 76th Annual Scientific Session of the American-Heart-Association CY NOV 07-12, 2003 CL ORLANDO, FLORIDA SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2003 VL 108 IS 17 SU S BP Y EP Y PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 739RQ UT WOS:000186360600060 ER PT J AU Mendez, MF Clark, DG Shapira, JS Cummings, JL AF Mendez, MF Clark, DG Shapira, JS Cummings, JL TI Speech and language in progressive nonfluent aphasia compared with early Alzheimer's disease SO NEUROLOGY LA English DT Article ID CONDUCTION APHASIA; FRONTOTEMPORAL DEMENTIA; DEGENERATION; FEATURES; NETWORK AB Background: Progressive nonfluent aphasia (PA) is a slow deterioration of language that remains relatively isolated from other cognitive or behavioral deficits for at least 2 years. The differentiation of PA from early Alzheimer's disease (AD) is important, given the presence of early language changes in AD. Methods: A language assessment was administered to 15 patients who met established criteria for PA, 15 patients with clinically probable AD and mild dementia, and 15 normal control subjects. The language battery included verbal fluency, the Boston Naming Test with cuing and recognition, and an aphasia test battery with a motor speech exam. Results: Pronounced literal paraphasic errors distinguished the PA patients from the AD patients. The PA group had anomia, decreased letter fluency, neologisms, difficulty on phrase repetition, decreased phrase length, and a decreased rate of verbal output. Interference from paraphasic anomia accounted for much of their decreased fluency. Conclusion: Many patients with PA have a primary defect in accessing sound-based representation of speech ( phonemes), similar to conduction aphasia, possibly as a consequence of disturbed white matter tracts in the left superior temporal region. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, 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 39 TC 29 Z9 32 U1 1 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 28 PY 2003 VL 61 IS 8 BP 1108 EP U7 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 736QK UT WOS:000186184500017 PM 14581673 ER PT J AU Waeber, C Moskowitz, MA AF Waeber, C Moskowitz, MA TI Therapeutic implications of central and peripheral neurologic mechanisms in migraine SO NEUROLOGY LA English DT Review ID CORTICAL SPREADING DEPRESSION; TRIGEMINAL NUCLEUS CAUDALIS; C-FOS EXPRESSION; NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; FAMILIAL HEMIPLEGIC MIGRAINE; TRANSCRANIAL MAGNETIC STIMULATION; PLASMA-PROTEIN EXTRAVASATION; 5-HT1F RECEPTOR AGONISTS; SUPERIOR SAGITTAL SINUS C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Neurosci Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. RP Waeber, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Neurosci Ctr, CNY149,Room 6403,149 13th St, Charlestown, MA 02129 USA. RI Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 NR 160 TC 46 Z9 46 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 28 PY 2003 VL 61 IS 8 SU 4 BP S9 EP S20 PG 12 WC Clinical Neurology SC Neurosciences & Neurology GA 736ZE UT WOS:000186202500003 PM 14581653 ER PT J AU Opitz, CA Kulke, M Leake, MC Neagoe, C Hinssen, H Hajjar, RJ Linke, WA AF Opitz, CA Kulke, M Leake, MC Neagoe, C Hinssen, H Hajjar, RJ Linke, WA TI Damped elastic recoil of the titin spring in myofibrils of human myocardium SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FORCE-VELOCITY RELATIONSHIP; CARDIAC-MUSCLE; SKELETAL-MUSCLE; STRIATED-MUSCLE; SHORTENING VELOCITY; PHYSIOLOGICAL-ROLE; SARCOMERE-LENGTH; HUMAN HEART; PEVK-TITIN; DYNAMICS AB The giant protein titin functions as a molecular spring in muscle and is responsible for most of the passive tension of myocardium. Because the titin spring is extended during diastolic stretch, it will recoil elastically during systole and potentially may influence the overall shortening behavior of cardiac muscle. Here, titin elastic recoil was quantified in single human heart myofibrils by using a high-speed charge-coupled device-line camera and a nanonewton-range force sensor. Application of a slack-test protocol revealed that the passive shortening velocity (V-p) of nonactivated cardio-myofibrils depends on: (i) initial sarcomere length, (ii) release-step amplitude, and (iii) temperature. Selective digestion of titin, with low doses of trypsin, decelerated myofibrillar passive recoil and eventually stopped it. Selective extraction of actin filaments with a Ca2+-independent gelsolin fragment greatly reduced the dependency of Vp on release-step size and temperature. These results are explained by the presence of viscous forces opposing myofibrillar passive recoil that are caused mainly by weak actin-titin interactions. Thus, Vp is determined by two distinct factors: titin elastic recoil and internal viscous drag forces. The recoil could be modeled as that of a damped entropic spring consisting of independent worm-like chains. The functional importance of myofibrillar elastic recoil was addressed by comparing instantaneous Vp to unloaded shortening velocity, which was measured in demembranated, fully Ca2+-activated, human cardiac fibers. Titin-driven passive recoil was much faster than active unloaded shortening velocity in early phases of isotonic contraction. Damped myofibrillar elastic recoil could help accelerate active contraction speed of human myocardium during early systolic shortening. C1 Univ Heidelberg, Inst Physiol & Pathophysiol, D-69120 Heidelberg, Germany. Univ Bielefeld, Dept Biochem Cell Biol, D-33501 Bielefeld, Germany. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Linke, WA (reprint author), Univ Heidelberg, Inst Physiol & Pathophysiol, Neuenheimer Feld 326, D-69120 Heidelberg, Germany. EM wolfgang.linke@urz.uni-heidelberg.de RI Neagoe, Ciprian/B-5863-2011; Leake, Mark/C-1245-2011; Linke, Wolfgang/E-8662-2012; Opitz, Christiane/I-9507-2012 OI Neagoe, Ciprian/0000-0002-7328-1654; Leake, Mark/0000-0002-1715-1249; Opitz, Christiane/0000-0001-5575-9821 NR 39 TC 61 Z9 64 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 28 PY 2003 VL 100 IS 22 BP 12688 EP 12693 DI 10.1073/pnas.2133733100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 738RF UT WOS:000186301100034 PM 14563922 ER PT J AU Hitchcock, AL Auld, K Gygi, SP Silver, PA AF Hitchcock, AL Auld, K Gygi, SP Silver, PA TI A subset of membrane-associated proteins is ubiquitinated in response to mutations in the endoplasmic reticulum degradation machinery SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BOUND TRANSCRIPTION FACTOR; SACCHAROMYCES-CEREVISIAE; MASS-SPECTROMETRY; ER; YEAST; PROTEOMICS; CHAPERONE; LIGASE; GENE; CDC48(UFD1/NPL4) AB Ubiquitination of membrane-associated proteins can direct their proteasome-mediated degradation or activation at the endoplasmic reticulum (ER), as well as their endocytosis and intracellular sorting. However, the full spectrum of ubiquitinated membrane proteins has not been determined. Here we combined proteomic analysis with yeast genetics to identify 211 ubiquitinated membrane-associated proteins in Saccharomyces cerevisiae and map >30 precise sites of ubiquitination. Major classes of identified ubiquitinated proteins include ER-resident membrane proteins, plasma membrane-localized permeases, receptors, and enzymes, and surprisingly, components of the actin cytoskeleton. By determining the differential abundance of ubiquitinated proteins in yeast mutated for NPL4 and UBC7, which are major components of ER-associated degradation (ERAD), we furthermore were able to classify 83 of these identified ubiquitinated membrane proteins as potential endogenous substrates of the ERAD pathway. These substrates are highly enriched for proteins that localize to or transit through the ER. Interestingly, we also identified novel membrane-bound transcription factors that may be subject to ubiquitin/proteasome-mediated cleavage and activation at the ER membrane. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Taplin Biol Mass Spectrometry Facil, Boston, MA 02115 USA. RP Silver, PA (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. NR 31 TC 107 Z9 150 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 28 PY 2003 VL 100 IS 22 BP 12735 EP 12740 DI 10.1073/pnas.2135500100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 738RF UT WOS:000186301100042 PM 14557538 ER PT J AU Jacoby, JJ Kalinowski, A Liu, MG Zhang, SSM Gao, Q Chai, GX Ji, L Iwamoto, Y Li, E Schneider, M Russell, KS Fu, XY AF Jacoby, JJ Kalinowski, A Liu, MG Zhang, SSM Gao, Q Chai, GX Ji, L Iwamoto, Y Li, E Schneider, M Russell, KS Fu, XY TI Cardiomyocyte-restricted knockout of STAT3 results in higher sensitivity to inflammation, cardiac fibrosis, and heart failure-with advanced age SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SIGNAL TRANSDUCER; GROWTH-FACTOR; INTERLEUKIN-6 FAMILY; TARGETED DISRUPTION; RAT-HEART; GP130; ACTIVATION; PATHWAY; MYOCYTES; EXPRESSION AB Cytokines and inflammation have been implicated in the pathogenesis of heart failure. For example, IL-6 family cytokines and the gp130 receptor play important roles in cardiac myocyte survival and hypertrophy. Signal transducer and activator of transcription 3 (STAT3) is a major signaling protein that is activated through gp130. We have created mice with a cardiomyocyte-restricted deletion of STAT3. As measured by serial echocardiograms, mice with cardiac specific deletion of STAT3 are significantly more susceptible to cardiac injury after doxorubicin treatment than age-matched controls. Intriguingly, STAT3 appears to have a critical role in protection of inflammation-induced heart damage. STAT3-deficient mice treated with lipopolysaccharide demonstrated significantly more apoptosis than their WT counterparts. At the cellular level, cardiomyocytes with STAT3 deleted secrete significantly more tumor necrosis factor a in response to lipopolysaccharide than those with WT STAT3. Furthermore, histologic examination of the cardiomyocyte-restricted STAT3-deficient mice reveals a dramatic increase in cardiac fibrosis in aged mice. Although no overt signs of heart failure are present in young STAT3-deficient mice, they spontaneously develop heart dysfunction with advancing age. These results indicate the crucial functions of STAT3 in cardiomyocyte resistance to inflammation and other acute injury and in pathogenesis of age-related heart failure. C1 Yale Univ, Sch Med, Dept Internal Med, Div Cardiovasc Med, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Baylor Coll Med, Mol Cardiol Unit, Houston, TX 77030 USA. Chinese Acad Med Sci, FuWai Heart Hosp, Cardiovasc Inst, Div Clin Electrophysiol, Beijing 100037, Peoples R China. RP Fu, XY (reprint author), Yale Univ, Sch Med, Dept Internal Med, Div Cardiovasc Med, 333 Cedar St, New Haven, CT 06520 USA. FU NIAID NIH HHS [AI 34522, R01 AI034522]; NIAMS NIH HHS [AR 44906] NR 24 TC 189 Z9 197 U1 0 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 28 PY 2003 VL 100 IS 22 BP 12929 EP 12934 DI 10.1073/pnas.2134694100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 738RF UT WOS:000186301100076 PM 14566054 ER PT J AU de Gelder, BC Frissen, I Barton, J Hadjikhani, N AF de Gelder, BC Frissen, I Barton, J Hadjikhani, N TI A modulatory role for facial expressions in prosopagnosia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE face recognition; amygdala; configural processes; inversion effect; emotion ID HUMAN EXTRASTRIATE CORTEX; HUMAN FUSIFORM GYRUS; HUMAN VISUAL-CORTEX; FACE RECOGNITION; NEURAL SYSTEMS; PERCEPTION; INVERSION; EMOTION; AREAS; CONFIGURATION AB Brain-damaged patients experience difficulties in recognizing a face (prosopagnosics), but they can still recognize its expression. The dissociation between these two face-related skills has served as a keystone of models of face processing. We now report that the presence of a facial expression can influence face identification. For normal viewers, the presence of a facial expression influences performance negatively, whereas for prosopagnosic patients, it improves performance dramatically. Accordingly, although prosopagnosic patients show a failure to process the facial configuration in the interest of face identification, that ability returns when the face shows an emotional expression. Accompanying brain-imaging results indicate activation in brain areas (amygdala, superior temporal sulcus, parietal cortex) outside the occipitotemporal areas normally activated for face identification and lesioned in these patients. This finding suggests a modulatory role of these areas in face identification that is independent of occipitotemporal face areas. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, Charlestown, MA 02129 USA. Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LA Tilburg, Netherlands. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP de Gelder, BC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, Bldg 36,1st St,Room 417, Charlestown, MA 02129 USA. RI Hadjikhani, Nouchine/C-2018-2008; Barton, Jason/A-6362-2012; Frank, David/E-8213-2012 OI Hadjikhani, Nouchine/0000-0003-4075-3106; FU NINDS NIH HHS [R01 NS 44824-01, R01 NS044824] NR 48 TC 65 Z9 67 U1 3 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 28 PY 2003 VL 100 IS 22 BP 13105 EP 13110 DI 10.1073/pnas.1735530100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 738RF UT WOS:000186301100107 PM 14561892 ER PT J AU Delmonico, FL Surman, OS AF Delmonico, FL Surman, OS TI Is this live-organ donor your patient? SO TRANSPLANTATION LA English DT Article ID DONATION; KIDNEY AB The transplant community is in the midst of an ethical reflection regarding the manner in which live-organ transplantation should be practiced. There is a fundamental aspect to be addressed and reaffirmed. It is the doctor-patient relationship between the transplant surgeon and the live-organ donor. This relationship brings a mutual responsibility to the physician and the donor patient to each other, which should not be abrogated by the claim of donor autonomy nor the obligation fostered by the recipient's needs. If equipoise is not affirmatively achieved in the risk-benefit calculation for the donor and the recipient, then sound medical judgment should override all other concerns. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Delmonico, FL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, White 505, Boston, MA 02114 USA. NR 17 TC 17 Z9 17 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD OCT 27 PY 2003 VL 76 IS 8 BP 1257 EP 1260 DI 10.1097/01.TP.0000089674.07433.DA PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 738CR UT WOS:000186269600026 PM 14578768 ER PT J AU Nasser, SM Cibas, ES Crum, CP Faquin, WC AF Nasser, SM Cibas, ES Crum, CP Faquin, WC TI The significance of the papanicolaou smear diagnosis of low-grade squamous intraepithelial lesion cannot exclude high-grade squamous intraepithelial lesion SO CANCER CYTOPATHOLOGY LA English DT Article DE Papanicolaou (Pap) smear; squamous intraepithelial lesion; human papillomavirus; cervical biopsy; indeterminate cytology; dysplasia ID HUMAN-PAPILLOMAVIRUS; UNDETERMINED SIGNIFICANCE; NATURAL-HISTORY; BIOPSY SPECIMENS; FOLLOW-UP; CELLS; CERVIX; MANAGEMENT; INFECTION; WOMEN AB BACKGROUND. Cervical cytologic specimens that show a low-grade squamous intraepithelial lesion (LSIL) occasionally contain a few cells that are suspicious for, but not diagnostic of, a high-grade squamous intraepithelial lesion (HSIL). In such cases, a diagnosis of LSIL cannot exclude HSIL is rendered. The objective of the Current study was to assess the positive predictive value (PPV) for HSIL in follow-up cervical biopsies for these cases. METHODS. one hundred forty-four women with a Papanicolaou (Pap) diagnosis of LSIL cannot exclude HSIL and their follow-up cervical biopsies were reviewed. Results were compared with a control group of 155 women with a Pap diagnosis of LSIL. A subset of biopsies was tested and typed for human papillomavirus (HPV) DNA by polymerase chain reaction amplification using consensus primers followed by restriction fragment length polymorphism analysis. HPVs were scored as low-risk or high-risk types. RESULTS. Women with LSIL cannot exclude HSIL had a higher incidence of HSIL (PPV = 29%) on follow-up cervical biopsy than the control group (PPV = 15%, P < 0.01). In addition, SIL, indeterminate grade was diagnosed in 10% of cervical biopsies in the study group as compared with 4% in controls. Review of Pap smears from the study group showed that there were 3 types of cells suspicions for a high-grade lesion: atypical squamous metaplastic cells (62%), atypical keratinized cells (20%), and dysplastic cells of borderline nuclear-to-cytoplasm ratio (18%). HPV analysis confirmed the presence of high-risk HPV types in the study cases with high-grade cervical biopsies. CONCLUSIONS. Women with a Pap diagnosis of LSIL cannot exclude HSIL appear to be more likely to harbor a high-grade lesion than those diagnosed with LSIL alone. Its use appears warranted. Women with this diagnosis merit appropriate clinical follow-up to exclude HSIL. (C) 2003 American Cancer Society. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Faquin, WC (reprint author), Massachusetts Gen Hosp, Dept Pathol, WRN 219,55 Fruit St, Boston, MA 02114 USA. NR 30 TC 30 Z9 32 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2003 VL 99 IS 5 BP 272 EP 276 DI 10.1002/cncr.11721 PG 5 WC Oncology; Pathology SC Oncology; Pathology GA 732VQ UT WOS:000185966600003 PM 14579293 ER PT J AU Morii, T Weissbach, L AF Morii, T Weissbach, L TI Sphingosine 1-phosphate and cell migration: resistance to angiogenesis inhibitors SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE sphingosine; 1-phosphate; angiogenesis; plasminogen-related protein-B; endostatin; endothelial cell ID TUMOR-GROWTH; LYSOPHOSPHATIDIC ACID; ENDOSTATIN; SPHINGOSINE-1-PHOSPHATE; VEGF; INVOLVEMENT; METASTASIS; GENERATION; PLATELETS AB Naturally occurring angiogenesis inhibitors can inhibit different steps of the angiogenic process, such as endothelial cell migration. However, the mechanisms underlying this inhibition have not been elucidated. We demonstrate that migration of human umbilical vein endothelial cells induced by the potent endothelial cell chemoattractant sphingosine I-phosphate is refractory to inhibition by well-characterized angiogenesis inhibitors such as endostatin and plasminogen-related protein-B. Our data support the contention that for effective blockage of tumor-induced angiogenesis, antagonists of both G protein-coupled receptor signaling and receptor tyrosine kinase signaling must be combined. (C) 2003 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Ortopaed Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Weissbach, L (reprint author), Massachusetts Gen Hosp, Ortopaed Res Labs, Boston, MA 02114 USA. NR 20 TC 5 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 24 PY 2003 VL 310 IS 3 BP 884 EP 888 DI 10.1016/j.bbrc.2003.09.089 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 733GK UT WOS:000185991400034 PM 14550287 ER PT J AU Kim, WJH Chereshnev, I Gazdoiua, M Fallon, JT Rollins, BJ Taubman, MB AF Kim, WJH Chereshnev, I Gazdoiua, M Fallon, JT Rollins, BJ Taubman, MB TI MCP-1 deficiency is associated with reduced intimal hyperplasia after arterial injury SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE chemokines; intimal hyperplasia; arterial injury; monocyte chemoattractant protein 1; smooth muscle proliferation ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; SMOOTH-MUSCLE CELLS; TISSUE FACTOR; BALLOON INJURY; CHEMOTACTIC PROTEIN-1; CHEMOKINE RECEPTOR; ATHEROSCLEROTIC LESIONS; NEOINTIMAL HYPERPLASIA; SIGNAL-TRANSDUCTION; MONOCLONAL-ANTIBODY AB Monocyte chemoattractant protein (MCP)-1 is abundant in smooth muscle cells (SMC) and macrophages of atherosclerotic plaques and in the injured arterial wall. MCP-1 and its receptor, CCR2, are important mediators of macrophage accumulation and atherosclerotic plaque progression. We have recently reported that CCR2(-/-) mice have a approximate to60% decrease in intimal hyperplasia and medial DNA synthesis in response to femoral arterial injury. We have now examined the response to femoral arterial injury in MCP1(-/-) mice. MCP-1 deficiency was associated with a approximate to30% reduction in intimal hyperplasia at 4 weeks and was not associated with diminished medial DNA synthesis. Despite inducing tissue factor in SMC culture, MCP-1 deficiency was not associated with a decrease in neointimal tissue factor after injury. These data Suggest that MCP-1 and CCR2 deficiencies have distinct effects on arterial injury. The effects of MCP-1 on intimal hyperplasia may be mediated largely through SMC migration. (C) 2003 Elsevier Inc. All rights reserved. C1 Mt Sinai Sch Med, Zena & Michael A Wiener Cardiovasc Inst, New York, NY USA. Mt Sinai Sch Med, Dept Med, New York, NY USA. Mt Sinai Sch Med, Dept Pathol, New York, NY USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Adult Oncol, Boston, MA USA. Mt Sinai Sch Med, Dept Physiol & Biophys, New York, NY USA. RP Taubman, MB (reprint author), Univ Rochester, Dept Med, Cariol Unit, 601 Elmwood Ave,Box 679, Rochester, NY 14627 USA. FU NHLBI NIH HHS [HL29019, HL61818] NR 60 TC 33 Z9 38 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 24 PY 2003 VL 310 IS 3 BP 936 EP 942 DI 10.1016/j.bbrc.2003.09.088 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 733GK UT WOS:000185991400041 PM 14550294 ER PT J AU Xu, KY Kuppusamy, SP Wang, JQ Li, HQ Cui, HM Dawson, TM Huang, PL Burnett, AL Kuppusamy, P Becker, LC AF Xu, KY Kuppusamy, SP Wang, JQ Li, HQ Cui, HM Dawson, TM Huang, PL Burnett, AL Kuppusamy, P Becker, LC TI Nitric oxide protects cardiac sarcolemmal membrane enzyme function and ion active transport against ischemia-induced inactivation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NA+-K+-ATPASE; FREE-RADICALS; SKELETAL-MUSCLE; ADENOSINE-TRIPHOSPHATASE; SARCOPLASMIC-RETICULUM; MYOCARDIAL-ISCHEMIA; ENDOTHELIAL-CELLS; HYDROXYL RADICALS; SYNTHASE; ISOFORMS AB Nitric oxide (NO.) generated from nitric oxide synthase (NOS) isoforms bound to cellular membranes may serve to modulate oxidative stresses in cardiac muscle and thereby regulate the function of key membrane-associated enzymes. Ischemia is known to inhibit the function of sarcolemmal enzymes, including the (Na+ + K+)-ATPase, but it is unknown whether concomitant injury to sarcolemma (SL)-associated NOS isoforms may contribute to this process by reducing the availability of locally generated NO.. Here we report that nNOS, as well as eNOS (SL NOSs), are tightly associated with cardiac SL membranes in several different species. In isolated perfused rat hearts, global ischemia caused a time-dependent irreversible injury to cardiac SL NOSs and a disruption of SL NO. generation. Pretreatment with low concentrations of the NO. donor 1-hydroxy-2-oxo-3-(N-3-methyl- aminopropyl)-3-methyl-1-triazene (NOC-7) markedly protected both SL NOS and (Na+ + K+)-ATPase functions against ischemia-induced inactivation. Moreover, ischemia impaired SL Na+/K+ binding, and NOC-7 significantly prevented ischemic injury to the ion binding sites on (Na+ + K+)-ATPase. These novel findings indicate that NO. can protect cardiac SL NOSs and (Na+ + K+)-ATPase against ischemia-induced inactivation and suggest that locally generated NO. may serve to regulate SL Na+/ K+ ion active transport in the heart. C1 Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Dept Neurol, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Dept Neurosci, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Inst Cell Engn, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21224 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02129 USA. Ohio State Univ, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA. RP Xu, KY (reprint author), Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Rm 308,108 N Greene St, Baltimore, MD 21201 USA. FU NHLBI NIH HHS [HL 33360, HL 52175]; NIDDK NIH HHS [DK 02568]; NINDS NIH HHS [NS 378090] NR 35 TC 33 Z9 34 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 24 PY 2003 VL 278 IS 43 BP 41798 EP 41803 DI 10.1074/jbc.M306865200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 733FP UT WOS:000185989500031 PM 12904295 ER PT J AU Seki, K Fujimori, T Savagner, P Hata, A Aikawa, T Ogata, N Nabeshima, Y Kaechoong, L AF Seki, K Fujimori, T Savagner, P Hata, A Aikawa, T Ogata, N Nabeshima, Y Kaechoong, L TI Mouse Snail family transcription repressors regulate chondrocyte, extracellular matrix, type II collagen, and aggrecan SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TISSUE-SPECIFIC EXPRESSION; ATDC5 IN-VITRO; ALGINATE BEADS; NEURAL CREST; TRANSGENIC MICE; GENE-EXPRESSION; MESSENGER-RNA; PROTEIN; DROSOPHILA; CARTILAGE AB Snail family genes are conserved among species during evolution and encode transcription factors expressed at different stages of development in different tissues. These genes are involved in a broad spectrum of biological functions: cell differentiation, cell motility, cell cycle regulation, and apoptosis. However, little is known about the target genes involved in these functions. Here we show that mouse Snail family members, Snail (Sna) and Slug (Slugh), are involved in chondrocyte differentiation by controlling the expression of type II collagen (Col2a1) and aggrecan. In situ hybridization analysis of developing mouse limb demonstrated that Snail and Slug mRNAs were highly expressed in hypertrophic chondrocytes. Inversely, the expression of collagen type II mRNA disappeared during hypertrophic differentiation. Snail and Slug mRNA expression was down-regulated during differentiation of the mouse chondrogenic cell line ATDC5 and overexpression of exogenous Snail or Slug in ATDC5 cells inhibited expression of collagen type II and aggrecan mRNA. Reporter analysis revealed Snail and Slug suppressed the promoter activity of Col2a1, and the E-boxes in the promoter region were the responsible element. Gel shift assay demonstrated the binding of Snail to the E-box. Because type II collagen and aggrecan are major functional components of extracellular matrix in cartilage, these results suggest an important role for Snail-related transcription repressors during chondrocyte differentiation. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Kyoto Univ, Grad Sch Med, Dept Pathol & Tumor Biol, Kyoto 6068501, Japan. INSERM 0229, F-34000 Montpellier, France. Tufts Univ, Sch Med, Dept Biochem, MCRI,Tufts New England Med Ctr, Boston, MA 02111 USA. RP Seki, K (reprint author), Kyoto Univ, Grad Sch Med, Sakyo Ku, Yoshida Konoe Cho, Kyoto 8501, Japan. RI Fujimori, Toshihiko/L-7711-2016 NR 47 TC 51 Z9 57 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 OCT 24 PY 2003 VL 278 IS 43 BP 41862 EP 41870 DI 10.1074/jbc.M308336200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 733FP UT WOS:000185989500039 PM 12917416 ER PT J AU Balasubramanian, S Kuppuswamy, D AF Balasubramanian, S Kuppuswamy, D TI RGD-containing peptides activate S6K1 through beta(3) integrin in adult cardiac muscle cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID KINASE SIGNALING PATHWAY; FOCAL COMPLEX-FORMATION; MATRIX METALLOPROTEINASES; MONOCLONAL-ANTIBODIES; PROTEIN-SYNTHESIS; HEART-FAILURE; IN-VIVO; C-SRC; P70; PHOSPHORYLATION AB The enzyme p70S6 kinase (S6K1) is critical for cell growth, and we have reported its activation during cardiac hypertrophy. Because cardiac hypertrophy also involves integrin activation, we analyzed whether integrins could contribute to S6K1 activation. Using adult feline cardiomyocytes, here we report that integrin-interacting Arg-Gly-Asp (RGD) peptides activate S6K1 as observed by band shifting, kinase activity and phosphorylation at Thr-389 and Thr-421/Ser-424 of S6K1, and S6 protein phosphorylation. Perturbation of specific integrin function with blocking antibodies and by overexpressing the beta(1A) cytoplasmic tail revealed that beta(3) but not beta(1) integrin mediates the RGD-induced S6K1 activation. This activation is focal adhesion complex-independent and is accompanied by the activation of extracellular signal-regulated kinases 1/2 (ERK) and mammalian target of rapamycin (mTOR). Studies using specific inhibitors and dominant negative c-Raf expression in cardiomyocytes indicate that the S6K1 activation involves mTOR, MEK/ERK, and phosphatidylinositol 3-kinase pathways and is independent of protein kinase C and c-Raf. Finally, addition of fluorescent-labeled RGD peptide to cardiomyocytes exhibits its internalization and localization to the endocytic vesicles, and pretreatment of cardiomyocytes with endocytic inhibitors reduced the S6K1 activation. These data suggest that RGD interaction with beta(3) integrin and its subsequent endocytosis trigger specific signaling pathway(s) for S6K1 activation in cardiomyocytes and that this process may contribute to hypertrophic growth and remodeling of myocardium. C1 Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Div Cardiol, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Kuppuswamy, D (reprint author), Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Div Cardiol, 114 Doughty St, Charleston, SC 29425 USA. FU NHLBI NIH HHS [HL 48788] NR 65 TC 32 Z9 36 U1 2 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 24 PY 2003 VL 278 IS 43 BP 42214 EP 42224 DI 10.1074/jbc.M303428200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 733FP UT WOS:000185989500080 PM 12909616 ER PT J AU Hanczyc, MM Fujikawa, SM Szostak, JW AF Hanczyc, MM Fujikawa, SM Szostak, JW TI Experimental models of primitive cellular compartments: Encapsulation, growth, and division SO SCIENCE LA English DT Article ID MURCHISON CARBONACEOUS CHONDRITE; LARGE UNILAMELLAR VESICLES; FATTY-ACID MEMBRANES; MONTMORILLONITE CATALYSIS; SIZE DISTRIBUTION; EXTRUSION; SURFACE; RNA; POLYMERIZATION; COMPONENTS AB The clay montmorillonite is known to catalyze the polymerization of RNA from activated ribonucleotides. Here we report that montmorillonite accelerates the spontaneous conversion of fatty acid micelles into vesicles. Clay particles often become encapsulated in these vesicles, thus providing a pathway for the prebiotic encapsulation of catalytically active surfaces within membrane vesicles. In addition, RNA adsorbed to clay can be encapsulated within vesicles. Once formed, such vesicles can grow by incorporating fatty acid supplied as micelles and can divide without dilution of their contents by extrusion through small pores. These processes mediate vesicle replication through cycles of growth and division. The formation, growth, and division of the earliest cells may have occurred in response to similar interactions with mineral particles and inputs of material and energy. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. OI Hanczyc, Martin/0000-0002-5453-2139 FU Howard Hughes Medical Institute NR 34 TC 370 Z9 385 U1 17 U2 106 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 OCT 24 PY 2003 VL 302 IS 5645 BP 618 EP 622 DI 10.1126/science.1089904 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 735MV UT WOS:000186119900051 PM 14576428 ER PT J AU Calvi, LM Adams, GB Weibrecht, KW Weber, JM Olson, DP Knight, MC Martin, RP Schipani, E Divieti, P Bringhurst, FR Milner, LA Kronenberg, HM Scadden, DT AF Calvi, LM Adams, GB Weibrecht, KW Weber, JM Olson, DP Knight, MC Martin, RP Schipani, E Divieti, P Bringhurst, FR Milner, LA Kronenberg, HM Scadden, DT TI Osteoblastic cells regulate the haematopoietic stem cell niche SO NATURE LA English DT Article ID BONE-MARROW; GROWTH-FACTOR; SELF-RENEWAL; NOTCH1; DIFFERENTIATION; CULTURES; LINEAGE; MOUSE AB Stem cell fate is influenced by specialized microenvironments that remain poorly defined in mammals(1-3). To explore the possibility that haematopoietic stem cells derive regulatory information from bone, accounting for the localization of haematopoiesis in bone marrow, we assessed mice that were genetically altered to produce osteoblast-specific, activated PTH/PTHrP receptors (PPRs)(4). Here we show that PPR-stimulated osteoblastic cells that are increased in number produce high levels of the Notch ligand jagged 1 and support an increase in the number of haematopoietic stem cells with evidence of Notch1 activation in vivo. Furthermore, ligand-dependent activation of PPR with parathyroid hormone (PTH) increased the number of osteoblasts in stromal cultures, and augmented ex vivo primitive haematopoietic cell growth that was abrogated by gamma-secretase inhibition of Notch activation. An increase in the number of stem cells was observed in wild-type animals after PTH injection, and survival after bone marrow transplantation was markedly improved. Therefore, osteoblastic cells are a regulatory component of the haematopoietic stem cell niche in vivo that influences stem cell function through Notch activation. Niche constituent cells or signalling pathways provide pharmacological targets with therapeutic potential for stem-cell-based therapies. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Canc Ctr, Partners AIDS Res Ctr,Ctr Regenerat Med & Technol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. Univ Rochester, Sch Med, Dept Med, Endocrine Unit, Rochester, NY 14642 USA. Univ Rochester, Sch Med, Dept Pediat, Ctr Human Genet & Mol Pediat Dis, Rochester, NY 14642 USA. RP Scadden, DT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Canc Ctr, Partners AIDS Res Ctr,Ctr Regenerat Med & Technol, Boston, MA 02114 USA. OI Calvi, Laura Maria/0000-0001-6969-239X FU NIDDK NIH HHS [K08 DK064381, K08 DK064381-02] NR 26 TC 1964 Z9 2049 U1 19 U2 121 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 23 PY 2003 VL 425 IS 6960 BP 841 EP 846 DI 10.1038/nature02040 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 735ME UT WOS:000186118500046 PM 14574413 ER PT J AU Thayer, SP di Magliano, MP Heiser, PW Nielsen, CM Roberts, DJ Lauwers, GY Qi, YP Gysin, S Fernandez-del Castillo, CF Yajnik, V Antoniu, B McMahon, M Warshaw, AL Hebrok, M AF Thayer, SP di Magliano, MP Heiser, PW Nielsen, CM Roberts, DJ Lauwers, GY Qi, YP Gysin, S Fernandez-del Castillo, CF Yajnik, V Antoniu, B McMahon, M Warshaw, AL Hebrok, M TI Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis SO NATURE LA English DT Article ID SONIC-HEDGEHOG; INTRAEPITHELIAL NEOPLASIA; SIGNALING PATHWAY; DUCT LESIONS; NEURAL-TUBE; EXPRESSION; GENE; ADENOCARCINOMA; INACTIVATION; CYCLOPAMINE AB Hedgehog signalling-an essential pathway during embryonic pancreatic development, the misregulation of which has been implicated in several forms of cancer-may also be an important mediator in human pancreatic carcinoma(1-8). Here we report that sonic hedgehog, a secreted hedgehog ligand, is abnormally expressed in pancreatic adenocarcinoma and its precursor lesions: pancreatic intraepithelial neoplasia (PanIN). Pancreata of Pdx-Shh mice (in which Shh is misexpressed in the pancreatic endoderm) develop abnormal tubular structures, a phenocopy of human PanIN-1 and -2. Moreover, these PanIN-like lesions also contain mutations in K-ras and overexpress HER-2/neu, which are genetic mutations found early in the progression of human pancreatic cancer. Furthermore, hedgehog signalling remains active in cell lines established from primary and metastatic pancreatic adenocarcinomas. Notably, inhibition of hedgehog signalling by cyclopamine induced apoptosis and blocked proliferation in a subset of the pancreatic cancer cell lines both in vitro and in vivo. These data suggest that this pathway may have an early and critical role in the genesis of this cancer, and that maintenance of hedgehog signalling is important for aberrant proliferation and tumorigenesis. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Med, Ctr Diabet, San Francisco, CA 94143 USA. Univ Calif San Francisco, Canc Res Inst, San Francisco, CA 94143 USA. RP Hebrok, M (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. FU NICHD NIH HHS [R29 HD034448-02]; NIDDK NIH HHS [R01 DK060533] NR 30 TC 950 Z9 1018 U1 12 U2 67 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 23 PY 2003 VL 425 IS 6960 BP 851 EP 856 DI 10.1038/nature02009 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 735ME UT WOS:000186118500048 PM 14520413 ER PT J AU Seminara, SB Messager, S Chatzidaki, EE Thresher, RR Acierno, JS Shagoury, JK Bo-Abbas, Y Kuohung, W Schwinof, KM Hendrick, AG Zahn, D Dixon, J Kaiser, UB Slaugenhaupt, SA Gusella, JF O'Rahilly, S Carlton, MBL Crowley, WF Aparicio, SAJR Colledge, WH AF Seminara, SB Messager, S Chatzidaki, EE Thresher, RR Acierno, JS Shagoury, JK Bo-Abbas, Y Kuohung, W Schwinof, KM Hendrick, AG Zahn, D Dixon, J Kaiser, UB Slaugenhaupt, SA Gusella, JF O'Rahilly, S Carlton, MBL Crowley, WF Aparicio, SAJR Colledge, WH TI The GPR54 gene as a regulator of puberty SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; METASTASIS-SUPPRESSOR GENE; PROTEIN-COUPLED RECEPTOR; LUTEINIZING-HORMONE; KALLMANNS-SYNDROME; MENSTRUAL-CYCLE; GNRH RECEPTOR; KISS-1; MEN AB BACKGROUND: Puberty, a complex biologic process involving sexual development, accelerated linear growth, and adrenal maturation, is initiated when gonadotropin-releasing hormone begins to be secreted by the hypothalamus. We conducted studies in humans and mice to identify the genetic factors that determine the onset of puberty. METHODS: We used complementary genetic approaches in humans and in mice. A consanguineous family with members who lacked pubertal development (idiopathic hypogonadotropic hypogonadism) was examined for mutations in a candidate gene, GPR54, which encodes a G protein-coupled receptor. Functional differences between wild-type and mutant GPR54 were examined in vitro. In parallel, a Gpr54-deficient mouse model was created and phenotyped. Responsiveness to exogenous gonadotropin-releasing hormone was assessed in both the humans and the mice. RESULTS: Affected patients in the index pedigree were homozygous for an L148S mutation in GPR54, and an unrelated proband with idiopathic hypogonadotropic hypogonadism was determined to have two separate mutations, R331X and X399R. The in vitro transfection of COS-7 cells with mutant constructs demonstrated a significantly decreased accumulation of inositol phosphate. The patient carrying the compound heterozygous mutations (R331X and X399R) had attenuated secretion of endogenous gonadotropin-releasing hormone and a left-shifted dose-response curve for gonadotropin-releasing hormone as compared with six patients who had idiopathic hypogonadotropic hypogonadism without GPR54 mutations. The Gpr54-deficient mice had isolated hypogonadotropic hypogonadism (small testes in male mice and a delay in vaginal opening and an absence of follicular maturation in female mice), but they showed responsiveness to both exogenous gonadotropins and gonadotropin-releasing hormone and had normal levels of gonadotropin-releasing hormone in the hypothalamus. CONCLUSIONS: Mutations in GPR54, a G protein-coupled receptor gene, cause autosomal recessive idiopathic hypogonadotropic hypogonadism in humans and mice, suggesting that this receptor is essential for normal gonadotropin-releasing hormone physiology and for puberty. C1 Paradigm Therapeut, Cambridge CB4 0WA, England. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Inst Human Genet, Boston, MA USA. Univ Cambridge, Dept Physiol, Cambridge, England. Univ Cambridge, Dept Oncol, Cambridge, England. Univ Cambridge, Dept Clin Biochem, Cambridge, England. Univ Cambridge, Addenbrookes Hosp, Cambridge Inst Med Res, Cambridge CB2 2QQ, England. Kuwait Univ, Fac Med, Al Jabriyah, Kuwait. RP Colledge, WH (reprint author), Paradigm Therapeut, 214 Cambridge Sci Pk,Milton Rd, Cambridge CB4 0WA, England. OI Colledge, William Henry/0000-0002-9603-4429 FU NCRR NIH HHS [3M01 RR01066-22S2]; NICHD NIH HHS [R01 HD015788, 5R01 HD15788-17, R01 HD043341, T32 HD40135, U54 HD028138, U54 HD029164, U54 HD28138-13]; NIGMS NIH HHS [GM61354] NR 37 TC 1227 Z9 1276 U1 3 U2 61 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 OCT 23 PY 2003 VL 349 IS 17 BP 1614 EP U8 DI 10.1056/NEJMoa035322 PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA 734ZT UT WOS:000186088400006 PM 14573733 ER PT J AU Finn, AV Antman, EM AF Finn, AV Antman, EM TI Isolated right ventricular infarction SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Finn, AV (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 23 PY 2003 VL 349 IS 17 BP 1636 EP 1636 DI 10.1056/NEJMicm030315 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 734ZT UT WOS:000186088400008 PM 14573735 ER PT J AU Soto, O Cros, DP Hedley-Whyte, ET AF Soto, O Cros, DP Hedley-Whyte, ET TI A 37-year-old man with a history of alcohol and drug abuse and sudden onset of leg weakness - Colchicine myoneuropathy. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID INDUCED RHABDOMYOLYSIS; AXOPLASMIC-TRANSPORT; INDUCED MYOPATHY; SKELETAL-MUSCLE; TOXICITY; NEUROPATHY; DISEASE; NEUROMYOPATHY; MYOTONIA; NERVE C1 Univ Navarra Clin, Dept Neurol, Navarra, Spain. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Soto, O (reprint author), Univ Navarra Clin, Dept Neurol, Navarra, Spain. NR 37 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 OCT 23 PY 2003 VL 349 IS 17 BP 1656 EP 1663 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 734ZT UT WOS:000186088400012 PM 14573738 ER PT J AU Fihn, SD AF Fihn, SD TI Acute uncomplicated urinary tract infection in women (vol 349, pg 259, 2003) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Correction C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Fihn, SD (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. NR 4 TC 0 Z9 0 U1 1 U2 3 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 OCT 23 PY 2003 VL 349 IS 17 BP 1675 EP 1676 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 734ZT UT WOS:000186088400032 ER PT J AU Harmes, DC Bresnick, E Lubin, EA Watson, JK Heim, KE Curtin, JC Suskind, AM Lamb, J DiRenzo, J AF Harmes, DC Bresnick, E Lubin, EA Watson, JK Heim, KE Curtin, JC Suskind, AM Lamb, J DiRenzo, J TI Positive and negative regulation of Delta N-p63 promoter activity by p53 and Delta N-p63-alpha contributes to differential regulation of p53 target genes SO ONCOGENE LA English DT Article DE p53; p63; mammary epithelia; gene regulation ID MAMMARY-GLAND; STEM-CELLS; NEOPLASTIC-CELLS; DNA-DAMAGE; P63; P73; EXPRESSION; APOPTOSIS; HOMOLOG; FAMILY AB Mammary epithelial regeneration implies the existence of cellular progenitors with retained replicative capacity, prolonged lifespan and developmental potency. Evidence exists that DeltaN-p63 isoforms preserve these features by modulating p53 activity in basal epithelia. DeltaN-p63 mRNA levels decline at the onset of differentiation suggesting that its transcriptional regulation may contribute to the initiation of differentiation. To study transcriptional regulation of DeltaN-p63, a 10.3 kbp fragment containing the DeltaN-p63 promoter was isolated. We report here that DeltaN-p63 is a positive and negative transcriptional target of p53 and DeltaN-p63-alpha, respectively. Disruption of p53 activity or expression abolishes the expression of DeltaN-p63-alpha. This regulation is mediated by a p53-binding element sufficient to confer these activities to a heterologous promoter. Chromatin immune-precipitation indicates that, in asynchronously growing cells, p53 occupies this element. In response to DNA damage, DeltaN-p63-alpha is recruited to this element as transcription of DeltaN-p63 declines. Disruption of DeltaN-p63-alpha expression had differential effects on the transcriptional regulation of several p53-target genes. These findings indicate that p53 contributes to the preservation of basal epithelia by driving the expression of DeltaN-p63 isoforms. These studies also suggest that in response to genotoxic stress, DeltaN-p63-alpha mediates the silencing of its own promoter thereby altering the pattern of p53-target gene expression. C1 Dartmouth Coll Sch Med, Dept Pharmacol & Toxicol, Hanover, NH 03755 USA. Dartmouth Coll Sch Med, Dept Biochem, Hanover, NH 03755 USA. Dartmouth Coll, Hanover, NH 03755 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP DiRenzo, J (reprint author), Dartmouth Coll Sch Med, Dept Pharmacol & Toxicol, 7650 Remsen, Hanover, NH 03755 USA. NR 37 TC 63 Z9 64 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 23 PY 2003 VL 22 IS 48 BP 7607 EP 7616 DI 10.1038/sj.onc.1207129 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 735KQ UT WOS:000186113000008 PM 14576823 ER PT J AU Yan, LJL Liu, K Matthews, KA Daviglus, ML Ferguson, TF Kiefe, CI AF Yan, LJL Liu, K Matthews, KA Daviglus, ML Ferguson, TF Kiefe, CI TI Psychosocial factors and risk of hypertension - The Coronary Artery Risk Development in Young Adults (CARDIA) study SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HIGH BLOOD-PRESSURE; A BEHAVIOR PATTERN; NUTRITION EXAMINATION SURVEY; HEART-DISEASE; PSYCHOLOGICAL PREDICTORS; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; EDUCATION-PROGRAM; NATIONAL-HEALTH; HOSTILITY AB Context Although psychosocial factors are correlated, previous studies on risk factors for hypertension have typically examined psychosocial factors individually and have yielded inconsistent findings. Objective To examine the role of psychosocial factors of time urgency/impatience (TUI), achievement striving/competitiveness (ASC), hostility, depression, and anxiety on long-term risk of hypertension. Design, Setting, and Study Population A population-based, prospective, observational study using participant data from the Coronary Artery Risk Development in Young Adults (CARDIA) study. A total of 3308 black and white adults aged 18 to 30 years (when recruited in 1985 and 1986) from 4 US metropolitan areas and followed up through 2000 to 2001. Main Outcome Measures Fifteen-year cumulative incidence of hypertension (systolic blood pressure of 140 mm Hg or higher, diastolic blood pressure of 90 mm Hg or higher, or taking anti hypertensive medication). Results The incidence of hypertension at year 15 was 15% from baseline and 13.6% from year 5. After adjusting for the same set of hypertension risk factors and each of the psychosocial factors of TUI, ASC, hostility, depression, and anxiety in 5 separate logistic regression models, higher TUI and hostility were significantly associated with risk of developing hypertension at 15-year follow-up for the total sample. Compared with the lowest score group, the adjusted odds ratio (OR) for TUI was 1.51 (95% confidence interval [CI], 1.12-2.03) for a score of 1; 1.47 (95% Cl, 1.08-2.02) for a score of 2; and 1.84 (95% Cl, 1.29-2.62) for a score of 3 to 4 (P for trend =.001). Compared with the lowest quartile group, the adjusted OR for hostility was 1.06 (95% Cl, 0.76-1.47) for quartile 2; 1.38 (95% Cl, 1.00-1.91) for quartile 3; and 1.84 (95% Cl, 1.33-2.54) for quartile 4 (P for trend <.001). No consistent patterns were found for ASC, depression, or anxiety. Race- and sex-specific analyses and multivariable models with simultaneous adjustment for all 5 psychosocial factors and other hypertension risk factors had generally similar results. Conclusion Among young adults, TUI and hostility were associated with a dose-response increase in the long-term risk of hypertension. C1 Northwestern Univ, Feinberg Sch Med, Dept Prevent Dent, Chicago, IL 60611 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. Univ Alabama, Div Prevent Med, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Yan, LJL (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Prevent Dent, 680 N Lake Shore Dr,Suite 1102, Chicago, IL 60611 USA. FU NHLBI NIH HHS [N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-95095] NR 55 TC 180 Z9 194 U1 1 U2 19 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 OCT 22 PY 2003 VL 290 IS 16 BP 2138 EP 2148 DI 10.1001/jama.290.16.2138 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 734CB UT WOS:000186036700023 PM 14570949 ER PT J AU Kris, MG Natale, RB Herbst, RS Lynch, TJ Prager, D Belani, CP Schiller, JH Kelly, K Spiridonidis, H Sandler, A Albain, KS Cella, D Wolf, MK Averbuch, SD Ochs, JJ Kay, AC AF Kris, MG Natale, RB Herbst, RS Lynch, TJ Prager, D Belani, CP Schiller, JH Kelly, K Spiridonidis, H Sandler, A Albain, KS Cella, D Wolf, MK Averbuch, SD Ochs, JJ Kay, AC TI Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer - A randomized trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID FUNCTIONAL ASSESSMENT; CHEMOTHERAPY REGIMENS; IMATINIB MESYLATE; ZD1839 IRESSA(TM); THERAPY; EXPRESSION; DOCETAXEL; PLATINUM; TUMORS; EGFR AB Context More persons in the United States die from non-small cell lung cancer (NSCLC) than from breast, colorectal, and prostate cancer combined. In preclinical testing, oral gefitinib inhibited the growth of NSCLC tumors that express the epidermal growth factor receptor (EGFR), a mediator of cell signaling, and phase 1 trials have demonstrated that a fraction of patients with NSCLC progressing after chemotherapy experience both a decrease in lung cancer symptoms and radiographic tumor shrinkages with gefitinib. Objective To assess differences in symptomatic and radiographic response among patients with NSCLC receiving 250-mg and 500-mg daily doses of gefitinib. Design, Setting, and Patients Double-blind, randomized phase 2 trial conducted from November 2000 to April 2001 in 30 US academic and community oncology centers. Patients (N =221) had either stage IIIB or IV NSCLC for which they had received at least 2 chemotherapy regimens. Intervention Daily oral gefitinib, either 500 mg (administered as two 250-mg gefitinib tablets) or 250 mg (administered as one 250-mg gefitinib tablet and 1 matching placebo). Main Outcome Measures Improvement of NSCLC symptoms (2-point or greater increase in score on the summed lung cancer subscale of the Functional Assessment of Cancer Therapy-Lung [FACT-L] instrument) and tumor regression (>50% decrease in lesion size on imaging studies). Results Of 221 patients enrolled, 216 received gefitinib as randomized. Symptoms of NSCLC improved in 43% (95% confidence interval [CI], 33%-53%) of patients receiving 250 mg of gefitinib and in 35% (95% Cl, 26%-45%) of patients receiving 500 mg. These benefits were observed within 3 weeks in 75% of patients. Partial radiographic responses occurred in 12% (95% Cl, 6%-20%) of individuals receiving 250 mg of gefitinib and in 9% (95% Cl, 4%-16%) of those receiving 500 mg. Symptoms improved in 96% of patients with partial radiographic responses. The overall survival at 1 year was 25%. There were no significant differences between the 250-mg and 500-mg doses in rates of symptom improvement (P=.26), radiographic tumor regression (P=.51), and projected 1-year survival (P=.54). The 500-mg dose was associated more frequently with transient acne-like rash (P=.04) and diarrhea (P=.006). Conclusions Gefitinib, a well-tolerated oral EGFR-tyrosine kinase inhibitor, improved disease-related symptoms and induced radiographic tumor regressions in patients with NSCLC persisting after chemotherapy. C1 Mem Sloan Kettering Canc Ctr, Dept Med, Div Solid Tumor Oncol, Thorac Oncol Serv, New York, NY 10021 USA. Cornell Univ, Weil Med Coll, New York, NY USA. Cedars Sinai Comprehens Canc Ctr, Los Angeles, CA USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Univ Wisconsin Hosp, Madison, WI USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Hematol Oncol Consultants Inc, Columbus, OH USA. Vanderbilt Univ, Nashville, TN USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Northwestern Univ, Evanston, IL USA. AstraZeneca, Wilmington, DE USA. RP Mem Sloan Kettering Canc Ctr, Dept Med, Div Solid Tumor Oncol, Thorac Oncol Serv, 1275 York Ave, New York, NY 10021 USA. OI Kris, Mark/0000-0002-7317-5341 NR 50 TC 1790 Z9 1927 U1 11 U2 73 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 22 PY 2003 VL 290 IS 16 BP 2149 EP 2158 DI 10.1001/jama.290.16.2149 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 734CB UT WOS:000186036700024 PM 14570950 ER PT J AU Steffes, MW Chavers, BM Molitch, ME Cleary, PA Lachin, JM Genuth, S Nathan, DM Genuth, S Nathan, D Engel, S Martinez, H Shamoon, H Engel, H Dahms, W Mayer, L Pendegras, S Zegarra, H Miller, D Singerman, L Smith-Brewer, S Genuth, S Brillion, D Lackaye, M Heinemann, M Repucci, V Lee, T Whitehouse, F Kruger, D Galpern, A Carey, JD Bergenstal, R Johnson, M Kendell, D Spencer, M Noller, D Morgan, K Etzwiler, D Jacobson, A Golden, E Sharuk, G ARrigg, P Baeser, R Ganda, O Rosenzweig, J Wolpert, H Economides, P Handy, O Rand, L Nathan, D Fritz, S Godine, J McKitrick, C Lou, P Service, FJ Ziegler, G Pach, J Lindsey, J Colwell, J Wood, D Mayfield, R Hermayer, K Szpiech, M Lyons, T Parker, J Farr, A Elsing, S Thompson, T Selby, J Bracey, M Molitch, M Schaefer, B Jampol, L Weinberg, D Lyon, A Strugula, Z Shankle, J Astlesford, P Kolterman, O Lorenzi, G Goldbaum, M Sivitz, W Bayless, M Zeither, R Weingeist, T Stone, E Boidt, HC Gehres, K Russell, S Counts, D Kowarski, A Ostrowski, D Donner, T Steidl, S Jones, B Herman, W Greene, D Martin, C Stevens, MJ Vine, AK Elner, S Bantle, J Rogness, B Olsen, T Steuer, E Goldstein, D Hitt, S Giangiacomo, J Hainsworth, D Schade, D Burge, M Canady, J Schluter, M Das, A Hornbeck, D Schwartz, S Bourne, PA Maschak-Carey, BJ Baker, L Braunstein, S Brucker, A Orchard, T Silvers, N Songer, T Doft, B Olson, S Bergren, RL Lobes, L Fineman, M Drash, A Malone, J Vaccaro-Kish, J Berger, C Gstalder, R Pavan, PR Morrison, A Dagogo-Jack, S Schussler, S Kitabchi, A Lambeth, H Murphy, MB Mosesr, S Meyer, D Iannacone, A Bryer-Ash, M Raskin, P Strowig, S Edwards, A Alappatt, J Wilson, C Park, S Ye, H Zinman, B Barnie, A MacLean, S Devenyi, R Mandelcorn, M Brent, M Palmer, J Catton, S Kinyoun, J Van Ottingham, L Ginsberg, J Dupre, J Harth, J Nicolle, D May, M Lorenz, R Lipps, J Survant, L Feman, S Tawansy, K Agarwal, A Adkins, T White, N Santiago, J Levandoski, L Boniuk, I Grand, G Thomas, M Burgess, D Joseph, D Blinder, K Shah, G Tamborlane, W Gatcomb, P Stoessel, K Taylor, K Dahms, B Trail, R Quin, J Lachin, J Cleary, P Kenny, D Backlund, J Diminick, L Determan, A Klump, K Hawkins, M Cowie, C Fradkin, J Siebert, C Eastman, R Davis, M Hubbard, L Geithman, P Kastorff, L Neider, M Badal, D Esser, B Miner, K Wabers, H Glander, K Joyce, J Robinson, N Hurtenbach, C Hannon, C Steffes, M Bucksa, J Chavers, B O'Leary, D Funk, L Polak, J Crow, R O'Donnell, C Gloeb, B Thomas, S Detrano, R Wong, N Fox, M Kim, L Oudiz, R Weir, G Clark, C D'Agostino, R Espeland, M Klein, B Manolio, T Rand, L Singer, D Stern, M Garvey, WT Lyons, TJ Jenkins, A Klein, R Lopes-Virella, M Virella, G Jaffa, AA Zheng, D Lackland, D McGee, D Mayfield, RK Brabham, M Boright, A Paterson, A Scherere, S Zinman, B Bruznell, J Hokanson, J Marcovina, S Purnell, J Sibley, S Deeb, S Edwards, K Nathan, D AF Steffes, MW Chavers, BM Molitch, ME Cleary, PA Lachin, JM Genuth, S Nathan, DM Genuth, S Nathan, D Engel, S Martinez, H Shamoon, H Engel, H Dahms, W Mayer, L Pendegras, S Zegarra, H Miller, D Singerman, L Smith-Brewer, S Genuth, S Brillion, D Lackaye, M Heinemann, M Repucci, V Lee, T Whitehouse, F Kruger, D Galpern, A Carey, JD Bergenstal, R Johnson, M Kendell, D Spencer, M Noller, D Morgan, K Etzwiler, D Jacobson, A Golden, E Sharuk, G ARrigg, P Baeser, R Ganda, O Rosenzweig, J Wolpert, H Economides, P Handy, O Rand, L Nathan, D Fritz, S Godine, J McKitrick, C Lou, P Service, FJ Ziegler, G Pach, J Lindsey, J Colwell, J Wood, D Mayfield, R Hermayer, K Szpiech, M Lyons, T Parker, J Farr, A Elsing, S Thompson, T Selby, J Bracey, M Molitch, M Schaefer, B Jampol, L Weinberg, D Lyon, A Strugula, Z Shankle, J Astlesford, P Kolterman, O Lorenzi, G Goldbaum, M Sivitz, W Bayless, M Zeither, R Weingeist, T Stone, E Boidt, HC Gehres, K Russell, S Counts, D Kowarski, A Ostrowski, D Donner, T Steidl, S Jones, B Herman, W Greene, D Martin, C Stevens, MJ Vine, AK Elner, S Bantle, J Rogness, B Olsen, T Steuer, E Goldstein, D Hitt, S Giangiacomo, J Hainsworth, D Schade, D Burge, M Canady, J Schluter, M Das, A Hornbeck, D Schwartz, S Bourne, PA Maschak-Carey, BJ Baker, L Braunstein, S Brucker, A Orchard, T Silvers, N Songer, T Doft, B Olson, S Bergren, RL Lobes, L Fineman, M Drash, A Malone, J Vaccaro-Kish, J Berger, C Gstalder, R Pavan, PR Morrison, A Dagogo-Jack, S Schussler, S Kitabchi, A Lambeth, H Murphy, MB Mosesr, S Meyer, D Iannacone, A Bryer-Ash, M Raskin, P Strowig, S Edwards, A Alappatt, J Wilson, C Park, S Ye, H Zinman, B Barnie, A MacLean, S Devenyi, R Mandelcorn, M Brent, M Palmer, J Catton, S Kinyoun, J Van Ottingham, L Ginsberg, J Dupre, J Harth, J Nicolle, D May, M Lorenz, R Lipps, J Survant, L Feman, S Tawansy, K Agarwal, A Adkins, T White, N Santiago, J Levandoski, L Boniuk, I Grand, G Thomas, M Burgess, D Joseph, D Blinder, K Shah, G Tamborlane, W Gatcomb, P Stoessel, K Taylor, K Dahms, B Trail, R Quin, J Lachin, J Cleary, P Kenny, D Backlund, J Diminick, L Determan, A Klump, K Hawkins, M Cowie, C Fradkin, J Siebert, C Eastman, R Davis, M Hubbard, L Geithman, P Kastorff, L Neider, M Badal, D Esser, B Miner, K Wabers, H Glander, K Joyce, J Robinson, N Hurtenbach, C Hannon, C Steffes, M Bucksa, J Chavers, B O'Leary, D Funk, L Polak, J Crow, R O'Donnell, C Gloeb, B Thomas, S Detrano, R Wong, N Fox, M Kim, L Oudiz, R Weir, G Clark, C D'Agostino, R Espeland, M Klein, B Manolio, T Rand, L Singer, D Stern, M Garvey, WT Lyons, TJ Jenkins, A Klein, R Lopes-Virella, M Virella, G Jaffa, AA Zheng, D Lackland, D McGee, D Mayfield, RK Brabham, M Boright, A Paterson, A Scherere, S Zinman, B Bruznell, J Hokanson, J Marcovina, S Purnell, J Sibley, S Deeb, S Edwards, K Nathan, D TI Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy - The Epidemiology of Diabetes Interventions and Complications (EDIC) study SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID TRIAL; RETINOPATHY; THERAPY; PRODUCTS AB Context The Diabetes Control and Complications Trial (DCCT) demonstrated the benefits of intensive treatment of diabetes in reducing glycemic levels and slowing the progression of diabetic nephropathy. The DCCT cohort has been examined annually for another 8 years as part of the follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. During the EDIC study, glycemic levels no longer differed substantially between the 2 original treatment groups. Objective To determine the long-term effects of intensive vs conventional diabetes treatment during the DCCT on kidney function during the EDIC study. Design, Setting, and Participants Observational study begun in 1993 (following DCCT closeout) in 28 medical centers in the United States and Canada. Participants were 1349 (of 1375) EDIC volunteers who had kidney evaluation at years 7 or 8. Main Outcome Measures Development of microalbuminuria, clinical-grade albuminuria, hypertension, or increase in serum creatinine level. Results Results were analyzed by intention-to-treat analyses, comparing the 2 original DCCT treatment groups. New cases of microalbuminuria occurred during the EDIC study in 39 (6.8%) of the participants originally assigned to the intensive-treatment group vs 87 (15.8%) of those assigned to the conventional-treatment group, for a 59% (95% confidence interval [CI], 39%-73%) reduction in odds, adjusted for baseline values, compared with a 59% (95% Cl, 36%-74%) reduction at the end of the DCCT (P<.001 for both comparisons). New cases of clinical albuminuria occurred in 9 (1.4%) of the participants in the original intensive-treatment group vs 59 (9.4%) of those in the original conventional-treatment group, representing an 84% reduction in odds (95% Cl, 67%-92%), compared with a reduction of 57% (95% Cl, -1% to +81%) at the end of the DCCT. Fewer cases of hypertension (prevalence at year 8, 29.9% vs 40.3%; P<.001) developed in the original intensive-treatment group. Significantly fewer participants reached a serum creatinine level of 2 mg/dL or greater in the intensive-treatment vs the conventional-treatment group (5 vs 19, P=.004), but there were no differences in mean log clearance values. Although small numbers of patients required dialysis and/or transplantation, fewer patients experienced either of these outcomes in the intensive group (4 vs 7, P=36). Conclusions The persistent beneficial effects on albumin excretion and the reduced incidence of hypertension 7 to 8 years after the end of the DCCT suggest that previous intensive treatment of diabetes with near-normal glycemia during the DCCT has an extended benefit in delaying progression of diabetic nephropathy. C1 Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA. Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. Case Western Reserve Univ, Sch Med, Div Clin & Mol Endocrinol, Cleveland, OH USA. Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. RP Nathan, D (reprint author), Massachusetts Gen Hosp, Diabet Unit, 32 Fruit St, Boston, MA 02114 USA. EM dnathan@partners.org RI Pavan, Peter/B-6473-2013; Zinman, Bernard/E-7266-2013 NR 27 TC 523 Z9 533 U1 2 U2 25 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 22 PY 2003 VL 290 IS 16 BP 2159 EP 2167 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 734CB UT WOS:000186036700025 ER PT J AU Reynolds, EE Singer, DE AF Reynolds, EE Singer, DE TI A 60-year-old woman with atrial fibrillation SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HIGH-RISK PATIENTS; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; ANTITHROMBOTIC THERAPY; ORAL ANTICOAGULATION; STROKE PREVENTION; CLINICAL-EXPERIENCE; RANDOMIZED-TRIALS; RHYTHM MANAGEMENT; ASPIRIN THERAPY; MAZE PROCEDURE C1 Massachusetts Gen Hosp, Clin Epidemiol Unit, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Reynolds, EE (reprint author), Massachusetts Gen Hosp, Clin Epidemiol Unit, Div Gen Med, S 50-9, Boston, MA 02114 USA. FU NIA NIH HHS [AG15478] NR 71 TC 4 Z9 4 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 22 PY 2003 VL 290 IS 16 BP 2182 EP 2189 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 734CB UT WOS:000186036700028 PM 14570954 ER PT J AU Sun, T Dong, HL Wu, LZ Kane, M Rowitch, DH Stiles, CD AF Sun, T Dong, HL Wu, LZ Kane, M Rowitch, DH Stiles, CD TI Cross-repressive interaction of the Olig2 and Nkx2.2 transcription factors in developing neural tube associated with formation of a specific physical complex SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Nkx2.2; Olig2; homeodomain; bHLH; neural tube; neuronal subtype specification; oligodendrocyte; interneuron ID PROTEIN-PROTEIN INTERACTIONS; PROGENITOR-CELL IDENTITY; LOOP-HELIX PROTEINS; MOTOR-NEURON; OLIGODENDROCYTE DIFFERENTIATION; HOMEODOMAIN PROTEINS; PRONEURAL GENES; HOMEOBOX GENES; BHLH PROTEINS; EXPRESSION AB In developing neural tube, the basic helix-loop-helix (bHLH) transcription factor Olig2 interacts with the homeodomain transcription factor Nkx2.2 at two distinct stages. During neuronogenesis, a cross-repressive interaction appears to establish the precise boundary between the p3 and pMN domains. At later times, a cooperative interaction is noted because Nkx2.2 promotes maturation of oligodendrocyte progenitor cells specified by expression of Olig2. We show here that the Olig2 protein can form a physical complex with Nkx2.2 protein in mammalian cells and yeast two-hybrid trap assay. This interaction is specific because Olig2 does not bind to a biologically irrelevant homeodomain transcription factor (Nkx6.1), and Nkx2.2 does not interact with a biologically irrelevant bHLH protein (NeuroD). Deletion mapping analysis suggests that formation of an Olig2-Nkx2.2 physical complex is insufficient for the induction of oligodendrocyte progenitors in developing spine; however, the protein-protein interaction observed might be important for the cross-repressive interaction between Olig2 and Nkx2.2 that helps to establish the pMN-p3 boundary in the developing spinal cord. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Rowitch, DH (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NICHD NIH HHS [HD24296]; NINDS NIH HHS [NS4051] NR 32 TC 41 Z9 45 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 22 PY 2003 VL 23 IS 29 BP 9547 EP 9556 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 735HL UT WOS:000186107100008 PM 14573534 ER PT J AU Meyerhardt, JA Catalano, PJ Schrag, D Ayanian, JZ Haller, DG Mayer, RJ Macdonald, JS Benson, AB Fuchs, CS AF Meyerhardt, JA Catalano, PJ Schrag, D Ayanian, JZ Haller, DG Mayer, RJ Macdonald, JS Benson, AB Fuchs, CS TI Association of hospital procedure volume and outcomes in patients with colon cancer at high risk for recurrence SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID ACHIEVING EXCELLENT OUTCOMES; QUALITY-IMPROVEMENT-PROGRAM; ABDOMINAL AORTIC-ANEURYSMS; 8 COMMON OPERATIONS; SURGICAL VOLUME; COLORECTAL RESECTION; SURGEON VOLUME; BREAST-CANCER; MORTALITY; COMORBIDITY AB Background: Studies that use registry data have demonstrated superior long-term overall survival after curative surgical resection of colon cancer at hospitals where the volume of such surgeries is high. However, because such administrative data lack information on cancer recurrence, the true nature of this relation remains uncertain. Objective: To determine whether hospital procedure volume predicts long-term outcomes of colon cancer surgery. Design: Nested cohort study within a randomized clinical trial. Setting: Intergroup 0089 national adjuvant colon cancer study conducted between 1988 and 1992. Patients: 3161 patients with high-risk stage II and stage III colon cancer. Measurements: overall survival and recurrence-free survival, by hospital procedure volume as defined by Medicare claims data. Results: With a median follow-up of 9.4 years, 5-year overall survival significantly differed across tertiles of hospital procedure volume (63.8% for patients who had resection at low-volume hospitals compared with 67.3% at high-volume hospitals; P = 0.04). After adjustment for other predictors of colon cancer outcome, the hazard ratio for overall mortality in patients treated at low-volume centers was 1.16 (95% Cl, 1.03 to 1.32). However, the risk for cancer recurrence was not associated with hospital procedure volume. Five-year recurrence-free survival was 63.9% for patients who had resection at low-volume hospitals compared with 63.0% at high-volume hospitals (adjusted hazard ratio, 1.03 [Cl, 0.89 to 1.18]). These findings did not materially change after stratification by other potential demographic and clinical predictors of outcome. Conclusions: According to prospectively recorded data from a large clinical trial, patients whose colon cancer was resected at low-volume hospitals experienced a higher risk for long-term mortality; however, this increased mortality was not attributable to differences in colon cancer recurrences. C1 Dana Farber Canc Inst, Eastern Cooperat Oncol Grp Stat Ctr, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. St Vincent Clin Canc Ctr, New York, NY USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Northwestern Univ, Chicago, IL 60611 USA. RP Meyerhardt, JA (reprint author), Dana Farber Canc Inst, Eastern Cooperat Oncol Grp Stat Ctr, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [1K07CA097992-01A1] NR 33 TC 86 Z9 88 U1 1 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 21 PY 2003 VL 139 IS 8 BP 649 EP 657 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 734DW UT WOS:000186040800003 PM 14568853 ER PT J AU Braunwald, E AF Braunwald, E TI Application of current guidelines to the management of unstable angina and non-ST-elevation myocardial infarction SO CIRCULATION LA English DT Article DE angina; angioplasty; antioxidants; myocardial infarction; platelets ID ACUTE CORONARY SYNDROMES; PLATELET GLYCOPROTEIN IIB/IIIA; RANDOMIZED CONTROLLED TRIAL; MOLECULAR-WEIGHT HEPARIN; TIMI-III REGISTRY; CARDIAC ISCHEMIC EVENTS; ASSOCIATION TASK-FORCE; LIPID-LOWERING THERAPY; HIGH-RISK PATIENTS; SEGMENT ELEVATION AB Unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI) is a common but heterogeneous disorder with patients exhibiting widely varying risks. Early risk stratification is at the center of the management program and can be achieved using clinical criteria and biomarkers, or a combination. In addition to anti-ischemic therapy and aspirin, the thienopyridine clopidogrel is indicated except in patients who are potential candidates for urgent coronary artery bypass grafting (CABG). Platelet glycoprotein (GP) IIb/IIIa antagonists are indicated in high-risk patients likely to undergo percutaneous coronary intervention (PCI) but are not indicated in the management of lower-risk patients who do not undergo PCI. There is a growing body of evidence to support the substitution of the low-molecular-weight heparin (LMWH) enoxaparin for unfractionated heparin (UFH). Three recent trials have demonstrated the benefit of an early invasive strategy with catheterization followed by revascularization in patients at high and intermediate risk. Lower-risk patients should undergo early noninvasive stress testing. An intensive program of secondary prevention is mandatory and should be begun before hospital discharge. C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Braunwald, E (reprint author), TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. NR 74 TC 38 Z9 41 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 2003 VL 108 IS 16 SU S BP 28 EP 37 DI 10.1161/01.CIR.0000086952.14979.32 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 736WY UT WOS:000186197200005 ER PT J AU Witzke, C Lowe, HC Waldman, H Palacios, IF AF Witzke, C Lowe, HC Waldman, H Palacios, IF TI Transient left ventricular apical ballooning SO CIRCULATION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Cardiac Catheterizat Labs, Div Cardiol, Boston, MA 02144 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Palacios, IF (reprint author), Massachusetts Gen Hosp, Cardiac Catheterizat Labs, Div Cardiol, 55 Fruit St,Bullfinch 105, Boston, MA 02144 USA. NR 0 TC 15 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 21 PY 2003 VL 108 IS 16 BP 2014 EP 2014 DI 10.1161/01.CIR.0000079313.93444.F1 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 734KT UT WOS:000186055600018 PM 14568886 ER PT J AU Jakobs, TC Ben, YX Masland, RH AF Jakobs, TC Ben, YX Masland, RH TI CD15 immunoreactive antacrine cells in the mouse retina SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE CD15; inner plexiform layer; amacrine cells; AMPA glutamate receptors ID AMACRINE CELLS; MAMMALIAN RETINA; RAT RETINA; IMMUNOCYTOCHEMICAL ANALYSIS; SPATIOTEMPORAL EXPRESSION; VERTEBRATE RETINA; GANGLION-CELLS; RABBIT RETINA; LOCALIZATION; DIVERSITY AB The mouse retina has become an important model in vision research, mainly because of the wide availability of transgenic animals. In order to study cell function and connectivity in the inner retina, antibodies that differentially stain one cell type, or a small number of cell types, are helpful as markers. Here we characterize the CD15 (3[alpha1-3]-fucosyl-N-acetyl-lactosamine)-positive cells in the mouse retina using immunofluorescence confocal microscopy and reverse-transcription polymerase chain reaction. CD15 immunoreactivity was observed in two distinct types of amacrine cells and, faintly, in some cone bipolar cells. Type I CD15(+) amacrine cells are GABAergic wide-field cells that stratify in lamina 3 and 4/5 of the inner plexiform layer. Type II CD15(+) amacrine cells are also GABAergic and costratify with the dopaminergic tyrosine hydroxylase-positive cells in lamina 1 of the inner plexiform layer. The densities of types I and II CD15(+) amacrine cells in mid-periphery were 258 cells/mm(2) and 274 cells/mm(2). Double labeling with several other markers for amacrine cell types showed that neither type belongs to another previously identified subpopulation of amacrine cells. Single-cell RT-PCR showed that CD15(+) amacrine cells coexpress several AMPA receptors - GluR1, GluR2, and GluR4 being the most common combination. (C) 2003 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Masland, RH (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, 50 Blossom St,Wellman 429, Boston, MA 02114 USA. NR 31 TC 22 Z9 22 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD OCT 20 PY 2003 VL 465 IS 3 BP 361 EP 371 DI 10.1002/cne.10845 PG 11 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 723JG UT WOS:000185428800004 PM 12966561 ER PT J AU Kim, WS Ordija, CM Freeman, MW AF Kim, WS Ordija, CM Freeman, MW TI Activation of signaling pathways by putative scavenger receptor class A (SR-A) ligands requires CD14 but not SR-A SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE scavenger receptor A; CD14; signal transduction; macrophage; PI3-kinase ID LOW-DENSITY-LIPOPROTEIN; PHOSPHATIDYLINOSITOL 3-KINASE; CHOLESTEROL DEPOSITION; MACROPHAGE RECEPTOR; BINDING-SITE; LDL RECEPTOR; ATHEROSCLEROSIS; PROTEIN; CELLS; RECOGNITION AB Macrophage scavenger class A type I and type 11 receptors (SR-A) are trimeric, integral membrane glycoproteins that bind all unusually broad array of macromolecular ligands. These ligands include modified proteins and lipoproteins, nucleic acids, and a variety of plant and microbial cell wall constituents, such as fucoidan and lipoteichoic acid. Early studies of SR-A functions indicated that the receptors bound, internalized, and degraded their ligands Without provoking any macrophage activating signaling events. More recent studies have provided evidence that several SR-A ligands can activate macrophage gene expression via utilization of a receptor-linked, PI3-kinase pathway. To investigate the role of SR-A in engaging signal transduction events, we employed macrophages taken from mice lacking these receptors. Using either fucoidan or lipoteichoic acid, we confirm that both ligands stimulate tyrosine phosphorylation of PI3-kinase and production of modest levels of the cytokine, TNFalpha. However, macrophages taken from SR-A null mice did not differ from wild type macrophages in these responses, indicating that these signaling events arise independently of SR-A activity. Employing mice lacking CD14, a GPI anchored receptor that binds bacterial lipopolysaccharide and signals via activation of Toll-like receptors, we show that the fucoidan and lipoteichoic acid responses are largely abrogated when CD14 is absent. These data do not provide support for direct SR-A involvement in signal transduction event, and suggest that the early characterization of these receptors as initiators of a non-phlogistic, pathogen clearance pathway was correct. (C) 2003 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Lipid Metab Unit, Boston, MA 02114 USA. RP Freeman, MW (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Lipid Metab Unit, Boston, MA 02114 USA. FU NCRR NIH HHS [RR14466]; NHLBI NIH HHS [HL45098]; NIDDK NIH HHS [DK50305] NR 36 TC 38 Z9 40 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 17 PY 2003 VL 310 IS 2 BP 542 EP 549 DI 10.1016/j.bbrc.2003.09.049 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 731UF UT WOS:000185904300043 PM 14521944 ER PT J AU Matsushita, K Morrell, CN Cambien, B Yang, SX Yamakuchi, M Bao, C Hara, MR Quick, RA Cao, W O'Rourke, B Lowenstein, JM Pevsner, J Wagner, DD Lowenstein, CJ AF Matsushita, K Morrell, CN Cambien, B Yang, SX Yamakuchi, M Bao, C Hara, MR Quick, RA Cao, W O'Rourke, B Lowenstein, JM Pevsner, J Wagner, DD Lowenstein, CJ TI Nitric oxide regulates exocytosis by S-nitrosylation of N-ethylmaleimdide-sensitive factor SO CELL LA English DT Article ID WEIBEL-PALADE BODIES; HUMAN-ENDOTHELIAL-CELLS; VON-WILLEBRAND-FACTOR; MEMBRANE-FUSION; TRANSPORT VESICLES; YEAST VACUOLES; KNOCKOUT MICE; P-SELECTIN; PROTEIN; NSF AB Nitric oxide (NO) inhibits vascular inflammation, but the molecular basis for its anti-inflammatory properties is unknown. We show that NO inhibits exocytosis of Weibel-Palade bodies, endothelial granules that mediate vascular inflammation and thrombosis, by regulating the activity of N-ethylmaleimide-sensitive factor (NSF). NO inhibits NSF disassembly of soluble NSF attachment protein receptor (SNARE) complexes by nitrosylating critical cysteine residues of NSF. NO may regulate exocytosis in a variety of physiological processes, including vascular inflammation, neuro-transmission, thrombosis, and cytotoxic T lymphocyte cell killing. C1 Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Comparat Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Kennedy Krieger Inst, Baltimore, MD 21205 USA. Brandeis Univ, Dept Biochem, Waltham, MA 02454 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Lowenstein, CJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. FU NCRR NIH HHS [RR07002, T32 RR007002]; NHLBI NIH HHS [R01 HL063706, HL074945, K08 HL074945, P01 HL056091, P01 HL056091-100003, P01 HL065608, P01 HL065608-050003, P01 HL56091, P01 HL65608, R01 HL074061, R01 HL074061-04, R01 HL078635, R01 HL078635-04, R01 HL63706-04, R37 HL041002, R37 HL41002] NR 51 TC 269 Z9 286 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 17 PY 2003 VL 115 IS 2 BP 139 EP 150 DI 10.1016/S0092-8674(03)00803-1 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 734DD UT WOS:000186039200006 PM 14567912 ER PT J AU Ubeda, M Habener, JF AF Ubeda, M Habener, JF TI CHOP transcription factor phosphorylation by casein kinase 2 inhibits transcriptional activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENDOPLASMIC-RETICULUM; GENE-TRANSCRIPTION; BUDDING YEAST; PROTEIN; CK2; CHECKPOINT; APOPTOSIS; CHOP/GADD153; CLEAVAGE; GADD153 AB The CAAT/enhancer binding protein homologous transcription factor CHOP, also known as GADD153, is involved in DNA damage, growth arrest, and the induction of apoptosis after endoplasmic reticulum stress and nutrient deprivation. CHOP dimerizes with and inhibits the binding of C/EBP-related transcription factors to their consensus DNA target sequences and also forms novel complexes with other transcriptional proteins ( e. g. c-Jun, c-Fos). The transcriptional activation of these complexes is modified by their phosphorylation. Phosphorylation of CHOP at serine 79 and serine 81 by p38-MAP kinase enhances its transcriptional activity. Here we show that an interactive association between CHOP and casein kinase II (CK2) results in the phosphorylation of its amino-terminal transactivation domain. Mapping of the functional domains of CHOP indicates that the region in CHOP required for association with CK2 differs from that required for its phosphorylation. Th binding of CK2 to CHOP requires only the carboxylterminal bZip domain of CHOP, whereas phosphorylation involves residues located in the amino-terminal domain. The presence of the bZip domain, however, facilitates the phosphorylation of CHOP. Analyses of the effect of point mutations of CHOP on its transcriptional activity and the effect of specific inhibitors of CK2 lead us to conclude that CK2-mediated phosphorylation of CHOP inhibits its transcriptional activity. Our findings suggest that inhibition of the proapoptotic functions of CHOP by CK2 may be a mechanism by which CK2 prevents apoptosis and promotes cellular proliferation. C1 Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Habener, JF (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, WEL320,55 Fruit St, Boston, MA 02114 USA. NR 25 TC 32 Z9 35 U1 1 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 OCT 17 PY 2003 VL 278 IS 42 BP 40514 EP 40520 DI 10.1074/jbc.M306404200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 730TX UT WOS:000185847200012 PM 12876286 ER PT J AU Kinoshita, A Shah, T Tangredi, MM Strickland, DK Hyman, BT AF Kinoshita, A Shah, T Tangredi, MM Strickland, DK Hyman, BT TI The intracellular domain of the low density lipoprotein receptor-related protein modulates transactivation mediated by amyloid precursor protein and Fe65 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIFETIME IMAGING MICROSCOPY; RESONANCE ENERGY-TRANSFER; CARBOXYL-TERMINAL DOMAIN; METHYL-D-ASPARTATE; ALZHEIMERS-DISEASE; ADAPTER PROTEIN; APOE RECEPTOR; BETA-PROTEIN; LRP; COMPLEX AB Low density lipoprotein-related protein (LRP) is a transmembrane receptor, localized mainly in hepatocytes, fibroblasts, and neurons. It is implicated in diverse biological processes both as an endocytic receptor and as a signaling molecule. Recent reports show that LRP undergoes sequential proteolytic cleavage in the ectodomain and transmembrane domain. The latter cleavage, mediated by the Alzheimer-related gamma-secretase activity that also cleaves amyloid precursor protein (APP) and Notch, results in the release of the LRP cytoplasmic domain (LRPICD) fragment. This relatively small cytoplasmic fragment has several motifs by which LRP interacts with various intracellular adaptor and scaffold proteins. However, the function of this fragment is largely unknown. Here we show that the LRPICD is translocated to the nucleus, where it colocalizes in the nucleus with a transcription modulator, Tip60, which is known to interact with Fe65 and with the APP-derived intracellular domain. LRPICD dramatically inhibits APP-derived intracellular domain/Fe65 transactivation mediated by Tip60. LRPICD has a close interaction with Tip60 in the nucleus, as shown by a fluorescence resonance energy transfer assay. These observations suggest that LRPICD has a novel signaling function, negatively impacting transcriptional activity of the APP, Fe65, and Tip60 complex in the nucleus, and shed new light on the function of LRP in transcriptional modulation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Alzheimer Dis Res Lab, Charlestown, MA 02129 USA. Amer Red Cross, Holland Lab, Rockville, MD 20855 USA. RP Hyman, BT (reprint author), Dept Neurol, Alzheimer Unit, 114 16th St,CAGN 2009, Charlestown, MA 02129 USA. FU NIA NIH HHS [P01AG05134, AG12406, AG15379] NR 36 TC 84 Z9 86 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 17 PY 2003 VL 278 IS 42 BP 41182 EP 41188 DI 10.1074/jbc.M306403200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 730TX UT WOS:000185847200095 PM 12888553 ER PT J AU Linseman, DA Bartley, CM Le, SS Laessig, TA Bouchard, RJ Meintzer, MK Li, MT Heidenreich, KA AF Linseman, DA Bartley, CM Le, SS Laessig, TA Bouchard, RJ Meintzer, MK Li, MT Heidenreich, KA TI Inactivation of the myocyte enhancer factor-2 repressor histone deacetylase-5 by endogenous Ca2+/calmodulin-dependent kinase II promotes depolarization-mediated cerebellar granule neuron survival SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; MEF2 TRANSCRIPTION FACTOR; CULTURED HIPPOCAMPAL-NEURONS; INDUCED NEURITE-OUTGROWTH; CENTRAL-NERVOUS-SYSTEM; FACTOR 2C EXPRESSION; MUSCLE FIBER-TYPE; GROWTH-FACTOR-I; CARDIAC-HYPERTROPHY; BRAIN-DEVELOPMENT AB Cerebellar granule neuron (CGN) survival depends on activity of the myocyte enhancer factor-2 (MEF2) transcription factors. Neuronal MEF2 activity is regulated by depolarization via a mechanism that is presently unclear. Here, we show that depolarization-mediated MEF2 activity and CGN survival are compromised by overexpression of the MEF2 repressor histone deacetylase-5 (HDAC5). Furthermore, removal of depolarization induced rapid cytoplasm-to-nuclear translocation of endogenous HDAC5. This effect was mimicked by addition of the calcium/calmodulin-dependent kinase ( CaMK) inhibitor KN93 to depolarizing medium. Removal of depolarization or KN93 addition resulted in dephosphorylation of HDAC5 and its co-precipitation with MEF2D. HDAC5 nuclear translocation triggered by KN93 induced a marked loss of MEF2 activity and subsequent apoptosis. To selectively decrease CaMKII, CGNs were incubated with an antisense oligonucleotide to CaMKIIalpha. This antisense decreased CaMKIIalpha expression and induced nuclear shuttling of HDAC5 in CGNs maintained in depolarizing medium. Selectivity of the CaMKIIalpha antisense was demonstrated by its lack of effect on CaMKIV-mediated CREB phosphorylation. Finally, antisense to CaMKIIalpha induced caspase-3 activation and apoptosis, whereas a missense control oligonucleotide had no effect on CGN survival. These results indicate that depolarization-mediated calcium influx acts through CaMKII to inhibit HDAC5, thereby sustaining high MEF2 activity in CGNs maintained under depolarizing conditions. C1 Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. RP Heidenreich, KA (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pharmacol C236, 4200 E 9th Ave, Denver, CO 80262 USA. RI Bartley, Christopher/G-4226-2012; OI Bartley, Christopher/0000-0002-1391-4130 FU NIGMS NIH HHS [T32 GM007205]; NINDS NIH HHS [NS38619-01A1] NR 59 TC 86 Z9 86 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 OCT 17 PY 2003 VL 278 IS 42 BP 41472 EP 41481 DI 10.1074/jbc.M307245200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 730TX UT WOS:000185847200127 PM 12896970 ER PT J AU Bogan, JS Hendon, N McKee, AE Tsao, TS Lodish, HF AF Bogan, JS Hendon, N McKee, AE Tsao, TS Lodish, HF TI Functional cloning of TUG as a regulator of GLUT4 glucose transporter trafficking SO NATURE LA English DT Article ID 3T3-L1 ADIPOCYTES; INSULIN; PROTEINS; CELLS; COMPARTMENTS; INTERACTS; MEMBRANE; DOMAIN; GENE; P47 AB Insulin stimulates glucose uptake in fat and muscle by mobilizing the GLUT4 glucose transporter. GLUT4 is sequestered intracellularly in the absence of insulin, and is redistributed to the plasma membrane within minutes of insulin stimulation(1,2). But the trafficking mechanisms that control GLUT4 sequestration have remained elusive. Here we describe a functional screen to identify proteins that modulate GLUT4 distribution, and identify TUG as a putative tether, containing a UBX domain, for GLUT4. In truncated form, TUG acts in a dominant-negative manner to inhibit insulin-stimulated GLUT4 redistribution in Chinese hamster ovary cells and 3T3-L1 adipocytes. Full-length TUG forms a complex specifically with GLUT4; in 3T3-L1 adipocytes, this complex is present in unstimulated cells and is largely disassembled by insulin. Endogenous TUG is localized with the insulin-mobilizable pool of GLUT4 in unstimulated 3T3-L1 adipocytes, and is not mobilized to the plasma membrane by insulin. Distinct regions of TUG are required to bind GLUT4 and to retain GLUT4 intracellularly in transfected, non-adipose cells. Our data suggest that TUG traps endocytosed GLUT4 and tethers it intracellularly, and that insulin mobilizes this pool of retained GLUT4 by releasing this tether. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. MIT, Dept Biol, Cambridge, MA 02142 USA. RP Bogan, JS (reprint author), Yale Univ, Sch Med, Dept Internal Med, 333 Cedar St,Box 208020, New Haven, CT 06520 USA. RI Bogan, Jonathan/A-1575-2010 OI Bogan, Jonathan/0000-0001-6463-8466 NR 22 TC 114 Z9 118 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 16 PY 2003 VL 425 IS 6959 BP 727 EP 733 DI 10.1038/nature01989 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 732DA UT WOS:000185924500044 PM 14562105 ER PT J AU Goodman, A Wilbur, DC AF Goodman, A Wilbur, DC TI Case 32-2003: A 37-year-old woman with atypical squamous cells on a Papanicolaou smear - Atypical squamous cells of unknown significance (on the Papanicolaou smear), with a negative test for high-risk human papillomavirus. The patient is currently not at increased risk for cervical cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID UNDETERMINED SIGNIFICANCE; NATURAL-HISTORY; MANAGEMENT; GUIDELINES; CYTOLOGY; WOMEN; TRIAL C1 Massachusetts Gen Hosp, Gillette Ctr Womens Canc, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Cytopathol Div, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Goodman, A (reprint author), Massachusetts Gen Hosp, Gillette Ctr Womens Canc, Boston, MA 02114 USA. NR 15 TC 7 Z9 9 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 OCT 16 PY 2003 VL 349 IS 16 BP 1555 EP 1564 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 731ZM UT WOS:000185916400011 PM 14561799 ER PT J AU Todaro, JF Shen, BJ Niaura, R Spiro, A Ward, KD AF Todaro, JF Shen, BJ Niaura, R Spiro, A Ward, KD TI Effect of negative emotions on frequency of coronary heart disease (The Normative Aging Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID DEPRESSION; MORTALITY; SYMPTOMS; ADULTS; PLASMA; RISK AB Negative emotions, such as depression and anxiety, have been associated with the development of coronary heart disease (CHD). In multivariate models, negative emotions have predicted CHD outcomes, such as nonfatal myocardial infarction and CHD mortality. Few studies, however, have investigated this relation while controlling for variables associated with the metabolic syndrome or those indicative of sympathetic nervous system activity. We prospectively examined the relation between negative emotions and incident CHD in older men (mean 60.3 +/- 7.9 years) participating in the Normative Aging Study (NAS). Four hundred ninety-eight men who completed the Minnesota Multiphasic Personality Inventory (MMPI) and who participated in a subsequent laboratory assessment were included in the study. All men were not on medication and free of diagnosed CHD and diabetes. Negative emotions were measured by the MMPI Welsh A scale, which is comprised of 39 items measuring symptoms of depression and anxiety. Negative emotion score, sociodemographic characteristics, health behaviors, components of the metabolic syndrome, and stress hormones were used to predict incident CHD over a 3-year follow-up period. During follow-up, 45 CHD events were observed. In unadjusted logistic regression analyses, negative emotions significantly predicted the incidence of CHD (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.01 to 1.10, p = 0.02). After adjusting for potential covariates, negative emotions continued to predict the incidence of CHD (OR 1.06, 95% CI 1.01 to 1.12, p = 0.02) A linear, dose-response relation was observed (chi-square 10.8, degree of freedom 2, p = 0.005): participants who had the highest level of negative emotions experienced the greatest incidence of CHD. (C) 2003 by Excerpta Medica, Inc. C1 Miriam Hosp, Providence, RI 02903 USA. Brown Med Sch, Ctr Behav & Prevent Med, Providence, RI 02903 USA. Univ Miami, Dept Psychol, Miami, FL USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. MAVERIC, Boston VA Healthcare Syst, Boston, MA USA. Univ Memphis, Ctr Community Hlth, Memphis, TN 38152 USA. RP Todaro, JF (reprint author), Brown Med Sch, Ctr Behav & Prevent Med, Coro Bldg,Suite 500,1 Hoppin St, Providence, RI 02903 USA. OI Spiro III, Avron/0000-0003-4080-8621 FU NHLBI NIH HHS [5K23 HL004473-02, HL37871]; NIA NIH HHS [AG02287] NR 14 TC 50 Z9 54 U1 0 U2 6 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 OCT 15 PY 2003 VL 92 IS 8 BP 901 EP 906 DI 10.1016/S0002-9149(03)00967-6 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 732DW UT WOS:000185926400001 PM 14556863 ER PT J AU Karha, J Murphy, SA Kirtane, AJ de Lemos, JA Aroesty, JM Cannon, CP Antman, EM Braunwald, E Gibson, CM AF Karha, J Murphy, SA Kirtane, AJ de Lemos, JA Aroesty, JM Cannon, CP Antman, EM Braunwald, E Gibson, CM CA TIMI Study Grp TI Evaluation of the association of proximal coronary culprit artery lesion location with clinical outcomes in acute myocardial infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID TISSUE-PLASMINOGEN-ACTIVATOR; TIMI FRAME COUNT; THROMBOLYTIC THERAPY; REPERFUSION THERAPY; TRIAL; FLOW; ANGIOPLASTY; PREDICTORS; ABCIXIMAB; NECROSIS AB Impaired coronary artery blood flow and left anterior descending (LAD) artery culprit location are angiographic variables that have been associated with poorer outcomes after fibrinolytic administration in patients with acute myocardial infarction (AMI). We hypothesized that culprit lesion location in the proximal portion of the culprit artery would also be associated with poorer clinical outcomes compared with a mid or distal location. Lesion location and clinical outcomes were evaluated in 2,488 patients from the Thrombolysis in Myocardial Infarction (TIMI) 4, 10A, 108, and 14 trials. Proximal lesions were located before or at the first major branch of the parent artery, mid lesions were between the first and the second major branches, and all other lesions were classified as distal. Proximal lesions were associated with a higher incidence of in-hospital death or recurrent AMI compared with mid or distal lesions (10.5% [n = 478] vs 6.1% [n = 1,498] vs 3.7% [n = 511], p <0.001), and they were associated with a higher rate of in-hospital death (6.7% [n = 478] vs 3.2% [n = 1,498] vs 2.5% [n = 511], p = 0.001). In a multiple logistic regression model adjusting for TIMI flow grade, age, gender, and pulse, the planimetered distance from the ostium to the LAD culprit lesion was associated with 30-day death or recurrent AMI (odds ratio 0.79 per centimeter increase in distance down the artery, p = 0.01). Proximal culprit lesion location is associated with an increased risk of adverse outcomes after fibrinolytic administration, which is likely due to a larger area of subtended myocardium. In patients with a LAD culprit lesion, proximal lesion location is a multivariate correlate of adverse outcomes even after adjustment for coronary blood flow and other covariates. (C) 2003 by Excerpta Medica, Inc. C1 Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Texas, SW Med Ctr, Dept Med, Dallas, TX USA. RP Gibson, CM (reprint author), TIMI Data Coordinating Ctr, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. NR 20 TC 37 Z9 39 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 OCT 15 PY 2003 VL 92 IS 8 BP 913 EP 918 DI 10.1016/S0002-9149(03)00969-X PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 732DW UT WOS:000185926400003 PM 14556865 ER PT J AU Bent, S Xu, L Lui, LY Nevitt, M Schneider, E Tian, GQ Guo, SS Cummings, S AF Bent, S Xu, L Lui, LY Nevitt, M Schneider, E Tian, GQ Guo, SS Cummings, S TI A randomized controlled trial of a Chinese herbal remedy to increase energy, memory, sexual function, and quality of life in elderly adults in Beijing, China SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID OLDER ADULTS; MEDICINE; DYSFUNCTION; STRENGTH AB BACKGROUND: Chinese herbal medicines are commonly used to improve general health and well-being despite limited scientific data to support their efficacy. We conducted a randomized, double-blind, placebo-controlled trial to determine whether an herbal remedy that is used widely in China was associated with changes in quality of life, energy, memory, sexual function, and qi (the Chinese concept of "vital energy" that is important in general health). METHODS: Residents (n = 237) of Beijing, China, who were aged greater than or equal to60 years and had self-reported decreased energy, memory, or sexual function, were randomly assigned to take four tablets of a Chinese herbal formula or of an identical placebo, three times a day for 30 days. Patients returned for one follow-up visit after 30 days for assessment of all outcomes. The main outcome measures were changes in quality of life at 30 days as measured by the 12-Item Short Form Health Survey (SF-12) Mental and Physical Component Summary scales. RESULTS: Use of Chinese herbs was associated with a small benefit in the Mental Component scale (difference of 1.9 points; 95% confidence interval [Cl]: 0.1 to 3.6) and no benefit in the Physical Component scale (difference of -0.1 points; 95% CI: -1.7 to 1.5) as compared with placebo. A small improvement in the qi scale was no longer significant after adjusting for baseline differences in this score between groups. There was no improvement in physical performance, memory, or sexual function. The herbal product was well tolerated. CONCLUSION: Short-term use of a mixture of Chinese herbs was associated with a small benefit in one measure of mental health that is of unclear clinical importance. (C) 2003 by Excerpta Medica Inc. C1 Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Osher Ctr Integrat Med, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94121 USA. San Francisco Vet Affairs Med Ctr, Dept Med, San Francisco, CA USA. Univ So Calif, Ethel Percy Andrus Gerontol Ctr, Los Angeles, CA 90089 USA. Beijing Union Med Coll Hosp, Beijing, Peoples R China. RP Bent, S (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Osher Ctr Integrat Med, 4150 Clement St,111A1, San Francisco, CA 94121 USA. FU NCCIH NIH HHS [KO8 AT01338-01] NR 20 TC 12 Z9 12 U1 3 U2 12 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT 15 PY 2003 VL 115 IS 6 BP 441 EP 447 DI 10.1016/S0002-9343(03)00421-2 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 733AX UT WOS:000185978700003 PM 14563500 ER PT J AU Oakes, SA Opferman, JT Pozzan, T Korsmeyer, SJ Scorrano, L AF Oakes, SA Opferman, JT Pozzan, T Korsmeyer, SJ Scorrano, L TI Regulation of endoplasmic reticulum Ca2+ dynamics by proapoptotic BCL-2 family members SO BIOCHEMICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT 5th International Conference on Apoptosis from Signalling Pathways to Therapeutic Tools CY JAN 29-FEB 01, 2003 CL LUXEMBOURG, LUXEMBOURG DE apoptosis; BCL-2; BAX; BAK; endoplasmic reticulum; Ca2+; oxidative stress ID MITOCHONDRIAL PERMEABILITY TRANSITION; CYTOCHROME-C; CELL-DEATH; INDUCED APOPTOSIS; ARACHIDONIC-ACID; BAX; CALCIUM; DYSFUNCTION; CHANNELS; 1,4,5-TRISPHOSPHATE AB Uncontrolled cytosolic Ca2+. overload is a common cause of cell death in several pathological conditions. Recent evidences reveal a more regulated role for intracellular Ca2+ stores in controlling cell death. Proteins of the BCL-2 family include anti- and proapoptotic members that control the mitochondrial amplification loop of apoptosis. The antiapoptotic protein BCL-2 prevents this mitochondrial loop, while the "multidomam" proapoptotic proteins BAX and BAK are crucial to initiate it. BCL-2, BAX and BAK localize also to the endoplasmic reticulum (ER), the main intracellular Ca2+ store. Overexpression of BCL-2 reduces resting ER Ca2+ and death in response to apoptotic stimuli that mobilize Ca. Our recent data indicate that multidomain proapoptotics also influence Ca metabolism. Cells deficient for Bax. Bak (DKO) display lowered steady state ER Ca2+ concentrations ([Ca2+](er)) and secondarily decreased mitochondrial Ca2+ uptake. Genetic and pharmacologic correction of [Ca2+](er) indicates that it controls death in response to Ca2+-dependent, mitochondria utilizing signals such as oxidative stress and lipid mediators; and that it participates in the regulation of the apoptotic response to most intrinsic stimuli, such as staurosporine. Thus, BAX and BAK control apoptosis not only at the mitochondria, but also at the ER. an obligate checkpoint for Ca2+-dependent apoptotic stimuli. (C) 2003 Elsevier Inc. All rights reserved. C1 Venetian Inst Mol Med, Dulbecco Telethon Inst, Padua, Italy. Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol & Med, Boston, MA 02115 USA. Univ Padua, Dept Biomed Sci, I-35100 Padua, Italy. RP Scorrano, L (reprint author), Venetian Inst Mol Med, Dulbecco Telethon Inst, Padua, Italy. RI Scorrano, Luca/A-6652-2008 OI Scorrano, Luca/0000-0002-8515-8928 FU NCI NIH HHS [R37CA50239]; NHLBI NIH HHS [T32HL07627]; Telethon [TCP02016] NR 55 TC 84 Z9 90 U1 0 U2 23 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD OCT 15 PY 2003 VL 66 IS 8 BP 1335 EP 1340 DI 10.1016/S0006-2952(03)00482-9 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 735NB UT WOS:000186120500004 PM 14555206 ER PT J AU Ardissino, D Merlini, PA Bauer, KA Galvani, M Ottani, F Franchi, F Bertocchi, F Rosenberg, RD Mannucci, PM AF Ardissino, D Merlini, PA Bauer, KA Galvani, M Ottani, F Franchi, F Bertocchi, F Rosenberg, RD Mannucci, PM TI Coagulation activation and long-term outcome in acute coronary syndromes SO BLOOD LA English DT Article ID UNSTABLE ANGINA-PECTORIS; PROTEIN-C; MYOCARDIAL-INFARCTION; RECOMBINANT HIRUDIN; THROMBIN GENERATION; HEPARIN; MECHANISM; PRIMATES; COMPLEX; HUMANS AB After an episode of unstable angina or myocardial infarction, a high proportion of patients show biochemical signs of coagulation activation, expressed as persistently elevated thrombin generation, in their blood. it is not known whether this has any influence on long-term outcome. In this prospective multicenter cohort study, we assessed the relation of persistently elevated thrombin generation to outcome in 319 consecutive patients with acute coronary syndromes enrolled in the Global Use of Strategies To Open occluded coronary arteries (GUSTO) IIb trial. Plasma prothrombin fragment 1 + 2 levels, an index of "in vivo" thrombin generation, was measured during the acute phase and after 1, 6, and 12 months, and its relation to outcome was assessed during a median 29-month follow-up period. The primary end point of cardiac death or myocardial (re)infarction occurred in 61 patients (19%). There was a U-shaped relationship between plasma prothrombin fragment 1 + 2 levels and the risk of developing the primary end point; intermediate levels (1.5-1.9 nM) were associated with the lowest risk, whereas both higher (> 1.9 nM) and lower (< 1.5 nM) values were associated with an increased risk (relative risk [RR] 1.56 and 95% confidence interval [CI], 1.25-2.28; RR, 1.35 and 95% CI, 1.11-1.86, respectively). After an episode of acute coronary syndrome, both high and low levels of thrombin generation are predictors of an increased risk of an unfavorable outcome. (C) 2003 by The American Society of Hematology. C1 Univ Parma, Osped Maggiore, Div Cardiol, I-43100 Parma, Italy. Osped Niguarda Ca Granda, Div Cardiol, Milan, Italy. Univ Milan, Osped Maggiore, Angelo Bianchi Bonomi Hemophilia & Thrombosis Ctr, I-20122 Milan, Italy. Univ Milan, Osped Maggiore, IRCCS, Dept Internal Med, I-20122 Milan, Italy. Boston VA Healthcare Syst, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. MIT, Dept Biol, Cambridge, MA USA. Osped Gian Battista Morgagni, Div Cardiol, Forli, Italy. Osped Vicenza, Div Cardiol, Vicenza, Italy. RP Ardissino, D (reprint author), Univ Parma, Osped Maggiore, Div Cardiol, Via Gramsci 14, I-43100 Parma, Italy. RI Mannucci, Pier/C-3102-2014 NR 22 TC 47 Z9 49 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 2003 VL 102 IS 8 BP 2731 EP 2735 DI 10.1182/blood-2002-03-0954 PG 5 WC Hematology SC Hematology GA 731HB UT WOS:000185877300014 PM 12843003 ER PT J AU Marty, FM Lee, SJ Fahey, MM Alyea, EP Soiffer, RJ Antin, JH Baden, LR AF Marty, FM Lee, SJ Fahey, MM Alyea, EP Soiffer, RJ Antin, JH Baden, LR TI Infliximab use in patients with severe graft-versus-host disease and other emerging risk factors of non-Candida invasive fungal infections in allogeneic hematopoietic stem cell transplant recipients: a cohort study SO BLOOD LA English DT Article ID NECROSIS-FACTOR-ALPHA; STEROID-REFRACTORY ACUTE; BONE-MARROW-TRANSPLANTATION; ASPERGILLOSIS; DACLIZUMAB; ANTIBODY; HISTOPLASMOSIS; PREVENTION; CONSENSUS; SURVIVAL AB Acute graft-versus-host disease (GVHD) is a common complication of allogeneic hematopoietic stem cell transplantation (HSCT). It has been proposed that tumor necrosis factor alpha (TNF-alpha) blockade with infliximab may be an effective treatment for severe (grades III-IV) GVHD. We determined if infliximab use in this high-risk population was associated with an additional increased risk of non-Candida invasive fungal infections (IFIs). Records of the 2000-2001 HSCT cohort at our institution were reviewed. Fifty-three (20%) of 264 evaluable patients developed severe GVHD and 11 of these 53 (21%) received infliximab for treatment. Proven or probable IFI was documented in 10 (119%) of 53 patients with severe GVHD (incidence rate of 0.99 cases/11000 GVHD patient-days). When stratified by infliximab use, 5 of 11 infliximab recipients developed an IFI (6.78 cases/1000 GVHD patient-days), compared with 5 of 42 IFI cases among nonrecipients (0.53 cases/11000 GVHD patient-days). In a time-dependent Cox regression model among patients with severe GVHD, the adjusted IFI hazard ratio of infliximab exposure was 13.6(P = .004; 95% Cl, 2.29-80.2). We conclude that infliximab administration is associated with a significantly increased risk of non-Candida IFI in HSCT recipients with severe GVHD disease. Pre-emptive systemic antifungal therapy against molds should be considered in patients who develop severe GVHD after HSCT if infliximab is used. (C) 2003 by The American Society of Hematology. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Hematopoiet Stem Cell Transplantat Serv, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Marty, FM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Infect Dis, 75 Francis St,PBB-A4, Boston, MA 02115 USA. NR 45 TC 123 Z9 127 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 2003 VL 102 IS 8 BP 2768 EP 2776 DI 10.1182/blood-2003-01-0267 PG 9 WC Hematology SC Hematology GA 731HB UT WOS:000185877300020 PM 12855583 ER PT J AU Granucci, F Petralia, F Urbano, M Citterio, S Di Tota, F Santambrogio, L Ricciardi-Castagnoli, P AF Granucci, F Petralia, F Urbano, M Citterio, S Di Tota, F Santambrogio, L Ricciardi-Castagnoli, P TI The scavenger receptor MARCO mediates cytoskeleton rearrangements in dendritic cells and microglia SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; INNATE IMMUNITY; GENE-TRANSFER; IN-VITRO; EXPRESSION; PROTEIN; MACROPHAGES; DIFFERENTIATION; INVOLVEMENT; MATURATION AB Macrophage receptor with collagenous structure (MARCO) is a scavenger receptor expressed in peritoneal macrophages and in a subpopulation of macrophages in the marginal zone of the spleen and in the medullary cord of lymph nodes. By global gene expression analysis, it has been found that the MARCO mRNA was one of the most up-regulated in splenic dendritic cells (DCs) following lipopolysaccharide or bacterial activation and in granulocyte-macrophage colony-stimulating factor (GM-CSF)-treated microglial cells. Here we show that MARCO is expressed on splenic DCs at late time points after activation and that its expression correlates with profound changes in actin cytoskeleton organization in DCs and microglia. During maturation, DCs undergo profound rearrangements of actin cytoskeleton. Immature DCs are adherent with visible actin cables, while fully mature, MARCO-expressing, splenic DCs are nonadherent, round in shape, and have an actin cytoskeleton with a punctate distribution. The simple expression of MARCO was sufficient to induce these cytoskeleton modifications in DCs. MARCO-transfected immature DCs acquired a typical morphology of mature DCs and did not rearrange the actin cytoskeleton following activation. More-over, DCs in which MARCO was knocked down did not reach the mature phenotype and maintained the typical morphology of transitional DCs. MARCO expression in DCs and microglial cells was also associated with a decrease of antigen internalization capacity. Thus, the MARCO receptor is important for actin cytoskeleton rearrangements and the down-regulation of antigen uptake function during DC and microglial cell maturation. (Blood. 2003; 102:2940-2947) (C) 2003 by The American Society of Hematology. C1 Univ Milano Bicocca, Dept Biotechnol & Biosci, I-20126 Milan, Italy. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Ricciardi-Castagnoli, P (reprint author), Univ Milano Bicocca, Dept Biotechnol & Biosci, Piazza Sci 2, I-20126 Milan, Italy. EM paola.castagnoli@unimib.it RI Castagnoli, Paola/E-8288-2010 NR 35 TC 69 Z9 70 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD OCT 15 PY 2003 VL 102 IS 8 BP 2940 EP 2947 DI 10.1182/blood-2002-12-3651 PG 8 WC Hematology SC Hematology GA 731HB UT WOS:000185877300043 PM 12842997 ER PT J AU Battle, TE Frank, DA AF Battle, TE Frank, DA TI STAT1 mediates differentiation of chronic lymphocytic leukemia cells in response to Bryostatin 1 SO BLOOD LA English DT Article ID PROTEIN-KINASE-C; NON-HODGKINS-LYMPHOMA; PHASE-I TRIAL; SIGNAL TRANSDUCER; T-CELLS; B-CELLS; ACTIVATION; APOPTOSIS; EXPRESSION; INTERFERONS AB Bryostatin 1 is known to exhibit in vitro and in vivo activity against chronic lymphocytic leukemia (CLL) cells by inducing their further maturation into plasmalike cells. Signal transducer and activator of transcription (STAT) proteins play a central role in B-lymphocyte growth and function and are aberrantly phosphorylated on serine residues in CLL cells. To determine whether STAT transcription factors are important in Bryostatin 1-induced differentiation of CLL cells, primary CLL cells were examined for signaling events following exposure to Bryostatin 1 in vitro. Western analysis and electrophoretic mobility shift assays revealed that Bryostatin 1 induced tyrosine phosphorylation and DNA binding of STAT1, yet there was no effect on constitutive serine phosphorylation of STAT1. Bryostatin 1-induced STAT1 activation occurred in a manner that was dependent on protein kinase C (PKC), mitogen-activated protein kinase (MAPK), and Janus tyrosine kinase (JAK) activation. Evidence indicates that Bryostatin 1 induces STAT1 activation through an interferon gamma (IFNgamma) autocrine loop. However, STAT1 activation by IFNgamma stimulation alone was not sufficient to induce differentiation. This insufficiency is due to the broader effect on gene expression caused by Bryostatin 1 compared with IFNgamma, as demonstrated by microarray analysis. Both up-regulation of CD22 expression and immunoglobulin M (IgM) production, markers of CLL differentiation, were inhibited by a decoy oligonucleotide for STAT1, indicating that STAT1 is necessary for Bryostatin 1-induced differentiation of CLL cells. This study implicates STAT transcription factors as important mediators of Bryostatin 1-induced differentiation of CLL cells and could possibly lead to improved therapeutic approaches for the treatment of CLL. (Blood. 2003;102: 3016-3024) (C) 2003 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Frank, DA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA81534, CA79547, CA93053] NR 49 TC 37 Z9 37 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 2003 VL 102 IS 8 BP 3016 EP 3024 DI 10.1182/blood-2002-09-2972 PG 9 WC Hematology SC Hematology GA 731HB UT WOS:000185877300053 PM 12855573 ER PT J AU del Carmen, MG Sehdev, AES Fader, AN Zahurak, ML Richardson, M Fruehauf, JP Montz, FJ Bristow, RE AF del Carmen, MG Sehdev, AES Fader, AN Zahurak, ML Richardson, M Fruehauf, JP Montz, FJ Bristow, RE TI Endometriosis-associated ovarian carcinoma - Differential expression of vascular endothelial growth factor and estrogen/progesterone receptors SO CANCER LA English DT Article ID ATYPICAL ENDOMETRIOSIS; LYSOPHOSPHATIDIC ACID; ASCITES-FORMATION; CLEAR-CELL; CANCER; ANGIOGENESIS; P53; PROLIFERATION; PERITONEAL; INHIBITION AB BACKGROUND. Multiple epidemiologic and histologic studies have suggested that ovarian endometriosis can give rise to malignant ovarian tumors, primarily those of epithelial origin. The progression of endometriosis to endometriosis-associated ovarian carcinoma (EAOC) has not been investigated thoroughly and is poorly understood at best. Using immunohistochemical. methods, we compared the differential expression patterns of various cytokines and growth factors in atypical endometriosis (AE) and EAOC. METHODS. Using the Johns Hopkins Pathology Data Bank, tissue blocks from patients diagnosed with EAOC or AE were identified. Tissue blocks were stained for 4 markers: vascular endothelial growth factor (VEGF), Ki-67, estrogen receptor (ER), and progesterone receptor (PR). RESULTS. Seventeen cases of EAOC and 8 cases of AE were identified. Staining for VEGF was documented in 16 of 17 (94%) EAOC tissue blocks and in only 1 of 8 (12.5%) AE tissue blocks (P < 0.0001). Only 4 of the 17 (23%) EAOC tissue blocks exhibited positive staining for ER, compared with 8 of 8 (100%) AE tissue blocks (P = 0.0005). Positive staining for PR was noted in only 6 of 17 (35%) EAOC samples but was present in 8 of 8 (100%) AE samples (P = 0.003). Seventy percent of EAOC samples exhibited positive staining for Ki-67, compared with 37.5% of AE samples (P = 0.19). CONCLUSIONS. EAOC appears to be associated with overexpression of VEGF and reduced expression of both ER and PR. Variations in VEGF expression may be associated with the malignant transformation of endometriosis and may present both diagnostic and therapeutic options for the treatment of ovarian malignancies. (C) 2003 American Cancer Society. C1 Johns Hopkins Univ Hosp, Dept Oncol, Dept Gynecol & Obstet, Kelly Gynecol Oncol Serv, Baltimore, MD USA. Johns Hopkins Univ Hosp, Dept Pathol, Dept Gynecol & Obstet, Div Gynecol Pathol, Baltimore, MD USA. Magee Womens Hosp, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. Johns Hopkins Univ Hosp, Johns Hopkins Oncol Ctr, Dept Biostat, Baltimore, MD USA. Inst Med, Baltimore, MD USA. Oncotech Inc, Irvine, CA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gillette Ctr Womens Canc,Gynecol Oncol Serv, Boston, MA USA. RP del Carmen, MG (reprint author), Gillette Ctr Womens Canc, Gynecol Oncol Serv, Cox 5,100 Blossom St, Boston, MA 02114 USA. EM mdelcar1@jhmi.edu NR 36 TC 22 Z9 22 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD OCT 15 PY 2003 VL 98 IS 8 BP 1658 EP 1663 DI 10.1002/cncr.11714 PG 6 WC Oncology SC Oncology GA 730BR UT WOS:000185809800015 PM 14534882 ER PT J AU Chen, DH Xu, WD Bales, E Colmenares, C Conacci-Sorrell, M Ishii, S Stavnezer, E Campisi, J Fisher, DE Ben-Ze'ev, A Medrano, EE AF Chen, DH Xu, WD Bales, E Colmenares, C Conacci-Sorrell, M Ishii, S Stavnezer, E Campisi, J Fisher, DE Ben-Ze'ev, A Medrano, EE TI SKI activates Wnt/beta-catenin signaling in human melanoma SO CANCER RESEARCH LA English DT Article ID TRANSFORMING-GROWTH-FACTOR; BETA-CATENIN; TRANSCRIPTION FACTOR; LIM-DOMAIN; NEURAL CREST; SMAD PROTEINS; CO-REPRESSOR; TARGET GENE; DNA-BINDING; CELL-LINES AB Overexpression of the oncoprotein SKI correlates with the progression of human melanoma in vivo. SKI is known to curtail the growth inhibitory activity of tumor growth factor beta through the formation of repressive transcriptional complexes with Smad2 and Smad3 at the p21(Waf-1) promoter. Here, we show that SKI also stimulates growth by activating the Wnt signaling pathway. From a yeast two-hybrid screen and immunoprecipitation studies, we identified the protein FHL2/DRAL as a novel SKI binding partner. FHL2, a LIM-only protein, binds beta-catenin and can function as either a transcriptional repressor or activator of the Wnt signaling pathway. SKI enhanced the activation of FHL2 and/or beta-catenin-regulated gene promoters in melanoma cells. Among the SKI targets were microphthalmia-associated transcription factor and Nr-CAM, two proteins associated with melanoma cell survival, growth, motility, and transformation. Transient overexpression of SKI and FHL2 in ski(-/-) melanocytes synergistically enhanced cell growth, and stable overexpression of SKI in a poorly clonogenic human melanoma cell line was sufficient to stimulate rapid proliferation, decreasing the number of cells in the G(1) phase of the cell cycle, and dramatically increasing clonogenicity, colony size and motility. Taken together, these results suggest that by targeting members of the tumor growth factor beta and beta-catenin pathways, SKI regulates crucial events required for melanoma growth, survival, and invasion. C1 Baylor Coll Med, Huffington Ctr Aging, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Dermatol, Houston, TX 77030 USA. Cleveland Clin Fdn, Dept Canc Biol, Cleveland, OH 44195 USA. Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. Riken Tsukuba Inst, Tsukuba, Ibaraki 3050074, Japan. Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USA. Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA 94720 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Medrano, EE (reprint author), Baylor Coll Med, Huffington Ctr Aging, 1 Baylor Plaza M-320, Houston, TX 77030 USA. RI Ishii, Shunsuke/A-5271-2016 FU NCI NIH HHS [CA43600, R01 CA84282]; NIA NIH HHS [AG099909] NR 60 TC 78 Z9 82 U1 1 U2 7 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 OCT 15 PY 2003 VL 63 IS 20 BP 6626 EP 6634 PG 9 WC Oncology SC Oncology GA 737DJ UT WOS:000186213800009 PM 14583455 ER PT J AU Mitsiades, CS Mitsiades, NS Bronson, RT Chauhan, D Munshi, N Treon, SP Maxwell, CA Pilarski, L Hideshima, T Hoffman, RM Anderson, KC AF Mitsiades, CS Mitsiades, NS Bronson, RT Chauhan, D Munshi, N Treon, SP Maxwell, CA Pilarski, L Hideshima, T Hoffman, RM Anderson, KC TI Fluorescence Imaging of multiple myeloma cells in a clinically relevant SCID/NOD in vivo model: Biologic and clinical implications SO CANCER RESEARCH LA English DT Article ID OVERCOMES DRUG-RESISTANCE; NF-KAPPA-B; THERAPEUTIC IMPLICATIONS; BONE-MARROW; ADHESION MOLECULES; PROTEIN EXPRESSION; ORGAN-PREFERENCE; ORTHOTOPIC MODEL; PROSTATE-CANCER; PHAGE DISPLAY AB The in vivo preclinical testing of investigational therapies for multiple myeloma (MM) is hampered by the fact that models generated to recapitulate the development of diffuse skeletal lesions after i.v. injections of tumor cells do not allow for ready detection of the exact site(s) of lesions or for comprehensive monitoring of their progression. We therefore developed an in vivo MM model in severe combined immunodeficient/ nonobese diabetic mice in which diffuse MM lesions developed after tail vein i.v. injection of human RPMI-8226/S MM cells stably transfected with a construct for green fluorescent protein (GFP). Using whole-body real-time fluorescence imaging to detect autofluorescent GFP(+) MM cells (and confirming the sensitivity and specificity of these findings both histologically and by flow cytometric detection of GFP(+) cells), we serially monitored, in a cohort of 75 mice, the development and progression of MM tumors. Their anatomical distribution and pathophysiological manifestations were consistent with the clinical course of MM in human patients, i.e., hallmarked by major involvement of the axial skeleton (e.g., spine, skull, and pelvis) and frequent development of paralysis secondary to spinal lesions without significant tumor spread to lungs, liver, spleen, or kidney. This model both recapitulates the diffuse bone disease of human MM and allows for serial whole-body visualization of its spatiotemporal progression. It therefore provides a valuable in vivo system to elucidate the molecular mechanisms underlying the marked osteotropism of MM, particularly for the axial skeleton, and for assessment of in vivo activity of novel anti-MM therapeutics. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Alberta, Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. Univ Calif San Diego, Dept Surg, San Diego, CA 92111 USA. AntiCanc Inc, San Diego, CA 92111 USA. RP Mitsiades, CS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. RI Maxwell, Christopher/B-3044-2011 OI Maxwell, Christopher/0000-0002-0860-4031 FU PHS HHS [R0-1-50947, P01-78378] NR 51 TC 75 Z9 78 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 OCT 15 PY 2003 VL 63 IS 20 BP 6689 EP 6696 PG 8 WC Oncology SC Oncology GA 737DJ UT WOS:000186213800017 PM 14583463 ER PT J AU Kircher, MF Allport, JR Graves, EE Love, V Josephson, L Lichtman, AH Weissleder, R AF Kircher, MF Allport, JR Graves, EE Love, V Josephson, L Lichtman, AH Weissleder, R TI In vivo high resolution three-dimensional imaging of antigen-specific cytotoxic T-lymphocyte trafficking to tumors SO CANCER RESEARCH LA English DT Article ID CELL THERAPY; TAT PEPTIDE; PROGENITOR CELLS; GENE-THERAPY; STEM-CELLS; TRACKING; CANCER; MIGRATION; MICE; IMMUNOTHERAPY AB Magnetic resonance imaging (MRI) allows noninvasive and three-dimensional visualization of whole organisms over time, and, therefore, would be ideally suited to monitor cell trafficking in vivo. Until now, systemically injected cells had been difficult to visualize by MRI because of relatively inefficient labeling methods. We developed a novel, biocompatible, and physiologically inert nanoparticle (highly derivatized crosslinked iron oxide nanoparticle; CLIO-HD) for highly efficient intracellular labeling of a variety of cell types that now allows in vivo MRI tracking of systemically injected cells at near single-cell resolution. CD8+ cytotoxic T lymphocytes labeled with CLIO-HD were detectable via MRI with a detection threshold of 2 cells/voxel in vitro and similar to3 cells/voxel in vivo in live mice. Using B16-OVA melanoma and CLIO-HD-labeled OVA-specific CD8+ T cells, we have demonstrated for the first time high resolution imaging of T-cell recruitment to intact tumors in vivo. We have revealed the extensive three-dimensional spatial heterogeneity of T-cell recruitment to target tumors and demonstrated a temporal regulation of T-cell recruitment within the tumor. Significantly, our data indicate that serial administrations of CD8+ T cells appear to home to different intratumoral locations, and may, therefore, provide a more effective treatment regimen than a single bolus administration. Together, these results demonstrate that CLIO-HD is uniquely suited for quantitative repetitive MRI of adoptively transferred cells and that this approach may be particularly useful for evaluating novel cell-based therapies in vivo. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Dept Pathol, Div Immunol Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, 13th St,Bldg 149,Room 5403, Charlestown, MA 02129 USA. EM weissleder@helix.mgh.harvard.edu FU NCI NIH HHS [CA96978-01]; NHLBI NIH HHS [HL36028]; NIAID NIH HHS [AI86782-02]; NIGMS NIH HHS [GM64931] NR 52 TC 254 Z9 264 U1 5 U2 33 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 2003 VL 63 IS 20 BP 6838 EP 6846 PG 9 WC Oncology SC Oncology GA 737DJ UT WOS:000186213800035 PM 14583481 ER PT J AU Kim, JH Herlyn, D Wong, KK Park, DC Schorge, JO Lu, KH Skates, SJ Cramer, DW Berkowitz, RS Mok, SC AF Kim, JH Herlyn, D Wong, KK Park, DC Schorge, JO Lu, KH Skates, SJ Cramer, DW Berkowitz, RS Mok, SC TI Identification of epithelial cell adhesion molecule autoantibody in patients with ovarian cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID CARCINOMA-ASSOCIATED ANTIGEN; EP-CAM; COLORECTAL-CARCINOMA; MONOCLONAL-ANTIBODIES; LUNG ADENOCARCINOMA; GENE-EXPRESSION; GLYCOPROTEIN; MARKERS; CDNA; GA733-2 AB The epithelial cell adhesion molecule (Ep-CAM) exhibited an ovarian cancer:normal human ovarian surface epithelium ratio of 444. For validation studies, real-time quantitative PCR analysis and immunohistochemistry were performed in normal and malignant ovarian epithelial cell lines and tissues. To evaluate the potential of the Ep-CAM autoantibody as a tumor marker, we examined the amount of Ep-CAM autoantibody in serum samples obtained from ovarian cancer patients and normal controls by an ELISA. Real-time quantitative PCR analysis revealed significant overexpression of Ep-CAM mRNA in cancer cell lines (P < 0.001) and microdissected cancer tissues (P < 0.05), compared with that in cultured normal human ovarian surface epithelium and microdissected germinal epithelium, respectively. Immunolocalization of the Ep-CAM autoantibody showed that the sera of ovarian cancer patients expressed higher levels of Ep-CAM autoantibody than benign tumor patients and normal controls (P < 0.05). The levels of Ep-CAM autoantibody found were as follows: 0.132 in 52 patients with ovarian cancer, 0.098 in 26 cases with benign gynecologic disease, and 0.090 in 26 normal women. This investigation has shown that the Ep-CAM autoantibody was found to be associated with ovarian cancer and suggested that future research assessing its clinical usefulness would be worthwhile. C1 Harvard Univ, Brigham & Womens Hosp,Sch Med, Lab Gynecol Oncol,Div Gynecol Oncol, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Catholic Univ Korea, Dept Obstet & Gynecol, St Vincent Hosp, Suwon, South Korea. Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Dallas, TX 75390 USA. Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. Dana Farber Harvard Canc Ctr, Gillette Ctr Womens Canc, Boston, MA 02115 USA. RP Mok, SC (reprint author), Harvard Univ, Brigham & Womens Hosp,Sch Med, Lab Gynecol Oncol,Div Gynecol Oncol, Dept Obstet Gynecol & Reprod Biol, 221 Longwood Ave, Boston, MA 02115 USA. OI Wong, Kwong-Kwok/0000-0002-0375-6669 FU NCI NIH HHS [CA86381] NR 35 TC 56 Z9 57 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 15 PY 2003 VL 9 IS 13 BP 4782 EP 4791 PG 10 WC Oncology SC Oncology GA 737CW UT WOS:000186212000017 PM 14581349 ER PT J AU Zorn, KK Jazaeri, AA Awtrey, CS Gardner, GJ Mok, SC Boyd, J Birrer, MJ AF Zorn, KK Jazaeri, AA Awtrey, CS Gardner, GJ Mok, SC Boyd, J Birrer, MJ TI Choice of normal ovarian control influences determination of differentially expressed genes in ovarian cancer expression profiling studies SO CLINICAL CANCER RESEARCH LA English DT Article ID MESSENGER-RNA AMPLIFICATION; EPITHELIAL-CELLS; CDNA MICROARRAY; IN-VITRO; CARCINOMAS; IDENTIFICATION; TELOMERASE; LINES AB Purpose: As with many cancers thought to be of epithelial origin, expression profiling studies of ovarian cancer have relied on a variety of sources of normal cells for comparison with tumors, including whole ovary samples (WO), ovarian surface epithelium (OSE) exposed to short-term culture, and immortalized OSE cell lines (IOSE). Our purpose was to assess the impact of the use of different types of normal controls on the determination of gene expression alterations in ovarian cancer studies. Experimental Design: We compared the gene expression profiles generated on an 11,000-element cDNA microarray of OSE brushings, whole ovary samples, short-term cultures of normal OSE, SV40 large T antigen-immortalized OSE cell lines, and telomerase-immortalized OSE cell lines. The function of the groups as normal controls was then assessed by separate comparisons of each group to a set of 24 serous ovarian carcinoma samples. Results: The normal groups formed robust, distinct clusters in hierarchical clustering and multidimensional scaling. The Pearson correlation coefficient for all combinations of any two of the groups ranged from 0.04 to 0.54, emphasizing the disparity of the groups. In the gene lists produced by comparing each normal group with the ovarian cancer samples, the majority of genes were unique to that normal-cancer comparison, with no gene appearing on all five lists. Conclusions: These results suggest that the selection of a normal control to compare with epithelial ovarian cancer samples in microarray studies strongly influences the genes that are identified as differentially expressed and complicates comparison with studies using a different normal control. C1 NCI, Dept Cell & Canc Biol, NIH, Rockville, MD 20850 USA. NCI, Lab Biosyst & Canc, Ctr Canc Res, NIH, Rockville, MD 20850 USA. Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Harvard Univ, Sch Med, Dana Farber Harvard Canc Ctr, Lab Gynecol Oncol, Boston, MA 02115 USA. RP Birrer, MJ (reprint author), NCI, Dept Cell & Canc Biol, NIH, 9610 Med Ctr Dr,Room 300, Rockville, MD 20850 USA. RI Jazaeri, Amir/A-2400-2008; Jazaeri, Amir/I-3458-2015 OI Jazaeri, Amir/0000-0003-4335-4151 FU NCI NIH HHS [U01 CA88175] NR 32 TC 72 Z9 74 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 15 PY 2003 VL 9 IS 13 BP 4811 EP 4818 PG 8 WC Oncology SC Oncology GA 737CW UT WOS:000186212000020 PM 14581352 ER PT J AU Qin, M Chen, S Yu, T Escuadro, B Sharma, S Batra, RK AF Qin, M Chen, S Yu, T Escuadro, B Sharma, S Batra, RK TI Coxsackievirus adenovirus receptor expression predicts the efficiency of adenoviral gene transfer into non-small cell lung cancer xenografts SO CLINICAL CANCER RESEARCH LA English DT Article ID DEACETYLASE INHIBITOR FR901228; EPITHELIAL-CELLS; APICAL SURFACE; 5 FIBER; THERAPY; ENDOCYTOSIS; INFECTION; EFFICACY; PROTEIN; VIRUSES AB Purpose: Current paradigms postulate that inefficient adenoviral (Ad) gene transfer is a consequence of poor Coxsackievirus adenovirus receptor (CAR) expression in tumors in vivo. To test whether exuberant CAR expression alone is sufficient to mediate efficient Ad gene transfer, we compared Ad gene transfer efficiency in a panel of non-small cell lung cancer (NSCLC) cell model systems in which we systematically measured CAR expression in vitro and in vivo. Experimental Design: NSCLC cells were selected for study on the basis of (a) differences in Ad transduction, (b) identical requirements for growth in vitro, (c) capacity to grow as xenografts in immunocompromised mice, and (d) similar amounts of alpha(nu) integrin expression as measured by flow cytometry. CAR expression and Ad transduction profiles of these NSCLC cells were generated in vitro and in vivo. Results: Ad transduction efficiency of NSCLC cells in vitro can be directly related to CAR expression at both the mRNA and protein level. CAR expression in vitro favorably predicts a comparable pattern of expression in transplanted NSCLC xenografts in vivo. Xenografts generated from NSCLC cells exhibiting increased CAR expression showed of transduction was reduced compared with in vitro measurements. Thus, in NSCLC cells with high basal expression of CAR, Ad vector doses that enabled uniform transduction in vitro achieve a gene transfer efficiency ranging from 10% to 70% after a single intratumoral injection in the xenografts. Conclusions: These studies indicate CAR expression is predictive for more efficient gene transfer into NSCLC cells in vitro and in vivo but is not sufficient to achieve uniform transduction by Group C Ad vectors in vivo. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Lung Canc Res Program, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90073 USA. Vet Adm Greater Los Angeles Hlth Care Syst, Div Pulm & Crit Care Med, Los Angeles, CA 90073 USA. RP Batra, RK (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, 111Q,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NCI NIH HHS [R01 CA078654-02, R01-CA78654]; PHS HHS [1P50-90388] NR 42 TC 28 Z9 34 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 15 PY 2003 VL 9 IS 13 BP 4992 EP 4999 PG 8 WC Oncology SC Oncology GA 737CW UT WOS:000186212000042 PM 14581374 ER PT J AU Hirsch, MS Steigbigel, RT Staszewski, S McMahon, D Fischl, MA Hirschel, B Squires, K DiNubile, MJ Harvey, CM Chen, J Leavitt, RY AF Hirsch, MS Steigbigel, RT Staszewski, S McMahon, D Fischl, MA Hirschel, B Squires, K DiNubile, MJ Harvey, CM Chen, J Leavitt, RY CA Protocol 039 Study Grp TI Long-term efficacy, safety, and tolerability of indinavir-based therapy in protease inhibitor-naive adults with advanced HIV infection SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS-INFECTION; TO-TREAT ANALYSIS; COMBINATION ANTIRETROVIRAL THERAPY; CONTROLLED-TRIAL; ZIDOVUDINE; LAMIVUDINE; MORTALITY; DISEASE AB A double-blind, randomized study of zidovudine-experienced, PI- and lamivudine-naive adults with baseline CD4 cell counts of less than or equal to50 cells/mm(3) had demonstrated that the HIV suppression achieved with zidovudine, lamivudine, and indinavir therapy was superior to that achieved with dual-nucleoside or indinavir-only regimens after 24 weeks of therapy. In a 192-week extension of the study, 371 participants received open-label indinavir with or without other antiretroviral drugs. One hundred and eight subjects were originally randomized to receive triple therapy. After 216 weeks, the proportion of subjects with HIV RNA levels of <500 copies/mL were 34%, according to a general estimating equation analysis, 92%, according to an observed data analysis, and 24%, according to an intention-to-treat analysis counting noncompleters as failures; the proportions of subjects with HIV RNA levels of <50 copies/mL were 31%, 85%, and 22%, respectively. Hyperbilirubinemia ( experienced by 31% of subjects), nausea (17%), abdominal pain (14%), and nephrolithiasis (13%) were the most common drug-related adverse events during the extension. C1 Merck Res Labs, W Point, PA 19486 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. SUNY Stony Brook, Univ Hosp, Stony Brook, NY 11794 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Univ Miami, Sch Med, Coral Gables, FL 33124 USA. Univ Alabama, Birmingham, AL USA. Univ Frankfurt Klinikum, D-6000 Frankfurt, Germany. Hop Cantonal Univ Geneva, Geneva, Switzerland. RP DiNubile, MJ (reprint author), Merck Res Labs, POB 4,BL3-4, W Point, PA 19486 USA. NR 18 TC 13 Z9 13 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 15 PY 2003 VL 37 IS 8 BP 1119 EP 1124 DI 10.1086/378063 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 727TT UT WOS:000185677500018 PM 14523778 ER PT J AU Haiman, CA Stram, DO Pike, MC Kolonel, LN Burtt, NP Altshuler, D Hirschhorn, J Henderson, BE AF Haiman, CA Stram, DO Pike, MC Kolonel, LN Burtt, NP Altshuler, D Hirschhorn, J Henderson, BE TI A comprehensive haplotype analysis of CYP19 and breast cancer risk: the Multiethnic Cohort SO HUMAN MOLECULAR GENETICS LA English DT Article ID FIRST-LINE THERAPY; HUMAN AROMATASE CYTOCHROME-P-450; TISSUE-SPECIFIC EXPRESSION; ENCODING HUMAN AROMATASE; POSTMENOPAUSAL WOMEN; LINKAGE-DISEQUILIBRIUM; HUMAN GENOME; LOS-ANGELES; GENE CYP19; POLYMORPHISM AB The CYP19 gene encodes for aromatase (P450arom), a key steroidogenic enzyme that catalyzes the final step of estrogen biosynthesis. Apart from rare mutations in CYP19 which result in severe phenotypes associated with estrogen insufficiency, little is known about whether common variation in CYP19 is associated with risk of hormone-related diseases. In this study, we employed a haplotype-based approach to search for common disease-associated variants in this candidate breast cancer susceptibility gene among African-American, Hawaiian, Japanese, Latina and White women in the Multiethnic Cohort Study (MEC). We utilized 74 densely spaced single-nucleotide polymorphisms (SNPs) (one every similar to2.6 kb) spanning 189.4 kb of the CYP19 locus to characterize linkage disequilibrium (LD) and haplotype patterns among 69-70 individuals from each ethnic population. We detected four regions of strong LD (blocks 1-4) that were quite closely conserved across populations. Within each block there was a limited diversity of common haplotypes (5 to 10 with a frequency greater than or equal to5%) and most haplotypes were observed to be shared across populations. Twenty-five haplotype-tagging SNPs (htSNPs) were selected to predict the common haplotypes with high probability (average R-h(2)=0.92) and genotyped in a breast cancer case-control study in the MEC (cases, n=1355; controls, n=2580). We first performed global tests for differences in risk according to the common haplotypes and observed significant haplotype-effects in block 2 [P=0.01; haplotypes 2b (OR=1.23; 95% CI, 1.07-1.40), 2d (OR=1.28; 95% CI, 1.01-1.62)]. We also found a common long-range haplotype comprised of block-specific haplotypes 2b and 3c to be associated with increased risk of breast cancer (haplotype 2b-3c: OR=1.31; 95% CI, 1.11-1.54). Our findings suggest the hypothesis that women with the long-range CYP19 haplotype 2b-3c may be carriers of a predisposing breast cancer susceptibility allele. C1 Univ So Calif, Keck Sch Med, USC Norris Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90089 USA. Univ Hawaii, Canc Res Ctr Hawaii, Canc Etiol Program, Honolulu, HI 96813 USA. Whitehead MIT Ctr Genome Res, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Dept Pediat, Boston, MA 02115 USA. RP Haiman, CA (reprint author), Univ So Calif, Keck Sch Med, USC Norris Comprehens Canc Ctr, Dept Prevent Med, 1441 Eastlake Ave,Rm 4441, Los Angeles, CA 90089 USA. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 FU NCI NIH HHS [CA 54281, CA 63464] NR 47 TC 118 Z9 122 U1 0 U2 3 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 OCT 15 PY 2003 VL 12 IS 20 BP 2679 EP 2692 DI 10.1093/hmg/ddg294 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 733RE UT WOS:000186013800011 PM 12944421 ER PT J AU Fromme, E Billings, JA AF Fromme, E Billings, JA TI Care of the dying doctor - On the other end of the stethoscope SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PHYSICIAN-PATIENT; MEDICAL-PRACTICE; ROLE REVERSAL; HEAL THYSELF; PERSPECTIVE; FAMILIES; ANXIETY; SICK; ILLNESS; QUALITY AB The challenges of caring for a dying doctor reflect both common issues in helping the terminally ill and unique problems in working with a physician-patient. The dying doctor must deal with a familiar environment and set of problems from a radically different perspective and must negotiate overlapping and conflicting personal and professional roles. Some of the cardinal virtues of physicians-professional identity, expertise, perfectionism, selflessness, and stoicism-may pose both strengths and liabilities in the patient's role. The treating physicians may also encounter new strains in caring for a colleague. They must guard against both overinvolvement and underinvolvement, and, as with all dying persons, they must serve as a guide through unfamiliar territory for dying patient and family-a companion who is not afraid to listen to or explore the most upsetting matters, a person who can speak frankly when others may be ignoring "the horse on the dining room table." The case of Dr B, an internist dying of myelofibrosis and congestive heart failure, whose son is also a physician, offers the reader the opportunity to reflect on these challenges and to draw lessons about how to best care for fellow physicians at a time of great need. We suggest strategies for negotiating the patient-physician relationship when the patient is also a physician. C1 Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Billings, JA (reprint author), Massachusetts Gen Hosp, Palliat Care Serv, FND 600,55 Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [R25 CA 66818-04, R25 CA 82174-02] NR 84 TC 17 Z9 18 U1 2 U2 6 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 OCT 15 PY 2003 VL 290 IS 15 BP 2048 EP 2055 DI 10.1001/jama.290.15.2048 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 732CX UT WOS:000185924200029 PM 14559959 ER PT J AU Serna, DS Lee, SJ Zhang, MJ Baker, KS Eapen, M Horowitz, MM Klein, JP Rizzo, JD Loberiza, FR AF Serna, DS Lee, SJ Zhang, MJ Baker, KS Eapen, M Horowitz, MM Klein, JP Rizzo, JD Loberiza, FR TI Trends in survival rates after allogeneic hematopoietic stem-cell transplantation for acute and chronic leukemia by ethnicity in the United States and Canada SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Hematol ID BREAST-CANCER SURVIVAL; BONE-MARROW TRANSPLANTATION; RACIAL-DIFFERENCES; RISK-FACTORS; CARDIOVASCULAR MORTALITY; SOCIOECONOMIC-STATUS; MANAGED CARE; HEALTH-CARE; RACE; DISPARITIES AB Purpose: Differences in survival among ethnic groups in the United States are reported in numerous diseases and treatment strategies. Whether survival after allogeneic hematopoietic stem-cell transplantation (HSCT) differs by ethnicity is uncertain. Patients and Methods: Patients (n = 6,443) receiving HLA-identical sibling HSCT for acute or chronic leukemia in the United States or Canada between 1985 and 1999 and reported to the International Bone Marrow Transplant Registry were included. The survival of recipients reported as white, black, Hispanic, or Asian was compared using Cox proportional hazards regression adjusting for other clinical factors. Three 5-year periods were studied to evaluate changes over time. Results: Hispanics compared with whites had lower 1-year (53% v65%; P < .001) and 3-year adjusted survival rates (38% v 53%; P < .001) between 1995 and 1999, the most recent period studied. We failed to find significant differences in survival rates comparing whites with blacks or with Asians in any of the time periods. Overall survival for the entire cohort improved over time, from 56% to 63% at 1 year and from 43% to 51% at 3 years, with greater improvements noted among blacks (45% to 61% at 1 year and 34% to 48% at 3 years). Conclusion: Disparities remain in survival rates between whites and Hispanics despite adjustment for clinical factors. Factors not accounted for in this analysis, such as comorbid disease, socioeconomic status, healthcare access and delivery, and psychosocial and cultural variables, require further prospective study. (C) 2003 by American Society of Clinical Oncology. C1 Med Coll Wisconsin, Int Bone Marrow Transplant Registry, Div Biostat, Hlth Policy Inst, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Div Neoplast Dis & Related Disorders, Dept Internal Med, Milwaukee, WI 53226 USA. Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Univ Minnesota, Pediat Blood & Marrow Transplant Program, Minneapolis, MN USA. RP Loberiza, FR (reprint author), Med Coll Wisconsin, Int Bone Marrow Transplant Registry, Div Biostat, Hlth Policy Inst, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. NR 39 TC 47 Z9 48 U1 2 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 15 PY 2003 VL 21 IS 20 BP 3754 EP 3760 DI 10.1200/JCO.2003.03.133 PG 7 WC Oncology SC Oncology GA 731VH UT WOS:000185906800009 PM 14551294 ER PT J AU Clark, JA Inui, TS Silliman, RA Bokhour, BG Krasnaw, SH Robinson, RA Spaulding, M Talcott, JA AF Clark, JA Inui, TS Silliman, RA Bokhour, BG Krasnaw, SH Robinson, RA Spaulding, M Talcott, JA TI Patients' perceptions of quality of life after treatment for early prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BEAM RADIATION-THERAPY; RADICAL PROSTATECTOMY; VETERANS-HEALTH; OUTCOMES; MEN; RADIOTHERAPY; RELIABILITY; VALIDITY; INDEX AB Purpose: Treatment for early prostate cancer produces problematic physical side effects, but prior studies have found little influence on patients' perceived health status. We examined psychosocial outcomes of treatment for early prostate cancer. Patients and Methods: Patients with previously treated prostate cancer and a reference group of men with a normal prostate-specific antigen (PSA) level and no history of prostate cancer completed questionnaires. Innovative scales assessed behavioral consequences of urinary dysfunction, sexuality, health worry, PSA concern, perceived cancer control, treatment decision making, decision regret, and cancer-related outlook. Urinary, bowel, and sexual dysfunction were assessed with symptom indexes; health status was assessed by the Physical and Mental Summaries of the Short Form (SF-12) Health Survey. Results: Compared with men without prostate cancer, prostate cancer patients reported greater urinary, bowel, and sexual dysfunction, but similar health status. They reported worse problems of urinary control, sexual intimacy and confidence, and masculinity, and greater PSA concern. Perceptions of cancer control and treatment decisions were positive, but varied by treatment: prostatectomy patients indicated the highest and observation patients indicated the lowest cancer control. Bowel and sexual dysfunction were associated with poorer sexual intimacy, masculinity, and perceived cancer control; masculinity and PSA concern were associated with greater confidence in treatment choice; and diminished sexual intimacy and less interest in PSA were associated with greater regret. Conclusion: The lack of change in global measures of health status after treatment for early prostate cancer obscures important influences in men's lives; cancer diagnosis and treatment complications may result in complex outcomes. Aggressive treatment may confer confidence in cancer control, yet be countered by diminished intimate relationships and masculinity, which accompany sexual dysfunction. (C) 2003 by American Society of Clinical Oncology. C1 Boston Univ, Sch Publ Hlth, Dept Hlth Serv, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Harvard Vanguard Med Associates, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Ctr Outcomes Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Edith Nourse Rogers Mem Vet Adm Hosp, Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Regenstrief Inst Hlth Care, Indianapolis, IN 46202 USA. Vet Affairs Med Ctr, Washington, DC 20422 USA. Vet Affairs Western New York Hlth Care Syst, Buffalo, NY USA. SUNY Buffalo, Sch Med, Buffalo, NY 14260 USA. RP Clark, JA (reprint author), Boston Univ, Sch Publ Hlth, Dept Hlth Serv, 715 Albany St,T3-W, Boston, MA 02118 USA. OI Bokhour, Barbara/0000-0001-8238-0745; Clark, Jack/0000-0002-7424-1670 NR 24 TC 110 Z9 112 U1 1 U2 11 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 15 PY 2003 VL 21 IS 20 BP 3777 EP 3784 DI 10.1200/JCO.2003.02.115 PG 8 WC Oncology SC Oncology GA 731VH UT WOS:000185906800012 PM 14551296 ER PT J AU Horton, AC Mahadevan, NR Ruvinsky, I Gibson-Brown, JJ AF Horton, AC Mahadevan, NR Ruvinsky, I Gibson-Brown, JJ TI Phylogenetic analyses alone are insufficient to determine whether genome duplication(s) occurred during early vertebrate evolution SO JOURNAL OF EXPERIMENTAL ZOOLOGY PART B-MOLECULAR AND DEVELOPMENTAL EVOLUTION LA English DT Article ID HUMAN GENE FAMILIES; CEPHALOCHORDATE AMPHIOXUS; CIONA-INTESTINALIS; LARGE-SCALE; CHORDATE; CLUSTER; CHROMOSOMES; INSIGHTS; LAMPREY; HISTORY AB The widely accepted notion that two whole-genome duplications occurred during early vertebrate evolution (the 2R hypothesis) stems from the fact that vertebrates often possess several genes corresponding to a single invertebrate homolog. However the number of genes predicted by the Human Genome Project is less than twice as many as in the Drosophila melanogaster or Caenorhabditis elegans genomes. This ratio could be explained by two rounds of genome duplication followed by extensive gene loss, by a single genome duplication, by sequential local duplications, or by a combination of any of the above. The traditional method used to distinguish between these possibilities is to reconstruct the phylogenetic relationships of vertebrate genes to their invertebrate orthologs; ratios of invertebrate-to-vertebrate counterparts are then used to infer the number of gene duplication events. The lancelet, amphioxus, is the closest living invertebrate relative of the vertebrates, and unlike protostomes such as flies or nematodes, is therefore the most appropriate outgroup for understanding the genomic composition of the last common ancestor of all vertebrates. We analyzed the relationships of all available amphioxus genes to their vertebrate homologs. In most cases, one to three vertebrate genes tire orthologous to each amphioxus gene (median number=2). Clearly this result, and those of previous studies using this approach, cannot distinguish between alternative scenarios of chordate genome expansion. We conclude that phylogenetic analyses alone will never be sufficient to determine whether genome duplication(s) occurred during early chordate evolution, and argue that a "phylogenomic" approach, which compares paralogous clusters of linked genes from complete amphioxus and human genome sequences, will be required if the pattern and process of early chordate genome evolution is ever to be reconstructed. (C) 2003 Wiley-Liss, Inc. C1 Washington Univ, Dept Biol, St Louis, MO 63130 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Gibson-Brown, JJ (reprint author), Washington Univ, Dept Biol, Campus Box 1229,1 Brookings Dr, St Louis, MO 63130 USA. EM gibbro@wustl.edu NR 54 TC 25 Z9 26 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-5007 J9 J EXP ZOOL PART B JI J. Exp. Zool. Part B PD OCT 15 PY 2003 VL 299B IS 1 BP 41 EP 53 DI 10.1002/jez.b.00040 PG 13 WC Evolutionary Biology; Developmental Biology; Zoology SC Evolutionary Biology; Developmental Biology; Zoology GA 729GR UT WOS:000185765400007 PM 14508816 ER PT J AU Boes, M Bertho, N Cerny, J den Brouw, MO Kirchhausen, T Ploegh, H AF Boes, M Bertho, N Cerny, J den Brouw, MO Kirchhausen, T Ploegh, H TI T cells induce extended class II MHC compartments in dendritic cells in a toll-like receptor-dependent manner SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INVARIANT CHAIN DEGRADATION; ANTIGEN PRESENTATION; DEFECTIVE INTERLEUKIN-1; LYSOSOMAL COMPARTMENTS; INFLAMMATORY STIMULI; FAMILY-MEMBER; COMPLEX; TRANSPORT; MYD88; DISTINCT AB Interaction of Ag-loaded dendritic cells with Ag-specific CD4 T cells induces the formation of long tubular class II MHC-positive compartments that polarize toward the T cell. We show involvement of a Toll-like receptor-mediated signal in this unusual form of intracellular class II MHC trafficking. First, wild-type dendritic cells loaded with LPS-free Ag failed to show formation of class II-positive tubules upon Ag-specific T cell engagement, but did so upon supplementation of the Ag with low concentrations of LPS. Second, Ag-loaded myeloid differentiation factor 88 -deficient dendritic cells failed to form these tubules upon interaction with T cells, regardless of the presence of LPS. Finally, inclusion of a cell-permeable peptide that blocks TNFR-associated factor 6 function, downstream of myeloid differentiation factor N, blocked T cell-dependent tubulation. A Toll-like receptor-dependent signal is thus required to allow Ag-loaded dendritic cells to respond to T cell contact by formation of extended endosomal compartments. This activation does not result in massive translocation of class II MHC molecules to the cell surface. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Charles Univ, Fac Sci, Prague, Czech Republic. RP Ploegh, H (reprint author), Harvard Univ, Sch Med, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. RI Cerny, Jan/C-1887-2012 NR 36 TC 52 Z9 53 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 2003 VL 171 IS 8 BP 4081 EP 4088 PG 8 WC Immunology SC Immunology GA 731CC UT WOS:000185866100023 PM 14530329 ER PT J AU Jang, MH Seth, NP Wucherpfennig, KW AF Jang, MH Seth, NP Wucherpfennig, KW TI Ex vivo analysis of thymic CD4 T cells in nonobese diabetic mice with tetramers generated from I-A(97)/class II-associated invariant chain peptide precursors SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLASS-II MHC; A BETA-CHAIN; NOD MICE; STRUCTURAL BASIS; HLA-DM; SUSCEPTIBILITY; BINDING; MELLITUS; MOLECULE; I-A(G7) AB The MHC determines susceptibility and resistance to type 1 diabetes in humans and nonobese diabetic (NOD) mice. To investigate how a disease-associated MHC molecule shapes the T cell repertoire in NOD mice, we generated a series of tetramers from I-A(g7)/class II-associated invariant chain peptide precursors by peptide exchange. No CD4 T cell populations could be identified for two glutamic acid decarboxylase 65 peptides, but tetramers with a peptide in mimetic recognized by the BDC-2.5 and other islet-specific T cell clones labeled a distinct population in the thymus of young NOD mice. Tetramer-positive cells were identified in the immature CD4(+)CD8(low) population that arises during positive selection, and in larger numbers in the more mature CD4(+)CD8(-) population. Tetramer labeling was specific based on the use of multiple control tetramers, including one with a single amino acid analog peptide in which a critical TCR contact residue was substituted. The T cell population was already present in the thymus of 2-wk-old NOD mice before the typical onset of insulitis and was detected in B10 mice congenic for the NOD MHC locus, but not B10 control mice. These results demonstrate that a T cell population can expand in the thymus of NOD mice to levels that are at least two to three orders of magnitude higher than estimated for a given specificity in the naive T cell pool. Based on these data, we propose a model in which I-A(g7) confers susceptibility to type I diabetes by biasing positive selection in the thymus and later presenting peptides from islet autoantigens to such T cells in the periphery. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Room D1410,4 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [P01 AI045757, P01 AI45757] NR 53 TC 31 Z9 33 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 OCT 15 PY 2003 VL 171 IS 8 BP 4175 EP 4186 PG 12 WC Immunology SC Immunology GA 731CC UT WOS:000185866100034 PM 14530340 ER PT J AU Ferrante, RJ Kubilus, JK Lee, J Ryu, H Beesen, A Zucker, B Smith, K Kowall, NW Ratan, RR Luthi-Carter, R Hersch, SM AF Ferrante, RJ Kubilus, JK Lee, J Ryu, H Beesen, A Zucker, B Smith, K Kowall, NW Ratan, RR Luthi-Carter, R Hersch, SM TI Histone deacetylase inhibition by sodium butyrate chemotherapy ameliorates the neurodegenerative phenotype in Huntington's disease mice SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Huntington's disease; therapy; sodium butyrate; histones; transcription; microarray analysis; neuroprotection; R6/2 transgenic mice ID TRANSGENIC MOUSE MODELS; SUBEROYLANILIDE HYDROXAMIC ACID; CREB-BINDING PROTEIN; D-ASPARTATE RECEPTOR; 3-NITROPROPIONIC ACID; EXPANDED POLYGLUTAMINE; OXIDATIVE STRESS; GENE-EXPRESSION; MAP KINASE; CORTICAL-NEURONS AB The precise cause of neuronal death in Huntington's disease (HD) is unknown. Although no single specific protein-protein interaction of mutant huntingtin has emerged as the pathologic trigger, transcriptional dysfunction may contribute to the neurodegeneration observed in HD. Pharmacological treatment using the histone deacetylase inhibitor sodium butyrate to modulate transcription significantly extended survival in a dose-dependent manner, improved body weight and motor performance, and delayed the neuropathological sequelae in the R6/2 transgenic mouse model of HD. Sodium butyrate also increased histone and Specificity protein-1 acetylation and protected against 3-nitropropionic acid neurotoxicity. Microarray analysis showed increased expression of alpha- and beta-globins and MAP kinase phosphatase-1 in sodium butyrate-treated R6/2 mice, indicative of improved oxidative phosphorylation and transcriptional regulation. These findings strengthen the hypothesis that transcriptional dysfunction plays a role in the pathogenesis of HD and suggest that therapies aimed at modulating transcription may target early pathological events and provide clinical benefits to HD patients. C1 Bedford Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Unit 182B, 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. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Serv Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Aging Genet & Neurogenerat, Charlestown, MA 02129 USA. RP Ferrante, RJ (reprint author), Bedford Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Unit 182B, 200 Springs Rd, Bedford, MA 01730 USA. RI Kowall, Neil/G-6364-2012 OI Kowall, Neil/0000-0002-6624-0213 FU NCCIH NIH HHS [AT00613]; NIA NIH HHS [AG12992, AG13846]; NINDS NIH HHS [NS35255] NR 69 TC 414 Z9 429 U1 1 U2 13 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 15 PY 2003 VL 23 IS 28 BP 9418 EP 9427 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 732LT UT WOS:000185948100018 PM 14561870 ER PT J AU Edge, SB Niland, JC Bookman, MA Theriault, RL Ottesen, R Lepisto, E Weeks, JC AF Edge, SB Niland, JC Bookman, MA Theriault, RL Ottesen, R Lepisto, E Weeks, JC TI Emergence of sentinel node biopsy in breast cancer as standard-of-care in academic comprehensive cancer centers SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID OUTCOMES RESEARCH DATABASE; LYMPH-NODE; AXILLARY DISSECTION; DATA-COLLECTION; LYMPHADENECTOMY; MORBIDITY; CARCINOMA; TRIAL; IMPLEMENTATION; VALIDATION AB Background: Ongoing clinical trials are addressing the accuracy and safety of sentinel node biopsy (SNB) in the treatment of breast cancer; however, SNB is already increasingly being used in clinical practice. This study examined the extent and time trends of the use of SNB in stage I and II breast cancer patients. Methods: Clinical data were collected from stage I and II (tumor size less than or equal to5.0 cm) breast cancer patients (n = 3003) who were treated at five comprehensive cancer centers between July 1, 1997, and December 31, 2000. Axillary surgery was classified as SNB alone, SNB + axillary node dissection (AND), AND alone, or none. Patterns of use of axillary surgery were summarized as the percentage of patients receiving each surgery type. The statistical significance of time trends for the use of SNB alone was analyzed by logistic regression models. All statistical tests were two-sided. Results: Overall, SNB alone was used in 13% of patients, SNB + AND in 22%, AND alone in 59%, and no axillary surgery in 6%. Use of SNB alone was statistically significantly associated with breast-conserving surgery of both smaller (less than or equal to2 cm) and larger tumors (2-5 cm) (P<.001 for both associations). For stage I cancer patients treated with breast-conserving surgery (n = 1763), use of SNB increased statistically significantly over the study period, from 8% in 1997 to 9%, 14%, 15%, 22%, 42%, and 58% for the next six consecutive 6-month time intervals, respectively. After controlling for center, age, and comorbidity, the odds ratio for the use of SNB alone was 2.30 (95% confidence interval = 1.88 to 2.82) for each 6-month interval (P<.001). Conclusions: Widespread use of SNB outside the clinical trial setting suggests that oncologists at cancer centers in our study have accepted SNB as standard-of-care for the treatment of breast cancer. This acceptance, if it occurs in other cancer centers and community practice, may affect accrual and generalizability of ongoing clinical trials of SNB. C1 New York State Dept Hlth, Roswell Pk Canc Inst, Buffalo, NY 14263 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Natl Comprehens Canc Network, Rockledge, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Edge, SB (reprint author), New York State Dept Hlth, Roswell Pk Canc Inst, Elm & Carlton Sts, Buffalo, NY 14263 USA. FU NCI NIH HHS [P50CA89393] NR 48 TC 75 Z9 78 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 15 PY 2003 VL 95 IS 20 BP 1514 EP 1521 DI 10.1093/jnci/djg076 PG 8 WC Oncology SC Oncology GA 732BQ UT WOS:000185921300013 PM 14559873 ER PT J AU Yun, SH Boudoux, C Tearney, GJ Bouma, BE AF Yun, SH Boudoux, C Tearney, GJ Bouma, BE TI High-speed wavelength-swept semiconductor laser with a polygon-scanner-based wavelength filter SO OPTICS LETTERS LA English DT Article ID ACOUSTOOPTIC TUNABLE FILTER; FIBER LASER; REFLECTOMETRY AB Ultrahigh-speed tuning of an extended-cavity semiconductor laser is demonstrated. The laser resonator comprises a unidirectional fiber-optic ring, a semiconductor optical amplifier as the gain medium, and a novel scanning filter based on a polygonal scanner. Variable tuning rates up to 1150 nm/ms (15.7-kHz repetition frequency) are demonstrated over a 70-nm wavelength span centered at 1.32 mum. This tuning rate is more than an order of magnitude faster than previously demonstrated and is facilitated in part by self-frequency shifting in the semiconductor optical amplifier. The instantaneous linewidth of the source is <0.1 nm for 9-mW cw output power and a low spontaneous-emission background of -80 dB. (C) 2003 Optical Society of America. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Dept Nucl Engn, Boston, MA 02114 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Boston, MA 02114 USA. RP Yun, SH (reprint author), Harvard Univ, Sch Med, 50 Blossom St,BAR 718, Boston, MA 02114 USA. RI Boudoux, Caroline/A-6399-2012 NR 12 TC 234 Z9 239 U1 0 U2 18 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD OCT 15 PY 2003 VL 28 IS 20 BP 1981 EP 1983 DI 10.1364/OL.28.001981 PG 3 WC Optics SC Optics GA 728ZM UT WOS:000185746300041 PM 14587796 ER PT J AU Jobin, CM Chen, H Lin, AJ Yacono, PW Igarashi, J Michel, T Golan, DE AF Jobin, CM Chen, H Lin, AJ Yacono, PW Igarashi, J Michel, T Golan, DE TI Receptor-regulated dynamic interaction between endothelial nitric oxide synthase and calmodulin revealed by fluorescence resonance energy transfer in living cells SO BIOCHEMISTRY LA English DT Article ID SPHINGOSINE 1-PHOSPHATE; SIGNAL-TRANSDUCTION; PLASMA-MEMBRANE; ENOS ACTIVATION; DUAL ACYLATION; CAVEOLIN; PROTEIN; ENZYME; INHIBITION; INDICATORS AB The endothelial isoform of nitric oxide synthase (eNOS), a key regulator of vascular tone, is activated in endothelial cells by diverse Ca2+-mobilizing agonists, including vascular endothelial growth factor (VEGF). Although the activation state of eNOS and the subcellular localization of the enzyme are both highly regulated, the relationship between enzyme activity and subcellular targeting remains obscure. We aim here to elucidate this relationship by direct dynamic imaging analysis of Ca2+/CaM-dependent eNOS activation in living endothelial cells, using high-resolution confocal microscopy and donor dequenching fluorescence resonance energy transfer (FRET) techniques. Confocal images show a complex pattern of eNOS subcellular distribution; the enzyme is concentrated in both the plasma membrane and internal membranes, with robust expression in the perinuclear region. We construct a fusion protein between eNOS and the FRET-based calcium sensor cameleon, and analyze the temporal and spatial pattern of VEGF-mediated calcium mobilization using donor dequenching FRET methods. We find that VEGF promotes rapid mobilization of intracellular calcium throughout the regions of the cell in which eNOS is distributed. We further create a series of fusion proteins and use FRET imaging methods to study the interactions between eNOS and its obligate allosteric activator protein calmodulin. We clone the FRET acceptor EYFP (enhanced yellow fluorescent protein) at the C-terminus of calmodulin, and the FRET donor ECFP (enhanced cyan fluorescent protein) into eNOS at a site adjacent to its calmodulin-binding domain. FRET imaging analysis of individual endothelial cells cotransfected with eNOS-ECFP and calmodulin-EYFP shows that VEGF induces interactions between eNOS and calmodulin wherever both are present in the cell. Our studies provide evidence that the pool of rapidly responsive receptor-activated eNOS is distributed throughout endothelial cells in both plasma membrane and internal membrane structures, and that this distribution parallels the localization of agonist-induced intracellular Ca2+ changes in the vicinity of eNOS. C1 Harvard Univ, Div Cardiovasc, Brigham & Womens Hosp, Med Sch,Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Div Hematol, Brigham & Womens Hosp, Med Sch,Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Michel, T (reprint author), Harvard Univ, Div Cardiovasc, Brigham & Womens Hosp, Med Sch,Dept Biol Chem & Mol Pharmacol, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL46457, HL15157, HL32854]; NIEHS NIH HHS [T32ES07155]; NIGMS NIH HHS [GM36259] NR 34 TC 19 Z9 20 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 14 PY 2003 VL 42 IS 40 BP 11716 EP 11725 DI 10.1021/bi035066w PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 730DW UT WOS:000185814800018 PM 14529282 ER PT J AU Widstrom, RL Norris, AW Van Der Veer, J Spector, AA AF Widstrom, RL Norris, AW Van Der Veer, J Spector, AA TI Fatty acid-binding proteins inhibit hydration of epoxyeicosatrienoic acids by soluble epoxide hydrolase SO BIOCHEMISTRY LA English DT Article ID ARACHIDONIC-ACID; ENDOTHELIAL-CELLS; CYTOCHROME-P450 METABOLITES; TYROSINE PHOSPHORYLATION; HYPERPOLARIZING FACTORS; P-450 METABOLITES; PATHWAYS; HEART; PHOSPHOLIPIDS; IDENTIFICATION AB Epoxyeicosatrienoic acids (EETs) are potent regulators of vascular homeostasis and are bound by cytosolic fatty acid-binding proteins (FABPs) with K-d values of similar to0.4 muM. To determine whether FABP binding modulates EET metabolism, we examined the effect of FABPs on the soluble epoxide hydrolase (sEH)-mediated conversion of EETs to dihydroxyeicosatrienoic acids (DHETs). Kinetic analysis of sEH conversion of racemic [H-3] 11, 12-EET yielded K-m = 0.45 +/- 0.08 muM and V-max = 9.2 +/- 1.4 mumol min(-1) mg(-1). Rat heart FABP (H-FABP) and rat liver FABP were potent inhibitors of 11,12-EET and 14,15-EET conversion to DHET. The resultant inhibition curves were best described by a substrate depletion model, with K-d = 0.17 +/- 0.01 muM for H-FABP binding to 11,12-EET, suggesting that FABP acts by reducing EET availability to sEH. The EET depletion by FABP was antagonized by the co-addition of arachidonic acid, oleic acid, linoleic acid, or 20-hydroxyeicosatetraenoic acid, presumably due to competitive displacement of FABP-bound EET. Collectively, these findings imply that FABP might potentiate the actions of EETs by limiting their conversion to DHET. However, the effectiveness of this process may depend on metabolic conditions that regulate the levels of competing FABP ligands. C1 Univ Iowa, Coll Med, Dept Biochem, Iowa City, IA 52242 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Widstrom, RL (reprint author), Univ Iowa, Coll Med, Dept Biochem, Iowa City, IA 52242 USA. FU NHLBI NIH HHS [HL49264, HL62984, HL72845]; NIDDK NIH HHS [T32-DK63702] NR 41 TC 25 Z9 26 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 14 PY 2003 VL 42 IS 40 BP 11762 EP 11767 DI 10.1021/bi034971d PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 730DW UT WOS:000185814800023 PM 14529287 ER PT J AU Naghavi, M Libby, P Falk, E Casscells, SW Litovsky, S Rumberger, J Badimon, JJ Stefanadis, C Moreno, P Pasterkamp, G Fayad, Z Stone, PH Waxman, S Raggi, P Madjid, M Zarrabi, A Burke, A Yuan, C Fitzgerald, PJ Siscovick, DS de Korte, CL Aikawa, M Airaksinen, KEJ Assmann, G Becker, CR Chesebro, JH Farb, A Galis, ZS Jackson, C Jang, IK Koenig, W Lodder, RA March, K Demirovic, J Navab, M Priori, SG Rekhter, MD Bahr, R Grundy, SM Mehran, R Colombo, A Boerwinkle, E Ballantyne, C Insull, W Schwartz, RS Vogel, R Serruys, PW Hansson, GK Faxon, DP Kaul, S Drexler, H Greenland, P Muller, JE Virmani, R Ridker, PM Zipes, DP Shah, PK Willerson, JT AF Naghavi, M Libby, P Falk, E Casscells, SW Litovsky, S Rumberger, J Badimon, JJ Stefanadis, C Moreno, P Pasterkamp, G Fayad, Z Stone, PH Waxman, S Raggi, P Madjid, M Zarrabi, A Burke, A Yuan, C Fitzgerald, PJ Siscovick, DS de Korte, CL Aikawa, M Airaksinen, KEJ Assmann, G Becker, CR Chesebro, JH Farb, A Galis, ZS Jackson, C Jang, IK Koenig, W Lodder, RA March, K Demirovic, J Navab, M Priori, SG Rekhter, MD Bahr, R Grundy, SM Mehran, R Colombo, A Boerwinkle, E Ballantyne, C Insull, W Schwartz, RS Vogel, R Serruys, PW Hansson, GK Faxon, DP Kaul, S Drexler, H Greenland, P Muller, JE Virmani, R Ridker, PM Zipes, DP Shah, PK Willerson, JT TI From vulnerable plaque to vulnerable patient - A call for new definitions and risk assessment strategies: Part II SO CIRCULATION LA English DT Review DE coronary disease; plaque; myocardial infarction; atherosclerosis; death, sudden ID CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; SUDDEN CARDIAC DEATH; PROSPECTIVE CARDIOVASCULAR MUNSTER; ACUTE MYOCARDIAL-INFARCTION; MIDDLE-AGED MEN; PRIMARY PREVENTION; ARTERY-DISEASE; CAROTID ATHEROSCLEROSIS; CLINICAL-PRACTICE AB Atherosclerotic cardiovascular disease results in > 19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. ( 2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood ( prone to thrombosis) and vulnerable myocardium ( prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. ( 3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document will focus on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques ( eg, CT and MRI), noninvasive electrophysiological tests ( for vulnerable myocardium), and emerging catheters ( to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients. C1 Univ Texas, Ctr Vulnerable Plaque Res, Texas Heart Inst, Houston, TX USA. Mem Hermann Hosp, President Bush Ctr Cardiovasc Hlth, Houston, TX USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Leducq Ctr Cardiovasc Res,Dept Med, Boston, MA 02115 USA. Aarhus Univ, Inst Expt Clin Res, DK-8000 Aarhus, Denmark. Aarhus Univ, Dept Cardiol, DK-8000 Aarhus, Denmark. Univ Utrecht, Med Ctr, Expt Cardiol Lab, Utrecht, Netherlands. Ohio State Univ, Columbus, OH 43210 USA. Mt Sinai Med Ctr, Zena & Michael A Wiener Cardiovasc Inst, New York, NY 10029 USA. Univ Kentucky, VA Med Ctr, Cardiac Catheterizat Lab, Lexington, KY USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiovasc Div, Boston, MA 02115 USA. Tufts Univ New England Med Ctr, Div Cardiol, Boston, MA 02111 USA. Tulane Univ, Sch Med, Dept Med, Cardiol Sect, New Orleans, LA 70112 USA. Armed Forces Inst Pathol, Dept Cardiovasc Pathol, Washington, DC 20306 USA. Univ Washington, Dept Radiol, Seattle, WA 98195 USA. Stanford Univ, Ctr Med, Stanford, CA 94305 USA. Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. Athens Med Sci, Dept Cardiol, Athens, Greece. Erasmus Univ, Thoraxctr, Catheterizat Lab, NL-3000 DR Rotterdam, Netherlands. Univ Turku, Dept Med, Div Cardiol, SF-20500 Turku, Finland. Hosp Univ Munster, Cent Lab, Inst Arteriosclerosis Res, Munich, Germany. Hosp Univ Munster, Cent Lab, Inst Clin Chem & Lab Med, Munich, Germany. Univ Munster, Dept Clin Radiol, Munich, Germany. Mayo Clin Jacksonville, Sch Med, Jacksonville, FL 32224 USA. Emory Univ, Sch Med, Dept Med, Div Cardiol, Atlanta, GA USA. Univ Bristol, Bristol Heart Inst, Bristol, Avon, England. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Univ Ulm, Dept Internal Med 2, D-7900 Ulm, Germany. Univ Kentucky, Lexington, KY USA. RL Roudebush VA Med Ctr, Indianapolis, IN USA. Univ Texas, Sch Publ Hlth, Houston, TX USA. Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA 90024 USA. Univ Pavia, Fdn Salvatore Maugeri, I-27100 Pavia, Italy. Ann Arbor Labs, Pfizer Global Res & Dev, Dept Cardiovasc Therapeut, Ann Arbor, MI USA. St Agnes HealthCare, Paul Dudley White Coronary Care Syst, Baltimore, MD USA. Univ Texas, Hlth Sci Ctr, Ctr Human Nutr, Dallas, TX 75235 USA. Lenox Hill Hosp, New York, NY 10021 USA. Univ Milan, Osped San Raffaele, Catheterizat Lab, I-20127 Milan, Italy. Emo Ctr Cuore Columbus, Milan, Italy. Inst Mol Med, Ctr Human Genet, Houston, TX USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Minneapolis Heart Inst & Fdn, Minneapolis, MN USA. Univ Maryland, Sch Med, Div Cardiol, Baltimore, MD 21201 USA. Karolinska Inst, Karolinska Hosp, Ctr Mol Med, S-10401 Stockholm, Sweden. Univ Chicago, Cardiol Sect, Chicago, IL 60637 USA. Cedars Sinai Med Ctr, Atherosclerosis Res Ctr, Vasc Physiol & Thrombosis Res Lab, Los Angeles, CA 90048 USA. Univ Hannover, Dept Cardiol, Hannover, Germany. Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. CIMIT, Boston, MA USA. Brigham & Womens Hosp, Div Prevent Med, Div Cardiovasc, Boston, MA 02115 USA. Indiana Univ, Sch Med, Krannert Inst Cardiol, Indianapolis, IN 46202 USA. RP Naghavi, M (reprint author), Assoc Eradicat Heart Attack, POB 20345, Houston, TX 77225 USA. RI Ballantyne, Christie/A-6599-2008; de Korte, Chris/C-1077-2008; Madjid, Mohammad/A-9697-2009; Hansson, Goran/B-7423-2012; Falk, Erling/A-7475-2015; OI de Korte, Chris/0000-0002-1987-6948; Falk, Erling/0000-0001-8566-9974; Zipes, Douglas/0000-0001-7141-6829 NR 62 TC 620 Z9 704 U1 9 U2 58 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 14 PY 2003 VL 108 IS 15 BP 1772 EP 1778 DI 10.1161/01.CIR.0000087481.55887.C9 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 731WH UT WOS:000185909100014 PM 14557340 ER PT J AU Rask-Madsen, C Dominguez, H Ihlemann, N Hermann, T Kober, L Torp-Pedersen, C AF Rask-Madsen, C Dominguez, H Ihlemann, N Hermann, T Kober, L Torp-Pedersen, C TI Tumor necrosis factor-alpha inhibits insulin's stimulating effect on glucose uptake and endothelium-dependent vasodilation in humans SO CIRCULATION LA English DT Article DE tumor necrosis factor; insulin; acetylcholine; blood flow; endothelium-derived factors ID TNF-ALPHA; HUMAN OBESITY; RESISTANCE; MUSCLE; DISEASE; EXPRESSION; VASCULATURE AB Background - Inflammatory mechanisms could be involved in the pathogenesis of both insulin resistance and atherosclerosis. Therefore, we aimed at examining whether the proinflammatory cytokine tumor necrosis factor (TNF)-alpha inhibits insulin-stimulated glucose uptake and insulin-stimulated endothelial function in humans. Methods and Results - Healthy, lean male volunteers were studied. On each study day, 3 acetylcholine (ACh) or sodium nitroprusside (SNP) dose-response studies were performed by infusion into the brachial artery. Before and during the last 2 dose-response studies, insulin and/or TNF-alpha were coinfused. During infusion of insulin alone for 20 minutes, forearm glucose uptake increased by 220 +/- 44%. This increase was completely inhibited during coinfusion of TNF-alpha ( started 10 min before insulin) with a more pronounced inhibition of glucose extraction than of blood flow. Furthermore, TNF-alpha inhibited the ACh forearm blood flow response ( P < 0.001), and this inhibition was larger during insulin infusion (P = 0.01) but not further increased by N-G-monomethyl-L-arginine acetate (P = 0.2). Insulin potentiated the SNP response less than the ACh response and the effect of TNF-α was smaller (P < 0.001); TNF-alpha had no effect on the SNP response without insulin infusion. Thus, TNF-alpha inhibition of the combined response to insulin and ACh was likely mediated through inhibition of NO production. Conclusion - These results support the concept that TNF-alpha could play a role in the development of insulin resistance in humans, both in muscle and in vascular tissue. C1 Joslin Diabet Ctr, Sect Vasc Cell Biol & Complicat, Boston, MA 02215 USA. Bispebjerg Univ Hosp, Dept Cardiol Y, Copenhagen, Denmark. Rigshosp Univ Hosp, Ctr Heart, Copenhagen, Denmark. RP Rask-Madsen, C (reprint author), Joslin Diabet Ctr, Sect Vasc Cell Biol & Complicat, 1 Joslin Pl,Room 4504, Boston, MA 02215 USA. RI Torp-Pedersen, Christian/E-5931-2013; OI DOMINGUEZ, HELENA/0000-0002-7089-2636 NR 24 TC 97 Z9 100 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 14 PY 2003 VL 108 IS 15 BP 1815 EP 1821 DI 10.1161/01.CIR.0000091406.72832.11 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 731WH UT WOS:000185909100022 PM 14530204 ER PT J AU McCabe, K Tyler, K Tanabe, J AF McCabe, K Tyler, K Tanabe, J TI Diffusion-weighted MRI abnormalities as a clue to the diagnosis of herpes simplex encephalitis SO NEUROLOGY LA English DT Editorial Material ID CENTRAL-NERVOUS-SYSTEM; INFECTIONS C1 Univ Colorado, Hlth Sci Ctr, Dept Radiol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Immunol, Denver, CO 80262 USA. Denver VA Med Ctr, Neurol Serv, Denver, CO USA. RP Tanabe, J (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Radiol, Campus Box A034,4200 E 9th Ave, Denver, CO 80262 USA. OI Tyler, Kenneth/0000-0003-3294-5888 NR 7 TC 47 Z9 48 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 OCT 14 PY 2003 VL 61 IS 7 BP 1015 EP 1016 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 731XH UT WOS:000185911400038 PM 14557588 ER PT J AU Hurt, JA Thibodeau, SA Hirsh, AS Pabo, CO Joung, JK AF Hurt, JA Thibodeau, SA Hirsh, AS Pabo, CO Joung, JK TI Highly specific zinc finger proteins obtained by directed domain shuffling and cell-based selection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ARTIFICIAL TRANSCRIPTION FACTORS; DNA-BINDING PROTEINS; CHIMERIC NUCLEASES; RECOGNITION CODE; BUILDING-BLOCKS; IN-VIVO; GENE; SEQUENCE; AFFINITY; COMPLEX AB Engineered Cys(2)His(2) zinc finger proteins (ZFPs) can mediate regulation of endogenous gene expression in mammalian cells. Ideally, all zinc fingers in an engineered multifinger protein should be optimized concurrently because cooperative and context-dependent contacts can affect DNA recognition. However, the simultaneous selection of key contacts in even three fingers from fully randomized libraries would require the consideration of >10(24) possible combinations. To address this challenge, we have developed a novel strategy that utilizes directed domain shuffling and rapid cell-based selections. Unlike previously described methods, our strategy is amenable to scale-up and does not sacrifice combinatorial diversity. Using this approach, we have successfully isolated multifinger proteins with improved in vitro and in vivo function. Our results demonstrate that both DNA binding affinity and specificity are important for cellular function and also provide a general approach for optimizing multidomain proteins. C1 Massachusetts Gen Hosp, Dept Pathol, Div Mol Pathol & Res, Mol Pathol Unit, Charlestown, MA 02129 USA. MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Joung, JK (reprint author), Massachusetts Gen Hosp, Dept Pathol, Div Mol Pathol & Res, Mol Pathol Unit, Charlestown, MA 02129 USA. FU NCI NIH HHS [5T32 CA 09216, T32 CA009216]; NIDDK NIH HHS [K08 DK002883, K08 DK 02883]; NIH HHS [DP1 OD006862] NR 36 TC 96 Z9 104 U1 2 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 14 PY 2003 VL 100 IS 21 BP 12271 EP 12276 DI 10.1073/pnas2135381100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 733WU UT WOS:000186024300062 PM 14527993 ER PT J AU Bacskai, BJ Hickey, GA Skoch, J Kajdasz, ST Wang, YM Huang, GF Mathis, CA Klunk, WE Hyman, BT AF Bacskai, BJ Hickey, GA Skoch, J Kajdasz, ST Wang, YM Huang, GF Mathis, CA Klunk, WE Hyman, BT TI Four-dimensional multiphoton imaging of brain entry, amyloid binding, and clearance of an amyloid-beta ligand in transgenic mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE positron emission tomography; senile plaques; Alzheimer's disease ID ALZHEIMERS-DISEASE; IN-VIVO; PRECURSOR PROTEIN; PLAQUES; MICROSCOPY; DIAGNOSIS; CRITERIA AB The lack of a specific biomarker makes preclinical diagnosis of Alzheimer's disease (AD) impossible, and it precludes assessment of therapies aimed at preventing or reversing the course of the disease. The development of a tool that enables direct, quantitative detection of the amyloid-beta deposits found in the disease would provide an excellent biomarker. This article demonstrates the real-time biodistribution kinetics of an imaging agent in transgenic mouse models of AD. Using multiphoton microscopy, Pittsburgh compound B (PIB) was imaged with sub-mum resolution in the brains of living transgenic mice during peripheral administration. PIB entered the brain quickly and labeled amyloid deposits within minutes. The nonspecific binding was cleared rapidly, whereas specific labeling was prolonged. WT mice showed rapid brain entry and clearance of PIB without any binding. These results demonstrate that the compound PIB has the properties required for a good amyloid-imaging agent in humans with or at risk for AD. C1 Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Dept Neurol, Boston, MA 02129 USA. Univ Pittsburgh, Sch Med, Dept Psychiat & Radiol, Pittsburgh, PA 15213 USA. RP Bacskai, BJ (reprint author), Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Dept Neurol, 114 16th St, Boston, MA 02129 USA. RI Mathis, Chester/A-8607-2009; OI Klunk, William/0000-0001-5512-0251 FU NIA NIH HHS [AG 01039, AG 020570, AG 08487, AG 15453, AG 18402, AG 20226, K02 AG001039, P01 AG015453, R01 AG008487, R01 AG018402, R01 AG020226, R01 AG020570]; NIBIB NIH HHS [R01 EB000768, EB 00768] NR 18 TC 166 Z9 175 U1 1 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 14 PY 2003 VL 100 IS 21 BP 12462 EP 12467 DI 10.1073/pnas.2034101100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 733WU UT WOS:000186024300094 PM 14517353 ER PT J AU Fitten, LJ AF Fitten, LJ TI Driver screening for older adults SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID DEMENTIA C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Sepulveda, CA 91343 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. RP Fitten, LJ (reprint author), Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, VHA 16111 Plummer St, Sepulveda, CA 91343 USA. NR 8 TC 11 Z9 12 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 13 PY 2003 VL 163 IS 18 BP 2129 EP 2131 DI 10.1001/archinte.163.18.2129 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 732GB UT WOS:000185931500003 PM 14557207 ER PT J AU Samarin, S Romero, S Kocks, C Didry, D Pantaloni, D Carlier, MF AF Samarin, S Romero, S Kocks, C Didry, D Pantaloni, D Carlier, MF TI How VASP enhances actin-based motility SO JOURNAL OF CELL BIOLOGY LA English DT Article DE Arp2/3; filament branching; site-directed polymerization; VASP; ActA ID VASODILATOR-STIMULATED PHOSPHOPROTEIN; FILAMENT BARBED ENDS; LISTERIA-MONOCYTOGENES; ENA/VASP PROTEINS; ARP2/3 COMPLEX; FIBROBLAST MOTILITY; TERMINAL DOMAIN; BINDING; POLYMERIZATION; FAMILY AB The function of vasodilator-stimulated phosphoprotein (VASP) in motility is analyzed using a biomimetic motility assay in which ActA-coated microspheres propel themselves in a medium containing actin, the Arp2/3 complex, and three regulatory proteins in the absence or presence of VASP. Propulsion is I inked to cycles of filament barbed end attachment-branching-detachment-growth in which the ActA-activated Arp2/3 complex incorporates at the junctions of branched filaments. VASP increases the velocity of beads. VASP increases branch spacing of filaments in the actin tail, as it does in lamellipodia in living cells. The effect of VASP on branch spacing of Arp2/3-induced branched actin arrays is opposed to the effect of capping proteins. However, VASP does not compete with capping proteins for binding barbed ends of actin filaments. VASP enhances branched actin polymerization only when ActA is immobilized on beads or on Listeria. VASP increases the rate of dissociation of the branch junction from immobilized ActA, which is the rate-limiting step in the catalytic cycle of site-directed filament branching. C1 CNRS, Lab Enzymol & Biocim Struct, F-91198 Gif Sur Yvette, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Carlier, MF (reprint author), CNRS, Lab Enzymol & Biocim Struct, Ave Terrasse, F-91198 Gif Sur Yvette, France. NR 47 TC 110 Z9 113 U1 1 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD OCT 13 PY 2003 VL 163 IS 1 BP 131 EP 142 DI 10.1083/jcb.200303191 PG 12 WC Cell Biology SC Cell Biology GA 732QJ UT WOS:000185956800012 PM 14557252 ER PT J AU Cao, C Leng, YM Huang, W Liu, X Kufe, D AF Cao, C Leng, YM Huang, W Liu, X Kufe, D TI Glutathione peroxidase 1 is regulated by the c-Abl and Arg tyrosine kinases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OXIDATIVE STRESS-RESPONSE; DEPENDENT PROTEIN-KINASE; GLUTATHIONE-PEROXIDASE; SUPEROXIDE-DISMUTASE; CELLULAR-RESPONSE; ACTIVATION; CELLS; MICE; SUSCEPTIBILITY; SENSITIVITY AB The c-Abl and Arg tyrosine kinases are activated in the cellular response to oxidative stress. The present studies demonstrate that c-Abl and Arg associate with glutathione peroxidase 1 (GPx1) and that this interaction is regulated by intracellular oxidant levels. The c-Abl and Arg SH3 domains bind directly to a proline-rich site in GPx1 at amino acids 132 - 145. GPx1 also functions as a substrate for c-Abl- and Arg-mediated phosphorylation on Tyr-96. The results further show that c-Abl and Arg stimulate GPx activity and that these kinases contribute to GPx-mediated protection of cells against oxidative stress. Our findings provide the first evidence that GPx1 is regulated by a signaling pathway that is activated in the oxidative stress response. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Beijing Inst Technol, Beijing 100850, Peoples R China. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA42802, CA98626] NR 23 TC 81 Z9 85 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 10 PY 2003 VL 278 IS 41 BP 39609 EP 39614 DI 10.1074/jbc.M305770200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 728JJ UT WOS:000185713800044 PM 12893824 ER PT J AU Yahata, Y Shirakata, Y Tokumaru, S Yamasaki, K Sayama, K Hanakawa, Y Detmar, M Hashimoto, K AF Yahata, Y Shirakata, Y Tokumaru, S Yamasaki, K Sayama, K Hanakawa, Y Detmar, M Hashimoto, K TI Nuclear translocation of phosphorylated STAT3 is essential for vascular endothelial growth factor-induced human dermal microvascular endothelial cell migration and tube formation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR TYROSINE KINASE; SIGNAL-TRANSDUCTION; EMBRYONIC LETHALITY; FACTOR VEGF; MAP KINASE; VASCULOGENESIS; ANGIOGENESIS; ACTIVATION; GENE; IDENTIFICATION AB Vascular endothelial growth factor (VEGF) is a potent, multifunctional, endothelial-cell-specific growth factor. It stimulates proliferation and migration of endothelial cells. Characterization of intracellular signal transduction after VEGF and VEGF receptor (VEGFR) interaction has demonstrated the involvement of the mitogen-activated protein kinase pathway. However, several studies indicated that signal transducers and activators of transcription (STAT) is another important pathway downstream of VEGF/VEGFR interaction. Therefore, we studied the role of STAT3 in the migration and tube formation of the human dermal microvascular endothelial cells (HDMEC). HDMEC expressed phosphorylated forms of STAT1, STAT3, and STAT5, and a marked increase of phosphorylated STAT3 in the nuclear fraction after addition of VEGF was observed by Western blot and immunohistochemical staining. To verify the functional implication of STAT3 phosphorylation in HDMEC migration, we introduced a dominant-negative STAT3 using adenovirus vector system. Dominant-negative STAT3 abolished the VEGF-induced nuclear translocation of phosphorylated STAT3 and inhibited HDMEC migration completely. Dominant-negative STAT3 also suppressed VEGF-induced HDMEC tube formation on Matrigel and on collagen gel. These data demonstrate that STAT3 and its phosphorylation are involved in the downstream pathway of VEGF/VEGFR interaction and regulate VEGF-induced HDMEC migration and tube formation. C1 Ehime Univ, Sch Med, Dept Dermatol, Onsen, Ehime 7910295, Japan. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Shirakata, Y (reprint author), Ehime Univ, Sch Med, Dept Dermatol, Onsen, Ehime 7910295, Japan. NR 43 TC 110 Z9 124 U1 1 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 10 PY 2003 VL 278 IS 41 BP 40026 EP 40031 DI 10.1074/jbc.M301866200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 728JJ UT WOS:000185713800092 PM 12874294 ER PT J AU Xiang, SH Wang, LP Abreu, M Huang, CC Kwong, PD Rosenberg, E Robinson, JE Sodroski, J AF Xiang, SH Wang, LP Abreu, M Huang, CC Kwong, PD Rosenberg, E Robinson, JE Sodroski, J TI Epitope mapping and characterization of a novel CD4-induced human monoclonal antibody capable of neutralizing primary HIV-1 strains SO VIROLOGY LA English DT Article DE human immunodeficiency virus (HIV-1); primary HIV-1 isolates; CD4-induced (CD4i) antibodies; neutralizing antibodies; epitope mapping; human monoclonal antibody E51; structured treatment interruption (STI); soluble CD4 (sCD4); envelope glycoprotein (gp120) ID HUMAN-IMMUNODEFICIENCY-VIRUS; GP120 ENVELOPE GLYCOPROTEIN; CD4 BINDING-SITE; PASSIVE IMMUNOTHERAPY; SYNERGISTIC NEUTRALIZATION; TYROSINE SULFATION; RECEPTOR-BINDING; TYPE-1; INFECTION; CCR5 AB Human immunodeficiency virus (HIV-1) enters target cells by binding its gp120 exterior envelope glycoprotein to CD4 and one of the chemokine receptors, CCR5 or CXCR4. CD4-induced (CD4i) antibodies bind gp120 more efficiently after CD4 binding and block the interaction with the chemokine receptor. Examples of CD4i antibodies are limited, and the prototypes of the CD4i antibodies exhibit only weak neutralizing activity against primary, clinical HIV-1 isolates. Here we report the identification of a novel antibody, E51, that exhibits CD4-induced binding to gp120 and neutralizes primary HIV-1 more efficiently than the prototypic CD4i antibodies. The E51 antibody blocks the interaction of gp120-CD4 complexes with CCR5 and binds to a highly conserved, basic gp120 element composed of the beta19-strand and surrounding structures. Thus, on primary HIV-1 isolates, this gp120 region, which has been previously implicated in chemokine receptor binding, is accessible to a subset of CD4i antibodies. (C) 2003 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div Aids, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr,Div Aids, Boston, MA 02115 USA. Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70012 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,Jimmy Fund Bldg,Room 824, Boston, MA 02115 USA. FU NIAID NIH HHS [AI28691, AI31783, AI39420, AI24755, AI41851] NR 68 TC 58 Z9 60 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD OCT 10 PY 2003 VL 315 IS 1 BP 124 EP 134 DI 10.1016/S0042-6822(03)00521-X PG 11 WC Virology SC Virology GA 739YE UT WOS:000186373700012 PM 14592765 ER PT J AU McIntire, JJ Umetsu, SE Macaubas, C Hoyte, EG Cinnioglu, C Cavalli-Sforza, LL Barsh, GS Hallmayer, JF Underhill, PA Risch, NJ Freeman, GJ DeKruyff, RH Umetsu, DT AF McIntire, JJ Umetsu, SE Macaubas, C Hoyte, EG Cinnioglu, C Cavalli-Sforza, LL Barsh, GS Hallmayer, JF Underhill, PA Risch, NJ Freeman, GJ DeKruyff, RH Umetsu, DT TI Hepatitis A virus link to atopic disease SO NATURE LA English DT Editorial Material ID HAY-FEVER; INFECTION; MARKERS C1 Stanford Univ, Dept Pediat, Div Immunol & Allergy, Stanford, CA 94305 USA. Stanford Univ, Dept Genet, Stanford, CA 94305 USA. Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Harvard Univ, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP McIntire, JJ (reprint author), Stanford Univ, Dept Pediat, Div Immunol & Allergy, Stanford, CA 94305 USA. RI Jones, Jennifer/C-8691-2015 OI Jones, Jennifer/0000-0002-9488-7719 NR 10 TC 150 Z9 164 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 9 PY 2003 VL 425 IS 6958 BP 576 EP 576 DI 10.1038/425576a PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 729XU UT WOS:000185801000026 PM 14534576 ER PT J AU Zhang, YJ Finegold, MJ Porteu, F Kanteti, P Wu, MX AF Zhang, YJ Finegold, MJ Porteu, F Kanteti, P Wu, MX TI Development of T-cell lymphomas in E mu-IEX-1 mice SO ONCOGENE LA English DT Article DE IEX-1; antiapoptosis; T-cell lymphoma; transgenic mice ID IMMEDIATE-EARLY GENE; NF-KAPPA-B; P53 TUMOR-SUPPRESSOR; EARLY-RESPONSE GENE; TRANSGENIC MICE; PROTEIN EXPRESSION; IEX-1; APOPTOSIS; SURVIVAL; BCL-2 AB Inhibition of apoptosis or abnormal cell survival can result in tumorigenesis by facilitating the insurgence of various mutations. Immediate-early response gene X-1 (IEX-1), protects T cells from apoptosis induced by the ligation of Fas or the T-cell receptor (TCR)/CD3 complex in Emu-IEX-1 mice that direct the gene expression in both T and B cell lineages under the control of the Emu enhancer. Consistent with a biased effect of IEX-1 towards T cells, Emu-IEX-1 mice selectively developed T-cell lymphomas in the spleen, when they aged, which may be associated with increased levels of IEX-1 phosphorylation in T cells compared to B cells. The lymphomas were single positive (CD4(+)CD8(-), CD4(-)CD8(+)), double positive (CD4(+)CD8(-)), or double negative (CD4(-)CD8(-)) T cells. They resulted from aberrantly clonal expansions of T cells expressing a specific TCR, as suggested by the TCR repertoire analysis using a panel of monoclonal antibodies recognizing TCR Vbeta chain, as well as by TCR beta gene rearrangements. The study provides, for the first time, unambiguous evidence of the oncogenic potential of IEX-1 in a cell-specific manner. The animal model may help our understanding of peripheral T-cell lymphoma development. C1 Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Boston Univ, Med Ctr, Dept Mol & Cell Biol, Boston, MA 02118 USA. Inst Cochin Genet Mol, Dept Hematol, INSERM, U567,CNRS,UMR 8104, F-75014 Paris, France. Univ Illinois, Dept Microbiol & Immunol, Chicago, IL 60612 USA. RP Wu, MX (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol, 50 Blossom St,Wellman 224, Boston, MA 02114 USA. RI PORTEU, Francoise/I-8445-2016 OI PORTEU, Francoise/0000-0002-2403-4163 FU NIAID NIH HHS [AI45003] NR 37 TC 26 Z9 28 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 9 PY 2003 VL 22 IS 44 BP 6845 EP 6851 DI 10.1038/sj.onc.1206707 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 730RH UT WOS:000185843400004 PM 14534530 ER PT J AU Shah, K Tang, Y Breakefield, X Weissleder, R AF Shah, K Tang, Y Breakefield, X Weissleder, R TI Real-time imaging of TRAIL-induced apoptosis of glioma tumors in vivo SO ONCOGENE LA English DT Article DE TRAIL; bioluminescence; apoptosis ID ANTITUMOR-ACTIVITY; LIGAND TRAIL; CELL-DEATH; DECOY RECEPTORS; GENE-EXPRESSION; CANCER-THERAPY; APO-2 LIGAND; VECTORS; MICE; APO2L/TRAIL AB Tumor necrosis factor-related apoptosis-inducing ligand ( TRAIL) has been shown to induce apoptosis in neoplastic cells. While many previous studies have been performed in cell culture, the delivery and efficiency of TRAIL variants in vivo is less well established. Using dual substrate/reporter bioluminescence imaging (Fluc: firefly luciferase - luciferin and Rluc: Renilla luciferase - coelenterazine), we tested the efficacy of TRAIL using replication deficient herpes simplex virus (HSV) type 1 amplicon vectors in gliomas. The cDNA for complete TRAIL and the extracellular domain of TRAIL (aa 114 - 281) were cloned into HSV amplicons and packaged into helper virus-free vectors. Both forms of TRAIL induced similar degrees of apoptosis in human glioma cells (Gli36) in culture within 24 h of infection with TRAIL amplicon vectors. Growth of tumors stably transfected with Fluc (Gli36fluc(+)) was readily monitored in vivo by bioluminescence imaging following luciferin administration. HSV amplicon vectors bearing the genes for TRAIL and Rluc injected directly into Gli36fluc(+)-expressing subcutaneous gliomas revealed peak Rluc activity 36 h after intratumoral injection as determined by coelenterazine injection followed by imaging. TRAIL-treated gliomas regressed in size over a period of 4 weeks as compared to the mock-injected gliomas. These results show the efficacy of vector delivered TRAIL in treating tumors in vivo and offer a unique way to monitor both gene delivery and efficacy of TRAIL-induced apoptosis in tumors in vivo in real time by dual enzyme substrate (Rluc/Fluc) imaging. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Mol Neurogenet Unit, Boston, MA USA. RP Shah, K (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,Room 5421, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA6924, P50 CA86335, R24-CA92782] NR 40 TC 94 Z9 100 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 9 PY 2003 VL 22 IS 44 BP 6865 EP 6872 DI 10.1038/sj.onc.1206748 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 730RH UT WOS:000185843400007 PM 14534533 ER PT J AU Harris, JP Weisman, MH Derebery, JM Espeland, MA Gantz, BJ Gulya, AJ Hammerschlag, PE Hannley, M Hughes, GB Moscicki, R Nelson, RA Niparko, JK Rauch, SD Telian, SA Brookhouser, PE AF Harris, JP Weisman, MH Derebery, JM Espeland, MA Gantz, BJ Gulya, AJ Hammerschlag, PE Hannley, M Hughes, GB Moscicki, R Nelson, RA Niparko, JK Rauch, SD Telian, SA Brookhouser, PE TI Treatment of corticosteroid-responsive autoimmune inner ear disease with methotrexate - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RHEUMATOID-ARTHRITIS; INFLIXIMAB; EFFICACY; THERAPY AB Context A number of therapies have been proposed for the long-term management of corticosteroid-responsive, rapidly progressive, bilateral sensorineural hearing loss (autoimmune inner ear disease [AIED]). Methotrexate has emerged as the benchmark agent but has not been rigorously evaluated for hearing improvement in patients with AIED. Objective To assess the efficacy of long-term methotrexate in maintaining hearing improvements achieved with glucocorticoid (prednisone) therapy in patients with AIED. Design, Setting, and Participants A randomized, double-blind, placebo-controlled trial conducted from February 3, 1998, to November 5, 2001, of 67 patients with rapidly progressive, bilateral sensorineural hearing loss at 10 tertiary care centers in the United States. Intervention Randomization to either oral methotrexate (15 to 20 mg/wk; n=33) or placebo (n=34), in combination with an 18-week prednisone taper. Follow-up examinations, including audiometric evaluation, were performed at 4, 8,12, 24, 36, 48, and 52 weeks, or until hearing loss was documented. Main Outcome Measure Maintenance of hearing improvement achieved from prednisone treatment. Results Sixty-seven patients (57.8%) enrolled in the prednisone challenge experienced hearing improvement. Twenty-five patients (37%) experienced hearing improvements in both ears. Of the individuals who reached study end points, 24 (80%) of 30 end points were because of measured hearing loss in the methotrexate group and 29 (93.5%) of 31 end points were because of measured hearing loss in the placebo group (P=.15). Methotrexate was no more effective than placebo in maintaining the hearing improvement achieved with prednisone treatment (hazard ratio, 1.31 95% confidence, interval, 0.79-2.17; P=30). Conclusion Methotrexate does not appear to be effective in maintaining the hearing improvement achieved with prednisone therapy in patients with AIED. C1 Univ Calif San Diego, Div Otolaryngol Head & Neck Surg, San Diego, CA 92103 USA. Cedars Sinai Med Ctr, Div Rheumatol, Los Angeles, CA 90048 USA. House Ear Res Inst, Los Angeles, CA USA. Wake Forest Univ, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. Univ Iowa, Dept Otolaryngol Head & Neck Surg, Iowa City, IA 52242 USA. Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA. NYU, Dept Otolaryngol Head & Neck Surg, New York, NY USA. Amer Acad Otolaryngol Head & Neck Surg, Res Dev, Alexandria, VA USA. Cleveland Clin, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Dept Allergy & Immunol, Boston, MA 02114 USA. Johns Hopkins Univ, Dept Otolaryngol, Baltimore, MD USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Univ Michigan, Dept Otolaryngol Head & Neck Surg, Ann Arbor, MI 48109 USA. Boys Town Natl Res Hosp, Omaha, NE 68131 USA. RP Harris, JP (reprint author), Univ Calif San Diego, Div Otolaryngol Head & Neck Surg, 200 W Arbor Dr,Mail Code 8895, San Diego, CA 92103 USA. FU NIDCD NIH HHS [5 U01 DC03209] NR 29 TC 76 Z9 82 U1 0 U2 5 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 OCT 8 PY 2003 VL 290 IS 14 BP 1875 EP 1883 DI 10.1001/jama.290.14.1875 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 729CB UT WOS:000185752600028 PM 14532316 ER PT J AU Lilliehook, C Bozdagi, O Yao, J Gomez-Ramirez, M Zaidi, NF Wasco, W Gandy, S Santucci, AC Haroutunian, V Huntley, GW Buxbaum, JD AF Lilliehook, C Bozdagi, O Yao, J Gomez-Ramirez, M Zaidi, NF Wasco, W Gandy, S Santucci, AC Haroutunian, V Huntley, GW Buxbaum, JD TI Altered A beta formation and long-term potentiation in a calsenilin knock-out SO JOURNAL OF NEUROSCIENCE LA English DT Article DE KChIP; DREAM; presenilin; APP; A beta; apoptosis; calcium; neuronal calcium sensor; Kv4 channel; long-term potentiation; A-type current ID HIPPOCAMPAL PYRAMIDAL NEURONS; CHANNEL-INTERACTING PROTEIN-2; GAMMA-SECRETASE CLEAVAGE; CALCIUM-BINDING PROTEIN; TRANSCRIPTIONAL REPRESSOR; ALZHEIMERS-DISEASE; POTASSIUM CHANNELS; MOLECULAR-CLONING; EXPRESSION; GENE AB Calsenilin has been identified as a presenilin-binding protein, a transcription factor regulating dynorphin expression, and a beta-subunit of Kv4 channels and could, thus, be a multifunctional protein. To study these functions of calsenilin in vivo and to determine the neuroanatomical expression pattern of calsenilin, we generated mice with a disruption of the calsenilin gene by the targeted insertion of the beta-galactosidase gene. We found that calsenilin expression (as represented by beta-galactosidase activity) is very restricted but overlaps better with that of presenilins and Kv4 channels than with dynorphin, suggesting that calsenilin may regulate presenilin and Kv4 channels in brain. Abeta peptide levels are reduced in calsenilin knock-out mice, demonstrating that calsenilin affects presenilin-dependent gamma-cleavage in vivo. Furthermore, long-term potentiation (LTP) in dentate gyrus of hippocampus, in which calsenilin is strongly and selectively expressed, is enhanced in calsenilin knock-out mice. This enhancement of LTP coincides with a downregulation of the Kv4 channel-dependent A-type current and can be mimicked in wild-type animals by a Kv4 channel blocker. The data presented here show that lack of calsenilin affects both Abeta formation and the A-type current. We suggest that these effects are separate events, caused by a common mechanism possibly involving protein transport. C1 NYU, Mt Sinai Med Ctr, Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. NYU, Mt Sinai Sch Med, Lab Mol Neuropsychiat, New York, NY 10029 USA. NYU, Mt Sinai Sch Med, Dept Neurobiol, New York, NY 10029 USA. Thomas Jefferson Univ, Farber Inst Neurosci, Philadelphia, PA 19107 USA. Manhattanville Coll, Dept Psychol, Purchase, NY 10577 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Genet & Aging Unit, Charlestown, MA 02129 USA. Vet Adm Med Ctr, Dept Psychiat, Bronx, NY 10468 USA. RP Buxbaum, JD (reprint author), NYU, Mt Sinai Med Ctr, Mt Sinai Sch Med, Dept Psychiat, Box 1668,1 Gustave L Levy Pl, New York, NY 10029 USA. FU NIA NIH HHS [AG15801, AG05138, AG10491] NR 41 TC 80 Z9 84 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 8 PY 2003 VL 23 IS 27 BP 9097 EP 9106 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 730GZ UT WOS:000185822200010 PM 14534243 ER PT J AU Song, BB Marvizon, JCG AF Song, BB Marvizon, JCG TI Dorsal horn neurons firing at high frequency, but not primary afferents, release opioid peptides that produce mu-opioid receptor internalization in the rat spinal cord SO JOURNAL OF NEUROSCIENCE LA English DT Article DE C-fiber; dynorphin; endocytosis; endomorphin; enkephalin; dorsal horn; dorsolateral funiculus; internalization; neurokinin; neurokinin 1 receptor; mu-opioid receptor; opioid; primary afferent; rat; release; spinal cord; substance P; tachykinin ID ENKEPHALIN-LIKE MATERIAL; SUBSTANCE-P RELEASE; GABA-IMMUNOREACTIVE NEURONS; NOXIOUS MECHANICAL STIMULI; CAPSAICIN-EVOKED RELEASE; D-ASPARTATE RECEPTORS; LONG-TERM DEPRESSION; IN-VIVO RELEASE; MET-ENKEPHALIN; NEUROKININ-1 RECEPTOR AB To determine what neural pathways trigger opioid release in the dorsal horn, we stimulated the dorsal root, the dorsal horn, or the dorsolateral funiculus (DLF) in spinal cord slices while superfusing them with peptidase inhibitors to prevent opioid degradation. Internalization of mu-opioid receptors (MOR) and neurokinin 1 receptors (NK1R) was measured to assess opioid and neurokinin release, respectively. Dorsal root stimulation at low, high, or mixed frequencies produced abundant NK1R internalization but no MOR internalization, indicating that primary afferents do not release opioids. Moreover, capsaicin and NMDA also failed to produce MOR internalization. In contrast, dorsal horn stimulation elicited MOR internalization that increased with the frequency, being negligible at <10 Hz and maximal at 500 Hz. The internalization was abolished by the MOR antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP), in the presence of low Ca2+ and by the Na+ channel blocker lidocaine, confirming that it was caused by opioid release and neuronal firing. DLF stimulation in "oblique" slices (encompassing the DLF and the dorsal horn of T11-L4) produced MOR internalization, but only in areas near the stimulation site. Moreover, cutting oblique slices across the dorsal horn (but not across the DLF) eliminated MOR internalization in areas distal to the cut, indicating that it was produced by signals traveling in the dorsal horn and not via the DLF. These findings demonstrate that some dorsal horn neurons release opioids when they fire at high frequencies, perhaps by integrating signals from the rostral ventromedial medulla, primary afferents, and other areas of the spinal cord. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Digest Dis,Ctr Neurovisceral Sci & Womens Hlt, Los Angeles, CA 90073 USA. RP Marvizon, JCG (reprint author), W Los Angeles Vet Affairs Med Ctr, Bldg 115,Room 119,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDA NIH HHS [R01 DA012609-01A1, R01 DA012609, R01 DA012609-02, R01 DA012609-03, R01-DA12609] NR 89 TC 32 Z9 32 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 8 PY 2003 VL 23 IS 27 BP 9171 EP 9184 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 730GZ UT WOS:000185822200018 PM 14534251 ER PT J AU Margolis, ML Christie, JD Silvestri, GA Kaiser, L Santiago, S Hansen-Flaschen, J AF Margolis, ML Christie, JD Silvestri, GA Kaiser, L Santiago, S Hansen-Flaschen, J TI Racial differences pertaining to a belief about lung cancer surgery - Results of a multicenter survey SO ANNALS OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 96th International Conference of the American-Thoracic-Society CY MAY 03-10, 2000 CL TORONTO, CANADA SP Amer Thorac Soc ID AFRICAN-AMERICANS; BREAST-CANCER; LOW-INCOME; ATTITUDES; BLACK; CARCINOMA; SURVIVAL; RACE AB Background: Patients at the Philadelphia Veterans Affairs Medical Center frequently voice concern that air exposure during lung cancer surgery might cause tumor spread. Several African-American patients asserted that this belief was common in the African-American community.. I. Objective: To assess the prevalence of the belief that air exposure during lung cancer surgery might cause tumor spread and gauge the influence of this belief on the willingness of African-American and white patients to have lung cancer surgery. Design: Prospective questionnaire survey. Setting: Philadelphia Veterans Affairs Medical Center and University of Pennsylvania, Philadelphia, Pennsylvania; Los Angeles Veterans Affairs Medical Center, Los Angeles, California; and Medical University of South Carolina, Charleston, South Carolina. Patients: 626 consecutive patients in pulmonary and lung cancer clinics. Results: 38% of patients (61% of whom were African American and 29% of whom were white) stated that they believe air exposure at surgery causes tumor spread. The most significant predictor of belief was African-American race (odds ratio, 3.5 [95% Cl, 1.9 to 6.5]), even after controlling for other relevant variables in a multivariable analysis. Nineteen percent of African Americans stated that this belief was a reason for opposing surgery, and 14% would not accept their physicians' assertion that the belief is false. These rates were also statistically significantly higher among African-American than white patients. Conclusions: Belief in accelerated tumor spread at surgery is prevalent among general pulmonary outpatients and lung cancer clinic patients facing lung surgery, particularly among African-American patients. Our findings may pertain to key racial disparities in lung cancer surgery and survival rates and suggest that culturally sensitive physician training or outreach programs directed at disparate beliefs and attitudes may help to address racial discrepancies in health care outcomes. C1 Philadelphia Vet Affairs Med Ctr, Pulm Sect, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. RP Margolis, ML (reprint author), Philadelphia Vet Affairs Med Ctr, Pulm Sect, Room 8A112,Univ & Woodland Ave, Philadelphia, PA 19104 USA. NR 29 TC 128 Z9 129 U1 3 U2 4 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 7 PY 2003 VL 139 IS 7 BP 558 EP 563 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 729AP UT WOS:000185748800003 PM 14530226 ER PT J AU Landefeld, CS Callahan, CM Woolard, N AF Landefeld, CS Callahan, CM Woolard, N TI General internal medicine and geriatrics: Building a foundation to improve the training of general internists in the care of older adults SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID 21ST-CENTURY; RESIDENTS AB Internists-"doctors for adults"-provide most of the medical care given to older Americans, especially those with serious chronic disease. Nonetheless, the United States lacks an adequate physician workforce with mastery in caring for older persons and with expertise in building knowledge about how best to provide this care. This supplement aims to strengthen the physician workforce by fostering incremental and sustained improvements in the training of internal medicine residents in the care of older adults and in the development of geriatrics-oriented general internal medicine faculty. It identifies 3 major barriers to these improvements: lack of adequately trained teachers and mentors, the belief that explicit training in geriatrics has little to offer the generalist, and inadequate funding. Three strategies offer particular promise in over-coming these barriers: engaging directors of internal medicine residency programs, funding centers to promote collaboration between teaching and research programs in general internal medicine and geriatrics, and providing substantial incremental funding on the national level to pay for the time required to care for frail older patients and to teach and do research about this care. The barriers and strategies identified in this supplement may also inform efforts to enhance the skills of practicing physicians and improve training and faculty development in family medicine and other disciplines. C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Regenstrief Inst Hlth Care, Indianapolis, IN 46202 USA. Indiana Univ, Indianapolis, IN 46204 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. RP Landefeld, CS (reprint author), Univ Calif San Francisco, Box 1265, San Francisco, CA 94143 USA. FU NIA NIH HHS [K07 AG000912, K-07 AG00912] NR 23 TC 28 Z9 28 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 7 PY 2003 VL 139 IS 7 BP 609 EP 614 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 729AP UT WOS:000185748800026 PM 14530244 ER PT J AU Naghavi, M Libby, P Falk, E Casscells, SW Litovsky, S Rumberger, J Badimon, JJ Stefanadis, C Moreno, P Pasterkamp, G Fayad, Z Stone, PH Waxman, S Raggi, P Madjid, M Zarrabi, A Burke, A Yuan, C Fitzgerald, PJ Siscovick, DS de Korte, CL Aikawa, M Airaksinen, KEJ Assmann, G Becker, CR Chesebro, JH Farb, A Galis, ZS Jackson, C Jang, IK Koenig, W Lodder, RA March, K Demirovic, J Navab, M Priori, SG Rekhter, MD Bahr, R Grundy, SM Mehran, R Colombo, A Boerwinkle, E Ballantyne, C Insull, W Schwartz, RS Vogel, R Serruys, PW Hansson, GK Faxon, DP Kaul, S Drexler, H Greenland, P Muller, JE Virmani, R Ridker, PM Zipes, DP Shah, PK Willerson, JT AF Naghavi, M Libby, P Falk, E Casscells, SW Litovsky, S Rumberger, J Badimon, JJ Stefanadis, C Moreno, P Pasterkamp, G Fayad, Z Stone, PH Waxman, S Raggi, P Madjid, M Zarrabi, A Burke, A Yuan, C Fitzgerald, PJ Siscovick, DS de Korte, CL Aikawa, M Airaksinen, KEJ Assmann, G Becker, CR Chesebro, JH Farb, A Galis, ZS Jackson, C Jang, IK Koenig, W Lodder, RA March, K Demirovic, J Navab, M Priori, SG Rekhter, MD Bahr, R Grundy, SM Mehran, R Colombo, A Boerwinkle, E Ballantyne, C Insull, W Schwartz, RS Vogel, R Serruys, PW Hansson, GK Faxon, DP Kaul, S Drexler, H Greenland, P Muller, JE Virmani, R Ridker, PM Zipes, DP Shah, PK Willerson, JT TI From vulnerable plaque to vulnerable patient - A call for new definitions and risk assessment strategies: Part I SO CIRCULATION LA English DT Review DE coronary disease; plaque; myocardial infarction; atherosclerosis; death, sudden ID CORONARY-ARTERY-DISEASE; OPTICAL COHERENCE TOMOGRAPHY; ACUTE MYOCARDIAL-INFARCTION; MULTISLICE COMPUTED-TOMOGRAPHY; SUDDEN CARDIAC DEATH; INTRAVASCULAR ULTRASOUND; ATHEROSCLEROTIC PLAQUES; HIGH-RESOLUTION; FIBROUS CAP; ENDOTHELIAL DYSFUNCTION AB Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document focuses on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients. C1 Univ Texas Houston, Texas Heart Inst, Ctr Vulnerable Plaque Res, Houston, TX USA. Mem Hermann Hosp, President Bush Ctr Cardiovasc Hlth, Houston, TX USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Aarhus Univ, Dept Cardiol, Aarhus, Denmark. Aarhus Univ, Inst Expt Clin Res, DK-8000 Aarhus, Denmark. Univ Med Ctr Utrecht, Expt Cardiol Lab, Utrecht, Netherlands. Ohio State Univ, Columbus, OH 43210 USA. Mt Sinai Med Ctr, Zena & Michael A Wiener Cardiovasc Inst, New York, NY 10029 USA. Univ Kentucky, Cardiac Catheterizat Lab, Lexington, KY USA. Univ Kentucky, VA Med Ctr, Lexington, KY USA. Harvard Univ, Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. Tufts Univ New England Med Ctr, Div Cardiol, Boston, MA 02111 USA. Tulane Univ, Sch Med, Dept Med, Cardiol Sect, New Orleans, LA 70112 USA. Armed Forces Inst Pathol, Dept Cardiovasc Pathol, Washington, DC 20306 USA. Univ Washington, Dept Radiol, Seattle, WA 98195 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. Athens Med Sch, Dept Cardiol, Athens, Greece. Erasmus Univ, Ctr Thorax, Catheterizat Lab, NL-3000 DR Rotterdam, Netherlands. Univ Turku, Dept Med, Div Cardiol, SF-20500 Turku, Finland. Hosp Univ Munster, Inst Arteriosclerosis Res, Cent Lab, Munich, Germany. Hosp Univ Munster, Inst Clin Chem & Lab Med, Cent Lab, Munich, Germany. Univ Munster, Dept Clin Radiol, D-4400 Munster, Germany. Mayo Clin, Sch Med, Jacksonville, FL 32224 USA. Emory Univ, Sch Med, Dept Med, Div Cardiol, Atlanta, GA USA. Univ Bristol, Bristol Heart Inst, Bristol, Avon, England. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Ulm, Dept Internal Med 2, D-7900 Ulm, Germany. Univ Kentucky, Lexington, KY USA. RL Roudebush VA Med Ctr, Indianapolis, IN USA. Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. Univ Pavia, Fdn Salvatore Maugeri, I-27100 Pavia, Italy. Ann Arbor Labs, Pfizer Global Res & Dev, Dept Cardiovasc Therapeut, Ann Arbor, MI USA. St Agnes HealthCare, Paul Dudley White Coronary Care Syst, Baltimore, MD USA. Univ Texas, Hlth Sci Ctr, Ctr Human Nutr, Dallas, TX 75235 USA. Lenox Hill Hosp, New York, NY 10021 USA. Univ Milan, Osped San Raffaele, Catheterizat Labs, I-20127 Milan, Italy. Emo Ctr Cuore Columbus, I-20127 Milan, Italy. Inst Mol Med, Ctr Human Genet, Houston, TX USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Minnesota Heart Inst & Fdn, Minneapolis, MN USA. Univ Maryland, Sch Med, Div Cardiol, Baltimore, MD 21201 USA. Karolinska Inst, Karolinska Hosp, Ctr Mol Med, S-10401 Stockholm, Sweden. Univ Chicago, Cardiol Sect, Chicago, IL 60637 USA. Cedars Sinai Med Ctr, Atherosclerosis Res Ctr, Vasc Physiol & Thrombosis Res Lab, Los Angeles, CA 90048 USA. Univ Hannover, Dept Cardiol, Hannover, Germany. Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. CIMIT, Boston, MA USA. Brigham & Womens Hosp, Div Prevent Med, Div Cardiovasc, Boston, MA 02115 USA. Indiana Univ, Sch Med, Krannert Inst Cardiol, Indianapolis, IN 46202 USA. RP Naghavi, M (reprint author), Assoc Eradicat Heart Attack, 2472 Bolsover,439, Houston, TX 77005 USA. RI Ballantyne, Christie/A-6599-2008; de Korte, Chris/C-1077-2008; Madjid, Mohammad/A-9697-2009; Hansson, Goran/B-7423-2012; Falk, Erling/A-7475-2015; OI de Korte, Chris/0000-0002-1987-6948; Falk, Erling/0000-0001-8566-9974; Zipes, Douglas/0000-0001-7141-6829 NR 94 TC 1365 Z9 1592 U1 21 U2 133 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 7 PY 2003 VL 108 IS 14 BP 1664 EP 1672 DI 10.1161/01.CIR.0000087480.94275.97 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 729HE UT WOS:000185767000003 PM 14530185 ER PT J AU Rexrode, KM Manson, JE Lee, IM Ridker, PM Sluss, PM Cook, NR Buring, JE AF Rexrode, KM Manson, JE Lee, IM Ridker, PM Sluss, PM Cook, NR Buring, JE TI Sex hormone levels and risk of cardiovascular events in postmenopausal women SO CIRCULATION LA English DT Article DE hormones; women; cardiovascular diseases; risk factors ID CORONARY-ARTERY DISEASE; BINDING GLOBULIN; RANCHO-BERNARDO; HEART-DISEASE; SERUM; MEN; ASSOCIATION; MORTALITY; ESTROGEN; DHEA-SO4 AB Background-Despite diffuse effects of sex hormones on the cardiovascular system, few prospective studies have examined the relationship of plasma androgens and estrogens with risk of cardiovascular disease (CVD) in postmenopausal women. Methods and Results-A nested case-control study was performed among women in the Women's Health Study. Two hundred women who developed CVD were matched 1:1 by age, smoking, and postmenopausal hormone therapy (HT) to controls who remained free of CVD. We measured testosterone, estradiol, and sex hormone binding globulin (SHBG) levels and calculated free androgen index (FAI), free estradiol index, and the FAI/free estradiol index ratio. Results were stratified by HT use. Among HT nonusers, cases had significantly higher androgen profiles (higher median FAI and lower SHBG levels) than controls. After adjustment for age, smoking, use of aspirin, vitamin E, and alcohol, family history of myocardial infarction, and physical activity, nonusers in the lowest SHBG quartile had an OR of 2.25 (95% CI, 1.03 to 4.91) for CVD, and there were significant trends across FAI quartiles (P for trend=0.03). Additional adjustment for body mass index, hypertension, diabetes, and elevated cholesterol eliminated associations with SHBG and FAI. Among women using HT, no significant differences in hormones or SHBG were observed among women who developed CVD and controls. Conclusions-Among HT nonusers, lower SHBG and higher FAI levels were noted among postmenopausal women who developed CVD events, but this was not independent of body mass index and other cardiovascular risk factors. Estradiol levels were not associated with risk of CVD in HT users or nonusers. C1 Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Assay Lab, Boston, MA 02114 USA. RP Rexrode, KM (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. RI Perez , Claudio Alejandro/F-8310-2010; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Rexrode, Kathryn/0000-0003-3387-8429 FU NCI NIH HHS [CA47988]; NHLBI NIH HHS [HL43851] NR 24 TC 127 Z9 131 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 7 PY 2003 VL 108 IS 14 BP 1688 EP 1693 DI 10.1161/01.CIR.0000091114.36254.F3 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 729HE UT WOS:000185767000008 PM 12975257 ER PT J AU Hayashi, T Boyko, EJ Leonetti, DL McNeely, MJ Newell-Morris, L Kahn, SE Fujimoto, WY AF Hayashi, T Boyko, EJ Leonetti, DL McNeely, MJ Newell-Morris, L Kahn, SE Fujimoto, WY TI Visceral adiposity and the prevalence of hypertension in Japanese Americans SO CIRCULATION LA English DT Article DE epidemiology; hypertension; visceral fat; obesity; risk factors ID IMPAIRED GLUCOSE-TOLERANCE; FASTING PLASMA-INSULIN; BODY-FAT DISTRIBUTION; BLOOD-PRESSURE; MEN; OBESITY; WOMEN; DISEASE; TISSUE; RISK AB Background-Visceral adiposity is generally considered to play a key role in the metabolic syndrome, including hypertension. The purpose of this study was to evaluate cross-sectionally whether visceral adiposity is associated with prevalence of hypertension independent of other adipose depots and fasting plasma insulin. Methods and Results-Study subjects included 563 Japanese Americans with normal or impaired glucose tolerance or diabetes but not taking oral hypoglycemic medication or insulin at entry. Variables included plasma glucose and insulin measured after an overnight fast and during an oral glucose tolerance test, and abdominal, thoracic, and thigh fat areas by CT. Total fat area (TFA) was calculated as the sum of these fat areas. Hypertension was defined as having a systolic blood pressure greater than or equal to140 mm Hg, having a diastolic blood pressure greater than or equal to90 mm Hg, or taking antihypertensive medications. Intra-abdominal fat area (IAFA) was associated with a higher prevalence of hypertension. Adjusted odds ratio of hypertension by IAFA was 1.68 for a 1-SD increase (95% CI, 1.20 to 2.37) after adjusting for age, sex, fasting plasma insulin, a nonlinear transformation of 2-hour plasma glucose, and TFA. IAFA remained a significant predictor of prevalence of hypertension even after adjustment for total subcutaneous fat area, abdominal subcutaneous fat area, body mass index, or waist circumference, but no measure of regional or total adiposity was associated with the odds of prevalence of hypertension in models that contained IAFA. Conclusions-Greater visceral adiposity increases the odds of hypertension in Japanese Americans independent of other adipose depots and fasting plasma insulin. C1 Vet Affairs Puget Sound Hlth Care Syst, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. RP Boyko, EJ (reprint author), Vet Affairs Puget Sound Hlth Care Syst S152E, 1660 S Columbian Way, Seattle, WA 98108 USA. RI Hayashi, Tomoshige/N-8508-2015; OI Kahn, Steven/0000-0001-7307-9002 FU NCRR NIH HHS [RR-00037]; NHLBI NIH HHS [HL-49293]; NIDDK NIH HHS [DK-35816, DK-02654, DK-17047, DK-31170] NR 23 TC 63 Z9 68 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 7 PY 2003 VL 108 IS 14 BP 1718 EP 1723 DI 10.1161/01.CIR.0000087597.59169.8D PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 729HE UT WOS:000185767000013 PM 12975250 ER PT J AU Figueredo, A Rumble, RB Maroun, J Earle, CC Cummings, B McLeod, R Zuraw, L Zwaal, C AF Figueredo, A Rumble, RB Maroun, J Earle, CC Cummings, B McLeod, R Zuraw, L Zwaal, C CA Gastrointestinal Canc Dis Site Grp TI Follow-up of patients with curatively resected colorectal cancer: a practice guideline SO BMC CANCER LA English DT Article ID QUALITY-OF-LIFE; RADICAL SURGERY; AMERICAN-SOCIETY; POSTOPERATIVE SURVEILLANCE; CLINICAL-ONCOLOGY; CONTROLLED-TRIAL; COLON-CANCER; CARCINOMA; METAANALYSIS; SURVIVAL AB Background: A systematic review was conducted to evaluate the literature regarding the impact of follow-up on colorectal cancer patient survival and, in a second phase, recommendations were developed. Methods: The MEDLINE, CANCERLIT, and Cochrane Library databases, and abstracts published in the 1997 to 2002 proceedings of the annual meeting of the American Society of Clinical Oncology were systematically searched for evidence. Study selection was limited to randomized trials and meta-analyses that examined different programs of follow-up after curative resection of colorectal cancer where five-year overall survival was reported. External review by Ontario practitioners was obtained through a mailed survey. Final approval of the practice guideline report was obtained from the Practice Guidelines Coordinating Committee. Results: Six randomized trials and two published meta-analyses of follow-up were obtained. Of six randomized trials comparing one follow-up program to a more intense program, only two individual trials detected a statistically significant survival benefit favouring the more intense follow-up program. Pooling of all six randomized trials demonstrated a significant improvement in survival favouring more intense follow-up ( Relative Risk Ratio 0.80 (95% CI, 0.70 to 0.91; p = 0.0008). Although the rate of recurrence was similar in both of the follow-up groups compared, asymptomatic recurrences and re-operations for cure of recurrences were more common in patients with more intensive follow-up. Trials including CEA monitoring and liver imaging also had significant results, whereas trials not including these tests did not. Conclusion: Follow-up programs for patients with curatively resected colorectal cancer do improve survival. These follow-up programs include frequent visits and performance of blood CEA, chest x-rays, liver imaging and colonoscopy, however, it is not clear which tests or frequency of visits is optimal. There is a suggestion that improved survival is due to diagnosis of recurrence at an earlier, asymptomatic stage which allows for more curative resection of recurrence. Based on this evidence and consideration of the biology of colorectal cancer and present practices, a guideline was developed. Patients should be made aware of the risk of disease recurrence or second bowel cancer, the potential benefits of follow-up and the uncertainties requiring further clinical trials. For patients at high-risk of recurrence ( stages IIb and III) clinical assessment is recommended when symptoms occur or at least every 6 months the first 3 years and yearly for at least 5 years. At the time of those visits, patients may have blood CEA, chest x-ray and liver imaging. For patients at lower risk of recurrence ( stages I and Ia) or those with co-morbidities impairing future surgery, only visits yearly or when symptoms occur. All patients should have a colonoscopy before or within 6 months of initial surgery, and repeated yearly if villous or tubular adenomas > 1 cm are found; otherwise repeat every 3 to 5 years. All patients having recurrences should be assessed by a multidisciplinary team in a cancer centre. C1 McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. McMaster Univ, Hamilton Reg Canc Ctr, Hamilton, ON, Canada. Univ Ottawa, Ottawa Reg Canc Ctr, Ottawa, ON, Canada. Harvard Univ, Dana Farber Canc Ctr, Boston, MA 02115 USA. Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. Univ Toronto, Toronto, ON, Canada. RP Rumble, RB (reprint author), McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. RI McLeod, Robin/K-1476-2013 NR 62 TC 182 Z9 188 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD OCT 6 PY 2003 VL 3 AR 26 DI 10.1186/1471-2407-3-26 PG 13 WC Oncology SC Oncology GA 740JW UT WOS:000186400100001 PM 14529575 ER PT J AU Apostolou, I Hao, ZY Rajewsky, K von Boehmer, H AF Apostolou, I Hao, ZY Rajewsky, K von Boehmer, H TI Effective destruction of Fas-deficient insulin-producing beta cells in type 1 diabetes SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE Fas receptor; diabetes; beta cell death; autoimmunity; conditional knockout ID MICE; LYMPHOCYTES AB In type I diabetes, autoimmune T cells cause destruction of pancreatic beta cells by largely unknown mechanism. Previous analyses have shown that beta cell destruction is delayed but can occur in perforin-deficient nonobese diabetic (NOD) mice and that Fas-deficient NOD mice do not develop diabetes. However, because of possible pleiotropic functions of Fas, it was not clear whether the Fas receptor was an essential mediator of beta cell death in type 1 diabetes. To directly test this hypothesis, we have generated a beta cell-specific knockout of the Fas gene in a transgenic model of type I autoimmune diabetes in which CD4(+) T cells with a transgenic TCR specific for influenza hemagglutinin (HA) are causing diabetes in mice that express HA under control of the rat insulin promoter. Here we show that the Fas-deficient mice develop autoimmune diabetes with slightly accelerated kinetics indicating that Fas-dependent apoptosis of beta cells is a dispensable mode of cell death in this disease. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Adv Med Discovery Inst, Toronto, ON M5G 2C1, Canada. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 17 TC 53 Z9 54 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 6 PY 2003 VL 198 IS 7 BP 1103 EP 1106 DI 10.1084/jem.20030698 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 730ZQ UT WOS:000185860400012 PM 14530378 ER PT J AU Volkmar, FR Pauls, D AF Volkmar, FR Pauls, D TI Autism SO LANCET LA English DT Review ID PERVASIVE DEVELOPMENTAL DISORDERS; PLACEBO-CONTROLLED TRIAL; LATENT-CLASS ANALYSIS; LINKAGE-DISEQUILIBRIUM; SPECTRUM DISORDERS; ASPERGER-SYNDROME; RUBELLA VACCINE; FAMILY HISTORY; GENOMIC SCREEN; PERSONALITY-CHARACTERISTICS AB Autism is a disorder characterised by severe difficulties in social interaction and communication, and with unusual behaviours. Once thought of as rare, autism is now recognised as being common. The role of CNS factors in pathogenesis is suggested by high rates of seizure disorder; research has highlighted the role of several specific brain regions in syndrome pathogenesis. Autism is a strongly genetic disorder and probably arises because of multiple genes; recurrence rates in families with one child are high. Early intervention with various techniques is helpful in many cases. Some pharmacological agents may help with certain problematic behaviours but do not address the underlying cause of the disorder. C1 Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Charlestown, MA USA. RP Volkmar, FR (reprint author), Yale Univ, Ctr Child Study, POB 207900, New Haven, CT 06520 USA. EM fred.volkmar@yale.edu NR 162 TC 168 Z9 176 U1 22 U2 46 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD OCT 4 PY 2003 VL 362 IS 9390 BP 1133 EP 1141 DI 10.1016/S0140-6736(03)14471-6 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 728HA UT WOS:000185710700024 PM 14550703 ER PT J AU Augood, SJ Keller-McGandy, CE Siriani, A Hewett, J Ramesh, V Sapp, E DiFiglia, M Breakefield, XO Standaert, DG AF Augood, SJ Keller-McGandy, CE Siriani, A Hewett, J Ramesh, V Sapp, E DiFiglia, M Breakefield, XO Standaert, DG TI Distribution and ultrastructural localization of torsinA immunoreactivity in the human brain SO BRAIN RESEARCH LA English DT Article DE dopamine; DYT1; dystonia; Parkinson's disease; TOR1A; axonal transport ID DYSTONIA GENE DYT1; GENERALIZED DYSTONIA; TYROSINE-HYDROXYLASE; ALPHA-SYNUCLEIN; MUTANT TORSINA; BASAL GANGLIA; PROTEIN; CELLS; STIMULATION; MEMBRANE AB We have examined the distribution and ultrastructural localization of torsinA, the protein product of the TOR1A gene, in the normal adult human and Macaque brain. TorsinA immunoreactivity was visualized using a monoclonal antibody raised against a fusion protein encoding exon 4 of human torsinA. Western blot analysis of brain homogenates revealed a major species of about 39 kDa, consistent with the predicted size of glycosylated torsinA protein. By light microscopy, torsinA like-immunoreactivity was enriched in gray matter in all brain regions examined. Immunoreactivity was concentrated in the neuropil and immunopositive cell bodies were not observed. Structures particularly enriched in torsinA like-immunoreactivity included the cerebral cortex, the caudate-putamen, globus pallidus, the hippocampal formation, the thalamus, the substantia nigra and molecular cell layer of the cerebellar cortex. Cell bodies of pigmented dopamine neurons in the substantia nigra. pars compacta were immunonegative. Biochemical fractionation of the human striata revealed a concentration of torsinA immunoreactivity in particulate fractions. Ultrastructural studies of the human and Macaque striata further revealed an association of torsinA immunostaining with small vesicles within axons and presynaptic terminals forming symmetric synapses. These ultrastructural studies are consistent with a pre-synaptic localization of torsinA protein in the adult striatum and are consistent with a role of torsinA in modulating striatal signaling, although the widespread localization of the protein suggests it probably also participates in signaling in other regions. (C) 2003 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neurogenet Unit, Charlestown, MA 02129 USA. RP Augood, SJ (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, CNY 114-2300 114 16th St, Charlestown, MA 02129 USA. OI Standaert, David/0000-0003-2921-8348 FU NIMH NIH HHS [MH/NS 31862]; NINDS NIH HHS [NS28384] NR 50 TC 39 Z9 40 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 3 PY 2003 VL 986 IS 1-2 BP 12 EP 21 DI 10.1016/S0006-8993(03)03164-0 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 723WF UT WOS:000185454000002 PM 12965225 ER PT J AU Chang, DC McWatters, HG Williams, JA Gotter, AL Levine, JD Reppert, SM AF Chang, DC McWatters, HG Williams, JA Gotter, AL Levine, JD Reppert, SM TI Constructing a feedback loop with circadian clock molecules from the silkmoth, Antheraea pernyi SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DROSOPHILA-PERIOD; TRANSCRIPTION FACTORS; POSITIONAL CLONING; GENE-EXPRESSION; HYPOXIA FACTORS; TIMELESS; PROTEIN; PAS; SEQUENCE; GENOME AB Circadian clocks are important regulators of behavior and physiology. The circadian clock of Drosophila depends on an autoinhibitory feedback loop involving dCLOCK, CYCLE (also called dBMAL, for Drosophila brain and muscle ARNT-like protein), dPERIOD, and dTIMELESS. Recent studies suggest that the clock mechanism in other insect species may differ strikingly from that of Drosophila. We cloned Clock, Bmal, and Timeless homologs (apClock, apBmal, and apTimeless) from the silkmoth Antheraea pernyi, from which a Period homolog (apPeriod) has already been cloned. In Schneider 2 (S2) cell culture assays, apCLOCK:apBMAL activates transcription through an E-box enhancer element found in the 5' region of the apPeriod gene. Furthermore, apPERIOD can robustly inhibit apCLOCK:apBMAL-mediated transactivation, and apTIMELESS can augment this inhibition. Thus, a complete feedback loop, resembling that found in Drosophila, can be constructed from silkmoth CLOCK, BMAL, PERIOD, and TIMELESS. Our results suggest that the circadian autoinhibitory feedback loop discovered in Drosophila is likely to be widespread among insects. However, whereas the transactivation domain in Drosophila lies in the C terminus of dCLOCK, in A. pernyi, it lies in the C terminus of apBMAL, which is highly conserved with the C termini of BMALs in other insects (except Drosophila) and in vertebrates. Our analysis sheds light on the molecular function and evolution of clock genes in the animal kingdom. C1 Univ Massachusetts, Sch Med, Dept Neurobiol, Med Ctr, Worcester, MA 01605 USA. Massachusetts Gen Hosp, MassGen Hosp Children, Lab Dev Chronobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Univ Massachusetts, Sch Med, Dept Neurobiol, Med Ctr, 364 Plantat St, Worcester, MA 01605 USA. EM steven.reppert@umassmed.edu FU NINDS NIH HHS [R01-NS39303] NR 51 TC 39 Z9 41 U1 1 U2 11 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 3 PY 2003 VL 278 IS 40 BP 38149 EP 38158 DI 10.1074/jbc.M306937200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 726AM UT WOS:000185575100009 PM 12869551 ER PT J AU Liu, YY Schultz, JJ Brent, GA AF Liu, YY Schultz, JJ Brent, GA TI A thyroid hormone receptor alpha gene mutation (P398H) is associated with visceral adiposity and impaired catecholamine-stimulated lipolysis in mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DOMINANT-NEGATIVE MUTATION; BETA-ADRENERGIC-RECEPTOR; RETINOID-X-RECEPTOR; FAT-CELL FUNCTION; INSULIN-RESISTANCE; DEFICIENT MICE; POSTNATAL-DEVELOPMENT; COREPRESSOR RELEASE; EXPRESSION; TISSUE AB Thyroid hormone has profound effects on metabolic homeostasis, regulating both lipogenesis and lipolysis, primarily by modulating adrenergic activity. We generated mice with a point mutation in the thyroid hormone receptor alpha (TRalpha) gene producing a dominant-negative TRalpha mutant receptor with a proline to histidine substitution (P398H). The heterozygous P398H mutant mice had a 3.4-fold (p < 0.02) increase in serum thyrotropin (TSH) levels. Serum triiodothyronine (T3) and thyroxine (T4) concentrations were slightly elevated compared with wild-type mice. The P398H mice had a 4.4-fold increase in body fat (as a fraction of total body weight) (p < 0.001) and a 5-fold increase in serum leptin levels (p < 0.005) compared with wild-type mice. A 3-fold increase in serum fasting insulin levels (p < 0.002) and a 55% increase in fasting glucose levels (p < 0.01) were observed in P398H compared with wild-type mice. There was a marked reduction in norepinephrine-induced lipolysis, as reflected in reduced glycerol release from white adipose tissue isolated from P398H mice. Heart rate and cold-induced adaptive thermogenesis, mediated by thyroid hormone-catecholamine interaction, were also reduced in P398H mice. In conclusion, the TRα P398H mutation is associated with visceral adiposity and insulin resistance primarily due to a marked reduction in catecholamine-stimulated lipolysis. The observed phenotype in the TRα P398H mouse is likely due to interference with TRα action as well as influence on other metabolic signaling pathways. The physiologic significance of these findings will ultimately depend on understanding the full range of actions of this mutation. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med,Mol Endocrinol Lab, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol,Mol Endocrinol Lab, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Brent, GA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med,Mol Endocrinol Lab, Vet Affairs Greater Los Angeles Healthcare Syst, Bldg 114,Rm 230,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NCI NIH HHS [CA-89364] NR 62 TC 98 Z9 101 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 3 PY 2003 VL 278 IS 40 BP 38913 EP 38920 DI 10.1074/jbc.M306120200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 726AM UT WOS:000185575100100 PM 12869545 ER PT J AU Yanagisawa, S Yoo, SD Sheen, J AF Yanagisawa, S Yoo, SD Sheen, J TI Differential regulation of EIN3 stability by glucose and ethylene signalling in plants SO NATURE LA English DT Article ID INDUCIBLE GENE-EXPRESSION; PROTEASOME PATHWAY; RESPONSE PATHWAY; ABSCISIC-ACID; ARABIDOPSIS; PROTEIN; LIGHT; TRANSDUCTION; MAIZE; ETHYLENE-INSENSITIVE3 AB Glucose is a global regulator of growth and metabolism that is evolutionarily conserved from unicellular microorganisms to multicellular animals and plants(1). In photosynthetic plants, glucose shows hormone-like activities and modulates many essential processes, including embryogenesis, germination, seedling development, vegetative growth, reproduction and senescence(2,3). Genetic and phenotypic analyses of Arabidopsis mutants with glucose-insensitive (gin) and glucose-oversensitive (glo) phenotypes have identified an unexpected antagonistic interaction between glucose and the plant stress hormone ethylene. The ethylene-insensitive etr1 and ein2 mutants have glo phenotypes, whereas the constitutive ethylene signalling mutant ctr1 is allelic to gin4 (refs 4, 5). The precise molecular mechanisms underlying the complex signalling network that governs plant growth and development in response to nutrients and plant hormones are mostly unknown. Here we show that glucose enhances the degradation of ETHYLENE-INSENSITIVE3 (EIN3), a key transcriptional regulator in ethylene signalling(6,7), through the plant glucose sensor hexokinase(8). Ethylene, by contrast, enhances the stability of EIN3. The ein3 mutant has a glo phenotype, and overexpression of EIN3 in transgenic Arabidopsis decreases glucose sensitivity. C1 Okayama Univ, Bioresources Res Inst, Kurashiki, Okayama 7100046, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Genet,Dept Mol Biol, Boston, MA 02114 USA. RP Yanagisawa, S (reprint author), Okayama Univ, Bioresources Res Inst, Chuo 2-20-1, Kurashiki, Okayama 7100046, Japan. NR 30 TC 272 Z9 298 U1 10 U2 62 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 2 PY 2003 VL 425 IS 6957 BP 521 EP 525 DI 10.1038/nature01984 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 727FN UT WOS:000185648100047 PM 14523448 ER PT J AU Kaplan, LD Afridi, NA Holmvang, G Zukerberg, LR Harris, NL Scadden, DT Ferrell, MA AF Kaplan, LD Afridi, NA Holmvang, G Zukerberg, LR Harris, NL Scadden, DT Ferrell, MA TI Case 31-2003: A 44-year-old man with HIV infection and a right atrial mass - Diffuse large-B-cell lymphoma of the heart, EBV-positive SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID IMMUNE-DEFICIENCY-SYNDROME; NON-HODGKINS-LYMPHOMA; HUMAN-IMMUNODEFICIENCY-VIRUS; PRIMARY CARDIAC LYMPHOMA; ACTIVE ANTIRETROVIRAL THERAPY; MALIGNANT-LYMPHOMA; KAPOSIS-SARCOMA; SYNDROME AIDS; CHEMOTHERAPY; TRANSPLANTATION C1 Univ Calif San Francisco, Sch Med, Dept Med, Div Hematol Oncol, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Cardiol, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Kaplan, LD (reprint author), Univ Calif San Francisco, Sch Med, Dept Med, Div Hematol Oncol, San Francisco, CA 94143 USA. NR 38 TC 10 Z9 10 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 2 PY 2003 VL 349 IS 14 BP 1369 EP 1377 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 727EM UT WOS:000185644000013 PM 14523146 ER PT J AU Gordon, JA Tancredi, DN Binder, WD Wilkerson, WM Shaffer, DW AF Gordon, JA Tancredi, DN Binder, WD Wilkerson, WM Shaffer, DW TI Assessment of a clinical performance evaluation tool for use in a simulator-based testing environment: A pilot study SO ACADEMIC MEDICINE LA English DT Article; Proceedings Paper CT 42nd Annual Conference on Research in Medical Education CY NOV 09-12, 2003 CL Washington, DC ID CERTIFICATION EXAMINATION; EMERGENCY MEDICINE; VALIDITY AB Purpose. This study assessed a clinical performance evaluation tool for use in a simulator-based testing environment. Method. Twenty-three subjects were evaluated during five standardized encounters using a patient simulator (six emergency medicine students, seven house officers, ten chief resident-fellows). Performance in each 15-minute session was compared with performance on an identical number of oral objective-structured clinical examination (OSCE) sessions used as controls. Each was scored by a faculty rater using a scoring system previously validated for oral certification examinations in emergency medicine (eight skills rated 1-8; passing = 5.75). Results. On both simulator exams and oral controls, chief resident-fellows earned (mean) "passing" scores [sim = 6.4 (95% CI: 6.0-6.8), oral = 6.4 (95% CI: 6.1-6.7)]; house officers earned "borderline" scores [sim = 5.6 (95% CI: 5.2-5.9), oral = 5.5 (95% CI: 5.0-5.9)]; and students earned "failing" scores [sim = 4.3 (95% CI: 3.8-4.7), oral = 4.5 (95% CI: 3.8-5.1)]. There were significant differences among mean scores for the three cohorts, for both oral and simulator test arms (p < .01). Conclusions. In this pilot, a standardized oral OSCE scoring system per-formed equally well in a simulator-based testing environment. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med,Program Med Simulat, Boston, MA 02114 USA. RP Gordon, JA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med,Program Med Simulat, 55 Fruit St,Clin 115, Boston, MA 02114 USA. EM gordon3@partners.org NR 9 TC 31 Z9 32 U1 0 U2 3 PU ASSOC AMER MEDICAL COLLEGES PI WASHINGTON PA 2450 N ST N W, WASHINGTON, DC 20037-1126 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD OCT PY 2003 VL 78 IS 10 SU S BP S45 EP S47 DI 10.1097/00001888-200310001-00015 PG 3 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 802CE UT WOS:000220140800015 PM 14557093 ER PT J AU Thrall, JH AF Thrall, JH TI Balancing mission and money in academic medicine SO ACADEMIC RADIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Thrall, JH (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD OCT PY 2003 VL 10 IS 10 BP 1185 EP 1186 DI 10.1016/S1076-6332(03)00332-5 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 732KR UT WOS:000185944700016 PM 14587639 ER PT J AU Ferguson, JJ Antman, EM Bates, ER Cohen, M Every, NR Harrington, RA Pepine, CJ Theroux, P AF Ferguson, JJ Antman, EM Bates, ER Cohen, M Every, NR Harrington, RA Pepine, CJ Theroux, P CA NICE-3 Investigators TI Combining enoxaparin and glycoprotein IIb/IIIa antagonists for the treatment of acute coronary syndromes: Final results of the National Investigators Collaborating on Enoxaparin-3 (NICE-3) study SO AMERICAN HEART JOURNAL LA English DT Article ID MOLECULAR-WEIGHT HEPARIN; WAVE MYOCARDIAL-INFARCTION; UNFRACTIONATED HEPARIN; UNSTABLE ANGINA; RANDOMIZED-TRIAL; ARTERY-DISEASE; TIMI 11B; TIROFIBAN; ESSENCE; BLOCKADE AB Background In high-risk patients with acute coronary syndromes (ACS), there have been concerns relating to the safety of using low molecular weight heparins (LMWH) in combination with a glycoprotein (GP) IIb/IIIa antagonist, and the continued use of LMWH in patients brought to the cardiac catheterization laboratory for percutaneous coronary intervention (PCI). Methods The National Investigators Collaborating on Enoxaparin-3 (NICE-3) study was an open-label observational study of enoxaparin in combination with any 1 of 3 available GP IIb/IIIa antagonists in patients presenting with non-ST-elevation ACS. The primary end point was the incidence of major bleeding not related to coronary artery bypass graft (CABG) surgery. Data were also recorded on the incidence of death, myocardial infarction (MI), and urgent revascularization for repeat ischemia. Results A total of 671 patients with validated data were treated with enoxaparin; 628 of these patients also received a GP IIb/IIIa antagonist (tirofiban, n = 229; eptifibatide, n = 272; abciximab, n = 127); 283 of 628 underwent percutaneous coronary intervention (PCI). The 30-day incidence of non-CABG major bleeding was 1.9%, and was not significantly higher than a prespecified historical control rate of 2.0%. Outcome events included death (1.0% at hospital discharge and 1.6% at 30 days), MI (3.5% and 5.1%, respectively), and urgent revascularization (2.7% and 6.8%, respectively). Conclusions The safety of enoxaparin plus a GP IIb/IIIa antagonist was comparable to that of unfractionated heparin plus a GP IIb/IIIa antagonist, as reported in other recent major trials. Patients undergoing PCI can be safely managed with enoxaparin and a GP IIb/IIIa antagonist, without supplemental use of unfractionated heparin. C1 St Lukes Episcopal Hosp, Houston, TX 77225 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Newark Beth Israel Med Ctr, Newark, NJ USA. VA Puget Sound Healthcare Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Florida, Gainesville, FL USA. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. RP Ferguson, JJ (reprint author), St Lukes Episcopal Hosp, POB 20269, Houston, TX 77225 USA. NR 27 TC 67 Z9 72 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 OCT PY 2003 VL 146 IS 4 BP 628 EP 634 DI 10.1067/S0002-8703(03)00165-0 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 733UN UT WOS:000186019200012 PM 14564315 ER PT J AU Beinart, SC Sales, AE Spertus, JA Plomondon, ME Every, NR Rumsfeld, JS AF Beinart, SC Sales, AE Spertus, JA Plomondon, ME Every, NR Rumsfeld, JS TI Impact of angina burden and other factors on treatment satisfaction after acute coronary syndromes SO AMERICAN HEART JOURNAL LA English DT Article ID QUALITY-OF-LIFE; PATIENT SATISFACTION; MEDICAL-CARE; COMMUNICATION-SKILLS; GENERAL-PRACTICE; ARTERY-DISEASE; HOSPITAL-CARE; CONSUMER SATISFACTION; FUNCTIONAL STATUS; VETERANS-AFFAIRS AB Purpose Although of great importance to clinicians, hospitals, and health care systems, little is known about factors that influence treatment satisfaction after acute coronary syndromes (ACS). The objective of this study was to identify potentially modifiable factors associated with treatment satisfaction 7 months after ACS. Methods The study population included 1957 patients with ACS who were enrolled in the multicenter, prospective Veterans' Health Administration Access to Cardiology Study. The primary outcome was treatment satisfaction 7 months after ACS as measured by the Seattle Angina Questionnaire. Multivariable regression models were developed to determine the association between treatment satisfaction and patient characteristics, physician-patient communication, and current angina frequency. Results Patient characteristics associated with reduced treatment satisfaction included a history of depression, atrial fibrillation, prior heart surgery, arthritis, hypertension, younger age, and a discharge diagnosis of unstable angina (as opposed to myocardial infarction). After adjusting for patient characteristics, patient-reported inability to reach one or more of their physicians (OR, 2.40; 95% CI, 1.47 to 3.91), being given confusing information (OR, 3.48; 95% CI, 2.08 to 5.83), and poor overall communication with one or more of their physicians (OR, 4.94; 95% CI, 2.93 to 8.34) were all associated with reduced satisfaction. Finally, after adjustment for both patient characteristics and physician communication, weekly (OR, 3.52; 95% CI, 2.28 to 5.45) and daily angina (OR, 3.88; 95% CI, 2.23 to 6.75) were associated with worse treatment satisfaction. Conclusions Current angina symptoms and aspects of physician communication are independently associated with treatment satisfaction after ACS. These results suggest that treatment satisfaction may be improved through better communication and better control of angina symptoms. C1 Denver VA Med Ctr, Denver, CO 80220 USA. VA Puget Sound Hlth Care Syst, Cardiovasc Outcomes Res Ctr, Seattle, WA USA. Emory Univ, Div Cardiol, Atlanta, GA 30322 USA. Univ Missouri, Kansas City, MO 64110 USA. RP Rumsfeld, JS (reprint author), Denver VA Med Ctr, 111B,1055 Clermont St, Denver, CO 80220 USA. OI Sales, Anne/0000-0001-9360-3334 NR 47 TC 24 Z9 26 U1 1 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2003 VL 146 IS 4 BP 646 EP 652 DI 10.1016/S0002-8703(03)00256-4 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 733UN UT WOS:000186019200015 PM 14564318 ER PT J AU Seshadri, N Dweik, RA Laskowski, D Pothier, C Rodriguez, L Young, JB Migrino, RQ AF Seshadri, N Dweik, RA Laskowski, D Pothier, C Rodriguez, L Young, JB Migrino, RQ TI Dysregulation of endogenous carbon monoxide and nitric oxide production in patients with advanced ischemic or nonischemic cardiomyopathy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID INDUCED ASTHMATIC RESPONSE; CONGESTIVE-HEART-FAILURE; HEME OXYGENASE; SUPPRESSES; DYSFUNCTION; APOPTOSIS; PULMONARY AB Carbon monoxide (CO) and nitric oxide (NO) are endogenous vasoregulatory molecules whose role in heart failure is not fully known. Exhaled CO and NO measurement provide novel noninvasive assessment of their endogenous production. We compared exhaled CO and NO in 24 patients with advanced ischemic and nonischemic cardiomyopathy and in 13 control subjects without known cardiac disease at rest and at 1 and 5 minutes after exercise testing. Exhaled CO was lower in patients with cardiomyopathy at rest (1.66 +/- 0.2 vs 1.80 +/- 0.5 ppm, p = 0.02) and 1 minute after exercise (1.35 +/- 0.2 vs 1.81 +/- 0.5 ppm, p = 0.009), with a similar trend at 5 minutes after exercise (1.45 +/- 0.3. vs 1.81 +/- 0.5 ppm, p = 0.14). Exhaled CO decreased in patients with cardiomyopathy after exercise (p <0.001 and p = 0.02 at rest vs 1 and 5 minutes after exercise, respectively) but was maintained in controls. Exhaled NO did not differ between patients with cardiomyopathy and controls at rest (9.48 +/- 1.4 vs 9.68 +/- 1.5 ppb, p = NS) and after exercise (1 minute: 10.911 +/- 1.8 vs 9.19 +/- 1.2 ppb; 5 minutes: 10.52 +/- 1.5 vs 8.90 +/- 1.2 ppb, p = NS). Exhaled NO increased after exercise in patients with cardiomyopathy (p = 0.01 and p = 0.04 rest vs exercise at 1 and 5 minutes, respectively), but was maintained in controls. Exhaled CO and NO were not correlated with peak oxygen consumption in patients with cardiomyopathy. The differential responses in exhaled CO and NO at rest or with exercise between patients with cardiomyopathy and normal controls may point to dysregulation in endogenous CO and NO production. (C) 2003 by Excerpta Medica, Inc. C1 Cleveland Clin Fdn, Dept Cardiovasc Med, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Pulm & Crit Care Med, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Dept Radiol & Med, Boston, MA USA. RP Migrino, RQ (reprint author), Jacksonville Ctr Clin Res, 4085 Univ Blvd S,Suite 1, Jacksonville, FL 32216 USA. FU NHLBI NIH HHS [HL-68863] NR 27 TC 6 Z9 6 U1 1 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 OCT 1 PY 2003 VL 92 IS 7 BP 820 EP 823 DI 10.1016/S0002-9149(03)00890-7 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 727VZ UT WOS:000185682700010 PM 14516883 ER PT J AU Hoffmann, U Globits, S Schima, W Loewe, C Puig, S Oberhuber, G Frank, H AF Hoffmann, U Globits, S Schima, W Loewe, C Puig, S Oberhuber, G Frank, H TI Usefulness of magnetic resonance Imaging of cardiac and paracardiac masses SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID DIAGNOSIS; DISEASE; BENIGN; MYXOMA; TUMORS; CT AB In this study, magnetic resonance imaging was compared with histology to evaluate the usefulness of magnetic resonance imaging to distinguish malignant from benign cardiac and paracardiac masses in 55 patients. Tumor location, tissue composition, and pericardial or pleural effusion all were identified as key predictors of lesion type. Observers were accurate in the prediction of lesion type (area under curve 0.88 and 0.92), and there was good interobserver variability (Cohen's kappa = 0.64). (C) 2003 by Excerpta Medica, Inc. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Vienna, Vienna, Austria. Gen Hosp, Dept Radiol, Vienna, Austria. Gen Hosp, Dept Internal Med 2, Div Cardiol, Vienna, Austria. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Dept Radiol, 100 Charles River Plaza,Suite 400, Boston, MA 02114 USA. OI Loewe, Christian/0000-0003-2502-0676 NR 17 TC 65 Z9 69 U1 1 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 OCT 1 PY 2003 VL 92 IS 7 BP 890 EP 895 DI 10.1016/S0002-9149(03)00911-1 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 727VZ UT WOS:000185682700030 PM 14516903 ER PT J AU Okunieff, P Meyn, RE Teicher, BA Thomas, CR Gaspar, LE Raben, D Giri, S Lavey, RS Turrisi, AT Swanson, GP Smalley, SR AF Okunieff, P Meyn, RE Teicher, BA Thomas, CR Gaspar, LE Raben, D Giri, S Lavey, RS Turrisi, AT Swanson, GP Smalley, SR TI Report from the Radiation Oncology Committee of the Southwest Oncology Group (SWOG) - Research objectives workshop 2003 SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article ID CELL LUNG-CANCER; ACCELERATED HYPERFRACTIONATED RADIATION; TOPOISOMERASE-I INHIBITOR; HUMAN TUMOR; PHASE-II; PANCREATIC-CANCER; GASTROINTESTINAL MALIGNANCIES; ANAPLASTIC ASTROCYTOMA; PULMONARY FIBROSIS; BONE-MARROW AB To achieve the ultimate goal of cancer treatment, which is 100% cancer control with negligible toxicity, the therapeutic window must be enlarged, allowing for higher doses of beneficial treatments with reduced toxicity. The advent of image- and metabolism-guided therapy offers the best opportunity to date for combining modem radiation targeting and imaging techniques. Indeed, for the first time, it is reasonable to locally target metastatic disease with the goal of sterilization. Combining these focal radiation techniques with novel targeted antiproliferative agents and full-dose classic cytotoxic chemotherapy will become more effective as we learn to use these compounds in a less systemically toxic manner and as radiation fields become more defined. In addition, increasing numbers of biologic modifiers of normal tissue response are becoming available, and they suggest great promise for decreasing the normal tissue toxicity resulting from both radiation and chemotherapy treatments. Thus, radiation metastectomy for gross metastases, used together with systemic control of micrometastatic disease, may yield improved survival rates. This hypothesis is ready for testing in cancers of the breast, prostate, colon, and in sarcomas. Enlarging the therapeutic window is a major goal that would allow for an increasingly favorable therapeutic gain. C1 Univ Rochester, Med Ctr, James P Wilmot Canc Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Genzyme Corp, Cambridge, MA USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Colorado, Hlth Sci Ctr, Aurora, CO USA. Eastern Virginia Med Sch, Norfolk, VA 23501 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. Med Univ S Carolina, Charleston, SC 29425 USA. Canc Care NW Deaconess Med Ctr, Spokane, WA USA. Olathe Reg Oncol Ctr, Olathe, KS USA. RP Okunieff, P (reprint author), Univ Rochester, Med Ctr, James P Wilmot Canc Ctr, Dept Radiat Oncol, 601 Elmwood Ave,Box 647, Rochester, NY 14642 USA. EM paul_okunieff@urmc.rochester.edu NR 82 TC 3 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD OCT PY 2003 VL 26 IS 5 BP 522 EP 529 DI 10.1097/01.coc.0000092253.71406.2b PG 8 WC Oncology SC Oncology GA 730KG UT WOS:000185829500019 PM 14528084 ER PT J AU Seddon, JM Santangelo, SL Book, K Chong, S Cote, J AF Seddon, JM Santangelo, SL Book, K Chong, S Cote, J TI A genomewide scan for age-related macular degeneration provides evidence for linkage to several chromosomal regions SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID BEAVER DAM EYE; FAMILIAL AGGREGATION; DIETARY-FAT; CLASSIFICATION-SYSTEM; RETINITIS-PIGMENTOSA; GENETIC ASSOCIATION; RETINAL DYSTROPHY; PEDIGREE ANALYSIS; 5-YEAR INCIDENCE; APOLIPOPROTEIN-E AB We report the results of a genomewide scan for age-related macular degeneration (AMD) in 158 multiplex families. AMD classification was based on fundus photography and was assigned a grade ranging from 1 ( no disease) to 5 (exudative disease). Genotyping was performed by the National Heart, Lung, and Blood Institute Mammalian Genotyping Service at Marshfield (404 short tandem repeat markers). The sample included 158 families with two or more siblings with AMD, 490 affected individuals, 101 unaffected individuals, and 38 whose affection status was unknown. Relative pairs included 511 affected sibling, 28 avuncular, 53 cousin, 7 grandparent-grandchild, and 9 grand-avuncular pairs. Two-point parametric and multipoint parametric and nonparametric analyses were performed. Maximum two-point LOD scores of 1.0-2.0 were found for markers on chromosomes 1, 2, 8, 10, 14, 15, and 22. Multipoint analyses were consistent with the two-point results for chromosomes 1, 2, 8, 10, and 22 and provided evidence for additional linkage regions on chromosomes 3, 6, 8, 12, 16, and X. Our signals on chromosomes 1q, 6p, and 10q are consistent with some other previously published results. Significant linkage to AMD was found for one marker on chromosome 2, two adjacent markers on chromosome 3, two adjacent markers on chromosome 6, and seven contiguous markers on chromosome 8, with empirical P values of .00001. The consistency of many of the other signals across both two-point and multipoint, as well as parametric and nonparametric, analyses indicate several other regions worthy of follow-up. C1 Massachusetts Eye & Ear Infirm, Ophthalmol Epidemiol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Charlestown, MA USA. RP Seddon, JM (reprint author), Massachusetts Eye & Ear Infirm, Epidemiol Unit, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [U10 EY011309, R01 EY011309, EY11309] NR 66 TC 143 Z9 146 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2003 VL 73 IS 4 BP 780 EP 790 DI 10.1086/378505 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 727TL UT WOS:000185676100006 PM 12945014 ER PT J AU Holley, JL Carmody, SS Moss, AH Sullivan, AM Cohen, LM Block, SD Arnold, RM AF Holley, JL Carmody, SS Moss, AH Sullivan, AM Cohen, LM Block, SD Arnold, RM TI The need for end-of-life care training in nephrology: National survey results of nephrology fellows SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE end-of-life care; medical training; medical education; long-term dialysis; end-stage renal disease (ESRD) ID INCORPORATING PALLIATIVE CARE; EDUCATION; PHYSICIANS AB Because of the high mortality rate of end-stage renal disease, nephrologists care for many dying patients. However, the education of nephrology fellows in palliative care has not been assessed. We surveyed second-year nephrology fellows to assess the quantity and quality of teaching they received in palliative medicine and also asked about their preparedness to manage patients at the end of life. A 63% survey response rate yielded 173 surveys for evaluation. Nearly all fellows (99%) agreed that physicians have a responsibility to help patients at the end of life; half thought it was very important to learn how to care for dying patients. On a 10-point scale in which 0 is no teaching and 10 is a lot of teaching, fellows reported significantly less teaching in end-of-life care (mean score, 3.8 +/- 2.6) than in managing a patient with distal renal tubular acidosis (mean score, 6.3 +/- 2.5) or on hemodialysis therapy (mean score, 8.9 +/- 1.5; all P < 0.0001). Specific palliative care content areas were taught infrequently; only 22% of fellows were taught how to tell a patient he or she is dying. Fellows who had contact with a palliative care specialist reported more education on end-of-life issues and believed they were better prepared to provide such care. Fellows' palliative care experiences during fellowship frequently occurred without attending nephrologist supervision; 32% of fellows had conducted 2 or fewer family meetings, and 26% of all family meetings occurred without an attending nephrologist. Fellows believed they were best prepared to manage a patient on hemodialysis therapy (mean score, 8.9 +/- 1) and least prepared to manage a patient at the end of life (mean score, 6.1 +/- 2; P < 0.0001). Our results show that most nephrology fellows believe they should learn how to care for dying patients, but most fellowship programs do not offer this training. Our study therefore suggests that training in palliative care be incorporated into fellowship program curricula. C1 Univ Virginia Hlth Syst, Div Nephrol, Charlottesville, VA 22908 USA. Univ Pittsburgh, Med Ctr, Sect Palliat Care & Med Eth, Pittsburgh, PA USA. W Virginia Univ, Ctr Hlth Eth & Law, Morgantown, WV 26506 USA. Dana Farber Canc Inst, Div Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Baystate Med Ctr, Psychiat Consultat Serv, Springfield, MA USA. RP Holley, JL (reprint author), Univ Virginia Hlth Syst, Div Nephrol, Box 800133, Charlottesville, VA 22908 USA. NR 17 TC 97 Z9 97 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 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD OCT PY 2003 VL 42 IS 4 BP 813 EP 820 DI 10.1053/S0272-6386(03)00868-0 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 728XK UT WOS:000185741500022 PM 14520633 ER PT J AU Fine, MJ Stone, RA Lave, JR Hough, LJ Obrosky, DS Mor, MK Kapoor, WN AF Fine, MJ Stone, RA Lave, JR Hough, LJ Obrosky, DS Mor, MK Kapoor, WN TI Implementation of an evidence-based guideline to reduce duration of intravenous antibiotic therapy and length of stay for patients hospitalized with community-acquired pneumonia: A randomized controlled trial SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID CLINICAL-PRACTICE GUIDELINES; RESEARCH TEAM COHORT; EARLY SWITCH; MEDICAL LITERATURE; USERS GUIDES; OUTCOMES; DISCHARGE; CARE; RECOMMENDATIONS; COSTS AB PURPOSE: Patients with pneumonia often remain hospitalized after they are stable clinically, and the duration of intravenous antibiotic therapy is a rate-limiting step for discharge. The purpose of this study was to determine whether implementation of an evidence-based guideline would reduce the duration of intravenous antibiotic therapy and length of stay for patients hospitalized with pneumonia. METHODS: In a seven-site, cluster randomized clinical trial, we enrolled 325 control and 283 intervention patients who were admitted by one of 116 physician groups. Within site, physician groups were assigned randomly to receive a practice guideline alone (control arm) or a practice guideline that was implemented using a multifaceted strategy (intervention arm). The effectiveness of guideline implementation was measured by the duration of intravenous antibiotic therapy and length of stay; differences in the rates of discontinuation and hospital discharge were assessed with proportional hazards models. Medical outcomes were assessed at 30 days. RESULTS: Intravenous antibiotic therapy was discontinued somewhat more quickly in the intervention group (hazard ratio [HR] = 1.23; 95% confidence interval [Cl]: 1.00 to 1.52; P = 0.06) than in the control group. Intervention patients were discharged more quickly, but the difference was not statistically significant (FIR = 1.16; 95% Cl: 0.97 to 1.38; P = 0.11). Fewer intervention (55% [157/283]) than control (63% [206/325]) patients had medical complications during the index hospitalization (P = 0.04), with no differences in other medical outcomes, including mortality, rehospitalization, and return to usual activities, between treatment arms. CONCLUSION: The multifaceted guideline implementation strategy resulted in a slight reduction in the duration of intravenous antibiotic therapy and a nonsignificant reduction in length of stay, without affecting patient outcomes. (C) 2003 by Excerpta Medica Inc. C1 Univ Pittsburgh, Grad Sch Publ Hlth, Div Gen Med, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Res Hlth Care, Div Gen Med, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Res Hlth Care, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Res Hlth Care, Dept Hlth Policy & Management, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Res Hlth Care, Dept Biostat, Pittsburgh, PA USA. VA Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Fine, MJ (reprint author), Vet Adm Med Ctr, 130-U,11th Floor,11E127,Univ Dr C, Pittsburgh, PA 15240 USA. FU AHRQ HHS [HS08282] NR 36 TC 60 Z9 61 U1 0 U2 4 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT 1 PY 2003 VL 115 IS 5 BP 343 EP 351 DI 10.1016/S0002-9343(03)00395-4 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 729MA UT WOS:000185776400001 PM 14553868 ER PT J AU Solomon, DH Finkelstein, JS Katz, JN Mogun, H Avorn, J AF Solomon, DH Finkelstein, JS Katz, JN Mogun, H Avorn, J TI Underuse of osteoporosis medications in elderly patients with fractures SO AMERICAN JOURNAL OF MEDICINE LA English DT Article C1 Brigham & Womens Hosp, Div Pharmacoepidemiol, Boston, MA 02120 USA. Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02120 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Solomon, DH (reprint author), Brigham & Womens Hosp, Div Pharmacoepidemiol, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA. FU NIAMS NIH HHS [AR02123, AR47782, AR48616]; NIDDK NIH HHS [DK02759] NR 9 TC 76 Z9 82 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT 1 PY 2003 VL 115 IS 5 BP 398 EP 400 DI 10.1016/S002-9343(03)00357-7 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 729MA UT WOS:000185776400009 PM 14553876 ER PT J AU Hathout, GM Duh, MJ El-Saden, SM AF Hathout, GM Duh, MJ El-Saden, SM TI Accuracy of contrast-enhanced MR angiography in predicting angiographic stenosis of the internal carotid artery: Linear regression analysis SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Radiological-Society-of-North-America CY DEC, 2002 CL CHICAGO, ILLINOIS SP Radiolog Soc North Amer ID MAGNETIC-RESONANCE ANGIOGRAPHY; CONVENTIONAL ANGIOGRAPHY; DIGITAL SUBTRACTION; SUPRAAORTIC VESSELS; HIGH-RESOLUTION; ENDARTERECTOMY; SONOGRAPHY; COMPLICATIONS; VARIABILITY; ULTRASOUND AB BACKGROUND AND PURPOSE: We sought to assess whether contrast-enhanced MR angiography is able to predict the degree of angiographic stenosis of the internal carotid artery within a clinically acceptable margin of error, thereby decreasing the need for angiography. In addition, we sought to assess whether adding ultrasound peak systolic velocity (PSV) as an additional regressor improves the accuracy of prediction. METHODS: A retrospective review of our institution's records for a 4-year period was conducted to identify all patients who had undergone evaluation of their carotid arteries using digital subtraction angiography, contrast-enhanced MR angiography, and ultrasonography. All internal carotid artery stenoses ranging from 10% to 90% at carotid angiography were selected (n = 22). Measurements were then obtained based on the North American Symptomatic Carotid Endarterectomy Trial style by using the digital subtraction angiograms and contrast-enhanced MR angiograms in a blinded fashion. The correlation between digital subtraction angiography data and contrast-enhanced MR angiography data was assessed by conducting linear regression analysis. Multiple regression analysis was then conducted to determine whether the inclusion of ultrasound PSV as an additional regressor increased the accuracy of prediction. RESULTS: The correlation between the degree of stenosis measured by digital subtraction angiography and that measured by contrast-enhanced MR angiography was r = 0.967. The 95% confidence interval for the line of means showed low errors bounds, ranging as low as +/-2.8%. The 95% confidence interval for individual prediction of angiographic stenosis based on a given contrast-enhanced MR angiographic measurement, however, was significantly larger, being no less than +/-13.6%. With the inclusion of PSV, the adjusted correlation was r = 0.965. CONCLUSION. A clear linear relationship exists between digital subtraction angiographic and contrast-enhanced MR angiographic measurements of carotid stenosis. Increasing severity of stenosis as measured by contrast-enhanced MR angiography corresponds to increasing severity at angiography. Although the predictive value of contrast-enhanced MR angiography is excellent in the mean, it is less reliable for predicting the degree of angiographic stenosis in the individual patient, showing rather wide confidence intervals. Furthermore, the inclusion of PSV as an additional regressor does not improve the predictive accuracy beyond that of contrast-enhanced MR angiography alone. C1 Calif State Univ Los Angeles, W Los Angeles Vet Adm Hosp, Dept Radiol, Los Angeles, CA 90073 USA. Calif State Univ Los Angeles, Ctr Med, Los Angeles, CA 90073 USA. RP Hathout, GM (reprint author), Calif State Univ Los Angeles, W Los Angeles Vet Adm Hosp, Dept Radiol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 33 TC 19 Z9 20 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 OCT PY 2003 VL 24 IS 9 BP 1747 EP 1756 PG 10 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 733WC UT WOS:000186022800006 PM 14561597 ER PT J AU Christoforidis, JB Caruso, PA Curtin, HD Fiore, T D'Amico, DJ AF Christoforidis, JB Caruso, PA Curtin, HD Fiore, T D'Amico, DJ TI CT characteristics of intraocular perfluoro-N-octane SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID LIQUID AB Perfluoro-N-octane (PFO) is a heavy liquid that is used as an aid for complicated retinal surgical procedures. Although PFO is usually removed intraoperatively, the radiographic appearance of retained PFO may mimic an intraocular foreign body or vitreous hemorrhage. As the use of PFO in retinal procedures has become more widespread, recognition of its imaging appearance has become important in the differential diagnosis of intraocular foreign body and ocular trauma. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Retina Serv FL 12, Sch Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Sch Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Radiol, Sch Med, Boston, MA 02114 USA. RP D'Amico, DJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Retina Serv FL 12, Sch Med, 243 Charles St, Boston, MA 02114 USA. NR 5 TC 2 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 OCT PY 2003 VL 24 IS 9 BP 1769 EP 1771 PG 3 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 733WC UT WOS:000186022800009 PM 14561600 ER PT J AU Eastwood, JD Lev, MH Wintermark, M Fitzek, C Barboriak, DP Delong, DM Lee, TY Azhari, T Herzau, M Chilukuri, VR Provenzale, JM AF Eastwood, JD Lev, MH Wintermark, M Fitzek, C Barboriak, DP Delong, DM Lee, TY Azhari, T Herzau, M Chilukuri, VR Provenzale, JM TI Correlation of early dynamic CT perfusion imaging with whole-brain MR diffusion and perfusion imaging in acute hemispheric stroke SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID CEREBRAL-ARTERY STROKE; COMPUTED-TOMOGRAPHY; BLOOD-FLOW; XENON CT; ADMISSION; TIME AB BACKGROUND AND PURPOSE: Compared with MR imaging, dynamic CT perfusion imaging covers only a fraction of the whole brain. An important assumption is that CT perfusion abnormalities correlate with total ischemic volume. The purpose of our study was to measure the degree of correlation between abnormalities seen on CT perfusion scans and the volumes of abnormality seen on MR diffusion and perfusion images in patients with acute large-vessel stroke. METHODS: Fourteen patients with acute hemispheric stroke symptoms less than 12 hours in duration were studied with single-slice CT perfusion imaging and multislice MR diffusion and perfusion imaging. CT and MR perfusion studies were completed within 2.5 hours of one another (mean, 77 minutes) and were reviewed independently by two neuroradiologists. Hemodynamic parameters included cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). Extents of abnormality on images were compared by using Kendall correlation. RESULTS: Statistically significant correlation was found between CT-CBF and MR-CBF abnormalities (tau = 0.60, P = .003) and CT-MTT and MR-MTT abnormalities (tau = 0.65, P = .001). Correlation of CT-CBV with MR-CBV approached significance (tau = 0.39, P = .06). Extent of initial hyperintensity on diffusion-weighted images correlated best with extent of MR-CBV abnormality (tau = 0.69, P = .001), extent of MR-MTT abnormality (tau = 0.67, P = .002), and extent of CT-CBV abnormality (tau = 0.47, P = .02). CONCLUSION. Good correlation was seen between CT and MR for CBF and MTT abnormalities. It remains uncertain whether CT perfusion CBV abnormalities correspond well to whole-brain abnormalities. C1 Duke Univ, Med Ctr, Dept Radiol, Div Neurol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Community & Family Med, Div Neurol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Div Neurol, Durham, NC 27710 USA. Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. Univ Lausanne Hosp, Dept Intervent Radiol, Lausanne, Switzerland. Univ Jena, Dept Diagnost & Intervent Radiol, D-6900 Jena, Germany. John P Robarts Res Inst, Imaging Res Labs, London, ON N6A 5K8, Canada. RP Eastwood, JD (reprint author), Duke Univ, Med Ctr, Dept Radiol, Div Neurol, Box 3808, Durham, NC 27710 USA. RI Lee, Ting-Yim/M-1721-2013; OI Wintermark, Max/0000-0002-6726-3951 NR 12 TC 130 Z9 136 U1 0 U2 4 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD OCT PY 2003 VL 24 IS 9 BP 1869 EP 1875 PG 7 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 733WC UT WOS:000186022800027 PM 14561618 ER PT J AU Jain, T Klein, NA Lee, DM Sluss, PM Soules, MR AF Jain, T Klein, NA Lee, DM Sluss, PM Soules, MR TI Endocrine assessment of relative reproductive age in normal eumenorrheic younger and older women across multiple cycles SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE follicle-stimulating hormone; estradiol; inhibin B; ovarian reserve; reproductive aging ID FOLLICLE-STIMULATING-HORMONE; IN-VITRO FERTILIZATION; HUMAN MENSTRUAL-CYCLE; DAY 3 ESTRADIOL; INHIBIN-B; INVITRO FERTILIZATION; DIMERIC INHIBIN; FEMALE FECUNDITY; ACTIVIN-A; SERUM AB OBJECTIVE: The aim of this study was to better characterize the ranges and intercycle variability for day 3 follicle-stimulating hormone, estradiol, and inhibin B levels in normal eumenorrheic women. STUDY DESIGN: Healthy eumenorrheic volunteers were recruited, of whom 27 women were 20 to 25 years old (peak reproductive age) and 36 women were 40 to 45 years old (study population). Blood samples were obtained on day 3 of two consecutive menstrual cycles. In some women, an additional blood sample on day 3 was obtained within 1 year. RESULTS: In normal women aged 20 to 25 years versus women aged 40 to 45 years, the day 3 follicle-stimulating hormone geometric mean is 5.6 IU/L (95% Cl, 3.3-9.5 IU/L) versus 9.6 IU/L (95% Cl, 3.8-23.8 IU/L), the day 3 estradiol geometric mean is 44.0 pg/mL (95% Cl, 20.4-95.0 pg/mL) versus 52.4 pg/mL (95% Cl, 22.4-122.8 pg/mL), and the day 3 inhibin B geometric mean is 100.4 pg/mL (95% Cl, 51.7-195.0 pg/mL) versus 52.4 pg/mL (95% Cl, 9.5-289.3 pg/mL). Furthermore, 22% of women in the older age group have a normal day 3 follicle-stimulating hormone and estradiol level in one cycle but an elevated value in a consecutive cycle (P = 008). CONCLUSION: In women of peak reproductive age, the upper limit of day 3 follicle-stimulating hormone and estradiol levels are 9.5 IU/L and 95.0 pg/mL, respectively, and the lower limit of day 3 inhibin B level is 51.7 pg/mL. If the initial day 3 follicle-stimulating hormone and estradiol levels in an older woman are normal, then a second measurement in a subsequent cycle should be obtained before counseling this woman regarding her reproductive potential. C1 Univ Washington, Med Ctr, Dept Obstet & Gynecol, Div Reproduct Endocrinol & Infertil, Seattle, WA 98195 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Reprod Endocrine Unit, Boston, MA USA. RP Jain, T (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02115 USA. OI Jain, Tarun/0000-0002-8889-084X NR 25 TC 18 Z9 18 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 OCT PY 2003 VL 189 IS 4 BP 1080 EP 1084 DI 10.1067/S0002-9378(03)00583-0 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 740BN UT WOS:000186381100038 PM 14586359 ER PT J AU Styer, AK Parker, HJ Roberts, DJ Palmer-Toy, D Toth, TL Ecker, JL AF Styer, AK Parker, HJ Roberts, DJ Palmer-Toy, D Toth, TL Ecker, JL TI Placental villitis of unclear etiology during ovum donor in vitro fertilization pregnancy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE ova donation; in vitro fertilization; villitis of unclear etiology; VUE ID MATERNAL FLOOR INFARCTION; MASSIVE CHRONIC INTERVILLOSITIS; UNKNOWN ETIOLOGY AB OBJECTIVE: Preliminary observations by a single pathologist at our institution revealed a 75% incidence of villitis of unexplained etiology in ovum donor in vitro fertilization pregnancies. Because the incidence of villitis of unexplained etiology in the general population is approximately 10%, we conducted a controlled study to compare the incidence of villitis of unexplained etiology in ovum donor in vitro fertilization pregnancies to that in in vitro fertilization pregnancies that do not use donated ova. STUDY DESIGN: Placental specimens of ovum donor in vitro fertilization pregnancies were matched randomly with pregnancies that resulted from both fresh and frozen/thawed native oocyte in vitro fertilization from March 5, 1995, to October 10, 2001, and examined in a blinded fashion by a single pathologist (D. J. R.) for villitis of unexplained cause. The incidence of villitis of unexplained etiology was analyzed in 27 patients who underwent ovum donor in vitro fertilization versus 37 patients who underwent native oocyte in vitro fertilization. RESULTS: Villitis of unexplained cause occurred in 22.2% of ovum donor in vitro fertilization pregnancies, 10.8% of native oocyte in vitro fertilization pregnancies (fresh and frozen/thawed combined), and 14.3% of frozen/thawed cycles (P = .21). CONCLUSION: Although the incidence was not statistically different than in in vitro fertilization that used native maternal oocytes, there was a 2-fold increase in villitis of unexplained cause in the ovum donor in vitro fertilization placentas, which suggests that immune-related disorders may be increased in ovum donor pregnancies. C1 Massachusetts Gen Hosp, Div Maternal Fetal Med, Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Reprod Endocrinol & Infertil, Boston, MA 02114 USA. RP Ecker, JL (reprint author), Massachusetts Gen Hosp, Div Maternal Fetal Med, Dept Obstet & Gynecol, Vincent Ctr Reprod Biol, 55 Fruit St, Boston, MA 02114 USA. NR 9 TC 15 Z9 17 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 2003 VL 189 IS 4 BP 1184 EP 1186 DI 10.1067/S0002-9378(03)00577-5 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 740BN UT WOS:000186381100054 PM 14586376 ER PT J AU Polanczyk, M Zamora, A Subramanian, S Matejuk, A Hess, DL Blankenhorn, EP Teuscher, C Vandenbark, AA Offner, H AF Polanczyk, M Zamora, A Subramanian, S Matejuk, A Hess, DL Blankenhorn, EP Teuscher, C Vandenbark, AA Offner, H TI The protective effect of 17b-estradiol on experimental autoimmune encephalomyelitis is mediated through estrogen receptor-a SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; ALPHA-DEFICIENT MICE; MULTIPLE-SCLEROSIS; KNOCKOUT MICE; FEMALE MICE; BETA; EXPRESSION; PREGNANCY; CHEMOKINE; IMMUNOSUPPRESSION AB Low-dose estrogen (E2) treatment significantly inhibits the clinical signs and histopathological lesions of experimental autoimmune encephalomyelitis (EAE), and is being used in clinical trials to treat multiple sclerosis. To assess the role of intracytoplasmic estrogen receptors in mediating suppression of EAE, we studied mice with disrupted estrogen receptor-alpha (Esr1) and -beta (Esr2) genes. We demonstrate that the protective effect of E2 is abrogated in B6.129-Esr1(tm1Unc) mice (Esr1-/-) but not in B6.129-Esr2(tm1Unc) mice (Esr2(-/-)). The loss of E2-mediated protection from EAE in Esr1(-/-) mice immunized with the encephalitogenic MOG-35-55 peptide was manifested phenotypically by the development of severe acute clinical signs and histopathological lesions even in the presence of moderately high serum E2 levels. This is in contrast to C57BL/6 wild-type (WT) mice and Esr2(-/-) mice in which E2 treatment resulted in comparable serum levels and markedly suppressed clinical signs of EAE and abolished inflammatory lesions in the CNS. This pattern showing a lack of E2-dependent inhibition of EAE in Esr1-/- mice was mirrored by an enhanced rather than a reduced secretion of TNF-alpha, IFN-gamma, and interleukin (IL)-6 in MOG-specific splenocytes; and a lack of inhibition of message for inflammatory cytokines, chemokines and chemokine receptors in CNS tissue. These results indicate that the immunomodulatory effects of E2 in EAE are dependent on Esr1 and not Esr2 signaling. C1 Portland VA Med Ctr, Neuroimmunol Res, R&D 31, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR USA. Agr Univ Warsaw, Fac Vet Med, Dept Food Hyg, Warsaw, Poland. Oregon Reg Primate Res Ctr, Beaverton, OR 97006 USA. Oregon Hlth & Sci Univ, Div Reprod Sci, Portland, OR USA. Drexel Univ, Coll Med, Dept Microbiol & Immunol, Philadelphia, PA 19104 USA. Univ Vermont, Dept Med, Burlington, VT USA. Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR USA. RP Offner, H (reprint author), Portland VA Med Ctr, Neuroimmunol Res, R&D 31, 3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. FU NIAID NIH HHS [AI41747, AI42376, AI45105, R01 AI041747]; NINDS NIH HHS [NS23221, NS23444, NS36526, R01 NS023221, R01 NS023444, R01 NS036526] NR 32 TC 99 Z9 103 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 2003 VL 163 IS 4 BP 1599 EP 1605 DI 10.1016/S0002-9440(10)63516-X PG 7 WC Pathology SC Pathology GA 724ZE UT WOS:000185517500036 PM 14507666 ER PT J AU Bouley, R Sun, TX Chenard, M McLaughlin, M McKee, M Lin, HY Brown, D Ausiello, DA AF Bouley, R Sun, TX Chenard, M McLaughlin, M McKee, M Lin, HY Brown, D Ausiello, DA TI Functional role of the NPxxY motif in internalization of the type 2 vasopressin receptor in LLC-PK1 cells SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE polarized cell culture; tyrosine motif; mu 1b adaptor motif; protein traffic ID PROTEIN-COUPLED RECEPTORS; RENAL EPITHELIAL-CELLS; CANINE KIDNEY-CELLS; NEPHROGENIC DIABETES-INSIPIDUS; SMOOTH-MUSCLE-CELLS; V2 RECEPTOR; SIGNAL-TRANSDUCTION; MEDIATED ENDOCYTOSIS; MDCK CELLS; BETA(2)-ADRENERGIC RECEPTOR AB Interaction of the type 2 vasopressin receptor (V2R) with hormone causes desensitization and internalization. To study the role of the V2R NPxxY motif ( which is involved in the clathrin-mediated endocytosis of several other receptors) in this process, we expressed FLAG-tagged wild-type V2R and a Y325F mutant V2R in LLC-PK1a epithelial cells that have low levels of endogenous V2R. Both proteins had a similar apical (35%) and basolateral (65%) membrane distribution. Substitution of Tyr(325) with Phe(325) prevented ligand-induced internalization of V2R determined by [H-3]AVP binding and immunofluorescence but did not prevent ligand binding or signal transduction via adenylyl cyclase. Desensitization and resensitization of the V2R-Y325F mutation occurred independently of internalization. The involvement of clathrin in V2R downregulation was also shown by immunogold electron microscopy. We conclude that the NPxxY motif of the V2R is critically involved in receptor downregulation via clathrin-mediated internalization. However, this motif is not essential for the apical/basolateral sorting and polarized distribution of the V2R in LLC-PK1a cells or for adenylyl cyclase-mediated signal transduction. C1 Massachusetts Gen Hosp, Dept Med, Program Membrane Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bouley, R (reprint author), Massachusetts Gen Hosp E, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK-38482, K08 DK-02716, DK-19406, DK-43351, DK-57521] NR 68 TC 31 Z9 31 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD OCT 1 PY 2003 VL 285 IS 4 BP C750 EP C762 DI 10.1152/ajpcell.00477.2002 PG 13 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 718GA UT WOS:000185135700004 PM 12801889 ER PT J AU Roelen, BAJ Cohen, OS Raychowdhury, MK Chadee, DN Zhang, Y Kyriakis, JM Alessandrini, AA Lin, HY AF Roelen, BAJ Cohen, OS Raychowdhury, MK Chadee, DN Zhang, Y Kyriakis, JM Alessandrini, AA Lin, HY TI Phosphorylation of threonine 276 in Smad4 is involved in transforming growth factor-beta-induced nuclear accumulation SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE signal transduction; mitogen-activated protein kinase; phosphopeptide mapping; extracellular signal-regulated kinase; phosphorylation site; luciferase reporter ID TUMOR-SUPPRESSOR SMAD4; CRYSTAL-STRUCTURE; ONCOGENIC RAS; RECEPTOR; GENE; DPC4; TRANSCRIPTION; REQUIREMENT; INDUCTION; MEDIATOR AB Smad4, the common Smad, is central for transforming growth factor (TGF)-beta superfamily ligand signaling. Smad4 has been shown to be constitutively phosphorylated (Nakao A, Imamura T, Souchelnytskyi S, Kawabata M, Ishisaki A, Oeda E, Tamaki K, Hanai J, Heldin C-H, Miyazono K, and ten Dijke P. EMBO J 16: 5353-5362, 1997), but the site(s) of phosphorylation, the kinase(s) that performs this phosphorylation, and the significance of the phosphorylation of Smad4 are currently unknown. This report describes the identification of a consensus ERK phosphorylation site in the linker region of Smad4 at Thr(276). Our data show that ERK can phosphorylate Smad4 in vitro but not Smad4 with mutated Thr(276). Flag-tagged Smad4-T276A mutant protein accumulates less efficiently in the nucleus after stimulation by TGF-beta and is less efficient in generating a transcriptional response than Smad4 wild-type protein. Tryptic phosphopeptide mapping identified a phosphopeptide in Smad4 wild-type protein that was absent in phosphorylated Smad4-T276A mutant protein. Our results suggest that MAP kinase can phosphorylate Thr(276) of Smad4 and that phosphorylation can lead to enhanced TGF-beta-induced nuclear accumulation and, as a consequence, enhanced transcriptional activity of Smad4. C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. Tufts Univ, Sch Med, New England Med Ctr, Mol Cardiol Res Inst, Boston, MA 02111 USA. RP Lin, HY (reprint author), Massachusetts Gen Hosp, Renal Unit, 13th St Bldg 149, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK-19406, DK-02716] NR 27 TC 31 Z9 38 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD OCT 1 PY 2003 VL 285 IS 4 BP C823 EP C830 DI 10.1152/ajpcell.00053.2003 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 718GA UT WOS:000185135700012 PM 12801888 ER PT J AU Wechsler, H Lee, JE Nelson, TF Lee, H AF Wechsler, H Lee, JE Nelson, TF Lee, H TI Drinking and driving among college students - The influence of alcohol-control policies SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID BINGE-DRINKING; HARVARD-SCHOOL; YOUNG-ADULTS; HEALTH; INTERVENTIONS; BEHAVIORS; DRIVERS AB Background: Studies have reported high rates of heavy episodic drinking and alcohol-related problems, including drinking and driving, among college students. However, most studies have been conducted in single colleges or states. This study used a national sample to examine policy factors associated with alcohol-involved driving. Methods: A random sample of full-time students (N=10,904) attending a nationally representative sample of 4-year colleges in 39 states (n= 119) completed self-administered questionnaires. The questionnaire examined driving after consuming any alcohol, driving after greater than or equal to5 drinks, and riding with a high or drunk driver. Individual-level data about driving after greater than or equal to5 drinks were linked to information on the policy environment at both local and state levels and to ratings of enforcements for drunk driving laws. Results: Drinking and driving behaviors are prevalent among a minority of college students and differ significantly among student subgroups. Students who attend colleges in states that have more restrictions on underaged drinking, high volume consumption, and sales of alcoholic beverages, and devote more resources to enforcing drunk driving laws, report less drinking and driving. Conclusion: The occurrence of drinking and driving among college students differs significantly according to the policy environment at local and state levels and the enforcement of those policies. Comprehensive policies and their strong enforcement are promising interventions to reduce drinking and driving among college students. C1 Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wechsler, H (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, 677 Huntington Ave, Boston, MA 02115 USA. NR 30 TC 59 Z9 60 U1 4 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2003 VL 25 IS 3 BP 212 EP 218 DI 10.1016/S0749-3797(03)00199-5 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 728MD UT WOS:000185720200005 PM 14507527 ER PT J AU Ackermann, RT Cheadle, A Sandhu, N Madsen, L Wagner, EH LoGerfo, JP AF Ackermann, RT Cheadle, A Sandhu, N Madsen, L Wagner, EH LoGerfo, JP TI Community exercise program use and changes in healthcare costs for older adults SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID INTERVENTIONS AB Background: Regular exercise is associated with many health benefits. Community-based exercise programs may increase exercise participation, but little is known about cost implications. Methods: A retrospective, matched cohort study was conducted to determine if changes in healthcare costs for Medicare-eligible adults who choose to participate in a community-based exercise program were different from similar individuals who did not participate. Exercise program participants included 1114 adults aged greater than or equal to65 years, who were continuously enrolled in Group Health Cooperative of Puget Sound (GHQ between October 1, 1997 and December 31, 2000 and who participated in the Lifetime Fitness (exercise) Program(R), (LFP) at least once; three GHC enrollees who never attended LFP were randomly selected as controls for each participant by matching on age and gender. Cost and utilization estimates from GHC administrative data for the time from LFP enrollment to December 31, 2000 were compared using multivariable regression models. Results: The average increase in annual total healthcare costs was less in participants compared to controls (+$642 vs +$1175; p=0.05). After adjusting for differences in age, gender, enrollment date, comorbidity index, and pre-exposure cost and utilization levels, total healthcare costs for participants were 94.1% (95% confidence interval [CI], 85.6%-103.5%) of control costs. However, for participants who attended the exercise program at an average rate of greater than or equal to1 visit weekly, total adjusted follow-up costs were 79.3% (95% Cl, 71.3%-88.2%) of controls. Conclusions: Including a community exercise program as a health insurance benefit shows promise as a strategy for helping some Medicare-eligible adults to improve their health through exercise. C1 Univ Washington, Robert Wood Johnson Clin Scholars Program, Hlth Sci Ctr H220, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Grp Hlth Cooperat Puget Sound, Hlth Improvement Program, Seattle, WA 98101 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth & Community Med, Hlth Promot Res Ctr, Seattle, WA 98195 USA. RP Ackermann, RT (reprint author), Univ Washington, Robert Wood Johnson Clin Scholars Program, Hlth Sci Ctr H220, Box 357183, Seattle, WA 98195 USA. FU ODCDC CDC HHS [U48/CCU009654-09] NR 14 TC 48 Z9 49 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD OCT PY 2003 VL 25 IS 3 BP 232 EP 237 DI 10.1016/S0749-3797(03)00196-X PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 728MD UT WOS:000185720200008 PM 14507530 ER PT J AU Ibrahim, SA Thomas, SB Fine, MJ AF Ibrahim, SA Thomas, SB Fine, MJ TI Achieving health equity: An incremental journey SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID RACIAL-DIFFERENCES C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Grad Sch Pub Hlth, Ctr Minor Hlth, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. RP Ibrahim, SA (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C,11-E 130 A-U, Pittsburgh, PA 15240 USA. NR 22 TC 13 Z9 13 U1 1 U2 1 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 OCT PY 2003 VL 93 IS 10 BP 1619 EP 1621 DI 10.2105/AJPH.93.10.1619 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 731JT UT WOS:000185881100006 PM 14534208 ER PT J AU Fine, MJ Demakis, JG AF Fine, MJ Demakis, JG TI The Veterans Health Administration's promotion of health equity for racial and ethnic minorities SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Ctr Res & Hlth Care, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Med, Sch Med, Pittsburgh, PA 15260 USA. VA Hlth Serv Res & Dev Serv, Washington, DC USA. RP Fine, MJ (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Univ Dr C 130-U, Pittsburgh, PA 15240 USA. NR 10 TC 9 Z9 9 U1 1 U2 1 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 OCT PY 2003 VL 93 IS 10 BP 1622 EP 1624 DI 10.2105/AJPH.93.10.1622 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 731JT UT WOS:000185881100007 PM 14534209 ER PT J AU Ibrahim, SA Whittle, J Bean-Mayberry, B Kelley, ME Good, C Conigliaro, J AF Ibrahim, SA Whittle, J Bean-Mayberry, B Kelley, ME Good, C Conigliaro, J TI Racial/ethnic variations in physician recommendations for cardiac revascularization SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID OF-VETERANS-AFFAIRS; CORONARY HEART-DISEASE; BYPASS GRAFT-SURGERY; RACIAL-DIFFERENCES; UNITED-STATES; BLACK POPULATIONS; ARTERY DISEASE; RATES; RACE; MORTALITY AB Objectives. We sought to examine whether physician recommendations for cardiac revascularization vary according to patient race. Methods. We studied patients scheduled for coronary angiography at 2 hospitals, one public and one private, between November 1997 and June 1999. Cardiologists were interviewed regarding their recommendations for cardiac resvacularization. Results. African American patients were less likely than Whites to be recommended for revascularization at the public hospital (adjusted odds ratio [OR]=0.31; 95% confidence interval [Cl]=0.12, 0.77) but not at the private hospital (adjusted OR=1.69; 95% CI=0.69, 4.14). Conclusions. Physician recommendations for cardiac revascularization vary by patient race. Further studies are needed to examine physician bias as a factor in racial disparities in cardiac care and outcomes. C1 Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15240 USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. RP Ibrahim, SA (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15240 USA. NR 29 TC 47 Z9 47 U1 1 U2 2 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 OCT PY 2003 VL 93 IS 10 BP 1689 EP 1693 DI 10.2105/AJPH.93.10.1689 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 731JT UT WOS:000185881100021 PM 14534223 ER PT J AU McGinnis, KA Fine, MJ Sharma, RK Skanderson, M Wagner, JH Rodriguez-Barradas, MC Rabeneck, L Justice, AC AF McGinnis, KA Fine, MJ Sharma, RK Skanderson, M Wagner, JH Rodriguez-Barradas, MC Rabeneck, L Justice, AC TI Understanding racial disparities in HIV using data from the veterans aging cohort 3-site study and VA administrative data SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID ANTIRETROVIRAL THERAPY; CARE SYSTEM; RACE/ETHNICITY; MORTALITY AB Objectives. We identified race-associated differences in survival among HIV-positive US veterans to examine possible etiologies for these differences. Methods. We used national administrative data to compare survival by race and used data from the Veterans Aging Cohort 3-Site Study (VACS 3) to compare patients' health status, clinical management, and adherence to medication by race. Results. Nationally, minority veterans had higher mortality rates than did white veterans with HIV. Minority veterans had poorer health than white veterans with HIV. No significant differences were found in clinical management or adherence. Conclusions. HIV-positive minority veterans experience poorer survival than white veterans. This difference may derive from differences in comorbidities and in the severity of illness of HIV-related disease. C1 W Haven VA Healthcare Syst, West Haven, CT 06516 USA. VA Pittsburgh Healthcare Syst, Vet Aging Cohort Study Ctr, Pittsburgh, PA USA. Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Div Gen Internal Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. VA Med Ctr, VA Hlth Serv Res & Dev Ctr Excellence, Houston, TX USA. Baylor Coll Med, Dept Med, Houston, TX USA. RP Justice, AC (reprint author), W Haven VA Healthcare Syst, 950 Campbell Ave,11-ACSLG, West Haven, CT 06516 USA. FU NIA NIH HHS [K23 AG00826]; NIAAA NIH HHS [U01 AA 13566, U01 AA013566]; NIAID NIH HHS [K24 AI001769, K24 AI01769-04]; NIDDK NIH HHS [K24 DK59318] NR 17 TC 73 Z9 73 U1 1 U2 2 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 OCT PY 2003 VL 93 IS 10 BP 1728 EP 1733 DI 10.2105/AJPH.93.10.1728 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 731JT UT WOS:000185881100027 PM 14534229 ER PT J AU Waxman, AB Mahboubi, K Knickelbein, RG Mantell, LL Manzo, N Pober, JS Elias, JA AF Waxman, AB Mahboubi, K Knickelbein, RG Mantell, LL Manzo, N Pober, JS Elias, JA TI Interleukin-11 and interleukin-6 protect cultured human endothelial cells from H2O2-induced cell death SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID SIGNAL TRANSDUCER GP130; LUNG INJURY; ANTIINFLAMMATORY CYTOKINE; OXIDATIVE STRESS; STAT3 ACTIVATION; GROWTH ARREST; IL-6; APOPTOSIS; OXYGEN; KINASE AB Acute lung injury is a frequent and treatment-limiting consequence of therapy with 100% oxygen. Previous studies have determined that both interleukin (IL)-6 and IL-11 are protective in oxygen toxicity. This protection was associated with markedly diminished alveolar-capillary protein leak, endothelial and epithelial membrane injury, lipid peroxidation, and pulmonary neutrophil recruitment. Hyperoxia also caused cell death with DNA fragmentation in the lungs of transgene (-) animals, and both IL-6 and IL-11 markedly diminished this cell death response. However, the mechanism(s) by which these cytokines protect cells from death is unclear. In the present study, we characterized the effects of H2O2 on subconfluent human umbilical vein endothelial cell (HUVEC) and human pulmonary microvascular endothelial cell (HPMEC) cultures. We found that preincubation of HUVEC cultures with either IL-6 or IL-11 diminished H2O2 (1.0 mM)-induced cell death. Similar effects were noted with HPMEC showing that this effect is not HUVEC-specific. The protective effects of both IL-6 and IL-11 were not associated with any changes in antioxidants and were decreased by similar to 80% in the presence of U0126, a specific inhibitor of MEK-1-dependent pathways. The cytoprotective effects of IL-11 and IL-6 were also completely eliminated in STAT3 dominant-negative transduced HUVEC cultures. These studies demonstrate that IL-6 and IL-11 both confer cytoprotective effects that diminish oxidant-mediated endothelial cell injury. They also demonstrate that this protection is mediated, at least in part, by a STAT3 and MEK-1-dependent specific signal transduction pathway(s). C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm Crit Care Unit, Boston, MA 02114 USA. Yale Univ, Sch Med, Boyer Ctr Mol Med, Interdepartmental Program Vasc Biol & Transplanta, New Haven, CT USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. NYU, Sch Med, Dept Surg, Cardiac Res Lab,N Shore Long Isl Jewish Med Ctr, Manhasset, NY USA. Yale Univ, Sch Med, Sect Pulm & Crit Care Med, Dept Internal Med, New Haven, CT USA. RP Waxman, AB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm Crit Care Unit, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA. FU NHLBI NIH HHS [R01-HL-62188, K08-HL-03888, R01-HL-64242] NR 51 TC 55 Z9 58 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD OCT PY 2003 VL 29 IS 4 BP 513 EP 522 DI 10.1165/rcmb.2002-0044OC PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 727EL UT WOS:000185643900013 PM 12730073 ER PT J AU Kassarjian, A Fishman, SJ Fox, VL Burrows, PE AF Kassarjian, A Fishman, SJ Fox, VL Burrows, PE TI Imaging characteristics of blue rubber bleb nevus syndrome SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Childrens Hosp, Div Gastroenterol & Nutr, Boston, MA 02115 USA. RP Kassarjian, A (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, 15 Parkman St,WACC 515, Boston, MA 02114 USA. NR 10 TC 28 Z9 32 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2003 VL 181 IS 4 BP 1041 EP 1048 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 724NB UT WOS:000185492700027 PM 14500226 ER PT J AU Sandner, SE Salama, AD Houser, SL Palmer, E Turka, LA Sayegh, MH AF Sandner, SE Salama, AD Houser, SL Palmer, E Turka, LA Sayegh, MH TI New TCR transgenic model for tracking allospecific CD4 T-cell activation and tolerance in vivo SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE alloimmunity; animal model; rejection; T cell costimulation; TCR transgenic mice; tolerance ID CLONAL EXPANSION; HOMEOSTATIC PROLIFERATION; ALLOGRAFT-REJECTION; CD28 COSTIMULATION; POSITIVE SELECTION; MEDIATED REJECTION; ISLET ALLOGRAFTS; CUTTING EDGE; NAIVE; MEMORY AB We have developed an adoptive transfer model system to visualize the dynamics of alloantigen-specific CD4(+) T-cell activation in vivo. Using TCR-transgenic (tg) mice reactive to I-A(bm12), we studied the clonal expansion and differentiation of alloreactive T cells by tracking the fate of adoptively transferred TCR-tg CD4(+) T cells in syngeneic mice transplanted with skin grafts expressing I-A(bm12). Following transplantation, alloantigen-specific TCR-tg CD4(+) T-cell expansion was observed initially in the draining lymph nodes followed by the spleen. TCR-tg CD4(+) T cells up-regulated CD69 and CD25. expression, developed an effector/memory surface phenotype and produced IFN-gamma in response to alloantigen ex vivo. Furthermore, we validate the model system as a means for studying the effects of tolerogenic regimens on alloreactive CD4(+) T cells, demonstrating that CTLA4Ig inhibits alloantigen-dependent clonal expansion and effector function of TCR-tg CD4(+) T cells in vivo. We describe the first model for tracking alloreactive CD4(+) T-cell. activation in vivo. It provides a powerful tool for studying CD4(+) T-dell mediated alloimmune responses and mechanisms of tolerance induction in vivo. C1 Harvard Univ, Sch Med, Childrens Hosp, Div Nephrol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Immunogenet & Transplantat, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Univ Basel Hosp, CH-4031 Basel, Switzerland. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. RP Sayegh, MH (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Div Nephrol, Boston, MA 02115 USA. RI Salama, Alan/B-5183-2010 FU NIAID NIH HHS [AI-37691, AI-41521, AI-51559] NR 36 TC 27 Z9 27 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD OCT PY 2003 VL 3 IS 10 BP 1242 EP 1250 DI 10.1046/j.1600-6143.2003.00220.x PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA 731RH UT WOS:000185899900010 PM 14510697 ER PT J AU Strack, S AF Strack, S TI Herman Feifel (1915-2003) - Obituary SO AMERICAN PSYCHOLOGIST LA English DT Biographical-Item C1 US Dept Vet Affairs, Los Angeles Ambulatory Care Ctr, Los Angeles, CA USA. RP Strack, S (reprint author), US Dept Vet Affairs, Los Angeles Ambulatory Care Ctr, Los Angeles, CA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD OCT PY 2003 VL 58 IS 10 BP 810 EP 810 DI 10.1037/0003-066X.58.10.810 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 735RF UT WOS:000186127800007 ER PT J AU Liu, JH Zingmond, D Etzioni, DA O'Connell, JB Maggard, MA Livingston, EH Liu, CD Ko, CY AF Liu, JH Zingmond, D Etzioni, DA O'Connell, JB Maggard, MA Livingston, EH Liu, CD Ko, CY TI Characterizing the performance and outcomes of obesity surgery in California SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT Annual Meeting of the Southern California Chapter of the American-College-of-Surgeons CY JAN 24-26, 2003 CL SANTA BARBARA, CALIFORNIA SP Amer Coll Surg, SO Calif Chapter ID GASTRIC BYPASS-SURGERY; UNITED-STATES; MORBID-OBESITY; RISK-FACTORS; VOLUME; MORTALITY; EPIDEMIC AB Between 1991 and 2000, the prevalence of obesity increased 65 per cent. As a result, increasing research is being directed at gastric bypass (GB) surgery, an operation that appears to achieve long-term weight reduction. Despite the rapid proliferation of this surgery, the quality of care at a population level is largely unknown. This study examines longitudinal trends in quality and identifies significant predictors of adverse outcomes. Using the California inpatient discharge database, all GB operations from 1996 to 2000 were identified. Demographic, comorbidity, complication, and volume data were obtained. Complications were defined as life-threatening cardiac, respiratory, or medical (renal failure or shock) events. Comorbidity was graded on a modified Charlson score. Annual hospital volume was categorized into four groups: <50, 50-99, 100-199, and 200+ cases. Based on these data, we calculated longitudinal trends in complication rate and performed logistic regression to identify predictors of complications. A total of 16,232 patients were included. The average age was 41 years; 84 per cent were female, and 83.5 per cent were white. The complication rate was 10.4 per cent. Between 1996 and 2000, rates of cardiac and respiratory complications decreased while rates of medical complications remained unchanged. Complications were more likely in men [odd ratio (OR) = 1.69 compared to women] and in patients with comorbidities (OR = 1.60 for each additional comorbid disease). Furthermore, when examining the effect of volume, patients at very low (<50) and low (50-99) volume hospitals were much more likely to have complications (OR = 2.72 and 2.70, respectively) compared to patients at high-volume hospitals (200+), even after controlling for differences in case-mix. The quality of care for obesity surgery has improved between 1996 and 2000. Despite operating on patients with more comorbidity, rates of cardiac and respiratory complications have decreased. Furthermore, this study identifies three independent predictors of complications: gender, comorbidity, and hospital volume. These findings are important initial steps toward improving quality in obesity surgery. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. W Los Angeles Vet Adm, Dept Surg, Los Angeles, CA USA. W Los Angeles Vet Adm, Dept Gen Internal Med, Los Angeles, CA USA. Univ Texas, SW Med Ctr, Dept Surg, Dallas, TX 75235 USA. RP Liu, JH (reprint author), 11301 W Olympic Blvd,648, Los Angeles, CA 90064 USA. NR 27 TC 60 Z9 60 U1 0 U2 1 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD OCT PY 2003 VL 69 IS 10 BP 823 EP 828 PG 6 WC Surgery SC Surgery GA 729KD UT WOS:000185771600001 PM 14570356 ER PT J AU O'Connell, JB Maggard, MA Liu, JH Etzioni, DA Livingston, EH Ko, CY AF O'Connell, JB Maggard, MA Liu, JH Etzioni, DA Livingston, EH Ko, CY TI Rates of colon and rectal cancers are increasing in young adults SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT Annual Meeting of the Southern California Chapter of the American-College-of-Surgeons CY JAN 24-26, 2003 CL SANTA BARBARA, CALIFORNIA SP Amer Coll Surg, SO Calif Chapter ID 40 YEARS OLD; COLORECTAL-CANCER; PATIENTS LESS; LARGE-BOWEL; 3 DECADES; CARCINOMA; AGE; ADENOCARCINOMA; LIFE; PROGNOSIS AB Incidence rates for colorectal cancer are decreasing in the United States, possibly due to preventative cancer screening. Because these programs target older patients, their beneficial effects may not apply to young patients. The purpose of this study was to compare incidence rates and tumor characteristics of colon and rectal cancers for young versus older patients using a population-based cancer registry. Colon and rectal cancer patients reported in the Surveillance, Epidemiology, and End Results registry (1973-1999) were separately analyzed. Incidence rates over time stage, and grade were compared for two age groups: young patients (20-40 years, n = 5383) And older patients (60+ years, n = 256,401). For older patients, colon cancer incidence remained stable while rectal cancer incidence decreased 11 per cent to 72.1/100,000 persons (P < 0.05). For the young, colon cancer incidence increased 17 per cent to 2.1 (P < 0.05), and rectal incidence rose 75 per cent to 1.4 (P < 0.05). Young patients had less localized tumors than older patients: colon (25.8% vs. 35.3%, P < 0.001); rectal (38.4% vs. 41.7%, P = 0.005). Young patients also had more poorly differentiated tumors: colon (22.2% vs. 14.7%, P < 0.001); rectal (16.4% vs. 12.3%, P < 0.001). Incidence rates for colon and rectal cancers in young patients are rising, and they have more advanced disease. Although the overall prevalence is low in this population, the increasing incidence suggests health-care providers should have heightened awareness when caring for this population. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. W Los Angles Vet Affairs Hosp, Dept Surg, Los Angeles, CA USA. Univ Texas, SW Med Ctr, Dept Surg, Dallas, TX 75235 USA. RP O'Connell, JB (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 19833 Le Conte Ave,72-215 CHS, Los Angeles, CA 90095 USA. NR 51 TC 131 Z9 134 U1 1 U2 7 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD OCT PY 2003 VL 69 IS 10 BP 866 EP 872 PG 7 WC Surgery SC Surgery GA 729KD UT WOS:000185771600010 PM 14570365 ER PT J AU Arteaga, JR Huerta, S Basa, NR Livingston, EH AF Arteaga, JR Huerta, S Basa, NR Livingston, EH TI Interval Jejunoileal bypass reduces the morbidity and mortality of Roux-en-y gastric bypass in the super-obese SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT Annual Meeting of the Southern California Chapter of the American-College-of-Surgeons CY JAN 24-26, 2003 CL SANTA BARBARA, CALIFORNIA SP Amer Coll Surg, SO Calif Chapter ID VERTICAL BANDED GASTROPLASTY; FOLLOW-UP; SURGERY; EPIDEMIC; WOMEN; TRIAL AB Among Roux-en-Y gastric bypass (RYGB) patients, large male patients carry the greatest risk for severe, life-threatening complications. The higher complication rate is partly related to large amounts of intra-abdominal fat that increases the technical difficulty of the RYGB. In order to minimize the risk for complications, we established a staged approach for weight loss surgery for high-risk, super-obese patients. Patients with intra-abdominal fat at exploration which precluded the performance of RYGB underwent jejunoileal bypass (JIB). Following an initial period of weight loss (6-24 months), they were converted to a RYGB during a second operation. Twenty-four patients underwent initial JIB that was associated with a major complication rate of 8.3 per cent (2/24) and no mortality. Eight patients lost 53.4 +/- 6.3 kg prior to their conversion to RYGB (mean, 14.1 months). There was one major complication (12%) and no deaths (0%). Following RYGB, an additional period of weight loss resulted in overall excess weight loss (EWL) totaling 62 per cent. A two-step procedure is a safe and effective approach for minimizing complications for high-risk patients undergoing RYGB. The initial JIB was associated with low morbidity and no mortality, and the follow-up RYGB procedure was a technically simple operation that could be performed with few complications. C1 Univ Calif Los Angeles, Ctr Human Nutr, Los Angeles, CA 90095 USA. VA Greater LA Healthcare Syst, Los Angeles, CA USA. Univ Texas, SW Med Ctr, Div Gastrointestinal & Endocrine Surg, Dallas, TX USA. RP Arteaga, JR (reprint author), Univ Calif Los Angeles, Ctr Human Nutr, 900 Vet Ave,Rm 12-217, Los Angeles, CA 90095 USA. NR 20 TC 3 Z9 3 U1 0 U2 0 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD OCT PY 2003 VL 69 IS 10 BP 873 EP 878 PG 6 WC Surgery SC Surgery GA 729KD UT WOS:000185771600011 PM 14570366 ER PT J AU Bhatia, K Finkel, M Emond, JA Camargo, CA AF Bhatia, K Finkel, M Emond, JA Camargo, CA TI Emergency department visits for ectopic pregnancy, 1992-2000 SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 12-13, 2003 CL BOSTON, MASSACHUSETTS SP Amer Coll Emergency Physicians C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2003 VL 42 IS 4 SU S MA 118 BP S32 EP S33 PG 2 WC Emergency Medicine SC Emergency Medicine GA 730JT UT WOS:000185828200117 ER PT J AU Clark, S Kim, S Hohrmann, JL Camargo, CA AF Clark, S Kim, S Hohrmann, JL Camargo, CA TI Body mass index among adults presenting to the emergency department SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 12-13, 2003 CL BOSTON, MASSACHUSETTS SP Amer Coll Emergency Physicians C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2003 VL 42 IS 4 SU S MA 259 BP S70 EP S70 PG 1 WC Emergency Medicine SC Emergency Medicine GA 730JT UT WOS:000185828200254 ER PT J AU Graham, GN Brown, DF Jones, DML Kim, S Emond, JA Camargo, CA AF Graham, GN Brown, DF Jones, DML Kim, S Emond, JA Camargo, CA TI National trends in emergency department visits for acute coronary syndromes and nontraumatic chest pain, 1992 to 2000 SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 12-13, 2003 CL BOSTON, MASSACHUSETTS SP Amer Coll Emergency Physicians C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2003 VL 42 IS 4 SU S MA 258 BP S70 EP S70 PG 1 WC Emergency Medicine SC Emergency Medicine GA 730JT UT WOS:000185828200253 ER PT J AU Hunter, GC Burbank-Schmitt, ER Brown, DF Camargo, CA AF Hunter, GC Burbank-Schmitt, ER Brown, DF Camargo, CA TI The effect of an enhanced emergency department information system on length of stay SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 12-13, 2003 CL BOSTON, MASSACHUSETTS SP Amer Coll Emergency Physicians C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2003 VL 42 IS 4 SU S MA 17 BP S6 EP S6 PG 1 WC Emergency Medicine SC Emergency Medicine GA 730JT UT WOS:000185828200018 ER PT J AU Kabrhel, C Liu, SW Thomas, SH AF Kabrhel, C Liu, SW Thomas, SH TI Creation of an online collection of emergency medicine literature for resident and medical student education SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 12-13, 2003 CL BOSTON, MASSACHUSETTS SP Amer Coll Emergency Physicians C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2003 VL 42 IS 4 SU S MA 379 BP S102 EP S102 PG 1 WC Emergency Medicine SC Emergency Medicine GA 730JT UT WOS:000185828200371 ER PT J AU Kabrhel, C Thomas, SH AF Kabrhel, C Thomas, SH TI The introduction of a rapid enzyme-linked immunosorbent assay D-dimer increases emergency department testing with no effect on the diagnosis of pulmonary embolism SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 12-13, 2003 CL BOSTON, MASSACHUSETTS SP Amer Coll Emergency Physicians C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2003 VL 42 IS 4 SU S MA 131 BP S36 EP S36 PG 1 WC Emergency Medicine SC Emergency Medicine GA 730JT UT WOS:000185828200130 ER PT J AU Kim, S Hohrmann, JL Clark, S Radeos, MS Camargo, CA AF Kim, S Hohrmann, JL Clark, S Radeos, MS Camargo, CA TI Potential adverse interactions between prescription and complementary or alternative medications among emergency department patients SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 12-13, 2003 CL BOSTON, MASSACHUSETTS SP Amer Coll Emergency Physicians C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2003 VL 42 IS 4 SU S MA 372 BP S101 EP S101 PG 1 WC Emergency Medicine SC Emergency Medicine GA 730JT UT WOS:000185828200365 ER PT J AU Liu, SW Thomas, SH AF Liu, SW Thomas, SH TI Why patients with primary care physicians seek emergency department SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 12-13, 2003 CL BOSTON, MASSACHUSETTS SP Amer Coll Emergency Physicians C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2003 VL 42 IS 4 SU S MA 302 BP S82 EP S82 PG 1 WC Emergency Medicine SC Emergency Medicine GA 730JT UT WOS:000185828200297 ER PT J AU Mansbach, JM Emond, JA Camargo, CA AF Mansbach, JM Emond, JA Camargo, CA TI US emergency department visits for bronchiolitis, 1992 to 2000 SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 12-13, 2003 CL BOSTON, MASSACHUSETTS SP Amer Coll Emergency Physicians C1 Childrens Hosp Boston, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2003 VL 42 IS 4 SU S MA 128 BP S35 EP S35 PG 1 WC Emergency Medicine SC Emergency Medicine GA 730JT UT WOS:000185828200127 ER PT J AU Nagurney, JT Brown, DF Chae, C Chang, Y Chung, WG Cranmer, H Dan, L Fisher, J Grossman, SA Tedrow, U Lewandrowski, K Jang, IK AF Nagurney, JT Brown, DF Chae, C Chang, Y Chung, WG Cranmer, H Dan, L Fisher, J Grossman, SA Tedrow, U Lewandrowski, K Jang, IK TI Emergency department providers are more suspicious of acute coronary syndrome than of acute myocardial infarction SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 12-13, 2003 CL BOSTON, MASSACHUSETTS SP Amer Coll Emergency Physicians C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2003 VL 42 IS 4 SU S MA 226 BP S62 EP S62 PG 1 WC Emergency Medicine SC Emergency Medicine GA 730JT UT WOS:000185828200223 ER PT J AU Nagurney, JT Brown, DF Chae, C Chang, Y Chung, WG Cranmer, H Dan, L Fisher, J Grossman, SA Tedrow, U Lewandrowski, K Jang, IK AF Nagurney, JT Brown, DF Chae, C Chang, Y Chung, WG Cranmer, H Dan, L Fisher, J Grossman, SA Tedrow, U Lewandrowski, K Jang, IK TI Applying cardiac markers using a six-hour strategy SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 12-13, 2003 CL BOSTON, MASSACHUSETTS SP Amer Coll Emergency Physicians C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2003 VL 42 IS 4 SU S MA 225 BP S61 EP S62 PG 2 WC Emergency Medicine SC Emergency Medicine GA 730JT UT WOS:000185828200222 ER PT J AU Pallin, DJ Kim, S Emond, JA Camargo, CA AF Pallin, DJ Kim, S Emond, JA Camargo, CA TI National study of pneumococcal and influenza vaccinations among adult emergency department patients, 1992 to 2000 SO ANNALS OF EMERGENCY MEDICINE LA English DT Meeting Abstract CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 12-13, 2003 CL BOSTON, MASSACHUSETTS SP Amer Coll Emergency Physicians C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Pallin, Daniel/H-6382-2013 OI Pallin, Daniel/0000-0002-8517-9702 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2003 VL 42 IS 4 SU S MA 257 BP S70 EP S70 PG 1 WC Emergency Medicine SC Emergency Medicine GA 730JT UT WOS:000185828200252 ER EF