FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Wong, JS Harris, JR AF Wong, JS Harris, JR TI Current status of radiation in the treatment of breast cancer - The Small article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID THERAPY C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02115 USA. RP Wong, JS (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD APR PY 2001 VL 15 IS 4 BP 476 EP + PG 3 WC Oncology SC Oncology GA 426DF UT WOS:000168334000016 ER PT J AU Suri, R Harthorne, JW Galvin, J AF Suri, R Harthorne, JW Galvin, J TI Automatically optimizing pacing output: An excellent idea, but with potentially lethal pitfalls SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE AutoCapture (AC); Ventricular Capture Management (VCM) AB AutoCapture (AC) and Ventricular Capture Management (VCM) are pacing algorithms that attempt to automatically optimize pacing output, providing consistent capture and enhancing device longevity. This report describes potentially serious consequences from use of these algorithms. In one pacemaker dependent patient, AC malfunction led to failure of ventricular capture. This was fixed with a software correction. The potential seriousness of AC malfunction leads to the recommendation that this software be downloaded into all susceptible pacemakers. In a second patient, VCM malfunction resulted in unnecessary high output pacing. Our experience illustrates the need for postmarketing surveillance when embracing newer technology. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Suri, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, 55 Fruit St, Boston, MA 02114 USA. NR 10 TC 7 Z9 7 U1 0 U2 0 PU FUTURA PUBL CO PI ARMONK PA 135 BEDFORD RD, PO BOX 418, ARMONK, NY 10504-0418 USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD APR PY 2001 VL 24 IS 4 BP 520 EP 523 DI 10.1046/j.1460-9592.2001.t01-1-00520.x PN 1 PG 4 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 426HD UT WOS:000168343000021 PM 11341095 ER PT J AU Woods, LL Ingelfinger, JR Nyengaard, JR Rasch, R AF Woods, LL Ingelfinger, JR Nyengaard, JR Rasch, R TI Maternal protein restriction suppresses the newborn renin-angiotensin system and programs adult hypertension in rats SO PEDIATRIC RESEARCH LA English DT Article ID SYSTOLIC BLOOD-PRESSURE; CORONARY HEART-DISEASE; BIRTH-WEIGHT; CARDIOVASCULAR-DISEASE; FETAL EXPOSURE; RENAL GROWTH; 11-BETA-HYDROXYSTEROID DEHYDROGENASE; CONVERTING ENZYME; GENE-EXPRESSION; PREGNANCY AB Restriction of maternal protein intake during rat pregnancy produces offspring that are hypertensive in adulthood, but the mechanisms are not well understood. Our purpose was to determine whether this adult hypertension could be programmed during development by suppression of the fetal/newborn renin-angiotensin system (RAS) and a consequent reduction in nephron number. Pregnant rats were fed a normal protein (19%, NP) or low-protein (8.5%, LP) diet throughout gestation. Birth weight was reduced by 13% (p < 0.0005), and the kidney/body weight ratio was reduced in LP pups. Renal renin mRNA levels were significantly reduced in newborn LP pups; renal renin concentration and renin immunostaining were suppressed. Renal tissue angiotensin II levels were also suppressed in newborn LP (0.079 0.002 ng/mg, LP versus 0.146 +/- 0.016 ng/mg, NP, p < 0.01). Mean arterial pressure in conscious, chronically instrumented adult offspring (21 wk) was higher in LP (135 1 mm Hg, LP versus 126 +/- 1 mm Hg, NP, p < 0.00007), and GFR normalized to kidney weight was reduced in LP (p < 0.04). The number of glomeruli per kidney was lower in adult LP offspring (21,567 +/- 1,694, LP versus 28,917 +/- 2,342, NP, p < 0.03), and individual glomerular volume was higher (1.81 0.16 10(6) mum(3), LP versus 1.11 +/- 0.10 10(6) mum(3), NP, p < 0.005); the total volume of all glomeruli per kidney was not significantly different.. Thus, perinatal protein restriction in the rat suppresses the newborn intrarenal RAS and leads to a reduced number of glomeruli, glomerular enlargement, and hypertension in the adult. C1 Oregon Hlth Sci Univ, Div Nephrol, Portland, OR 97201 USA. Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. Aarhus Univ, Inst Anat, Dept Cell Biol, DK-8000 Aarhus, Denmark. Aarhus Univ, Stereol Res Lab, DK-8000 Aarhus, Denmark. RP Woods, LL (reprint author), Oregon Hlth Sci Univ, Div Nephrol, L463,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. FU NHLBI NIH HHS [HL40210, HL48455]; NICHD NIH HHS [1P01 HD34430-01A1] NR 56 TC 347 Z9 355 U1 0 U2 17 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2001 VL 49 IS 4 BP 460 EP 467 DI 10.1203/00006450-200104000-00005 PG 8 WC Pediatrics SC Pediatrics GA 418MR UT WOS:000167896400005 PM 11264427 ER PT J AU Fusunyan, RD Nanthakumar, NN Baldeon, ME Walker, WA AF Fusunyan, RD Nanthakumar, NN Baldeon, ME Walker, WA TI Evidence for an innate immune response in the immature human intestine: Toll-like receptors on fetal enterocytes SO PEDIATRIC RESEARCH LA English DT Article ID SIGNALING PATHWAYS; DROSOPHILA TOLL; KAPPA-B; CELLS; INFLAMMATION; RECOGNITION; SYSTEM; FAMILY AB The intestinal epithelium is an active participant in the mucosal immune response against luminal pathogens. Microorganisms and their cell wall products, i.e. lipopolysaccharide (LPS), can stimulate the enterocyte to produce an innate immune response with the increased production of IL-8 via an activation of the transcription factor NF kappaB. The innate response mechanism, however, has not been understood until the recent description of a family of human toll-like receptors (hTLR) on immune cells that interact with LPS and modulate the IL-8 response via an intracellular signal transduction pathway similar to that of the IL-1 receptor family. Accordingly, in this study we have sought to determine the constitutive and regulated expression of hTLR on a nonmalignant human fetal primary small intestinal cell line (H4 cells) and on small intestinal samples of ileum from human fetuses (age 18-21 wk). Specimens were examined by reverse-transcription PCR, Western blot analysis, and immunofluorescence for hTLR2 and hTLR4 mRNA and protein and to determine whether their expression was regulated by LPS or by an endogenous inflammatory stimulus, IL-1 beta. hTLR2 and hTLR4 were expressed constitutively on H4 cells and on human fetal small intestinal enterocytes, predominantly on the basolateral surface of crypt enterocytes. Inflammatory stimuli appeared to regulate hTLR transcription (IL-IP increased both hTLR2 and hTLR4 whereas LPS decreased hTLR4) and possibly translation (qualitative observations). The presence of hTLR on human fetal enterocyte suggests a mechanism for the innate immune response to pathogens and could provide the basis for further study of the accentuated inflammatory response in age-dependent gastrointestinal diseases such as necrotizing enterocolitis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dev Gastroenterol Lab,Combined Program Pediat Gas, Charlestown, MA 02129 USA. RP Walker, WA (reprint author), Massachusetts Gen Hosp E, Dev Gastroenterol Lab, Combines Program Pediat Gastroenterol & Nutr, 149 13th St 149-3404, Charlestown, MA 02129 USA. FU NICHD NIH HHS [R01 HD31852, R37 HD12437]; NIDDK NIH HHS [P01 DK33506, K08 DK02481] NR 22 TC 112 Z9 114 U1 0 U2 6 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2001 VL 49 IS 4 BP 589 EP 593 DI 10.1203/00006450-200104000-00023 PG 5 WC Pediatrics SC Pediatrics GA 418MR UT WOS:000167896400023 PM 11264445 ER PT J AU Stein, MT Katz, RM Jelinek, MS Cassidy, L Olness, K AF Stein, MT Katz, RM Jelinek, MS Cassidy, L Olness, K TI Cyclic vomiting SO PEDIATRICS LA English DT Article DE child; cyclic vomiting syndrome ID MIGRAINE C1 Univ Calif San Diego, Sch Med, Div Primary Care Pediat & Adolescent Med, San Diego, CA 92103 USA. Johns Hopkins Univ, Sch Med, Div Pediat Gastroenterol & Nutr, Baltimore, MD USA. Kennedy Krieger Inst, Feeding Disorders Program, Baltimore, MD USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Case Western Reserve Univ, Div Gen Acad Pediat, Cleveland, OH 44106 USA. RP Stein, MT (reprint author), Univ Calif San Diego, Sch Med, Div Primary Care Pediat & Adolescent Med, San Diego, CA 92103 USA. NR 18 TC 1 Z9 1 U1 0 U2 2 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 APR PY 2001 VL 107 IS 4 SU S BP 940 EP 944 PG 5 WC Pediatrics SC Pediatrics GA 422QD UT WOS:000168130000027 ER PT J AU Stavrev, P Niemierko, A Stavreva, N Goitein, A AF Stavrev, P Niemierko, A Stavreva, N Goitein, A TI The application of biological models to clinical data SO PHYSICA MEDICA LA English DT Article DE biological modeling; NTCP; critical volume; model fitting ID RADIATION-INDUCED COMPLICATIONS; DOSE-VOLUME HISTOGRAMS; NORMAL TISSUE; PARALLEL ARCHITECTURE; IRRADIATION; PROBABILITY; TOLERANCE; RADIOTHERAPY; OPTIMIZATION; PNEUMONITIS AB This paper presents a methodology for applying biological models to clinical data with the goal of being able to estimate the probability of complication in an organ or normal tissue when exposed to a non-uniform irradiation. For purposes of illustration, and in order to provide information which may be useful in clinical practice, the discussion is presented for the particular case of the population averaged critical volume model applied to the set of dose-volume tolerances published by Emami et al. [5] and to the data on radiation hepatitis from the University of Michigan Medical Center [9]. The paper includes pseudo-code allowing the assessment of the probability of complication for an inhomogeneous dose distribution using the standard critical volume model for normal tissue complication probability (NTCP). The model has four parameters. In order to obtain estimates of the model parameters for different organs, the model is fitted to the data using the maximum likelihood method. As a result, the best-fit parameter values for a variety of organs are obtained with their errors. Graphs illustrating the goodness of the fit are also presented as well as the formalism for estimating goodness of fit. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 21 TC 23 Z9 23 U1 1 U2 2 PU ISTITUTI EDITORIALI E POLGRAFICI INTERNAZIONALI PI PISA PA CASELLA POSTALE N 1, SUCCURSALE N 8, 56123 PISA, ITALY SN 1120-1797 J9 PHYS MEDICA JI Phys. Medica PD APR-JUN PY 2001 VL 17 IS 2 BP 71 EP 82 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 467BG UT WOS:000170680200003 ER PT J AU Kyriakis, JM Avruch, J AF Kyriakis, JM Avruch, J TI Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation SO PHYSIOLOGICAL REVIEWS LA English DT Review ID TUMOR-NECROSIS-FACTOR; N-TERMINAL KINASE; GERMINAL CENTER KINASE; JUN NH2-TERMINAL KINASE; KAPPA-B ACTIVATION; P38 MAP KINASE; RECEPTOR-ASSOCIATED FACTOR-2; EPIDERMAL GROWTH-FACTOR; TOLL-LIKE RECEPTOR-4; T-CELL ACTIVATION AB The molecular details of mammalian stress-activated signal transduction pathways have only begun to be dissected. This, despite the fact that the impact of these pathways on the pathology elf chronic inflammation, heart disease, stroke, the debilitating effects of diabetes mellitus, and the side effects of cancer therapy, not to mention embryonic development, innate and acquired immunity, is profound. Cardiovascular disease and diabetes alone represent the most significant health care problems in the developed world. Thus it is not surprising that understanding these pathways has attracted nide interest, and in the past 10 years, dramatic progress has been made. Accordingly, it is now becoming possible to envisage the transition of these findings to the development of novel treatment strategies. This review focuses on the biochemical components and regulation of mammalian stress-regulated mitogen-activated protein kinase (MAPK) pathways. The nuclear factor-kappaB pathway, a second stress signaling paradigm, has been the subject of several excellent recent reviews (258, 260). C1 Massachusetts Gen Hosp E, Diabet Res Lab, Med Serv, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Kyriakis, JM (reprint author), Massachusetts Gen Hosp E, Diabet Res Lab, Med Serv, 149 13th St, Charlestown, MA 02129 USA. NR 369 TC 2260 Z9 2383 U1 26 U2 223 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0031-9333 J9 PHYSIOL REV JI Physiol. Rev. PD APR PY 2001 VL 81 IS 2 BP 807 EP 869 PG 63 WC Physiology SC Physiology GA 413YC UT WOS:000167638300008 PM 11274345 ER PT J AU Ahmed, NU Shioda, T Coser, KR Ichihashi, M Ueda, M AF Ahmed, NU Shioda, T Coser, KR Ichihashi, M Ueda, M TI Aberrant expression of MSG1 transcriptional activator in human malignant melanoma in vivo SO PIGMENT CELL RESEARCH LA English DT Article DE pigmentation; TGF beta; immunohistochemistry ID NUCLEAR-PROTEIN; MRG1; GENE; TRANSACTIVATOR; CELLS; BETA AB MSG1 was originally isolated as a candidate pigmentation-related gene. MSG1 mRNA transcripts were expressed strongly in cultured human and mouse normal epidermal melanocytes, and in highly pigmented mouse melanoma cells, while its expression was very weak in cultured non-pigmented human melanoma cells. Thus, MSG1 was initially proposed to be a melanocyte-specific gene, and its possible role in pigmentation has been speculated. It was found recently that the MSG1 protein interacts functionally with Smad4, which plays a pivotal role in signal transduction of transforming growth factor-p, In this study, we analyzed MSG1 protein expression by immunohistochemistry using human tumor samples from nevus and malignant melanoma to reveal its role in pigmentation and melanoma development in vivo. A relatively strong but heterogeneous expression of MSG1 protein was seen in melanomas compared with weak expression in nevi, In nevi, MSG1 expression was mostly confined to the pigmented region, while it was expressed in both pigmented and non-pigmented regions in melanoma, Intracellularly, MSG1 protein was localized in the cytoplasm of nevus cells, but was seen in both nuclei and cytoplasm of melanoma cells. These results support a hypothesis that MSG1 plays a role in pigmentation. It is also suggested that MSG1 may be involved in malignant transformation of pigment cells. Alternatively, the aberrant expression of MSG1 in melanoma cells might be due to the abnormal environment, including aberrant cytokine or growth factor expression, associated with melanoma formation. C1 Kobe Univ, Sch Med, Dept Dermatol, Chuo Ku, Kobe, Hyogo 6500017, Japan. Massachusetts Gen Hosp East, MGH Canc Ctr, Lab Tumor Biol, Charlestown, MA 02129 USA. RP Ueda, M (reprint author), Kobe Univ, Sch Med, Dept Dermatol, Chuo Ku, 7-5-1 Kusunokicho, Kobe, Hyogo 6500017, Japan. NR 11 TC 6 Z9 6 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD APR PY 2001 VL 14 IS 2 BP 140 EP 143 PG 4 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA 421CY UT WOS:000168045600009 PM 11310794 ER PT J AU Yaremchuk, MJ AF Yaremchuk, MJ TI Subperiosteal and full-thickness skin rhytidectomy SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Editorial Material ID FACE LIFT; FACIAL REJUVENATION; FOREHEAD LIFT; BROW; CHEEK; BLEPHAROPLASTY; COMPLICATIONS; SUSPENSION; MIDFACE; SURGERY AB Subperiosteal lateral brow and midface elevation, upper lid blepharoplasty, transconjunctival retroseptal fat removal, lower lid skin excision, and full-thickness skin rhytidectomy are combined in one operation to rejuvenate the entire face. This combination of procedures is designed to restore both anthropometric and subjective attributes of youth. The attributes of a youthful face may be summarized as brews with an apex lateral slant, eyes that are narrow, lower lids that are shore, cheeks that are full, and necks that are well defined. In addition to restoring a youthful appearance, the techniques described avoid some common iatrogenic sequelae of facial rejuvenative surgery, In a clinical experience with 28 patients over 3 years, this combination of procedures has proved to be safe and predictable. C1 Massachusetts Gen Hosp, Div Plast Surg, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Yaremchuk, MJ (reprint author), Massachusetts Gen Hosp, Div Plast Surg, Dept Surg, WACC-453, Boston, MA 02114 USA. NR 57 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD APR 1 PY 2001 VL 107 IS 4 BP 1045 EP 1058 DI 10.1097/00006534-200104010-00023 PG 14 WC Surgery SC Surgery GA 412JQ UT WOS:000167551600022 PM 11252102 ER PT J AU Lee, WPA AF Lee, WPA TI Composite tissue transplantation: More science and patience needed SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Editorial Material ID RENAL-ALLOGRAFT REJECTION; HAND TRANSPLANTATION; LIMB ALLOGRAFTS; MOFETIL THERAPY; TOLERANCE; MODEL; CYCLOSPORINE; INDUCTION; PRIMATES; RECIPIENTS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA 02114 USA. RP Lee, WPA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, WAC-453,15 Parkman St, Boston, MA 02114 USA. NR 37 TC 27 Z9 29 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD APR 1 PY 2001 VL 107 IS 4 BP 1066 EP 1070 PG 5 WC Surgery SC Surgery GA 412JQ UT WOS:000167551600025 PM 11252105 ER PT J AU Bergeron, B AF Bergeron, B TI The form factor SO POSTGRADUATE MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bergeron, B (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 USA SN 0032-5481 J9 POSTGRAD MED JI Postgrad. Med. PD APR PY 2001 VL 109 IS 4 BP SS18 EP SS18 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 421HR UT WOS:000168059400013 ER PT J AU Emmons, KM Wong, M Hammond, SK Velicer, WF Fava, JL Monroe, AD Evans, JL AF Emmons, KM Wong, M Hammond, SK Velicer, WF Fava, JL Monroe, AD Evans, JL TI Intervention and policy issues related to children's exposure to environmental tobacco smoke SO PREVENTIVE MEDICINE LA English DT Article DE second-hand smoke; smoking cessation; feedback ID PASSIVE SMOKING; ASTHMATIC-CHILDREN; MAJOR DEPRESSION; MATERNAL SMOKING; CESSATION; COTININE; RESTRICTIONS; DEPENDENCE; HOUSEHOLD; REDUCTION AB Background. Children's exposure to environmental tobacco smoke (ETS) is unacceptably high; almost 40% of children in the United States are regularly exposed to ETS. Methods. This paper presents a review of the literature that evaluates interventions designed to reduce ETS exposure among young children. In addition, it presents the study design for Project KISS (keeping Infants Safe from Smoke), an intervention designed to utilize exposure-related feedback to increase parents' motivation for ETS reduction and to reduce household ETS levels. Baseline data are presented to illustrate factors that should be addressed in ETS interventions. Results. The literature review demonstrates the dearth of studies in the literature targeting ETS reduction among children. Participants in Project KISS believed that smoking had affected their children's health and were in later stages of motivational readiness to quit smoking than is typically observed. However, they face a number of challenges to smoking, such as high prevalence of nicotine dependence, high prevalence of living with other smokers, and socioeconomic and stress-related barriers. Conclusions. The policy implications of this research are discussed, and recommendations are made for future research. (C) 2001 American Health Foundation and Academic Press. C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Community Based Res, Boston, MA 02115 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. Univ Rhode Isl, Kingston, RI 02881 USA. Mem Hosp Rhode Isl, Providence, RI 02912 USA. Brown Univ, Providence, RI 02912 USA. RP Emmons, KM (reprint author), Harvard Univ, Sch Publ Hlth, 44 Binney St, Boston, MA 02115 USA. RI Travers, Mark/C-7832-2011 FU NCI NIH HHS [R01 CA73242] NR 51 TC 33 Z9 33 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD APR PY 2001 VL 32 IS 4 BP 321 EP 331 DI 10.1006/pmed.2000.0822 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 419HX UT WOS:000167944200003 PM 11304093 ER PT J AU Rivas-Vazquez, RA Blais, MA Rey, GJ Rivas-Vazquez, AA AF Rivas-Vazquez, RA Blais, MA Rey, GJ Rivas-Vazquez, AA TI A brief reminder about documenting the psychological consultation SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article AB The documentation of clinical services has taken on unprecedented importance for practicing psychologists. Structuring quality care, decreasing liability exposure, and fulfilling requirements for reimbursement are primary objectives in pursuing thorough documentation practices. As a practice aid and a brief reminder, the authors review the basic structure for documenting an initial evaluation, highlighting content areas that are felt to be important for attaining the objectives noted above. The authors suggest that psychologists use the term psychological consultation to specify this procedure, designating it as a distinct process from psychological testing or psychological treatment. C1 Univ Miami, Sch Med, Dept Neurol, Coral Gables, FL 33124 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 10 TC 3 Z9 3 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7028 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD APR PY 2001 VL 32 IS 2 BP 194 EP 199 DI 10.1037/0735-7028.32.2.194 PG 6 WC Psychology, Multidisciplinary SC Psychology GA 470WB UT WOS:000170893200012 ER PT J AU Short, MK Jeffrey, PD Demirjian, A Margolies, MN AF Short, MK Jeffrey, PD Demirjian, A Margolies, MN TI A single H : CDR3 residue in the anti-digoxin antibody 26-10 modulates specificity for C16-substituted digoxin analogs SO PROTEIN ENGINEERING LA English DT Article DE antibody specificity; bacteriophage display; digoxin; immunoglobulin fragments; protein structure ID AMINO-ACID SUBSTITUTION; PHAGE DISPLAY; MONOCLONAL-ANTIBODY; HIGH-AFFINITY; LIBRARIES; MUTATIONS; MATURATION; SITE; COMPLEMENTARITY; RECOGNITION AB We constructed Fab libraries of bacteriophage-displayed H:CDR3 mutants in the high-affinity anti-digoxin antibody 26-10 to determine structural constraints on affinity and specificity for digoxin. Libraries of mutant Fabs randomized at five or 10 contiguous positions were panned against digoxin and three C16-substituted analogs, gitoxin (16-OH), 16-formylgitoxin and 16-acetylgitoxin. The sequence data from 83 different mutant Fabs showed highly restricted consensus patterns at positions H:100, 100a and 100b for binding to digoxin; these residues contact digoxin in the 26-10:digoxin co-crystal structure. Several mutant Fabs obtained following panning on digoxin-BSA showed increased affinity for digoxin compared with 26-10 and retained the wild-type (wt) Trp at position 100. Those Fabs selected following panning on C16-substituted analogs showed enhanced binding to the analogs. Replacement of H:Trp100 by Arg resulted in mutants that bound better to the analogs than to digoxin. This specificity change was unexpected, as C16 lies on the opposite side of digoxin from H:CDR3, Substitution of wt Trp by Arg appears to alter specificity by allowing the hapten to shift toward H:CDR3, thereby providing room for C16 substituents in the region of H:CDR1. C1 Massachusetts Gen Hosp, Dept Surg, Antibody Engn Lab, MGH E, Charlestown, MA 02129 USA. Mem Sloan Kettering Canc Ctr, Dept Cellular Biochem & Biophys, New York, NY 10021 USA. RP Margolies, MN (reprint author), Massachusetts Gen Hosp, Dept Surg, Antibody Engn Lab, MGH E, 149 13th St,Box 31, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [R01 HL47415] NR 36 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD APR PY 2001 VL 14 IS 4 BP 287 EP 296 DI 10.1093/protein/14.4.287 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 444FU UT WOS:000169390100010 PM 11391021 ER PT J AU Seeman, TE Singer, B Wikinson, CW McEwen, B AF Seeman, TE Singer, B Wikinson, CW McEwen, B TI Gender differences in age-related changes in HPA axis reactivity SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE age differences; gender differences; HPA axis reactivity; cognitive challenge ID PITUITARY-ADRENAL AXIS; BEHAVIORAL STRESS RESPONSES; SEX-DIFFERENCES; ORAL-CONTRACEPTIVES; ADRENOCORTICAL RESPONSIVENESS; PSYCHOLOGICAL STRESS; POSTMENOPAUSAL WOMEN; CORTISOL; 17-BETA-ESTRADIOL; NEUROENDOCRINE AB Possible differences between men acid women in age-related patterns of hypothalamic-pituitary-adrenal (HPA) axis response to challenge were examined to test the hypothesis that women show greater age-related increase in HPA axis reactivity to challenge. Twenty-six younger subjects, 9 men and 17 women, ages 22-26 and 14 older subjects, 7 men and 7 women, ages 67-88 participated in the study. Patterns of change in salivary "free" cortisol were measured in response to a standardized, 30-minute cognitive challenge, administered individually to each subject beginning at 1600 h, Consistent with previous research, there was a significant main effect for age with respect to baseline cortisol: older age was associated with higher baseline cortisol (P = <0 .001). Results also provide support for the hypothesized age-by-gender interaction with respect to patterns of response to challenge. There was a significant interaction with respect to maximum percentage increase over baseline (P<0.002): among younger adults, the men exhibited greater increases whereas among the older adults, the women exhibited greater increases. A similar, though only marginally significant pattern was seen for total area under the response curve (P=0.07). Repeated measures ANOVA confirmed the gender-by-age differences in the patterns of response (P=0.01 for time*age*gender interaction). (C) 2001 Elsevier Science Ltd, All rights reserved. C1 Univ Calif Los Angeles, Sch Med, Div Geriatr, Los Angeles, CA 90095 USA. Princeton Univ, Off Populat Res, Princeton, NJ 08544 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98195 USA. Rockefeller Univ, Neuroendocrinol Lab, New York, NY 10021 USA. RP Seeman, TE (reprint author), Univ Calif Los Angeles, Sch Med, Div Geriatr, 10945 Le Conte Ave,Suite 2339, Los Angeles, CA 90095 USA. FU NIA NIH HHS [AG-00586, AG-05142, AG-10418, AG-17056] NR 59 TC 132 Z9 136 U1 2 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD APR PY 2001 VL 26 IS 3 BP 225 EP 240 DI 10.1016/S0306-4530(00)00043-3 PG 16 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 409WJ UT WOS:000167408400001 PM 11166486 ER PT J AU Levin-Plotnik, D Hamilton, RJ Niemierko, A Akselrod, S AF Levin-Plotnik, D Hamilton, RJ Niemierko, A Akselrod, S TI A model for optimizing normal tissue complication probability in the spinal cord using a generalized incomplete repair scheme SO RADIATION RESEARCH LA English DT Article ID HIGH-DOSE-RATE; RADIATION MYELOPATHY; SUBLETHAL DAMAGE; RADIOTHERAPY; BRACHYTHERAPY; IRRADIATION; PROTOCOLS; TOLERANCE; MULTIPLE; MYELITIS AB The purpose of this study was to determine the treatment protocol, in terms of dose fractions and interfraction intervals, which minimizes normal tissue complication probability in the spinal cord for a given total treatment dose and treatment time. We generalize the concept of incomplete repair in the linear-quadratic model, allowing for arbitrary dose fractions and interfraction intervals. This is incorporated into a previously presented model of normal tissue complication probability for the spinal cord. Equations are derived for both mono-exponential and bi-exponential repair schemes, regarding each dose fraction and interfraction interval as an independent parameter, subject to the constraints of fixed total treatment dose and treatment time. When the interfraction intervals are fixed and equal, an exact analytical solution is found. The general problem is nonlinear and is solved numerically using simulated annealing, For constant interfraction intervals and varying dose fractions, we find that optimal normal tissue complication probability is obtained by two large and equal doses at the start and conclusion of the treatment, with the rest of the doses equal to one another and smaller than the two dose spikes. A similar result is obtained for bi-exponential repair. For the general case where the interfraction intervals are discrete and also vary, the pattern of two large dose spikes is maintained, while the interfraction intervals oscillate between the smallest two values. As the minimum interfraction interval is reduced, the normal tissue complication probability decreases, indicating that the global minimum is achieved in the continuum limit, where the dose delivered by the "middle" fractions is given continuously at a low dose rate. Furthermore, for bi-exponential repair, it is seen that as the slow component of repair becomes increasingly dominant as the magnitude of the dose spikes decreases. Continuous low-dose-rate irradiation with dose spikes at the start and end of treatment yields the lowest normal tissue complication probability in the spinal cord, given a fixed total dose and total treatment time, for both mono-exponential and bi-exponential repair. The magnitudes of the dose spikes can be calculated analytically, and are in close agreement with the numerical results. (C) 2001 by Radiation Research Society. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Oncol, Boston, MA 02114 USA. Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. Tel Aviv Univ, Sackler Fac Exact Sci, Abramson Inst Med Phys, IL-69978 Ramat Aviv, Israel. RP Levin-Plotnik, D (reprint author), Dept Radiat & Cellular Oncol, 5758 S Maryland Ave,MC 9006, Chicago, IL 60637 USA. NR 27 TC 2 Z9 2 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 APR PY 2001 VL 155 IS 4 BP 593 EP 602 DI 10.1667/0033-7587(2001)155[0593:AMFONT]2.0.CO;2 PG 10 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 418GB UT WOS:000167881600009 PM 11260661 ER PT J AU McMahon, PM Bosch, JL Gleason, S Halpern, EF Lester, JS Gazelle, GS AF McMahon, PM Bosch, JL Gleason, S Halpern, EF Lester, JS Gazelle, GS TI Cost-effectiveness of colorectal cancer screening SO RADIOLOGY LA English DT Article DE cancer screening; colon neoplasms, diagnosis; colonoscopy; cost-effectiveness ID FECAL-OCCULT-BLOOD; DOUBLE-CONTRAST BARIUM; HEALTH-CARE; COLONOSCOPY; ENEMA; ENDOSCOPY; MORTALITY; COMPLICATIONS; SIGMOIDOSCOPY; PREVENTION AB PURPOSE: To determine the most cost-effective colorectal cancer screening strategy costing less than $100,000 per life-year saved and to determine how available strategies compare with each other. MATERIALS AND METHODS: Standardized methods were used to calculate incremental cost-effectiveness ratios (ICERs) from published estimates of cost and effectiveness of colorectal cancer screening strategies, and the direction and magnitude of any effect on the ratio from parameter estimate adjustments based on literature values were estimated. RESULTS: Strategies in which double-contrast barium enema examination was performed emerged as optimal from all studies included. In average-risk individuals, screening with double-contrast barium enema examination every 3 years, or every 5 years with annual fecal occult blood testing, had an ICER of less than $55,600 per life-year saved. However, double-contrast barium enema examination screening every 3 years plus annual fecal occult blood testing had an ICER of more than $100,000 per life-year saved. Colonoscopic screening had an ICER of more than $100,000 per life-year saved, was dominated by other screening strategies, and offered less benefit than did double-contrast barium enema examination screening. CONCLUSION: Double-contrast barium enema examination can be a cost-effective component of colorectal cancer screening, but further modeling efforts are necessary. C1 Massachusetts Gen Hosp, Dept Radiol, Decis Anal & Technol Assessment Grp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Gazelle, GS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Decis Anal & Technol Assessment Grp, 0 Emerson Pl,Ste 2H, Boston, MA 02114 USA. NR 72 TC 23 Z9 23 U1 1 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 2001 VL 219 IS 1 BP 44 EP 50 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 414LD UT WOS:000167667400007 PM 11274533 ER PT J AU Goldberg, SN Ahmed, M Gazelle, GS Kruskal, JB Huertas, JC Halpern, EF Oliver, BS Lenkinski, RE AF Goldberg, SN Ahmed, M Gazelle, GS Kruskal, JB Huertas, JC Halpern, EF Oliver, BS Lenkinski, RE TI Radio-frequency thermal ablation with NaCl solution injection: Effect of electrical conductivity on tissue heating and coagulation-phantom and porcine liver study SO RADIOLOGY LA English DT Article DE liver, interventional procedures; liver neoplasms, therapy; radiofrequency (RF) ablation ID SMALL HEPATOCELLULAR-CARCINOMA; PERCUTANEOUS RADIOFREQUENCY ABLATION; INTERSTITIAL LASER PHOTOCOAGULATION; TUMOR ABLATION; MICROWAVE COAGULATION; ETHANOL INJECTION; HEPATIC-TUMORS; BLOOD-FLOW; IN-VIVO; ELECTRODE AB PURPOSE: To characterize the effects of NaCl concentration on tissue electrical conductivity, radio-frequency (RF) deposition, and heating in phantoms and optimize adjunctive NaCl solution injection for RF ablation in an in vivo model. MATERIALS AND METHODS: RF was applied for 12-15 minutes with internally cooled electrodes. For phantom experiments (n = 51), the NaCl concentration in standardized 5% agar was varied (0%-25.0%). A nonlinear simplex optimization strategy was then used in normal porcine liver (n = 44) to determine optimal pre-RF NaCl solution injection parameters (concentration, 0%-38.5%; volume, 0-25 mi). NaCl concentration and tissue conductivity were correlated with RF energy deposition, tissue heating, and induced coagulation. RESULTS: NaCl concentration had significant but nonlinear effects on electrical conductivity, RF deposition, and heating of agar phantoms (P < .01). Progressively greater heating was observed to 5.0% NaCl, with reduced temperatures at higher concentrations. For in vivo liver, NaCl solution volume and concentration significantly influenced both tissue heating and coagulation (P < .001). Maximum heating 20 mm from the electrode (102.9 degreesC +/- 4.3 [SD]) and coagulation (7.1 cm +/- 1.1) occurred with injection of 6 mL of 38.5% (saturated) NaCl solution. CONCLUSION: Injection of NaCl solution before RF ablation can increase energy deposition, tissue heating, and induced coagulation, which will likely benefit clinical RF ablation. In normal well-perfused liver, maximum coagulation (7.0 cm) occurs with injection of small volumes of saturated NaCl solution. C1 Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Goldberg, SN (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA. RI Lenkinski, Robert/F-9045-2014; OI Lenkinski, Robert/0000-0001-7371-5048 NR 42 TC 182 Z9 187 U1 2 U2 9 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 2001 VL 219 IS 1 BP 157 EP 165 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 414LD UT WOS:000167667400023 PM 11274551 ER PT J AU Weber, DC Nouet, P Kurtz, JM Allal, AS AF Weber, DC Nouet, P Kurtz, JM Allal, AS TI Assessment of target dose delivery in anal cancer using in vivo thermoluminescent dosimetry SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE anal canal carcinoma; radiation therapy; thermoluminescent dosimeter anal verge measurements; late anorectal function ID QUALITY-OF-LIFE; INTENT RADIATION-THERAPY; CONSERVATIVE TREATMENT; CARCINOMA; RADIOTHERAPY; COMPLICATIONS; CHEMOTHERAPY; IRRADIATION AB Purpose: To measure anal dose during external beam radiotherapy (EBRT) using in vivo dosimetry, to study the difference of measured from prescribed dose values, and to evaluate possible associations of such differences with acute and late skin/mucosal toxicity and anorectal function. Materials: Thirty-one patients with localized anal carcinoma underwent in vivo measurements during the first EBRT session. Themoluminescent dosimeters (TLD) were placed at the center of the anal verge according to a localization protocol. No bolus was used. Patients received a median dose of 39.6 Gy (range: 36-45 Gy) by anteroposterior opposed AP/PA pelvic fields with 6 or 18 MV photons, followed by a median boost dose of 29 Gy (range: 13-24 Gy). Concomitant chemotherapy (CCT), consisting of 1-2 cycles of continuous infusion 5-fluorouracil (5-FU) and bolus mitomycin-C (MMC), was usually administered during the first weeks of the pelvic and boost EBRT courses. Acute and late skin/mucosal reactions were recorded according to the Radiation Therapy Oncology Group (RTOG) toxicity scale. Anal sphincter function was assessed using the Memorial Sloan Kettering Cancer Center (MSKCC) scale. Results: TLD anal doses differed by a mean of 5.8% (SD: 5.8) in comparison to the central axis prescribed dose. Differences of at least 10% and at least 15% were observed in eight (26%) and three (9.7%) patients, respectively. TLD doses did not significantly correlate with acute or late grade 2-3 skin or mucosal toxicity. However, patients having good-fair MSKCC anal function had a significantly,greater mean difference in anal TLD dose (10.5%, SD: 5.9) than patients having excellent function (3.8%, SD: 4.6) (P = 0.004). Prescribed dose values, length of follow-up, and age at diagnosis did not correlate with late sphincter function. Conclusions: These data show that AP/PA fields using megavoltage photons deliver adequate dose to the anal verge. However, in about one quarter of patients treated with this technique the anal dose varied from the prescribed dose by at least 10%. The observed correlation of TLD values and late sphincter function suggests that direct measurement of the dose delivered to the anal verge might be clinically relevant. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Hosp, Dept Radiat Oncol, Geneva, Switzerland. RP Weber, DC (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. NR 18 TC 13 Z9 14 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD APR PY 2001 VL 59 IS 1 BP 39 EP 43 DI 10.1016/S0167-8140(01)00334-6 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 426MD UT WOS:000168352200006 PM 11295204 ER PT J AU Allgood, GS Kuter, DJ Roll, KT Taylor, SL Zorich, NL AF Allgood, GS Kuter, DJ Roll, KT Taylor, SL Zorich, NL TI Postmarketing surveillance of new food ingredients: Results from the program with the fat replacer olestra SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE allergy; fat consumption; fat substitute; gastrointestinal; Olean; olestra; postmarketing; surveillance; Procter & Gamble; vitamin K; warfarin ID CONSUMER RECHALLENGE TEST; GASTROINTESTINAL SYMPTOMS; OBJECTIVE MEASURES; SENTINEL SITE; SALTED SNACKS; POTATO-CHIPS; DOUBLE-BLIND; CONSUMPTION; WARFARIN; DIARRHEA AB Market introduction of savory snacks containing olestra offered an opportunity to evaluate the safety of olestra in a free-living population and thereby compare the outcome to the previously established safety profile determined in clinical trials in which subjects were required to eat predetermined amounts at prescribed intervals. Therefore, a multifaceted postmarketing surveillance program was designed to evaluate consumer experience and safety of olestra in the marketplace. Customer comments were solicited through toll-free telephone numbers. Collected data mere evaluated by both internal and external medical experts. About 10% of toll-free telephone calls reported health effects, most of which were gastrointestinal (GI) in nature. Clinical studies were designed and conducted to determine potential GI effects under the range of consumption patterns reported by toll-free calls. Health effects reported were those found commonly in the general population and analyses of the data found no biological reason to conclude that serious or meaningful health effects were the result of olestra consumption. (C) 2001 Academic Press. C1 Procter & Gamble Co, Food & Beverage Div, Cincinnati, OH 45224 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hematol Unit, Boston, MA USA. Univ Nebraska, Food & Allergy Res & Resource Program, Lincoln, NE USA. RP Allgood, GS (reprint author), Procter & Gamble Co, Food & Beverage Div, Cincinnati, OH 45224 USA. NR 29 TC 17 Z9 19 U1 3 U2 6 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD APR PY 2001 VL 33 IS 2 BP 224 EP 233 DI 10.1006/rtph.2001.1460 PG 10 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 433VQ UT WOS:000168781700013 PM 11350205 ER PT J AU Donnellan, P Breathnach, O Crown, JP AF Donnellan, P Breathnach, O Crown, JP TI Odynorgasmia SO SCANDINAVIAN JOURNAL OF UROLOGY AND NEPHROLOGY LA English DT Article DE colorectal cancer; ejaculation; pain AB Painful ejaculation ("odynorgasmia") is not well recognized. When it occurs it may indicate the precise site of pathology. C1 Guys & St Thomas Hosp Trust, Dept Med Oncol, London, England. Dana Farber Canc Inst, Boston, MA 02115 USA. St Vincents Univ Hosp, Dublin, Ireland. RP Donnellan, P (reprint author), St Thomas Hosp, Lambeth Palace Rd, London SE1 7EH, England. NR 1 TC 3 Z9 3 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 0036-5599 J9 SCAND J UROL NEPHROL JI Scand. J. Urol. Nephrol. PD APR PY 2001 VL 35 IS 2 BP 158 EP 158 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 436TL UT WOS:000168951900019 PM 11411663 ER PT J AU Anderson, KC AF Anderson, KC TI Advances in disease biology: Therapeutic implications SO SEMINARS IN HEMATOLOGY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Hematology CY DEC 03-08, 1999 CL NEW ORLEANS, LOUISIANA SP Amer Soc Hematol ID MULTIPLE-MYELOMA CELLS; THALIDOMIDE; APOPTOSIS; INTERLEUKIN-6 C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med, 44 Binney St, Boston, MA 02115 USA. NR 11 TC 43 Z9 47 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD APR PY 2001 VL 38 IS 2 SU 3 BP 6 EP 10 DI 10.1053/shem.2001.21065 PG 5 WC Hematology SC Hematology GA 424TZ UT WOS:000168249700002 PM 11309702 ER PT J AU Sallan, S AF Sallan, S TI Management of acute tumor lysis syndrome SO SEMINARS IN ONCOLOGY LA English DT Review ID NON-HODGKINS-LYMPHOMA; MALIGNANCIES; HYPERKALEMIA; CANCER C1 Dana Farber canc Ctr, Dept Pediat Oncol, Boston, MA 02115 USA. RP Sallan, S (reprint author), Dana Farber canc Ctr, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. NR 19 TC 33 Z9 35 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 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 2001 VL 28 IS 2 SU 5 BP 9 EP 12 DI 10.1053/sonc.2001.21183 PG 4 WC Oncology SC Oncology GA 423HX UT WOS:000168171000003 PM 11343272 ER PT J AU Rosenthal, DI Treat, ME Mankin, HJ Rosenberg, AE Jennings, CL AF Rosenthal, DI Treat, ME Mankin, HJ Rosenberg, AE Jennings, CL TI Treatment of epithelioid hemangioendothelioma of bone using a novel combined approach SO SKELETAL RADIOLOGY LA English DT Article DE radiofrequency ablation; epithelioid hemangioendothelioma; bone; primary malignancy; computed tomography ID RADIOFREQUENCY TISSUE ABLATION; ELECTRODE; CANCER; TUMOR AB Radiofrequency (RF) treatment has been used for a variety of malignant and benign conditions. However, treatment of a bone malignancy has yet to be reported. The authors present a 21-year old woman with multifocal epithelioid hemangioendothelioma (EH) treated by a combination of surgical excision, chemotherapy and four RF ablations. Follow-up radiographs of the RF-treated sites reveal no evidence of recurrent disease 71, 58, 49 and 33 months, respectively, after treatment. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rosenthal, DI (reprint author), Massachusetts Gen Hosp, 515 Wang ACC,15 Parkman St, Boston, MA 02114 USA. NR 21 TC 29 Z9 30 U1 0 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 APR PY 2001 VL 30 IS 4 BP 219 EP 222 PG 4 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 429VF UT WOS:000168537900006 PM 11392296 ER PT J AU Puniello, MS McGibbon, CA Krebs, DE AF Puniello, MS McGibbon, CA Krebs, DE TI Lifting strategy and stability in strength-impaired elders SO SPINE LA English DT Article DE elders; falls; lifting; prevention; strength ID GAIT; BIOMECHANICS; COMPRESSION; PRESSURE; EXERCISE; PROGRAM; BALANCE; JOINT; KNEE; HIP AB Study Design. Ninety-six subjects underwent biomechanical analysis of freestyle box lifting. Objectives. To relate lifting strategy to lower extremity muscle strength and postural stability in functionally limited elders. Summary of Background Data. Back pain and postural instability in elders is rampant and poorly understood. Much of the literature on lifting relates to young subjects. Methods. Lifting strategy for 91 functionally limited elders was classified by timing of peak power in the back and knee joints. Isometric hip and knee extensor strength and postural stability were compared among strategy classifications. Postural stability was analyzed by measuring center of gravity (CG) displacement during lifting. Results. Three lift strategy groups were established: back-lift, or back dominant strategy (BDS); leg-lift, or leg dominant strategy (LDS); and leg-dominant back-first mixed strategy (LDB). Subjects with relatively strong hip and knee extensors used leg dominant strategy; subjects with relatively strong knee, but weak hip, extensors used leg-dominant back-first mixed strategy; and subjects with weak hip and knee extensors used back dominant strategy. Leg dominant strategy and leg-dominant back-first mixed strategy engendered less center of gravity displacement and thus were posturally more stable than the back dominant strategy. Conclusion. Subjects apparently chose their lift strategy based on their hip and knee extensor strength. Weaker elders using a less stable back dominant strategy could be susceptible to falls and subsequent long bone and vertebral body fractures. Clinicians could identify at-risk elders by muscle testing. Beyond emphasizing strength and endurance exercise in elderly patients, weak elders should be taught to use a leg dominant lifting strategy, or if they are not physically able, to use a combined back/leg strategy. C1 Massachusetts Gen Hosp, Biomot Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP Krebs, DE (reprint author), Massachusetts Gen Hosp, Biomot Lab, 101 Merrimac St, Boston, MA 02114 USA. NR 26 TC 11 Z9 11 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD APR 1 PY 2001 VL 26 IS 7 BP 731 EP 737 DI 10.1097/00007632-200104010-00005 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 416YZ UT WOS:000167809300003 PM 11295889 ER PT J AU Ghogawala, Z Mansfield, FL Borges, LF AF Ghogawala, Z Mansfield, FL Borges, LF TI Spinal radiation before surgical decompression adversely affects outcomes of surgery for symptomatic metastatic spinal cord compression SO SPINE LA English DT Article DE infection; neoplasm metastasis; outcome; radiation; surgery; spinal cord compression; wound ID STABILIZATION; RADIOTHERAPY; TISSUES; DISEASE AB Study Design. a retrospective chart review was performed. Objective. To determine whether preoperative spinal radiation increases the number of major wound complications in patients with cancer who have symptomatic spinal cord compression. Summary of Background Data. Many factors have increased the number of patients hospitalized with symptomatic spinal cord compression after spinal irradiation. The surgical management of metastatic spinal cord compression may be complicated by preoperative radiation. Methods. A retrospective review of 123 patients admitted with symptomatic metastatic spinal cord compression from 1970 through 1996 was conducted. The final study population of 85 patients was separated into three treatment groups: 1) radiation only, 2) radiation followed by surgery, and 3) de novo surgery followed by radiation. Results. The major wound complication rate for patients who had radiation before surgical decompression and stabilization was 32%, or threefold, higher than the 12% observed in patients who had de novo surgery (P < 0.05). No other clinical factor or condition predicted the development of a major wound complication. Patients treated initially with surgery had superior functional outcomes in an analysis stratified by Frankel grade (P < 0.05). Of the ambulatory patients who underwent de novo surgery, 75% remained ambulatory and continent 30 days after treatment, whereas only 50% of those treated with radiation before surgery had similar outcomes. Conclusions. Spinal radiation before surgical decompression for metastatic spinal cord compression is associated with a significantly higher major wound complication rate. In addition, preoperative spinal irradiation might adversely affect the surgical outcome. C1 Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthoped, Boston, MA 02114 USA. RP Borges, LF (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, White Bldg 1205, Boston, MA 02114 USA. RI Grams, Michael/G-5197-2011 NR 26 TC 105 Z9 112 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD APR 1 PY 2001 VL 26 IS 7 BP 818 EP 824 DI 10.1097/00007632-200104010-00025 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 416YZ UT WOS:000167809300020 PM 11295906 ER PT J AU Ibrahim, JG Chen, MH Sinha, D AF Ibrahim, JG Chen, MH Sinha, D TI Criterion-based methods for Bayesian model assessment SO STATISTICA SINICA LA English DT Article DE calibration; model selection; predictive criterion; predictive distribution; variable selection ID IMMUNODEFICIENCY-VIRUS INFECTION; REGRESSION MODELS; VARIABLE SELECTION; CONTROLLED TRIAL; SURVIVAL-DATA; ZIDOVUDINE AB We propose a general Bayesian criterion fur model assessment. The criterion is constructed from the posterior predictive distribution of the data, and can he written as a sum of two components, one involving the means of the posterior predictive. distribution and the other involving the variances. It can be viewed as a Bayesian goodness-of-fit statistic which measures the performance of a model by a combination of how close its predictions are to the observed data and the variability of the predictions. We call this proposed predictive criterion the L measure, it is motivated hy earlier work of Ibrahim and Laud (1994) and related to a criterion of Gelfand and Ghosh (1998). We examine the L measure in detail for the class of generalized linear models and survival models with right censored or interval censored data. We also propose a calibration of the L measure, defined as the prior predictive distribution of the difference between the L measures of the candidate model and the criterion minimizing model, and call it the calibration distribution. The calibration distribution will allow us to formally compare tao competing models based on their L measure values. We discuss theoretical properties of the calibration distribution in detail, and provide Monte Carlo methods for computing it. For the linear model, we derive an analytic closed form expression for the L measure and the calibration distribution, and;also derive a closed form expression for the mean of the calibration distribution. These novel developments will enable us to fully characterize the properties of the L measure for each model under consideration and will facilitate a direct formal comparison between several models, including non-nested models. Informative priors based on historical data and computational techniques are discussed. Several simulated and real datasets are used to demonstrate the proposed methodology. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Cambridge, MA 02138 USA. Worcester Polytech Inst, Dept Math Sci, Worcester, MA 01609 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC USA. RP Ibrahim, JG (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Cambridge, MA 02138 USA. NR 31 TC 43 Z9 44 U1 0 U2 2 PU STATISTICA SINICA PI TAIPEI PA C/O DR H C HO, INST STATISTICAL SCIENCE, ACADEMIA SINICA, TAIPEI 115, TAIWAN SN 1017-0405 J9 STAT SINICA JI Stat. Sin. PD APR PY 2001 VL 11 IS 2 BP 419 EP 443 PG 25 WC Statistics & Probability SC Mathematics GA 429DY UT WOS:000168501800017 ER PT J AU Wu, O Koroshetz, WJ Ostergaard, L Buonanno, FS Copen, WA Gonzalez, RG Rordorf, G Rosen, BR Schwamm, LH Weisskoff, RM Sorensen, AG AF Wu, O Koroshetz, WJ Ostergaard, L Buonanno, FS Copen, WA Gonzalez, RG Rordorf, G Rosen, BR Schwamm, LH Weisskoff, RM Sorensen, AG TI Predicting tissue outcome in acute human cerebral ischemia using combined diffusion- and perfusion-weighted MR imaging SO STROKE LA English DT Article DE cerebral ischemia; magnetic resonance imaging, diffusion-weighted; magnetic resonance imaging, perfusion-weighted; stroke, acute ID HIGH-RESOLUTION MEASUREMENT; TRACER BOLUS PASSAGES; ACUTE STROKE; BLOOD-FLOW; HYPERACUTE STROKE; TIME-COURSE; PENUMBRA; MODEL; RECANALIZATION; THRESHOLDS AB Background and Purpose-Tissue signatures from acute MR imaging of the brain may be able to categorize physiological status and thereby assist clinical decision making. We designed and analyzed statistical algorithms to evaluate the risk of infarction for each voxel of tissue using acute human functional MRI. Methods-Diffusion-weighted MR images (DWI) and perfusion-weighted MR images (PWI) from acute stroke patients scanned within 12 hours of symptom onset were retrospectively studied and used to develop thresholding and generalized Linear model (GLM) algorithms predicting tissue outcome as determined by follow-up MRI, The performances of the algorithms were evaluated for each patient by using receiver operating characteristic curves. Results-At their optimal operating points, thresholding algorithms combining DWI and PWI provided 66% sensitivity and 83% specificity, and GLM algorithms combining DWI and PWI predicted with 66% sensitivity and 84% specificity voxels that proceeded to infarct, Thresholding algorithms that combined DWI and PWI provided significant improvement to algorithms that utilized DWI alone (P=0.02) but no significant improvement over algorithms utilizing PWI alone (P=0.21). GLM algorithms that combined DWI and PWI showed significant improvement over algorithms that used only DWI (P=0.02) or PWI (P=0.04). The performances of thresholding and GLM algorithms were comparable (P>0.2). Conclusions-Algorithms that combine acute DWI and PWI can assess the risk of infarction with higher specificity and sensitivity than algorithms that use DWI or PWI individually. Methods for quantitatively assessing the risk of infarction on a voxel-by-voxel basis show promise as techniques for investigating the natural spatial evolution of ischemic damage in humans. C1 Massachusetts Gen Hosp, MGH NMR Ctr, Dept Radiol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA. MIT, Cambridge, MA 02139 USA. RP Wu, O (reprint author), Massachusetts Gen Hosp, MGH NMR Ctr, Dept Radiol, Mailcode CNY149-2301, Boston, MA 02129 USA. RI Bonefeld, Birgit/B-7936-2010; Ostergaard, Leif/A-9281-2008; OI Ostergaard, Leif/0000-0003-2930-6997; Schwamm, Lee/0000-0003-0592-9145 FU NCI NIH HHS [CA83159]; NCRR NIH HHS [5P41-RR14075, RR13213]; NHLBI NIH HHS [R01-HL39810]; NINDS NIH HHS [NS34626] NR 48 TC 171 Z9 176 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2001 VL 32 IS 4 BP 933 EP 942 PG 10 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 419LV UT WOS:000167951300023 PM 11283394 ER PT J AU Amin-Hanjani, S Stagliano, NE Yamada, M Huang, PL Liao, JK Moskowitz, MA AF Amin-Hanjani, S Stagliano, NE Yamada, M Huang, PL Liao, JK Moskowitz, MA TI Mevastatin, an HMG-CoA reductase inhibitor, reduces stroke damage and upregulates endothelial nitric oxide synthase in mice SO STROKE LA English DT Article DE cerebral ischemia; endothelial nitric oxide synthase; HMG-CoA reductase inhibitors; mice ID FOCAL CEREBRAL-ISCHEMIA; BLOOD-FLOW; L-ARGININE; PRAVASTATIN; SIMVASTATIN; MODEL AB Background and Purpose-The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) lower serum cholesterol and decrease the incidence of stroke and cardiovascular disease. There is growing evidence that statins exert some of their beneficial effects independent of cholesterol lowering. Indeed, we have previously demonstrated that chronic simvastatin administration upregulates endothelial nitric oxide synthase (eNOS), resulting in more functional protein, augmentation of cerebral blood flow, and neuroprotection in a murine model of cerebral ischemia. In this report we examined whether another member of the statin family shared these effects and whether eNOS upregulation is sustained with longer treatment. Methods-Mevastatin (2 mg/kg or 20 mg/kg per day) was administered to 18- to 22-g male mice for 7, 14, or 28 days before 2-hour middle cerebral artery occlusion with the use of the filament model (n = 9 to 12). Neurological deficits and cerebral infarct volumes were assessed at 24 hours. Arterial blood pressure and gases, relative cerebral blood flow, and blood cholesterol levels were monitored in a subset of animals (n=5). Absolute cerebral blood flow was measured by the [C-14]iodoamphetamine indicator fractionation technique (n=6), eNOS mRNA and protein levels were determined. Results-Mevastatin increased levels of eNOS mRNA and protein, reduced infarct size, and improved neurological deficits in a dose- and time-dependent manner. Greatest protection was seen with 13- and 25-day high-dose treatment (26% and 37% infarct reduction, respectively). Cholesterol levels were reduced only after 28 days of treatment and did not correlate with infarct reduction. Baseline absolute cerebral blood flow was 30% higher after 14-day high-dose treatment. Conclusions-Chronic prophylactic treatment with mevastatin upregulated eNOS and augmented cerebral blood flow. These changes occurred in the absence of changes in serum cholesterol levels, were sustained for up to 1 month of treatment, and resulted in neuroprotection after middle cerebral artery occlusion. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. RP Moskowitz, MA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, 149 13th St,Room 6403, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 FU NHLBI NIH HHS [1-RO1-HL62602]; NINDS NIH HHS [5-P50-NS10828] NR 24 TC 229 Z9 239 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 2001 VL 32 IS 4 BP 980 EP 985 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 419LV UT WOS:000167951300030 PM 11283400 ER PT J AU Vacanti, JP AF Vacanti, JP TI Looking back and looking ahead SO TISSUE ENGINEERING LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, 55 Fruit St Warren 1157, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD APR PY 2001 VL 7 IS 2 BP 107 EP 109 DI 10.1089/107632701300062679 PG 3 WC Cell & Tissue Engineering SC Cell Biology GA 425DZ UT WOS:000168274200001 ER PT J AU Tolcher, AW Kennedy, A Padley, RJ Majeed, N Pollak, M Kantoff, PW AF Tolcher, AW Kennedy, A Padley, RJ Majeed, N Pollak, M Kantoff, PW TI Other novel agents: Rationale and current status as chemopreventive agents SO UROLOGY LA English DT Article; Proceedings Paper CT National-Cancer-Institute Workshop CY 1999 CL ROCKVILLE, MARYLAND SP NCI ID ACTIVATED RECEPTOR-GAMMA; FACTOR BINDING-PROTEINS; BOWMAN-BIRK INHIBITOR; HUMAN PROSTATE-CANCER; GROWTH-FACTOR-II; PPAR-GAMMA; PROTEASE INHIBITOR; IN-VITRO; IGF BINDING-PROTEIN-3; INCREASED EXPRESSION AB Several novel targets are currently being evaluated both preclinically and clinically for the prevention of prostate cancer. Four divergent and novel approaches were discussed at the National Cancer Institute-sponsored workshop entitled, "New Clinical Strategies in Prostate Cancer Prevention," These interventions are further categorized into soy protein-based serine-protease inhibitors that reduce superoxide-induced DNA damage, and molecularly targeted approaches that are directed toward endothelin-1 expression/overexpression, peroxisome proliferator-activated receptor ligands, and insulinlike growth factors. Understanding each of these approaches has offered insights into the process of malignant transformation of prostatic epithelium, and further illustrates the difficulties of developing new agents in the treatment and prevention of prostate cancer, Close scrutiny of the clinical data emerging with these approaches, including validation of biologic endpoints, is required before large-scale prevention studies with these novel agents and targets can be considered. (C) 2001, Elsevier Science Inc. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. McGill Univ, Montreal, PQ, Canada. Abbott Labs, Abbott Pk, IL 60064 USA. Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Canc Therapy & Res Ctr, Inst Drug Dev, San Antonio, TX 78229 USA. RP Tolcher, AW (reprint author), Canc Therapy & Res Ctr, Inst Drug Dev, 8122 Datapoint Dr,Suite 250, San Antonio, TX 78229 USA. RI Pollak, Michael/G-9094-2011 OI Pollak, Michael/0000-0003-3047-0604 NR 41 TC 11 Z9 12 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD APR PY 2001 VL 57 IS 4A SU S BP 86 EP 89 DI 10.1016/S0090-4295(00)00948-1 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 423HT UT WOS:000168170400015 PM 11295602 ER PT J AU Fisher, WE AF Fisher, WE TI Diabetes: Risk factor for the development of pancreatic cancer or manifestation of the disease? SO WORLD JOURNAL OF SURGERY LA English DT Article ID MEDICAL HISTORY; GLUCOSE-METABOLISM; SYRIAN-HAMSTERS; MELLITUS; STREPTOZOTOCIN; INSULIN; CARCINOMA; ALCOHOL; COFFEE; GROWTH AB The objective of this study was to summarize the English-language literature that addresses diabetes mellitus as a potential risk factor for the development of pancreatic cancer. Studies exploring the relation between diabetes and pancreatic cancer published between 1970 and 1999 were identified from a MEDLINE search and are summarized. They showed that diabetes mellitus occurs more frequently in patients with pancreatic cancer than in the general population. Most of the literature supports the view that diabetes of at least 5 years' duration increases the risk of subsequently developing pancreatic cancer. In addition, experimental forms of diabetes clearly affect the induction and growth of pancreatic cancer. The currently available literature thus suggests that diabetes is a risk factor for the subsequent development of pancreatic cancer. C1 Baylor Coll Med, Surg Serv 112, Houston Vet Adm Med Ctr, Houston, TX 77030 USA. RP Fisher, WE (reprint author), Baylor Coll Med, Surg Serv 112, Houston Vet Adm Med Ctr, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 58 TC 35 Z9 48 U1 0 U2 5 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 APR PY 2001 VL 25 IS 4 BP 503 EP 508 PG 6 WC Surgery SC Surgery GA 430CQ UT WOS:000168556300018 PM 11396427 ER PT J AU Song, SU Boyce, FM AF Song, SU Boyce, FM TI Combination treatment for osteosarcoma with baculoviral vector mediated gene therapy (p53) and chemotherapy (adriamycin) SO EXPERIMENTAL AND MOLECULAR MEDICINE LA English DT Article DE combination therapy; baculoviral vector; p53 tumor suppressor gene; chemotherapeutic drug ID TUMOR-SUPPRESSOR GENE; MAMMALIAN-CELLS; LUNG-CANCER; APOPTOSIS; EXPRESSION; INDUCTION AB The insect baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) has been evaluated as a vector for gene delivery to human tumor cells. A human osteogenic sarcoma cell line, Saos-2, was found to be highly susceptible to infection with a baculoviral vector, with nearly 100% of Saos-2 cells being able to express a lacZ reporter gene after a brief exposure to the virus at a m.o.i. of 30 pfu/cell. The production of beta -galactosidase protein was 18-times greater than that in HepG2 cells which were previously thought to be the mammalian cells most susceptible to the baculovirus. The possibility of developing a baculovirus as a cytotoxic vector for p53-defective cancer was tested by destruction of Saos-2 cells (p53(-/-)) with a recombinant baculovirus containing the wild type pas gene (BV-p53) in vitro. The p53 baculovirus induced apoptotic cell death in tumor cells in a dose-dependent manner with similar to 60% killing at an m.o.i. of 160 pfu/cell. Combined treatments of gene therapy (p53) and chemotherapy (adriamycin) resulted in synergistic and potent killing of the osteogenic sarcoma cells. For example, greater than 95% of Saos-2 cells were killed by the combination of BV-p53 (m.o.i. of 100) and adriamycin (35 ng/ml), whereas similar to 50% and similar to 55% cells were killed by BV-p53 and adriamycin alone, respectively. These results indicate that a baculoviral gene delivery vector can be used to efficiently target certain types of mammalian cells and the combination treatment of gene-therapy mediated by a baculovirus and chemotherapy may enhance induction of apoptosis in cancer cells. C1 Inha Univ, Coll Med, Clin Res Ctr, Inchon 400711, South Korea. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA76656-02] NR 17 TC 37 Z9 41 U1 0 U2 1 PU KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY PI SEOUL PA #812 KOFST, 635-4 YOKSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1226-3613 J9 EXP MOL MED JI Exp. Mol. Med. PD MAR 31 PY 2001 VL 33 IS 1 BP 46 EP 53 PG 8 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA 421MD UT WOS:000168067400009 PM 11322486 ER PT J AU Pootanakit, K Brunken, WJ AF Pootanakit, K Brunken, WJ TI Identification of 5-HT3A and 5-HT3B receptor subunits in mammalian retinae: potential pre-synaptic modulators of photoreceptors SO BRAIN RESEARCH LA English DT Article DE 5-HT3A receptor subunit; 5-HT3B receptor subunit; rod pathway; presynaptic modulator; rabbit; human ID INDOLEAMINE-ACCUMULATING NEURONS; RABBIT RETINA; PRESYNAPTIC INHIBITION; FUNCTIONAL EXPRESSION; AXON TERMINALS; SPINAL-CORD; RAT RETINA; SEROTONIN; CELLS; RELEASE AB Although serotonin (5-HT) is found in the mammalian retina only at low levels, considerable evidence suggests that it plays a role in visual processing. Pharmacological experiments indicate that numerous receptors for 5-HT are present in the mammalian retina. One of these is the ionotropic 5-HT3 receptor. So far, two subunits for this receptor have been identified in the nervous system, 5-HT3A and 5-HT3B. Go-expression of these subunits in Xenopus oocytes is sufficient to reconstitute native 5-MT3 receptor properties. Thus, it is believed that a native neuronal 5-HT3 receptor is multimeric similar to the related acetylcholine receptor family. To determine whether this receptor is expressed in the mammalian retina, we first performed reverse transcription polymerase chain reaction and first demonstrated the presence of transcripts for both the 5-HT3A and 5-HT3B receptor subunits. Then using a well-characterized polyclonal antiserum against the 5-HT3A receptor subunit, we demonstrated 5-HT3A receptor immunoreactivity (IR) in the rabbit, rat, and human retina. This IR was localized specifically to the rod photoreceptor terminals in all three species, suggesting that this receptor may modulate the rod signaling pathway by controlling the output at the rod terminals. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. RP Brunken, WJ (reprint author), Massachusetts Gen Hosp E, Cutaneous Biol Res Ctr, 3rd Floor,Bldg 149,13th St, Charlestown, MA 02129 USA. NR 53 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 30 PY 2001 VL 896 IS 1-2 BP 77 EP 85 DI 10.1016/S0006-8993(01)01998-9 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 419KL UT WOS:000167947900010 PM 11277976 ER PT J AU Hasirci, V Lewandrowski, K Gresser, JD Wise, DL Trantolo, DJ AF Hasirci, V Lewandrowski, K Gresser, JD Wise, DL Trantolo, DJ TI Versatility of biodegradable biopolymers: degradability and an in vivo application SO JOURNAL OF BIOTECHNOLOGY LA English DT Article; Proceedings Paper CT Interim Meeting of the International-Society-of-Environmental-Biotechnology (ISEB) CY MAR 02-05, 1999 CL LEIPZIG, GERMANY SP Int Soc Environm Biotechnol DE biodegradation; interpenetrating networks; molecular reinforcement; osteointegration; polypropylene fumarate ID HYDROXYBUTYRATE-HYDROXYVALERATE COPOLYMERS; STRUCTURE PROPERTY RELATIONSHIPS; GUIDED TISSUE REGENERATION; ETHYLENE GLYCOL) HYDROGELS; IN-VITRO; FRACTURE FIXATION; BONE REGENERATION; MEDICAL DEVICES; AQUEOUS-MEDIA; DEGRADATION AB Biodegradable materials have various important applications in the biomedical field. There are basically two groups of polyesters which have significant importance in this field. These are polylactides and polyhydroxybutyrates. Both groups degrade via hydrolysis with the rates of degradation depending on medium properties such as pH, temperature, solvent and presence of biocatalysts, as well as on chemical compositions. In order for these biomaterials to be suitable for use in load bearing applications without deformation or warping their strengths and their capability to maintain their form must be improved. To insure dimensional stability during degradation and to match modulus and strength to that of bone, introduction of a reinforcing structure for those applications to plate fixation through the creation of an interpenetrating network might be a feasible approach. In this study, poly(lactide-co-glycolide) (PLGA), was the major structural element to be strengthened by a three-dimensional network or 'scaffold' of another biodegradable polymer, poly(propylene fumarate) (PPF). PPF would be crosslinked with a biocompatible vinyl monomer, vinylpyrrolidone (VP). Three different approaches were tested to create dimensionally stable bone plates. First, via in situ crosslinking of PPF in the presence of PLGA. Secondly, by blending of precrosslinked PPF with PLGA. Finally, by simultaneous crosslinking and molding of the PLGA, PPF and VP. These were compared against extruded or compression molded PLGA controls. Results showed that compression molding at room temperature followed by crosslinking under pressure at elevated temperature and subsequently by gamma -irradiation appeared to yield the most favorable product as judged by swelling, hardness and flexural strength data. The composition of the implant material, PLGA(3):PPF(1):VP(0.7), appeared to be suitable and formed the compositional and procedural basis for in vivo biocompatibility studies. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Middle E Tech Univ, Dept Biol Sci, Biotechnol Res Unit, TR-06531 Ankara, Turkey. Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. Cambridge Sci Inc, Belmont, MA 02478 USA. RP Hasirci, V (reprint author), Middle E Tech Univ, Dept Biol Sci, Biotechnol Res Unit, TR-06531 Ankara, Turkey. FU NIAMS NIH HHS [1 R43 AR44317-01] NR 38 TC 85 Z9 95 U1 3 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1656 J9 J BIOTECHNOL JI J. Biotechnol. PD MAR 30 PY 2001 VL 86 IS 2 SI SI BP 135 EP 150 DI 10.1016/S0168-1656(00)00409-0 PG 16 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 415XU UT WOS:000167749500007 PM 11245902 ER PT J AU Ulbert, I Halgren, E Heit, G Karmos, G AF Ulbert, I Halgren, E Heit, G Karmos, G TI Multiple microelectrode-recording system for human intracortical applications SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE evoked potentials; neocortex; hippocampus; epilepsy; multielectrode; unit activity; multiple unit activity; CSD ID SOURCE-DENSITY ANALYSIS; INDUCED EPILEPTIC PHENOMENA; HIPPOCAMPAL THETA-RHYTHM; FREELY MOVING RATS; FIELD POTENTIALS; UNIT-ACTIVITY; EVOKED-POTENTIALS; IFCN COMMITTEE; ANURAN CEREBELLUM; INTERICTAL SPIKES AB The human brain is dominated by the neocortex, a large folded surface, whose cellular and synaptic elements are arranged in layers. Since cortical structure is relatively constant across its surface, local information processing can be inferred From multiple laminar recordings of its electrical activity along a line perpendicular to its surface. Such recordings need to be spaced at least as close together as the cortical layers, and need to be wideband in order to sample both low frequency synaptic currents as well as high-frequency action potentials. Finally, any device used in the human brain must comply with strict safety standards. The current paper presents details of a system melting these criteria, together with sample results obtained from epileptic subjects undergoing acute or chronic intracranial monitoring for definition of the epileptogenic region. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Hungarian Acad Sci, Inst Psychol, Budapest, Hungary. Stanford Univ, Med Ctr, Dept Neurosurg, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA USA. RP Ulbert, I (reprint author), Hungarian Acad Sci, Inst Psychol, Budapest, Hungary. RI Ulbert, Istvan/F-2213-2010 FU NINDS NIH HHS [NS 18741, R01 NS018741] NR 51 TC 92 Z9 94 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD MAR 30 PY 2001 VL 106 IS 1 BP 69 EP 79 DI 10.1016/S0165-0270(01)00330-2 PG 11 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 419AX UT WOS:000167928100008 PM 11248342 ER PT J AU Gould, RA Mueser, KT Bolton, E Mays, V Goff, D AF Gould, RA Mueser, KT Bolton, E Mays, V Goff, D TI Cognitive therapy for psychosis in schizophrenia: an effect size analysis SO SCHIZOPHRENIA RESEARCH LA English DT Article DE cognitive therapy; meta-analysis; positive symptoms; schizophrenia ID RANDOMIZED CONTROLLED TRIAL; BEHAVIORAL THERAPY; FOLLOW-UP; SYMPTOMS; RESISTANT AB We conducted a meta-analysis using all available controlled treatment outcome studies of cognitive therapy (CT) for psychotic symptoms in schizophrenia. Effect sizes were calculated for seven studies involving 340 subjects. The mean effect size for reduction of psychotic symptoms was 0.65. The findings suggest that cognitive therapy is an effective treatment for patients with schizophrenia who have persistent psychotic symptoms. Follow-up analyses in four studies indicated that patients recieving CT continued to make gains over time (ES = 0.93). Further research is needed to determine the replicability of standardized cognitive interventions, to evaluate the clinical significance of cognitive therapy for schizophrenia, and to determine which patients are most likely to benefit from this intervention. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychot Disorders Program, Boston, MA 02114 USA. Dartmouth Med Sch, Dept Psychiat, Concord, NH 03301 USA. New Hampshire Dartmouth Psychiat Res Ctr, Concord, NH 03301 USA. RP Gould, RA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychot Disorders Program, Boston, MA 02114 USA. NR 39 TC 187 Z9 192 U1 4 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD MAR 30 PY 2001 VL 48 IS 2-3 BP 335 EP 342 DI 10.1016/S0920-9964(00)00145-6 PG 8 WC Psychiatry SC Psychiatry GA 424EZ UT WOS:000168220300017 PM 11295385 ER PT J AU Pellman, D AF Pellman, D TI Cancer - A CINtillating new job for the APC tumor suppressor SO SCIENCE LA English DT Editorial Material ID PROTEIN C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. RP Pellman, D (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. NR 16 TC 20 Z9 22 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAR 30 PY 2001 VL 291 IS 5513 BP 2555 EP 2556 DI 10.1126/science.1057337 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 417XP UT WOS:000167861000025 PM 11286276 ER PT J AU Legedza, ATR Ibrahim, JG AF Legedza, ATR Ibrahim, JG TI Heterogeneity in phase I clinical trials: prior elicitation and computation using the continual reassessment method SO STATISTICS IN MEDICINE LA English DT Article ID DESIGN AB Heterogeneity in a phase I clinical trial patient population may lead to distinctly different dose-response relationships along covariate values. For a given target probability of toxicity, this implies different maximum tolerated doses (MTDs) for each distinct subpopulation. Within the framework of O'Quigley, Pepe and Fisher's (1990) continual reassessment method, we propose the notion of average and patient-specific MTDs by augmenting the dose-response model with other covariates to account for such differences. A method to elicit prior distributions on the dose and other covariate parameters are proposed, based on the predictive approach of Ibrahim and Laud (1994), Laud and Ibrahim (1995), and Ibrahim, Ryan and Chen (1998). This approach relies on prior predictions for the response vector y(0) and a quantity ao specifying uncertainty in y(0) Then, y(0) and a(0) are used to specify a prior for the regression coefficients in a semi-automatic fashion. The elicitation scheme for y(0) uses results from previous phase I cancer clinical trials. The average and patient-specific MTDs and an elicitation method are demonstrated in logistic regression examples. Copyright (C) 2001 John Wiley & Sons, Ltd. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Legedza, ATR (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 665 Huntington Ave, Boston, MA 02115 USA. FU NCI NIH HHS [5 T32 CA09337, CA 70101-01, CA 74015-01] NR 11 TC 15 Z9 15 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAR 30 PY 2001 VL 20 IS 6 BP 867 EP 882 DI 10.1002/sim.701 PG 16 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 414MQ UT WOS:000167670800004 PM 11252009 ER PT J AU Livingston, DM AF Livingston, DM TI Cancer - Chromosome defects in the colon SO NATURE LA English DT Editorial Material ID BINDING PROTEIN EB1; APC; MICROTUBULES; SPINDLE; YEAST C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Livingston, DM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, 44 Binney St, Boston, MA 02115 USA. NR 17 TC 7 Z9 8 U1 0 U2 0 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 29 PY 2001 VL 410 IS 6828 BP 536 EP 537 DI 10.1038/35069185 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 417WW UT WOS:000167859300032 PM 11279479 ER PT J AU Kim, DH Nelson, HH Wiencke, JK Christiani, DC Wain, JC Mark, EJ Kelsey, KT AF Kim, DH Nelson, HH Wiencke, JK Christiani, DC Wain, JC Mark, EJ Kelsey, KT TI Promoter methylation of DAP-kinase: association with advanced stage in non-small cell lung cancer SO ONCOGENE LA English DT Article DE DAP-kinase; k-ras; p53; methylation; nonsmall cell lung cancer ID TUMOR-SUPPRESSOR GENES; DNA METHYLATION; CPG ISLAND; SIGNALING PATHWAY; HYPERMETHYLATION; METHYLTRANSFERASE; PROTEIN; DEATH; IDENTIFICATION; APOPTOSIS AB Death associated protein (DAP)-kinase is a 16 kDa calmodulin-dependent serine/threonine kinase that carries a death domain at its C-terminus. DAP-kinase functions as a positive mediator of apoptosis that is induced by interferon-gamma. Recent studies suggest that DAP-kinase is involved in tumor metastasis and that it can be inactivated by methylation of CpG islands in the promoter region of the gene in some human tumors. However, little is known about the factors that are associated with the occurrence of DAP-kinase promoter methylation. We investigated both the possible associations of tobacco carcinogen and asbestos exposure with DAP-kinase promoter methylation, and the demographic and clinical factors associated with DAP-kinase promoter methylation in non-small cell lung cancer (NSCLC), One hundred and eighty-five patients diagnosed with NSCLC undergoing surgical resection from June, 1992 through December, 1996 at Massachusetts General Hospital participated in this study, Methylation-Specific PCR (MSP), performed using fresh-frozen tissue, was used to determine the methylation status of the promoter region of the DAP-kinase gene. Forty-seven (25%) of 185 tumors showed DAP-kinase promoter methylation. There was a significant association between methylation and an advanced pathologic stage (P=0.003, Fisher's exact test). Methylation of the DAP-kinase promoter was also associated with an increase in tumor size (P=0.009, Fisher's exact test) and lymph node involvement (P=0.04), No association was found between promoter methylation of DAP-kinase and k-ras or p53 mutation. In addition there was no association with a history of exposure to tobacco or asbestos. Controlling for age, sex, and histology, the odds ratios describing the association of DAP-kinase hypermethylation with stage were 2.70 (1.13-6.45), 3.11 (1.37-7.08) and 7.77 (1.21-50.03) in stages II, III and IV, respectively. Stage I cases with DAP-kinase promoter methylation had worse overall survival, but with the small sample size and limited follow-up this did not reach statistical significance. Our findings suggest that methylation of the promoter region of the DAP-kinase gene is not associated with exposure to tobacco or asbestos. However, they strongly suggest that DAP-kinase may be important in the progression of non-small cell lung cancer from early to late stage disease. C1 Harvard Univ, Sch Publ Hlth, Dept Canc Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, Lab Mol Epidemiol, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Thorac Surg Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kelsey, KT (reprint author), Harvard Univ, Sch Publ Hlth, Dept Canc Cell Biol, 665 Huntington Ave,Bldg 1,Rm 207, Boston, MA 02115 USA. RI Kelsey, Karl/I-1252-2014 FU NCI NIH HHS [CA74386, CA08357, CA06717]; NIEHS NIH HHS [ES00002, ES/CA 06409] NR 29 TC 109 Z9 117 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 29 PY 2001 VL 20 IS 14 BP 1765 EP 1770 DI 10.1038/sj.onc.1204302 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 415YJ UT WOS:000167750900009 PM 11313923 ER PT J AU Whittington, DA Rosenzweig, AC Frederick, CA Lippard, SJ AF Whittington, DA Rosenzweig, AC Frederick, CA Lippard, SJ TI Xenon and halogenated alkanes track putative substrate binding cavities in the soluble methane monooxygenase hydroxylase SO BIOCHEMISTRY LA English DT Article ID METHYLOCOCCUS-CAPSULATUS BATH; COMPONENT INTERACTIONS; CRYSTAL-STRUCTURE; MOLECULAR-DYNAMICS; PROTEIN; MYOGLOBIN; SITE; ELECTRON; CRYSTALLOGRAPHY; FLUCTUATIONS AB To investigate the role of protein cavities in facilitating movement of the substrates, methane and dioxygen, in the soluble methane monooxygenase hydroxylase (MMOH), we determined the X-ray structures of MMOH from Methylococcus capsulatus (Bath) cocrystallized with dibromomethane or iodoethane, or by using crystals pressurized with xenon gas. The halogenated alkanes bind in two cavities within the alpha -subunit that extend from one surface of the protein to the buried dinuclear iron active site. Two additional binding sites were located in the beta -subunit. Pressurization of two crystal forms of MMOH with xenon resulted in the identification of six binding sites located exclusively in the alpha -subunit. These results indicate that hydrophobic species bind preferentially in preexisting cavities in MMOH and support the hypothesis that such cavities may play a functional role in sequestering and enhancing the availability of the physiological substrates for reaction at the active site. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. MIT, Dept Chem, Cambridge, MA 02139 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lippard, SJ (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM32134, GM48388] NR 44 TC 61 Z9 61 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 27 PY 2001 VL 40 IS 12 BP 3476 EP 3482 DI 10.1021/bi0022487 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 416UJ UT WOS:000167798300008 PM 11297413 ER PT J AU Beckman, JA Goldfine, AB Gordon, MB Creager, MA AF Beckman, JA Goldfine, AB Gordon, MB Creager, MA TI Ascorbate restores endothelium-dependent vasodilation impaired by acute hyperglycemia in humans SO CIRCULATION LA English DT Article DE nitric oxide; diabetes mellitus; antioxidants; glucose ID NITRIC-OXIDE SYNTHASE; PROTEIN-KINASE-C; VASCULAR SMOOTH-MUSCLE; DIABETES-MELLITUS; VITAMIN-C; MEDIATED VASODILATION; PLATELET ACTIVATION; SUPEROXIDE ANION; FREE-RADICALS; SHEAR-STRESS AB Background-Endothelium-dependent vasodilation is impaired in patients with insulin-dependent and non-insulin-dependent diabetes mellitus and restored by vitamin C administration, implicating a causative role for oxidant stress. Hyperglycemia per se attenuates endothelium-dependent vasodilation;in healthy subjects. Accordingly, this study investigated whether impaired endothelium-dependent vasodilation caused by hyperglycemia in nondiabetic humans is restored by administration of the antioxidant vitamin C. Methods and Results-Endothelium-dependent vasodilation was measured by incremental brachial artery administration of methacholine chloride (0.3 to 10 mug/min) during euglycemia, after 6 hours of hyperglycemia (300 mg/dL) created by dextrose (50%) intra-arterial infusion, and with coadministration of vitamin C (24 mg/min) during hyperglycemia. Endothelium-dependent vasodilation was significantly diminished by hyperglycemia (P=0.02 by ANOVA) and restored by vitamin C (P=0.04). In contrast, endothelium-dependent vasodilation was not affected by equimolar infusions of mannitol, with and without vitamin C coinfusion (P NS). Endothelium-independent vasodilation was measured by incremental infusion of verapamil chloride (10 to 300 mug/min) without and with coadministration of N-G-monomerhyl-L-arginine (L-NMMA). In the absence of L-NMMA, endothelium-independent vasodilation was not significantly altered during hyperglycemia (P=NS) but was augmented by vitamin C (P=0.04). The coadministration of L-NMMA eliminated the vitamin C-related augmentation in verapamil-mediated vasodilation. Conclusions-Vitamin C administration restores endothelium-dependent vasodilation impaired by acute hyperglycemia in healthy humans in vivo. These findings suggest that hyperglycemia may contribute in part to impaired vascular function through production of superoxide anion. C1 Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Cellular & Mol Physiol, Boston, MA USA. RP Creager, MA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. OI Beckman, Joshua/0000-0001-8332-8439 FU NHLBI NIH HHS [HL-48743, HL-56607] NR 40 TC 191 Z9 201 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 MAR 27 PY 2001 VL 103 IS 12 BP 1618 EP 1623 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 417TH UT WOS:000167849900014 PM 11273987 ER PT J AU Counihan, TJ Shinobu, LA Eskandar, EN Cosgrove, GR Penney, JB AF Counihan, TJ Shinobu, LA Eskandar, EN Cosgrove, GR Penney, JB TI Outcomes following staged bilateral pallidotomy in advanced Parkinson's disease SO NEUROLOGY LA English DT Article ID POSTEROVENTRAL PALLIDOTOMY; MEDIAL PALLIDOTOMY AB The authors assessed clinical outcome for up to one year after staged bilateral pallidotomy in 14 patients with advanced PD. One year after surgery, dyskinesias were virtually abolished and there were significant reductions in "off" time (67%) and activities of daily living "off" scores (24%), as well as nonsignificant reduction in "off' motor score (39%); "on" scores were unchanged. One patient developed a visual field deficit; two had transient confusion. Staged bilateral pallidotomy improves motor function in selected patients with advanced PD. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Counihan, TJ (reprint author), Univ Rochester, Dept Neurol, Box 673,601 Elmwood Ave, Rochester, NY 14642 USA. NR 10 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 27 PY 2001 VL 56 IS 6 BP 799 EP 802 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 414ZY UT WOS:000167697100025 PM 11274323 ER PT J AU Liebeskind, DS Ostrzega, N Wasterlain, CG Buttner, EA AF Liebeskind, DS Ostrzega, N Wasterlain, CG Buttner, EA TI Neurologic manifestations of disseminated infection with Mycobacterium abscessus SO NEUROLOGY LA English DT Article ID RAPIDLY GROWING MYCOBACTERIA; CHELONAE; THERAPY AB Mycobacterium abscessus is a ubiquitous, saprophytic organism with low pathogenic potential. The authors describe the previously unreported clinical features of meningitis and native valve endocarditis caused by this rapidly growing atypical mycobacterium. The fatal outcome of this unusual case coincides with the grim prognosis of this disseminated infection and the significant mortality rate associated with neurologic complications of infective endocarditis. C1 Univ Penn, Med Ctr, Comprehens Stroke Ctr, Philadelphia, PA 19104 USA. Univ Calif Los Angeles, Sch Med, Dept Pathol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Liebeskind, DS (reprint author), Univ Penn, Med Ctr, Comprehens Stroke Ctr, 3 W Gates Bldg,3400 Spruce St, Philadelphia, PA 19104 USA. NR 10 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 27 PY 2001 VL 56 IS 6 BP 810 EP 813 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 414ZY UT WOS:000167697100029 PM 11274327 ER PT J AU Singhal, AB Singhal, BS Ursekar, MA Koroshetz, WJ AF Singhal, AB Singhal, BS Ursekar, MA Koroshetz, WJ TI Serial MR angiography and contrast-enhanced MRI in chickenpox-associated stroke SO NEUROLOGY LA English DT Article ID INFARCTION; CHILDHOOD; CHILDREN C1 Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Bombay Hosp Inst Med Sci, Dept Neurol, Bombay, Maharashtra, India. RP Singhal, AB (reprint author), Massachusetts Gen Hosp, Dept Neurol, Stroke Serv, VBK-802,55 Fruit St, Boston, MA 02114 USA. NR 6 TC 11 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 27 PY 2001 VL 56 IS 6 BP 815 EP 817 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 414ZY UT WOS:000167697100032 PM 11274330 ER PT J AU Wilson, DS Keefe, AD Szostak, JW AF Wilson, DS Keefe, AD Szostak, JW TI The use of mRNA display to select high-affinity protein-binding peptides SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE affinity tag; peptide library; peptide aptamer; Strep-tag; streptavidin ID IN-VITRO SELECTION; PHAGE DISPLAY; RIBOSOME DISPLAY; LIGAND-BINDING; LIBRARIES; STREPTAVIDIN; ANTIBODIES; PURIFICATION; RNA; FRAGMENT AB We report the use of "mRNA display," an in vitro selection technique, to identify peptide aptamers to a protein target, mRNA display allows for the preparation of polypeptide libraries with far greater complexity than is possible with phage display. Starting with a library of approximate to 10(13) random peptides, 20 different aptamers to streptavidin were obtained, with dissociation constants as low as 5 nM, These aptamers function without the aid of disulfide bridges or engineered scaffolds, yet possess affinities comparable to those for monoclonal antibody-antigen complexes. The aptamers bind streptavidin with three to four orders of magnitude higher affinity than those isolated previously by phage display from lower complexity libraries of shorter random peptides. Like previously isolated peptides, they contain an HPQ consensus motif. This study shows that, given sufficient length and diversity, high-affinity aptamers can be obtained even from random nonconstrained peptide libraries. By engineering structural constraints into these ultrahigh complexity peptide libraries, it may be possible to produce binding agents with subnanomolar binding constants. 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. NR 35 TC 227 Z9 232 U1 6 U2 46 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 27 PY 2001 VL 98 IS 7 BP 3750 EP 3755 DI 10.1073/pnas.061028198 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 417KG UT WOS:000167833700027 PM 11274392 ER PT J AU Michael, LF Wu, ZD Cheatham, RB Puigserver, P Adelmant, G Lehman, JJ Kelly, DP Spiegelman, BM AF Michael, LF Wu, ZD Cheatham, RB Puigserver, P Adelmant, G Lehman, JJ Kelly, DP Spiegelman, BM TI Restoration of insulin-sensitive glucose transporter (GLUT4) gene expression in muscle cells by the transcriptional coactivator PGC-1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE MEF2; diabetes ID RAT SKELETAL-MUSCLE; TRANSGENIC MICE; MITOCHONDRIAL BIOGENESIS; MOLECULAR MECHANISMS; OVEREXPRESSION; STIMULATION; PROTEIN; DOMAIN; SITE AB Muscle tissue is the major site for insulin-stimulated glucose uptake in vivo, due primarily to the recruitment of the insulin-sensitive glucose transporter (GLUT4) to the plasma membrane. Surprisingly, virtually all cultured muscle cells express little or no GLUT4, We show here that adenovirus-mediated expression of the transcriptional coactivator PGC-1, which is expressed in muscle in vivo but is also deficient in cultured muscle cells, causes the total restoration of GLUT4 mRNA levels to those observed in vivo. This increased GLUT4 expression correlates with a 3-fold increase in glucose transport, although much of this protein is transported to the plasma membrane even in the absence of insulin. PGC-1 mediates this increased GLUT4 expression, in large part, by binding to and coactivating the muscle-selective transcription factor MEF2C, These data indicate that PGC-1 is a coactivator of MEF2C and can control the level of endogenous GLUT4 gene expression in muscle. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Washington Univ, Sch Med, Dept Med & Mol Biol & Pharmacol, Cardiovasc Res Ctr, St Louis, MO 63110 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Cell Biol, 1 Jimmy Fund Way,44 Binney St,Smith 958, Boston, MA 02115 USA. FU NIDDK NIH HHS [R01 DK054477, R56 DK054477, DK54477]; NIGMS NIH HHS [F32 GM019680, GM19680] NR 31 TC 371 Z9 397 U1 0 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 MAR 27 PY 2001 VL 98 IS 7 BP 3820 EP 3825 DI 10.1073/pnas.061035098 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 417KG UT WOS:000167833700039 PM 11274399 ER PT J AU Hong, KH Bonventre, JC O'Leary, E Bonventre, JV Lander, ES AF Hong, KH Bonventre, JC O'Leary, E Bonventre, JV Lander, ES TI Deletion of cytosolic phospholipase A(2) suppresses Apc(Min)-induced tumorigenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MULTIPLE INTESTINAL NEOPLASIA; APC(DELTA-716) KNOCKOUT MICE; MAST-CELLS; ARACHIDONIC-ACID; MAJOR MODIFIER; MOUSE MODEL; GENE; CYCLOOXYGENASE-2; RESISTANCE; POLYPOSIS AB Although nonsteroidal antiinflammatory drugs (NSAIDs) show great promise as therapies for colon cancer, a dispute remains regarding their mechanism of action, NSAIDs are known to inhibit cyclooxygenase (COX) enzymes, which convert arachidonic acid (AA) to prostaglandins (PGs). Therefore, NSAIDs may suppress tumorigenesis by inhibiting PC synthesis, However, various experimental studies have suggested the possibility of PC-independent mechanisms, Notably, disruption of the mouse group IIA secretory phospholipase Az locus (Pla2g2a), a potential source of AA for COX-2, increases tumor number despite the fact that the mutation has been predicted to decrease PG production, Some authors have attempted to reconcile the results by suggesting that the level of the precursor (AA), not the products (PGs), is the critical factor. To clarify the role of AA in tumorigenesis, we have examined the effect of deleting the group IV cytosolic phospholipase Az (cPLA(2)) locus (Pla2g4). We report that Apc(Min/+), cPLA(2)(-/-) mice show an 83% reduction in tumor number in the small intestine compared with littermates with genotypes Apc(Min/+), cPLA(2)(+/-) and Apc(Min/+), cPLA(2)(+/+). This tumor phenotype parallels that of COX-2 knockout mice, suggesting that cPLA2 is the predominant source of AA for COX-2 in the intestine. The protective effect of cPLA2 deletion is thus most likely attributed to a decrease in the AA supply to COX-2 and a resultant decrease in PG synthesis. The tumorigenic effect of sPLA(2) mutations is likely to be through a completely different pathway. C1 Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. Harvard Mit Div Hlth Sci & Technol, Div Hlth Sci & Technol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Med Serv, Charlestown, MA 02129 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Lander, ES (reprint author), Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. FU NIDDK NIH HHS [DK38452, DK39773, P01 DK038452, R01 DK039773, R37 DK039773]; NINDS NIH HHS [F32 NS010828, NS10828, P01 NS010828, P50 NS010828] NR 28 TC 107 Z9 108 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 27 PY 2001 VL 98 IS 7 BP 3935 EP 3939 DI 10.1073/pnas.051635898 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 417KG UT WOS:000167833700060 PM 11274413 ER PT J AU Stevenson, LF Kennedy, BK Harlow, E AF Stevenson, LF Kennedy, BK Harlow, E TI A large-scale overexpression screen in Saccharomyces cerevisiae identifies previously uncharacterized cell cycle genes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DIVISION CYCLE; PROTEIN-KINASE; CHROMOSOME SEGREGATION; NUCLEAR DIVISION; BUDDING YEAST; MITOSIS; PROGRESSION; PROTEOLYSIS; INITIATION; DELETION AB We have undertaken an extensive screen to identify Saccharomyces cerevisiae genes whose products are involved in cell cycle progression. We report the identification of 113 genes, including 19 hypothetical ORFs, which confer arrest or delay in specific compartments of the cell cycle when overexpressed, The collection of genes identified by this screen overlaps with those identified in loss-of-function cde screens but also includes genes whose products have not previously been implicated in cell cycle control. Through analysis of strains lacking these hypothetical ORFs, we have identified a variety of new CDC and checkpoint genes. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Stevenson, LF (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 36 TC 68 Z9 71 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 27 PY 2001 VL 98 IS 7 BP 3946 EP 3951 DI 10.1073/pnas.051013498 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 417KG UT WOS:000167833700062 PM 11274415 ER PT J AU Kang, ZB Ge, YL Chen, ZH Cluette-Brown, J Laposata, M Leaf, A Kang, JX AF Kang, ZB Ge, YL Chen, ZH Cluette-Brown, J Laposata, M Leaf, A Kang, JX TI Adenoviral gene transfer of Caenorhabditis elegans n-3 fatty acid desaturase optimizes fatty acid composition in mammalian cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HETEROLOGOUS EXPRESSION; OMEGA-3-FATTY-ACIDS; IDENTIFICATION; CANCER AB Omega-3 polyunsaturated fatty acids (PUFAs) are essential components required for normal cellular function and have been shown to exert many preventive and therapeutic actions. The amount of n-3 PUFAs is insufficient in most Western people, whereas the level of n-6 PUFAs is relatively too high, with an n-6/n-3 ratio of >18. These two classes of PUFAs are metabolically and functionally distinct and often have important opposing physiological functions; their balance is important for homeostasis and normal development. Elevating tissue concentrations of n-3 PUFAs in mammals relies on chronic dietary intake of fat rich in n-3 PUFAs, because mammalian cells lack enzymatic activities necessary either to synthesize the precursor of n-3 PUFAs or to convert n-6 to n-3 PUFAs. Here we report that adenovirus-mediated introduction of the Caenorhabditis elegans fat-1 gene encoding an n-3 fatty acid desaturase into mammalian cells can quickly and effectively elevate the cellular n - 3 PUFA contents and dramatically balance the ratio of n-6/n-3 PUFAs, Heterologous expression of the fat-1 gene in rat cardiac myocytes rendered cells capable of converting various n-6 PUFAs to the corresponding n-3 PUFAs, and changed the n-6/n-3 ratio from about 15:1 to 1:1. In addition, an eicosanoid derived from n-6 PUFA (i.e., arachidonic acid) was reduced significantly in the transgenic cells. This study demonstrates an effective approach to modifying fatty acid composition of mammalian cells and also provides a basis for potential applications of this gene transfer in experimental and clinical settings. C1 Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Dept Med, Room 4433,149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA79553] NR 27 TC 76 Z9 98 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 27 PY 2001 VL 98 IS 7 BP 4050 EP 4054 DI 10.1073/pnas.061040198 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 417KG UT WOS:000167833700080 PM 11259654 ER PT J AU Denis, CV Andre, P Saffaripour, S Wagner, DD AF Denis, CV Andre, P Saffaripour, S Wagner, DD TI Defect in regulated secretion of P-selectin affects leukocyte recruitment in von Willebrand factor-deficient mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID WEIBEL-PALADE BODIES; GRANULE MEMBRANE-PROTEIN; HUMAN-ENDOTHELIAL CELLS; VONWILLEBRAND-FACTOR; CYTOPLASMIC DOMAIN; IN-VIVO; PLATELETS; INTERLEUKIN-8; HEMOSTASIS; ORGANELLES AB Stimulation of endothelial cells by various inflammatory mediators leads to release of Weibel-Palade bodies and therefore to exocytosis of both P-selectin (adhesion receptor for leukocytes) and von Willebrand factor (vWf) (platelet ligand), The potential role of vWf in leukocyte recruitment was investigated with the use of vWf-deficient mice. We report a strong reduction of leukocyte rolling in venules of vWf-deficient mice. Similarly, vWf deficiency led to a decrease in neutrophil recruitment in a cytokine-induced meningitis model as well as in early skin wounds. In all instances with an antibody that preferentially recognizes plasma membrane P-selectin, we observed a dramatic reduction in P-selectin expression at the cell surface of vWf-deficient endothelium, With confocal microscopy, we found that the typical rodlike shape of the Weihel-Palade body is missing in vWf -/- endothelial cells and that part of the P-selectin content in the vWf -/- cells colocalized with LAMP-1, a lysosomal marker. However, intracellular P-selectin levels were similar in tumor necrosis factor alpha- and lipopolysaccharide-activated cells of both genotypes, We conclude that the absence of vWf, as found in severe von Willebrand disease, leads to a defect in Weibel-Palade body formation. This defect results in decreased P-selectin translocation to the cell surface and reduced leukocyte recruitment in early phases of inflammation. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Denis , Cecile/A-7649-2011 OI Denis , Cecile/0000-0001-5152-9156 FU NHLBI NIH HHS [R37 HL41002, R37 HL041002] NR 31 TC 87 Z9 88 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 27 PY 2001 VL 98 IS 7 BP 4072 EP 4077 DI 10.1073/pnas.061307098 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 417KG UT WOS:000167833700084 PM 11274431 ER PT J AU Ackermann, RT Mulrow, CD Ramirez, G Gardner, CD Morbidoni, L Lawrence, VA AF Ackermann, RT Mulrow, CD Ramirez, G Gardner, CD Morbidoni, L Lawrence, VA TI Garlic shows promise for improving some cardiovascular risk factors SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT Evidence-based Complementary Medicine Congress CY APR 08, 2000 CL MUNICH, GERMANY ID ALLIUM-SATIVUM; BLOOD-LIPIDS; CONTROLLED TRIAL; PLASMA-LIPIDS; SERUM-LIPIDS; HYPERCHOLESTEROLEMIC MEN; FIBRINOLYTIC-ACTIVITY; PLATELET-AGGREGATION; CHOLESTEROL LEVELS; FISH-OIL AB Objectives: To summarize the effects of garlic on several cardiovascular-related factors and to note its adverse effects. Methods: English and non-English citations were identified from 11 electronic databases. references, manufacturers, and experts from January 1966 through February 2000 (depending on the database searched). Reports of cardiovascular-related effects were limited to randomized controlled trials lasting at least 4 weeks. Reports of adverse effects were not limited by study design. From 1798 pertinent records, 45 randomized trials and 73 additional studies reporting adverse events were identified. Two physicians abstracted outcomes and assessed adequacy of randomization, blinding, and handling of dropouts. Standardized mean differences of lipid outcomes from placebo-controlled trials were adjusted for baseline differences and pooled using random effects methods. Results: Compared with placebo, garlic preparations may lead to small reductions in the total cholesterol level at 1 month (range of average pooled reductions, 0.03-0.45 mmol/L [1.2-17.3 mg/dL]) and at 3 months (range of average pooled reductions 0.32-0.66 mmol/L [12.4-25.4 mg/dL]), but not at 6 months, Changes in low-density lipoprotein levels and triglyceride levels paralleled total cholesterol level results; no statistically significant changes in high-density lipoprotein levels were observed. Trials also reported significant reductions in platelet aggregation and mixed effects on blood pressure outcomes. No effects on glycemic-related outcomes were found. Proven adverse effects included malodorous breath and body odor. Other unproven effects included flatulence, esophageal and abdominal pain, allergic reactions, and bleeding. Conclusions: Trials suggest possible small short-term benefits of garlic on some lipid and antiplatelet factors, insignificant effects on blood pressure, and no effect on glucose levels. Conclusions regarding clinical significance are Limited by the marginal quality and short duration of many trials and by the unpredictable release and inadequate definition of active constituents in study preparations. C1 Audie L Murphy Mem Vet Hosp, Vet Evidence Based Res Disseminat Implementat Ctr, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, San Antonio Evidence Based Practice Ctr, San Antonio, TX USA. Stanford Univ, Ctr Res Dis Prevent, Palo Alto, CA 94304 USA. Univ Ancona, Ist Med Clin, Ancona, Italy. RP Mulrow, CD (reprint author), Audie L Murphy Mem Vet Hosp, Vet Evidence Based Res Disseminat Implementat Ctr, 7400 Merton Minter Blvd 11C6, San Antonio, TX 78284 USA. NR 77 TC 124 Z9 133 U1 2 U2 17 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 26 PY 2001 VL 161 IS 6 BP 813 EP 824 DI 10.1001/archinte.161.6.813 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 413KK UT WOS:000167611200003 PM 11268223 ER PT J AU Tritos, NA Mastaitis, JW Kokkotou, E Maratos-Flier, E AF Tritos, NA Mastaitis, JW Kokkotou, E Maratos-Flier, E TI Characterization of melanin concentrating hormone and preproorexin expression in the murine hypothalamus SO BRAIN RESEARCH LA English DT Article DE obesity; hypothalamus; melanin concentrating hormone; orexin; hypocretin; neuropeptide Y ID PROOPIOMELANOCORTIN MESSENGER-RNA; AGOUTI-RELATED PROTEIN; TOXIN-A MICE; NEUROPEPTIDE-Y; FEEDING-BEHAVIOR; BODY-WEIGHT; FOOD-INTAKE; OBESE GENE; RAT-BRAIN; OREXIN-A AB Melanin concentrating hormone (MCH) and the orexins (A and B) have been identified as neuropeptides localized to the lateral hypothalamic area (LHA) and are potential regulators of energy homeostasis. Potential factors regulating expression of both MCH and the orexins include fasting and leptin. Previous studies have generated conflicting data and, as there is little leptin receptor expressed in the lateral hypothalamus. it is likely that any observed leptin effects on these peptides are indirect. In this study, we examined MCH and preproorexin expression in mice in physiological states of starvation, with or without leptin administration, in addition to characterizing MCH and preproorexin expression in well-known obesity models, including ob/ob and UCP-DTA mice. Neuropeptide Y (NPY) expression in the arcuate nucleus was used as a positive control. After a 60-h fast, expression of both NPY and MCH mRNA was increased (by 148 and 33%, respectively) while preproorexin expression in the murine LHA did not change. Leptin administration to fasted mice blunted the rise in MCH and NPY expression towards control levels. In contrast, there was a 78% increase in preproorexin expression in fasted mice in response to peripheral leptin administration. MCH expression was increased (by 116%) in ob/ob mice at baseline. as we have previously reported. In addition, leptin treatment of ob/ob mice blunted the increase in MCH expression. In contrast, preproorexin expression did not differ in the leptin-deficient ob/ob mice or in the obese hyperleptinemic brown adipose tissue deficient (UCP-DTA) mice in comparison with controls. In summary. MCH expression is increased in two states of decreased leptin, fasting and ob/ob mice, and leptin replacement blunts MCH expression in both paradigms. Thus, MCH expression appears to be regulated by leptin. In contrast, preproorexin expression does not respond acutely to fasting, although it is acutely increased by leptin treatment during fasting. These preproorexin responses are in contrast to those seen with well-characterized orexigenic neuropeptides, such as NPY and AgRP, suggesting that appetite regulation may not be a significant physiological role of orexins. This conclusion is further supported by the observation that orexin ablated mice have arousal and not feeding deficits. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Joslin Diabet Ctr, Elliot P Joslin Lab, Boston, MA 02215 USA. RP Tritos, NA (reprint author), Joslin Diabet Ctr, Elliot P Joslin Lab, Rm 653,1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK 53978-01] NR 36 TC 69 Z9 70 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 23 PY 2001 VL 895 IS 1-2 BP 160 EP 166 DI 10.1016/S0006-8993(01)02066-2 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 415UR UT WOS:000167742400021 PM 11259773 ER PT J AU Kulke, MH Odze, RD Thakore, KS Thomas, G Wang, H Loda, M Eng, C AF Kulke, MH Odze, RD Thakore, KS Thomas, G Wang, H Loda, M Eng, C TI Allelic loss of 10q23, the PTEN tumour suppressor gene locus, in Barrett's oesophagus-associated adenocarcinoma SO BRITISH JOURNAL OF CANCER LA English DT Article DE PTEN; Barrett's oesophagus; oesophageal adenocarcinoma; 10q23 ID HUMAN ESOPHAGEAL CANCERS; PTEN/MMAC1 GENE; BREAST CARCINOMAS; PROSTATE-CANCER; MUTATIONAL ANALYSIS; COWDEN-DISEASE; P53 PROTEIN; HIGH-GRADE; PROGNOSTIC-SIGNIFICANCE; HOMOZYGOUS DELETION AB PTEN is a putative tumour suppressor gene located on chromosome band 10q23. Mutations in PTEN have been identified in numerous human malignancies, including cancers of the brain, endometrium ovary, and prostate. In this study, we screened 80 Barrett's oesophagus-associated adenocarcinomas (BOAd) for loss of heterozygosity (LOH) at 10q23, using the microsatellite markers D10S541, D105219, and D10S551. Tumours demonstrating LOH were then screened for the presence or absence of PTEN mutations. LOH at one or more loci was identified in 17/80 (21%) cases. In none of these cases did we detect mutations in PTEN. The presence of LOH did not correlate with patient age, tumour stage, degree of differentiation, presence of perineural or vascular invasion, or overall survival. We conclude that LOH at chromosome 10q23 is uncommon in BOAd, is not associated with mutations in the PTEN tumour suppressor gene, and does not correlate with the clinical or pathologic features of these tumours. It is possible that PTEN is inactivated through other mechanisms in BOAd. (C) 2001 Cancer Research Campaign http://www.bjcancer.com. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Ohio State Univ, Human Canc Genet Program, Columbus, OH 43210 USA. Univ Cambridge, CRC, Human Canc Genet Res Grp, Cambridge, England. RP Kulke, MH (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. OI Eng, Charis/0000-0002-3693-5145 NR 83 TC 10 Z9 12 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAR 23 PY 2001 VL 84 IS 6 BP 748 EP 753 DI 10.1054/bjoc.2000.1660 PG 6 WC Oncology SC Oncology GA 416MH UT WOS:000167784400003 PM 11259087 ER PT J AU Mackay, CR von Andrian, UH AF Mackay, CR von Andrian, UH TI Immunology - Memory T cells - Local heroes in the struggle for immunity SO SCIENCE LA English DT Editorial Material ID NAIVE C1 Garvan Inst Med Res, Arthrit & Asthma Program, Darlinghurst, NSW 2010, Australia. Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, Boston, MA 02115 USA. RP Mackay, CR (reprint author), Garvan Inst Med Res, Arthrit & Asthma Program, Darlinghurst, NSW 2010, Australia. RI von Andrian, Ulrich/A-5775-2008; Mackay, Charles/A-9673-2008 OI Mackay, Charles/0000-0002-6338-7340 NR 8 TC 31 Z9 33 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAR 23 PY 2001 VL 291 IS 5512 BP 2323 EP 2324 DI 10.1126/science.1059984 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 413UH UT WOS:000167618700028 PM 11269302 ER PT J AU Samad, TA Moore, KA Sapirstein, A Billet, S Allchorne, A Poole, S Bonventre, JV Woolf, CJ AF Samad, TA Moore, KA Sapirstein, A Billet, S Allchorne, A Poole, S Bonventre, JV Woolf, CJ TI Interleukin-1 beta-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity SO NATURE LA English DT Article ID PROSTAGLANDIN E-2 RELEASE; RAT SPINAL-CORD; CYTOSOLIC PHOSPHOLIPASE A(2); ION CHANNELS; HYPERALGESIA; CELLS; CYCLOOXYGENASE-2; MICE; EXPRESSION; ALLODYNIA AB Inflammation causes the induction of cyclooxygenase-2 (Cox-2)(1), leading to the release of prostanoids, which sensitize peripheral nociceptor terminals and produce localized pain hypersensitivity(2). Peripheral inflammation also generates pain hypersensitivity in neighbouring uninjured tissue (secondary hyperalgesia), because of increased neuronal excitability in the spinal cord (central sensitization)(3), and a syndrome comprising diffuse muscle and joint pain, fever, lethargy and anorexia(4). Here we show that Cox-2 may be involved in these central nervous system (CNS) responses, by finding a widespread induction of Cox-2 expression in spinal cord neurons and in other regions of the CNS, elevating prostaglandin E(2) (PGE(2)) levels in the cerebrospinal fluid. The major inducer of central Cox-2 upregulation is interleukin-1 beta in the CNS, and as basal phospholipase A(2) activity in the CNS does not change with peripheral inflammation, Cox-2 levels must regulate central prostanoid production. Intraspinal administration of an interleukin-converting enzyme or Cox-2 inhibitor decreases inflammation-induced central PGE(2) levels and mechanical hyperalgesia. Thus, preventing central prostanoid production by inhibiting the interleukin-1 beta -mediated induction of Cox-2 in neurons or by inhibiting central Cox-2 activity reduces centrally generated inflammatory pain hypersensitivity. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. UCL, Dept Anat, London WC1E 6BT, England. Natl Inst Biol Stand & Controls, S Mimms EN6 3QG, Herts, England. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neural Plast Res Grp, Charlestown, MA 02129 USA. EM woolf.clifford@mgh.harvard.edu NR 30 TC 790 Z9 837 U1 4 U2 24 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 22 PY 2001 VL 410 IS 6827 BP 471 EP 475 DI 10.1038/35068566 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 412YX UT WOS:000167583800042 PM 11260714 ER PT J AU Ezekowitz, RAB AF Ezekowitz, RAB TI What is the best way to treat inherited disorders? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CHRONIC GRANULOMATOUS-DISEASE C1 MassGen Hosp Children, Boston, MA 02114 USA. RP Ezekowitz, RAB (reprint author), MassGen Hosp Children, Boston, MA 02114 USA. NR 10 TC 2 Z9 3 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 22 PY 2001 VL 344 IS 12 BP 926 EP 927 DI 10.1056/NEJM200103223441210 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 412PN UT WOS:000167563700010 PM 11259728 ER PT J AU Gage, BF Fihn, SD White, RH AF Gage, BF Fihn, SD White, RH TI Warfarin therapy for an octogenarian who has atrial fibrillation SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID ORAL ANTICOAGULANT-THERAPY; RANDOMIZED CONTROLLED TRIAL; MOLECULAR-WEIGHT HEPARIN; FIXED MINIDOSE WARFARIN; RISK-FACTORS; BLEEDING COMPLICATIONS; ANTITHROMBOTIC THERAPY; VITAMIN-K; OUTPATIENT ANTICOAGULATION; EXCESSIVE ANTICOAGULATION AB In North America, atrial fibrillation is associated with at least 75 000 ischemic strokes each year. Most of these strokes occur in patients older than 75 years of age. The high incidence of stroke in very elderly persons reflects the increasing prevalence of atrial fibrillation that occurs with advanced age, the high incidence of stroke in elderly patients, and the failure of physicians to prescribe antithrombotic therapy in most of these patients. This failure is related to the increased risk for major hemorrhage with advanced age, obfuscating the decision to institute stroke prophylaxis with antithrombotic therapy. This case-based review describes the risk and benefits of prescribing antithrombotic therapy for a hypothetical 80-year-old man who has atrial fibrillation and hypertension, and it offers practical advice on managing warfarin therapy. After concluding that the benefits of warfarin outweigh its risks in this patient, we describe how to initiate warfarin therapy cautiously and how to monitor and dose the drug. We then review five recent randomized, controlled trials that document the increased risk for stroke when an international normalized ratio (INR) of less than 2.0 is targeted among patients with atrial fibrillation. Next, we make the case that cardioversion is not needed for this asymptomatic patient with chronic atrial fibrillation. Instead, we choose to leave the patient in atrial fibrillation and to central his ventricular rate with atenolol. Later, when the INR increases to 4.9, we advocate withholding one dose of warfarin and repeating the INR test. Finally, when the patient develops dental pain, we review the analgesic agents that are safe to take with warfarin and explain why warfarin therapy does not have to be interrupted during a subsequent dental extraction. C1 Washington Univ, Sch Med, Div Gen Med Sci, St Louis, MO 63110 USA. Univ Washington, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Calif Davis, Sacramento, CA 95817 USA. RP Gage, BF (reprint author), Washington Univ, Sch Med, Div Gen Med Sci, Campus Box 8005,660 S Euclid Ave, St Louis, MO 63110 USA. FU AHRQ HHS [R01 HS10133] NR 116 TC 32 Z9 32 U1 0 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 MAR 20 PY 2001 VL 134 IS 6 BP 465 EP 474 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 409VF UT WOS:000167405800005 PM 11255522 ER PT J AU Wilson, PWF Kauppila, LI O'Donnell, CJ Kiel, DP Hannan, M Polak, JM Cupples, LA AF Wilson, PWF Kauppila, LI O'Donnell, CJ Kiel, DP Hannan, M Polak, JM Cupples, LA TI Abdominal aortic calcific deposits are an important predictor of vascular morbidity and mortality SO CIRCULATION LA English DT Article DE coronary disease; calcium; risk factors ID RISK-FACTORS; CORONARY CALCIUM; ATHEROSCLEROTIC PLAQUES; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; NATURAL-HISTORY; FOLLOW-UP; OSTEOPONTIN; ASSOCIATION; LESIONS AB Background-The impact of abdominal arterial calcific deposits on the prediction of cardiovascular disease (CVD) over a long follow-up interval deserves greater scrutiny. Methods and Results-Lateral lumbar radiographs were studied as a predictor of incident coronary heart disease (CHD), CVD, and CVD mortality in 1049 men and 1466 women (mean age, 61 years) who were followed from 1967 to 1989. Anterior and posterior wall calcific deposits in the aorta at the level of the first through fourth lumbar vertebrae were graded according to increasing severity using a previously validated rating scale for abdominal aortic calcium (AAC) that ranges from 0 to 24 points. There were 454 cases of CHD, 709 cases of CVD, and 365 CVD deaths. Proportional hazards logistic regression was used to test for associations between AAC and later events after adjustment for age, cigarette use, diabetes mellitus, systolic blood pressure, left ventricular hypertrophy, body mass index, cholesterol, and HDL cholesterol. In comparisons with the lowest AAC tertile, the multivariate age-adjusted relative risks (RR) for CVD were increased in tertile 2 (men: RR, 1.33; 95% confidence interval [CI], 1.02 to 1.74; women: RR, 1.25; 95% CI, 0.95 to 1.65) and tertile 3 (men: RR, 1.68; 95% CI, 1.25 to 2.27; women: RR, 1.78; 95% CI, 1.33 to 2.38). Similar results were obtained with CHD and CVD mortality. Conclusions-AAC deposits, detected by lateral lumbar radiograms, are a marker of subdinical atherosclerotic disease and an independent predictor of subsequent vascular morbidity and mortality. C1 Boston Univ, Sch Publ Hlth, Dept Biostat & Epidemiol, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. Harvard Univ, Sch Med, Div Aging, Hebrew Rehabil Ctr Aged, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA USA. Boston Univ, Sch Med, Framingham Heart Study, NHLBI, Framingham, MA 01702 USA. RP Wilson, PWF (reprint author), Boston Univ, Sch Med, Framingham Heart Study, NHLBI, 5 Thurber St, Framingham, MA 01702 USA. OI Kiel, Douglas/0000-0001-8474-0310 FU NHLBI NIH HHS [N01-HC-38038]; NIAMS NIH HHS [AR/AG 41398] NR 34 TC 320 Z9 337 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 20 PY 2001 VL 103 IS 11 BP 1529 EP 1534 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 413XL UT WOS:000167636800009 PM 11257080 ER PT J AU Huang, DR Wang, JT Kivisakk, P Rollins, BJ Ransohoff, RM AF Huang, DR Wang, JT Kivisakk, P Rollins, BJ Ransohoff, RM TI Absence of monocyte chemoattractant protein 1 in mice leads to decreased local macrophage recruitment and antigen-specific T helper cell type 1 immune response in experimental autoimmune encephalomyelitis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE autoimmune disease; chemokine; chemokine receptor; macrophage; T helper cell type 1/T helper cell type 2 ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS LESIONS; CHEMOKINE RECEPTOR EXPRESSION; DELAYED-TYPE HYPERSENSITIVITY; COSTIMULATORY MOLECULES B7-1; MYELIN PROTEOLIPID PROTEIN; C-C CHEMOKINES; CUTTING EDGE; DIFFERENTIAL EXPRESSION AB Monocyte chemoattractant protein (MCP)-1 plays a critical role in innate immunity by directing the migration of monocytes into inflammatory sites. Recent data indicated a function for this chemokine in adaptive immunity as a regulator of T cell commitment to T helper cell type 2 (Th2) effector function. Studies in a Th1-dependent animal model, experimental autoimmune encephalomyelitis (EAE), showed that MCP-1 was highly expressed in the central nervous system (CNS) of affected rodents, and MCP-1 antibodies could block relapses of the disease. Mice deficient for the major MCP-1 receptor, CC chemokine receptor (CCR)2, did not develop EAE after active immunization but generated effector cells that could transfer the disease to naive wild-type recipients. We analyzed EAE in mice deficient for MCP-1 to define the relevant ligand fur CCR2, which responds to murine MCP-1, MCP-2, MCP-3, and MCP-5. We found that C57BL/6 MCP-1-null mice were markedly resistant to EAE after active immunization, with drastically impaired recruitment of macrophages to the CNS, yet able to generate effector T cells that transferred severe disease to naive wild-type recipients. By contrast, adoptive transfer of primed T cells from wild-type mice into naive MCP-1-null recipients did riot mediate clinical EAE. On the SJL background, disruption of the MCP-1 gene produced a milder EAE phenotype with diminished relapses that mimicked previous findings using anti-MCP-l antibodies. There was no compensatory upregulation of MCP-2, MCP-3, or MCP-5 ill MCP-l-null mice with EAE. These results indicated that MCP-I is the major CCR2. ligand in mice with EAE, and provided an opportunity to define the role of MCP-1 in EAE, Compared with wild-type littermates, MCP-1(-/-) mice exhibited reduced expression of interferon gamma in draining lymph node and CNS and increased antigen-specific immunoglobulin G1 antibody production. Taken together, these data demonstrate that MCP-1 is crucial for Th1 immune responses in EAE induction and that macrophage recruitment to the inflamed CNS target organ is required for primed T cells to execute a Th1 effector program in EAE. C1 Cleveland Clin Fdn, Dept Neurosci NC30, Lerner Res Inst, Cleveland, OH 44195 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Ransohoff, RM (reprint author), Cleveland Clin Fdn, Dept Neurosci NC30, Lerner Res Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA. FU NCI NIH HHS [2RO1 CA53091, R01 CA053091]; NINDS NIH HHS [R01 NS032151, 2RO1 NS32151, 1PO1 NS38667, P01 NS038667] NR 84 TC 408 Z9 424 U1 1 U2 13 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 19 PY 2001 VL 193 IS 6 BP 713 EP 725 DI 10.1084/jem.193.6.713 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 413UZ UT WOS:000167631100007 PM 11257138 ER PT J AU Huang, WB Carlsen, B Rudkin, GH Shah, N Chung, C Ishida, K Yamaguchi, DT Miller, TA AF Huang, WB Carlsen, B Rudkin, GH Shah, N Chung, C Ishida, K Yamaguchi, DT Miller, TA TI Effect of serial passage on gene expression in MC3T3-E1 preosteoblastic cells: A microarray study SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HUMAN FIBROBLASTS; REPLICATIVE SENESCENCE; GENOME; OSTEOPONTIN; MATRIX AB The osteoblastic function of mouse preosteoblastic MC3T3-E1 cells, as measured by alkaline phosphatase activity and osteocalcin secretion, decreases after serial passage. To uncover genes responsible for decreased osteoblastic function in high-passage cells, we have studied passage dependent change of gene expression in MC3T3-E1 cells. Changes in the expression pattern of 2000 selected genes were examined simultaneously by comparing mRNA levels between MC3T3-E1 cells at passage 20 and passage 60 using the cDNA microarray analysis. Significant changes in the steady-state abundance of 27 mRNAs were observed in response to different passage numbers, including 17 known genes, 4 ESTs with homology to known genes, and 6 genes with no previously described function or homology. Northern blot analysis was used to verify and quantify the expression of selected genes, and revealed a significant higher level of up- and downregulation compared to microarray data. These re suits indicate the existence of a significant change in gene expression in osteoblastic cells undergoing serial passages. Such changes might be responsible for a reduction in bone regeneration in older osteoblasts. Potential roles of selected genes in bone aging are discussed. (C) 2001 Academic Press. C1 Va Greater Los Angeles Healthcare Syst, Plast Surg Sect, Los Angeles, CA 90073 USA. Va Greater Los Angeles Healthcare Syst, GRECC, Los Angeles, CA 90073 USA. Va Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Surg, Los Angeles, CA 90095 USA. RP Miller, TA (reprint author), Va Greater Los Angeles Healthcare Syst, Plast Surg Sect, Los Angeles, CA 90073 USA. NR 23 TC 21 Z9 22 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 16 PY 2001 VL 281 IS 5 BP 1120 EP 1126 DI 10.1006/bbrc.2001.4458 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 414AA UT WOS:000167642700010 PM 11243851 ER PT J AU Hoare, SRJ Gardella, TJ Usdin, TB AF Hoare, SRJ Gardella, TJ Usdin, TB TI Evaluating the signal transduction mechanism of the parathyroid hormone 1 receptor - Effect of receptor-G-protein interaction on the ligand binding mechanism and receptor conformation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID (PTH)/PTH-RELATED PEPTIDE RECEPTOR; FIRST EXTRACELLULAR LOOP; RADIOLIGAND BINDING; PTH/PTHRP RECEPTOR; CHIMERIC RECEPTORS; GUANINE-NUCLEOTIDE; TERMINAL REGION; KIDNEY-CELLS; AFFINITY; AGONIST AB Ligand binding to the PTH1 receptor is described by a "two-site" model, in which the C-terminal portion of the ligand interacts with the N-terminal domain of the receptor (N interaction), and the N-terminal region of the ligand binds the juxtamembrane domain of the receptor (J interaction). Previous studies have not considered the dynamic nature of receptor conformation in ligand binding and receptor activation. In this study the ligand binding mechanism was compared for the G-protein-coupled (RG) and uncoupled (R) PTH1 receptor conformations. The two site model was confirmed by demonstration of spatially distinct binding sites for PTH(3-34) and PTH(1-14): PTH(1-11), which binds predominantly to the J domain, only partially inhibited binding of I-125-PTH(3-34); and PTH(3-34), shown to bind predominantly to the N domain, only partially inhibited PTH(1-14)-stimulated cAMP accumulation. To assess the effect of R-G coupling, ligand binding to R was measured by displacement of I-125-PTH(3-34) with 30 muM guanosine 5'-3-O-(thio)triphosphate (GTP gammaS) present, and binding to RG was measured by displacement of I-125-[MAP]PTHrP(1-36) (where MAP is model amphipathic peptide), a new radioligand that binds selectively to RG. Agonists bound with higher affinity to RG than R, whereas antagonists bound similarly to these states. The J interaction was responsible for enhanced agonist binding to RG: residues 1 and 2 were required for increased PTB(1-34) affinity for RG; residue 5 of MAP-PTHrP(1-36) was a determinant of R/RG binding selectivity, and PTH(1-14) bound selectively to RG. The N interaction was insensitive to R-G coupling; PTH(3-34) binding was GTP gammaS-insensitive. Finally, several observations suggest the receptor conformation is more "closed" at RG than R. At the R state, an open conformation is suggested by the simultaneous binding of PTH(1-14) and PTH(3-34). At RG PTH(1-14) better occluded binding of I-125-PTH(3-34) and agonist ligands bound pseudo-irreversibly, suggesting a more closed conformation of this receptor state. The results extend the two-site model to take into account R and RG conformations and suggest a model for differences of receptor conformation between these states. C1 NIMH, Cell Biol Unit, Genet Lab, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Usdin, TB (reprint author), NIMH, Cell Biol Unit, Genet Lab, Rm 3D06,Bldg 36,36 Convent Dr, Bethesda, MD 20892 USA. NR 57 TC 58 Z9 58 U1 2 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 16 PY 2001 VL 276 IS 11 BP 7741 EP 7753 DI 10.1074/jbc.M009395200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 411AA UT WOS:000167474900012 PM 11108715 ER PT J AU Claas, C Stipp, CS Hemler, ME AF Claas, C Stipp, CS Hemler, ME TI Evaluation of prototype transmembrane 4 superfamily protein complexes and their relation to lipid rafts SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DIPHTHERIA-TOXIN RECEPTOR; GPI-ANCHORED PROTEINS; HUMAN-MELANOMA CELLS; LOW-BUOYANT DENSITY; PLASMA-MEMBRANE; GROWTH-FACTOR; PHOSPHATIDYLINOSITOL 4-KINASE; TM4SF PROTEINS; T-CELLS; INTEGRIN ALPHA-3-BETA-1 AB Recent literature suggests that tetraspanin proteins (transmembrane 4 superfamily; TM4SF proteins) may associate with each other and with many other transmembrane proteins to form large complexes that sometimes may be found in lipid rafts. Here we show that prototype complexes of CD9 or CD81 (TM4SF proteins) with alpha (3)beta (1) (an integrin) and complexes of CD63 (a TM4SF protein) with phosphatidylinositol 4-kinase (PtdIns 4-K) may indeed localize within lipid raft-like microdomains, as seen by three different criteria, First, these complexes localize to low density light membrane fractions in sucrose gradients. Second, CD9 and alpha (3) integrin colocalized with ganglioside GM1 as seen by double staining of Bred cells. Third, CD9-alpha3 beta1 and CD81-alpha3 beta1 complexes were shifted to a higher density upon cholesterol depletion from intact cells or cell lysate. However, CD9-alpha3 beta1, CD81-alpha3 beta1, and CD63-PtdIns 4-K complex formation itself was not dependent on localization into raftlike lipid microdomains, These complexes did not require cholesterol for stabilization, were maintained within well solubilized dense fractions from sucrose gradients, were stable at 37 degreesC, and were small enough to be included within CL6B gel filtration columns. In summary, prototype TM4SF protein complexes (CD9-alpha3 beta1, CD81-alpha3 beta1, and CD63-PtdIns 4-K) can be solubilized as discrete units, independent of lipid microdomains, although they do associate with microdomains resembling lipid rafts. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Rm D-1430,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA42368]; NIGMS NIH HHS [GM38903] NR 90 TC 230 Z9 233 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 16 PY 2001 VL 276 IS 11 BP 7974 EP 7984 DI 10.1074/jbc.M008650200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 411AA UT WOS:000167474900044 PM 11113129 ER PT J AU Qin, ZH Wan, YM Kikly, KK Sapp, E Kegel, KB Aronin, N DiFiglia, M AF Qin, ZH Wan, YM Kikly, KK Sapp, E Kegel, KB Aronin, N DiFiglia, M TI Pro-caspase-8 is predominantly localized in mitochondria and released into cytoplasm upon apoptotic stimulation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-NECROSIS-FACTOR; CYTOCHROME-C RELEASE; PERMEABILITY TRANSITION PORE; INDUCED-PROXIMITY MODEL; CELL-DEATH; NEURONAL APOPTOSIS; CYCLOSPORINE-A; MEDIATED APOPTOSIS; CASPASE ACTIVATION; FACTOR RECEPTOR AB The recruitment and cleavage of pro-caspase-8 to produce the active form of caspase-8 is a critical biochemical event in death receptor-mediated apoptosis, However, the source of pro-caspase-8 available for activation by apoptotic triggers is unknown. In human fibroblasts and mouse clonal striatal cells, confocal microscopy revealed that pro-caspase-8 immunofluorescence was colocalized with cytochrome c in mitochondria and was also distributed diffusely in some nuclei. Biochemical analysis of subcellular fractions indicated that pro-caspase-8 was enriched in mitochondria and in nuclei. Pro-caspase-8 was found in the intermembrane space, inner membrane, and matrix of mitochondria after limited digestion of mitochondrial fractions, and this distribution was confirmed by immunogold electron microscopy. Pro-caspase-8 and cytochrome c were released from isolated mitochondria that were treated with an inhibitor of the ADP/ATP carrier atractyloside, which opens the mitochondria permeability transition pore. Release was blocked by the mitochondria permeability transition pore inhibitor cyclosporin A (CsA), After clonal striatal cells were exposed for 6 h to an apoptotic inducer tumor necrosis factor-alpha (TNF-alpha), mitochondria immunoreactive for cytochrome c and pro-caspase-8 became clustered at perinuclear sites. Pro-caspase-8 and cytochrome c levels decreased in mitochondrial fractions and increased, along with pro-caspase-8 cleavage products, in the cytoplasm of the TNF-alpha -treated striatal cells. CsA blocked the TNF-alpha -induced release of pro-caspase 8 but not cytochrome c, Internucleosomal DNA fragmentation started at 6 h and peaked 12 h after TNF-alpha treatment. These results suggest that pro-caspase 8 is predominantly localized in mitochondria and is released upon apoptotic stimulation through a CsA-sensitive mechanism. C1 Massachusetts Gen Hosp, Lab Cellular Neurobiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. SmithKline Beecham Pharmaceut, Dept Immunol, King Of Prussia, PA 19406 USA. Univ Massachusetts, Med Ctr, Dept Med & Cell Biol, Worcester, MA 01655 USA. RP Qin, ZH (reprint author), Massachusetts Gen Hosp, Lab Cellular Neurobiol, Bldg 149,Rm 6604,13th St, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS 38194, NS 16367, NS 35711] NR 65 TC 87 Z9 89 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 16 PY 2001 VL 276 IS 11 BP 8079 EP 8086 DI 10.1074/jbc.M007028200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 411AA UT WOS:000167474900058 PM 11102441 ER PT J AU Krykbaev, RA Liu, WR Jeffrey, PD Margolies, MN AF Krykbaev, RA Liu, WR Jeffrey, PD Margolies, MN TI Phage display-selected sequences of the heavy-chain CDR3 loop of the anti-digoxin antibody 26-10 define a high affinity binding site for position 16-substituted analogs of digoxin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID V-GENE LIBRARIES; FINE SPECIFICITY; VARIABLE REGION; FAB FRAGMENT; MUTAGENESIS; MUTATIONS; COMPLEMENTARITY; HUMANIZATION; IMMUNIZATION; REPERTOIRES AB The heavy-chain CDR3 region of the high affinity (K-alpha = 1.3 x 10(10) M-1) anti-digoxin monoclonal antibody 26-10 was modified previously to shift its specificity, by substitution of tryptophan 100 by arginine, toward binding analogs of digoxin containing substitutions at position 16. To further change specificity, two 5 mer libraries of the randomly mutagenized phage displayed 26-10 HCDR3 region (positions 94-98) were penned against digoxin-bovine serum albumin (BSA) as well as against 16-acetylgitoxin-BSA. When a mutant Fab that binds 16-substituted analogs preferentially was used as a parent sequence, clones were obtained with affinities for digoxin increased 2-4-fold, by panning on digoxin-BSA yet retaining the specificity shift. Selection on 16-acetylgitoxin-BSA, however, resulted in nine clones that bound gitoxin (16-OH) up to 150-fold higher than the wild-type 26-10, due to a consensus mutation of Ser(H95) to Gly(H95). The residues at both position H95 (serine) and position H100 (tryptophan) contact hapten in the crystal structure of the Fab 26-10-digoxin complex. Thus, by mutating hapten contact residues, it is possible to reorder the combining site of a high affinity antibody, resulting in altered specificity, yet retain or substantially increase the relative affinity for the cross-reactive ligand. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Mem Sloan Kettering Canc Ctr, Dept Cellular Biochem & Biophys, Crystallog Facil, New York, NY 10021 USA. RP Margolies, MN (reprint author), Massachusetts Gen Hosp E, Antibody Engn Lab, 149 13th St,Box 31, Charlestown, MA 02129 USA. EM mmargolies@partners.org FU NHLBI NIH HHS [HL47415] NR 40 TC 7 Z9 7 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 16 PY 2001 VL 276 IS 11 BP 8149 EP 8158 DI 10.1074/jbc.M008108200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 411AA UT WOS:000167474900067 PM 11060305 ER PT J AU Elman, I Krause, S Karlsgodt, K Schoenfeld, DA Gollub, RL Breiter, HC Gastfriend, DR AF Elman, I Krause, S Karlsgodt, K Schoenfeld, DA Gollub, RL Breiter, HC Gastfriend, DR TI Clinical outcomes following cocaine infusion in nontreatment-seeking individuals with cocaine dependence SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Addiction Severity Index; depression; radioimmunoassay of hair; cocaine; research ethics; brain imaging ID ISSUES; ABUSE AB Background: In this study we explored if laboratory-based cocaine administration to human subjects was associated with long-term adverse outcomes. Methods: Twenty-one non-treatment seeking individuals with cocaine dependence were evaluated at baseline and again 5 and 10 months following cocaine infusion in a brain imaging study. Outcomes included computer-driven multidimensional clinical assessments and radioimmuno-assay of hair For comparison, identical data were collected from 19 cocaine-dependent subjects who did not receive the infusion. Results: The infused and noninfused groups did not differ on frequency of cocaine use (corroborated by radioimmunoassay of hair), Addiction Severity Index drug composite score, or Hamilton Rating Scale for Depression score at both follow-lip time points. In a time-related trend analysis, both groups showed significant reductions in frequency of cocaine use. Conclusions: Laboratory-based cocaine administration can be a safe paradigm even in individuals who are not engaged in treatment, Biol Psychiatry 2001;49:553-555 (C) 2001 Society of Biological Psychiatry. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Addict Res Program,Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Motivat & Emot Neurosci Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Biostat Program, Boston, MA 02114 USA. RP Elman, I (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Addict Res Program,Dept Psychiat, 15 Parkman St,WACC-812, Boston, MA 02114 USA. RI Karlsgodt, Katherine/H-2964-2013; OI Karlsgodt, Katherine/0000-0003-3332-4231; Gollub, Randy L./0000-0002-9434-4044 FU NIDA NIH HHS [DA 00265-01, DA 00275-01, DA 0878, DA 09467-02] NR 11 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 15 PY 2001 VL 49 IS 6 BP 553 EP 555 DI 10.1016/S0006-3223(00)01096-9 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 411TY UT WOS:000167516400009 PM 11257241 ER PT J AU Kadambi, A Carreira, CM Yun, C Padera, TP Dolmans, DEJGJ Carmeliet, P Fukumura, D Jain, RK AF Kadambi, A Carreira, CM Yun, C Padera, TP Dolmans, DEJGJ Carmeliet, P Fukumura, D Jain, RK TI Vascular endothelial growth factor (VEGF)-C differentially affects tumor vascular function and leukocyte recruitment: Role of VEGF-receptor 2 and host VEGF-A SO CANCER RESEARCH LA English DT Article ID FACTOR-C; ANGIOGENESIS; PERMEABILITY; EXPRESSION; PATHWAYS; CANCER; CELLS AB Unlike vascular endothelial growth factor (VEGF)-A, the effect of VEGF-C on tumor angiogenesis, vascular permeability, and leukocyte recruitment is not known. To this end, we quantified in vivo growth and vascular function in tumors derived from two VEGF-C-overexpressing (VC+) and mock-transfected cell lines (T241 fibrosarcoma and VEGF-A(-/-) embryonic stem cells) grown in murine dorsal skinfold chambers. VC+ tumors grew more rapidly than mock-transfected tumors and exhibited parallel increases in tumor angiogenesis. Furthermore, VEGF-C overexpression elevated vascular permeability in T241 tumors, but not in VEGF-A(-/-) tumors. Surprisingly, unlike VEGF-A, VEGF-C did not increase leukocyte rolling or adhesion in tumor vessels. Administration of VEGF receptor (VEGFR)-2 neutralizing antibody DC101 reduced vascular density and permeability of both VC+ and mock-transduced T241 tumors. These data suggest that VEGFR-2 signaling is critical for tumor angiogenesis and vascular permeability and that VEGFR-3 signaling does not compensate for VEGFR-2 blockade. An alternate VEGFR, VEGFR-1 or neuropilin-1, may modulate adhesion of leukocytes to tumor vessels. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. Katholieke Univ Leuven, Ctr Transgene Technol & Gene Therapy, B-3000 Louvain, Belgium. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 7, Boston, MA 02114 USA. OI Yun, Chae-Ok/0000-0002-9466-4531 FU NCI NIH HHS [F32-CA83351, R24-CA85140, R35-CA56591] NR 23 TC 69 Z9 73 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2001 VL 61 IS 6 BP 2404 EP 2408 PG 5 WC Oncology SC Oncology GA 415AC UT WOS:000167697500012 PM 11289105 ER PT J AU Bok, RA Halabi, S Fei, DT Rodriquez, CR Hayes, DF Vogelzang, NJ Kantoff, P Shuman, MA Small, EJ AF Bok, RA Halabi, S Fei, DT Rodriquez, CR Hayes, DF Vogelzang, NJ Kantoff, P Shuman, MA Small, EJ TI Vascular endothelial growth factor and basic fibroblast growth factor urine levels as predictors of outcome in hormone-refractory prostate cancer patients: A cancer and leukemia group B study SO CANCER RESEARCH LA English DT Article ID ANGIOGENIC PEPTIDE; ELEVATED LEVELS; PLASMA; ANTIGEN; SURAMIN AB Better prognostic markers are needed for hormone-refractory prostate cancer (HRPC) patients. No single biochemical or clinical parameter ran reliably predict patient response to therapy or rapidity of disease progression. Peptide factors involved in major cancer growth pathways, such as tumor angiogenesis, are attractive candidates as markers of low- and high-risk HRPC patients. We analyzed prospectively collected urine specimens from 100 of 390 HRPC patients undergoing therapy with the growth factor antagonist suramin as part of CALGB 9480. Levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were assessed from day 1 of therapy (D1) and day 29 (D29) urine samples from this subset of 100 randomly selected patients. Growth factor levels were determined by standardized ELISA microtiter plate assays from a commercial (bFGF) or proprietary (VEGF) source. Pretreatment urine VEGF levels were predictive of survival. In univariate analysis, patients whose baseline urine VEGF level was less than or equal to 28 pg/ml (the median level) had an average survival of 17 months; those with baseline VEGF >28 pg/ml had a significantly shorter survival of 10 months (P = 0.024). This difference corresponded to a 60% increased risk of dying for the higher urine VEGF patients (hazard ratio, 1.62; P = 0.03) and remained significant in multivariate analysis (hazard ratio, 1.72, P = 0.02). No significant correlations between urine bFGF level or change in bFGF levels and survival were found. These results support the notion that certain peptide growth factor-mediated, mitogenic pathways are important in HRPC and that their levels can predict outcome. C1 Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. CALGB Stat Ctr, Durham, NC 27710 USA. Genentech Inc, S San Francisco, CA 94080 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bok, RA (reprint author), Univ Calif San Francisco, Ctr Comprehens Canc, 1600 Divisadero,3rd Floor, San Francisco, CA 94143 USA. FU NCI NIH HHS [CA71323, CA31946, CA33601] NR 23 TC 116 Z9 125 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2001 VL 61 IS 6 BP 2533 EP 2536 PG 4 WC Oncology SC Oncology GA 415AC UT WOS:000167697500033 PM 11289126 ER PT J AU Hooper, DC AF Hooper, DC TI Mechanisms of action of antimicrobials: Focus on fluoroquinolones SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID COMPLETE GENOME SEQUENCE; VANCOMYCIN-RESISTANT ENTEROCOCCI; PENICILLIN-BINDING PROTEINS; ESCHERICHIA-COLI K-12; TOPOISOMERASE-IV; DNA GYRASE; STREPTOCOCCUS-PNEUMONIAE; STAPHYLOCOCCUS-AUREUS; QUINOLONE RESISTANCE; PEPTIDOGLYCAN BIOSYNTHESIS AB Five bacterial targets have been exploited in the development of antimicrobial drugs: cell wall synthesis, protein synthesis, ribonucleic acid synthesis, deoxyribonucleic acid (DNA) synthesis, and intermediary metabolism. Because resistance to drugs that interact with these targets is widespread, new antimicrobials and an understanding of their mechanisms of action are vital. The fluoroquinolones are the only direct inhibitors of DNA synthesis; by binding to the enzyme-DNA complex, they stabilize DNA strand breaks created by DNA gyrase and topoisomerase IV. Ternary complexes of drug, enzyme, and DNA block progress of the replication fork. Cytotoxicity of fluoroquinolones is likely a 2-step process involving (1) conversion of the topoisomerase-quinolone-DNA complex to an irreversible form and (2) generation of a double-strand break by denaturation of the topoisomerase. The molecular factors necessary for the transition from step 1 to step 2 remain unclear, but downstream pathways for cell death may overlap with those used by other bactericidal antimicrobials. Studies of fluoroquinolone-resistant mutants and purified topoisomerases indicate that many quinolones have differing activities against the two targets. Drugs with similar activities against both targets may prove less likely to select de novo resistance. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. NR 58 TC 158 Z9 160 U1 6 U2 17 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 15 PY 2001 VL 32 SU 1 BP S9 EP S15 DI 10.1086/319370 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 411JR UT WOS:000167495700002 PM 11249823 ER PT J AU Chen, ZY Hasson, T Zhang, DS Schwender, BJ Derfler, BH Mooseker, MS Corey, DP AF Chen, ZY Hasson, T Zhang, DS Schwender, BJ Derfler, BH Mooseker, MS Corey, DP TI Myosin-VIIb, a novel unconventional myosin, is a constituent of microvilli in transporting epithelia SO GENOMICS LA English DT Article ID SYNDROME TYPE 1B; SENSORY EPITHELIA; BINDING PROTEIN; DEAFNESS DFNB3; HAIR-CELLS; GENE; EXPRESSION; MOUSE; MEMBRANE; DOMAINS AB Mouse myosin-VIIb, a novel unconventional myosin, was cloned from the inner ear and kidney. The human myosin-VIIb (HGMW-approved symbol MYO7B) sequence and exon structure were then deduced from a human BAC clone, The mouse gene was mapped to chromosome 18, approximately 0.5 cM proximal to D18Mit12, The human gene location at 2q21.1 was deduced from the map location of the BAC and confirmed by fluorescence in situ hybridization. Myosin-VIIb has a conserved myosin head domain, five IQ domains, two MyTH4 domains coupled to two FERM domains, and an SH3 domain. A phylogenetic analysis based on the MyTH4 domains suggests that the coupled MyTH and FERM domains were duplicated in myosin evolution before separation into different classes. Myosin-VIIb is expressed primarily in kidney and intestine, as shown by Northern and immunoblot analyses. An antibody to myosin-VIIb labeled proximal tubule cells of the kidney and enterocytes of the intestine, specifically the distal tips of apical microvilli on these transporting epithelial cells. (C) 2001 Academic Press. C1 Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Calif San Diego, Div Biol, La Jolla, CA 92093 USA. Yale Univ, Dept MCD Biol, New Haven, CT 06520 USA. Yale Univ, Dept Cell Biol, New Haven, CT 06520 USA. Yale Univ, Dept Pathol, New Haven, CT 06520 USA. RP Chen, ZY (reprint author), Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. OI Corey, David/0000-0003-4497-6016 FU NIDCD NIH HHS [R01-DC02281]; NIDDK NIH HHS [R37-DK25387, P01-DK38979] NR 46 TC 28 Z9 29 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD MAR 15 PY 2001 VL 72 IS 3 BP 285 EP 296 DI 10.1006/geno.2000.6456 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 418UB UT WOS:000167908800008 PM 11401444 ER PT J AU Pai, HH Thornton, A Katznelson, L Finkelstein, DM Adams, JA Fullerton, BC Loeffler, JS Leibsch, NJ Klibanski, A Munzenrider, JE AF Pai, HH Thornton, A Katznelson, L Finkelstein, DM Adams, JA Fullerton, BC Loeffler, JS Leibsch, NJ Klibanski, A Munzenrider, JE TI Hypothalamic/pituitary function following high-dose conformal radiotherapy to the base of skull: Demonstration of a dose-effect relationship using dose-volume histogram analysis SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO 99) CY OCT 30-NOV 04, 1999 CL SAN ANTONIO, TEXAS SP Amer Soc Therapeut Radiol & Oncol DE protons; pituitary gland; hypothalamus; dose; stereotactic radiotherapy (SRT) ID PROTON RADIATION-THERAPY; NASOPHARYNGEAL CARCINOMA; PITUITARY-ADENOMAS; TUMORS; HYPOPITUITARISM; IRRADIATION; CHORDOMA; CHONDROSARCOMA; THYROTROPIN AB Purpose: To evaluate the incidence and pattern of hypopituitarism from hypothalamic (HT) and pituitary gland (PG) damage following high-dose conformal fractionated proton-photon beam radiotherapy (PPRT) to the base of skull (BOS) region in adults, The relationship between dose, volume, and PG function is explored. Methods and Materials: Between May 1982 to October 1997, 107 adults with non-PG and non-MT neoplasms (predominantly chordoma and chondrosarcomas) of the BOS were treated with PPRT after subtotal resection(s). The median age was 41.2 years (range, 17-75) with 58 males and 49 females. Median prescribed target dose was 68.4 cobalt gray equivalent (CGE) (range, 55.8-79 CGE) at 1.80-1.92 CGE per fraction per day (where CGE = proton Gy x 1.1), The MT and PG were outlined on planning CT scans to allow dose-volume histograms (DVH) analysis. All patients had baseline and follow-up clinical testing of anterior and posterior pituitary function including biochemical assessment of thyroid, adrenal, and gonadal function, and prolactin secretion, Results: The 10-year actuarial overall survival rate was 87%, with median endocrine follow-up time of 5.5 years, thus the majority of patients were available for long-term follow-up. Five-year actuarial rates of endocrinopathy were as follows: 72% for hyperprolactinemia, 30% for hypothyroidism, 29% for hypogonadism, and 19% for hypoadrenalism, The respective 10-year endocrinopathy rates were 84%, 63%, 36%, and 28%. No patient developed diabetes insipidus (vasopressin deficiency). Growth hormone deficiency was not routinely followed in this study. Minimum target dose (Dmin) to the PG was found to be predictive of endocrinopathy: patients receiving 50 CGE or greater at Dmin to the PG experiencing a higher incidence and severity (defined as the number of endocrinopathies occurring per patient) of endocrine dysfunction. Dmax of 70 CGE or greater to the PG and Dmax of 50 CGE or greater to the HT were also predictive of higher rates of endocrine dysfunction, Conclusion: Radiation-induced damage to the HT & PG occurs frequently after high-dose PPRT to the BOS and is manifested by anterior pituitary gland dysfunction, Hyperprolactinemia was detected in the majority of patients. Posterior pituitary dysfunction, represented by vasopressin activity with diabetes insipidus, was not observed in this dose range. Limiting the dose to the MT and PG when feasible should reduce the risk of developing clinical hypopituitarism, (C) 2001 Elsevier Science Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Clin Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Biostat Grp, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Biophys, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA USA. RP Pai, HH (reprint author), Vancouver Isl Canc Ctr, Dept Radiat Oncol, 1900 Ft St, Victoria, BC V8R 1J8, Canada. NR 34 TC 80 Z9 87 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 15 PY 2001 VL 49 IS 4 BP 1079 EP 1092 DI 10.1016/S0360-3016(00)01387-0 PG 14 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 408LG UT WOS:000167327200020 PM 11240250 ER PT J AU Abiko, T Abiko, A Martin, L Clermont, AC Tsujikawa, A Shoelson, B King, GL Bursell, SE AF Abiko, T Abiko, A Martin, L Clermont, AC Tsujikawa, A Shoelson, B King, GL Bursell, SE TI Regulation of oxidant formation by PKC-beta inhibition, a potential mechanism for normalizing retinal leukostasis in diabetic rats. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Eye Res Sect, Boston, MA 02215 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 1111 BP S207 EP S207 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392101102 ER PT J AU Adams, SM McGee, TL Berson, EL Dryja, TP AF Adams, SM McGee, TL Berson, EL Dryja, TP TI A screen for mutations of the RP1 gene in patients with autosomal recessive retinitis pigmentosa and Leber congenital amaurosis. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Mol Genet Inst, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 3455 BP S643 EP S643 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392103419 ER PT J AU Afshari, MA Krzystolik, MG Adamis, AP O'Neill, CA Gragoudas, ES Michaud, NA Li, W Connolly, E Hartmangruber, ML Miller, JW AF Afshari, MA Krzystolik, MG Adamis, AP O'Neill, CA Gragoudas, ES Michaud, NA Li, W Connolly, E Hartmangruber, ML Miller, JW TI Therapeutic and prophylactic effects of a recombinant human binding fragment of a monoclonal antibody directed to vascular endothelial growth factor (rhuFab VEGF) in a monkey model of laser-induced choroidal neovascularization. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. Genentech Inc, Dept Toxicol, San Francisco, CA 94080 USA. RI Li, Wenjun/F-5634-2015 OI Li, Wenjun/0000-0001-5335-7386 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 5001 BP S933 EP S933 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392104964 ER PT J AU Ahmadi, AJ Woog, JJ Patrinely, J Soparkar, C Jakobiec, FA AF Ahmadi, AJ Woog, JJ Patrinely, J Soparkar, C Jakobiec, FA TI Histopathological analysis of porous polyethylene lower eyelid spacer graft in humans. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. Baylor Sch Med, Dept Ophthalmol, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 1821 BP S337 EP S337 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392101791 ER PT J AU Ambati, BK Joussen, AM Ambati, J Moromizato, Y Guha, C O'Reilly, M Adamis, AP AF Ambati, BK Joussen, AM Ambati, J Moromizato, Y Guha, C O'Reilly, M Adamis, AP TI An angiostatin-producing tumor inhibits and regresses corneal neovascularization. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Harvard Univ, Sch Med, Surg Res Lab, Boston, MA 02115 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 2584 BP S479 EP S479 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392102553 ER PT J AU Ambati, J Taguchi, H Ambati, BK Joussen, AM Gragoudas, ES Miller, JW Adamis, AP AF Ambati, J Taguchi, H Ambati, BK Joussen, AM Gragoudas, ES Miller, JW Adamis, AP TI Targeted disruption of the CD18 or ICAM-1 gene inhibits choroidal neovascularization. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 4999 BP S932 EP S932 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392104962 ER PT J AU Banks, MC Pasquale, L Rizzo, JF AF Banks, MC Pasquale, L Rizzo, JF TI Scanning laser polarimetry of the optic nerve head in unilateral disc edema. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 110 BP S19 EP S19 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392100100 ER PT J AU Bhoi, KC Kumari, S Aziz, NA Foster, CS Ahmed, AR AF Bhoi, KC Kumari, S Aziz, NA Foster, CS Ahmed, AR TI Interleukin-1 components in ocular cicatricial pemphigoid: Role of intravenous immunoglobulin therapy. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 2515 BP S466 EP S466 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392102484 ER PT J AU Borboli, S Fan, JT Ang, RT Grosskreutz, CL Pasquale, LR Chen, TC AF Borboli, S Fan, JT Ang, RT Grosskreutz, CL Pasquale, LR Chen, TC TI Brimonidine 0.2% versus apraclonidine 0.5% for prevention of intraocular pressure elevations following neodymium(Nd): YAG anterior segment laser surgery. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA USA. Retina & Vitreous Associates, Fountain Valley, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 4495 BP S837 EP S837 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392104458 ER PT J AU Branco, A Blumenkranz, M Miller, J Slakter, J Sanislo, S Woodburn, K Rowe, T Simpson, G AF Branco, A Blumenkranz, M Miller, J Slakter, J Sanislo, S Woodburn, K Rowe, T Simpson, G TI Photodynamic angiography: A new technique utilizing Lutex. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Stanford Univ, Palo Alto, CA 94304 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Vitreous Retina Macula Consultants NY, New York, NY USA. Pharmacyclics, Sunnyvale, CA USA. Alcon Labs Inc, Ft Worth, TX 76101 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 2757 BP S512 EP S512 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392102726 ER PT J AU Brusie, SR Lussier, R Pasquale, LR AF Brusie, SR Lussier, R Pasquale, LR TI The blue arc phenomenon as a test for retinal nerve fiber layer function in glaucoma. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Georgetown Univ, Med Ctr, Ctr Sight, Washington, DC 20007 USA. Growtech, Waltham, MA USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 798 BP S149 EP S149 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392100789 ER PT J AU Cahill, M Clermont, AC Cai, WY Wong, JS Bursell, SE Aiello, LP AF Cahill, M Clermont, AC Cai, WY Wong, JS Bursell, SE Aiello, LP TI Hepatocyte growth factor/scatter factor (HGF/SF) increases retinal permeability but not retinal blood flow (RBF) through a PI3-kinase-mediated pathway. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Ophthalmol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 493 BP S89 EP S89 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392100483 ER PT J AU Chalfin, S Belote, LR AF Chalfin, S Belote, LR TI Recovery from blindness: The South Texas Veterans Health Care System experience. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, Dept Ophthalmol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Dept Social Work, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 4594 BP S856 EP S856 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392104557 ER PT J AU Chang, JH Savage, J Proctor, C Lin, HC Kure, T Gabison, EE Jain, S Azar, DT AF Chang, JH Savage, J Proctor, C Lin, HC Kure, T Gabison, EE Jain, S Azar, DT TI Characterization of anti-angiogenic precursor collagens, types XV and XVIII, in murine cornea: Role of MMP-7. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 665 BP S124 EP S124 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392100656 ER PT J AU Chao, CW Johnson, JD Harissi-Dagher, M Jeun, R Pineda, R Yoo, S Azar, DT AF Chao, CW Johnson, JD Harissi-Dagher, M Jeun, R Pineda, R Yoo, S Azar, DT TI Diffuse lamellar keratitis: Incidence, characteristics, and visual outcomes. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Univ Montreal, Dept Ophthalmol, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 2667 BP S494 EP S494 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392102636 ER PT J AU Chu, DS Razzaque, MS Ahmed, AR Foster, CS AF Chu, DS Razzaque, MS Ahmed, AR Foster, CS TI Localization of collagen IV, SPARC, and tenascin in conjunctiva in ocular cicatricial pemphegoid. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, Boston, MA USA. Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 2523 BP S467 EP S467 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392102492 ER PT J AU Claudepierre, T Koch, M Burgeson, RE Hunter, DD Brunken, WJ AF Claudepierre, T Koch, M Burgeson, RE Hunter, DD Brunken, WJ TI Characterization of a novel netrin in mature and developing retinae. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, CBRC, Boston, MA USA. Tufts Univ, Sch Med, Dept Neurosci, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 1080 BP S201 EP S201 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392101071 ER PT J AU Clermont, AC Cahill, MT Bursell, SE Bouck, N Aiello, LP AF Clermont, AC Cahill, MT Bursell, SE Bouck, N Aiello, LP TI Pigment epithelium-derived factor (PEDF) inhibits vascular endothelial growth factor (VEGF)-induced retinal permeability and blood flow in vivo. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. Northwestern Univ, Sch Med, Chicago, IL USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 511 BP S92 EP S92 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392100501 ER PT J AU Colon, JE Letko, E Bhol, K Razzaque, MS Foster, CS Ahmed, AR AF Colon, JE Letko, E Bhol, K Razzaque, MS Foster, CS Ahmed, AR TI An in vitro organ culture model for toxic epidermal necrolysis. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Dent Med, Dept Oral Med, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 2517 BP S466 EP S466 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392102486 ER PT J AU D'Amico, DJ Adamis, AP Duker, J Regillo, C Schneebaum, C Beasley, C AF D'Amico, DJ Adamis, AP Duker, J Regillo, C Schneebaum, C Beasley, C TI Sub-Tenon's retrobulbar Anecortave Acetate with and without Visudyne PDT in patients with subfoveal age-related macular degeneration (AMD) - a review of the emerging clinical safety profile of this new experimental treatment. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA USA. New England Eye Ctr, Boston, MA USA. Wills Eye Hosp, Philadelphia, PA USA. Beth Israel Hosp, New York, NY USA. Alcon Res Ltd, Ft Worth, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 1251 BP S232 EP S232 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392101242 ER PT J AU DeAngelis, MM Berson, EL Dryja, TP AF DeAngelis, MM Berson, EL Dryja, TP TI Evaluation of the VMD2 gene in patients with various forms of retinal degeneration. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Mol Genet Lab, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. RI DeAngelis, e/J-7863-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 3475 BP S646 EP S646 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392103439 ER PT J AU Demers-Turco, P Sonsino, J Arai, M Hirose, T AF Demers-Turco, P Sonsino, J Arai, M Hirose, T TI Comparison of three 10X low vision reading devices. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Vis Rehabil Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Schepens Retina Associates, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 4598 BP S856 EP S856 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392104561 ER PT J AU Drexler, W Hartl, I Ko, T Ghanta, RK Schuman, JS Bursell, SE Fujimoto, JG AF Drexler, W Hartl, I Ko, T Ghanta, RK Schuman, JS Bursell, SE Fujimoto, JG TI Ultrahigh resolution imaging of retinal diseases with optical coherence tomography. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. Univ Vienna, Inst Med Phys, A-1010 Vienna, Austria. Tufts Univ, Sch Med, New England Eye Ctr, Boston, MA 02111 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 637 BP S118 EP S118 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392100628 ER PT J AU Durrani, K Letko, E Nguyen, QD Sangwan, V Beaton, MA Samson, CM Harper, SL Shawkat, M Schuman, JS Foster, CS AF Durrani, K Letko, E Nguyen, QD Sangwan, V Beaton, MA Samson, CM Harper, SL Shawkat, M Schuman, JS Foster, CS TI Aqueous outflow facility in ocular cicatricial pemphigoid. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Immunol & Uveitis Serv, Boston, MA USA. Tufts Univ, Sch Med, New England Eye Ctr, Glaucoma Serv, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 4391 BP S818 EP S818 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392104354 ER PT J AU Egan, KM Gragoudas, ES AF Egan, KM Gragoudas, ES TI Mortality after diagnosis with indeterminate pigmented lesions of the choroid. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 376 BP S68 EP S68 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392100366 ER PT J AU Elliott, JL Wesley, J Scilley, K Owsley, C Kuyk, T AF Elliott, JL Wesley, J Scilley, K Owsley, C Kuyk, T TI Self-reported mobility performance among older veterans completing a blind rehabilitation program. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Alabama, Birmingham, AL USA. RI Owsley, Cynthia/B-7986-2014 NR 0 TC 0 Z9 0 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 4591 BP S855 EP S855 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392104554 ER PT J AU Ezra, E Zacks, DN Michaud, N Gragoudas, ES Miller, JW AF Ezra, E Zacks, DN Michaud, N Gragoudas, ES Miller, JW TI Verteporfin photodynamic therapy in the rat model of choroidal neovascularization. II. Histologic characterization. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Angiogenesis Lab, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 5004 BP S933 EP S933 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392104967 ER PT J AU Gabison, EE Hoang-Xuan, T Kure, T Ye, HQ Ang, RT Kato, T Chang, JH Shapiro, SD Azar, DT AF Gabison, EE Hoang-Xuan, T Kure, T Ye, HQ Ang, RT Kato, T Chang, JH Shapiro, SD Azar, DT TI Enhanced expression of human metalloelastase in ocular surface disorders. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Univ Paris 07, Dept Ophthalmol, Bichat Hosp, Paris, France. Univ Paris 07, Fdn A De Rothschild, Paris, France. NEI, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Barnes Jewish Hosp, Dept Internal Med & Cell Biol & Physiol, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 2616 BP S485 EP S485 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392102585 ER PT J AU Gatinel, D Malet, J Azar, D Xuan, TH AF Gatinel, D Malet, J Azar, D Xuan, TH TI Theoretical analysis of the maximal depth of tissue ablation induced by apheric customized profiles of ablation to correct myopia. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Fdn Rothschild, Paris, France. Univ Paris 06, Inst Stat, Paris, France. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 3895 BP S725 EP S725 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392103858 ER PT J AU Goldstein, L Muffat, J Cherny, R Faget, K Coccia, J Fraser, F Masters, C Tanzi, R Chylack, L Bush, A AF Goldstein, L Muffat, J Cherny, R Faget, K Coccia, J Fraser, F Masters, C Tanzi, R Chylack, L Bush, A TI A beta peptides in human and amyloid-bearing transgenic mouse lens: Implications for Alzheimer's disease and cataracts. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Ophthalm Res, Boston, MA USA. Massachusetts Gen Hosp, Lab Oxidat Biol, Charlestown, MA USA. Massachusetts Gen Hosp, Genet & Aging Unit, Charlestown, MA USA. Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia. Ecole Normale Super, Dept Bioengn, Cachan, France. RI Muffat, Julien/P-2298-2014 NR 0 TC 1 Z9 1 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 1614 BP S299 EP S299 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392101604 ER PT J AU Grimsby, JL DeAngelis, MM Berson, EL Dryja, TP AF Grimsby, JL DeAngelis, MM Berson, EL Dryja, TP TI Two novel missense changes in the neural retina leucine zipper (NRL) gene in patients with autosomal dominant retinitis pigmentosa. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Mol Genet Inst, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Retinal Degenerat, Boston, MA USA. RI DeAngelis, e/J-7863-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 3452 BP S642 EP S642 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392103416 ER PT J AU Hagstrom, SA Zhang, K Baehr, W He, W Wensel, TG Berson, EL Dryja, TP AF Hagstrom, SA Zhang, K Baehr, W He, W Wensel, TG Berson, EL Dryja, TP TI Comprehensive mutation screen in the RGS9 gene in 558 patients with inherited retinal degenerations. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Mol Genet Inst, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. Univ Utah, Moran Eye Ctr, Salt Lake City, UT USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 3476 BP S646 EP S646 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392103440 ER PT J AU Halpern, L Rizzo, J AF Halpern, L Rizzo, J TI The efficacy and safety of pulse-taper corticosteroid therapy in the management of giant cell arteritis: A retrospective study of 61 patients. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 1763 BP S327 EP S327 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392101733 ER PT J AU Haouat, MP Gatinel, D Azard, D Prisant, O Xuan, TH AF Haouat, MP Gatinel, D Azard, D Prisant, O Xuan, TH TI Comparison between theoretical and measured variation of the corneal asphericity after myopic photorefractive keratectomy with an excimer laser. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Fdn Rothschild, Paris, France. Hop Intercommunal Poissy, Poissy, France. Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 3256 BP S606 EP S606 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392103220 ER PT J AU Hartl, I Ko, T Ghanta, RK Drexler, W Clermont, A Bursell, SE Fujimoto, JG AF Hartl, I Ko, T Ghanta, RK Drexler, W Clermont, A Bursell, SE Fujimoto, JG TI In vivo ultrahigh resolution optical coherence tomography for the quantification of retinal structure in normal and transgenic mice. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 MIT, Elect Res Lab, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. Univ Vienna, Inst Med Phys, Vienna, Austria. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 4252 BP S793 EP S793 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392104215 ER PT J AU Hatton, MP Chen, PW Wistow, G Perez, VL Ksander, BR AF Hatton, MP Chen, PW Wistow, G Perez, VL Ksander, BR TI Melastatin-2 gene transcription in normal and malignant uveal melanocytes. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 598 BP S110 EP S110 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392100588 ER PT J AU Hicks, D Molday, LL Sauer, CG Champliaud-Steiner, MF Weber, BHF Molday, RS AF Hicks, D Molday, LL Sauer, CG Champliaud-Steiner, MF Weber, BHF Molday, RS TI Retinoschisin 1 (Xlrs1) localizes to photoreceptor and bipolar cell surfaces in mammalian retinas in vivo and in vitro. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Univ Teaching Hosp, INSERM ULP E9918, Clin Med A, Strasbourg, France. Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V5Z 1M9, Canada. Biozentrum, Inst Humangenet, Wurzburg, Germany. Massachusetts Gen Hosp East, Cutaneous Biol Res Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 1601 BP S297 EP S297 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392101591 ER PT J AU Hunter, DD Egles, C Pinzon-Duarte, G Arongo-Gonzalez, B Guenther, E AF Hunter, DD Egles, C Pinzon-Duarte, G Arongo-Gonzalez, B Guenther, E TI Effects of laminin fragments on development and differentiation of mammalian retinae. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Tufts Univ, Sch Med, Boston, MA 02111 USA. Univ Eye Hosp, Tubingen, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 2038 BP S378 EP S378 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392102008 ER PT J AU Jain, S Gabison, EE Chang, JH Paton, B Kure, T Savage, J Matrisian, LM Azar, DT AF Jain, S Gabison, EE Chang, JH Paton, B Kure, T Savage, J Matrisian, LM Azar, DT TI Corneal infections in matrix metalloproteinase deficient mice. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Vanderbilt Univ, Dept Cell Biol, Nashville, TN 37232 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 193 BP S34 EP S34 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392100183 ER PT J AU Joussen, AM Poulaki, V Esser, PJ Aiello, LP Adamis, AP AF Joussen, AM Poulaki, V Esser, PJ Aiello, LP Adamis, AP TI Diabetic leukocytes induce Fas-mediated endothelial cell apoptosis. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA USA. Univ Cologne, D-5000 Cologne 41, Germany. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 1110 BP S206 EP S206 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392101101 ER PT J AU Katai, N Katai, M Way, KJ King, GL AF Katai, N Katai, M Way, KJ King, GL TI Bovine retinal pericytes exposed to high glucose induce the sustained activation of extracellular signal-regulated kinase and inhibit pericyte growth after mechanical stretch. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 1095 BP S204 EP S204 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392101086 ER PT J AU Kato, T Kure, T Chang, JH Gabison, EE Itohara, S Azar, DT AF Kato, T Kure, T Chang, JH Gabison, EE Itohara, S Azar, DT TI Corneal angiogenesis in gelatinase A-deficient mice. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. RIKEN, Inst Phys & Chem Res, Wako, Saitama 35101, Japan. RI Itohara, Shigeyoshi/I-8769-2012 OI Itohara, Shigeyoshi/0000-0002-2410-9989 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 2593 BP S480 EP S480 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392102562 ER PT J AU Kim, EC Kahn, B Dohlman, CH Grosskreutz, CL AF Kim, EC Kahn, B Dohlman, CH Grosskreutz, CL TI The use of diode laser cyclophotocoagulation (CYC) for prevention and treatment of glaucoma associated with keratoprosthesis (KPro). SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Univ Calif San Francisco, Sch Med, San Francisco, CA USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 2945 BP S549 EP S549 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392102911 ER PT J AU Krause, M Xiong, J Gragoudas, ES Young, LHY AF Krause, M Xiong, J Gragoudas, ES Young, LHY TI Treatment of experimental choroidal melanoma with a Nd : YLF laser at 1047nm. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Univ Saarlandes, Univ Eye Hosp Homburg, Homburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 1184 BP S220 EP S220 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392101175 ER PT J AU Kumari, S Bhol, KC Simmons, RK Razzaque, MS Letko, E Foster, CS Ahmed, AR AF Kumari, S Bhol, KC Simmons, RK Razzaque, MS Letko, E Foster, CS Ahmed, AR TI Antibody to cytoplasmic domain of human beta 4 integrin is pathogenic in ocular cicatricial pemphigoid. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 2516 BP S466 EP S466 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392102485 ER PT J AU Lauritzen, DB Kurimoto, Y Gage, FH Klassen, H Young, MJ AF Lauritzen, DB Kurimoto, Y Gage, FH Klassen, H Young, MJ TI Retinal transplantation of neural progenitor cells in rats transgenic for mutant rhodopsin. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Salk Inst, La Jolla, CA USA. Childrens Hosp Orange Cty, Orange, CA 92668 USA. Retina Specialists Boston, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 1064 BP S198 EP S198 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392101055 ER PT J AU Letko, E Miserocchi, E Aziz, NA Christen, W Foster, CS Ahmed, AR AF Letko, E Miserocchi, E Aziz, NA Christen, W Foster, CS Ahmed, AR TI A prospective non-randomized clinical trial comparing efficacy and safety of intravenous immunoglobulin to conventional therapy. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, Boston, MA USA. Harvard Univ, Sch Dent Med, Dept Oral Med & Oral Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 2521 BP S467 EP S467 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392102490 ER PT J AU Li, T Adamian, M Hong, D AF Li, T Adamian, M Hong, D TI Immunolocalization of the RPGR interacting protein (RPGRIP) in the retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 3528 BP S656 EP S656 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392103492 ER PT J AU Lit, ES Gotzaridis, EV D'Amico, DJ AF Lit, ES Gotzaridis, EV D'Amico, DJ TI Feasibility of trans-vitreal lamina cribosa ("lamina puncture") surgery for central retinal vein occlusion. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 1297 BP S240 EP S240 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392101287 ER PT J AU Luukkaa, VA Poulin, NR Grosskreutz, CL AF Luukkaa, VA Poulin, NR Grosskreutz, CL TI Increased caspase 3 expression in the saline model of experimental glaucoma in the rat. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 2753 BP S511 EP S511 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392102722 ER PT J AU Ma, JJK Afshari, MA Pineda, R Ho, J Starr, CE Paton, BG Afshari, NA AF Ma, JJK Afshari, MA Pineda, R Ho, J Starr, CE Paton, BG Afshari, NA TI Emerging resistance patterns of bacterial keratitis: Is fluoroquinolone monotherapy adequate? SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 1373 BP S254 EP S254 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392101363 ER PT J AU McGee, TL Adams, SM Grimsby, JL Hong, DH Li, T Andreasson, S Berson, EL Dryja, TP AF McGee, TL Adams, SM Grimsby, JL Hong, DH Li, T Andreasson, S Berson, EL Dryja, TP TI Null mutations in the RPGR-interacting protein gene (RPGRIP) in patients with Leber congenital amaurosis. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab, Boston, MA USA. Univ Lund Hosp, Dept Ophthalmol, S-22185 Lund, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 3465 BP S644 EP S644 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392103429 ER PT J AU Miserocchi, E Roque, MR Ahmed, AR Foster, CS AF Miserocchi, E Roque, MR Ahmed, AR Foster, CS TI Disuse progression in ocular cicatricial pemphigoid: Treatment-related side effects. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 2518 BP S467 EP S467 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392102487 ER PT J AU Morita, Y Kure, T Chang, JH Azar, NF AF Morita, Y Kure, T Chang, JH Azar, NF TI Immunohistochemical localization of stromelysin 1 in human extraocular muscle. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 889 BP S166 EP S166 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392100880 ER PT J AU Obritsch, WF Van Remmen, H Fan, D Ferrington, DA AF Obritsch, WF Van Remmen, H Fan, D Ferrington, DA TI Protection of the retinal pigment epithelium by antioxidant enzymes. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Univ Minnesota, Dept Ophthalmol, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Biochem, Minneapolis, MN 55455 USA. S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 4053 BP S756 EP S756 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392104016 ER PT J AU Ocampo, VD Durand, M Foster, CS AF Ocampo, VD Durand, M Foster, CS TI Toxicity of topically-applied chlorhexidine gluconate on the cornea and its adjacent structures. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Infect Dis Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 3117 BP S580 EP S580 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392103082 ER PT J AU Pasquale, LR Kang, JH Rosner, B Willet, W Faberowski, N Hankinson, SE AF Pasquale, LR Kang, JH Rosner, B Willet, W Faberowski, N Hankinson, SE TI Antioxidant consumption and primary open-angle glaucoma in two prospective cohorts. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Div Ophthalmol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Glaucoma Serv, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 556 BP S102 EP S102 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392100546 ER PT J AU Pawlyk, BS Li, T Scimeca, MS Sandberg, MA Berson, EL AF Pawlyk, BS Li, T Scimeca, MS Sandberg, MA Berson, EL TI No photoreceptor rescue by D-cis-diltiazem in retinal degeneration (rd) mice. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Grund Lab Study Retinal Degenerat, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 3387 BP S630 EP S630 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392103351 ER PT J AU Perez, VL Gregory, M Repp, A Hohlbaum, AM Marshak-Rothstein, A Ksander, B AF Perez, VL Gregory, M Repp, A Hohlbaum, AM Marshak-Rothstein, A Ksander, B TI The ratio of membrane to soluble Fas ligand in the cornea induces or prevents immune-mediated keratitis. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Schepens Eye Res Inst, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 3090 BP S575 EP S575 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392103055 ER PT J AU Poulaki, V Mitsiades, C Mitsiades, N AF Poulaki, V Mitsiades, C Mitsiades, N TI Inhibition of NF-kB activity induces loss of mitochondrial transmembrane potential and caspase-independent apoptosis in retinoblastoma cells. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 1784 BP S331 EP S331 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392101754 ER PT J AU Proano, CE Mulroy, L Azar, DT Redmond, RW Kochevar, IE AF Proano, CE Mulroy, L Azar, DT Redmond, RW Kochevar, IE TI In vivo Photochemical Keratodesmos in corneal incisions and penetrating keratoplasty wounds. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 152 BP S27 EP S27 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392100142 ER PT J AU Qin, W Poulaki, V Hurlbut, PR Adamis, AP AF Qin, W Poulaki, V Hurlbut, PR Adamis, AP TI Intensive insulin treatment upregulates VEGF gene statement in vivo through the hypoxia-inducible factor HIF-1a. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Massachusetts, Sch Med, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 1917 BP S354 EP S354 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392101887 ER PT J AU Rabe, VW Sharon, D Berson, EL Dryja, TP AF Rabe, VW Sharon, D Berson, EL Dryja, TP TI The mutation spectrum of RPGR-ORF15 in North American patients with X-linked retinitis pigmentosa (XLRP). SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Ocular Mol Genet Lab, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. RI Sharon, Dror/P-4539-2015 OI Sharon, Dror/0000-0002-1789-5811 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 3450 BP S642 EP S642 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392103414 ER PT J AU Rauniyar, RK Suzuma, K Aiello, LP King, GL AF Rauniyar, RK Suzuma, K Aiello, LP King, GL TI Compounds derived from human bactericidal/permeability increasing protein suppress VEGF-induced retinal endothelial cell growth and hypoxia-induced retinal neovascularization while enhancing retinal pericyte growth. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 1314 BP S243 EP S243 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392101304 ER PT J AU Ray, SK Hatton, MP AF Ray, SK Hatton, MP TI Orbital and adnexal trauma in open globe injuries. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 3659 BP S680 EP S680 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392103622 ER PT J AU Razavi, S Corjay, MH Thomas, MA Soubrane, G Coscas, G Gragoudas, ES Miller, JW AF Razavi, S Corjay, MH Thomas, MA Soubrane, G Coscas, G Gragoudas, ES Miller, JW TI Expression of integrins alpha(v)beta(3) and alpha(v)beta(5) in human choroidal neovascular membranes. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Hop Intercommunal, Creteil, France. Dupont Merck Res Labs, Wilmington, DE USA. Barnes Retina Inst, St Louis, MO USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 4142 BP S773 EP S773 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392104105 ER PT J AU Razzaque, MS Chu, DS Kumari, S Foster, CS Taguchi, T Ahmed, AR AF Razzaque, MS Chu, DS Kumari, S Foster, CS Taguchi, T Ahmed, AR TI Conjunctival expression of collagens and collagen-binding heat shock protein 47 in ocular cicatricial pemphigoid. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Immunol & Uveitis Serv, Boston, MA USA. Nagasaki Univ, Sch Med, Dept Pathol, Nagasaki 852, Japan. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 2803 BP S521 EP S521 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392102770 ER PT J AU Renno, R Youssri, A Michaud, N Gragoudas, E Miller, J AF Renno, R Youssri, A Michaud, N Gragoudas, E Miller, J TI A role for pigment-epithelium derived factor in choroidal neovascular membrane development. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Retina Res Inst, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 1224 BP S227 EP S227 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392101215 ER PT J AU Rivolta, C Peck, NE Fishman, GA Fulton, AB Berson, EL Dryja, TP AF Rivolta, C Peck, NE Fishman, GA Fulton, AB Berson, EL Dryja, TP TI Mutations in CRX in patients with Leber congenital amaurosis and cone-rod dystrophy. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. Univ Illinois, Eye & Ear Infirm, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 3437 BP S640 EP S640 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392103401 ER PT J AU Rosenblatt, MI Thompson, H Ray, SK AF Rosenblatt, MI Thompson, H Ray, SK TI Post-operative target refraction following intraocular lens implantation. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 70 BP S12 EP S12 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392100060 ER PT J AU Sami, N Letko, E Aziz, NA Colon, JE Bhol, KC Foster, CS Ahmed, AR AF Sami, N Letko, E Aziz, NA Colon, JE Bhol, KC Foster, CS Ahmed, AR TI Ocular cicatricial pemphigoid: Interaction of IL-5 and eosinophils. A preliminary observation. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 NE Baptist Hosp, Dept Med, Boston, MA USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol,Uveitis & Immunol Serv, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 2522 BP S467 EP S467 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392102491 ER PT J AU Sarraf, D AF Sarraf, D TI Clinical evaluation of choroidal folds. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Charles R Drew Univ Med & Sci, Sch Med, Martin Luther King Hosp, Los Angeles, CA 90059 USA. Greater Los Angeles Vet Adm Healthcare Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 2317 BP S430 EP S430 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392102287 ER PT J AU Savage, JM Chang, JH Gabison, EE Azar, DT AF Savage, JM Chang, JH Gabison, EE Azar, DT TI In vitro characterization of angiostatin-like molecules in epithelial cell-keratocyte interactions. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 2592 BP S480 EP S480 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392102561 ER PT J AU Schwartz, SD Blumenkranz, M Rosenfeld, PJ Miller, JW Haller, J Fish, G Lobes, L Singerman, L Greene, WL Reimann, J AF Schwartz, SD Blumenkranz, M Rosenfeld, PJ Miller, JW Haller, J Fish, G Lobes, L Singerman, L Greene, WL Reimann, J TI Safety of rhuFab V2, an anti-VEGF antibody fragment, as a single intravitreal injection in subjects with neovascular age-related macular degeneration. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90024 USA. Stanford Univ, Dept Ophthalmol, Stanford, CA 94305 USA. Univ Miami, Bascom Palmer Eye Inst, Miami, FL 33152 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA USA. Johns Hopkins Univ, Dept Ophthalmol, Baltimore, MD USA. Texas Retina Associates, Dallas, TX USA. Retina Vitreous Consultants, Pittsburgh, PA USA. Retina Associates Cleveland, Cleveland, OH USA. Genentech Inc, S San Francisco, CA 94080 USA. NR 0 TC 11 Z9 11 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 2807 BP S522 EP S522 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392102774 ER PT J AU Seddon, JM Rosner, B Sperduto, RD Yannuzzi, L Haller, JA Blair, NP Willett, W AF Seddon, JM Rosner, B Sperduto, RD Yannuzzi, L Haller, JA Blair, NP Willett, W TI Dietary fat and risk of advanced age-related macular degeneration. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NEI, Bethesda, MD 20892 USA. Manhattan Eye Ear & Throat Hosp, New York, NY 10021 USA. Wilmer Eye Inst, Baltimore, MD USA. Univ Illinois, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 2419 BP S448 EP S448 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392102389 ER PT J AU Sharon, D Blackshaw, S Berson, EL Cepko, CL Dryja, TP AF Sharon, D Blackshaw, S Berson, EL Cepko, CL Dryja, TP TI Expression profiling of the human peripheral retina, fovea and RPE using serial analysis of gene expression (SAGE). SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Lab, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RI Sharon, Dror/P-4539-2015 OI Sharon, Dror/0000-0002-1789-5811 NR 0 TC 0 Z9 0 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 4132 BP S771 EP S771 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392104095 ER PT J AU Shatos, MA Kano, H Rios, J Rubin, P Garza, G Dartt, DA AF Shatos, MA Kano, H Rios, J Rubin, P Garza, G Dartt, DA TI Isolation and characterization of human goblet cells in vitro: Regulation of proliferation and activation of mitogen-activated protein kinase by EGF and cholinergic agonists. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 2800 BP S520 EP S520 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392102767 ER PT J AU Shire, DB Wyatt, JL Rizzo, JF AF Shire, DB Wyatt, JL Rizzo, JF TI Progress toward an inflatable neural prosthesis. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Cornell Univ, Cornell Nanofabricat Facil, Ithaca, NY USA. MIT, Cambridge, MA 02139 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 4357 BP S812 EP S812 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392104320 ER PT J AU Shoelson, B Clermont, A Bursell, SE AF Shoelson, B Clermont, A Bursell, SE TI Automated quantification of the retinal microcirculation from video fluorescein angiograms. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 2821 BP S525 EP S525 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392102788 ER PT J AU Slezak, SJ Tavee, W Perlman, JI Klineman, BS DePinto, DJ Hines, E AF Slezak, SJ Tavee, W Perlman, JI Klineman, BS DePinto, DJ Hines, E TI Effect of cardiopulmonary bypass surgery on intraocular pressure. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. Loyola Univ, Dept Ophthalmol, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Anesthesiol, Maywood, IL 60153 USA. Loyola Univ, Thorac Cardiovasc Surg, Maywood, IL 60153 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 3364 BP S626 EP S626 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392103328 ER PT J AU Starr, CE Primack, JD Rowe, SG Pineda, RP AF Starr, CE Primack, JD Rowe, SG Pineda, RP TI Determination of corneal keratometric power after LASIK surgery. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 3248 BP S605 EP S605 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392103212 ER PT J AU Stechschulte, S Joussen, AM von Recum, HA Poulaki, V Moromizato, Y Yuan, J D'Amato, RJ Kuo, C Adamis, AP AF Stechschulte, S Joussen, AM von Recum, HA Poulaki, V Moromizato, Y Yuan, J D'Amato, RJ Kuo, C Adamis, AP TI Rapid ocular angiogenic control via naked DNA delivery to cornea. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Discover Vis Ctr, Kansas City, MO 64155 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Childrens Hosp, Surg Res Lab, Boston, MA 02115 USA. RI von Recum, Horst/F-5911-2012 OI von Recum, Horst/0000-0002-9323-8100 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 666 BP S124 EP S124 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392100657 ER PT J AU Sun, JK Paton, BG Morris, MR Afshari, NA Afshari, MA AF Sun, JK Paton, BG Morris, MR Afshari, NA Afshari, MA TI An analysis of the current microbiologic spectrum and antibiotic sensitivities of intraocular cultures for suspected endophthalmitis. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 1350 BP S250 EP S250 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392101340 ER PT J AU Suzuma, I Suzuma, K Ueki, K Feener, EP King, GL Aiello, LP AF Suzuma, I Suzuma, K Ueki, K Feener, EP King, GL Aiello, LP TI Stretch-induced VEGF expression is mediated by PI3 kinase & PKC zeta but not ERK1/2 or AKT in bovine retinal pericytes (BRPC). SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 1096 BP S204 EP S204 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392101087 ER PT J AU Suzuma, K Takahara, N Suzuma, I Ueki, K Leitges, M Aiello, LP King, GL AF Suzuma, K Takahara, N Suzuma, I Ueki, K Leitges, M Aiello, LP King, GL TI PKC beta isoform activation selectively enhances hypoxia-induced retinal angiogenesis and VEGF-mediated endothelial cell growth and migration. but not differentiation. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 497 BP S90 EP S90 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392100487 ER PT J AU Taguchi, H Kim, RY Youssri, A Connolly, EJ Harte, KJ Sliski, AP Gragoudas, ES Miller, JW AF Taguchi, H Kim, RY Youssri, A Connolly, EJ Harte, KJ Sliski, AP Gragoudas, ES Miller, JW TI Safety and efficacy of intraocular photon radiosurgery system for experimental choroidal neovascularization in non-human primates. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Takamatsu Red Cross Hosp, Kagawa, Japan. Photoelect Corp, Lexington, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 1258 BP S233 EP S233 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392101249 ER PT J AU Thakker, MM Ray, S AF Thakker, MM Ray, S TI Causes of visual limitation in zones I, II, & III open globe injuries. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 4383 BP S817 EP S817 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392104346 ER PT J AU Tsao, K Kazlas, MA AF Tsao, K Kazlas, MA TI Retinal hole size and intraocular pressure at which Perfluoron (R) egresses to the subretinal space. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Retina Specialists, Boston, MA USA. Schepens Eye Res Inst, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 2411 BP S447 EP S447 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392102381 ER PT J AU Vavvas, D Ray, S AF Vavvas, D Ray, S TI Non-traumatic sub-conjuctival hemorrhage, dilated fundus exam and associated findings. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 371 BP S67 EP S67 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392100361 ER PT J AU Yuen, SA Rubin, P AF Yuen, SA Rubin, P TI Idiopathic orbital inflammation: Distribution, clinical features, and treatment failure analysis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 2525 BP S468 EP S468 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392102494 ER PT J AU Zacks, DN Ezra, E Michaud, N Gragoudas, ES Miller, JW AF Zacks, DN Ezra, E Michaud, N Gragoudas, ES Miller, JW TI Verteporfin photodynamic therapy in the rat model of choroidal neovascularization. I. Angiographic characterization. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Angiogenesis Lab, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 5003 BP S933 EP S933 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392104966 ER PT J AU Zafirakis, P Baltatzis, S Voudouri, A Livir-Rallatos, C Livir-Rallatos, G Markomichelakis, N Foster, CS AF Zafirakis, P Baltatzis, S Voudouri, A Livir-Rallatos, C Livir-Rallatos, G Markomichelakis, N Foster, CS TI Immunopathology of ocular rosacea. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Gen Hosp, Dept Ophthalmol, Athens, Greece. Univ Athens, Sch Med, Dept Ophthalmol, Gen Hosp, GR-11527 Athens, Greece. Asklepei Gen Hosp, Dept Ophthalmol, Athens, Greece. Tulane Univ, Vitreoretinal Serv, New Orleans, LA 70118 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Hilles Immunol Lab, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 3101 BP S577 EP S577 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392103066 ER PT J AU Zhao, T Letko, E Ahmed, AR Foster, CS AF Zhao, T Letko, E Ahmed, AR Foster, CS TI Treatment of ocular cicatricial pemphigoid with tacrolimus (FK 506). SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Uveitis & Immunol Serv, Boston, MA USA. Harvard Univ, Sch Dent Med, Dept Oral Med & Oral Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 2520 BP S467 EP S467 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392102489 ER PT J AU Gelber, S Coates, AS Goldhirsch, A Castiglione-Gertsch, M Marini, G Lindtner, J Edelmann, DZ Gudgeon, A Harvey, V Gelber, RD AF Gelber, S Coates, AS Goldhirsch, A Castiglione-Gertsch, M Marini, G Lindtner, J Edelmann, DZ Gudgeon, A Harvey, V Gelber, RD CA Int Breast Canc Study Grp TI Effect of pregnancy on overall survival after the diagnosis of early-stage breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SUBSEQUENT; CARCINOMA; WOMEN AB Purpose: To evaluate the impact of subsequent pregnancy on the prognosis of patients with early breast cancer. Patients and Methods: One hundred eight patients who became pregnant after diagnosis of early-stage breast cancer were identified in institutions participating in International Breast Cancer Study Group (IBCSG) studies. Fourteen had relapse of breast cancer before their first subsequent pregnancy. The remaining 94 patients (including eight who relapsed during pregnancy) formed the study group reported here. A comparison group of 188 was obtained by randomly selecting two patients, matched for nodal status, tumor size, age, and year of diagnosis from the IBCSG database, who were free of relapse for at least as long as the time between breast cancer diagnosis and completion of pregnancy for each pregnant patient. Survival comparison used Cox proportional hazards regression models. Results: Overall 5- and 10-year survival percentages (+/- SE) measured from the diagnosis of early-stage breast cancer among the 94 study group patients were 92% +/- 3% and 86% +/- 4%, respectively. For the matched comparison group survival was 85% +/- 3% at 5 years and 74% +/- 4% at 10 years (risk ratio, 0.44; 95% confidence interval, 0.21 to 0.96; P =.04). Conclusion: Subsequent pregnancy does not adversely affect the prognosis of early-stage breast cancer. The superior survival seen in this and other controlled series may merely reflect a healthy patient selection bias, but is also consistent with an antitumor effect of the pregnancy. (C) 2001 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Dept Biostat Sci, Breast Canc Study Grp, Ctr Stat, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn, Brookline, MA USA. Australian Canc Soc, Sydney, NSW, Australia. Univ Sydney, Sydney, NSW 2006, Australia. European Inst Oncol, Dept Med Oncol, Milan, Italy. Osped Civile, Lugano, Switzerland. Clin S Anna, Lugano, Switzerland. Int Breast Canc Study Grp Coordinating Ctr, Bern, Switzerland. Inst Oncol, Ljubljana, Slovenia. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. Groote Schuur Hosp, ZA-7925 Cape Town, South Africa. Auckland Hosp, Auckland, New Zealand. RP Gelber, S (reprint author), Dana Farber Canc Inst, Dept Biostat Sci, Breast Canc Study Grp, Ctr Stat, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA-75362] NR 23 TC 119 Z9 126 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 15 PY 2001 VL 19 IS 6 BP 1671 EP 1675 PG 5 WC Oncology SC Oncology GA 414EG UT WOS:000167652500011 PM 11250996 ER PT J AU Harris, LN Liotcheva, V Broadwater, G Ramirez, MJ Maimonis, P Anderson, S Everett, T Harpole, D Moore, MB Berry, DA Rizzeri, D Vredenburgh, JJ Bentley, RC AF Harris, LN Liotcheva, V Broadwater, G Ramirez, MJ Maimonis, P Anderson, S Everett, T Harpole, D Moore, MB Berry, DA Rizzeri, D Vredenburgh, JJ Bentley, RC TI Comparison of methods of measuring HER-2 in metastatic breast cancer patients treated with high-dose chemotherapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PROGNOSTIC-SIGNIFICANCE; NEU-ONCOGENE; ONCOPROTEIN EXPRESSION; ERBB2 AMPLIFICATION; PROTO-ONCOGENE; FOLLOW-UP; C-ERBB-2; SERUM; RECEPTOR; THERAPY AB Purpose: HER-2 is overexpressed in 20% to 30% of human breast cancer and is associated with poor outcome. Studies suggest an association between HER-2 overexpression and resistance to alkylating agents. To further evaluate this relationship, we assessed the interaction of HER-2, measured by different methods, and outcome after dose intensification with alkylating agents in metastatic breast cancer. Patients and Methods: From 1988 to 1995 at Duke University, 425 patients with metastatic breast cancer were enrolled in a study of high-dose alkylating agents (HDC) with autologous cellular support after doxorubicin-based therapy (AFM). HER-2 was measured in serum for shed extracellular domain (ECD) and in tissue by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). Results: HER-2 ECD was positive in 29%(19 of 65) of patients pre-AFM and in 11.7% (34 of 290) pre-HDC. Higher pre-AFM and higher pre-HDC HER-2 ECD predicted worse overall survival (P =.045 and P =.0096, respectively). HER-2 overexpression by IHC and FISH showed no correlation with worse disease-free survival or overall survival. FISH and ECD were highly specific for IHC (97.3% and 97.7% respectively). However, ECD had a low sensitivity for IHC- only 22% of patients with HER-2 in the primary tumor shed ECD into the serum. Conclusion: These data suggest that the method of measuring HER-2 is important in predicting clinical outcome. HER2 ECD may identify a poor prognosis subgroup of HER-2-positive tumors. Lack of association of HER2 by IHC/FISH with worse outcome suggests that therapy with AFM and/or HDC therapy may be able to overcome the effect of this prognostic factor or it may not be a prognostic factor in this setting. (C) 2001 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Bayer Diagnost, Walpole, MA USA. Labcorp Inc, Res Triangle Pk, NC USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. MD Anderson Canc Ctr, Houston, TX USA. RP Harris, LN (reprint author), Dana Farber Canc Inst, Dana 1210,44 Binney St, Boston, MA 02115 USA. NR 35 TC 72 Z9 72 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 15 PY 2001 VL 19 IS 6 BP 1698 EP 1706 PG 9 WC Oncology SC Oncology GA 414EG UT WOS:000167652500014 PM 11250999 ER PT J AU Breathnach, OS Freidlin, B Conley, B Green, MR Johnson, DH Gandara, DR O'Connell, M Shepherd, FA Johnson, BE AF Breathnach, OS Freidlin, B Conley, B Green, MR Johnson, DH Gandara, DR O'Connell, M Shepherd, FA Johnson, BE TI Twenty-two years of phase III trials for patients with advanced non-small-cell lung cancer: Sobering results SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SOUTHWEST-ONCOLOGY-GROUP; VINDESINE PLUS CISPLATIN; RANDOMIZED TRIAL; COMBINATION CHEMOTHERAPY; BRONCHOGENIC-CARCINOMA; SINGLE-AGENT; MITOMYCIN-C; DOXORUBICIN; CYCLOPHOSPHAMIDE; REGIMENS AB Purpose: To determine the changes in clinical trials and outcomes of patients with advanced-stage nonsmall-cell lung cancer (NSCLC) treated on phase III randomized trials initiated in North America from 1973 to 1994, Patients and Methods: Phase III trials for patients with advanced-stage NSCLC were identified through a search of the National Cancer Institute's Cancer Therapy Evaluation Program database from 1973 to 1994, contact with Cooperative Groups, and by literature search of MEDLINE. Patients with advanced NSCLC treated during a similar time interval were also examined in the SEER database. Trends were tested in the number of trials, in the number and sex of patients entered on the trials, and in survival over time, Results: Thirty-three phase III trials were initiated between 1973 and 1994. Twenty-four trials (73%) were initiated within the first half of this period (1973 to 1983) and accounted for 5,359 (64%) of the 8,434 eligible patients. The median number of patients treated per arm of the trials rose from 77 (1973 to 1983) to 121 (1984 to 1994) (P < .001). five trials (15%) showed a statistically significant difference in survival between treatment arms, with a median prolongation of the median survival of 2 months (range, 0.7 to 2.7 months). Conclusion: Analysis of past trials in North America shows that the prolongation in median survival between two arms of a randomized study was rarely in excess of 2 months. Techniques for improved use of patient resources and appropriate trial design for phase III randomized therapeutic trials with patients with advanced NSCLC need to be developed. <(c)> 2001 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Thorac Oncol Program, Lowe Ctr Thorac Oncol, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. NCI, Div Canc Treatment & Diag, Canc Therapy Evaluat Program, Biometr Res Branch,Clin Invest Branch, Bethesda, MD 20892 USA. Canc & Leukemia Grp B, Chicago, IL USA. Eastern Cooperat Oncol Grp, Pittsburgh, PA USA. SW Oncol Grp, San Antonio, TX USA. N Cent Canc Treatment Grp Philadelphia, Philadelphia, PA USA. Natl Canc Inst, Canada Clin Trials Grp, Kingston, ON, Canada. RP Breathnach, OS (reprint author), Dana Farber Canc Inst, Thorac Oncol Program, Lowe Ctr Thorac Oncol, Dept Adult Oncol, Ste 1234,44 Binney St, Boston, MA 02115 USA. RI Johnson, David/A-7437-2009 NR 50 TC 249 Z9 259 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 15 PY 2001 VL 19 IS 6 BP 1734 EP 1742 PG 9 WC Oncology SC Oncology GA 414EG UT WOS:000167652500019 PM 11251004 ER PT J AU Su, MWC Yu, CL Burakoff, SJ Jin, YJ AF Su, MWC Yu, CL Burakoff, SJ Jin, YJ TI Targeting Src homology 2 domain-containing tyrosine phosphatase (SHP-1) into lipid rafts inhibits CD3-induced T cell activation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECEPTOR SIGNAL-TRANSDUCTION; ANTIGEN-RECEPTOR; ZETA-CHAIN; PHOSPHOTYROSINE PHOSPHATASE; MEMBRANE COMPARTMENTATION; LYMPHOCYTE-ACTIVATION; ADAPTER PROTEINS; PLASMA-MEMBRANE; KINASE; ZAP-70 AB To study the mechanism by which protein tyrosine phosphatases (PTPs) regulate CD3-induced tyrosine phosphorylation, we investigated the distribution of PTPs in subdomains of plasma membrane. We report here that the bulk PTP activity associated with T cell membrane is present outside the lipid rafts, as determined by sucrose density gradient sedimentation. In Jurkat T cells, similar to5-10% of Src homology 2 domain-containing tyrosine phosphatase (SHP-1) is constitutively associated with plasma membrane, and nearly 50% of SHP-2 is translocated to plasma membrane after vanadate treatment. Similar to transmembrane PTP, CD45, the membrane-associated populations of SHP-1 and SHP-2 are essentially excluded from lipid rafts, where other signaling molecules such as Lck, linker for activation of T cells, and CD3 zeta are enriched. We further demonstrated that CD3-induced tyrosine phosphorylation of these substrates is largely restricted to lipid rafts, unless PTPs are inhibited. It suggests that a restricted partition of PTPs among membrane subdomains may regulate protein tyrosine phosphorylation in T cell membrane. To test this hypothesis, we targeted SHP-1 into lipid rafts by using the N-terminal region of Lck (residues 1-14). The results indicate that the expression of Lck/SHP-1 chimera inside lipid rafts profoundly inhibits CD3-induced tyrosine phosphorylation of CD3 zeta/epsilon, IL-2 generation, and nuclear mobilization of NF-AT, Collectively, these results suggest that the exclusion of PTPs from lipid rafts may be a mechanism that potentiates TCR/CD3 activation. C1 Harvard Univ, Dept Pediat Oncol, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. RP Jin, YJ (reprint author), Harvard Univ, Dept Pediat Oncol, Dana Farber Canc Inst, Sch Med, Room M654,44 Binney St, Boston, MA 02115 USA. RI Yu, Chao-Lan/D-1834-2011 OI Yu, Chao-Lan/0000-0002-9381-6011 NR 43 TC 51 Z9 56 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2001 VL 166 IS 6 BP 3975 EP 3982 PG 8 WC Immunology SC Immunology GA 410JW UT WOS:000167437700046 PM 11238643 ER PT J AU Sato, K Balla, J Otterbein, L Smith, RN Brouard, S Lin, Y Csizmadia, E Sevigny, J Robson, SC Vercellotti, G Choi, AM Bach, FH Soares, MP AF Sato, K Balla, J Otterbein, L Smith, RN Brouard, S Lin, Y Csizmadia, E Sevigny, J Robson, SC Vercellotti, G Choi, AM Bach, FH Soares, MP TI Carbon monoxide generated by heme oxygenase-1 suppresses the rejection of mouse-to-rat cardiac transplants SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SMOOTH-MUSCLE-CELLS; INDUCED LUNG INJURY; XENOGRAFT REJECTION; ENDOTHELIAL-CELLS; PROVIDES PROTECTION; EXPRESSION; ACCOMMODATION; COMPLEMENT; SURVIVAL; GENE AB Mouse-to-rat cardiac transplants survive long term after transient complement depletion by cobra venom factor and T cell immunosuppression by cyclosporin A. Expression of heme oxygenase-1 (HO-1) by the graft vasculature is critical to achieve graft survival. In the present study, we asked whether this protective effect was attributable to the generation of one of the catabolic products of HO-1, carbon monoxide (CO), Our present data suggests that this is the case, Under the same immunosuppressive regimen that allows mouse-to-rat cardiac transplants to survive long term (i,e,, cobra venom factor plus cyclosporin A), inhibition of HO-1 activity by tin protoporphyrin, caused graft rejection in 3-7 days. Rejection was associated with widespread platelet sequestration, thrombosis of coronary arterioles, myocardial infarction, and apoptosis of endothelial cells as well as cardiac myocytes, Under inhibition of HO-1 activity by tin protoporphyrin, exogenous CO suppressed graft rejection and restored longterm graft survival. This effect of CO was associated with inhibition of platelet aggregation, thrombosis, myocardial infarction, and apoptosis, We also found that expression of HO-1 by endothelial cells in vitro inhibits platelet aggregation and protects endothelial cells from apoptosis, Both these actions of HO-1 are mediated through the generation of CO. These data suggests that HO-1 suppresses the rejection of mouse-to-rat cardiac transplants through a mechanism that involves the generation of CO, Presumably CO suppresses graft rejection by inhibiting platelet aggregation that facilitates vascular thrombosis and myocardial infarction, Additional mechanisms hy which CO overcomes graft rejection may involve its ability to suppress endothelial cell apoptosis. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Immunobiol Res Ctr, Boston, MA 02215 USA. Univ Debrecen, Sch Med, Dept Med, Debrecen, Hungary. Yale Univ, Sch Med, Dept Internal Med Pulm, New Haven, CT 06520 USA. Yale Univ, Sch Med, Crit Care Sect, New Haven, CT 06520 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Univ Minnesota, Div Hematol, Minneapolis, MN 55455 USA. RP Soares, MP (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Immunobiol Res Ctr, 99 Brookline Ave, Boston, MA 02215 USA. EM msoares@caregroup.harvard.edu RI Sevigny, Jean/E-8039-2012; brouard, sophie/Q-1285-2016; OI Sevigny, Jean/0000-0003-2922-1600; Soares, Miguel/0000-0002-9314-4833 FU NHLBI NIH HHS [HL58688] NR 38 TC 363 Z9 392 U1 1 U2 14 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2001 VL 166 IS 6 BP 4185 EP 4194 PG 10 WC Immunology SC Immunology GA 410JW UT WOS:000167437700073 PM 11238670 ER PT J AU Ancuta, P Bakri, Y Chomont, N Hocini, H Gabuzda, D Haeffner-Cavaillon, N AF Ancuta, P Bakri, Y Chomont, N Hocini, H Gabuzda, D Haeffner-Cavaillon, N TI Opposite effects of IL-10 on the ability of dendritic cells and macrophages to replicate primary CXCR4-dependent HIV-1 strains SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MONOCYTE-DERIVED MACROPHAGES; PERIPHERAL-BLOOD MONOCYTES; CD4(+) T-CELLS; IN-VITRO; DISEASE PROGRESSION; TYPE-2 CYTOKINES; CCR5 EXPRESSION; ANTIRETROVIRAL THERAPY; INFECTED INDIVIDUALS AB We investigated the effect of IL-10 on replication of primary CXCR4-dependent (X4) HIV-1 strains by monocyte-derived dendritic cells (DCs) and macrophages (M Phis). M Phis efficiently replicated CXCR4-dependent HIV-1 (X4 HIV-1) strains NDK and VN44, whereas low levels of p24 were detected in supernatants of infected DCs. IL-10 significantly increased X4 HIV-I replication by DCs but blocked viral production by M Phis as determined by p24 levels and semiquantitative nested PCR. IL-IO up-regulated CXCR4 mRNA and protein expression on DCs and M Phis, suggesting that IL-IO enhances virus entry in DCs but blocks an entry and/or postentry step in M Phis. The effect of IL-IO on the ability of DCs and M Phis to transmit virus to autologous CD4(+) T lymphocytes was investigated in coculture experiments. DCs exhibited a greater ability than did M Phis to transmit a vigorous infection to CD4(+) T cells despite their very low replication capacity, IL-IO had no effect on HIV-1 replication in DC:T cell cocultures but markedly decreased viral production in M Phi :T cell cocultures. These results demonstrate that IL-IO has opposite effects on the replication of primary X4 HIV-I strains by DCs and M Phis. IL-10 increases X4-HIV-1 replication in DCs but does not alter their capacity to transmit virus to CD4(+) T lymphocytes. These findings suggest that increased levels of IL-10 observed in HIV-l-infected patients with disease progression may favor the replication of X4 HIV-1 strains in vivo. C1 Hop Broussais, INSERM U430, Unite Immunopathol Humaine, F-75674 Paris 14, France. Fac Med St Antoine, INSERM E0013, Paris, France. Fac Sci, Lab Biochim Immunol, JER 3012 AUPELF, Rabat, Morocco. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Ancuta, P (reprint author), Hop Broussais, INSERM U430, Unite Immunopathol Humaine, 96 Rue Didot, F-75674 Paris 14, France. RI Haeffner-Cavaillon, Nicole/A-1921-2013 OI Haeffner-Cavaillon, Nicole/0000-0002-1703-8561 NR 75 TC 32 Z9 34 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2001 VL 166 IS 6 BP 4244 EP 4253 PG 10 WC Immunology SC Immunology GA 410JW UT WOS:000167437700081 PM 11238678 ER PT J AU Rao, VLR Dogan, A Todd, KG Bowen, KK Kim, BT Rothstein, JD Dempsey, RJ AF Rao, VLR Dogan, A Todd, KG Bowen, KK Kim, BT Rothstein, JD Dempsey, RJ TI Antisense knockdown of the glial glutamate transporter GLT-1, but not the neuronal glutamate transporter EAAC1, exacerbates transient focal cerebral ischemia-induced neuronal damage in rat brain SO JOURNAL OF NEUROSCIENCE LA English DT Article DE antisense knockdown; EAAC1; focal cerebral ischemia; GLT-1; glutamate transporters; middle cerebral artery occlusion; neuronal damage; stroke ID ARTERY OCCLUSION; IN-VIVO; RELEASE; INJURY; EXPRESSION; STRIATUM; GLAST; DEATH; LOCALIZATION; HIPPOCAMPUS AB Transient focal cerebral ischemia leads to extensive neuronal damage in cerebral cortex and striatum. Normal functioning of glutamate transporters clears the synaptically released glutamate to prevent excitotoxic neuronal death. This study evaluated the functional role of the glial (GLT-1) and neuronal (EAAC1) glutamate transporters in mediating ischemic neuronal damage after transient middle cerebral artery occlusion (MCAO). Transient MCAO in rats infused with GLT-1 antisense oligodeoxynucleotides (ODNs) led to increased infarct volume (45 +/- 8%; p < 0.05), worsened neurological status, and in-creased mortality rate, compared with GLT-1 sense/random ODN-infused controls. Transient MCAO in rats infused with EAAC1 antisense ODNs had no significant effect on any of these parameters. This study suggests that GLT-1, but not EAAC1, knockdown exacerbates the neuronal death and thus neurological deficit after stroke. C1 Univ Wisconsin, Dept Neurol Surg, Madison, WI 53792 USA. Univ Wisconsin, Cardiovasc Res Ctr, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Hosp, Madison, WI 53792 USA. Univ Alberta, Dept Psychiat, Edmonton, AB T6G 2B7, Canada. Soonchunhyang Univ, Dept Neurosurg, Seoul, South Korea. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA. RP Rao, VLR (reprint author), Univ Wisconsin, Dept Neurol Surg, F4-309 CSC,600 Highland Ave, Madison, WI 53792 USA. RI rothstein, jeffrey/C-9470-2013 FU NINDS NIH HHS [NS28000, NS31220] NR 44 TC 150 Z9 159 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 15 PY 2001 VL 21 IS 6 BP 1876 EP 1883 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 410CJ UT WOS:000167422200010 PM 11245672 ER PT J AU Rosen, FS AF Rosen, FS TI Summon up the blood: In dogged pursuit of the blood cell regulators SO NATURE LA English DT Book Review C1 Ctr Blood Res, Boston, MA 02115 USA. RP Rosen, FS (reprint author), Ctr Blood Res, Warren Alpert Bldg,200 Longwood Ave, Boston, MA 02115 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 15 PY 2001 VL 410 IS 6826 BP 302 EP 303 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 410WM UT WOS:000167464100018 ER PT J AU Freedberg, KA Losina, E Weinstein, MC Paltiel, AD Cohen, CJ Seage, GR Craven, DE Zhang, H Kimmel, AD Goldie, SJ AF Freedberg, KA Losina, E Weinstein, MC Paltiel, AD Cohen, CJ Seage, GR Craven, DE Zhang, H Kimmel, AD Goldie, SJ TI The cost effectiveness of combination antiretroviral therapy for HIV disease. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; IMMUNODEFICIENCY-VIRUS INFECTION; MYCOBACTERIUM-AVIUM COMPLEX; PLUS INDINAVIR; PROPHYLAXIS; ZIDOVUDINE; ADULTS; TRIAL; PREVENTION; LAMIVUDINE AB Background: Combination antiretroviral therapy with a combination of three or more drugs has become the standard of care for patients with human immunodeficiency virus (HIV) infection in the United States. We estimated the clinical benefits and cost effectiveness of three-drug antiretroviral regimens. Methods: We developed a mathematical simulation model of HIV disease, using the CD4 cell count and HIV RNA level as predictors of the progression of disease. Outcome measures included life expectancy, life expectancy adjusted for the quality of life, lifetime direct medical costs, and cost effectiveness in dollars per quality-adjusted year of life gained. Clinical data were derived from major clinical trials, including the AIDS Clinical Trials Group 320 Study. Data on costs were based on the national AIDS Cost and Services Utilization Survey, with drug costs obtained from the Red Book. Results: For patients similar to those in the AIDS Clinical Trials Group 320 Study (mean CD4 cell count, 87 per cubic millimeter), life expectancy adjusted for the quality of life increased from 1.53 to 2.91 years, and per-person lifetime costs increased from $45,460 to $77,300 with three-drug therapy as compared with no therapy. The incremental cost per quality-adjusted year of life gained, as compared with no therapy, was $23,000. On the basis of additional data from other major studies, the cost-effectiveness ratio for three-drug therapy ranged from $13,000 to $23,000 per quality-adjusted year of life gained. The initial CD4 cell count and drug costs were the most important determinants of costs, clinical benefits, and cost effectiveness. Conclusions: Treatment of HIV infection with a combination of three antiretroviral drugs is a cost-effective use of resources. (N Engl J Med 2001;344:824-31.) Copyright (C) 2001 Massachusetts Medical Society. C1 Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Ctr Risk Anal, Boston, MA 02115 USA. Community Res Initiat New England, Boston, MA USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Boston Med Ctr, Dept Med, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Freedberg, KA (reprint author), Massachusetts Gen Hosp, Div Gen Internal Med, 50 Staniford St,9th Fl, Boston, MA 02114 USA. FU NIAID NIH HHS [UO1 AI.8838, R01 AI042006, R01 AI058736, R01-AI42006]; PHS HHS [U64/CCU 114927] NR 47 TC 328 Z9 334 U1 4 U2 15 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 15 PY 2001 VL 344 IS 11 BP 824 EP 831 DI 10.1056/NEJM200103153441108 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 410LA UT WOS:000167440400008 PM 11248160 ER PT J AU Intano, GW McMahan, CA Walter, RB McCarrey, JR Walter, CA AF Intano, GW McMahan, CA Walter, RB McCarrey, JR Walter, CA TI Mixed spermatogenic germ cell nuclear extracts exhibit high base excision repair activity SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA-POLYMERASE-BETA; STRAND BREAK REPAIR; LIGASE-III; POLY(ADP-RIBOSE) POLYMERASE; MORPHOLOGICAL CHARACTERIZATION; DIFFERENTIAL EXPRESSION; MEIOTIC RECOMBINATION; MOLECULAR-CLONING; MAMMALIAN-CELLS; TRANSGENIC MICE AB Spermatogenic cells exhibit a lower spontaneous mutation frequency than somatic tissues in a lad transgene and many base excision repair (BER) genes display the highest observed level of expression-in the:testis. In this study, uracil-DNA glycosylase-initiated BER activity was measured in nuclear extracts prepared from tissues obtained from each of three mouse strains, Extracts from mixed spermatogenic germ cells displayed the greatest activity followed by liver then brain for all three strains, and the activity for a given tissue was consistent among the three strains, Levels of various BER proteins were examined by western blot analyses and-found to be consistent with activity levels. Nuclear extracts prepared from purified Sertoli cells, a somatic component of the seminiferous epithelium, exhibited significantly lower activity than mixed spermatogenic cell-type nuclear extracts, thereby suggesting that the high BER activity observed in mixed germ cell nuclear extracts was not a characteristic of all testicular cell types, Nuclear extracts from: thymocytes and small intestines were assayed to assess activity in a mitotically active cell type: and tissue. Overall, the order of tissues/cells exhibiting the greatest to lowest activity was mixed germ cells > Sertoli cells > thymocytes > small intestine > liver > brain. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. SW Texas State Univ, Dept Chem & Biochem, San Marcos, TX 78666 USA. SW Fdn Biomed Res, Dept Genet, San Marcos, TX 78245 USA. Audie L Murphy Mem Vet Hosp, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. RP Walter, CA (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, Mail Code 7762,7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NIA NIH HHS [AG14674, AG00205, T32 AG000205, AG13560]; NIEHS NIH HHS [ES09136] NR 62 TC 36 Z9 36 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAR 15 PY 2001 VL 29 IS 6 BP 1366 EP 1372 DI 10.1093/nar/29.6.1366 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 411ZH UT WOS:000167529200013 PM 11239003 ER PT J AU Fischman, AJ Bonab, AA Babich, JW Livni, E Alpert, NM Meltzer, PC Madras, BK AF Fischman, AJ Bonab, AA Babich, JW Livni, E Alpert, NM Meltzer, PC Madras, BK TI [C-11,I-127] altropane: A highly selective ligand for PET imaging of dopamine transporter sites SO SYNAPSE LA English DT Article DE dopamine neurons; movement disorders; cocaine; Parkinson disease; SPECT imaging; WIN 35,428 ID POSITRON-EMISSION-TOMOGRAPHY; I-123 BETA-CIT; COCAINE RECOGNITION SITES; MONOAMINE REUPTAKE SITES; HEALTHY-HUMAN SUBJECTS; CFT WIN 35,428; LIVING HUMAN BRAIN; PARKINSONS-DISEASE; PRIMATE BRAIN; MONKEY BRAIN AB The E isomer of I-123-2 beta -carbomethoxy-3 beta-(4-fluorophenyl)prop-1-en-3-yl)nortropane (Altropane(R)) shows high affinity (IC50 = 6.62 +/- 0.78 nmol) and selectivity (DA/5-HT = 25) for DAT sites in the striatum. Recently, dynamic SPECT studies in healthy volunteers and patients with Parkinson disease demonstrated that the kinetics of striatal accumulation followed a pattern that is characteristic of a reversible tracer with maximal accumulation within 30 min after injection. These findings suggested that radiolabeling Altropane with [C-11] might provide an equivalent and complementary tracer for PET studies. [I-127] Altropane was treated with HCl to hydrolyze the methyl ester bond and yield a precursor for [C-11] labeling. Introduction of an [C-11] methyl ester group was achieved by treatment with [C-11] CH3I followed by HPLC purification. Five healthy rhesus monkeys were injected with similar to 10 mCi of [I-127,C-11] Altropane and dynamic PET images were acquired over 90 min. Arterial blood samples were collected in parallel with imaging and metabolite analysis was performed by HPLC. The PET and metabolite corrected arterial blood data were to calculate k(3)/k(4) by two methods: 1) nonlinear least-squares fitting, and 2) a linear graphical method for reversible ligands. The synthetic procedure yielded high specific activity tracer, >1,000 mCi/mu mole, with radiochemical purity >95%. Synthesis time was similar to 30 min. The PET images revealed excellent striatal definition, with clear separation of caudate nucleus and putamen and minimal accumulation in brain regions with high 5HT transporter density. Metabolite analysis demonstrated that at 60 min after injection, similar to 80% of circulating tracer was intact [I-127,C-11] Altropane and the remainder was converted to polar metabolites. Values for k(3)/k(4) calculated by two analysis methods were remarkably similar: Method 1, 3.48 +/- 0.41; Method 2, 3.77 +/- 0.45 (mean +/- SEM, t = 2.31, df = 8, P = 0.64). These results establish that Altropane has the important characteristics of: 1) rapid and specific striatal binding; 2) high selectivity for DA vs. 5-HT transporter sites; 3) reversible binding kinetics; 4) potential for multiple injection studies; 5) high efficiency labeling with either [C-11] or [I-123]; 6) applicability for both PET and SPECT. These properties make Altropane an important DAT ligand for both research and clinical applications. Synapse 39:332-342, 2001, (C) 2001 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Organix Inc, Woburn, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Div Neurochem,New England Reg Primate Res Ctr, Southborough, MA 01772 USA. RP Fischman, AJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, 32 Fruit St, Boston, MA 02114 USA. FU NIDA NIH HHS [DA 11558, DA 00304, DA 06303] NR 61 TC 41 Z9 41 U1 1 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD MAR 15 PY 2001 VL 39 IS 4 BP 332 EP 342 DI 10.1002/1098-2396(20010315)39:4<332::AID-SYN1017>3.0.CO;2-X PG 11 WC Neurosciences SC Neurosciences & Neurology GA 396YR UT WOS:000166666300008 PM 11169784 ER PT J AU Crespo, M Pascual, M Tolkoff-Rubin, N Mauiyyedi, S Collins, AB Fitzpatrick, D Farrell, ML Williams, WW Delmonico, FL Cosimi, AB Colvin, RB Saidman, SL AF Crespo, M Pascual, M Tolkoff-Rubin, N Mauiyyedi, S Collins, AB Fitzpatrick, D Farrell, ML Williams, WW Delmonico, FL Cosimi, AB Colvin, RB Saidman, SL TI Acute humoral rejection in renal allograft recipients: I. Incidence, serology and clinical characteristics SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 1st Joint Meeting of the American-Society-of-Transplantation/American-Society-of-Transplant-Surge ons CY MAY 13-17, 2000 CL CHICAGO, ILLINOIS SP Amer Soc Transplantat, Amer Transplant Surgeons ID CROSS-MATCH; PATHOLOGICAL FEATURES; GRAFT-REJECTION; KIDNEY-TRANSPLANTATION; MEDIATED REJECTION; FLOW-CYTOMETRY; ANTIBODY; COMPLEMENT; ACTIVATION; INDUCTION AB Background. Acute rejection (AR) associated with de novo production of donor-specific antibodies (DSA) is a clinicopathological entity that carries a poor prognosis (acute humoral rejection, AHR), The aim of this study was to determine the incidence and clinical characteristics of AHR in renal allograft recipients, and to further analyze the antibodies involved. Methods. During a 4-year period, 232 renal transplants (Tx) were performed at our institution. Assays for DSA included T and B cell cytotoxic and/or flow cytometric cross-matches and cytotoxic antibody screens (PRA), C4d complement staining was performed on frozen biopsy tissue. Results. A total of 81 patients (35%) suffered at least one episode of AR within the first 3 months: 51 had steroid-insensitive AR whereas the remaining 30 had steroid-sensitive AR. No DSA were found in patients with steroid-sensitive AR. In contrast, circulating DSA were found in 19/51 patients (37%) with steroid-insensitive AR, and widespread C4d deposits in peritubular capillaries were present in 18 of these 19 (95%), In at least three cases, antibodies were against donor HLA class II antigens. DSA were not found in the remaining 32 patients but C4d staining was positive in 2 of 32. The DSA/C4d positive (n=18) and DSA/C4d negative (n=30) groups differed in pre-Tx PRA levels, percentage of re-Tx patients, refractoriness to antilymphocyte therapy, and outcome. Plasmapheresis and tacrolimus-mycophenolate mofetil rescue reversed rejection in 9 of 10 recipients with refractory AHR, Conclusion. More than one-third of the patients with steroid-insensitive AR had evidence of AHR, often resistant to antilymphocyte therapy. Most cases (95%) with DSA at the time of rejection had widespread C4d deposits in peritubular capillaries, suggesting a pathogenic role of the circulating alloantibody, Combined DSA testing and C4d staining provides a useful approach for the early diagnosis of AHR, a condition that often necessitates a more intensive therapeutic rescue regimen. C1 Massachusetts Gen Hosp, Histocompatibil Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Saidman, SL (reprint author), Massachusetts Gen Hosp, Histocompatibil Lab, Room White 544,55 Fruit St, Boston, MA 02114 USA. OI Crespo, Marta/0000-0001-6992-6379 NR 36 TC 251 Z9 272 U1 0 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 MAR 15 PY 2001 VL 71 IS 5 BP 652 EP 658 DI 10.1097/00007890-200103150-00013 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 419KC UT WOS:000167947000013 PM 11292296 ER PT J AU Zhang, BM Kohli, V Adachi, R Lopez, JA Udden, MM Sullivan, R AF Zhang, BM Kohli, V Adachi, R Lopez, JA Udden, MM Sullivan, R TI Calmodulin binding to the C-terminus of the small-conductance Ca2+-activated K+ channel hSK1 is affected by alternative splicing SO BIOCHEMISTRY LA English DT Article ID ACTIVATED POTASSIUM CHANNELS; HUMAN T-LYMPHOCYTES; RED-CELLS; ERYTHROCYTES; RECEPTORS; PROTEINS; KINASE; GENE AB We identified three splice variants of hSK1 whose C-terminal structures are determined by the independent deletion of two contiguous nucleotide sequences. The upstream sequence extends 25 bases in length, is initiated by a donor splice site within exon 8, and terminates at the end of the exon. The downstream sequence consists of nine bases that compose exon 9, When the upstream sequence (hSK1(-25b)) Or both sequences (hSK1(-34h)), deleted, truncated proteins are encoded in which the terminal 118 amino acids are absent. The binding of calmodulin to these variants is diminished, particularly in the absence of Ca2+ ions. The first 20 amino acids of the segment deleted from hSK1(-25b) and hSK1(-34b) contain a 1-8-14 Ca2+-calmodulin binding motif, and synthetic oligopeptides based on this region bind calmodulin better in the presence than absence of Ca2+ ions. When the downstream sequence (hSK1(-9b)) alone is deleted, only the three amino acids A452, Q453, and K454, are removed, and calmodulin binding is not reduced. On the basis of the relative abundance of mRNA encoding each of the four isoforms, the full-length variant appears to account for most hSK1 in the human hippocampus, while hSK1(-34b) predominates in reticulocytes, and hSK1(-9b) is especially abundant in human erythroleukemia cells in culture. We conclude that the binding of calmodulin by hSK1 can be modulated through alternative splicing. C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol Physiol & Biophys, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol Genet, Houston, TX 77030 USA. VA Med Ctr, Res Dept, Houston, TX 77030 USA. RP Sullivan, R (reprint author), Houston VA Med Ctr, Mail Stop 111H,2002 Holcombe, Houston, TX 77030 USA. FU NHLBI NIH HHS [HL 54218] NR 26 TC 17 Z9 18 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 13 PY 2001 VL 40 IS 10 BP 3189 EP 3195 DI 10.1021/bi001675h PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 409VU UT WOS:000167407000022 PM 11258935 ER PT J AU Lethor, JP de Moor, M AF Lethor, JP de Moor, M TI Multiple cardiac tumors in the fetus SO CIRCULATION LA English DT Editorial Material C1 Cardiol Infantile CHU Nancy, F-54511 Vandoeuvre Nancy, France. Massachusetts Gen Hosp, Pediat Cardiol Unit, Boston, MA 02114 USA. RP Lethor, JP (reprint author), Cardiol Infantile CHU Nancy, Rue Morvan, F-54511 Vandoeuvre Nancy, France. NR 0 TC 5 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 13 PY 2001 VL 103 IS 10 BP E55 EP E55 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 413XJ UT WOS:000167636600001 PM 11245658 ER PT J AU Fanin, M Pegoraro, E Matsuda-Asada, C Brown, RH Angelini, C AF Fanin, M Pegoraro, E Matsuda-Asada, C Brown, RH Angelini, C TI Calpain-3 and dysferlin protein screening in patients with limb-girdle dystrophy and myopathy SO NEUROLOGY LA English DT Article ID MUSCULAR-DYSTROPHY; MIYOSHI MYOPATHY; GENETIC FEATURES; CHROMOSOME 2P; MUTATIONS; EXPRESSION; 2A; DEFICIENCY; POPULATION; LINKAGE AB Background: Mutations in the genes encoding for calpain-3 and dysferlin are responsible for limb-girdle muscular dystrophy (LGMD) type 2A and 2B, the most common forms of autosomal recessive LGMD. Objective: To identify calpain-3 or dysferlin deficiency in a large cohort of patients with as yet unclassified LGMD and myopathy through candidate protein analysis. Methods: The authors' muscle biopsy database search identified 407 candidate muscle biopsies with normal dystrophin and sarcoglycan. Calpain-3 and dysferlin were studied by Western blotting and immunohistochemistry. Results: Combined calpain-3 and dysferlin Western blot analysis identified calpain-3 deficiency in 66 (16%) muscle biopsies. In 31 cases (47%), the protein was absent, and in 35 (53%), it was severely reduced in amount (3 to 50% of control). Dysferlin deficiency was found in 26 (6.5%) muscle biopsies. In 9, the protein was absent (35%), and in 17 (65%), it was severely reduced in amount (traces to 20% of control). Twenty-eight percent (53/191) of patients with LGMD phenotype had calpain-3 deficiency, Sixty percent (21/35) of patients with distal myopathy had dysferlin deficiency. Dysferlin immunohistochemistry showed, in the completely dysferlin-deficient patients, absent reaction at the sarcolemma but positive nuclear membrane labeling and, in the partially dysferlin-deficient patients, scattered granular positive cytoplasmic areas and diffuse reaction in regenerating fibers. Conclusion: About 25% of previously unclassified dystrophy/ myopathy cases are due to calpain-3 or dysferlin protein deficiency. These results suggest that immunoblot analysis may be used to define patients for calpain-3 and dysferlin gene mutation studies. C1 Univ Padua, Dept Neurol & Psychiat Sci, Neuromuscular Ctr, I-35128 Padua, Italy. Massachusetts Gen Hosp, Cecil B Day Lab Neuromuscular Res, Charlestown, MA USA. RP Fanin, M (reprint author), Univ Padua, Dept Neurol & Psychiat Sci, Neuromuscular Ctr, Via Giustiniani 5, I-35128 Padua, Italy. OI Angelini, Corrado/0000-0002-9554-8794 FU Telethon [1114, C.54] NR 31 TC 45 Z9 46 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 13 PY 2001 VL 56 IS 5 BP 660 EP 665 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 409ZF UT WOS:000167415000017 PM 11245721 ER PT J AU Stephen, AE Masiakos, PT Segev, DL Vacanti, JP Donahoe, PK MacLaughlin, DT AF Stephen, AE Masiakos, PT Segev, DL Vacanti, JP Donahoe, PK MacLaughlin, DT TI Tissue-engineered cells producing complex recombinant proteins inhibit ovarian cancer in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE tissue engineering; Mullerian Inhibiting Substance ID ANTI-MULLERIAN HORMONE; HUMAN-TUMOR XENOGRAFTS; GROWTH FACTOR-BETA; FOLLICULAR-FLUID; COLONY GROWTH; II RECEPTOR; NUDE-MICE; SUBSTANCE; EXPRESSION; TRANSPLANTATION AB Techniques of tissue engineering and cell and molecular biology were used to create a biodegradable scaffold for transfected cells to produce complex proteins. Mullerian Inhibiting Substance (MIS) causes regression of Mullerian ducts in the mammalian embryo. MIS also causes regression in vitro of ovarian tumor cell lines and primary cells from ovarian carcinomas, which derive from Mullerian structures. In a strategy to circumvent the complicated purification protocols for MIS, Chinese hamster ovary cells transfected with the human MIS gene were seeded onto biodegradable polymers of polyglycolic acid fibers and secretion of MIS confirmed. The polymer-cell graft was implanted into the right ovarian pedicle of severe combined immunodeficient mice. Serum MIS in the mice rose to supraphysiologic levels over time. One week after implantation of the polymer-cell graft, IGROV-1 human tumors were implanted under the renal capsule of the left kidney. Growth of the IGROV-1 tumors was significantly inhibited in the animals with a polymer-cell graft of MIS-producing cells, compared with centrols. This novel MIS delivery system could have broader applications for other inhibitory agents not amenable to efficient purification and provides in vivo evidence for a role of MIS in the treatment of ovarian cancer. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Res Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Tissue Engn & Organ Fabricat, Boston, MA 02114 USA. RP MacLaughlin, DT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Surg Res Lab, Boston, MA 02114 USA. FU NCI NIH HHS [T32 CA071345, CA71345-04, F32 CA077945, F32 CA77945-01A1, R01 CA017393, R01 CA17393, T32 CA71345] NR 43 TC 21 Z9 22 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 13 PY 2001 VL 98 IS 6 BP 3214 EP 3219 DI 10.1073/pnas.051625998 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 411WB UT WOS:000167521300052 PM 11248058 ER PT J AU Sekiguchi, J Ferguson, DO Chen, HT Yang, EM Earle, J Frank, K Whitlow, S Gu, YS Xu, Y Nussenzweig, A Alt, FW AF Sekiguchi, J Ferguson, DO Chen, HT Yang, EM Earle, J Frank, K Whitlow, S Gu, YS Xu, Y Nussenzweig, A Alt, FW TI Genetic interactions between ATM and the nonhomologous end-joining factors in genomic stability and development SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DNA-LIGASE-IV; STRAND BREAK REPAIR; CENTRAL-NERVOUS-SYSTEM; V(D)J RECOMBINATION; ATAXIA-TELANGIECTASIA; DEPENDENT PHOSPHORYLATION; CHROMOSOMAL-ABERRATIONS; DEFECTIVE NEUROGENESIS; TARGETED DISRUPTION; EMBRYONIC LETHALITY AB DNA ligase IV (Lig4) and the DNA-dependent protein kinase (DNA-PK) function in nonhomologous end joining (NHEJ). However, although Lig4 deficiency causes late embryonic lethality, deficiency in DNA-PK subunits (Ku70, Ku80, and DNA-PKcs) does not. Here we demonstrate that, similar to p53 deficiency, ataxia-telangiectasia-mutated (ATM) gene deficiency rescues the embryonic lethality and neuronal apoptosis, but not impaired lymphocyte development, associated with Lig4 deficiency. However, in contrast to p53 deficiency, ATM deficiency enhances deleterious effects of Lig4 deficiency on growth potential of embryonic fibroblasts (MEFs) and genomic instability in both MEFs and cultured progenitor lymphocytes, demonstrating significant differences in the interplay of p53 vs. ATM with respect to NHEJ. Finally, in dramatic contrast to effects on Lig4 deficiency, ATM deficiency causes early embryonic lethality in Ku- or DNA-PKcs-deficient mice, providing evidence for an NHEJ-independent role for the DNA-PK holoenzyme. C1 Childrens Hosp, Harvard Med Sch, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Alt, FW (reprint author), Childrens Hosp, Harvard Med Sch, 300 Longwood Ave,Enders 861, Boston, MA 02115 USA. OI Sekiguchi, JoAnn/0000-0002-7178-4258 FU NCI NIH HHS [R01 CA077563, CA77563]; NIAID NIH HHS [R01 AI020047, AI35714, AI01428, AI20047, P01 AI035714, R37 AI020047] NR 39 TC 107 Z9 108 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 13 PY 2001 VL 98 IS 6 BP 3243 EP 3248 DI 10.1073/pnas.051632098 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 411WB UT WOS:000167521300057 PM 11248063 ER PT J AU Lee, RS Yamada, K Houser, SL Womer, KL Maloney, ME Rose, HS Sayegh, MH Madsen, JC AF Lee, RS Yamada, K Houser, SL Womer, KL Maloney, ME Rose, HS Sayegh, MH Madsen, JC TI Indirect recognition of allopeptides promotes the development of cardiac allograft vasculopathy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; TRANSPLANTED MOUSE HEARTS; CHRONIC REJECTION; MINIATURE SWINE; INTERFERON-GAMMA; ARTERIOSCLEROSIS; MECHANISMS; ALLORECOGNITION; ATHEROSCLEROSIS; COSTIMULATION AB Graft loss from chronic rejection has become the major obstacle to the long-term success of whole organ transplantation. In cardiac allografts, chronic rejection is manifested as a diffuse and accelerated form of arteriosclerosis, termed cardiac allograft vasculopathy. It has been suggested that T-cell recognition of processed alloantigens (allopeptides) presented by recipient antigen-presenting cells through the indirect pathway of allorecognition plays a critical role in the development and progression of chronic rejection. However, definitive preclinical evidence to support this hypothesis is lacking. To examine the role of indirect allorecognition in a clinically relevant large animal model of cardiac allograft vasculopathy, we immunized MHC inbred miniature swine with synthetic polymorphic peptides spanning the alpha (1) domain of an allogeneic donor-derived swine leukocyte antigen class I gene, Pigs immunized with swine leukocyte antigen class I allopeptides showed in vitro proliferative responses and in vivo delayed-type hypersensitivity responses to the allogeneic peptides. Donor MHC class I disparate hearts transplanted into peptide-immunized cyclosporine-treated pigs not only rejected faster than unimmunized cyclosporine-treated controls (mean survival time = 5.5 +/- 1.7 vs. 54.7 +/- 3,8 days, P < 0.001), but they also developed obstructive fibroproliferative coronary artery lesions much earlier than unimmunized controls (<9 vs. >30 days), These results definitively link indirect allorecognition and cardiac allograft vasculopathy. C1 Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Brigham & Womens Hosp, Lab Immunogenet & Transplantat, Boston, MA 02115 USA. RP Madsen, JC (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Cardiac Surg, EDR 105, Boston, MA 02114 USA. FU NHLBI NIH HHS [2RO1-HL54211-04, R01 HL054211] NR 39 TC 90 Z9 92 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 13 PY 2001 VL 98 IS 6 BP 3276 EP 3281 DI 10.1073/pnas.051584498 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 411WB UT WOS:000167521300063 PM 11248069 ER PT J AU De Windt, LJ Lim, HW Bueno, OF Liang, QR Delling, U Braz, JC Glascock, BJ Kimball, TF del Monte, F Hajjar, RJ Molkentin, JD AF De Windt, LJ Lim, HW Bueno, OF Liang, QR Delling, U Braz, JC Glascock, BJ Kimball, TF del Monte, F Hajjar, RJ Molkentin, JD TI Targeted inhibition of calcineurin attenuates cardiac hypertrophy in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LEFT-VENTRICULAR HYPERTROPHY; PRESSURE-OVERLOAD HYPERTROPHY; ADENOVIRAL GENE-TRANSFER; HEART-FAILURE; SIGNALING PATHWAYS; DOWN-SYNDROME; RAT HEARTS; PROTEIN; CYCLOSPORINE; HYPERTENSION AB The Ca(2+)-calmodulin-activated Ser/Thr protein phosphatase calcineurin and the downstream transcriptional effecters of calcineurin, nuclear factor of activated T cells, have been implicated in the hypertrophic response of the myocardium. Recently, the calcineurin inhibitory agents cyclosporine A and FK506 have been extensively used to evaluate the importance of this signaling pathway in rodent models of cardiac hypertrophy. However, pharmacologic approaches have rendered equivocal results necessitating more specific or genetic-based inhibitory strategies. In this regard, we have generated Tg mice expressing the calcineurin inhibitory domains of Cain/Cabin-1 and A-kinase anchoring protein 79 specifically in the heart. Delta Cain and DeltaA-kinase-anchoring protein Tg mice demonstrated reduced cardiac calcineurin activity and reduced hypertrophy in response to catecholamine infusion or pressure overload. In a second approach, adenoviral-mediated gene transfer of Delta Cain was performed in the adult rat myocardium to evaluate the effectiveness of an acute intervention and any potential species dependency. Delta Cain adenoviral gene transfer inhibited cardiac calcineurin activity and reduced hypertrophy in response to pressure overload without reducing aortic pressure. These results provide genetic evidence implicating calcineurin as an important mediator of the cardiac hypertrophic response in vivo. C1 Childrens Hosp, Med Ctr, Div Mol Cardiovasc Biol, Dept Pediat, Cincinnati, OH 45229 USA. Childrens Hosp, Med Ctr, Div Cardiol, Dept Pediat, Cincinnati, OH 45229 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Molkentin, JD (reprint author), Childrens Hosp, Med Ctr, Div Mol Cardiovasc Biol, Dept Pediat, 3333 Burnet Ave, Cincinnati, OH 45229 USA. EM molkj0@chmcc.org FU NHLBI NIH HHS [R01 HL062927, HL50361, HL52318, HL57623, HL62927, HL69562, P50 HL052318] NR 44 TC 129 Z9 130 U1 2 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 MAR 13 PY 2001 VL 98 IS 6 BP 3322 EP 3327 DI 10.1073/pnas.031371998 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 411WB UT WOS:000167521300071 PM 11248077 ER PT J AU Lee, KH Rudolph, KL Ju, YJ Greenberg, RA Cannizzaro, L Chin, L Weiler, SR DePinho, RA AF Lee, KH Rudolph, KL Ju, YJ Greenberg, RA Cannizzaro, L Chin, L Weiler, SR DePinho, RA TI Telomere dysfunction alters the chemotherapeutic profile of transformed cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TUMOR-SUPPRESSOR GENE; P53-DEPENDENT APOPTOSIS; HOMOLOGOUS RECOMBINATION; MOUSE TELOMERASE; P53 MUTATIONS; STRAND BREAKS; LIFE-SPAN; CANCER; P19(ARF); MDM2 AB Telomerase inhibition has been touted as a novel cancer-selective therapeutic goal based on the observation of high telomerase levels in most cancers and the importance of telomere maintenance in long-term cellular growth and survival. Here, the impact of telomere dysfunction on chemotherapeutic responses was assessed in normal and neoplastic cells derived from telomerase RNA null (mTERC(-/-)) mice. Telomere dysfunction, rather than telomerase per se, was found to be the principal determinant governing chemosensitivity specifically to agents that induced double-stranded DNA breaks (DSB). Enhanced chemosensitivity in telomere dysfunctional cells was linked to therapy-induced fragmentation and multichromosomal fusions, whereas telomerase reconstitution restored genomic integrity and chemoresistance. Loss of p53 function muted the cytotoxic effects of DSB-inducing agents in cells with telomere dysfunction. Together, these results point to the combined use of DSB-inducing agents and telomere maintenance inhibition as an effective anticancer therapeutic approach particularly in cells with intact p53-depdendent checkpoint responses. C1 Harvard Univ, Sch Med, Dept Adult Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Korea Canc Ctr Hosp, Mol Oncol Lab, Seoul 139240, South Korea. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Albert Einstein Coll Med, Montefiore Med Ctr, Dept Pathol, Bronx, NY 10461 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dept Adult Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. FU NIAMS NIH HHS [K08AR02104-01]; NICHD NIH HHS [R01HD28317, R01HD34880]; NIGMS NIH HHS [T32 GM007491, 5T32GM07491] NR 45 TC 100 Z9 107 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 13 PY 2001 VL 98 IS 6 BP 3381 EP 3386 DI 10.1073/pnas.051629198 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 411WB UT WOS:000167521300081 PM 11248087 ER PT J AU Trbovich, AM Sluss, PM Laurich, VM O'Neill, FH NacLaughlin, DT Donahoe, PK Teixeira, J AF Trbovich, AM Sluss, PM Laurich, VM O'Neill, FH NacLaughlin, DT Donahoe, PK Teixeira, J TI Mullerian Inhibiting Substance lowers testosterone in luteinizing hormone-stimulated rodents SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LEYDIG-CELLS; STEROIDOGENIC ENZYMES; SEXUAL DEVELOPMENT; TRANSGENIC MICE; OOCYTE MEIOSIS; EXPRESSION; RAT; DIFFERENTIATION; RECEPTORS; INVITRO AB Mullerian Inhibiting Substance (MIS) expression is inversely proportional to the serum concentration of testosterone in males after birth and in vitro studies have shown that MIS can lower testosterone production by Leydig cells. Also, mice overexpressing MIS exhibited Leydig cell hypoplasia and lower levels of serum testosterone, but it is not clear whether this is a result of MIS affecting the development of Leydig cells or their capacity to produce testosterone. To examine the hypothesis that MIS treatment will result in decreased testosterone production by mature Leydig cells in vivo, we treated luteinizing hormone (LH)-stimulated adult male rats and mice with MIS and demonstrated that it can lead to a several-fold reduction in testosterone in serum and in testicular extracts. There was also a slight decrease in 17-OH-progesterone compared to the more significant decrease in testosterone, suggesting that MIS might be regulating the lyase activity of cytochrome P450c17 hydroxylase/lyase (Cyp17), but not its hydroxylase activity. Northern analysis showed that, in both MIS-treated rats and mice, the mRNA for Cyp17, which catalyzes the committed step in androgen synthesis, was down-regulated. In rats, the mRNA for cytochrome P450 side-chain cleavage (P450scc) was also downregulated by MIS. This was not observed in mice, indicating that there might be species-specific regulation by MIS of the enzymes involved in the testosterone biosynthetic pathway. Our results show that MIS can be used in vivo to lower testosterone production by mature rodent Leydig cells and suggest that MIS-mediated down-regulation of the expression of Cyp17, and perhaps P450scc, contributes to that effect. C1 Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Teixeira, J (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Labs, 32 Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [R01 CA017393, R29CA79459, R01CA17393, R29 CA079459-02, R29 CA079459]; NICHD NIH HHS [U54 HD028138, U54HD28138] NR 30 TC 39 Z9 42 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 13 PY 2001 VL 98 IS 6 BP 3393 EP 3397 DI 10.1073/pnas.051632298 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 411WB UT WOS:000167521300083 PM 11248089 ER PT J AU Reynet, C Kahn, CR AF Reynet, C Kahn, CR TI Unbalanced expression of the different subunits of elongation factor 1 in diabetic skeletal muscle SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gene expression; insulin; diabetes mellitus ID ACTIN-BINDING PROTEIN; FACTOR 1-ALPHA; MESSENGER-RNA; FACTOR-I; INSULIN-RECEPTOR; GENE-EXPRESSION; FACTOR-1-ALPHA; TRANSLATION; HUMANS; CELLS AB In studies using subtraction cloning to screen for alterations in mRNA expression in skeletal muscle from humans with Type 2 diabetes mellitus and control subjects, one of the most prominent differences was in the mRNA for elongation factor (EF)-1 alpha. With Northern blot analysis, EF-1 alpha expression was enhanced by 2- to 6-fold in both Types 1 and 2 human diabetics, In contrast, no changes in expression of EF-1 beta or -gamma were noted. We observed similar results in animal models of Type 1 diabetes, EF-1 alpha expression, but not EF-1 beta or -gamma expression, was also enhanced in streptozotocin-induced diabetic rats, and this effect was reversed by insulin treatment, An increased level of EF-1 alpha mRNA was also observed in nonobese diabetic mice. This unbalanced regulation of the expression of the different subunits of EF-1 may contribute to alterations not only in protein synthesis but also in other cellular events observed in the diabetic state. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [P30 DK036836, DK 33201, DK 36836, R01 DK033201] NR 47 TC 12 Z9 13 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 13 PY 2001 VL 98 IS 6 BP 3422 EP 3427 DI 10.1073/pnas.051630398 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 411WB UT WOS:000167521300088 PM 11248094 ER PT J AU Vuilleumier, P Sagiv, N Hazeltine, E Poldrack, RA Swick, D Rafal, RD Gabrieli, JDE AF Vuilleumier, P Sagiv, N Hazeltine, E Poldrack, RA Swick, D Rafal, RD Gabrieli, JDE TI Neural fate of seen and unseen faces in visuospatial neglect: A combined event-related functional MRI and event-related potential study SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN EXTRASTRIATE CORTEX; PRIMARY VISUAL-CORTEX; HUMAN FUSIFORM GYRUS; UNILATERAL NEGLECT; SPATIAL NEGLECT; HUMAN BRAIN; PERCEPTION; ATTENTION; EXTINCTION; AWARENESS AB To compare neural activity produced by visual events that escape or reach conscious awareness, we used event-related MRI and evoked potentials in a patient who had neglect and extinction after focal right parietal damage, but intact visual fields. This neurological disorder entails a loss of awareness for stimuli in the field contralateral to a brain lesion when stimuli are simultaneously presented on the ipsilateral side, even though early visual areas may be intact, and single contralateral stimuli may still be perceived. Functional MRI and event-related potential study were performed during a task where faces or shapes appeared in the right, left, or both fields. Unilateral stimuli produced normal responses in V1 and extrastriate areas. In bilateral events, left faces that were not perceived still activated right V1 and inferior temporal cortex and evoked nonsignificantly reduced N1 potentials, with preserved face-specific negative potentials at 170 ms. When left faces were perceived, the same stimuli produced greater activity in a distributed network of areas including right V1 and cuneus, bilateral fusiform gyri, and left parietal cortex. Also, effective connectivity between visual, parietal, and frontal areas increased during perception of faces. These results suggest that activity can occur in V1 and ventral temporal cortex without awareness, whereas coupling with dorsal parietal and frontal areas may be critical for such activity to afford conscious perception. C1 UCL, Inst Cognit Neurosci, London WC1 3AR, England. Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA. Vet Adm Med Ctr, Martinez, CA 94553 USA. Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. NASA, Ames Res Ctr, Moffett Field, CA 94035 USA. Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Sch Psychol, Bangor LLS7 2DG, Gwynedd, Wales. RP Vuilleumier, P (reprint author), UCL, Inst Cognit Neurosci, Alexandra House,17 Queen Sq, London WC1 3AR, England. EM p.vuilleumier@ucl.ac.uk NR 49 TC 143 Z9 146 U1 4 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 MAR 13 PY 2001 VL 98 IS 6 BP 3495 EP 3500 DI 10.1073/pnas.051436898 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 411WB UT WOS:000167521300100 PM 11248106 ER PT J AU Xiao, YF Ke, QG Wang, SY Auktor, K Yang, YK Wang, GK Morgan, JP Leaf, A AF Xiao, YF Ke, QG Wang, SY Auktor, K Yang, YK Wang, GK Morgan, JP Leaf, A TI Single point mutations affect fatty acid block of human myocardial sodium channel a subunit Na+ channels SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE human cardiac Na+ channel; beta(1) subunit; polyunsaturated fatty acids ID LOCAL-ANESTHETICS; VENTRICULAR MYOCYTES; ANTIARRHYTHMIC DRUGS; ALPHA-SUBUNIT; BATRACHOTOXIN; RECEPTOR; INACTIVATION; COEXPRESSION; RESISTANT; BINDING AB Suppression of cardiac voltage-gated Naf currents is probably one of the important factors for the cardioprotective effects of the n-3 polyunsaturated fatty acids (PUFAs) against lethal arrhythmias. The a subunit of the human cardiac Na+ channel (hH1(alpha)) and its mutants were expressed in human embryonic kidney (HEK293t) cells. The effects of single amino acid point mutations on fatty acid-induced inhibition of the hH1(alpha) Na+ current (I-Na) were assessed. Eicosapentaenoic acid (EPA, C20:5n-3) significantly reduced INa in HEK293t cells expressing the wild type, Y1767K, and F1760K of hH1(alpha) Na+ channels. The inhibition was voltage and concentration-dependent with a significant hyperpolarizing shift of the steady state of IN,. In contrast, the mutant N406K was significantly less sensitive to the inhibitory effect of EPA. The values of the shift at 1, 5, and 10 muM EPA were significantly smaller for N406K than for the wild type. Coexpression of the beta (1) subunit and N406K further decreased the inhibitory effects of EPA on IN, in HEK293t cells. In addition, EPA produced a smaller hyperpolarizing shift of the V-1/2 of the steady-state inactivation in HEK293t cells coexpressing the pr subunit and N406K. These results demonstrate that substitution of asparagine with lysine at the site of 406 in the domain-1-segment-6 region (D1-56) significantly decreased the inhibitory effect of PUFAs on I-Na, and coexpression with beta (1) decreased this effect even more. Therefore, asparagine at the 406 site in hH1(alpha) may be important for the inhibition by the PUFAs of cardiac voltage-gated Na+ currents, which play a significant role in the antiarrhythmic actions of PUFAs. C1 Beth Israel Deaconess Med Ctr, Charles A Dana Res Inst, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Harvard Thorndike Lab, Div Cardiovasc, Dept Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. SUNY Albany, Dept Biol, Albany, NY 12222 USA. RP Leaf, A (reprint author), Massachusetts Gen Hosp, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL62284]; NIDA NIH HHS [DA11762]; NIDDK NIH HHS [DK38165]; NIGMS NIH HHS [GM35401] NR 25 TC 82 Z9 85 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 13 PY 2001 VL 98 IS 6 BP 3606 EP 3611 DI 10.1073/pnas.061003798 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 411WB UT WOS:000167521300119 PM 11248125 ER PT J AU Kohlwes, RJ Koepsell, TD Rhodes, LA Pearlman, RA AF Kohlwes, RJ Koepsell, TD Rhodes, LA Pearlman, RA TI Physicians' responses to patients' requests for physician-assisted suicide SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID WASHINGTON-STATE; TERMINALLY ILL; EUTHANASIA; OREGON; DEATH; EXPERIENCES; NETHERLANDS; DEPRESSION; ATTITUDES; CARE AB Background: Studies show that patient requests for physician-assisted suicide (PAS) are a relatively common clinical occurrence. The purpose of this study was to describe how experienced physicians assess and respond to requests for assisted suicide. Methods: Focused ethnography in the offices of 11 acquired immunodeficiency syndrome physicians, 8 oncologists, and 1 hospice physician who had received requests for assisted suicide in their practice. Ten had facilitated PAS. Results: Informants had a similar approach to evaluating patients who requested assisted suicide, often asking, "Why do you want to die now?" Reasons for requests fell into 3 broad categories: physical symptoms, psychological issues, and existential suffering. Physicians thought they competently addressed patients' physical symptoms, and this obviated most requests. They treated depression empirically and believed they did not assist depressed patients with assisted suicide. Physicians had difficult); addressing patients' existential suffering, which led to most facilitated requests. Informants rarely talked to colleagues about requests for assisted suicide, suggesting a "professional code of silence." Conclusions: Regardless of divergent attitudes about PAS, physicians respond similarly to requests for assisted suicide from their patients, creating a common ground for professional dialogue. Our sample addressed physical suffering aggressively, treated depression empirically, but struggled with requests arising from existential suffering. A professional code of silence regarding PAS creates professional isolation. Clinicians do not share knowledge or receive social support from peers about their decisions regarding assisted suicide. Educational strategies drawing on approaches used by experienced clinicians may create an atmosphere that enables physicians with divergent beliefs to discuss this difficult subject. C1 Univ Calif San Francisco, Vet Affairs Med Ctr, Dept Med, San Francisco, CA 94121 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Hlth Serv & Epidemiol, Seattle, WA 98195 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med Anthropol, Seattle, WA 98195 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98195 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med Hist & Eth, Seattle, WA 98195 USA. RP Kohlwes, RJ (reprint author), Univ Calif San Francisco, Vet Affairs Med Ctr, Dept Med, 4150 Clement St,Campus Box 111, San Francisco, CA 94121 USA. NR 28 TC 33 Z9 34 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 12 PY 2001 VL 161 IS 5 BP 657 EP 663 DI 10.1001/archinte.161.5.657 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 408QM UT WOS:000167339200003 PM 11231697 ER PT J AU Rhew, DC Tu, GS Ofman, J Henning, JM Richards, MS Weingarten, SR AF Rhew, DC Tu, GS Ofman, J Henning, JM Richards, MS Weingarten, SR TI Early switch and early discharge strategies in patients with community-acquired pneumonia - A meta-analysis SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 5th Annual International Meeting of the International-Society-for-Pharmacoeconomics-and-Outcomes-Research (ISPOR) CY MAY 23, 2000 CL WASHINGTON, D.C. SP Int soc Pharmacoecon & Outcomes Res ID PRACTICE GUIDELINE; THERAPY; ANTIBIOTICS; OUTCOMES; DURATION; TRIAL; COST AB Background: The effectiveness of early switch and early discharge strategies in patients with community-acquired pneumonia remains unknown. Methods: We searched the MEDLINE, HEALTHSTAR, EMBASE, Cochrane Collaboration, and Best Evidence databases from January 1, 1980, to March 31, 2000, for community-acquired pneumonia studies that included specific switch criteria or recommendations to switch on a particular day. Results: From 1794 titles identified, 121 articles were reviewed. We identified 10 prospective, interventional, community-acquired pneumonia-specific studies that evaluated length of stay (LOS). Nine studies applied an early switch from parenteral to oral antibiotic criteria. Six different criteria for switching were applied in the 9 studies. Five of the studies that applied early switch criteria also applied separate criteria for early discharge. Six studies applied an early switch and early discharge strategy to an intervention and control group, and 5 of these provided SD values for LOS. The mean change in LOS was not significantly (P=.05) reduced in studies of early switch and early discharge (-1.64 days; 95% confidence inter val, -3.30 to 0.02 days). However, when the 2 studies in which the recommended LOS was longer than the control LOS were excluded from the analysis, the mean change in LOS was reduced by 3 days (-3.04 days; 95% confidence interval, -4.90 to -1.19 days). Studies did not reveal significant differences in clinical outcomes between the intervention and control groups. Conclusions: There is considerable variability in early switch from parenteral to oral antibiotic criteria for patients with community-acquired pneumonia. Early switch and early discharge strategies may significantly and safely reduce the mean LOS when the recommended LOS is shorter than the actual LOS. C1 Zynx Hlth Inc, Cedars Sinai Dept Med & Hlth Serv Res, Beverly Hills, CA 90212 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. TAP Pharmaceut Prod Inc, Lake Forest, IL USA. RP Rhew, DC (reprint author), Zynx Hlth Inc, Cedars Sinai Dept Med & Hlth Serv Res, 9100 Wilshire Blvd,Suite 655,East Tower, Beverly Hills, CA 90212 USA. NR 16 TC 76 Z9 82 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 12 PY 2001 VL 161 IS 5 BP 722 EP 727 DI 10.1001/archinte.161.5.722 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 408QM UT WOS:000167339200012 PM 11231705 ER PT J AU Rocco, JW Sidransky, D AF Rocco, JW Sidransky, D TI p16(MTS-1/CDKN2/INK4a) in cancer progression SO EXPERIMENTAL CELL RESEARCH LA English DT Review ID TUMOR-SUPPRESSOR GENE; ACUTE LYMPHOBLASTIC-LEUKEMIA; SQUAMOUS-CELL CARCINOMA; KINASE-4 INHIBITOR GENE; NON-HODGKINS-LYMPHOMAS; IN-SITU HYBRIDIZATION; CUTANEOUS MALIGNANT-MELANOMA; HUMAN PITUITARY-TUMORS; CDKN2 MTS1/P16(INK4A) GENE; SPORADIC PRIMARY MELANOMAS AB Since its discovery as an inhibitor of cyclin-dependent kinases 4 and 6, the tumor suppressor pie has continued to gain widespread importance in cancer. The high frequency of deletions of p16 in tumor cell lines first suggested an important role for p16 in carcinogenesis. This initial genetic evidence was subsequently strengthened by numerous studies documenting p16 inactivation in kindreds with familial melanoma. Moreover, a high frequency of p16 gene alterations was found in primary tumors, while recent studies have identified p16 promoter methylation as a major mechanism of tumor-suppressor-gene silencing. Additional insight into pie's role in cancer has come from the genetic analysis of precancerous lesions and various tissue culture models. It is now believed that loss of pie is an early and often critical event in tumor progression. Consequently, pie is a major tumor-suppressor gene whose frequent loss occurs early in many human cancers. (C) 2001 Academic Press. C1 Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. Johns Hopkins Hosp, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21202 USA. RP Sidransky, D (reprint author), Johns Hopkins Univ, Dept Otolaryngol, 720 Rutland Ave,Ross 818, Baltimore, MD 21205 USA. NR 260 TC 307 Z9 339 U1 3 U2 11 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAR 10 PY 2001 VL 264 IS 1 BP 42 EP 55 DI 10.1006/excr.2000.5149 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 413QQ UT WOS:000167623600005 PM 11237522 ER PT J AU Scully, R AF Scully, R TI Interactions between BRCA proteins and DNA structure SO EXPERIMENTAL CELL RESEARCH LA English DT Review ID DOUBLE-STRAND BREAKS; TRANSCRIPTION-COUPLED REPAIR; CANCER SUSCEPTIBILITY GENE; EMBRYONIC CELLULAR PROLIFERATION; ATM-DEPENDENT PHOSPHORYLATION; YEAST RAD51 PROTEIN; S-PHASE CHECKPOINT; DAMAGE RESPONSE; SCHIZOSACCHAROMYCES-POMBE; SACCHAROMYCES-CEREVISIAE C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Scully, R (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Scully, Ralph/F-5008-2013 FU NCI NIH HHS [K01 CA079576] NR 103 TC 10 Z9 10 U1 1 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAR 10 PY 2001 VL 264 IS 1 BP 67 EP 73 DI 10.1006/excr.2000.5132 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 413QQ UT WOS:000167623600007 PM 11237524 ER PT J AU Kondo, K Kaelin, WG AF Kondo, K Kaelin, WG TI The von Hippel-Lindau tumor suppressor gene SO EXPERIMENTAL CELL RESEARCH LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; CENTRAL-NERVOUS-SYSTEM; SPORADIC CEREBELLAR HEMANGIOBLASTOMAS; BIOLOGICALLY-ACTIVE PRODUCT; UBIQUITIN LIGASE ACTIVITY; FACTOR-ALPHA; GERMLINE MUTATIONS; SOMATIC MUTATIONS; CLEAR-CELL AB Germline mutations of the von Hippel-Lindau tumor suppressor gene (VHL) in humans causes a hereditary cancer syndrome characterized by the development of retinal and central nervous system hemangioblastomas. Other tumors associated with von Hippel-Lindau disease include clear cell renal carcinomas and pheochromocytomas. Tumor development in this setting is due to functional loss of the remaining wild-type VHL allele. Biallelic VHL inactivation is also common in nonhereditary hemangioblastomas and clear cell renal carcinomas, in keeping with Knudson's 2-Hit Model of carcinogenesis. The VHL gene product, pVHL, is a component of an E3 ubiquitin ligase that targets the a subunits of the HIF (hypoxia-inducible factor) transcription factor for destruction in the presence of oxygen. Consequently, tumor cells lacking pVHL overproduce the products of HIF target genes such as vascular endothelial growth factor and transforming growth factor alpha. pVHL has been implicated in a variety of processes that are central to carcinogenesis including cell-cycle control, differentiation, extracellular matrix formation and turnover, and ansogenesis. (C) 2001 Academic Press. 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, Boston, MA 02115 USA. NR 121 TC 149 Z9 159 U1 0 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAR 10 PY 2001 VL 264 IS 1 BP 117 EP 125 DI 10.1006/excr.2000.5139 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 413QQ UT WOS:000167623600011 PM 11237528 ER PT J AU Zang, Q Springer, TA AF Zang, Q Springer, TA TI Amino acid residues in the PSI domain and cysteine-rich repeats of the integrin beta(2) subunit that restrain activation of the integrin alpha(x)beta(2) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIGAND-BINDING REGION; I-DOMAIN; MONOCLONAL-ANTIBODY; A-DOMAIN; PROPELLER DOMAIN; LEUKOCYTE DIFFERENTIATION; CONFORMATIONAL-CHANGES; REGULATED EXPRESSION; P150,95 CD11C/CD18; RECOGNITION SITE AB The leukocyte integrin alpha (X)beta (2) (p150,95) recognizes the iC3b complement fragment and functions as the complement receptor type 4. alpha (X)beta (2) is more resistant to activation than other beta (2) integrins and is inactive in transfected cells. However, when human alpha (X) is paired with chicken or mouse beta (2), alpha (X)beta (2) is activated for binding to iC3b. Activating substitutions were mapped to individual residues or groups of residues in the N-terminal plexin/semaphorin/integrin (PSI) domain and C-terminal cysteine-rich repeats 2 and 3. These regions are linked,by a long range disulfide bond. Substitutions in the PSI domain synergized with substitutions in the cysteine-rich repeats. Substitutions T4P, T22A, Q5255, and V526L gave full activation. Activation of binding to iC3b: correlated with exposure of the CBR LFA-1/2 epitope in cysteine-rich repeat 3. The data suggest that the activating substitutions are present in an interface that restrains the human alpha (X)/human beta (2) integrin in the inactive state. The opening of this interface is linked to structural rearrangements in other domains that activate ligand binding. C1 Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA 31799] NR 50 TC 46 Z9 47 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 9 PY 2001 VL 276 IS 10 BP 6922 EP 6929 DI 10.1074/jbc.M005868200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 410MC UT WOS:000167442900010 PM 11096074 ER PT J AU Donnet, C Arystarkhova, E Sweadner, KJ AF Donnet, C Arystarkhova, E Sweadner, KJ TI Thermal denaturation of the Na,K-ATPase provides evidence for alpha-alpha oligomeric interaction and gamma subunit association with the C-terminal domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SODIUM DODECYL-SULFATE; TRANSFORM INFRARED-SPECTROSCOPY; MEMBRANE H+-ATPASE; P-TYPE ATPASES; NA+/K+-ATPASE; SARCOPLASMIC-RETICULUM; NA/K-ATPASE; RENAL NA,K-ATPASE; CROSS-LINKING; TRYPSINIZED NA,K-ATPASE AB Thermal denaturation can help elucidate protein domain substructure. We previously showed that the Na,K-ATPase partially unfolded when heated to 55 degreesC (Arystarkhova, E,, Gibbons, D. L,, and Sweadner, K, J. (1995) J, Biol, Chem, 270, 8785-8796). The beta subunit unfolded without leaving the membrane, but three transmembrane spans (M8-M10) and the C terminus of the alpha subunit were extruded, while the rest of alpha retained its normal topology with respect to the lipid bilayer, Here we investigated thermal denaturation further, with several salient results. First, trypsin sensitivity at both surfaces of alpha was increased, but not sensitivity to V8 protease, suggesting that the cytoplasmic domains and extruded domain were less tightly packed but still retained secondary structure. Second, thermal denaturation was accompanied by SDS-resistant aggregation of a subunits as dimers, trimers, and tetramers without beta or gamma subunits, This implies specific alpha-alpha contact. Third, the gamma subunit, like the C-terminal spans of alpha, was selectively lost from the membrane. This suggests its association with M8-M10 rather than the more firmly anchored transmembrane spans. The picture that emerges is of a Na,K-ATPase complex of alpha, beta, and gamma subunits in which a can associate in assemblies as large as tetramers via its cytoplasmic domain, while beta and gamma subunits associate with alpha primarily in its C-terminal portion, which has a unique structure and thermal instability. C1 Massachusetts Gen Hosp, Ctr Neurosci, Lab Membrane Biol, Charlestown, MA 02129 USA. RP Sweadner, KJ (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Lab Membrane Biol, Charlestown, MA 02129 USA. EM sweadner@helix.mgh.harvard.edu FU NHLBI NIH HHS [R01 HL36271] NR 65 TC 61 Z9 61 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 9 PY 2001 VL 276 IS 10 BP 7357 EP 7365 DI 10.1074/jbc.M009131200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 410MC UT WOS:000167442900069 PM 11099502 ER PT J AU Elman, I Goldstein, DS Adler, CM Shoaf, SE Breier, A AF Elman, I Goldstein, DS Adler, CM Shoaf, SE Breier, A TI Inverse relationship between plasma epinephrine and testosterone levels during acute glucoprivation in healthy men SO LIFE SCIENCES LA English DT Article DE deoxyglucose; stress; catecholamines; norepinephrine; HVA; 5-HIAA ID INSULIN-INDUCED HYPOGLYCEMIA; HOMOVANILLIC-ACID; 5-HYDROXYINDOLEACETIC ACID; NOREPINEPHRINE UPTAKE; CEREBROSPINAL-FLUID; BLOOD-FLOW; CATECHOLAMINES; STRESS; BRAIN; RATS AB In healthy men, a decrease in plasma testosterone levels was observed in the context of metabolic stress. While physiological mechanisms underlying this response are unclear, there are several lines of evidence suggesting circulating epinephrine's influence on plasma testosterone levels. The purpose of this study was to directly relate stress-induced changes in plasma testosterone and epinephrine. The stressor used was blockade of glucose metabolism with pharmacological doses (40mg/kg) of 2 deoxyglucose (2DG). Arterial plasma samples from 10 healthy males were assayed at 20 minutes intervals for 60 minutes for the concentrations of testosterone, epinephrine and related biochemicals. Bolus administration of 2DG resulted in progressive decline in testosterone and increases in epinephrine and norepinephrine plasma levels (mean change from baseline: 29, 2530 and 186%, respectively). Inverse correlation was detected between both absolute (r(s)= -0.72; df=8; p=0.017) and baseline-corrected testosterone concentrations at the 60 minute time point and epinephrine area under the curve values. Our results suggest that adrenomedullary activation may be involved in stress-induced testosterone effects. The implications of these data for the understanding of the role of catecholamines in glucoprivic stress response are discussed. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Addict Serv, Boston, MA 02114 USA. NINDS, Clin Cardiol Sect, Bethesda, MD 20892 USA. NIMH, Expt Therapeut Branch, Bethesda, MD 20892 USA. NIAAA, Clin Studies Lab, Bethesda, MD 20892 USA. Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. RP Elman, I (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Addict Serv, 15 Parkman St WACC-812, Boston, MA 02114 USA. NR 35 TC 15 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD MAR 9 PY 2001 VL 68 IS 16 BP 1889 EP 1898 DI 10.1016/S0024-3205(01)00982-1 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 412VQ UT WOS:000167575400007 PM 11292066 ER PT J AU Smoller, JW Acierno, JS Rosenbaum, JF Biederman, J Pollack, MH Meminger, S Pava, JA Chadwick, LH White, C Bulzacchelli, M Slaugenhaupt, SA AF Smoller, JW Acierno, JS Rosenbaum, JF Biederman, J Pollack, MH Meminger, S Pava, JA Chadwick, LH White, C Bulzacchelli, M Slaugenhaupt, SA TI Targeted genome screen of panic disorder and anxiety disorder proneness using homology to murine QTL regions SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article; Proceedings Paper CT 49th Annual Meeting of the American-Society-of-Human-Genetics CY OCT 19-23, 1999 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Human Genet DE panic disorder; linkage analysis; genome scan; mouse genetics ID QUANTITATIVE TRAIT LOCI; RECOMBINANT INBRED STRAINS; BEHAVIORAL-INHIBITION; PSYCHIATRIC-DISORDERS; SEGREGATION ANALYSIS; GENETIC DISSECTION; MAJOR DEPRESSION; LINKAGE ANALYSIS; COMPLEX TRAITS; MOUSE STRAINS AB Family and twin studies have indicated that genes influence susceptibility to panic and phobic anxiety disorders, but the location of the genes involved remains unknown. Animal models can simplify gene-mapping efforts by overcoming problems that complicate human pedigree studies including genetic heterogeneity and high phenocopy rates. Homology between rodent and human genomes can be exploited to map human genes underlying complex traits. We used regions identified by quantitative trait locus (QTL)-mapping of anxiety phenotypes in mice to guide a linkage analysis of a large multiplex pedigree (99 members, 75 genotyped) segregating panic disorder/agoraphobia. Two phenotypes were studied: panic disorder/agoraphobia and a phenotype ("D-type") designed to capture early-onset susceptibility to anxiety disorders. A total of 99 markers across II chromosomal regions were typed, Parametric lod score analysis provided suggestive evidence of linkage (lod=2,38) to a locus on chromosome 10q under a dominant model with reduced penetrance for the anxiety-proneness D-type) phenotype, Nonparametric (NPL) analysis provided evidence of linkage for panic disorder/agoraphobia to a locus on chromosome 12q13 (NPL=4.96, P=0.006), Modest evidence of linkage by NPL analysis was also found for the D-type phenotype to a region of chromosome 1q (peak NPL = 2.05, P=0.035), While these linkage results are merely suggestive, this study illustrates the potential advantages of using mouse gene-mapping results and exploring alternative phenotype definitions in linkage studies of anxiety disorder, (C) 2001 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Inst Human Genet, Boston, MA USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02114 USA. RP Smoller, JW (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WACC-815, Boston, MA 02114 USA. FU NIMH NIH HHS [T32MH17119, R25MH60485] NR 75 TC 75 Z9 75 U1 2 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAR 8 PY 2001 VL 105 IS 2 BP 195 EP 206 DI 10.1002/ajmg.1209 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 417YB UT WOS:000167862100013 PM 11304837 ER PT J AU Cavacini, LA Eder, JP Kufe, DW Schlom, J Posner, MR AF Cavacini, LA Eder, JP Kufe, DW Schlom, J Posner, MR TI Antibodies to prostate surface antigens in patients immunized with prostate specific antigen (PSA) SO FASEB JOURNAL LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 2001 VL 15 IS 5 BP A1198 EP A1198 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454202795 ER PT J AU Clarke, MSF Hammond, DK Caldwell, RW Bamman, MM Vanderburg, CR Feeback, DL AF Clarke, MSF Hammond, DK Caldwell, RW Bamman, MM Vanderburg, CR Feeback, DL TI Cholesterol-mediated modulation of skeletal muscle membrane calcium pump function during mechanical unloading SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Space Res Assoc, Houston, TX 77058 USA. Wiley Labs, Houston, TX 77058 USA. Med Coll Georgia, Augusta, GA 30912 USA. Univ Alabama, Birmingham, AL 35294 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NASA, Lyndon B Johnson Space Ctr, Houston, TX 77058 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 2001 VL 15 IS 5 BP A1116 EP A1116 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454202327 ER PT J AU Dodd, C Mountz, J Chu, WJ Josephson, L Zhang, HG Weissleder, R Mountz, JM Zinn, K Mountz, JD Hsu, HC AF Dodd, C Mountz, J Chu, WJ Josephson, L Zhang, HG Weissleder, R Mountz, JM Zinn, K Mountz, JD Hsu, HC TI In vivo magnetic resonance imaging (MRI) of T cells loaded with HIV transactivator (tat) peptide-derived super-paramagnetic nanoparticles. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Alabama, Birmingham, AL 35294 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. VAMC, Birmingham, AL 35233 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 2001 VL 15 IS 5 BP A744 EP A744 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454200179 ER PT J AU Geng, LP Pfister, S Rudd, CE AF Geng, LP Pfister, S Rudd, CE TI Immune adaptor FYB regulates Fc epsilon RI mediated histamine release and adherence to fibronectin-coated surfaces in mast cell line RBL-2H3 SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RI Pfister, Stefan/F-6860-2013 OI Pfister, Stefan/0000-0002-5447-5322 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 2001 VL 15 IS 5 BP A1039 EP A1039 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454201880 ER PT J AU Greenwald, RJ Boussiotis, VA Lorsbach, RB Abbas, AK Sharpe, AH AF Greenwald, RJ Boussiotis, VA Lorsbach, RB Abbas, AK Sharpe, AH TI CTLA-4 regulates peripheral T cell tolerance in vivo SO FASEB JOURNAL LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 2001 VL 15 IS 5 BP A1217 EP A1217 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454202905 ER PT J AU Hamazaki, T Iiboshi, Y Oka, M Papst, PJ Meacham, AM Zon, LI Terada, N AF Hamazaki, T Iiboshi, Y Oka, M Papst, PJ Meacham, AM Zon, LI Terada, N TI Hepatic maturation in differentiating embryonic stem cells in vitro SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Florida, Dept Pathol, Gainesville, FL 32610 USA. Natl Jewish Med & Res Ctr, Denver, CO 80206 USA. Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 2001 VL 15 IS 5 BP A1084 EP A1084 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454202143 ER PT J AU Kling, DE Brandon, KL Schnitzer, JJ AF Kling, DE Brandon, KL Schnitzer, JJ TI MAP kinase activities and expression during rat lung development SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 2001 VL 15 IS 5 BP A902 EP A902 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454201083 ER PT J AU Marshansky, V Brown, D Bonventre, JV AF Marshansky, V Brown, D Bonventre, JV TI Trafficking of membrane proteins from Golgi to plasma membrane in kidney epithelial cells expressing cytosolic PLA(2). SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Membrane Biol, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 2001 VL 15 IS 5 BP A1176 EP A1176 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454202667 ER PT J AU Popov, S Vlasak, J Rasmussen, RA Hofmann-Lehmann, R Chalmers, AS Li, PL Wang, YL Ruprecht, RM AF Popov, S Vlasak, J Rasmussen, RA Hofmann-Lehmann, R Chalmers, AS Li, PL Wang, YL Ruprecht, RM TI Selection of aggressive progeny virus based on viral fitness, rather than evasion of host antibody responses SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RI Hofmann-Lehmann, Regina/C-6528-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 2001 VL 15 IS 5 BP A1010 EP A1010 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454201712 ER PT J AU Rao, A AF Rao, A TI Concerted dephosphorylation of the transcription factor NFAT1 induces a conformational switch that regulates transcriptional activity SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 7 U2 7 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 2001 VL 15 IS 5 BP A723 EP A723 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454200058 ER PT J AU Rimmer, DM Jones, SP Huang, PL Lefer, DJ AF Rimmer, DM Jones, SP Huang, PL Lefer, DJ TI Differing responses to myocardial ischemia in two separate lines of endothelial nitric oxide synthase knockout mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 2001 VL 15 IS 5 BP A782 EP A782 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454200395 ER PT J AU Swamy, MN Wan, JM Shankar, P Hieshima, K Springer, TA Lieberman, J von Andrian, UH AF Swamy, MN Wan, JM Shankar, P Hieshima, K Springer, TA Lieberman, J von Andrian, UH TI Differential induction of effector and memory cytotoxic T lymphocytes by interleukins 2, 7 and 15. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 2001 VL 15 IS 5 BP A1055 EP A1055 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454201976 ER PT J AU Xie, Y Chen, CM Calderwood, SK AF Xie, Y Chen, CM Calderwood, SK TI Transcription repression by HSF1 SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 2001 VL 15 IS 5 BP A1224 EP A1224 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454202945 ER PT J AU Yan, XT Agrawal, A Kheradmand, F Corry, DB Tuvim, M Dickey, BF AF Yan, XT Agrawal, A Kheradmand, F Corry, DB Tuvim, M Dickey, BF TI Expression of the exocytic regulatory protein, Munc18-2, accompanies goblet cell metaplasia of airway epithelium in a mouse asthma model SO FASEB JOURNAL LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Houston VAMC, Houston, TX 77025 USA. RI Agrawal, Anurag/A-7312-2009 NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 2001 VL 15 IS 5 BP A1015 EP A1015 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454201741 ER PT J AU Yoshida, K Kufe, D AF Yoshida, K Kufe, D TI Protein kinase C delta regulates SHPTP1 tyrosine phosphate activity in response to DNA damage SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 2001 VL 15 IS 5 BP A1170 EP A1170 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454202637 ER PT J AU Zhang, SL Filep, JG Tang, SS Ingelfinger, JR Chan, JSD Chiasson, JL AF Zhang, SL Filep, JG Tang, SS Ingelfinger, JR Chan, JSD Chiasson, JL TI Hyperglycemia induces insulin resistance on angiotensinogen (ANG) gene expression in diabetic rat renal proximal tubular cells (RPTCs). SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Montreal, CHUM, Montreal, PQ H2W 1T8, Canada. Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 2001 VL 15 IS 5 BP A834 EP A834 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454200697 ER PT J AU Blumenthal, D AF Blumenthal, D TI Controlling health care expenditures. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID COSTS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Blumenthal, D (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 28 TC 49 Z9 49 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 8 PY 2001 VL 344 IS 10 BP 766 EP 769 DI 10.1056/NEJM200103083441012 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 408AX UT WOS:000167305300012 PM 11236784 ER PT J AU Allport, JR Lim, YC Shipley, JM Senior, RM Shapiro, SD Vestweber, D Matsuyoshi, N Luscinskas, FW AF Allport, JR Lim, YC Shipley, JM Senior, RM Shapiro, SD Vestweber, D Matsuyoshi, N Luscinskas, FW TI Murine neutrophil transendothelial migration under flow in vitro does not require elastase or MMP-9 SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02129 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Washington Univ, Sch Med, St Louis, MO USA. Univ Munster, D-4400 Munster, Germany. Kyoto Univ, Kyoto, Japan. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A392 EP A392 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438102243 ER PT J AU Annaiah, C Tang, M Carroll, M Georgopoulos, K Pillai, S AF Annaiah, C Tang, M Carroll, M Georgopoulos, K Pillai, S TI The follicular versus marginal zone B lymphocyte cell-fate decision is regulated by Aiolos, Btk, and CD21 SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A318 EP A318 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438101818 ER PT J AU Brown, JA Dorfman, DM Butler, M Nunes, R Latchman, Y Long, AJ Iwai, Y Bourque, K Boussiotis, VA Chernova, T Nishimura, H Fitz, L Malenkovich, N Honjo, T Wood, CR Nadler, LM Sharpe, AH Freeman, GJ AF Brown, JA Dorfman, DM Butler, M Nunes, R Latchman, Y Long, AJ Iwai, Y Bourque, K Boussiotis, VA Chernova, T Nishimura, H Fitz, L Malenkovich, N Honjo, T Wood, CR Nadler, LM Sharpe, AH Freeman, GJ TI Expression and functional consequences of PD-1 ligands on natural APCS and tumors SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Genet Inst, Cambridge, MA 02140 USA. Kyoto Univ, Kyoto 6068501, Japan. RI Honjo, Tasuku/N-4470-2016 NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A345 EP A345 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438101972 ER PT J AU Drugea, IA Kovacs, EJ Rollins, BJ Burns, AL DiPietro, LA AF Drugea, IA Kovacs, EJ Rollins, BJ Burns, AL DiPietro, LA TI Wound healing in MCP-1 genetically deficient mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 Loyola Univ, Med Ctr, Burn & Shock Trauma Inst, Maywood, IL 60153 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A243 EP A243 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438101389 ER PT J AU Dutta, A Jonsson, Z Dhar, SK Narlikar, G AF Dutta, A Jonsson, Z Dhar, SK Narlikar, G TI Rvb1p/Rvb2p, implicated in cell transformation by Myc and in DNA repair and apoptosis, is an ATP dependent chromatin remodeling factor SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Jonsson, Zophonias/E-1960-2015; Dutta, Anindya/P-3203-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A504 EP A504 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438102882 ER PT J AU Fathallah, DM Guedel, N Essafi, M Barbouche, RM Arnaout, AM Dellagi, KM AF Fathallah, DM Guedel, N Essafi, M Barbouche, RM Arnaout, AM Dellagi, KM TI Cloning, expression and characterization of single-chain variable fragments (ScFv) of two monoclonal antibodies (Mab) to the human beta 2 integrin subunit CD11b SO FASEB JOURNAL LA English DT Meeting Abstract C1 Inst Pasteur, Tunis 1002, Tunisia. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A681 EP A681 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438103907 ER PT J AU Fisher, JS Pastor-Soler, N Sharpe, RM Brown, D Breton, S AF Fisher, JS Pastor-Soler, N Sharpe, RM Brown, D Breton, S TI Regulation of epididymal H+-ATPase in peripubertal rats after steroid treatment SO FASEB JOURNAL LA English DT Meeting Abstract C1 MRC, Edinburgh EH3 9ET, Midlothian, Scotland. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RI Sharpe, Richard/D-2725-2013 OI Sharpe, Richard/0000-0003-1686-8085 NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A439 EP A439 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438102512 ER PT J AU Garrity, DM Warren, KS Baker, K Mohideen, MA Fishman, MC AF Garrity, DM Warren, KS Baker, K Mohideen, MA Fishman, MC TI The zebrafish mutant tremblor has a "fibrillating" heart SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. Roger Williams Univ, Bristol, RI 02809 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Penn State Univ, University Pk, PA 16802 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A481 EP A481 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438102750 ER PT J AU Han, ED Mulligan, A MacFarlane, RC Davis, AE AF Han, ED Mulligan, A MacFarlane, RC Davis, AE TI Targeted disruption of the mouse C1 inhibitor gene results in enhanced vascular permeability SO FASEB JOURNAL LA English DT Meeting Abstract C1 Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A687 EP A687 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438103945 ER PT J AU Hsu, HC Dodd, C Chu, WJ Yang, PA Josephson, L Sun, SH Zhang, HG Weissleder, R Mountz, JD AF Hsu, HC Dodd, C Chu, WJ Yang, PA Josephson, L Sun, SH Zhang, HG Weissleder, R Mountz, JD TI Normal response of T cells loaded with HIV transactivator (tat) peptide-derived super-paramagnetic nanoparticles for magnetic resonance imaging (MRI). SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Alabama, Birmingham, AL 35294 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Univ Alabama, Birmingham, AL 35233 USA. VAMC, Birmingham, AL 35233 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A330 EP A330 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438101888 ER PT J AU Hsu, HC Williams, RW Geiger, H Shehon, BJ Yang, PA Zhang, HG Van Zant, G Mountz, JD AF Hsu, HC Williams, RW Geiger, H Shehon, BJ Yang, PA Zhang, HG Van Zant, G Mountz, JD TI Thymic involution is associated with a genetic locus on mouse chromosome 11. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Alabama, Birmingham, AL 35294 USA. Univ Tennessee, Memphis, TN 38163 USA. Univ Kentucky, Med Ctr, Lexington, KY 40536 USA. Univ Alabama, Birmingham, AL 35233 USA. Birmingham VAMC, Birmingham, AL 35233 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A312 EP A312 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438101782 ER PT J AU Husain, Z Alper, CA Dubey, DP AF Husain, Z Alper, CA Dubey, DP TI Multiple receptors on NK cells: Subset size, function and receptor distribution in single cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A653 EP A653 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438103750 ER PT J AU Kingston, R AF Kingston, R TI Regulation of chromatin structure by SWI/SNF and polycomb SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A504 EP A504 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438102881 ER PT J AU Kurtz, JM Ito, H Shaffer, J Sykes, M AF Kurtz, JM Ito, H Shaffer, J Sykes, M TI Rapid induction of donor-specific thymocyte tolerance across a full MHC barrier through BMT and costimulatory blockade SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A669 EP A669 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438103840 ER PT J AU Latchman, Y Wood, C Chemova, T Iwai, Y Malenkovich, N Long, A Bourque, K Boussiotis, V Nishimura, H Honjo, T Sharpe, A Freeman, G AF Latchman, Y Wood, C Chemova, T Iwai, Y Malenkovich, N Long, A Bourque, K Boussiotis, V Nishimura, H Honjo, T Sharpe, A Freeman, G TI PD-L2, a novel B7 homologue, is a second ligand for PD-1 and inhibits T cell activation. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Genet Inst, Cambridge, MA 02140 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Kyoto Univ, Kyoto 6068501, Japan. RI Honjo, Tasuku/N-4470-2016 NR 0 TC 1 Z9 1 U1 1 U2 10 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A345 EP A345 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438101975 ER PT J AU Lima, B Gleit, ZL Germana, S LeGuern, C Sachs, DH Huang, C AF Lima, B Gleit, ZL Germana, S LeGuern, C Sachs, DH Huang, C TI Mixed hematopoietic chimerism in a large animal model: Evidence for multilineage stem cell engraftment in long-term chimeras SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A665 EP A665 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438103817 ER PT J AU Marshansky, V Wang, X Bertrand, R Luo, HY Duguid, W Chinnadurai, G Kanaan, N Vu, MD Wu, JP AF Marshansky, V Wang, X Bertrand, R Luo, HY Duguid, W Chinnadurai, G Kanaan, N Vu, MD Wu, JP TI A novel role for the proteasome in the regulation of apoptosis. "To Bik or Not to Bik, that is the question." SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Membrane Biol, Boston, MA 02129 USA. Univ Montreal, Notre Dame Hosp, Res Ctr, CHUM, Montreal, PQ H2L 4M1, Canada. St Louis Univ, Hlth Sci Ctr, Inst Mol Virol, St Louis, MO 63110 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A388 EP A388 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438102220 ER PT J AU Matsuki, Y Hsu, HC Zhou, T Cecconi, F Gruss, P Mountz, JD AF Matsuki, Y Hsu, HC Zhou, T Cecconi, F Gruss, P Mountz, JD TI Defective death by neglect and negative selection in thymic development of Apaf-1-deficient mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Alabama Birmingham, Birmingham, AL 35294 USA. Max Planck Inst Biophys Chem, D-37077 Gottingen, Germany. Univ Alabama Birmingham, Birmingham, AL 35233 USA. Birmingham VAMC, Birmingham, AL 35233 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A312 EP A312 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438101784 ER PT J AU Matyal, R Mascarenhas, M Force, T Hales, CA Quinn, DA AF Matyal, R Mascarenhas, M Force, T Hales, CA Quinn, DA TI Cyclic stretch and hypoxia alter pulmonary artery endothelial cell control of smooth muscle cell growth SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A157 EP A157 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438100895 ER PT J AU McAdam, AJ Greenwald, R Levin, M Ling, V Chernova, T Malenkovich, N Freeman, G Sharpe, A AF McAdam, AJ Greenwald, R Levin, M Ling, V Chernova, T Malenkovich, N Freeman, G Sharpe, A TI The inducible costimulatory (ICOS) molecule is critical for antibody class switching SO FASEB JOURNAL LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Genet Inst, Cambridge, MA 02140 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A345 EP A345 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438101976 ER PT J AU Milstone, DS O'Donnell, PE Davis, VM Mortensen, RM Rosen, E Stavrakis, G AF Milstone, DS O'Donnell, PE Davis, VM Mortensen, RM Rosen, E Stavrakis, G TI PPAR gamma is expressed and regulates placental development and trophoblast differentiation in both humans and mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A583 EP A583 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438103338 ER PT J AU Mukhin, YV Vlasova, TM Grewal, JS Ullian, ME Tholanikunnel, BG Raymond, JR Garnovskaya, MN AF Mukhin, YV Vlasova, TM Grewal, JS Ullian, ME Tholanikunnel, BG Raymond, JR Garnovskaya, MN TI ERK is an intermediate for rapid phosphorylation of Serine(795) of the retinoblastoma gene product in vascular smooth muscle cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A205 EP A205 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438101168 ER PT J AU Onami, TM Harrington, LE Manjunath, N Baum, L Ahmed, R AF Onami, TM Harrington, LE Manjunath, N Baum, L Ahmed, R TI Dynamic regulation of CD43 on T cells during a viral response. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Univ Calif Los Angeles, Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A343 EP A343 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438101959 ER PT J AU Oosterwegel, MA Mandelbrot, DA Freeman, GJ Sharpe, AH AF Oosterwegel, MA Mandelbrot, DA Freeman, GJ Sharpe, AH TI B7-dependent costimulation present in mice lacking CD28 and CTLA-4 SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Utrecht, Med Ctr, NL-3584 EA Utrecht, Netherlands. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A345 EP A345 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438101971 ER PT J AU Pahlavani, MA AF Pahlavani, MA TI Activation-induced apoptosis in T cells: Effect of age and caloric restriction SO FASEB JOURNAL LA English DT Meeting Abstract C1 Audie L Murphy Mem Vet Hosp, Ctr Geriatr Res Educ & Clin, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A352 EP A352 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438102011 ER PT J AU Pastor-Soler, NM Bagnis, C Sabolic, I Tyszkowski, R McKee, M Van Hoek, A Brown, D Breton, S AF Pastor-Soler, NM Bagnis, C Sabolic, I Tyszkowski, R McKee, M Van Hoek, A Brown, D Breton, S TI Aquaporin 9 expression along the male reproductive tract: Downregulation by the anti-androgen flutamide. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Program in Membrane Biol, Charlestown, MA 02129 USA. Inst Med Res & Occupat Hlth, Zagreb 10001, Croatia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A438 EP A438 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438102503 ER PT J AU Ren, XP Cao, C Zhu, LB Yoshida, I Kharbanda, S Kufe, D AF Ren, XP Cao, C Zhu, LB Yoshida, I Kharbanda, S Kufe, D TI Lyn tyrosine kinase regulates the p53 tumor suppressor by inhibiting nuclear export of the p53-Mdm2 complex SO FASEB JOURNAL LA English DT Meeting Abstract C1 Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A3 EP A3 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438100017 ER PT J AU Rumbaut, RE Williams, DA Huxley, VH AF Rumbaut, RE Williams, DA Huxley, VH TI Similar effects of nitric oxide synthase inhibitors on microvascular permeability in three animal species SO FASEB JOURNAL LA English DT Meeting Abstract C1 Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA. Univ Missouri, Columbia, MO 65212 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A46 EP A46 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438100260 ER PT J AU Scheuner, D Song, BB McEwen, E Bonner-Weir, S Kaufman, RJ AF Scheuner, D Song, BB McEwen, E Bonner-Weir, S Kaufman, RJ TI Translational control is required for insulin production, glucose honeastasis, and the unfolded protein response SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A1 EP A1 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438100005 ER PT J AU Segev, DL Hoshiya, Y Stephen, AE Hoshiya, M Tran, TT Donahoe, PK Maheswaran, S AF Segev, DL Hoshiya, Y Stephen, AE Hoshiya, M Tran, TT Donahoe, PK Maheswaran, S TI Mullerian inhibiting substance inhibits normal breast proliferation SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A69 EP A69 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438100391 ER PT J AU Shankar, P Chen, G Skolnik, PR Wu, LJ Swamy, MN Lieberman, J AF Shankar, P Chen, G Skolnik, PR Wu, LJ Swamy, MN Lieberman, J TI Expression of cytolytic effector molecules and lymph node homing receptors in circulating HIV-specific CD8 T cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Tufts Univ, Sch Med, New England Med Ctr, Boston, MA 02111 USA. LeukoSite Inc, Cambridge, MA 02142 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A308 EP A308 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438101758 ER PT J AU Tuaillon, N Shen, D Berger, RB Lu, B Rollins, BJ Chan, CC AF Tuaillon, N Shen, D Berger, RB Lu, B Rollins, BJ Chan, CC TI Lack of lipopolysaccharide-induced ocular inflammation in MCP-1 deficient mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 NEI, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A361 EP A361 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438102069 ER PT J AU Tzachanis, D Hirano, N Freeman, GJ Nadler, LM Boussiotis, VA AF Tzachanis, D Hirano, N Freeman, GJ Nadler, LM Boussiotis, VA TI Tob, a novel Tob/BTG1 family member mediates active inhibition of IL-2 transcription in adrenergic T cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A353 EP A353 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438102018 ER PT J AU Wang, KS Ritz, J AF Wang, KS Ritz, J TI Identification of IL-12 induced genes in human T cells and NK cells by gene expression profiling. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A348 EP A348 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438101988 ER PT J AU Weninger, W Crowley, MA Manjunath, N von Andrian, UH AF Weninger, W Crowley, MA Manjunath, N von Andrian, UH TI Migratory properties of naive, effector, and central memory CD8+T cells in vivo SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A330 EP A330 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438101887 ER PT J AU Yan, XT AF Yan, XT TI Coordinate expression by GATA factors of the regulated secretory phenotype in mast cell development and activation SO FASEB JOURNAL LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77025 USA. Houston VAMC, Houston, TX 77025 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A713 EP A713 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438104096 ER PT J AU Yoshida, K Kufe, D AF Yoshida, K Kufe, D TI Role for c-Abl tyrosine kinase as a regulator of Rad9 in the apoptotic response to DNA damage SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A510 EP A510 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438102916 ER PT J AU Zahedi, K Prada, AE Mulligan, A Davis, AE AF Zahedi, K Prada, AE Mulligan, A Davis, AE TI Transcriptional regulation of the C1 inhibitor gene SO FASEB JOURNAL LA English DT Meeting Abstract C1 Childrens Hosp Res Fdn, Cincinnati, OH 45229 USA. Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A684 EP A684 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438103927 ER PT J AU Zhang, SL Filep, JG Tang, SS Ingelfinger, JR Chan, JSD Chiasson, JL AF Zhang, SL Filep, JG Tang, SS Ingelfinger, JR Chan, JSD Chiasson, JL TI Role(s) of intra-renal renin-angiotensin system (RAS) in transforming growth factor-beta 1 (TGF-beta 1) gene expression and induction of hypertrophy in renal proximal tubular cells in high glucose medium SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Montreal, Montreal, PQ H2W IT8, Canada. Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A100 EP A100 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438100565 ER PT J AU Zhang, ZQ Apse, K Stanton, RC AF Zhang, ZQ Apse, K Stanton, RC TI Differential effects of high glucose on glucose 6-phosphate dehydrogenase activity in endothelial cells and renal mesangial cells is mediated, at least in part, by cAMP SO FASEB JOURNAL LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A170 EP A170 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438100964 ER PT J AU Fleischmann, J Liu, H AF Fleischmann, J Liu, H TI Polyadenylation of ribosomal RNA by Candida albicans SO GENE LA English DT Article DE hypha; pseudohypha; differential display; germination; serum ID MESSENGER-RNA; HYPHAL FORMATION; TRANSCRIPTION FACTOR; POLYMERASE SWITCH; YEAST; KINASE; MORPHOGENESIS; EUKARYOTES; CEREVISIAE; VIRULENCE AB Candida albicans is the leading fungal pathogen in immunocompromised patients such as those with AIDS and malignancies. It is a polymorphic organism existing as a unicellular yeast or as filamentous forms that include pseudohyphae and true hyphae. While studying the early period of hyphal transformation. comparing cDNAs from yeast to those in early transition, we were surprised to find 25S rRNA represented frequently in our differential display assays, suggesting that our reverse transcription with poly-T primers was copying rRNA with extended poly-A 3' ends. We now report that both the yeast forms and germinating organisms polyadenylate some of their 25S rRNA transcripts. We also found a rapid and transient enhancement of this process upon stimulation with serum. These data indicate that 25S rRNA polyadenylation is part of the biological repertoire of C. albicans and its transient upregulation just prior to hyphal development raises the possibility of a regulatory role in this transition. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Dent, Dept Oral Biol & Med, Los Angeles, CA 90095 USA. RP Fleischmann, J (reprint author), Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Dept Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 26 TC 13 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAR 7 PY 2001 VL 265 IS 1-2 BP 71 EP 76 DI 10.1016/S0378-1119(01)00362-6 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 415WX UT WOS:000167747500008 PM 11255009 ER PT J AU Chaturvedi, N AF Chaturvedi, N CA ACE Inhibitors in Diab Nephro TI Should all patients with type 1 diabetes mellitus and microalbuminuria receive angiotensin-converting enzyme inhibitors? A meta-analysis of individual patient data SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CLINICAL-TRIALS; IDDM PATIENTS; INCIPIENT NEPHROPATHY; GLOMERULAR STRUCTURE; PROGRESSION; METAANALYSIS; CAPTOPRIL; PROTEINURIA; ALBUMINURIA; PREVENTION AB Purpose: To determine whether response of albumin excretion rate, to angiotensin-converting enzyme (ACE) inhibitors has a threshold in patients with type 1 diabetes mellitus and microalbuminuria and to examine treatment effect according to covariates. Data Sources: Studies were identified by searching MEDLINE and related bibliographies. Study Selection: selected studies included at least 10 normotensive patients with type 1 diabetes mellitus and microalbuminuria, had a placebo or nonintervention group, and included at least 1 year of follow-up. Data Extraction: Raw data were obtained for 698 patients from the 12 identified trials. Analysis of treatment effect at 2 years was restricted to trials with at least 2 years of follow-up (646 patients from 10 trials). Data Synthesis: In patients receiving ACE inhibitors, progression to macroalbuminuria was reduced (odds ratio, 0.38 [95% Cl, 0.25 to 0.57]) and the odds ratio for regression to normoalbuminuria was 3.07 (Cl, 2.15 to 4.44). At 2 years, albumin excretion rate was 50.5% (Cl, 29.2% to 65.5%) lower in treated patients than in those receiving placebo (P < 0.001). Estimated treatment effect varied by baseline albumin excretion rate (74.1% and 17.8% in patients with a rate of 200 g/min and 20 mug/min, respectively [P = 0.04]) but not by patient subgroup. Adjustment for change in blood pressure attenuated the treatment difference in albumin excretion rate at 2 years to 45.1% (Cl, 18.6% to 63.1%; P < 0.001). Conclusions: In normotensive patients with type 1 diabetes mellitus and microalbuminuria, ACE inhibitors significantly reduced progression to macroalbuminuria and increased chances of regression. Beneficial effects were weaker at the lowest levels of microalbuminuria but did not differ according to other baseline risk factors. Changes in blood pressure cannot entirely explain the antiproteinuric effect of ACE inhibitors. C1 Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London W2 1PG, England. Univ Birmingham, Birmingham B15 2TT, W Midlands, England. S Cleveland Hosp, Middlesbrough, Cleveland, England. Univ Warwick, Coventry CV4 7AL, W Midlands, England. Univ London Kings Coll, London WC2R 2LS, England. Linkoping Univ Hosp, S-58185 Linkoping, Sweden. Univ Padua & Sassari, Padua, Italy. Natl Res Ctr Study Aging, Padua, Italy. Hop Broussais, F-75674 Paris, France. Steno Diabet Ctr, Copenhagen, Denmark. Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Chaturvedi, N (reprint author), Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, Norfolk Pl, London W2 1PG, England. OI Marre, Michel/0000-0002-3071-1837 NR 33 TC 227 Z9 229 U1 3 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAR 6 PY 2001 VL 134 IS 5 BP 370 EP 379 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 405ZJ UT WOS:000167190200003 ER PT J AU Meigs, JB Larson, MG D'Agostino, RB Levy, D Clouse, ME Nathan, DM Wilson, PWF O'Donnell, CJ AF Meigs, JB Larson, MG D'Agostino, RB Levy, D Clouse, ME Nathan, DM Wilson, PWF O'Donnell, CJ TI Coronary artery calcification in type 2 diabetes and insulin resistance: the Framingham Offspring Study SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Framingham, MA USA. Boston Univ, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Framingham, 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 MAR 6 PY 2001 VL 103 IS 9 MA 0002 BP 1344 EP 1344 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 412NX UT WOS:000167562200030 ER PT J AU Mukamal, KJ Nesto, RW Cohen, MC Muller, JE Maclure, M Sherwood, JB Mittleman, MA AF Mukamal, KJ Nesto, RW Cohen, MC Muller, JE Maclure, M Sherwood, JB Mittleman, MA TI Diabetes and long-term survival after acute myocardial infarction: Comparability of risk with prior myocardial infarction SO CIRCULATION LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Lahey Clin Med Ctr, Burlington, MA 01803 USA. Maine Med Ctr, Portland, ME 04102 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, 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 MAR 6 PY 2001 VL 103 IS 9 MA 0027 BP 1349 EP 1349 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 412NX UT WOS:000167562200055 ER PT J AU O'Donnell, CJ Benjamin, EJ Corey, D Newton-Cheh, C Levy, D D'Agostino, RB Larson, MG AF O'Donnell, CJ Benjamin, EJ Corey, D Newton-Cheh, C Levy, D D'Agostino, RB Larson, MG TI The PR interval is a heritable quantitative trait with evidence for linkage to chromosome 4 in a genome-wide scan: The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Med Ctr, Framingham, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, 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 MAR 6 PY 2001 VL 103 IS 9 MA P19 BP 1354 EP 1354 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 412NX UT WOS:000167562200079 ER PT J AU Jack, C Berezovska, O Wolfe, MS Hyman, BT AF Jack, C Berezovska, O Wolfe, MS Hyman, BT TI Effect of PS1 deficiency and an APP gamma-secretase inhibitor on Notch1 signaling in primary mammalian neurons SO MOLECULAR BRAIN RESEARCH LA English DT Article DE Notch; presenilin; gamma-secretase; Alzheimer's disease; amyloid precursor protein ID CAENORHABDITIS-ELEGANS; NUCLEAR TRANSLOCATION; DROSOPHILA PRESENILIN; ALZHEIMERS-DISEASE; RECEPTOR; GENE; DIFFERENTIATION; LOCALIZATION; PROTEOLYSIS; MUTATIONS AB Presenilin 1 (PSI) has been implicated in normal Notch1 processing and signaling in several experimental systems. In the present study, the relationship between PS1 and Notch1 in mammalian neurons is studied by analyzing Notch1 cleavage and C-terminal nuclear translocation as well as Notch I signaling via the transactivation of a CBFI-luciferase reporter construct. We show that full-length Notch1 [NI(FL)I transfected into wild type (WT) primary neurons is cleaved in the presence of its biological ligand Delta (DI) and translocated to the nucleus within 1-3 min of ligand addition. PS1 deficient neurons show normal Notch1 insertion into the cellular membrane, yet lack Notch1 activation resulting in markedly inhibited nuclear translocation of the C-terminal Notch fragment (NICD). PSI deficient neurons also have impaired Notch 1 signaling which can be restored fully or partially to levels seen in WT littermates by transfection with WT or familial Alzheimer's disease-associated M146L mutant PS1, respectively. We also show that pharmacological inhibition of PS1-associated gamma -secretase activity parallels the effects of genetic PS1 deficiency in these assays. These results support the hypothesis that PS1 deficiency blocks neuronal Notch1 processing and signaling. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. RP Hyman, BT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Alzheimers Dis Res Lab, 149 13th St, Charlestown, MA 02129 USA. NR 33 TC 22 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD MAR 5 PY 2001 VL 87 IS 2 BP 166 EP 174 DI 10.1016/S0169-328X(01)00010-9 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 411YG UT WOS:000167526800003 ER PT J AU Rebeck, GW Moir, RD Mui, S Strickland, DK Tanzi, RE Hyman, BT AF Rebeck, GW Moir, RD Mui, S Strickland, DK Tanzi, RE Hyman, BT TI Association of membrane-bound amyloid precursor protein APP with the apolipoprotein E receptor LRP SO MOLECULAR BRAIN RESEARCH LA English DT Article DE Alzheimer's; endocytosis; apoE; lipoprotein; Kunitz protease inhibitor ID PSEUDOMONAS EXOTOXIN-A; ALZHEIMERS-DISEASE; BETA-PROTEIN; ALPHA-2-MACROGLOBULIN RECEPTOR; GENETIC ASSOCIATION; LIPOPROTEIN; DEGRADATION; SECRETION; INHIBITOR; MULTIPLE AB In order to identify cell surface proteins that interact with the amyloid precursor protein (APP), we biotinylated H4 human neuroglioma cells in culture with a water soluble biotinylating agent, immunoprecipitated APP with an antibody specific to the intracellular domain, and probed the precipitated proteins with anti-biotin. In human neuroglioma cells overexpressing APP751, we found a high molecular weight protein that immunoprecipitated with APP. This band was identified as the low density lipoprotein receptor-related protein (LRP) by three criteria: first, the band immunolabeled with anti-LRP antibodies; second, the band bound the LRP receptor associated protein, RAP; and third, this band was present in LRP-expressing fibroblasts, but not LRP-deficient fibroblasts. In complementary experiments, we found that APP co-precipitated with LRP, with a preference for an isoform of APP containing the Kunitz protease inhibitor domain. Interaction of APP and LRP on the surface of living cells was demonstrated by crosslinking APP and LRP with the water-soluble cross-linking agent BS3. APP and LRP were shown by confocal microscopy to colocalize in perinuclear structures, but to primarily remain separate in vesicles and on the cell surface. We propose that full-length APP can transiently interact with the receptor LRP on the cell surface, affecting the processing and intracellular transport of APP. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Alzheimer Res Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neurogenet & Aging Unit, Charlestown, MA 02129 USA. Amer Red Cross, Rockville, MD 20855 USA. RP Rebeck, GW (reprint author), Massachusetts Gen Hosp, Alzheimer Res Unit, 149 13th St, Charlestown, MA 02129 USA. NR 37 TC 22 Z9 22 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD MAR 5 PY 2001 VL 87 IS 2 BP 238 EP 245 DI 10.1016/S0169-328X(01)00006-7 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 411YG UT WOS:000167526800011 ER PT J AU Sumii, T Singhal, AB Asahi, M Shimizu-Sasamata, M Suzuki, M Miyata, K Lo, EH AF Sumii, T Singhal, AB Asahi, M Shimizu-Sasamata, M Suzuki, M Miyata, K Lo, EH TI Protective effects of pamiteplase, a modified t-PA, in a rat model of embolic stroke SO NEUROREPORT LA English DT Article DE modified t-PA; neuroprotection; stroke; thrombolysis ID TISSUE-PLASMINOGEN ACTIVATOR; ACUTE ISCHEMIC STROKE; THROMBOLYTIC THERAPY; CEREBRAL-ISCHEMIA; YM866; HEMORRHAGE; ALTEPLASE; HEMATOMA; TRIAL; ECASS AB The effects of alteplase (tissue plasminogen activator, t-PA) and pamiteplase (a modified t-PA with longer half-life and increased potency) were compared in a clinically relevant model of embolic stroke. Rats were treated with pamiteplase (0.5 mg/kg or 1 mg/kg bolus), alteplase (10 mg/kg infusion) or normal saline. Pamiteplase (1 mg/kg) was as effective as alteplase in reducing 24 h brain infarct volumes, neurological deficit scores and residual clot grades. Cerebral blood flow recovery at 30 min after thrombolytic treatment was partial and did not correlate with 24 h infarct volumes or neurological deficits. However, there was good correlation between 24 h residual clot grades and infarct volumes, suggesting a delayed timeframe for pamiteplase- and alteplase-induced reperfusion. NeuroReport 12:615-618 (C) 2001 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Cambridge, MA 02138 USA. Kinki Univ, Sch Med, Dept Neurosurg, Osaka 589, Japan. Yamanouchi Pharmaceut Co Ltd, Inst Drug Discovery Res, Pharmacol Labs, Tsukuba, Ibaraki, Japan. RP Lo, EH (reprint author), Massachusetts Gen Hosp, Neuroprotect Res Lab, Dept Neurol, MGH E 149-2322, Charlestown, MA 02129 USA. FU NINDS NIH HHS [R01-NS38731, R01-NS37074, R29-NS32806] NR 21 TC 3 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAR 5 PY 2001 VL 12 IS 3 BP 615 EP 618 DI 10.1097/00001756-200103050-00037 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 403XT UT WOS:000167069000037 PM 11234775 ER PT J AU Martinez, V Tache, Y AF Martinez, V Tache, Y TI Role of CRF receptor 1 in central CRF-induced stimulation of colonic propulsion in rats SO BRAIN RESEARCH LA English DT Article DE corticotropin-releasing factor; CRF receptor; astressin; NBI-27914; stress; colonic motility; gastric emptying; brain-gut ID CORTICOTROPIN-RELEASING FACTOR; IRRITABLE-BOWEL-SYNDROME; IMPAIRED STRESS-RESPONSE; WATER-AVOIDANCE STRESS; PARAVENTRICULAR NUCLEUS; FOS EXPRESSION; MOTOR RESPONSE; ANTAGONIST; BRAIN; HYPOTHALAMUS AB The CRF receptor subtype mediating the colonic and gastric motor responses to central CRF was investigated in conscious rats. CRF (0.6 mug/rat) injected intracerebroventicularly (i.c.v.) or 1 h water avoidance stress stimulated defecation (pellet/60 min: 4.1 +/- 1.0 and 8.7 +/- 0.7 respectively vs. 0.3 +/- 0.3 in i.c.v. vehicle/no stress). The CRF receptor 1 (CRF-RI) antagonist, NBI-27914 (50-100 mug/rat) injected i.c.v., abolished the colonic response to i.c.v. CRF and dose-dependently reduced that induced by water avoidance stress. NBI-27914 (100 mug/rat) injected peripherally did not influence the defecatory response to stress. The peptide CRF-R1/R2 antagonist, astressin (10 mug/rat, i.c.v.) inhibited the colonic motor response to i.c.v. CRF and stress similarly as NBI-27914 injected i.c.v. at 100 mug/rat. Intracisternal (i.c.) injection of astressin (10 mug/rat) also completely prevented CRF (0.6 g, i.c.)-induced delayed gastric emptying while i.c. NBI-27914 (50 or 100 mug) had no effect. These results indicate a differential role of central CRF receptor subtypes in the colonic stimulatory and gastric inhibitory motor responses to central CRF and that the CRF component of stress-related activation of colonic expulsion is primarily mediated by CRF-R1. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, DDRC, CURE,Dept Med,Digest Dis Div, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. Cardenal Herrera Univ, Sch Vet, Dept Basic Biomed Sci, Valencia 46113, Spain. RP Tache, Y (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, DDRC, CURE,Dept Med,Digest Dis Div, Bldg 115,Room 203,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [DK-41301, DK33061] NR 38 TC 84 Z9 88 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 2 PY 2001 VL 893 IS 1-2 BP 29 EP 35 DI 10.1016/S0006-8993(00)03277-7 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 406QA UT WOS:000167225600004 PM 11222989 ER PT J AU Tu, YZ Kucik, DF Wu, CY AF Tu, YZ Kucik, DF Wu, CY TI Identification and kinetic analysis of the interaction between Nck-2 and DOCK180 SO FEBS LETTERS LA English DT Article DE DOCK180; Nck-2; SH3 domain; protein protein interaction; two-hybrid assay; surface plasmon resonance ID SURFACE-PLASMON RESONANCE; SH2/SH3 ADAPTER PROTEIN; SIGNALING PATHWAYS; SH3 DOMAIN; EXPRESSION; MEMBRANE; AFFINITY; BINDING AB Nck-2 is a newly identified adapter protein comprising three N-terminal SH3 domains and one C-terminal SH2 domain. We have identified in a yeast two-hybrid brid screen DOCK180, a signaling protein implicated in the regulation of membrane ruffling and migration, as a binding protein for Nck-2, Surface plasmon resonance analyses reveal that the second and the third SH3 domains interact with the C-terminal region of DOCK180. The interactions mediated by the individual SH3 domains, however, are much weaker than that of the full length Nck-2. Furthermore, a point mutation that inactivates the second or the third SH3 domain dramatically reduced the interaction of Nck-2 with DOCK180, suggesting that both SH3 domains contribute to the DOCK180 binding. A major Nck-2 binding site, which is recognized primarily by the third St13 domain, has been mapped to residues 1819-1836 of DOCK180. Two additional, albeit much,weaker, Nck-2 SH3 binding sites are located to DOCK180 residues 1793-1810 and 1835-1852 respectively. Consistent with the mutational studies, kinetic analyses by surface plasmon resonance suggest that two binding events with equilibrium dissociation constants of 4.15+/-1.9x10(-7) hi and 3.24+/-1.9 x 10(-9) M mediate the binding of GS5T-Nck-2 to CST fusion protein containing the C-terminal region of DOCK180, These studies identify a novel interaction between Nck-2 and DOCK180, Furthermore, they provide a detailed analysis of a protein complex formation mediated by multiple St13 domains revealing that tandem SH3 domains significantly enhance the weak interactions mediated by each individual SH3 domain. (C) 2001 Federation of European Biochemical Societies. published by Elsevier Science B.V. All rights reserved. C1 Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15261 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35233 USA. Birmingham VA Med Ctr, Birmingham, AL 35233 USA. RP Wu, CY (reprint author), Univ Pittsburgh, Dept Pathol, 707B Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. FU NIAMS NIH HHS [AR47716]; NIDDK NIH HHS [DK54639] NR 25 TC 34 Z9 37 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAR 2 PY 2001 VL 491 IS 3 BP 193 EP 199 DI 10.1016/S0014-5793(01)02195-0 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 408XT UT WOS:000167352800006 PM 11240126 ER PT J AU Li, YQ Kuwahara, H Ren, J Wen, GY Kufe, D AF Li, YQ Kuwahara, H Ren, J Wen, GY Kufe, D TI The c-Src tyrosine kinase regulates signaling of the human DF3/MUC1 carcinoma-associated antigen with GSK3 beta and beta-catenin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR LEF-1; TUMOR-SUPPRESSOR PROTEIN; MONOCLONAL-ANTIBODY DF3; CELL-CELL ADHESION; GROWTH-FACTOR; HUMAN CANCER; RECEPTOR; REACTIVITY; BINDING; COMPLEXES AB The DF3/MUC1 mucin-like glycoprotein is aberrantly overexpressed in most human carcinomas. The cytoplasmic domain of MUC1 interacts with glycogen synthase kinase 3 beta (GSK3 beta) and thereby decreases binding of MUC1 and beta -catenin. The present studies demonstrate that MUC1 associates with the c-Src tyrosine kinase. c-Src phosphorylates the MUC1 cytoplasmic domain at a YEKV motif located between sites involved in interactions with GSK3 beta and beta -catenin. The results demonstrate that the c-Src SH2 domain binds directly to pYEKV and inhibits the interaction between MUC1 and GSK3 beta. Moreover and in contrast to GSK3 beta, in vitro and in vivo studies demonstrate that c-Src-mediated phosphorylation of MUC1 increases binding of MUC1 and beta -catenin. The findings support a novel role for c-Src in regulating interactions of MUC1 with GSK3 beta and beta -catenin. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA87421] NR 34 TC 175 Z9 182 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 2 PY 2001 VL 276 IS 9 BP 6061 EP 6064 DI 10.1074/jbc.C000754200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 407FF UT WOS:000167261000002 PM 11152665 ER PT J AU Humphrey, GW Wang, YH Russanova, VR Hirai, T Qin, J Nakatani, Y Howard, BH AF Humphrey, GW Wang, YH Russanova, VR Hirai, T Qin, J Nakatani, Y Howard, BH TI Stable histone deacetylase complexes distinguished by the presence of SANT domain proteins CoREST/kiaa0071 and Mta-L1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTIONAL REPRESSION; NUCLEAR MATRIX; POLYAMINE OXIDASE; BINDING-PROTEINS; DNA METHYLATION; N-COR; YEAST; GENE; RPD3; SUPERFAMILY AB Human histone deacetylases I (HDAC1) and II (HDAC2) are homologous proteins (84% identity) that catalyze release of acetyl groups from modified N-terminal lysines of core histones, Histone deacetylation is correlated with both transient and persistent states of transcriptional inactivity (i.e. silencing) in many eukaryotes, In this study, we analyzed complexes containing HDAC1 and HDAC2 to identify the proteins most stably associated with these deacetylases. Complex cI (9.5 S) contained transcriptional corepressor CoREST/ kiaa0071 and a protein homologous to FAD-dependent oxidoreductases, kiaa0601, Complex cII (15 S) contained greater than or equal to 15 proteins, including CHD3/4 (Mi-2), Mta-L1, RbAp48/ 46, and MBD3, characteristic of vertebrate nucleosome-remodeling complexes. Under native conditions, cI and cII may contain HDAC1, HDAC2 or both; these can be dissociated to cI and cII core complexes containing only HDAC1 or HDAC2, The (m)CpG-binding protein MBD2 was associated only with the HDAC1 cII core complex, A model is proposed in which HDAC1 core complexes can be targeted to methylated DNA via MBD2 with recruitment of HDAC2 occurring through formation of HDAC1/2 cII dimers, We note that the cI component CoREST/kiaa0071 and the cII component Mta-L1 share a region of homology that includes a SANT domain; this domain may play a role in complex assembly. C1 NICHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Baylor Coll Med, Dept Biochem, Houston, TX 77030 USA. Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. RP Howard, BH (reprint author), NICHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. NR 52 TC 212 Z9 230 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 2 PY 2001 VL 276 IS 9 BP 6817 EP 6824 DI 10.1074/jbc.M007372200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 407FF UT WOS:000167261000095 PM 11102443 ER PT J AU Sugimori, H Speller, H Finklestein, SP AF Sugimori, H Speller, H Finklestein, SP TI Intravenous basic fibroblast growth factor produces a persistent reduction in infarct volume following permanent focal ischemia in rats SO NEUROSCIENCE LETTERS LA English DT Article DE focal cerebral ischemia; stroke; basic fibroblast growth factor ID CEREBRAL-ISCHEMIA; HIPPOCAMPAL-NEURONS; MODEL; SIZE; HOMEOSTASIS; GLUTAMATE; INJURY; DEATH AB Basic fibroblast growth factor (bFGF) is a polypeptide with potent survival-promoting and protective effects on brain cells. In previous studies, we showed that intravenous administration of bFGF reduced infarct volume in models of focal cerebral ischemia in rats, mice, and cats. In these previous studies, infarct volume was measured within 1-7 days of the onset of ischemia, The current study was undertaken to determine whether the reduction in infarct volume by bFGF was persistent beyond the first week after stroke. Mature male Sprague-Dawley rats received an intravenous infusion of bFGF (50 mug/kg per h) or vehicle during 0.5-3.5 h after permanent proximal middle cerebral artery occlusion. We found a 27% reduction in infarct volume in bFGF- compared to vehicle-treated animals at three months after infarction (P < 0.05). The data show that intravenous bFGF treatment produces a persistent reduction in infarct volume, at least up to three months following focal stroke. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, CNS, Growth Factor Res Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Finklestein, SP (reprint author), Massachusetts Gen Hosp, CNS, Growth Factor Res Lab, Warren 408, Boston, MA 02114 USA. NR 21 TC 19 Z9 25 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAR 2 PY 2001 VL 300 IS 1 BP 13 EP 16 DI 10.1016/S0304-3940(01)01549-X PG 4 WC Neurosciences SC Neurosciences & Neurology GA 404FA UT WOS:000167085700004 PM 11172928 ER PT J AU Sahani, D Saini, S Sharma, R O'Malley, M Hahn, P AF Sahani, D Saini, S Sharma, R O'Malley, M Hahn, P TI Dynamic T1-weighted ferumoxides enhanced MRI for imaging liver hemangiomas: preliminary observations SO ABDOMINAL IMAGING LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Roentgen-Ray-Society CY MAY 08, 2000 CL WASHINGTON, D.C. SP Amer Roentgen Ray Soc DE ferumoxides; liver hemangiomas; MRI ID SUPERPARAMAGNETIC IRON-OXIDE; CONTRAST AGENTS; HEPATIC-LESIONS; FERUMOXTRAN; METASTASES; TUMORS; CT AB The T1-based signal-enhancing effects of ferumoxides was studied in five liver hemangiomas on short echo-time gradient-recalled echo dynamic magnetic resonance imaging to assess the utility of this technique to image perfusion patterns in liver hemangiomas. We observed peripheral nodular enhancement with centripetal fill in all hemangiomas. Our results suggest that this imaging technique, after rapid injection of ferumoxides, can be used for lesion characterization. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Saini, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Ellison 234E,55 Fruit St, Boston, MA 02114 USA. NR 21 TC 5 Z9 7 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0942-8925 J9 ABDOM IMAGING JI Abdom. Imaging PD MAR-APR PY 2001 VL 26 IS 2 BP 166 EP 170 PG 5 WC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging SC Gastroenterology & Hepatology; Radiology, Nuclear Medicine & Medical Imaging GA 406LR UT WOS:000167218100010 PM 11178694 ER PT J AU Novelline, RA Scheiner, JD Mehta, A Mullins, M AF Novelline, RA Scheiner, JD Mehta, A Mullins, M TI Preparing medical students for a filmless environment: Instruction on the preparation of electronic case presentations from PACS SO ACADEMIC RADIOLOGY LA English DT Article DE education; images, display; images, storage and retrieval; picture archiving and communication system (PACS) ID RADIOLOGY; SYSTEM; FILE AB Rationale and Objectives. As the use of picture archiving and communication systems (PACS) expands and radiology departments become increasingly filmless, it will become increasingly necessary to teach physicians how to use PACS and download diagnostic images. The authors developed an instruction method in which medical students enrolled in a radiology clerkship were taught how to use the PACS, download digital images, and incorporate them into an electronic case presentation. The feasibility and potential benefits of this instructional method were studied prospectively. Materials and Methods. Between June and October 1999, all 36 medical students enrolled in Harvard Medical School's core radiology clerkship at Massachusetts General Hospital, Boston, were required to give an electronic radiology case presentation with images downloaded from the departmental PACS. They were taught how to download images, edit them, and then import them into PowerPoint software. They were also given access to the hospital information system to obtain pertinent clinical information. At the formal presentations, the images were displayed with a liquid crystal display (LCD) projector. The students were surveyed on the Ist and last days of the clerkship regarding their learning experiences. Results. Before the radiology clerkship, 81% of the students had never given an electronic presentation with computer and LCD projector, 83% had no PACS experience, and 56% had no PowerPoint experience. All students learned to pre pare and deliver electronic presentations of radiologic cases downloaded from PACS. Their presentations were informative, innovative, and entertaining, and the images were well displayed. The students praised the instruction highly and thought their new skills would serve them well. Conclusion. Teaching medical students how to prepare and deliver electronic presentations of radiologic cases downloaded from PACS proved to be very feasible and well appreciated by the students. C1 Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02116 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Rhode Isl Hosp, Dept Diagnost Imaging, Providence, RI USA. Brown Univ, Sch Med, Providence, RI 02912 USA. RP Novelline, RA (reprint author), Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02116 USA. NR 16 TC 7 Z9 8 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 MAR PY 2001 VL 8 IS 3 BP 266 EP 268 DI 10.1016/S1076-6332(03)80537-8 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 433QE UT WOS:000168770600009 PM 11249091 ER PT J AU Murthy, V Stemmer-Rachamimov, AO Haddad, LA Roy, JE Cutone, AN Beauchamp, RL Smith, N Louis, DN Ramesh, V AF Murthy, V Stemmer-Rachamimov, AO Haddad, LA Roy, JE Cutone, AN Beauchamp, RL Smith, N Louis, DN Ramesh, V TI Developmental expression of the tuberous sclerosis proteins tuberin and hamartin SO ACTA NEUROPATHOLOGICA LA English DT Article DE tuberin; hamartin; tuberous sclerosis; development ID NERVOUS-SYSTEM TISSUES; TSC2 PRODUCT TUBERIN; GENE-PRODUCTS; GROWTH SUPPRESSOR; CHROMOSOME 9Q34; TARGET RAP1; CELL-TYPE; HETEROZYGOSITY; IDENTIFICATION; KIDNEY AB Tuberous sclerosis complex is an autosomal dominant multisystem disorder, characterized by the development of hamartomas in multiple organs, primarily the skin, heart, kidney, and brain. The tuberous sclerosis genes, TSC1 and TSC2, encode hamartin and tuberin, respectively. Employing specific antibodies for hamartin and tuberin, we analyzed the expression of these two proteins by Western blot analyses in normal developing human and rat tissues. Both proteins are expressed ubiquitously in human fetal tissues and placenta, but are expressed at relatively low levels in human adult tissues, except brain. Similarly, high expression of these two proteins is observed in rat embryonic tissues, with a progressive decline after birth. To better characterize the developmental expression of tuberin and hamartin, we conducted a detailed study in rat tissues from embryonic day 13 to adult by Western blot analysis and immunohistochemistry. Immunohistochemical staining of rat tissues for tuberin and hamartin revealed tissue-specific expression patterns throughout development. Both tuberin and hamartin are expressed in epithelia, muscle (smooth, cardiac and skeletal muscle) and the nervous system (neurons, glia, choroid plexus and arachnoid). Except for the central nervous system, immunostaining intensity declines with age, confirming the protein blot analysis. These results indicate that tuberin and hamartin may play a critical role in development, and thus provide a framework for understanding the developmental and hamartomatous manifestations of tuberous sclerosis. These findings also suggest that tuberin and hamartin have additional functions in the adult brain, consistent with the marked neurological problems that afflict many patients with tuberous sclerosis. C1 Massachusetts Gen Hosp E, Dept Neurol, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Pathol & Neurosurg, Mol Neurooncol Lab, Charlestown, MA 02129 USA. RP Ramesh, V (reprint author), Massachusetts Gen Hosp E, Dept Neurol, Mol Neurogenet Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. EM louis@helix.mgh.harvard.edu; ramesh@helix.mgh.harvard.edu RI Haddad, Luciana/D-8002-2012 FU NINDS NIH HHS [NS24279] NR 45 TC 22 Z9 22 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-6322 EI 1432-0533 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD MAR PY 2001 VL 101 IS 3 BP 202 EP 210 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 411YA UT WOS:000167526200004 PM 11307618 ER PT J AU Jain, RK AF Jain, RK TI Delivery of molecular and cellular medicine to solid tumors SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE tumor microcirculation; angiogenesis; blood flow; vascular permeability; diffusion and convection; receptor-ligand binding; interstitial pressure; lymphatics; cell adhesion and deformation; cancer detection and treatment ID INTERSTITIAL FLUID PRESSURE; ENDOTHELIAL GROWTH-FACTOR; NATURAL-KILLER-CELLS; VASCULAR-PERMEABILITY FACTOR; COLON ADENOCARCINOMA XENOGRAFT; ENZYME-CONJUGATED ANTIBODIES; POSITRON EMISSION TOMOGRAPHY; INDUCED LEUKOCYTE ADHESION; HUMAN-MELANOMA XENOGRAFTS; NECROSIS-FACTOR-ALPHA AB To reach cancer cells in a tumor, a blood-borne therapeutic molecule or cell must make its way into the blood vessels of the tumor and across the vessel wall into the interstitium, and finally migrate through the interstitium. Unfortunately, tumors often develop in ways that hinder each of these steps. Our research goals are to analyze each of these steps experimentally and theoretically, and then integrate the resulting information in a unified theoretical framework. This paradigm of analysis and synthesis has allowed us to obtain a better understanding of physiological barriers in solid tumors, and to develop novel strategies to exploit and/or to overcome these barriers for improved cancer detection and treatment. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu NR 148 TC 394 Z9 404 U1 2 U2 49 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X EI 1872-8294 J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD MAR 1 PY 2001 VL 46 IS 1-3 BP 149 EP 168 DI 10.1016/S0169-409X(00)00131-9 PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 413KJ UT WOS:000167611100010 PM 11259838 ER PT J AU O'Connell, JX Nielsen, GP Rosenberg, AE AF O'Connell, JX Nielsen, GP Rosenberg, AE TI Epithelioid vascular tumors of bone: A review and proposal of a classification scheme SO ADVANCES IN ANATOMIC PATHOLOGY LA English DT Review DE hemangioma; hemangioendothelioma; angiosarcoma; bone; epithelioid ID HEMANGIOENDOTHELIOMA ANGIOSARCOMA; HISTIOCYTOID HEMANGIOMA; DIAGNOSIS; MISTAKEN; LESIONS; SKIN AB Skeletal vascular tumors composed of epithelioid endothelial cells commonly result in diagnostic difficulty. Although tumors with this morphology have been recognized for many years, there is a considerable degree of confusion regarding their nomenclature and classification. In this article what is believed to represent the morphologic features of this family of tumors is outlined, the historical context of epithelioid endothelial tumors is briefly discussed, and pertinent literature and texts pertaining to the subject is reviewed. It is proposed that the osseous epithelioid endothelial tumors should be classified in a similar manner to their soft tissue counterparts and it is suggested that this approach should help to clarify the confusion surrounding this subject of surgical pathology. C1 Surrey Mem Hosp, Dept Pathol, Surrey, BC V3V 1Z2, Canada. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP O'Connell, JX (reprint author), Surrey Mem Hosp, Dept Pathol, 13750 96th Ave, Surrey, BC V3V 1Z2, Canada. NR 55 TC 43 Z9 46 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-4109 J9 ADV ANAT PATHOL JI Adv. Anat. Pathol. PD MAR PY 2001 VL 8 IS 2 BP 74 EP 82 DI 10.1097/00125480-200103000-00003 PG 9 WC Pathology SC Pathology GA 406AA UT WOS:000167191700003 PM 11236956 ER PT J AU Hasaba, A Laposata, M AF Hasaba, A Laposata, M TI The synthesis and secretion of fatty acid ethyl esters from HepG2 cells are stimulated by lipoproteins and albumin SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ethanol; albumin; lipoproteins; fatty acid ethyl esters ID NONOXIDATIVE ETHANOL-METABOLISM; LIVER-MICROSOMES; HUMAN SERUM; SYNTHASE; PURIFICATION; MYOCARDIUM; BINDING AB Background: Fatty acid ethyl esters (FAEEs) are nonoxidative metabolites of ethanol produced by theesterification of fatty acids and ethanol. FAEEs have been implicated as mediators of ethanol-induced organ damage in vivo and in vitro. They are detectable in the blood and in many organs after ethanol ingestion, and on this basis they are useful markers of ethanol intake in living patients as well as subjects at autopsy. FAEEs found in human plasma, after ethanol ingestion bind to lipoproteins and albumin. Methods: In this study, we used a hepatoblastoma cell model (HepG2) to determine if lipoproteins or albumin stimulates the synthesis and/or secretion of FAEEs from HepG2 cells. Because FAEEs have been shown to decrease HepG2 cellular proliferation and protein synthesis, their removal from cells potentially could reestablish normal cell activity. HepG2 cells were incubated with 100 mM ethanol and 6 nM H-3 oleic acid to generate H-3-FAEEs within the cells. Dose response and time course studies were performed by using low density lipoproteins, high density lipoproteins, and albumin as FAEE accepters. Results: The results indicate that FAEEs are extracted efficiently by each of these FAEE carriers and that FAEE synthesis also is stimulated by the addition of FAEE carriers to the extracellular medium. Conclusion: These observations indicate that lipoproteins and albumin can extract ethyl esters from HepG2 cells and thereby may limit alcohol-induced liver damage. C1 Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, 55 Fruit St Gray 235, Boston, MA 02114 USA. NR 25 TC 7 Z9 7 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAR PY 2001 VL 25 IS 3 BP 338 EP 343 DI 10.1111/j.1530-0277.2001.tb02219.x PG 6 WC Substance Abuse SC Substance Abuse GA 413DH UT WOS:000167594300003 PM 11290843 ER PT J AU Schulenberg, J Maggs, JL Long, SW Sher, KJ Gotham, HJ Baer, JS Kivlahan, DR Marlatt, GA Zucker, RA AF Schulenberg, J Maggs, JL Long, SW Sher, KJ Gotham, HJ Baer, JS Kivlahan, DR Marlatt, GA Zucker, RA TI The problem of college drinking: Insights from a developmental perspective SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE binge drinking; college drinking; developmental disturbance model; alcohol use disorders; alcohol expectancies; brief intervention; developmental course ID BRIEF INTERVENTION; YOUNG ADULTHOOD; BINGE-DRINKING; STUDENTS AB This article represents the proceedings of a symposium at the 2000 RSA Meeting in Denver, Colorado. John Schulenberg and Jennifer L. Maggs were Organizers. Stephen W. Long was Chair and provided opening remarks. The presentations were: (1) I'm not a drunk, just a college student: Binge drinking during college as a developmental disturbance, by John Schulenberg; (2) Course of alcohol use disorders during college, by Kenneth J. Sher; (3) How do students experience alcohol and its effects? Positive versus negative expectancies and consequences, by Jennifer L. Maggs; and (4) Brief intervention in the context of developmental trends in college drinking, by G. Alan Marlatt. Critique and commentary were provided by Robert A. Zucker. C1 Univ Michigan, Inst Social Res, Ann Arbor, MI 48106 USA. Univ Michigan, Dept Psychol, Ann Arbor, MI 48106 USA. Univ Michigan, Alcohol Res Ctr, Ann Arbor, MI 48106 USA. Univ Arizona, Div Family Studies & Human Dev, Tucson, AZ USA. NIAAA, Bethesda, MD USA. Univ Missouri, Dept Psychol, Columbia, MO USA. St Louis VAMC, St Louis, MO USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Schulenberg, J (reprint author), Univ Michigan, Inst Social Res, Ann Arbor, MI 48106 USA. RI Schulenberg, John/A-2212-2008 OI Schulenberg, John/0000-0003-2129-8486 FU NIAAA NIH HHS [AA06324, R37AA05591, R37AA7231] NR 15 TC 76 Z9 76 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD MAR PY 2001 VL 25 IS 3 BP 473 EP 477 DI 10.1111/j.1530-0277.2001.tb02237.x PG 5 WC Substance Abuse SC Substance Abuse GA 413DH UT WOS:000167594300021 PM 11290861 ER PT J AU Cooper, WO Kuhlthau, K AF Cooper, WO Kuhlthau, K TI Evaluating medicaid managed care programs for children SO AMBULATORY PEDIATRICS LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the Ambulatory-Pediatric-Association CY MAY 01-08, 1998 CL NEW ORLEANS, LOUISIANA SP Ambulatory Pediat Assoc DE Medicaid; health insurance; health services research ID HIGH-RISK CHILDREN; PERINATAL OUTCOMES; HEALTH-CARE; TENNCARE; ORGANIZATIONS; CONTINUITY; ENROLLMENT; TENNESSEE; REFORM; IMPLEMENTATION AB Nearly every state has implemented some form of managed care for Medicaid recipients, partly in response to rapid increases in Medicaid expenditures. The unique features of children's health and the differences among states in the implementation and scope of their Medicaid managed care programs provide child health services researchers many opportunities to identify program features that result in favorable health outcomes and those that are less successful. Key stakeholders with interest in this information include state governments and managed care organizations charged with developing and implementing efficient delivery systems, as well as providers interested in understanding the best mechanisms for delivering care to children. This paper outlines potential approaches to evaluating Medicaid managed care programs for children, focusing on identification of appropriate data sources and selection of quality measures encompassing the structure, processes, and outcomes of health care. C1 Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA. MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Cooper, WO (reprint author), Vanderbilt Childrens Hosp, Div Gen Pediat, Suite 5028 MCE, Nashville, TN 37232 USA. NR 39 TC 11 Z9 11 U1 0 U2 2 PU AMBULATORY PEDIATRIC ASSOC PI MCLEAN PA 6728 OLD MCLEAN VILLAGE DR, MCLEAN, VA 22101-3906 USA SN 1530-1567 J9 AMBUL PEDIATR JI Ambul. Pediatr. PD MAR-APR PY 2001 VL 1 IS 2 BP 112 EP 116 DI 10.1367/1539-4409(2001)001<0112:EMMCPF>2.0.CO;2 PG 5 WC Pediatrics SC Pediatrics GA 473YG UT WOS:000171076400009 PM 11888383 ER PT J AU Cannon, CP McCabe, CH Wilcox, RG Bentley, JH Braunwald, E AF Cannon, CP McCabe, CH Wilcox, RG Bentley, JH Braunwald, E CA OPUS-TIMI 16 Investigators TI Association of white blood cell count with increased mortality in acute myocardial infarction and unstable angina pectoris SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID C-REACTIVE PROTEIN; ACUTE CORONARY SYNDROMES; PROGNOSTIC VALUE; LEUKOCYTE COUNT; TRIAL; RISK; EVENTS; INFLAMMATION; PRAVASTATIN; PREDICTOR C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Queens Med Ctr, Nottingham NG7 2UH, England. Nottingham Clin Res Grp, Nottingham, England. RP Cannon, CP (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. NR 19 TC 115 Z9 126 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 1 PY 2001 VL 87 IS 5 BP 636 EP 639 DI 10.1016/S0002-9149(00)01444-2 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 406LQ UT WOS:000167218000025 PM 11230853 ER PT J AU Paietta, E Neuberg, D Richards, S Bennett, JM Han, L Racevskis, J Dewald, G Rowe, JM Wiernik, PH AF Paietta, E Neuberg, D Richards, S Bennett, JM Han, L Racevskis, J Dewald, G Rowe, JM Wiernik, PH CA Eastern Cooperative Oncology Grp TI Rare adult acute lymphocytic leukemia with CD56 expression in the ECOG experience shows unexpected phenotypic and genotypic heterogeneity SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE acute lymphocytic leukemia; CD56 antigen ID ACUTE LYMPHOBLASTIC-LEUKEMIA; NATURAL-KILLER-CELLS; P-GLYCOPROTEIN EXPRESSION; ACUTE MYELOID-LEUKEMIA; B-LINEAGE CELLS; T-CELL; PERIPHERAL-BLOOD; NK-CELL; BONE-MARROW; LYMPHOMAS AB Expression of CD56, a marker of natural killer (NK) cells, in acute lymphocytic leukemia (ALL) is rare and, to date, has been described only in non-B lineage ALL. Among 194 patients with CD56 analysis on the ongoing Eastern Cooperative Oncology Group (ECOG) ALL trial, E2993, 6 cases of CD56(+) ALL were found (3.1%) with a median of 95% of blast cells expressing CD56, compared with a median of 1% of blast cells in CD56(-) ALL (P = 0.0001). FAB-L2 characteristics dominated, without granulation. Blast cells from four CD56(+) patients expressed T-cell antigens at variable levels of maturation. A clonal rearrangement of the T-cell receptor beta (TCR beta) gene was detected only in one patient. TCR beta variable gene usage studies in this and one other CD56(+) ALL patient demonstrated a significantly perturbed usage pattern in both patients when compared with control lymphocytes, The two remaining cases typed as early pre-B ALL (CD19(+), CD10(+)), with one case co-expressing CD7, Cytogenetically, 4 patients were normal, 1 complex abnormal, and 1 Philadelphia chromosome positive. Epstein-Barr virus (EBV) sequences were detected in one T- and both B-lymphoid cases. Our data suggest that CD56 is expressed at a precursor stage common to the T- and the B-cell lineage. Am. J, Hematol, 66:189-196, 2001, (C) 2001 Wiley-Liss, Inc. C1 New York Med Coll, Our Lady Mercy Canc Ctr, Immunol Lab, Bronx, NY 10466 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. MRC, London, England. Univ Rochester, Rochester, NY USA. Abbott NW Hosp, Minneapolis, MN 55407 USA. Mayo Clin, Rochester, MN USA. Rambam Med Ctr, Haifa, Israel. Eastern Cooperat Oncol Grp, Brookline, MA USA. RP Paietta, E (reprint author), New York Med Coll, Our Lady Mercy Canc Ctr, Immunol Lab, 600 E 233rd St, Bronx, NY 10466 USA. FU NCI NIH HHS [CA23318, CA21115, CA11083] NR 40 TC 16 Z9 16 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 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAR PY 2001 VL 66 IS 3 BP 189 EP 196 DI 10.1002/1096-8652(200103)66:3<189::AID-AJH1043>3.0.CO;2-A PG 8 WC Hematology SC Hematology GA 402CU UT WOS:000166969100005 PM 11279625 ER PT J AU Slaugenhaupt, SA Blumenfeld, A Gill, SP Leyne, M Mull, J Cuajungco, MP Liebert, CB Chadwick, B Idelson, M Reznik, L Robbins, CM Makalowska, I Brownstein, MJ Krappmann, D Scheidereit, C Maayan, C Axelrod, FB Gusella, JF AF Slaugenhaupt, SA Blumenfeld, A Gill, SP Leyne, M Mull, J Cuajungco, MP Liebert, CB Chadwick, B Idelson, M Reznik, L Robbins, CM Makalowska, I Brownstein, MJ Krappmann, D Scheidereit, C Maayan, C Axelrod, FB Gusella, JF TI Tissue-specific expression of a splicing mutation in the IKBKAP gene causes familial dysautonomia SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID PROTEIN; LOCALIZATION; CLONING; 9Q31 AB Familial dysautonomia (FD; also known as "Riley-Day syndrome"), an Ashkenazi Jewish disorder, is the best known and most frequent of a group of congenital sensory neuropathies and is characterized by widespread sensory and variable autonomic dysfunction. Previously, we had mapped the FD gene, DYS, to a 0.5-cM region on chromosome 9q31 and had shown that the ethnic bias is due to a founder effect, with >99.5% of disease alleles sharing a common ancestral haplotype. To investigate the molecular basis of FD, we sequenced the minimal candidate region and cloned and characterized its five genes. One of these, IKBKAP, harbors two mutations that can cause FD. The major haplotype mutation is located in the donor splice site of intron 20. This mutation can result in skipping of exon 20 in the mRNA of patients with FD, although they continue to express varying levels of wild-type message in a tissue-specific manner. RNA isolated from lymphoblasts of patients is primarily wild-type, whereas only the deleted message is seen in RNA isolated from brain. The mutation associated with the minor haplotype in four patients is a missense (R696P) mutation in exon 19, which is predicted to disrupt a potential phosphorylation site. Our findings indicate that almost all cases of FD are caused by an unusual splice defect that displays tissue-specific expression; and they also provide the basis for rapid carrier screening in the Ashkenazi Jewish population. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Harvard Inst Human Genet, Boston, MA USA. Hadassah Univ Hosp, Dept Clin Biochem, IL-91120 Jerusalem, Israel. Hadassah Univ Hosp, Dept Pediat, IL-91120 Jerusalem, Israel. NIMH, Genet Lab, NIH, Bethesda, MD 20892 USA. NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. Max Delbruck Ctr Mol Med, Berlin, Germany. NYU Med Ctr, Dept Pediat, New York, NY 10016 USA. RP Gusella, JF (reprint author), Massachusetts Gen Hosp E, Room 6214,149 13th St, Charlestown, MA 02129 USA. RI Brownstein, Michael/B-8609-2009; Cuajungco, Math/B-2647-2008; OI Cuajungco, Math/0000-0003-0749-9564; Krappmann, Daniel/0000-0001-7640-3234 FU NINDS NIH HHS [NS 36326] NR 21 TC 319 Z9 323 U1 0 U2 17 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD MAR PY 2001 VL 68 IS 3 BP 598 EP 605 DI 10.1086/318810 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 402ND UT WOS:000166994200005 PM 11179008 ER PT J AU Maung, HM Elangovan, L Frazao, JM Bower, JD Kelley, BJ Acchiardo, SR Rodriguez, HJ Norris, KC Sigala, JF Rutkowski, M Robertson, JA Goodman, WG Levine, BS Chesney, RW Mazess, RB Kyllo, DM Douglass, LL Bishop, CW Coburn, JW AF Maung, HM Elangovan, L Frazao, JM Bower, JD Kelley, BJ Acchiardo, SR Rodriguez, HJ Norris, KC Sigala, JF Rutkowski, M Robertson, JA Goodman, WG Levine, BS Chesney, RW Mazess, RB Kyllo, DM Douglass, LL Bishop, CW Coburn, JW TI Efficacy and side effects of intermittent intravenous and oral doxercalciferol (1 alpha-hydroxyvitamin D-2) in dialysis patients with secondary hyperparathyroidism: A sequential comparison SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE intact parathyroid hormone (iPTH); renal osteodystrophy; secondary hyperparathyroidism; hemodialysis (HD); renal failure; 1 alpha-hydroxyvitamin D-2 (1 alpha D-2); doxercalciferol (1 alpha D-2); intravenous trial; oral trial; vitamin D; hypercalcemia; hyperphosphatemia ID HEMODIALYSIS-PATIENTS; PARATHYROID-HORMONE; CALCITRIOL THERAPY; VITAMIN-D-2; SUPPRESSION; PATHWAY AB Most reports on the effectiveness and side effects of oral versus parenteral calcitriol or alfacalcidol in hemodialysis patients with secondary hyperparathyroidism show no advantage of parenteral treatment. The efficacy and safety of intravenous doxercalciferol (1 alphaD(2)) were studied in hemodialysis patients with secondary hyperparathyroidism (plasma intact parathyroid hormone [iPTH]: range, 266 to 3,644 pg/mL; median, 707 pg/mL). These results were compared with those of a previous trial using intermittent oral 1 alphaD(2); the same 70 patients were entered onto both trials, and 64 patients completed both trials per protocol. Twelve weeks of open-label treatment in both trials were preceded by identical 8-week washout periods. Degrees of IPTH suppression from baseline were similar in the two trials, with iPTH level reductions less than 50% in 89% and 78% of patients during oral and intravenous treatment, respectively. Grouping patients according to entry IPTH levels (<750 and 750 pg/mL) showed similar but more rapid iPTH suppression in the low-iPTH groups, whereas longer treatment and larger doses were required by the high-iPTH groups. Highest serum calcium levels averaged 9.82 +/- 0.14 and 9.67 +/- 0.11 mg/dL during oral and intravenous 1 alphaD(2) treatment, respectively (P = not significant [NS]), Prevalences of serum calcium levels greater than 11.2 mg/dL during oral and intravenous treatment were 3.62% and 0.86% of calcium measurements, respectively (P < 0.001), Highest serum phosphorus levels during oral and intravenous treatment averaged 5.82 +/- 0.21 and 5.60 +/- 0.21 mg/dL, respectively (P = NS). The percentage of increments in serum phosphorus levels during oral treatment exceeded that during Intravenous treatment during 5 of 12 treatment weeks. Thus, intermittent oral and intravenous therapy with 1D-2 reduced iPTH levels effectively and similarly, hypercalcemia was less frequent, and serum phosphorus levels increased less during Intravenous than oral 1 alphaD(2) therapy, suggesting that intravenous 1 alphaD(2) therapy may be advantageous In patients prone to hypercalcemia or hyperphosphatemia. (C) 2001 by the National Kidney Foundation, Inc. C1 Vet Affairs W Los Angeles Healthcare Ctr, Med Serv, Los Angeles, CA USA. Vet Affairs W Los Angeles Healthcare Ctr, Res Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Cedars Sinai Med Ctr, Dept Med, Sch Med, Los Angeles, CA 90048 USA. Charles R Drew Univ, Dept Med, Los Angeles, CA USA. Univ Tennessee, Dept Pediat, Memphis, TN USA. Univ Tennessee, Dept Med, Memphis, TN USA. Univ Mississippi, Div Nephrol, Jackson, MS 39216 USA. Bone Care Int Inc, Madison, WI USA. RP Coburn, JW (reprint author), W Los Angeles Vet Affairs Med Ctr, Nephrol Sect 111L, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Frazao, Joao/J-9811-2013 OI Frazao, Joao/0000-0002-8081-5474 FU NCRR NIH HHS [1 P20 RR11145-01] NR 19 TC 78 Z9 79 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD MAR PY 2001 VL 37 IS 3 BP 532 EP 543 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 411JQ UT WOS:000167495600010 PM 11228177 ER PT J AU Glassman, PA Good, CB Kelley, ME Bradley, M Valentino, M Ogden, J Kizer, KW AF Glassman, PA Good, CB Kelley, ME Bradley, M Valentino, M Ogden, J Kizer, KW TI Physician perceptions of a National Formulary SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the Society-of-General-Internal-Medicine CY APR 29-MAY 01, 1999 CL SAN FRANCISCO, CALIFORNIA SP Soc Gen Internal Med ID HEALTH MAINTENANCE ORGANIZATIONS; ATTITUDES; SYSTEM; COST; RESTRICTIONS; GUIDELINES; MANAGEMENT; BENEFITS; SERVICES; PROGRAM AB Objectives: To assess the perceptions of US Department of Veterans Affairs (VA) physicians regarding effects of a National Formulary (NF) on patient care, access to drugs, physician workload, and resident training approximately 1 year after it was implemented. Study Design: Cross-sectional survey. Methods: A questionnaire was sent to attending physicians working within the VA healthcare system. Participants included general internists (n = 2824), neurologists.(n = 238), psychiatrists (n = 997), general surgeons (n = 429), and urologists (n = 152). The response rate was 45%. Results: Most physicians (63%) thought that they could prescribe needed drugs; 65% agreed that patients could obtain needed nonformulary drugs. One third disagreed that access to prescription pharmaceuticals had increased; 29% stated the NF impinged on providing quality care to their own patients, and 21% thought it did so to patients from other VA facilities. Thirty eight percent of physicians perceived the NF to be more restrictive than private sector formularies; 16% thought that the NF diminished the ability to train residents for managed care. Forty percent thought that the NF added to workload. Generalists more often perceived that the NF improved their ability to provide care compared with neurologists (27% vs 18%, P=.046), psychiatrists (27% vs 22%, P=.027), and internal medicine sub specialists (27% vs 18%, P =.001). Physicians with more clinic time were more likely to perceive that the NF increased workload. Conclusion: Although differences of opinions among physicians were noted, most responding VA physicians did not perceive that the NF adversely affected patient care, access to pharmaceuticals, physician workload, or resident training. C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Pittsburgh, Vet Affairs Med Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. RAND, Survey Res Grp, Washington, DC USA. Vet Affairs Hosp, Pharm Benefits Management Strateg Healthcare Grp, Hines, IL USA. Dept Vet Affairs, Pharm Benefits Management Strateg Healthcare Grp, Washington, DC USA. Natl Qual Forum, Washington, DC USA. RP Glassman, PA (reprint author), W Los Angeles Vet Affairs Med Ctr, Div Gen Internal Med, 111G,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 47 TC 12 Z9 12 U1 0 U2 2 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD MAR PY 2001 VL 7 IS 3 BP 241 EP 251 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 409AN UT WOS:000167362500002 PM 11258142 ER PT J AU Bellon, RJ Putman, CM Budzik, RF Pergolizzi, RS Reinking, GF Norbash, AM AF Bellon, RJ Putman, CM Budzik, RF Pergolizzi, RS Reinking, GF Norbash, AM TI Rheolytic thrombectomy of the occluded internal carotid artery in the setting of acute ischemic stroke SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Neuroradiology CY APR, 2000 CL ATLANTA, GEORGIA SP Amer Soc Neuroradiol ID MYOCARDIAL-INFARCTION; RAPID THROMBECTOMY; CATHETER; ANGIOJET; PROUROKINASE; THROMBOLYSIS; OCCLUSION; PROACT; TRIAL AB BACKGROUND AND PURPOSE: Acute thromboembolic stroke complicated by ipsilateral carotid occlusion may present both mechanical and inflow-related barriers to effective intracranial thrombolysis. We sought to review our experience with a novel method of mechanical thrombectomy, in such cases, using the Possis AngioJet system, a rheolytic thrombectomy device. METHODS: A review of our interventional neuroradiology database revealed three patients in whom an occluded cervical internal carotid artery was encountered during endovascular treatment for acute stroke and in whom thrombectomy was attempted, using the 5F Possis AngioJet thrombectomy catheter. The medical records and radiographic studies of these patients were reviewed. RESULTS: Three patients were identified (ages, 52-84 years). Two patients had isolated occlusion of the internal carotid artery; in one patient, thrombus extended down into the common carotid artery. Treatment was initiated within 190 to 360 minutes of stroke onset. Thrombectomy of the carotid artery was deemed necessary because of poor collateral flow to the affected hemisphere (chronic contralateral internal carotid artery occlusion [one patient] and thrombus extending to the carotid "T" [one patient]) or inability to pass a microcatheter through the occluded vessel (one patient). Adjunctive therapy included pharmacologic thrombolysis with tissue plasminogen activator (all patients), carotid angioplasty and stenting (two patients), and middle cerebral artery angioplasty (one patient). Patency of the carotid artery was reestablished in two patients, with some residual thrombus burden. In the third patient, the device was able to create a channel through the column of thrombus, allowing intracranial access. CONCLUSION: Rheolytic thrombectomy shows potential for rapid, large-burden thrombus removal in cases of internal carotid artery thrombosis, allowing expedient access to the intracranial circulation for additional thrombolytic therapy. C1 Massachusetts Gen Hosp, Dept Intervent Neuroradiol, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Bellon, RJ (reprint author), Massachusetts Gen Hosp, Dept Intervent Neuroradiol, GRB 289,55 Fruit St, Boston, MA 02114 USA. NR 16 TC 66 Z9 67 U1 0 U2 1 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAR PY 2001 VL 22 IS 3 BP 526 EP 530 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 409VC UT WOS:000167405500021 PM 11237980 ER PT J AU Eskey, CJ Ogilvy, CS AF Eskey, CJ Ogilvy, CS TI Fluoroscopy-guided lumbar puncture: Decreased frequency of traumatic tap and implications for the assessment of CT-negative acute subarachnoid hemorrhage SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Neuroradiology CY APR, 2000 CL ATLANTA, GEORGIA SP Amer Soc Neuroradiol ID INTRACRANIAL ANEURYSMS; COMPUTED-TOMOGRAPHY; ANGIOGRAPHY; EXPERIENCE; FLUID AB BACKGROUND AND PURPOSE: In patients with suspected subarachnoid hemorrhage (SAH) and negative CT findings, the iatrogenic introduction of RBCs into the CSF during lumbar puncture may lead to a misdiagnosis. We tested the hypothesis that the risk off traumatic lumbar puncture is lower with the fluoroscopy-guided technique than with the standard bedside technique. METHODS: Data were collected retrospectively from two populations: adult inpatients undergoing standard bedside lumbar puncture for any reason and adult patients undergoing fluoroscopy-guided lumbar puncture for myelography. Patients with SAH and CSF samples with significant abnormalities other than erythrocytosis (ie, CSF leukocytosis, xanthochromia, or elevated protein) were excluded. In all, 1489 bedside procedures and 723 fluoroscopy-guided procedures met the criteria. RESULTS: We found a significant difference in the level of iatrogenic CSF erythrocytosis produced by the two procedures. Using a cutoff of 1000 cells/mm(3), the frequency of traumatic lumbar puncture was 10.1% for bedside lumbar puncture and 3.5% for fluoroscopy-guided lumbar puncture. With fluoroscopic guidance, the frequency of a traumatic tap varied significantly with the operator, ranging from 0% to 24%. CONCLUSION: The use of fluoroscopy-guided lumbar puncture in patients with suspected SAH and negative CT findings should reduce the frequency of false-positive diagnoses of acute SAH as well as the number of unnecessary angiograms for patients with suspected SAH but no underlying intracranial vascular malformation. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Eskey, CJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, GR-285,55 Fruit St, Boston, MA 02114 USA. NR 24 TC 42 Z9 42 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD MAR PY 2001 VL 22 IS 3 BP 571 EP 576 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 409VC UT WOS:000167405500027 PM 11237986 ER PT J AU Berman, S Richardson, DK Cohen, AP Pursley, DM Lieberman, E AF Berman, S Richardson, DK Cohen, AP Pursley, DM Lieberman, E TI Relationship of race and severity of neonatal illness SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 19th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY JAN 18-23, 1999 CL SAN FRANCISCO, CALIFORNIA SP Soc Maternal Fetal Med DE neonatal outcome; race; severity of illness; prematurity ID LOW-BIRTH-WEIGHT; RACIAL-DIFFERENCES; PREDICTIVE VALUE; INTENSIVE-CARE; MORTALITY; MORBIDITY; NEWBORNS; HEALTH; INDEX; RISK AB OBJECTIVE: Our goal was to determine whether there are racial differences in the severity of illness on admission for premature newborn infants independent of gestational age. STUDY DESIGN: The study population consisted of all African American and Caucasian singleton infants with gestational ages < 34 weeks who were admitted to the neonatal intensive care unit at Brigham and Women's Hospital between December 1994 and November 1995. Illness severity was measured with a neonatal severity of illness score, the SNAP score (Score for Neonatal Acute Physiology). The SNAP score is a physiologic scoring system that ranks the worst physiologic derangements in each organ system in the first 12 hours of life. It is an objective measure of neonatal illness severity with scores ranging from 0 (healthy) to 42 (most severely ill). Student t tests, chi (2) analysis, and Fisher exact tests were used to assess statistical significance. Linear and logistic regression analyses were used to examine associations while confounding factors were controlled for. RESULTS: There were 129 (79%) Caucasian and 36 (22%) African American newborns included in the analysis. Caucasian newborns had significantly higher mean SNAP scores than African American newborns (8.8 vs 6.3; P < .05). Compared with African American newborns, Caucasian newborns were more than twice as likely to have a SNAP score > 10 (33% vs 14%; P < .05). In a linear regression analysis in which we controlled for gestational age, birth weight, preterm premature rupture of membranes, preterm labor, preeclampsia, intrapartum fever greater than or equal to 100.4 degreesF, route of delivery, and other maternal and fetal factors, African American newborns were predicted to have a SNAP score that was on average 3.0 points lower than that of Caucasian newborns (P = .005). In a logistic regression in which we controlled for the above-mentioned confounders, African American newborns were only 14% as likely to have a SNAP score > 10 when compared with Caucasian newborns (odds ratio, 0.14; 95% confidence interval, 0.04-0.51). CONCLUSIONS: Over a broad range of prematurity, Caucasian newborns were more ill than African American newborns on admission to the neonatal intensive care unit. C1 Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Detroit, MI 48201 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, Childrens Hosp, Div Newborn Med,Beth Osrael Deaconess Med Ctr, Cambridge, MA 02138 USA. Harvard Univ, Brigham & Womens Hosp, Dept Obstet & Gynecol, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Maternal & Child Hlth, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Berman, S (reprint author), Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, 4707 St Antoine Blvd, Detroit, MI 48201 USA. FU AHRQ HHS [R03-HS08830, R01-HS07015] NR 26 TC 13 Z9 13 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 2001 VL 184 IS 4 BP 668 EP 672 DI 10.1067/mob.2001.109941 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 417NP UT WOS:000167841300024 PM 11262470 ER PT J AU DeAngelis, MM McGee, TL Keats, BJB Slim, R Berson, EL Dryja, TP AF DeAngelis, MM McGee, TL Keats, BJB Slim, R Berson, EL Dryja, TP TI Two families from New England with Usher syndrome type IC with distinct haplotypes SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID SYNDROME TYPE 1C; CANDIDATE GENES; LOCUS; LOCALIZATION; REGION; MAPS; HYPERINSULINISM; CHROMOSOME-11; ARM AB PURPOSE: To search for patients with Usher syndrome type IC among those with Usher syndrome type I who reside in New England. METHODS: Genotype analysis of microsatellite markers closely linked to the USH1C locus was done using the polymerase chain reaction. We compared the haplotype of our patients who were homozygous in the USH1C region with the haplotypes found in previously reported USH1C Acadian families who reside in southwestern Louisiana and from a single family residing in Lebanon, RESULTS: Of 46 unrelated cases of Usher syndrome type I residing in New England, two were homozygous at genetic markers in the USH1C region. Of these, one carried the Acadian USH1C haplotype and had Acadian ancestors (that is, from Nova Scotia) who did not participate in the 1755 migration of Acadians to Louisiana, The second family had a haplotype that proved to be the same as that of a family with USH1C residing in Lebanon, Each of the two families had haplotypes distinct from the other. CONCLUSION: This is the first report that some patients residing in New England have Usher syndrome type IC, Patients with Usher syndrome type IC can have the Acadian haplotype or the Lebanese haplotype compatible with the idea that at least two independently arising pathogenic mutations have occurred in the yet-to-be identified USH1C gene. (Am J Ophthalmol 2001;131:355-358, (C) 2001 by Elsevier Science Inc. All rights reserved.). C1 Massachusetts Eye & Ear Infirm, Ocular Mol Genet Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. Louisiana State Univ, Hlth Sci Ctr, Dept Biometry & Genet, New Orleans, LA USA. Amer Univ Beirut, Dept Biochem, Beirut, Lebanon. RP Dryja, TP (reprint author), Massachusetts Eye & Ear Infirm, Ocular Mol Genet Inst, 243 Charles St, Boston, MA 02114 USA. RI DeAngelis, e/J-7863-2015 FU NEI NIH HHS [EY00169, EY08683] NR 17 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAR PY 2001 VL 131 IS 3 BP 355 EP 358 DI 10.1016/S0002-9394(00)00807-2 PG 4 WC Ophthalmology SC Ophthalmology GA 408QP UT WOS:000167339400011 PM 11239869 ER PT J AU Christie, R Yamada, M Moskowitz, M Hyman, B AF Christie, R Yamada, M Moskowitz, M Hyman, B TI Structural and functional disruption of vascular smooth muscle cells in a transgenic mouse model of amyloid angiopathy SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ALZHEIMERS-DISEASE; BETA; VASOACTIVITY; HEMORRHAGE; PEPTIDES AB The deposition of amyloid AP peptide in the wall of cerebral vessels (cerebral amyloid angiopathy), can lead to weakness and rupture of the vessel wall, resulting in hemorrhagic stroke. The Tg2576 transgenic mouse line, overexpressing mutant amyloid precursor protein in an age-dependent manner, forms amyloid angiopathy morphologically similar to that seen in the human. We report here the structural and functional disruption of smooth muscle cells (SMCs) in the walls of pial vessels affected by amyloid deposition in the Tg2576 mouse. We demonstrate, using multiphoton imaging, that the arrangement of SMCs becomes disorganized before the onset of cell death, and that these disorganized SMCs are unable to respond appropriately to application of endothelial-dependent and endothelial-independent vasodilators in a closed-cranial window preparation. C1 Massachusetts Gen Hosp, Dept Neurol, Alzheimer Res Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurosurg, Charlestown, MA 02129 USA. RP Hyman, B (reprint author), Massachusetts Gen Hosp, Dept Neurol, Alzheimer Res Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [P01 AG015453, R01 AG008487, P01 AG 15453, AG 08487]; NINDS NIH HHS [P50 NS 10828, P50 NS010828] NR 20 TC 86 Z9 88 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 MAR PY 2001 VL 158 IS 3 BP 1065 EP 1071 DI 10.1016/S0002-9440(10)64053-9 PG 7 WC Pathology SC Pathology GA 409XN UT WOS:000167411100030 PM 11238054 ER PT J AU Schwesinger, C Yee, C Rohan, RM Joussen, AM Fernandez, A Meyer, TN Poulaki, V Ma, JJK Redmond, TM Liu, SY Adamis, AP D'Amato, RJ AF Schwesinger, C Yee, C Rohan, RM Joussen, AM Fernandez, A Meyer, TN Poulaki, V Ma, JJK Redmond, TM Liu, SY Adamis, AP D'Amato, RJ TI Intrachoroidal neovascularization in transgenic mice overexpressing vascular endothelial growth factor in the retinal pigment epithelium SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SUBFOVEAL FIBROVASCULAR MEMBRANES; KRYPTON LASER PHOTOCOAGULATION; EXPRESSION IN-VIVO; MACULAR DEGENERATION; SUBRETINAL NEOVASCULARIZATION; CHOROIDAL NEOVASCULARIZATION; PERMEABILITY FACTOR; TYROSINE KINASE; BRUCHS MEMBRANE; ANGIOGENESIS AB Choroidal neovascularization in age-related macular degeneration is a frequent and poorly treatable cause of vision loss in elderly Caucasians. This choroidal neovascularization has been associated with the expression of vascular endothelial growth factor (VEGF). In current animal models choroidal neovascularization is induced by subretinal injection of growth factors or vectors encoding growth factors such as VEGF, or by disruption of the Bruch's membrane/retinal pigment epithelium complex with laser treatment. We wished to establish a transgenic murine model of age-related macular degeneration, in which the overexpression of VEGF by the retinal pigment epithelium induces choroidal neovascularization. A construct consisting of a tissue-specific murine retinal pigment epithelium promoter (RPE65 promoter) coupled to murine VEGF(164) cDNA with a rabbit beta -globin-3' UTR was introduced into the genome of albino mice. Transgene mRNA was expressed in the retinal pigment epithelium at all ages peaking at 4 months. The expression of VEGF protein was increased in both the retinal pigment epithelium and choroid. An increase of intravascular adherent leukocytes and vessel leakage was observed. Histopathology revealed intrachoroidal neovascularization that did not penetrate through an intact Bruch's membrane. These results support the hypothesis that additional insults to the integrity of Bruch's membrane are required to induce growth of choroidal vessels into the subretinal space as seen in age-related macular degeneration. This model may be useful to screen for inhibitors of choroidal vessel growth. C1 Childrens Hosp, Surg Res Lab, Boston, MA 02115 USA. Univ Freiburg, Freiburg, Germany. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP D'Amato, RJ (reprint author), Childrens Hosp, Surg Res Lab, Enders Bldg 1006,300 Longwood Ave, Boston, MA 02115 USA. OI Redmond, T. Michael/0000-0002-1813-5291 NR 52 TC 148 Z9 156 U1 1 U2 9 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD MAR PY 2001 VL 158 IS 3 BP 1161 EP 1172 DI 10.1016/S0002-9440(10)64063-1 PG 12 WC Pathology SC Pathology GA 409XN UT WOS:000167411100040 PM 11238064 ER PT J AU Brown, EN Meehan, PM Dempster, AP AF Brown, EN Meehan, PM Dempster, AP TI A stochastic differential equation model of diurnal cortisol patterns SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE circadian rhythms; deconvolution; kinetics; sensitivity analysis; ultradian rhythms ID HUMAN CIRCADIAN PACEMAKER; MAJOR DEPRESSIVE-ILLNESS; HORMONE-SECRETION; TIME-SERIES; EPISODIC SECRETION; ADRENOCORTICOTROPIN; AMPLITUDE; FREQUENCY; CORTICOTROPIN; PULSES AB Circadian modulation of episodic bursts is recognized as the normal physiological pattern of diurnal variation in plasma cortisol levels. The primary physiological factors underlying these diurnal patterns are the ultradian timing of secretory events, circadian modulation of the amplitude of secretory events, infusion of the hormone from the adrenal gland into the plasma, and clearance of the hormone from the plasma by the liver. Each measured plasma cortisol level has an error arising from the cortisol immunoassay. We demonstrate that all of these three physiological principles can be succinctly summarized in a single stochastic differential equation plus measurement error model and show that physiologically consistent ranges of the model parameters can be determined from published reports. We summarize the model parameters in terms of the multivariate Gaussian probability density and establish the plausibility of the model with a series of simulation studies. Our framework makes possible a sensitivity analysis in which all model parameters are allowed to vary simultaneously. The model offers an approach for simultaneously representing cortisol's ultradian, circadian, and kinetic properties. Our modeling paradigm provides a framework for simulation studies and data analysis that should be readily adaptable to the analysis of other endocrine hormone systems. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Neurosci Stat Res Lab, MIT,Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. RP Brown, EN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Neurosci Stat Res Lab, MIT,Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. FU NIA NIH HHS [1-P01-AG-09975, 1-R01-AG-06072]; NIGMS NIH HHS [1-R01-GM-53559] NR 57 TC 35 Z9 35 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD MAR PY 2001 VL 280 IS 3 BP E450 EP E461 PG 12 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 402DE UT WOS:000166970100010 PM 11171600 ER PT J AU Yu, YM Ryan, CM Castillo, L Lu, XM Beaumier, L Tompkins, RG Young, VR AF Yu, YM Ryan, CM Castillo, L Lu, XM Beaumier, L Tompkins, RG Young, VR TI Arginine and ornithine kinetics in severely burned patients: increased rate of arginine disposal SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE leucine; de novo synthesis; oxidation; basal phase; total parental nutrition ID PLASMA PROLINE KINETICS; LEUCINE KINETICS; ALPHA-KETOGLUTARATE; NEONATAL PIGLETS; THERMAL-INJURY; FREE DIETS; METABOLISM; PROTEIN; TRACER; MEN AB Arginine serves multiple roles in the pathophysiological response to burn injury. Our previous studies in burn patients demonstrated a limited net rate of arginine de novo synthesis despite a significantly increased arginine turnover (flux), suggesting that this amino acid is a conditionally indispensable amino acid after major burns. This study used [N-15(2)-guanidino-5,5-2H(2)]arginine and [5-C-13] ornithine as tracers to assess the rate of arginine disposal via its conversion to and subsequent oxidation of ornithine; [5,5-H-2(2)]proline and [5,5,5-H-2(3)]leucine were also used to assess proline and protein kinetics. Nine severely burned patients were studied during a protein-free fast ("basal" or fast) and total parenteral nutrition (TPN) feedings. Compared with values from healthy volunteers, burn injury significantly increased 1) fluxes of arginine, ornithine, leucine, and proline; 2) arginine-to-ornithine conversion; 3) ornithine oxidation; and 4) arginine oxidation. TPN increased arginine-to-ornithine conversion and proportionally increased irreversible arginine oxidation. The elevated arginine oxidation, with limited net de novo synthesis from its immediate precursors, further implies that arginine is a conditionally indispensable amino acid in severely burned patients receiving TPN. C1 Shriners Burn Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Trauma Serv, Boston, MA 02114 USA. MIT, Human Nutr Lab, Cambridge, MA 02139 USA. MIT, Clin Res Ctr, Cambridge, MA 02139 USA. RP Young, VR (reprint author), Shriners Burn Hosp, 51 Blossom St, Boston, MA 02114 USA. FU NCRR NIH HHS [RR-88]; NIDDK NIH HHS [DK-15856]; NIGMS NIH HHS [GM-02700] NR 41 TC 56 Z9 57 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD MAR PY 2001 VL 280 IS 3 BP E509 EP E517 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 402DE UT WOS:000166970100017 PM 11171607 ER PT J AU Akiba, Y Furukawa, O Guth, PH Engel, E Nastaskin, I Kaunitz, JD AF Akiba, Y Furukawa, O Guth, PH Engel, E Nastaskin, I Kaunitz, JD TI Sensory pathways and cyclooxygenase regulate mucus gel thickness in rat duodenum SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE fluorescent microspheres; capsaicin-sensitive afferent nerves; bradykinin; capsazepine; indomethacin ID SENSITIVE AFFERENT NEURONS; GENE-RELATED PEPTIDE; NITRIC-OXIDE DONORS; LUMINAL ACID; SECRETION; CAPSAICIN; BRADYKININ; NERVES; PROSTAGLANDINS; STOMACH AB We previously showed that the duodenal hyperemic response to acid occurs through activation of capsaicin-sensitive afferent nerves with subsequent release of vasodilatory substances such as calcitonin gene-related peptide (CGRP) and nitric oxide. We then tested the hypothesis that similar factors regulate duodenal mucus gel thickness. Gel thickness was optically measured using in vivo microscopy in anesthetized rats. Duodenal mucosae were superfused with pH 7.0 buffer with vanilloid receptor agonist capsaicin, bradykinin, or PGE(2) injection or were challenged with pH 2.2 solution, with or without the vanilloid antagonist capsazepine, human CGRP-(8-37), N-G-nitro-L-arginine methyl ester, and indomethacin. Other rats underwent sensory ablation with high-dose capsaicin pretreatment. Acid, bradykinin, capsaicin, and PGE(2) all quickly thickened the gel. Antagonism of vanilloid and CGRP receptors, inhibition of nitric oxide synthase, and sensory deafferentation delayed gel thickening, suggesting that the capsaicin pathway mediated the initial burst of mucus secretion that thickened the gel. Indomethacin abolished gel thickening due to acid, bradykinin, and capsaicin. Inhibition of gel thickening by indomethacin in response to multiple agonists suggests that cyclooxygenase activity is essential for duodenal gel thickness regulation. Duodenal afferent neural pathways play an important role in the modulation of cyclooxygenase-mediated physiological control of gel thickness. C1 Univ Calif Los Angeles, Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, CURE, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Biomath, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Coll Letters & Sci, Los Angeles, CA 90073 USA. RP Kaunitz, JD (reprint author), W Los Angeles VA Med Ctr, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-54221] NR 24 TC 28 Z9 31 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAR PY 2001 VL 280 IS 3 BP G470 EP G474 PG 5 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 401FP UT WOS:000166917800019 PM 11171630 ER PT J AU Schutzer, WE Reed, JF Bliziotes, M Mader, SL AF Schutzer, WE Reed, JF Bliziotes, M Mader, SL TI Upregulation of G protein-linked receptor kinases with advancing age in rat aorta SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE beta-adrenergic receptor kinase; beta-adrenergic receptor; vasorelaxation ID VASCULAR SMOOTH-MUSCLE; ADENYLATE-CYCLASE; DESENSITIZATION; HYPERTENSION; RELAXATION; EXPRESSION; RESPONSES; AGONIST; PHOSPHORYLATION; MECHANISMS AB The age-related decline in beta -adrenergic receptor (beta -AR)-mediated vasorelaxation is associated with desensitization of beta -ARs without significant downregulation. The primary mode of this homologous beta -AR desensitization, in general, is via G protein receptor kinases (GRK). Therefore, we hypothesize that age-related changes in GRKs are causative to this etiology in rat aorta. Herein, we investigate the activity and cellular distribution (cytoplasmic vs. membrane) of several GRK isoforms and beta -arrestin proteins. GRK activity was assessed in extracts from aortic tissue of 6-wk, 6-mo, 12-mo, and 24-mo-old male Fischer-344 rats using a rhodopsin phosphorylation assay. We also performed immunoblots on lysates from aorta with specific antibodies to GRK-2, -3, -5, and beta -arrestin-1. Results show an age-related increase in GRK activity. Furthermore, expression of GRK-2 (cytoplasmic and membrane), GRK-3 (cytoplasmic and membrane), and beta -arrestin (soluble) increased with advancing age, whereas GRK-5 (membrane) expression remained unchanged. These results suggest that age is associated with increased activity and expression of specific GRKs. This increase likely results in enhanced phosphorylation and desensitization of beta -ARs. These biochemical changes are consistent with observed aging physiology. C1 Portland VA Med Ctr, Res Serv R&D 26, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Sch Med, Portland, OR 97201 USA. RP Portland VA Med Ctr, Res Serv R&D 26, 3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. EM scott.mader@med.va.gov FU NIDDK NIH HHS [DK-54415] NR 33 TC 19 Z9 20 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 EI 1522-1490 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD MAR PY 2001 VL 280 IS 3 BP R897 EP R903 PG 7 WC Physiology SC Physiology GA 401FQ UT WOS:000166917900036 PM 11171671 ER PT J AU Bagnis, C Marshansky V Breton, S Brown, D AF Bagnis, C Marshansky, V Breton, S Brown, D TI Remodeling the cellular profile of collecting ducts by chronic carbonic anhydrase inhibition SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE acetazolamide; carbonic anhydrase II; rat kidney; hydrogenadenosine 5 '-triphosphatase; sodium/hydrogen exchanger regulatory factor; AE1 anion exchanger; aquaporin 2; immunocytochemistry; principal cell; intercalated cell ID RAT-KIDNEY; INTERCALATED CELLS; H+-ATPASE; ADENOSINE-TRIPHOSPHATASE; BICARBONATE TRANSPORT; RESPIRATORY-ACIDOSIS; METABOLIC-ACIDOSIS; EPITHELIAL-CELLS; ALKALI LOADS; PROTON AB Factors regulating the differentiated phenotype of principal cells (PC) and A- and B-intercalated cells (IC) in kidney collecting ducts are poorly understood. However, we have shown previously that carbonic anhydrase II (CAII)-deficient mice have no IC in their medullary collecting ducts, suggesting a potential role for this enzyme in determining the cellular composition of this tubule segment. We now report that the cellular profile of the collecting ducts of adult rats can be remodeled by inhibiting CA activity in rats by using osmotic pumps containing acetazolamide. The 31-kDa subunit of the vacuolar H(+)-ATPase, the sodium/hydrogen exchanger regulatory factor NHE-RF, and the anion exchanger AE1 were used to identify IC subtypes by immunofluorescence staining, while aquaporin 2 and aquaporin 4 were used to identify PC. In the cortical collecting ducts of animals treated with acetazolamide for 2 wk, the percentage of B-IC decreased significantly (18 +/- 2 vs. 36 +/- 4%, P< 0.01) whereas the percentage of A- IC increased (82 +/- 2 vs. 64 +/- 4%, P< 0.01) with no change in the percentage of total IC in the epithelium. In some treated rats, B-IC were virtually undetectable. In the inner stripe of the outer medulla, the percentage of IC increased in treated animals (48 +/- 2 vs. 37 +/- 3%, P< 0.05) and the percentage of PC decreased (52 +/- 2 vs. 63 +/- 3%, P< 0.05). Moreover, IC appeared bulkier, protruded into the lumen, and showed a significant increase in the length of their apical (20.8 +/- 0.5 vs. 14.6 +/- 0.4 mum, P< 0.05) and basolateral membranes (25.8 +/- 0.4 vs. 23.8 +/- 0.5 m, P< 0.05) compared with control rats. In the inner medullary collecting ducts of treated animals, the number of IC in the proximal third of the papilla was reduced compared with controls (11 +/- 4 vs. 40 +/- 11 IC/mm(2), P< 0.05). These data suggest that CA activity plays an important role in determining the differentiated phenotype of medullary collecting duct epithelial cells and that the cellular profile of collecting ducts can be remodeled even in adult rats. The relative depletion of cortical B-IC and the relative increase in number and hyperplasia of A- IC in the medulla may be adaptive processes that would tend to correct or stabilize the metabolic acidosis that would otherwise ensue following systemic carbonic anhydrase inhibition. C1 Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02120 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02120 USA. RP Bagnis, C (reprint author), Massachusetts Gen Hosp E, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. EM bagnis@receptor.mgh.harvard.edu FU NIDDK NIH HHS [DK-38452, DK-42956] NR 54 TC 58 Z9 58 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAR PY 2001 VL 280 IS 3 BP F437 EP F448 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 402KG UT WOS:000166985700007 PM 11181405 ER PT J AU Bagnis, C Marsolais, M Biemesderfer, D Laprade, R Breton, S AF Bagnis, C Marsolais, M Biemesderfer, D Laprade, R Breton, S TI Na+/H+-exchange activity and immunolocalization of NHE3 in rat epididymis SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE male reproductive tract; transepithelial acid base transport; acidification; immunofluorescence; intracellular pH ID MALE REPRODUCTIVE-TRACT; RENAL BRUSH-BORDER; CARBONIC-ANHYDRASE; PROXIMAL TUBULE; FUNCTIONAL EXPRESSION; CAUDA-EPIDIDYMIDIS; DUCTULI EFFERENTES; SODIUM-BICARBONATE; MOLECULAR-CLONING; SPERM MOTILITY AB An acidic luminal pH in the epididymis and vas deferens (VD) helps maintain mature sperm in an immotile state during storage. We have previously shown that the majority of proton secretion in the VD is due to the activity of the vacuolar H+-ATPase. Acidification is dependent on luminal sodium in more proximal regions of the epididymis, and we examined the distribution of the Na+/H+ exchanger, NHE3, by immunofluorescence and measured Na+/H+ exchange (NHE) activity in isolated epididymal tubules. NHE3 was detected in the apical pole of nonciliated cells of the efferent ducts and principal cells (PC) of the epididymis. No staining was seen in the distal cauda epididymidis and the VD. Isolated tubules from the distal initial segment (DIS) and proximal cauda epididymidis were perfused in vitro and loaded with the pH-sensitive dye 2',7'-bis(carboxyethyl)5(6')-carboxyfluorescein. Ethylisopropyl amiloride (EIPA) (50 muM) reduced the initial rate of intracellular pH recovery (dpH(i) dt), in response to an acute acid load, by 51% and 45% in the DIS and cauda epididymidis, respectively. In the DIS, removal of luminal sodium reduced dpH(i)/dt by 52%. HOE694 (50 mM) inhibited all EIPA-sensitive dpH(i)/dt in the DIS, despite the previously reported absence of NHE2 in this region (Cheng Chew SB, Leung GPH, Leung PY, Tse CM, and Wong PYD, Biol Reprod 62: 755-758, 2000). These data indicate that HOE694- and EIPA-sensitive Na+/H+ exchange may participate, together with the H+-ATPase, in luminal acidification in the male excurrent duct. C1 Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA 02129 USA. Univ Montreal, Grp Rech Transport Membranaire, Montreal, PQ H3C 3J7, Canada. Yale Univ, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Breton, S (reprint author), Massachusetts Gen Hosp E, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. EM sbreton@receptor.mgh.harvard.edu FU NIDDK NIH HHS [DK-38452, DK-33793] NR 56 TC 36 Z9 37 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAR PY 2001 VL 280 IS 3 BP F426 EP F436 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 402KG UT WOS:000166985700006 PM 11181404 ER PT J AU Adinoff, R Devous, MD Best, SM George, MS Alexander, D Payne, K AF Adinoff, R Devous, MD Best, SM George, MS Alexander, D Payne, K TI Limbic responsiveness to procaine in cocaine-addicted subjects SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 34th Annual Winter Conference on Brain Research CY JAN 20-24, 2001 CL STEAMBOAT SPRINGS, COLORADO ID POSITRON-EMISSION-TOMOGRAPHY; FUNCTIONAL NEUROANATOMY; ORBITOFRONTAL CORTEX; CEREBRAL PERFUSION; PANIC DISORDER; SPECT; ABUSE; ACTIVATION; EXPERIENCES; VOLUNTEERS AB Objective: The limbic system plays a critical role in motivation, emotional expression, and memory. The authors investigated whether a state of permanent limbic neuronal hyperexcitability, or sensitization, is present in cocaine addicts as a consequence of repeated cocaine use. Method: Single photon emission computed tomography (SPECT) of regional cerebral blood flow (rCBF) was used to compare the central nervous system response to the limbic stimulus procaine in 10 cocaine-dependent male patients and 10 healthy comparison male subjects. Results: The cocaine-addicted subjects demonstrated bilateral activation of the orbitofrontal cortex after the procaine challenge, whereas the comparison subjects showed activation of the anterior cingulate, bilateral insular, and right amygdalar regions. After receiving placebo, the cocaine-addicted subjects showed markedly lower rCBF in the bilateral orbitofrontal cortex than the comparison subjects. Conclusions: The pattern of hypoperfusion in the placebo state followed by heightened activation with procaine in the cocaine-addicted subjects is similar to the pattern of interictal hypoperfusion and ictal hyperperfusion that has been observed in subjects with epilepsy. The findings for the cocaine-addicted subjects may thus represent evidence of localized (orbitofrontal) sensitization. C1 Ralph H Johnson VA Med Ctr, Charleston, SC USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. VA N Texas Hlth Care Syst, Dallas, TX USA. Univ Texas, SW Med Ctr, Nucl Med Ctr, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Radiol & Nucl Med, Dallas, TX USA. RP Adinoff, R (reprint author), Vet Adm Med Ctr, 116A5,4500 S Lancaster Rd, Dallas, TX 75216 USA. NR 47 TC 12 Z9 12 U1 3 U2 5 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 2001 VL 158 IS 3 BP 390 EP 398 PG 9 WC Psychiatry SC Psychiatry GA 408JL UT WOS:000167323000009 ER PT J AU McElroy, SL Altshuler, LL Suppes, T Keck, PE Frye, MA Denicoff, KD Nolen, WA Kupka, RW Leverich, GS Rochussen, JR Rush, AJ Post, RM AF McElroy, SL Altshuler, LL Suppes, T Keck, PE Frye, MA Denicoff, KD Nolen, WA Kupka, RW Leverich, GS Rochussen, JR Rush, AJ Post, RM TI Axis I psychiatric comorbidity and its relationship to historical illness variables in 288 patients with bipolar disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; SUBSTANCE-ABUSE; CO-MORBIDITY; DSM-III; 1ST HOSPITALIZATION; GENERAL-POPULATION; MENTAL-DISORDERS; EATING DISORDER; PANIC DISORDER; MANIC PATIENTS AB Objective: Bipolar disorder often co-occurs with other axis I disorders, but little is known about the relationships between the clinical features of bipolar illness and these comorbid conditions. Therefore, the authors assessed comorbid lifetime and current axis I disorders in 288 patients with bipolar disorder and the relationships of these comorbid disorders to selected demographic and historical illness variables. Method: They evaluated 288 outpatients with bipolar I or II disorder, using structured diagnostic interviews and clinician-administered and self-rated questionnaires to determine the diagnosis of bipolar disorder, comorbid axis I disorder diagnoses, and demographic and historical illness characteristics. Results: One hundred eighty-seven (65%) of the patients with bipolar disorder also met DSM-IV criteria for at least one comorbid lifetime axis I disorder. More patients had comorbid anxiety disorders (N=78, 42%) and substance use disorders (N=78, 42%) than had eating disorders (N=9, 5%). There were no differences in comorbidity between patients with bipolar I and bipolar II disorder. Both lifetime axis I comorbidity and current axis I comorbidity were associated with earlier age at onset of affective symptoms and syndromal bipolar disorder. Current axis I comorbidity was associated with a history of development of both cycle acceleration and more severe episodes over time. Conclusions: Patients with bipolar disorder often have comorbid anxiety, substance use, and, to a lesser extent, eating disorders. Moreover, axis I comorbidity, especially current comorbidity, may be associated with an earlier age at onset and worsening course of bipolar illness. Further research into the prognostic and treatment response implications of axis I comorbidity in bipolar disorder is important and is in progress. C1 Acad Hosp, Utrecht, Netherlands. Willem Arntsz Huis, HC Rumke Grp, Utrecht, Netherlands. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. SW Med Ctr, Dallas, TX USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Inst Neuropsychiat, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Univ Cincinnati, Coll Med, Biol Psychiat Program, Cincinnati, OH 45267 USA. RP McElroy, SL (reprint author), Univ Cincinnati, Coll Med, Biol Psychiat Program, POB 670559,231 Bethesda Ave, Cincinnati, OH 45267 USA. RI Nolen, Willem/E-9006-2014; OI Rush, Augustus/0000-0003-2004-2382 NR 46 TC 439 Z9 450 U1 4 U2 39 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 2001 VL 158 IS 3 BP 420 EP 426 DI 10.1176/appi.ajp.158.3.420 PG 7 WC Psychiatry SC Psychiatry GA 408JL UT WOS:000167323000013 PM 11229983 ER PT J AU LaMontagne, AD Kelsey, KT AF LaMontagne, AD Kelsey, KT TI Evaluating OSHA's ethylene oxide standard: Exposure determinants in Massachusetts hospitals SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID MEDICAL SURVEILLANCE; OCCUPATIONAL-HEALTH; WORKERS; MORTALITY; SAFETY; COHORT; MODEL; LEAD AB Objectives. This study sought to identify determinants of workplace exposures to ethylene oxide to assess the effect of the Occupational Safety and Health Administration's (OSHA's) 1984 ethylene oxide standard. Methods. An in-depth survey of all hospitals in Massachusetts that used ethylene oxide from 1990 through 1992 (96% participation, N=90) was conducted. Three types of exposure events were modeled with logistic regression: exceeding the 8-hour action level, exceeding the 15-minute excursion limit, and worker exposures during unmeasured accidental releases. Covariates were drawn from data representing an ecologic framework including direct and indirect potential exposure determinants. Results. After adjustment for frequencies of ethylene oxide use and exposure monitoring, a significant inverse relation was observed between exceeding the action level and the use of combined sterilizer-aerators, an engineering control technology developed after the passage of the OSHA standard. Conversely, the use of positive-pressure sterilizers that employ ethylene oxide gas mixtures was strongly related to both exceeding the excursion limit and the occurrence of accidental releases. Conclusions These findings provide evidence of a positive effect of OSHA's ethylene oxide standard and specific targets for future prevention and control efforts. C1 Dana Farber Canc Inst, Ctr Community Based Res, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Canc Biol, Boston, MA 02115 USA. RP LaMontagne, AD (reprint author), Alfred Hosp, Monash Med Sch, Dept Epidemiol & Prevent Med, Commercial Rd, Prahran, Vic 3181, Australia. RI Kelsey, Karl/I-1252-2014 FU NIEHS NIH HHS [ES00002]; NIOSH CDC HHS [R03 OH03088, 1R01 OH03932] NR 44 TC 11 Z9 11 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 MAR PY 2001 VL 91 IS 3 BP 412 EP 417 DI 10.2105/AJPH.91.3.412 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 461BL UT WOS:000170345000013 PM 11236406 ER PT J AU Silverman, ES De Sanctis, GT Boyce, J MacLean, JA Jiao, AP Green, FHY Grasemann, H Faunce, D Fitzmaurice, G Shi, GP Stein-Streilein, J Milbrandt, J Collins, T Drazen, JM AF Silverman, ES De Sanctis, GT Boyce, J MacLean, JA Jiao, AP Green, FHY Grasemann, H Faunce, D Fitzmaurice, G Shi, GP Stein-Streilein, J Milbrandt, J Collins, T Drazen, JM TI The transcription factor early growth-response factor 1 modulates tumor necrosis factor-alpha, immunoglobulin E and airway responsiveness in mice SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID ENDOTHELIAL-CELLS; DEFICIENT MICE; NGFI-A; HYPERRESPONSIVENESS; GENE; EXPRESSION; DIFFERENTIATION; PROMOTER; EGR-1; INFLAMMATION AB Early growth-response factor 1 (Egr-1) is a sequence-specific transcription factor that plays a regulatory role in the expression of many genes important in inflammation, cell growth, apoptosis, and the pathogenesis of disease. In vitro studies suggest that Egr-1 is capable of regulating the expression of tumor necrosis factor-alpha (TNF-alpha) and other genes involved in airway inflammation and reactivity following allergen stimulation. On the basis of these data, we hypothesized that in the absence of Egr-1, the TNF-alpha response and subsequent downstream inflammatory events that usually follow allergen challenge would be diminished. To test our hypothesis Egr-1 knock-out (KO) mice were examined in an ovalbumin (OVA)-induced model of airway inflammation and reactivity, and compared with identically treated wild-type (WT) control mice. In response to OVA sensitization and airway challenge, KO mice had diminished TNF-alpha mRNA and protein in the lungs and mast cells compared with WT mice. Interestingly, the KO mice had elevated IgE levels at baseline and after allergen challenge compared with WT mice. Furthermore, the airways of KO mice were hyporespon sive to methacholine challenge at baseline and after allergen challenge. These data indicate that Egr-1 modulates TNF-alpha, IgE, and airway responsiveness in mice. C1 Univ Calgary, Resp Res Grp, Calgary, AB, Canada. Washington Univ, Sch Med, Dept Pathol & Internal Med, St Louis, MO USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Immunol & Allergy Unit, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Immunol & Allergy Div, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Pulm & Crit Care Div, Boston, MA 02115 USA. RP Silverman, ES (reprint author), Brigham & Womens Hosp, Div Pulm, 75 Francis St, Boston, MA 02115 USA. RI Drazen, Jeffrey/E-5841-2012 FU NHLBI NIH HHS [HL03827, HL36110, HL56383] NR 33 TC 34 Z9 43 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 2001 VL 163 IS 3 BP 778 EP 785 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 419HW UT WOS:000167944100033 PM 11254538 ER PT J AU Christiani, DC Wang, XR Pan, LD Zhang, HX Sun, BX Dai, HL Eisen, EA Wegman, DH Olenchock, SA AF Christiani, DC Wang, XR Pan, LD Zhang, HX Sun, BX Dai, HL Eisen, EA Wegman, DH Olenchock, SA TI Longitudinal changes in pulmonary function and respiratory symptoms in cotton textile workers - A 15-yr follow-up study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID CHRONIC LUNG-DISEASE; ACROSS-SHIFT DROP; DUST; ENDOTOXIN; EXPOSURE; MILLS; BYSSINOSIS; OPERATIVES; FEV(1); 5-YEAR AB To evaluate the chronic effects of exposure to cotton dust, a 15-yr follow-up study in cotton textile workers was performed in Shanghai, China from 1981 to 1996. Testing occurred four times during the 15-yr period. The achieved follow-up rates were 76-88% of the original 447 cotton textile workers, and 70-85% of the original 472 silk textile workers (as a control group). Identical questionnaires, equipment, and methods were used throughout the study. The prevalence of byssinosis increased over time in cotton workers, with 15.3% at the last survey versus 7.6% at the baseline, whereas no byssinosis was found in silk workers. More workers in the cotton group consistently reported symptoms than in the silk group, although symptom reporting varied considerably from survey to survey. Cotton workers had small, but significantly greater, adjusted annual declines in FEV1 and FVC than did the silk workers. Years worked in cotton mills, high level of exposure to endotoxin, and across-shift drops in FEV1 were found to be significant determinants for longitudinal change in FEV1, after controlling for appropriate confounders. Furthermore, there were statistically significant associations between excessive loss of FEV1 and byssinosis, chest tightness at work, and chronic bronchitis in cotton workers. Workers who consistently (three or four of the surveys) reported byssinosis or chest tightness at work had a significantly greater 15-yr loss of FEV1. We conclude that long-term exposure to cotton dust is associated with chronic or permanent obstructive impairments. Consistent reporting of respiratory symptoms, including byssinosis and chest tightness at work is of value to predict the magnitude and severity of chronic impairments in textile workers. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Med, Pulm & Crit Care Unit, Boston, MA USA. Shanghai Text Bureau, First Hosp, Shanghai, Peoples R China. Univ Massachusetts, Dept Work Environm, Lowell, MA USA. NIOSH, Morgantown, WV USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. RI Lin, Sihao/A-8412-2012 NR 33 TC 82 Z9 86 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 2001 VL 163 IS 4 BP 847 EP 853 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 421GY UT WOS:000168057700016 PM 11282755 ER PT J AU Cakirer, B Hans, MG Graham, G Aylor, J Tishler, PV Redline, S AF Cakirer, B Hans, MG Graham, G Aylor, J Tishler, PV Redline, S TI The relationship between craniofacial morphology and obstructive sleep apnea in whites and in African-Americans SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID CEPHALOMETRIC ANALYSIS; HEAD POSTURE; RISK-FACTORS; AIRWAY; RESPIRATION; ADULTS AB Previous studies of craniofacial risk factors for obstructive sleep apnea (OSA) have been based predominantly on cephalometry. However, differences in head form (measured by the cranial index [CII) and facial form (measured by the facial index [FI]) are considered by anthropologists to provide a basis for structural variation in craniofacial anatomy. We assessed the association of head and facial form with the apnea hypopnea index (AHI) in 364 white individuals and 165 African-Americans. Data collected included cranial and facial dimensions (using anthropometric calipers), body mass index (BMI), neck circumference, and the AHI. CI and FI differed for whites with OSA (AHI greater than or equal to 15) versus those without OSA (AHI < 5) (increased CI and decreased FI in subjects with OSA, p = 0.005 and p = 0.006, respectively). CI and FI did not differ in OSA versus non-OSA groups of African-Americans. In subjects with OSA, the CI in whites was again greater and the Fl smaller than those in African-Americans (p = 0.007 and p = 0.004, for CI and Fl.) We conclude that brachycephaly is associated with an increased AHI in whites but not in African-Americans. The CI may useful in phenotyping and identifying population subsets with OSA. C1 Case Western Reserve Univ, Div Clin Epidemiol, Sch Dent, Dept Orthodont, Cleveland, OH 44106 USA. Case Western Reserve Univ, Div Clin Epidemiol, Dept Pediat, Cleveland, OH 44106 USA. VA Boston Healthcare Syst, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Redline, S (reprint author), Rainbow Babies & Childrens Hosp, 11100 Euclid Ave, Cleveland, OH 44106 USA. FU NHLBI NIH HHS [HL-46380] NR 35 TC 88 Z9 93 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 2001 VL 163 IS 4 BP 947 EP 950 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 421GY UT WOS:000168057700032 PM 11282771 ER PT J AU Comtois, AS Barreiro, E Huang, PL Marette, A Perrault, M Hussain, SNA AF Comtois, AS Barreiro, E Huang, PL Marette, A Perrault, M Hussain, SNA TI Lipopolysaccharide-induced diaphragmatic contractile dysfunction and sarcolemmal injury in mice lacking the neuronal nitric oxide synthase SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID RESPIRATORY MUSCLE DYSFUNCTION; SKELETAL-MUSCLE; RAT DIAPHRAGM; ENDOTOXIN; INHIBITION; EXPRESSION; INDUCTION; SEPSIS; GENE AB In this study we evaluated the role of the neuronal nitric oxide synthase (nNOS) in lipopolysaccharide (LPS)-induced diaphragmatic contractile dysfunction and sarcolemmal injury. Wild-type (WT) mice or mice deficient in the nNOS gene (nNOS(-/-)) were injected with either saline (control) or Escherichia coli LPS (LPS groups) and sacrificed 12 h later. The diaphragm was then examined for NOS expression, NOS activity, and in-vitro contractility. We also assessed sarcolemmal injury in isolated muscle strips under resting condition and after 3 min of artificial stimulations. In WT mice, LPS injection reduced maximum force to about 75% of that of control animals and raised total NOS activity significantly due to the induction of the iNOS isoform. Although muscle fiber injury was minimal under resting condition, the percentage of injured fibers in control and LPS-injected mice approached 27% and 40% of total fibers, respectively, in response to artificial stimulation. By comparison, LPS injection in nNOS-/- mice elicited a worsening of muscle contractility (maximum force < 60% of control animals) but elicited degrees of sarcolemmal injury similar to those observed in the WT animals. In addition, muscle NOS activity and iNOS protein level in nNOS(-/-) mice injected with LPS reached about 10% and 60% of that of WT animals, respectively (p < 0.05 compared with WT animals). Protein level of endothelial NOS isoform in the diaphragm was not altered by LPS injection in either WT or nNOS(-/-) animals. We conclude that nNOS plays a protective role in attenuating the negative influence of sepsis on diaphragmatic contractility but is not involved in the pathogenesis of sepsis-induced sarcolemmal injury. C1 McGill Univ, Royal Victoria Hosp, Div Resp & Crit Care, Montreal, PQ, Canada. McGill Univ, Meakins Christie Labs, Montreal, PQ, Canada. Univ Montreal, CHUM, Ctr Rech, Resp Div, Montreal, PQ, Canada. Univ Laval, Hosp Res Ctr, Dept Physiol, Ste Foy, PQ G1K 7P4, Canada. Univ Laval, Hosp Res Ctr, Lipid Res Unit, Ste Foy, PQ G1K 7P4, Canada. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Hussain, SNA (reprint author), Room L3-05,687 Pine Ave W, Montreal, PQ H3A 1A1, Canada. EM shussain@rvhmed.lan.mcgill.ca RI Marette, Andre/E-9342-2013; Barreiro, E/D-6919-2014 OI Barreiro, E/0000-0003-2708-3443 NR 24 TC 26 Z9 26 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR PY 2001 VL 163 IS 4 BP 977 EP 982 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 421GY UT WOS:000168057700037 PM 11282776 ER PT J AU Megibow, AJ Jacob, G Heiken, JP Paulson, EK Hopper, KD Sica, G Saini, S Birnbaum, BA Redvanley, R Fishman, EK AF Megibow, AJ Jacob, G Heiken, JP Paulson, EK Hopper, KD Sica, G Saini, S Birnbaum, BA Redvanley, R Fishman, EK TI Quantitative and qualitative evaluation of volume of low osmolality contrast medium needed for routine helical abdominal CT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Roentgen-Ray-Society CY MAY 08, 2000 CL WASHINGTON, D.C. SP Amer Roentgen Ray Soc ID COMPUTED-TOMOGRAPHY; ADVERSE REACTIONS; SPIRAL CT; LIVER CT; ENHANCEMENT; AGENT; COST; UNIVERSAL; IOHEXOL; EVENTS AB OBJECTIVE. The purpose of our study was to determine the minimum optimal dose of IV contrast medium for helical CT that can preserve image quality while reducing cost. SUBJECTS AND METHODS. Four hundred sixty-three patients fr om six centers were enrolled in a prospective trial in which patients were randomized into one of four weight-based dose categories of iopromide, 300 mg I/mL: 1.25. 1.50, 1.75, and 2.0 mL/kg. Six of 463 patients were excluded from analysis. A radiologist at each center who was unaware of the volume of contrast medium administered determined whether the scans were acceptable. The responses were analyzed by dose, in aggregate. and by weight. Enhancement values (in Hounsfield units) in regions of interest in the liver, pancreas, aorta, and kidneys were obtained at a single time during the scan. The participating radiologist was unaware of these values. Finally, three additional nonparticipating site observers assessed the images for acceptability. diagnostic quality, and overall level of confidence. A cost mt,del comparing incurred charges in using 150 or 100 mL, or 1.5 mL/kg, of low osmolality contrast medium was developed from experience in an additional 303 patients. RESULTS. We found no clinically significant difference in acceptability of scans at doses greater than 1.5 mL/kg. However, significant variability occurred among the centers, The use of 1.5 mL/kg led to a savings of $9977.16 for 303 patients when compared with the use of 150 mL at list price. The cost is the same for 1.5 mL/kg or use of 100 mt of contrast medium. CONCLUSION. A weight-based dose at 1.5 mL/kg of low osmolality contrast medium can provide acceptable scans in most patients, with a significant cost savings. C1 NYU, Med Ctr, Dept Radiol, New York, NY 10016 USA. Berlex Labs Inc, Montville, NJ 07045 USA. Edward Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. Penn State Univ, Coll Med, Dept Radiol, Hershey, PA 17033 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Hosp Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. Charlotte Radiol Associates, Charlotte, NC 28230 USA. Johns Hopkins Hosp, Dept Radiol, Baltimore, MD 21287 USA. RP Megibow, AJ (reprint author), NYU, Med Ctr, Dept Radiol, 550 1St Ave,RM HW 205, New York, NY 10016 USA. NR 27 TC 28 Z9 30 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2001 VL 176 IS 3 BP 583 EP 589 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 404TZ UT WOS:000167118800004 PM 11222185 ER PT J AU Smith, JJ Berlin, L AF Smith, JJ Berlin, L TI Malpractice issues in radiology - The HIV-positive patient and confidentiality SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 Rush N Shore Med Ctr, Dept Radiol, Skokie, IL 60076 USA. Rush Med Coll, Chicago, IL 60612 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Berlin, L (reprint author), Rush N Shore Med Ctr, Dept Radiol, 9600 Gross Point Rd, Skokie, IL 60076 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2001 VL 176 IS 3 BP 599 EP 602 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 404TZ UT WOS:000167118800006 PM 11222187 ER PT J AU Zalis, ME Hahn, PF AF Zalis, ME Hahn, PF TI Technical innovation. Digital subtraction bower cleansing in CT colonography SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID COLONOSCOPY C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Zalis, ME (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, White 270,55 Fruit St, Boston, MA 02114 USA. NR 4 TC 102 Z9 105 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2001 VL 176 IS 3 BP 646 EP 648 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 404TZ UT WOS:000167118800014 PM 11222197 ER PT J AU Jackson, PG Gleiber, MA Askari, R Evans, SRT AF Jackson, PG Gleiber, MA Askari, R Evans, SRT TI Predictors of outcome in 100 consecutive laparoscopic antireflux procedures SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE gastroesophageal reflux disease; laparoscopic antireflux surgery; predictors; age; typical symptoms; acid suppression ID GASTROESOPHAGEAL REFLUX DISEASE; QUALITY-OF-LIFE; NISSEN FUNDOPLICATION; CLINICAL USE; ESOPHAGITIS; OMEPRAZOLE; SURGERY; RANITIDINE; DIAGNOSIS; EFFICACY AB Background: Published success rates for surgical intervention in gastroesophageal reflux disease exceed 90%. The goal of this study was to determine if any preoperative factors could accurately predict postoperative symptom relief. Methods: One hundred consecutive patients undergoing laparoscopic antireflux surgery completed a detailed preoperative questionnaire, and underwent endoscopy, manometry, and 24-hour esophageal pH monitoring. Two surgeons performed all procedures in a standardized fashion. At least 2 months following operative intervention, a single interviewer, blinded to all preoperative information and procedure performed, recorded Visick and Gastroesophageal Reflux Disease-Health-Related Quality of Life scores for all patients. All follow-up was performed within 3 years of antireflux procedure. Results: The surgical success rate, as defined by Visick scores of 1-2, was 91%. Three variables were predictive of postoperative success: age < 50, presence of typical symptoms at presentation, and complete resolution of symptoms with acid suppression therapy. Conclusion: The study shows that surgical strategies can reproducibly control gastroesophageal reflux disease symptoms in more than 90% of patients. The optimal surgical candidate is a patient under the age of 50 whose typical symptoms completely resolve with acid suppression therapy, (C) 2001 Excerpta Medica, Inc. All rights reserved. C1 George Washington Univ, Med Ctr, Dept Surg, Washington, DC 20037 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Evans, SRT (reprint author), George Washington Univ, Med Ctr, Dept Surg, 2150 Penn Ave,NW 6B, Washington, DC 20037 USA. NR 33 TC 33 Z9 34 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD MAR PY 2001 VL 181 IS 3 BP 231 EP 235 DI 10.1016/S0002-9610(01)00553-0 PG 5 WC Surgery SC Surgery GA 435GQ UT WOS:000168869400009 PM 11376577 ER PT J AU Granter, SR McKee, PH Calonje, E Mihm, MC Busam, M AF Granter, SR McKee, PH Calonje, E Mihm, MC Busam, M TI Melanoma associated with blue nevus and melanoma mimicking cellular blue nevus - A clinicopathologic study of 10 cases on the spectrum of so-called 'malignant blue nevus' SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE blue nevus; cellular blue nevus; melanoma; malignant blue nevus; malignant cellular blue nevus ID METASTASIS; BENIGN; SCALP; LIGHT AB The term "malignant blue nevus" refers to a ran and heterogeneous group of melanomas that arise in several clinical settings. This includes melanomas arising in association with a common or cellular blue nevus and those arising de novo and resembling cellular blue nevi. We reviewed the clinicopathologic features of 10 cases of malignant blue nevi. Six cases proved to be de novo melanoma mimicking cellular blue nevus, but lacking a clear-cut benign component. Two melanomas arose in association with a common blue nevus, and two with a cellular blue news. The patients' (5 males, 5 females) ages ranged from 11 to 77 years (average age, 48.1 years). The head and neck was the most common location (6 of 10 patients), with five scalp tumors. Four tumors were located on the trunk; none was located on the extremities. Tumor size ranged from 0.5 to 2.2 cm (average size, 1.1 cm). Most lesions had been present for many years before surgical removal. Pigmented dendritic cells were observed in 9 of 10 cases. The malignant and benign components were easily distinguished in the four cases that arose in association with a common or cellular blue nevus. Abrupt transition between a benign blue nevus and melanoma was readily recognized at scanning magnification as distinctive nodules of epithelioid to spindled cells with a sheet-like growth pattern. In dr cases, malignancy was evidenced by increased mitotic rate, necrosis, nuclear atypia, pleomorphism, hyperchromasia, and prominent nucleoli. All 7 patients with followup information experienced recurrence (3 patients) or metastasis (4 patients). Three patients died of disease. Malignant blue news is a heterogeneous group of melanomas that are highly aggressive and often lethal, with a propensity for metastasis to the lymph nodes and lungs. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Dermatopathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Div Dermatopathol, Boston, MA 02114 USA. St Thomas Hosp, Dept Dermatopathol, St Johns Inst Dermatol, London, England. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Granter, SR (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 33 TC 85 Z9 86 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAR PY 2001 VL 25 IS 3 BP 316 EP 323 DI 10.1097/00000478-200103000-00005 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 405JC UT WOS:000167155400005 PM 11224601 ER PT J AU de Leval, L Savilo, E Longtine, J Ferry, JA Harris, NL AF de Leval, L Savilo, E Longtine, J Ferry, JA Harris, NL TI Peripheral T-cell lymphoma with follicular involvement and a CD4+/bcl-6+phenotype SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE lymphoma; T cell; peripheral; follicular dendritic cell; nodular; Bcl-6 ID GRADIENT GEL-ELECTROPHORESIS; GAMMA GENE REARRANGEMENTS; POLYMERASE CHAIN-REACTION; BCL-6 PROTEIN; B-CELLS; CLASSIFICATION; NEOPLASMS; PROPOSAL; FEATURES; PATTERN AB A truly follicular pattern is thought to be restricted to B-cell lymphomas. We observed a prominent follicular growth pattern in three cases of nodal peripheral T-cell lymphomas, of which two were initially diagnosed as follicular lymphomas. All three patients were male, ranged in age from 50 to 70 years, and had generalized lymphadenopathy at the time of diagnosis. The follicles were sharply demarcated in two cases and large and vague in one case; in all cases, they contained abundant follicular dendritic cells. Neoplastic cells were small to medium, with irregular cleaved or round nuclei and clear cytoplasm, which was abundant in one case. Lymphoma cells in all cases were CD4(+) CD8(-)CD57(-) bcl-6, with CD10 coexpression in 2 cases. Clonal rearrangement of the gamma chain of the T-cell receptor gene was demonstrated in each case. These cases expand the differential diagnosis of lymphomas with a follicular growth pattern and suggest that neoplastic T cells may have the capacity to induce or home to follicular structures. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Hamilton Hlth Sci Corp, Hamilton, ON, Canada. RP Harris, NL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2,55 Fruit St, Boston, MA 02114 USA. NR 20 TC 63 Z9 65 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD MAR PY 2001 VL 25 IS 3 BP 395 EP 400 DI 10.1097/00000478-200103000-00015 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 405JC UT WOS:000167155400015 PM 11224611 ER PT J AU Paul, AC AF Paul, AC TI Muscle length affects the architecture and pattern of innervation differently in leg muscles of mouse, guinea pig, and rabbit compared to those of human and monkey muscles SO ANATOMICAL RECORD LA English DT Article DE muscle; tendon; innervation; fascicle length; neuromuscular junction; primate evolution; intrafascicular termination ID MULTIPLE INNERVATION; SKELETAL-MUSCLE; FIBERED MUSCLES AB The innervation pattern and fascicular anatomy of muscles of different lengths in mouse, guinea pig, rabbit, macaque monkey and human legs were analyzed. Neuromuscular junctions, muscle tendon junctions and ends of intrafascicularly terminating fibers were stained for acetylcholinesterase, and fascicle lengths measured. A high correlation between increasing fascicle length and increasing number of neuromuscular junctions was found, with non-primate (mouse, guinea pig, rabbit) and primate (macaque monkey, human) muscles forming two discrete groups. In non-primates, muscles with a single endplate band, fascicles were always shorter than 35 mm, fixing the limit of fiber length served by one neuromuscular junction. Muscles with fascicles longer than this had multiple discrete bands of motor endplates crossing their width at regular intervals. An increase in muscle length across or within species corresponded to an equivalent, standard increase of 10-12 mm fascicle length per motor endplate band. All human and monkey leg muscles, with the exception of gracilis and sartorius, were singly innervated and all muscle fibers ran the full distance from tendon to tendon. Singly innervated primate muscle fibers were up to 140 mm long whereas the mean distance between endplate bands in the two multiply innervated muscles was also considerably greater than in non-primates. These data indicate that allometric effects of increasing fascicle length, are distinct in common laboratory animals and two primates, when architecture and pattern of innervation are compared. Anat Rec 262:301-309, 2001. (C) 2001 Wiley-Liss, Inc. C1 Univ Otago, Sch Med Sci, Dept Anat & Struct Biol, Dunedin, New Zealand. RP Paul, AC (reprint author), Massachusetts Gen Hosp East, Cardiovasc Res Ctr, 149 13th St, Boston, MA 02129 USA. NR 36 TC 35 Z9 35 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 0003-276X J9 ANAT REC JI Anat. Rec. PD MAR 1 PY 2001 VL 262 IS 3 BP 301 EP 309 DI 10.1002/1097-0185(20010301)262:3<301::AID-AR1045>3.0.CO;2-H PG 9 WC Anatomy & Morphology SC Anatomy & Morphology GA 404RE UT WOS:000167113800007 PM 11241198 ER PT J AU Hahn, WC Meyerson, M AF Hahn, WC Meyerson, M TI Telomerase activation, cellular immortalization and cancer SO ANNALS OF MEDICINE LA English DT Article DE cancer; cell immortalization; telomerase; telomeres ID REVERSE-TRANSCRIPTASE GENE; NORMAL HUMAN-CELLS; HUMAN PAPILLOMAVIRUS TYPE-16; CATALYTIC SUBUNIT GENE; TEMPLATE RNA COMPONENT; HUMAN TUMOR-CELLS; HUMAN-CHROMOSOMES; EPITHELIAL-CELLS; LIFE-SPAN; IN-VITRO AB The maintenance of specialized nucleoprotein structures termed telomeres is essential for chromosome stability. Without new synthesis of telomeres at chromosome ends the chromosomes shorten with progressive cell division, eventually triggering either replicative senescence or apoptosis when telomere length becomes critically short, The regulation of telomerase activity in human cells plays a significant role in the development of cancer, Telomerase is tightly repressed in the vast majority of normal human somatic cells but becomes activated during cellular immortalization and in cancers, While the mechanisms for telomerase activation in cancers have not been fully defined, they include telomerase catalytic subunit gene (hTERT) amplification and trans-activation of the hTERT promoter by the myc oncogene product. Ectopic expression of hTERT is sufficient to restore telomerase activity in cells that lack the enzyme and can immortalize many cell types. Understanding telomerase biology will eventually lead to several clinically relevant telomerase-based therapies. These applications include inhibiting or targeting telomerase as a novel antineoplastic strategy and using cells immortalized by telomerase for therapeutic applications. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Meyerson, Matthew/E-7123-2012 NR 99 TC 87 Z9 102 U1 2 U2 5 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1M 8AE, ENGLAND SN 0785-3890 J9 ANN MED JI Ann. Med. PD MAR PY 2001 VL 33 IS 2 BP 123 EP 129 DI 10.3109/07853890109002067 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 421HU UT WOS:000168059600006 PM 11327115 ER PT J AU Hartwig, W Jimenez, RE Fernandez-del Castillo, C Kelliher, A Jones, R Warshaw, AL AF Hartwig, W Jimenez, RE Fernandez-del Castillo, C Kelliher, A Jones, R Warshaw, AL TI Expression of the adhesion molecules Mac-1 and L-selectin on neutrophils in acute pancreatitis is protease- and complement-dependent SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 85th Annual Clinical Congress of the American-College-of-Surgeons CY OCT 10-15, 1999 CL SAN FRANCISCO, CALIFORNIA SP Amer Coll Surg ID TRYPSINOGEN-ACTIVATION PEPTIDES; MEDIATED LUNG INJURY; UP-REGULATION; RATS; ACCUMULATION; INFLAMMATION; COMPONENT; ANTIBODY; SEVERITY; PROTEINS AB Objective To examine the effect of pancreatic proteases on the expression of the adhesion molecules Mac-1 and L-selectin on neutrophils, and the role of complement activation in this process. Summary Background Data Sequestration of neutrophils in the pancreatic and pulmonary microvasculature characterizes acute pancreatitis. Methods Serum was collected from inbred rats after induction of necrotizing pancreatitis; trypsinogen activation peptide was measured to quantify trypsin activation. Normal rat serum was also collected and subjected to limited trypsin digestion with and without the addition of complement inhibitor. Both groups of sera were incubated in vitro with healthy leukocytes. Expression of Mac-1 and L-selectin on neutrophils was measured quantitatively by flow cyometry. To assess the consequences of these events in vivo, trypsinated serum with or without complement inhibition or control serum was infused intravenous into rats. Soybean trypsin inhibitor was added to serum before injections to block residual trypsin activity. Pancreatic and pulmonary injury was quantitiated by histology, measurement of edema, and myeloperoxidase activity. Results Mac-1 expression on neutrophils incubated with pancreatitis serum was increased compared with controls, whereas L-selectin was decreased. Neutrophils incubated with trypsinated serum also showed upregulation of Mac-1 and downregulation of L-selectin, particularly with trypsin at 10(-4) mol/L. Addition of soluble complement receptor 1 abrogated both Mac-1 upregulation and L-selectin downregulation. Lungs of animals injected with trypsinated serum showed increased edema and myeloperoxidase activity, which were reduced by soluble complement receptor 1. Conclusions Trypsin-generated complement activation participates in the upregulation of Mac-1 and shedding of L-selectin on neutrophils in acute pancreatitis. Protease or complement inhibition may be effective in preventing leukocyte migration and subsequent local and remote organ injury. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, Dept Surg, WHT 506, Boston, MA 02114 USA. FU PHS HHS [R01 45737] NR 35 TC 28 Z9 29 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD MAR PY 2001 VL 233 IS 3 BP 371 EP 378 DI 10.1097/00000658-200103000-00011 PG 8 WC Surgery SC Surgery GA 407AX UT WOS:000167250200011 PM 11224625 ER PT J AU Balch, CM Soong, S Smith, T Ross, MI Urist, MM Karakousis, CP Temple, WJ Mihm, MC Barnhill, RL Jewell, WR Wanebo, HJ Desmond, R AF Balch, CM Soong, S Smith, T Ross, MI Urist, MM Karakousis, CP Temple, WJ Mihm, MC Barnhill, RL Jewell, WR Wanebo, HJ Desmond, R CA Investigators Intergroup Melanoma TI Long-term results of a prospective surgical trial comparing 2 cm vs. 4 cm excision margins for 740 patients with 1-4 mm melanomas SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 53rd Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 16-19, 2000 CL NEW ORLEANS, LOUISIANA SP Soc Surg Oncol DE melanoma; surgical excision margins; neoplasm staging; Cox regression; risk factors ID CUTANEOUS MALIGNANT-MELANOMA; STAGE-I MELANOMA; PROGNOSTIC FACTORS; LOCAL RECURRENCE; TUMOR THICKNESS; MULTIFACTORIAL ANALYSIS; RESECTION MARGINS; SKIN; EFFICACY; HEAD AB Background: The Intergroup Melanoma Surgical Trial began in 1983 to examine the optimal surgical margins of excision for primary melanomas of intermediate thickness (i.e., 1-4 mm). There is now a median 10-year follow-up. Methods: There were two cohorts entered into a prospective multi-institutional trial: (1) 468 patients with melanomas on the trunk or proximal extremity who randomly received a 2 cm or 4 cm radial excision margin and (2) 272 patients with melanomas on the head, neck, or distal extremities who received a 2 cm radial excision margin. Results: A local recurrence (LR) was associated with a high mortality rate, with a 5-year survival rate of only 9% (as a first relapse) or 11% (anytime) compared with an 86% survival for those patients who did trot have a LR (P < .0001). The 10-year survival for all patients with a LR was 5%. The 10-year survival rates were not significantly different when comparing 2 cm vs. 4 cm margins of excision (70% vs. 77%) or comparing the management of the regional lymph nodes (observation vs, elective node dissection). The incidences of LR were the same for patients having a 2 cm vs. 4 cm excision margin regardless of whether the comparisons were made as first relapse (0.4% vs. 0.9%) or at anytime (2.1% vs. 2.6%). When analyzed by anatomic site, the LR rates were 1.1% for melanomas arising on the proximal extremity, 3.1% for the trunk, 5.3% fur the distal extremities, and 9.4%, for the head and neck. The most profound influence on LR rates was the presence or absence of ulceration; it was 6.6% vs. 1.1% in the randomized group involving the trunk and proximal extremity and was 16.2% vs. 2.1% in the nun-randomized group involving the distal extremity and head and neck (P < .001). A multivariate (Cox) regression analysis showed that ulceration was an adverse and independent factor (P = .0001) as was head and neck melanoma site (P = .01), while the remaining factors were not significant (all with P > .12). Conclusion: For this group of melanoma patients, a local recurrence is associated with a high mortality rate, a 2-cm margin of excision is safe and ulceration of the primary melanoma is the most significant prognostic factor heralding an increased risk for a local recurrence. C1 Johns Hopkins Med Ctr, Baltimore, MD USA. Univ Alabama, Birmingham, AL USA. Morristown Mem Hosp, Morristown, NJ USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Univ Calgary, Calgary, AB, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Kansas, Kansas City, KS USA. Roger Williams Hosp, Providence, RI USA. RP Balch, CM (reprint author), 1900 Duke St,Suite 200, Alexandria, VA 22314 USA. NR 29 TC 189 Z9 196 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAR PY 2001 VL 8 IS 2 BP 101 EP 108 DI 10.1245/aso.2001.8.2.101 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 408TX UT WOS:000167344700004 PM 11258773 ER PT J AU Khuri, SF AF Khuri, SF TI Proper timing of blood cardioplegia in infant lambs: Superiority of a multiple-dose regimen - Invited commentary SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02132 USA. RP Khuri, SF (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, 1400 Vet Foreign Wars Pkwy, Boston, MA 02132 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAR PY 2001 VL 71 IS 3 BP 876 EP 876 DI 10.1016/S0003-4975(00)02671-0 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 410KM UT WOS:000167439200027 ER PT J AU Aziz, I Lewis, JR Baker, JD de Virgilio, C AF Aziz, I Lewis, JR Baker, JD de Virgilio, C TI Cardiac morbidity and mortality following carotid endarterectomy: The importance of diabetes and multiple Eagle risk factors SO ANNALS OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the Southern California-Vascular-Surgical-Society CY MAY 05-07, 2000 CL INDIAN WELLS, CALIFORNIA SP So Calif Vasc Surg Soc ID VASCULAR-SURGERY; DIPYRIDAMOLE-THALLIUM AB The objectives of this study were to (1) determine cardiac morbidity and mortality in patients undergoing carotid endarterectomy (CEA) and (2) to determine whether any Eagle risk factors and/or the indication for CEA are associated with a higher risk of an adverse cardiac event. The records of 123 male patients who underwent CEA were retrospectively reviewed. The Eagle risk factors for adverse cardiac events, indications for CEA, and adverse cardiac events were recorded and analyzed. In males undergoing CEA, the presence of diabetes or multiple Eagle risk factors significantly increases the risk of an adverse postoperative cardiac event. There is no difference in cardiac event rate between symptomatic and asymptomatic CEA. Thus, asymptomatic CEA should be approached with caution in these higher cardiac risk patients. C1 Univ Calif Los Angeles, Harbor Med Ctr, Div Vasc Surg, Dept Surg, Torrance, CA 90509 USA. Univ Calif Los Angeles, Harbor Med Ctr, Div Vasc Surg, Dept Surg, Torrance, CA 90509 USA. Univ Calif Los Angeles, Harbor Med Ctr, Dept Emergency Med, Torrance, CA 90509 USA. W Los Angeles VA Med Ctr, Dept Emergency Med, Torrance, CA USA. RP de Virgilio, C (reprint author), Univ Calif Los Angeles, Harbor Med Ctr, Div Vasc Surg, Dept Surg, 1000 W Carson St, Torrance, CA 90509 USA. NR 14 TC 21 Z9 23 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD MAR PY 2001 VL 15 IS 2 BP 243 EP 246 DI 10.1007/s100160010056 PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 417NK UT WOS:000167840900018 PM 11265091 ER PT J AU Farooq, MM Kling, K Yamini, D Gelabert, HA Baker, JD Freischlag, JA AF Farooq, MM Kling, K Yamini, D Gelabert, HA Baker, JD Freischlag, JA TI Penetrating ulceration of the infrarenal aorta: Case reports of an embolic and an asymptomatic lesion SO ANNALS OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the Southern California-Vascular-Surgical-Society CY MAY 05-07, 2000 CL INDIAN WELLS, CALIFORNIA SP So Calif Vasc Surg Soc ID RUPTURE AB Penetrating aortic ulceration is uncommon in the infrarenal aorta. We describe a patient with a penetrating infrarenal aortic ulcer manifesting as blue toe syndrome, and a second patient with a similar lesion identified as an incidental finding. These two patients were treated for penetrating infrarenal; aortic ulceration within the past 9 months at two university-affiliate hospitals, a regional Veterans Administration Medical Center, and a County Medical Center. Both lesions demonstrated aneurysm changes with varying degrees of mural thrombus. The lesion filled with fresh thrombus proved labile, with embolization manifesting as blue toe syndrome. We support the aggressive treatment of aneurysmal penetrating aortic ulcer with aortic graft replacement to eliminate the potential for distal embolization and to obviate the risk of rupture and death. C1 Univ Calif Los Angeles, Gonda Goldschmied Vasc Ctr, Div Vasc Surg, Los Angeles, CA 90095 USA. W Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. RP Farooq, MM (reprint author), Univ Calif Los Angeles, Gonda Goldschmied Vasc Ctr, Div Vasc Surg, 200 Med Plaza,Suite 510-6, Los Angeles, CA 90095 USA. NR 7 TC 7 Z9 8 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD MAR PY 2001 VL 15 IS 2 BP 255 EP 259 DI 10.1007/s100160010062 PG 5 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 417NK UT WOS:000167840900021 PM 11265094 ER PT J AU Salgia, R Harpole, D Herndon, JE Pisick, E Elias, A Skarin, AT AF Salgia, R Harpole, D Herndon, JE Pisick, E Elias, A Skarin, AT TI Role of serum tumor markers CA 125 and CEA in non-small cell lung cancer SO ANTICANCER RESEARCH LA English DT Article DE early and late stage lung cancer; chemotherapy; surgical therapy; indicator of disease progression ID MONOCLONAL-ANTIBODY; MONITORING PATIENTS; OVARIAN-CANCER; CARCINOMA; CHEMOTHERAPY; INDICATOR; CA125 AB Background: CA 125 and CEA are valuable serum tumor markers that can be used to monitor response to therapy in patients with various solid tumors. Systemic studies of CA125 and CEA have not been evaluated in lung cancer. In this study, we report the serum levels of CA 125 and compared it to CEA in newly diagnosed lung cancer and analyzed the serum levels of these markers pre- and post-therapy. Materials and Methods: Two hundred and sixteen patients with newly diagnosed nonsmall lung cancer were evaluated CA 125 and CEA levels were correlated with stage and histopathology. Results: CA 125 levels and CEA levels were shown to be lower in patients with early stage disease as compared to patients with unresectable or metastatic disease. CEA levels were significantly higher among patients with adenocarcinoma, while there was no statistically significant relationship between histology and CA 125. There was a statistically significant difference in the CEA and CA 125 levels dependent on tumor size. Thirty-seven patients were analysed for responses to chemotherapy and responders al e mol e likely to have decreases in CA 125 or CEA. Conclusion: When abnormally elevated inpatients witlrlung cancer; CA 125 and CEA me useful indicators of disease extent, a useful clinical therapeutic marker; and may potentially have important prognostic value. C1 Duke Univ, Med Ctr, Durham, NC 27710 USA. Brigham & Womens Hosp, Dept Adult Oncol, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Salgia, R (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 75348-04, R29-CA73980] NR 14 TC 39 Z9 44 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAR-APR PY 2001 VL 21 IS 2B BP 1241 EP 1246 PG 6 WC Oncology SC Oncology GA 437UR UT WOS:000169012400001 PM 11396194 ER PT J AU Takeshita, H Kusuzaki, K Kuzuhara, A Tsuji, Y Ashihara, T Gebhardt, MC Mankin, HJ Springfield, DS Hirasawa, Y AF Takeshita, H Kusuzaki, K Kuzuhara, A Tsuji, Y Ashihara, T Gebhardt, MC Mankin, HJ Springfield, DS Hirasawa, Y TI Relationship between histologic grade and cytofluorometric cellular DNA and RNA content in primary bone tumors SO ANTICANCER RESEARCH LA English DT Article DE bone tumors; DNA-RNA cytofluorometry; aneuploid; diploid ID CLINICAL IMPORTANCE; PLOIDY ANALYSIS; OSTEO-SARCOMA; FLOW; CHEMOTHERAPY; OSTEOSARCOMAS; LESIONS AB The diagnosis and grading of bone tumors remains a challenging problem. We studied the relationship between histologic grade and cytofluorometric cellular DNA and RNA content in 108 primary bone tumors. The data included DNA ploidy, mean DNA content (MDC), S-phase fraction (SPF), mean RNA content (MRC) and RNA/DNA ratio (RDR; MRC/MDC) which represents the RNA content normalized for the DNA content. Benign tumors had a diploid stem line with low MDC (mean;1.04), low SPF (0.9), high MRC (2.41) and high RDR (2.31). Giant cell tumors of bone, which ar e locally agressive benign tumors, showed diploidy with relatively higher MDC (1.07, p <0.01) and SPF (2.6 p <0.01) and lower MRC (1.82, p <0.01) and RDR (1.69 p <0.01). Similar results were obtained in low-grade sarcomas. In high-grade sar comas, the data depended on the histologic findings. Pleomorphic sarcomas such as osteosarcomas revealed aneuploidy with remarkably higher MDC (1.70 in osteosarcomas, p <0.01) and SPF (6.5, p <0.01), but lower RDR (1.70, p <0.02). In contrast, small cell sarcomas, such as Ewing's sal comas, showed diploidy with low MDC (1.11 in Ewing's sarcomas, N.S.) and SPF (2.5, p <0.01) and extremely low RDR (1.34, p <0.01). The RDR value was higher in well-differentiated tumors than in primitive tumors, rendering it useful in grading bone tumors with a diploid stem fine. By combining the RDR value with the MDC value 96 % of diploid sarcomas could be distinguished from benign tumors. These results indicate that cellular DNA and RNA content analysis may be of value in assessing the malignant potential of diploid as well as aneuploid bone sarcomas. C1 Otsu Municipal Hosp, Dept Orthopaed Surg, Otsu, Shiga 520, Japan. Kyoto Prefectural Univ Med, Dept Orthopaed Surg, Kyoto 602, Japan. Kyoto Prefectural Univ Med, Dept Pathol 1, Kyoto 602, Japan. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Mt Sinai Med Ctr, Dept Orthopaed Surg, New York, NY 10029 USA. RP Takeshita, H (reprint author), Otsu Municipal Hosp, Dept Orthopaed Surg, 2 Chome, Otsu, Shiga 520, Japan. NR 27 TC 3 Z9 3 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAR-APR PY 2001 VL 21 IS 2B BP 1271 EP 1277 PG 7 WC Oncology SC Oncology GA 437UR UT WOS:000169012400005 PM 11396198 ER PT J AU Andes, D Stamsted, T Conklin, R AF Andes, D Stamsted, T Conklin, R TI Pharmacodynamics of amphotericin B in a neutropenic-mouse disseminated-candidiasis model SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ANTIFUNGAL AGENTS; PEAK CONCENTRATION; IN-VITRO; MICE; FLUCONAZOLE; PARAMETERS; INFECTIONS; ALBICANS; TARGETS; RATIO AB In vivo pharmacodynamic parameters have been described for a variety of antibacterials, These parameters have been studied in correlation with in vivo outcomes in order to determine which dosing parameter is predictive of outcome and the magnitude of that parameter associated with efficacy, Very little is known about pharmacodynamics for antifungal agents. We utilized a nentropenic mouse model of disseminated candidiasis to correlate pharmacodynamic parameters (percent time above MIG [T > MIG], area under the concentration time curve [AUG]/MIC ratio, and peak serum level/MIC ratio) for amphotericin B in vivo with efficacy, as measured by organism number in homogenized kidney cultures after 72 h of therapy. Amphotericin B was administered by the intraperitoneal route. Drug kinetics for amphotericin B in infected mice were nonlinear, Serum half-lives ranged from 13 to 27 h, Infection was achieved by intravenous inoculation with 10(6) CFU of yeast cells per mi via the lateral tail vein of neutropenic mice. Groups of mice were treated with fourfold escalating total doses of amphotericin B ranging from 0.08 to 20 mg/kg of body weight divided into 1, 3, or 6 doses over 72 h, Increasing doses produced concentration-dependent killing, ranging from 0 to 2 log(10) CFU/kidney compared to the organism number at the start of therapy. Amphotericin B also produced prolonged dose-dependent suppression of growth after serum levels had fallen below the MIG. Nonlinear regression analysis was used to determine which pharmacodynamic parameter best correlated with efficacy. Peak serum level in relation to the MIG (peak serum level/MIC ratio) was the parameter best predictive of outcome, while the AUC/MIC ratio and T > MIC were only slightly less predictive (peak serum level/MIC ratio, coefficient of determination [R-2] = 90 fo 93%; AUC/MIC ratio, R-2 = 49 to 69%; T > MIG, R-2 = 67 to 85%), The total amount of drug necessary to achieve various microbiological outcomes over the treatment period was 4,8- to 7.6-fold smaller when the dosing schedule called for large single doses than when the same amount of total drug was administered in 2 to 6 doses, Given the narrow therapeutic window of amphotericin B and frequent treatment failures, these results suggest the need for a reevaluation of current dosing regimens. C1 Univ Wisconsin, Sch Med, Dept Med, Infect Dis Sect, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Hosp, Dept Med, Clin Pharmacol Sect, Madison, WI USA. RP Andes, D (reprint author), Univ Wisconsin, Sch Med, Dept Med, Infect Dis Sect, Room H4-570,600 Highland Ave, Madison, WI 53792 USA. NR 25 TC 94 Z9 98 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAR PY 2001 VL 45 IS 3 BP 922 EP 926 DI 10.1128/AAC.45.3.922-926.2001 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 405AJ UT WOS:000167134800044 PM 11181381 ER PT J AU Jungbluth, AA King, R Fisher, DE Iversen, K Coplan, K Kolb, D Williamson, B Chen, YT Stockert, E Old, LJ Busam, KJ AF Jungbluth, AA King, R Fisher, DE Iversen, K Coplan, K Kolb, D Williamson, B Chen, YT Stockert, E Old, LJ Busam, KJ TI Immunohistochemical and reverse transcription-polymerase chain reaction expression analysis of tyrosinase and microphthalmia-associated transcription factor in angiomyolipomas SO APPLIED IMMUNOHISTOCHEMISTRY & MOLECULAR MORPHOLOGY LA English DT Article DE angiomyolipoma; microphthalmia-associated transcription factor; D5; tyrosinase; T311 ID X-CHROMOSOME INACTIVATION; PARAFFIN-EMBEDDED TISSUES; CYTOLYTIC T-LYMPHOCYTES; MELANOCYTE LINEAGE; RENAL ANGIOMYOLIPOMAS; MONOCLONAL-ANTIBODY; ANTIGEN GP100; TUBEROUS SCLEROSIS; HLA-A2 MELANOMAS; SMOOTH-MUSCLE AB Angiomyolipomas (AMLs) show a characteristic immunoreactivity with melanocyte differentiation markers such as monoclonal antibody (mAb) HMB45, which detects melanocyte differentiation antigen gp100 and mAb A103 reacting with Melan-A/MART-1. Monoclonal antibody T311 to tyrosinase (a key enzyme of melanogenesis) and mAb D5 to the microphthalmia (Mitf) antigen are two newly available markers of melanocytic differentiation. The authors tested 15 AMLs with T311 and D5 by irmnunohistochemistry and a subset of 3 cases by reverse transcription-polymerase chain reaction for their expression of tyrosinase and Mitf mRNA. T311 showed poor sensitivity in AMLs because only focal staining was seen in 1 out of 15 cases, although tyrosinase mRNA was found in all tested cases. Mitf mRNA was present in 3 of 3 tested cases, and D5 was positive in 15 of 15 AMLs. However, D5 immunostaining often was focal and not as homogeneous as A103, which was analyzed in a previous study. D5 staining also could be seen in other cell types such as normal renal tubular cells, macrophages, and renal cell carcinoma. The current results show that in contrast with HMB45 and A103, T311 has little or no value in the diagnosis of AMLs. D5 may be useful in a panel of antibodies in the diagnosis of AMLs. C1 Mem Sloan Kettering Canc Ctr, Ludwig Inst Canc Res, New York, NY 10021 USA. Knoxville Dermatopathol Lab, Knoxville, TN USA. Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. New York Presbyterian Hosp, Cornell Med Sch, Dept Pathol, New York, NY USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. RP Jungbluth, AA (reprint author), Mem Sloan Kettering Canc Ctr, Ludwig Inst Canc Res, 1275 York Ave,Box 32, New York, NY 10021 USA. NR 45 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-3345 J9 APPL IMMUNOHISTO M M JI Appl. Immunohistochem. PD MAR PY 2001 VL 9 IS 1 BP 29 EP 34 DI 10.1097/00022744-200103000-00007 PG 6 WC Anatomy & Morphology; Medical Laboratory Technology; Pathology SC Anatomy & Morphology; Medical Laboratory Technology; Pathology GA 405ZE UT WOS:000167189800007 PM 11277411 ER PT J AU Tsao, H Nadiminti, U Sober, AJ Bigby, M AF Tsao, H Nadiminti, U Sober, AJ Bigby, M TI A meta-analysis of reverse transcriptase-polymerase chain reaction for tyrosinase mRNA as a marker for circulating tumor cells in cutaneous melanoma SO ARCHIVES OF DERMATOLOGY LA English DT Article ID MESSENGER-RNA DETECTION; MALIGNANT-MELANOMA; PERIPHERAL-BLOOD; METASTATIC MELANOMA; CURRENT CONTROVERSY; PROSTATE-CANCER; PROGNOSTIC-SIGNIFICANCE; NEOPLASTIC-CELLS; CLINICAL STAGE; REACTION ASSAY AB Objective: To systematically review the use of reverse transcriptase-polymerase chain reaction (RT-PCR) for tyrosinase messenger RNA as a molecular serum marker for metastatic melanoma. Data Sources: Computerized searches (1966-1999) of the PubMed and MDConsult databases and a manual search of retrieved article references. Study Selection: Cohort studies containing test subjects and negative controls were reviewed. Data Extraction: Three investigators independently screened abstracts for relevant studies and 2 investigators independently reviewed all eligible studies. Data Synthesist Of 127 identified studies, 50 were reviewed in detail and 23 met all inclusion criteria. From these 23 studies, the PCR methods, the total number of patients, the number of control subjects, and the number of RT-PCR-positive patients per stage were analyzed. Results of RT-PCR for tyrosinase messenger RNA were positive in 18% (95% confidence interval [CI],3%-22%) patients for stage I disease, 28% (95% CI, 23%-34%) for stage II disease, 19% (95% CI, 16%-21%) for stage I/II localized disease, 30% (95% CI, 26%-34%) for stage III disease, and 45% (95% CI, 41%-50%) for stage IV disease. Specificities were 100% in all but 1 study. Results of RT-PCR were positive in only 0.4% of healthy controls and patients with nonmelanoma cancer. Conclusions: The lack of data on the outcome of stage I, II, and III patients who were RT-PCR positive and the low prevalence of RT-PCR positivity in patients with known stage IV disease limit the applicability of this test at this lime. Ongoing and future studies on a quantitative RT-PCR, amplification of multiple melanoma-associated antigens, and use of the test as a prognostic indicator might improve the utility of this molecular serologic tool. C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Melanoma Ctr, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Dermatol, Boston, MA 02215 USA. Univ S Florida, Coll Med, Tampa, FL USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Bartlett 622,48 Blossom St, Boston, MA 02114 USA. NR 38 TC 61 Z9 61 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD MAR PY 2001 VL 137 IS 3 BP 325 EP 330 PG 6 WC Dermatology SC Dermatology GA 410LM UT WOS:000167441500011 PM 11255333 ER PT J AU Hauser, R Godleski, JJ Hatch, V Christiani, DC AF Hauser, R Godleski, JJ Hatch, V Christiani, DC TI Ultrafine particles in human lung macrophages SO ARCHIVES OF ENVIRONMENTAL HEALTH LA English DT Article DE bronchoalveolar lavage; human lung macrophages; ultrafine particles ID AIR-POLLUTION; PULMONARY; TRANSLOCATION; INJURY; LAVAGE AB As knowledge about size dependency of particle toxicity continues to grow, attention has been focused on ultrafine particles (i.e., < 0.1 pm in diameter). In recent studies with rats, investigators learned that ultrafine particles likely have greater pulmonary toxicity than larger particles, and it is possible that exposure to, and accumulation of, these particles in the human lung may be associated with adverse respiratory health effects. As part of an ongoing study, the authors performed bronchoalveolar lavage in 14 healthy current nonsmokers to investigate the extent to which ultrafine particles were present in lung macrophages. In addition, 10 of the 14 subjects performed pulmonary function tests. Eleven of the 14 subjects were utility workers, and 3 were nonmaintenance employees of a university. The authors used a Zeiss CEM902 electron microscope to study macrophages isolated from bronchoalveolar ravage fluid. Morphometric quantification revealed ultrafine particles in lung macrophages of all 14 volunteers; the average number of ultrafine particles/mum(3) cytoplasm per cell (UFavg) ranged from 34 to 231 (mean = 95, standard deviation = 54). Regression analysis showed that the UFavg was associated inversely with percent predicted forced expiratory volume in 1 second (FEV1.0) (beta = -1.2 percent predicted FEV1.0/10 ultrafine particles mum(3) cytoplasm per cell [standard error = 0.45, p = .03]). The demonstration of ultrafine particles in all 14 subjects, independent of occupational exposure, suggests that there is environmental exposure to ultrafine particles. The negative association between the number of ultrafine particles and ventilatory function demonstrates a need for further investigation into the pulmonary health effects of ultrafine particles. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Physiol Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Boston, MA 02115 USA. RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Bldg 1,Room 1405,665 Huntington Ave, Boston, MA 02115 USA. FU NIEHS NIH HHS [ES05947, ES07069, ES08129, P30 ES000002] NR 25 TC 36 Z9 36 U1 0 U2 5 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 0003-9896 J9 ARCH ENVIRON HEALTH JI Arch. Environ. Health PD MAR-APR PY 2001 VL 56 IS 2 BP 150 EP 156 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 426QR UT WOS:000168360300008 PM 11339679 ER PT J AU Steinhauer, SR Morrow, LA Condray, R Scott, AJ AF Steinhauer, SR Morrow, LA Condray, R Scott, AJ TI Respiratory sinus arrhythmia in persons with organic solvent exposure: Comparisons with anxiety patients and controls SO ARCHIVES OF ENVIRONMENTAL HEALTH LA English DT Article DE anxiety; heart rate variability; respiratory sinus arrhythmia; solvent exposure ID R INTERVAL VARIABILITY; AUTONOMIC NEUROPATHY; HEART-RATE; DISORDER; WORKERS; TOLUENE; TONE; AGE AB Persons exposed to organic solvents have psychiatric symptomatology and cognitive impairments. The results of several studies have suggested that some psychiatric symptoms in these patients reflect similar reactions observed in patients with anxiety disorders. Respiratory sinus arrhythmia provides an indication of impaired autonomic functioning. Whereas decreased respiratory sinus arrhythmia has been reported in anxiety patients, investigators have also noted that higher respiratory rates in these patients obscure differentiation of respiratory sinus arrhythmia from normal values. In this study the authors recorded multiple parameters of respiratory sinus arrhythmia under a paced-breathing condition in 28 patients with solvent exposure, in 18 patients with anxiety disorder, and in 31 controls. The authors observed a high 1-y retest reliability for a subset of the subjects. Significantly reduced respiratory sinus arrhythmia was observed in both anxiety and solvent-exposed patients, compared with controls. Maximum mean heart rates/cycle did not differ among groups, but minimum heart rates were significantly lower for controls than for the two patient groups. The findings suggested that reduced respiratory sinus arrhythmia among patients is not related to higher maximum rates but, rather, to a decrease in vagally mediated alteration associated with respiratory changes observed in both patient groups. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Armstrong Occupat Hlth Care, Kittaning, PA USA. RP Steinhauer, SR (reprint author), VA Pittsburgh Healthcare Syst, 151R,7180 Highland Dr, Pittsburgh, PA 15206 USA. FU NIMH NIH HHS [MH-43846, MH-55762] NR 27 TC 4 Z9 4 U1 0 U2 0 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 0003-9896 J9 ARCH ENVIRON HEALTH JI Arch. Environ. Health PD MAR-APR PY 2001 VL 56 IS 2 BP 175 EP 180 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 426QR UT WOS:000168360300011 PM 11339682 ER PT J AU Stern, Y Jacobs, D Goldman, J Gomez-Tortosa, E Hyman, BT Liu, Y Troncoso, J Marder, K Tang, MX Brandt, J Albert, M AF Stern, Y Jacobs, D Goldman, J Gomez-Tortosa, E Hyman, BT Liu, Y Troncoso, J Marder, K Tang, MX Brandt, J Albert, M TI An investigation of clinical correlates of Lewy bodies in autopsy-proven Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID BODY VARIANT; EXTRAPYRAMIDAL SIGNS; DEMENTIA; CONSORTIUM; ESTABLISH; DIAGNOSIS; REGISTRY AB Background: Studies of patients meeting clinical and pathologic criteria for Alzheimer disease (AD) have not consistently found associations between the presence of Lewy bodies (LBs) at postmortem examination and a higher frequency during life of the clinical features of dementia with LBs. Objective: To evaluate the clinical correlates of LBs in patients with XD. Design and Methods: Fifty-one patients were diagnosed as having probable AD during life and met pathologic criteria for AD. Semiquantitative ratings for LBs were obtained in 4 brain regions: substantia nigra, cingulate, insular cortex, and hippocampus. The patients had been followed up semiannually for up to 9.9 years before death, and clinical features associated with dementia with LBs, including extrapyramidal signs and visual hallucinations, were assessed at each study visit. logistic regression analyses determined whether patients who had LBs were more likely than those without LBs to express specific clinical signs during follow-up. Cox analyses determined whether patients with LBs developed clinical signs or died earlier. Generalized estimating equations were used to compare rates of cognitive or functional change. Results: Nineteen of the 51 patients had at least 1 LB in one of the studied regions. In no case was a significant relation noted between LBs and the presence of a measured clinical sign. No LB measure was associated with an increased risk of developing any of the evaluated clinical signs earlier in the disease. There was no association between the presence of LBs and more rapid mortality or more rapid disease progression. Conclusions: In patients diagnosed as having AD during life, we did not observe a relation of LBs noted during postmortem examination with the presence of any clinical feature that we assessed or with the rapidity of disease progression. The relation between LBs and specific clinical manifestations may be tenuous in these patients. C1 Columbia Univ, Coll Phys & Surg, Gertrude H Sergievsky Ctr, New York, NY 10032 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. Johns Hopkins Univ, Sch Med, Alzheimers Dis Res Ctr, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD USA. Columbia Univ, Coll Phys & Surg, Taub Alzheimers Dis Res Ctr, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Biostat, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. RP Stern, Y (reprint author), Columbia Univ, Coll Phys & Surg, Gertrude H Sergievsky Ctr, 630 W 168th St, New York, NY 10032 USA. OI Brandt, Jason/0000-0001-7381-6244 FU NCRR NIH HHS [RR00645]; NIA NIH HHS [AG07370, AG07232] NR 28 TC 37 Z9 37 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD MAR PY 2001 VL 58 IS 3 BP 460 EP 465 DI 10.1001/archneur.58.3.460 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 410LR UT WOS:000167441900016 PM 11255450 ER PT J AU Li, WJ Judge, H Gragoudas, ES Seddon, JM Egan, KM AF Li, WJ Judge, H Gragoudas, ES Seddon, JM Egan, KM TI Patterns of tumor initiation in choroidal melanoma SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. RP Egan, KM (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD MAR PY 2001 VL 119 IS 3 BP 430 EP 430 PG 1 WC Ophthalmology SC Ophthalmology GA 409CY UT WOS:000167368000016 ER PT J AU Webster, JB Bell, KR Hussey, JD Natale, TK Lakshminarayan, S AF Webster, JB Bell, KR Hussey, JD Natale, TK Lakshminarayan, S TI Sleep apnea in adults with traumatic brain injury: A preliminary investigation SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT 59th Annual Assembly of the American-Academy-of-Physical-Medicine-and-Rehabilitation CY NOV 13-16, 1997 CL ATLANTA, GEORGIA SP Amer Acad Phys Med & Rehabil DE brain injuries; sleep apnea syndromes; rehabilitation ID EXCESSIVE DAYTIME SLEEPINESS; PREVALENCE; EPIDEMIOLOGY; DISTURBANCES; COMPLAINTS; STROKE; MEN AB Objective: To determine the occurrence and nature of sleep-related breathing disorders in adults with traumatic brain injury (TBI). Design: Prospective, observational, consecutive sample en rollment of subjects admitted for rehabilitation after TBT. Setting: Inpatient rehabilitation and subacute rehabilitation units of a tertiary care university medical system. Participants: Subjects (n = 28) included adults with TBI and a Rancho Los Amigos Scale level of 3 or greater who were less than 3 months postinjury and admitted for comprehensive inpatient rehabilitation. Interventions: Overnight sleep study using portable 6-channel monitoring system. Main Outcome Measure: Respiratory disturbance index (RDI), which is the number of apneic and hypopneic episodes per hour of sleep. Results: Evidence of sleep apnea was found in 10 of 28 (36%) subjects as measured by a RDI level of 5 or greater and in 3 of 28 (11%) subjects as measured by a RDI level of 10 or greater. This rate of sleep apnea is significantly (p = .002) higher than would be predicted based on population norms. No correlation was found between the occurrence of significant sleep apnea and measures of TBI severity or other demographic variables. Sleep-related breathing disorders were primarily central though obstructive apneas were also noted. Conclusion: In this preliminary investigation, sleep-related breathing disorders as defined by a respiratory disturbance index of 5 or greater appears to be common in adult subjects with TBI. C1 Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Dept Resp Therapy, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Dept Pulm Med, Seattle, WA USA. RP Webster, JB (reprint author), E Carolina Univ, Dept PM&R, Moye Blvd, Greenville, NC 27858 USA. RI Sanguansri, Luz/B-6630-2011 OI Sanguansri, Luz/0000-0003-1908-7604 NR 33 TC 37 Z9 37 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 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD MAR PY 2001 VL 82 IS 3 BP 316 EP 321 DI 10.1053/apmr.2001.20840 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 407RG UT WOS:000167284100005 PM 11245752 ER PT J AU Cariani, PA AF Cariani, PA TI Specialist and generalist strategies in sensory evolution SO ARTIFICIAL LIFE LA English DT Article DE sensory evolution; adaptability; specialization; neurocomputation; evolutionary robotics C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. RP Cariani, PA (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, 234 Charles St, Boston, MA 02114 USA. NR 9 TC 4 Z9 4 U1 0 U2 1 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 1064-5462 J9 ARTIF LIFE JI Artif. Life PD SPR PY 2001 VL 7 IS 2 BP 211 EP 214 DI 10.1162/106454601753139014 PG 4 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods SC Computer Science GA 476PE UT WOS:000171237300007 PM 11580881 ER PT J AU Elhai, JD Frueh, BC AF Elhai, JD Frueh, BC TI Subtypes of clinical presentations in malingerers of posttraumatic stress disorder: An MMPI-2 cluster analysis SO ASSESSMENT LA English DT Article DE MMPI-2; malingering; Posttraumatic Stress Disorder; cluster analysis ID COMPENSATION SEEKING STATUS; COMBAT VETERANS; PTSD; EXAGGERATION; POPULATION; VIETNAM AB This paper investigated subtypes of individuals trained and instructed to malinger Posttraumatic Stress Disorder (PTSD) through a cluster analysis of their Minnesota Multiphasic Personality Inventory-2 (MMPI-2) clinical and validity scales. Participants were 84 men and women college students at a community college in the southeastern United States. Two well fitting MMPI-2 cluster solutions were evaluated with discriminant analyses and multivariate analyses of variance (MANOVAs); a 2-cluster solution was deemed optimal. Significant between-cluster differences emerged in follow-up analyses on most of the content scales of the MMPI-2. Most demographic variables did not account for differences in cluster membership. Clusters differed in their reported clarity of the materials used to educate them about PTSD. Discriminant analyses yielded better correct classification rates than those from previous studies, when the more severely symptomatic cluster was compared with a sample of clinical combat-related PTSD veterans. Implications are considered in conducting future malingered PTSD investigations. C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Frueh, BC (reprint author), Vet Affairs Med Ctr, Mental Hlth Serv 116, 109 Bee St, Charleston, SC 29401 USA. NR 33 TC 5 Z9 5 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1073-1911 J9 ASSESSMENT JI Assessment PD MAR PY 2001 VL 8 IS 1 BP 75 EP 84 DI 10.1177/107319110100800107 PG 10 WC Psychology, Clinical SC Psychology GA 531YV UT WOS:000174445600007 PM 11310728 ER PT J AU Weissleder, R Bogdanov, A Tung, CH Weinmann, HJ AF Weissleder, R Bogdanov, A Tung, CH Weinmann, HJ TI Size optimization of synthetic graft copolymers for in vivo angiogenesis imaging SO BIOCONJUGATE CHEMISTRY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; TUMOR ANGIOGENESIS; VASCULAR-PERMEABILITY; ANTIBODY; MODEL AB Angiogenesis is a critical step in tumor development and more than 25 angiogenesis inhibitors are currently in clinical trials. Noninvasive in vivo imaging of angiogenesis represents a unique opportunity of repeatedly quantitating microvascular parameters prior to and during anti-angiogenic treatments. While several imaging tracers have been proposed for MR and nuclear imaging, there does not exist any consensus of what constitutes an ideal size of an imaging agent. A series of synthetic pegylated DOTA derivatized graft copolymers (30, 60, 120 kDa) were synthesized and their in vivo behavior tested in two breast cancer models differing in vascular endothelial growth factor (VEGF) expression. Polymers were labeled with different lanthanides (Eu, Gd, Dy) and absolute blood and tumor concentrations were determined by ICP-AES measurements. DOTA and the 30 kDa polymers underwent renal clearance resulting in low plasma levels. Slow leakage across neovasculature into tumor interstitium was clearly dependent on the molecular mass of all tested agents in MCF-7 tumors. However, a cutoff was observed with minimal extravasation occurring at and above 120 kDa in well differentiated MCF-7 tumors. VEGF overexpression caused detectable differences in extravasation of all polymers, including the 120 kDa compound. We conclude that large molecular weight contrast agents with a molecular mass of <120 kDa extravasate from experimental tumor neovasculature and may not be an accurate marker for measuring true blood volume fractions when in vivo imaging is performed in the steady state. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. Schering AG, D-1000 Berlin, Germany. RP Weissleder, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. OI Tung, Ching-Hsuan/0000-0001-6648-6195 NR 25 TC 68 Z9 69 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD MAR-APR PY 2001 VL 12 IS 2 BP 213 EP 219 DI 10.1021/bc000091p PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 416TU UT WOS:000167796900011 PM 11312682 ER PT J AU Pettegrew, JW Panchalingam, K Levine, J McClure, RJ Gershon, S Yao, JK AF Pettegrew, JW Panchalingam, K Levine, J McClure, RJ Gershon, S Yao, JK TI Chronic myo-inositol increases rat brain phosphatidylethanolamine plasmalogen SO BIOLOGICAL PSYCHIATRY LA English DT Article DE myo-inositol; phosphatidylethanolamine plasmalogen; major depression; phospholipid metabolism; P-31 NMR; HPTLC ID P-31 NMR; MAGNETIC-RESONANCE; ETHANOLAMINE PLASMALOGENS; MYOINOSITOL TRANSPORT; TISSUE PHOSPHOLIPIDS; ALZHEIMERS-DISEASE; DOUBLE-BLIND; SYSTEM; MEMBRANES; DISORDER AB Background: Oral myo-inositol (12-18 g/day) has shown beneficial effect in placebo-controlled studies of major depression, panic disorder, and obsessive compulsive disorder, and preliminary data suggest it also map be effective in bipolar depression. Evidence linking antidepressant activity to membrane phospholipid alterations suggested the examination of acute and chronic myoinositol effects on rat brain membrane phospholipid metabolism. Methods: With both P-31 nuclear magnetic resonance (NMR) and quantitative high-performance thin-layer chromatography (HPTLC; hydrolysis) methods, rat brain phospholipid levels were measured after acute (n = 20, each group) and chronic myo-inositol administration (n = 10, each group), With P-31 NMR, we measured myoinositol rat brain levels after acute and chronic myoinositol administration. Results: Brain myo-inositol increased by 17% after acute myo-inositol administration and by 5% after chronic administration, as compared with the control groups. Chronic myo-inositol administration increased brain phosphatidylethanolamine (PtdEtn) plasmalogen by 10% and decreased brain PtdEtn by 5%, thus increasing the ratio PtdEtn plasmalogen (PtdEtn-Plas)/PtdEtn by 15%. Phosphatidylethanolamine plasmalogen levels quantified by P-31 NMR and HPTLC were highly correlated. The validity and reliability of the P-31 NMR method for phospholipid analysis were demonstrated with phospholipid standards. Conclusions: The observed alteration in the PtdEtn-Plas/PtdEtn ratio could provide insights into the therapeutic effect of myo-inositol in affective disorders. Biol Psychiatry 2001;49:444-453 (C) 2001 Society of Biological Psychiatry. C1 Univ Pittsburgh, Sch Med, Neurophys Lab, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Ben Gurion Univ Negev, Fac Hlth Sci, Dept Psychiat, Beer Sheva, Israel. RP Pettegrew, JW (reprint author), Univ Pittsburgh, Sch Med, Neurophys Lab, Room A741,Crabtree Hall,130 De Soto St, Pittsburgh, PA 15213 USA. FU NIA NIH HHS [AG08974] NR 44 TC 13 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 2001 VL 49 IS 5 BP 444 EP 453 DI 10.1016/S0006-3223(00)00953-7 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 409VN UT WOS:000167406500007 PM 11274656 ER PT J AU McConnell, KA Nahas, Z Shastri, A Lorberbaum, JP Kozel, FA Bohning, DE George, MS AF McConnell, KA Nahas, Z Shastri, A Lorberbaum, JP Kozel, FA Bohning, DE George, MS TI The transcranial magnetic stimulation motor threshold depends on the distance from coil to underlying cortex: A replication in healthy adults comparing two methods of assessing the distance to cortex SO BIOLOGICAL PSYCHIATRY LA English DT Article DE transcranial magnetic stimulation; motor threshold; motor cortex; prefrontal cortex; MRI; depression AB Using transcranial magnetic stimulation (TMS), a hand-held electrified copper coil against the scalp produces a powerful and rapidly oscillating magnetic field, which in turn induces electrical currents in the brain. The amount of electrical energy needed for TMS to induce motor movement (called the motor threshold [MT]), varies widely across individuals. The intensity of TMS is dosed relative to the MT. Kozel et al observed in a depressed cohort that MT increases as a function of distance from coil to cortex, This article examines this relationship in a healthy cohort and compares the two methods of assessing distance to cortex. Seventeen healthy adults had their TMS MT determined and marked with a fiducial. Magnetic resonance images showed the fiducials marking motor cortex, allowing researchers to measure distance from scalp to motor and prefontal cortex using two methods: 1) measuring a line from scalp to the nearest cortex and 2) sampling the distance from scalp to cortex of two 18-mm-square areas. Confirming Kozel's previous finding, we observe that motor threshold increases as distance to motor cortex increased for both methods of measuring distance and that no significant correlation exists between MT and prefontal cortex distance. Distance from TMS coil to motor cortex is an important determinant of MT in healthy and depressed adults. Distance to prefontal cortex is not correlated with MT, raising questions about the common practice of dosing prefontal stimulation using MT determined over motor cortex. Biol Psychiatry 2001;49:454-459 (C) 2001 Society of Biological Psychiatry. C1 Med Univ S Carolina, Dept Radiol, Brain Stimulat Lab, Charleston, SC 29425 USA. Med Univ S Carolina, Funct Neuroimaging Div, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Brain Stimulat Lab, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Brain Stimulat Lab, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Dept Psychiat, Charleston, SC USA. RP George, MS (reprint author), Med Univ S Carolina, Dept Radiol, Brain Stimulat Lab, 171 Ashley Ave, Charleston, SC 29425 USA. RI Kozel, Frank/I-5366-2012 NR 10 TC 118 Z9 121 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 1 PY 2001 VL 49 IS 5 BP 454 EP 459 DI 10.1016/S0006-3223(00)01039-8 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 409VN UT WOS:000167406500008 PM 11274657 ER PT J AU Pru, JK Rueda, BR Austin, KJ Thatcher, WW Guzeloglu, A Hansen, TR AF Pru, JK Rueda, BR Austin, KJ Thatcher, WW Guzeloglu, A Hansen, TR TI Interferon-tau suppresses prostaglandin F-2 alpha secretion independently of the mitogen-activated protein kinase and nuclear factor kappa B pathways SO BIOLOGY OF REPRODUCTION LA English DT Article DE conceptus; mechanisms of hormone action; pregnancy; signal transduction; uterus ID BOVINE ENDOMETRIAL CELLS; EPITHELIAL-CELLS; CELLULAR MECHANISMS; PREGNANCY RECOGNITION; OVINE ENDOMETRIUM; GENE-EXPRESSION; STROMAL CELLS; MAP KINASE; IN-VITRO; OXYTOCIN AB Pregnancy is established in ruminants through inhibitory actions of interferon (IFN)-tau on the release of prostaglandin F-2 alpha (PGF), which allows the corpus luteum to survive and continue to produce progesterone. Experiments were designed to 1) delineate the signal transduction pathway coordinating the synthesis of PGE, 2) determine how rapidly recombinant bovine (rb) IFN-tau attenuated phorbol ester (PDBu)-induced secretion of PGF, and 3) establish the site at which rbIFN-tau attenuates the secretion of PGF in cultured bovine endometrial (BEND) cells. BEND cells were untreated (control) or treated for 5, 10, 60, 180, or 300 min with PDBu (100 ng/ml), rbIFN-tau (50 or 500 ng/ml), PDBu + rbIFN-tau, or PDBu + PD98059 (MEK-1 inhibitor; 50 muM). Secretion of PGF was induced (P < 0.0001) by PDBu within 180 min, but induction was inhibited 74% by the addition of rbIFN- (P < 0.0001) and was ablated completely by PD98059. Parallel results were obtained for cyclooxygenase (COX)-2 protein expression. PDBu induced (P < 0.05) activation of the Raf-1/MEK-1/ERK-1/2 pathway, which was obligatory for the expression of COX-2 and secretion of PGF but was not altered by cotreatment with rbIFN-tau. PDBu induced (P < 0.05) transcription of c-jun and c-fos mRNAs within 30 min; induction was inhibited (P < 0.05) by cotreatment with PD98059 but not by cotreatment with rbIFN-tau. Treatment of BEND cells with rbIFN-tau also did not attenuate PDBu-induced degradation of I kappaB alpha, suggesting that the I kappaB alpha /NF kappaB pathway is not a site of IFN-tau inhibition of PGF. However, rbIFN-tau did block transcription of the COX-2 gene induced by PDBu within 30 min. In conclusion, COX-2 expression and PGF secretion induced by PDBu is mediated through the Raf-1/MEK-1/ERK-1/2 pathway, but this pathway is not disrupted by rbIFN-tau. Because rbIFN-tau inhibits COX-2 mRNAs within 30 min, we hypothesized that transcription factors activated by rbIFN-tau rapidly and directly attenuate COX-2 gene expression, thereby suppressing secretion of PGF. C1 Univ Wyoming, Dept Anim Sci, Laramie, WY 82071 USA. Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Univ Florida, Dept Poultry & Dairy Sci, Gainesville, FL 32601 USA. RP Hansen, TR (reprint author), Univ Wyoming, Dept Anim Sci, Laramie, WY 82071 USA. FU PHS HHS [R01-32475] NR 50 TC 21 Z9 21 U1 0 U2 3 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD MAR PY 2001 VL 64 IS 3 BP 965 EP 973 DI 10.1095/biolreprod64.3.965 PG 9 WC Reproductive Biology SC Reproductive Biology GA 404UP UT WOS:000167120400029 PM 11207214 ER PT J AU Fitzmaurice, GM Lipsitz, SR Molenberghs, G Ibrahim, JG AF Fitzmaurice, GM Lipsitz, SR Molenberghs, G Ibrahim, JG TI Bias in estimating association parameters for longitudinal binary responses with drop-outs SO BIOMETRICS LA English DT Article DE generalized estimating equations; missing data; repeated measures ID MISSING DATA; REGRESSION AB This paper considers the impact of bias in the estimation of the association parameters for longitudinal binary responses when there are drop-outs. A number of different estimating equation approaches are considered for the case where drop-out cannot be assumed to be a completely random process. In particular, standard generalized estimating equations (GEE), GEE based on conditional residuals, GEE based on multivariate normal estimating equations for the covariance matrix, and second-order estimating equations (GEE2) are examined. These different GEE estimators are compared in terms of finite sample and asymptotic bias under a variety of drop-out processes. Finally, the relationship between bias in the estimation of the association parameters and bias in the estimation of the mean parameters is explored. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Limburgs Univ Ctr, B-3590 Diepenbeek, Belgium. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Fitzmaurice, GM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. FU NIEHS NIH HHS [ES07142]; NIGMS NIH HHS [GM29745]; NIMH NIH HHS [MH17119] NR 16 TC 16 Z9 16 U1 0 U2 2 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 2001 VL 57 IS 1 BP 15 EP 21 DI 10.1111/j.0006-341X.2001.00015.x PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 409GW UT WOS:000167376900003 PM 11252590 ER PT J AU Chen, MH Ibrahim, JG AF Chen, MH Ibrahim, JG TI Maximum likelihood methods for cure rate models with missing covariates SO BIOMETRICS LA English DT Article DE cure rate model; ENT algorithm; Gibbs sampling; latent variables; missing data ID PROPORTIONAL HAZARDS REGRESSION; FAILURE-TIME REGRESSION; CENSORED SURVIVAL-DATA; MIXTURE-MODELS; MONTE-CARLO; DATA AUGMENTATION; EM ALGORITHM; FRACTION; TESTS; RISK AB We propose maximum likelihood methods for parameter estimation for a novel class of semiparametric survival models with a cure fraction, in which the covariates are allowed to be missing. We allow the covariates to be either categorical or continuous and specify a parametric distribution for the covariates that is written as a sequence of one-dimensional conditional distributions. We propose a novel EM algorithm for maximum likelihood estimation and derive standard errors by using Louis's formula (Louis, 1982, Journal of the Royal Statistical Society, Series B 44, 226-233). Computational techniques using the Monte Carlo EM algorithm are discussed and implemented. A real data set involving a melanoma cancer clinical trial is examined in detail to demonstrate the methodology. C1 Worcester Polytech Inst, Dept Math Sci, Worcester, MA 01609 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Chen, MH (reprint author), Worcester Polytech Inst, Dept Math Sci, Worcester, MA 01609 USA. NR 46 TC 38 Z9 40 U1 0 U2 3 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 2001 VL 57 IS 1 BP 43 EP 52 DI 10.1111/j.0006-341X.2001.00043.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 409GW UT WOS:000167376900006 PM 11252617 ER PT J AU Yeap, BY Davidian, M AF Yeap, BY Davidian, M TI Robust two-stage estimation in hierarchical nonlinear models SO BIOMETRICS LA English DT Article DE M-estimation; mixed effects; outliers; repeated measurements ID MIXED EFFECTS MODELS; LINEAR-MODELS AB Hierarchical models encompass two sources of variation, namely within and among individuals in the population; thus, it is important to identify outliers that may arise at each sampling level. A two-stage approach to analyzing nonlinear repeated measurements naturally allows parametric modeling of the respective variance structure for the intraindividual random errors and interindividual random effects. We propose a robust two-stage procedure based on Huber's (1981, Robust Statistics) theory of M-estimation to accommodate separately aberrant responses within an experimental unit and subjects deviating from the study population when the usual assumptions of normality are violated. A toxicology study of chronic ozone exposure in rats illustrates the impact of outliers on the population inference and hence the advantage of adopting the robust methodology. The robust weights generated by the two-stage M-estimation process also serve as diagnostics for gauging the relative influence of outliers at each level of the hierarchical model. A practical appeal of our proposal is the computational simplicity since the estimation algorithm may be implemented using standard statistical software with a nonlinear least squares routine and iterative capability. C1 Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. RP Yeap, BY (reprint author), Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. FU NIAID NIH HHS [R01-AI24643, R01-AI41214, U01-AI38855] NR 16 TC 10 Z9 10 U1 0 U2 2 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 2001 VL 57 IS 1 BP 266 EP 272 DI 10.1111/j.0006-341X.2001.00266.x PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 409GW UT WOS:000167376900036 PM 11252609 ER PT J AU Betensky, RA Schoenfeld, DA AF Betensky, RA Schoenfeld, DA TI Nonparametric estimation in a cure model with random cure times SO BIOMETRICS LA English DT Article DE competing risks; cure rate; Greenwood's formula; mixture model; variance ID COMPETING RISKS; MIXTURE MODEL; SURVIVAL-DATA AB Acute respiratory distress syndrome (ARDS) is a life-threatening acute condition that sometimes follows pneumonia or surgery. Patients who recover and leave the hospital are considered to have been cured at the time they leave the hospital. These data differ from typical data in which cure is a possibility: death times are not observed for patients who are cured and cure times are observed and vary among patients. Here we apply a competing risks model to these data and show it to be equivalent to a mixture model, the more common approach for cure data. Further, we derive an estimator for the variance of the cumulative incidence function from the competing risks model, and thus for the cure rate, based on elementary calculations. We compare our variance estimator to Gray's (1988, Annals of Statistics 16, 1140-1154) estimator, which is based on counting process theory. We find our estimator to be slightly more accurate in small samples. We apply these results to data from an ARDS clinical trial. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Betensky, RA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA 75971]; NHLBI NIH HHS [HR-94-04] NR 15 TC 23 Z9 24 U1 0 U2 3 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 2001 VL 57 IS 1 BP 282 EP 286 DI 10.1111/j.0006-341X.2001.00282.x PG 5 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 409GW UT WOS:000167376900038 PM 11252611 ER PT J AU Nusser, Z Naylor, D Mody, I AF Nusser, Z Naylor, D Mody, I TI Synapse-specific contribution of the variation of transmitter concentration to the decay of inhibitory postsynaptic currents SO BIOPHYSICAL JOURNAL LA English DT Article ID GABA(A) RECEPTOR SUBUNITS; SINGLE-CHANNEL PROPERTIES; CEREBELLAR GRANULE CELLS; CENTRAL-NERVOUS-SYSTEM; ADULT-RAT BRAIN; HIPPOCAMPAL SYNAPSES; MINIATURE IPSCS; MESSENGER-RNAS; RELEASE SITES; QUANTAL SIZE AB Synaptic transmission is characterized by a remarkable trial-to-trial variability in the postsynaptic response, influencing the way in which information is processed in neuronal networks. This variability may originate from the probabilistic nature of quantal transmitter release, from the stochastic behavior of the receptors, or from the fluctuation of the transmitter concentration in the cleft. We combined nonstationary noise analysis and modeling techniques to estimate the contribution of transmitter fluctuation to miniature inhibitory postsynaptic current (mlPSC) variability. A substantial variability (similar to 30%) in mlPSC decay was found in all cell types studied (neocortical layer2/3 pyramidal cells, granule cells of the olfactory bulb, and interneurons of the cerebellar molecular layer). This large variability was not solely the consequence of the expression of multiple types of GABA, receptors, as a similar mlPSC decay variability was observed in cerebellar interneurons that express only a single type (alpha (1)beta (2)gamma (2)) of GABA(A) receptor. At large synapses on these cells, all variance in mlPSC decay could be accounted for by the stochastic behavior of similar to 36 pS channels, consistent with the conductance of alpha (1)beta (2)gamma (2) GABA(A) receptors at physiological temperatures. In contrast, at small synapses, a significant amount of variability in the synaptic cleft GABA transient had to be present to account for the additional variance in IPSC decay over that produced by stochastic channel openings. Thus, our results suggest a synapse-specific contribution of the variation of the spatiotemporal profile of GABA to the decay of IPSCs. C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Reed Neurol Res Ctr, Los Angeles, CA 90095 USA. VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90095 USA. RP Mody, I (reprint author), Univ Calif Los Angeles, Sch Med, Dept Neurol, Reed Neurol Res Ctr, 710 Westwood Pl,RNRC 3-155, Los Angeles, CA 90095 USA. RI Nusser, Zoltan/K-8587-2014; OI Nusser, Zoltan/0000-0001-7004-4111 FU NINDS NIH HHS [NS 30549] NR 51 TC 78 Z9 81 U1 1 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAR PY 2001 VL 80 IS 3 BP 1251 EP 1261 PG 11 WC Biophysics SC Biophysics GA 405VW UT WOS:000167182100019 PM 11222289 ER PT J AU Silverman, LB Gelber, RD Dalton, VK Asselin, BL Barr, RD Clavell, LA Hurwitz, CA Moghrabi, A Samson, Y Schorin, MA Arkin, S Declerck, L Cohen, HJ Sallan, SE AF Silverman, LB Gelber, RD Dalton, VK Asselin, BL Barr, RD Clavell, LA Hurwitz, CA Moghrabi, A Samson, Y Schorin, MA Arkin, S Declerck, L Cohen, HJ Sallan, SE TI Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01 SO BLOOD LA English DT Article ID MINIMAL RESIDUAL DISEASE; PEDIATRIC-ONCOLOGY-GROUP; ACUTE LYMPHOCYTIC-LEUKEMIA; INTRAVENOUS METHOTREXATE; INTENSIVE ASPARAGINASE; CRANIAL IRRADIATION; MENINGEAL LEUKEMIA; COGNITIVE SEQUELAE; CANCER-GROUP; NON-T AB The Dana-Farber Cancer Institute (DFCI) acute lymphoblastic leukemia (ALL) Consortium Protocol 91-01 was designed to improve the outcome of children with newly diagnosed ALL while minimizing toxicity, Compared with prior protocols, past-remission therapy was intensified by substituting dexamethasone for prednisone and prolonging the asparaginase intensification from 20 to 30 weeks, Between 1991 and 1995, 377 patients (age, 0-18 years) were enrolled; 137 patients were considered standard risk (SR), and 240 patients were high risk (HR), Following a 5.0-year median follow-up, the estimated 5-year event-free survival (EFS) +/- SE for all patients was 83% +/- 2%, which is superior to prior DFCI ALL Consortium protocols conducted between 1981 and 1991 (P = .03), There was no significant difference in 5-year EFS based upon risk group (87% +/- 3% for SR and 81% +/- 3% for HR, P = .24), Age at diagnosis was a statistically significant prognostic factor (P = .03), with inferior outcomes observed in infants and children 9 years or older, Patients who tolerated 25 or fewer weeks of asparaginase had a significantly worse outcome than those who received at least 26 weeks of asparaginase (P < .01, both univariate and multivariate). Older children (at least 9 years of age) were significantly more likely to have tolerated 25 or fewer weeks of asparaginase (P < .01), Treatment on Protocol 91-01 significantly improved the outcome of children with ALL, perhaps due to the prolonged asparaginase intensification and/or the use of dexamethasone. The inferior outcome of older children may be due, in part, to increased intolerance of intensive therapy. (Blood. 2001;97:1211-1218) (C) 2001 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Univ Rochester, Med Ctr, Dept Hematol Oncol, Rochester, NY 14642 USA. McMaster Univ, Med Ctr, Dept Pediat, Hamilton, ON, Canada. San Jorge Childrens Hosp, San Juan, PR USA. Maine Med Ctr, Barbara Bush Childrens Hosp, Maine Childrens Canc Program, Portland, ME 04102 USA. Hosp St Justine, Montreal, PQ, Canada. Univ Laval, Ctr Hosp, Laval, PQ, Canada. Oschsner Inst, Dept Pediat, New Orleans, LA USA. Schneider Childrens Hosp, New Hyde Park, NY USA. Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA. RP Silverman, LB (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA 68484, CA06516] NR 41 TC 411 Z9 430 U1 0 U2 10 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 2001 VL 97 IS 5 BP 1211 EP 1218 DI 10.1182/blood.V97.5.1211 PG 8 WC Hematology SC Hematology GA 404TQ UT WOS:000167117500007 PM 11222362 ER PT J AU Reichert, A Heisterkamp, N Daley, GQ Groffen, J AF Reichert, A Heisterkamp, N Daley, GQ Groffen, J TI Treatment of Bcr/Abl-positive acute lymphoblastic leukemia in P190 transgenic mice with the farnesyl transferase inhibitor SCH66336 SO BLOOD LA English DT Article ID ONCOGENIC MUTATIONS; CELL-GROWTH; RAS; PROTEIN; TRANSFORMATION; REQUIREMENT AB The Philadelphia (Ph) chromosome is found in approximately 3% of pediatric patients with acute lymphoblastic leukemia (ALL) and the percentage markedly increases in adult patients. The prognosis for this class of patients is poor, and no standard chemotherapy combination so far has demonstrated long-term efficacy. The Ph-translocation joins the BCR and ABL genes and leads to expression of a chimeric Bcr/Abl protein with enhanced tyrosine kinase activity. This increase in activity leads to malignant transformation by interference with basic cellular functions such as the control of proliferation, adherence to stroma and extracellular matrix, and apoptosis. One important pathway activated by Bcr/Abl is the Ras pathway. Ras proteins have to undergo a series of posttranslational modifications to become biologically active. The first modification is the farnesylation of the C-terminus catalyzed by farnesyl transferase. We studied the effect of the farnesyl transferase inhibitor SCH66336 in an in vivo murine model of Bcr/Abl-positive acute lymphoblastic leukemia. In the early leukemic phase, mice were randomly assigned to a treatment, a vehicle, and a nontreatment group. The treatment was well tolerated without any detectable side effects. All animals of the control groups died of leukemia/lymphoma within 103 days (range, 18-103 days). In contrast, 80% of the drug-receiving group survived without any signs of leukemia or lymphoma until termination of treatment, after a median treatment period of 200 days (range, 179-232 days). We conclude that farnesyl transferase inhibitor SCH66336 is able to revert early signs of leukemia and significantly prolongs survival in a murine ALL model. (Blood, 2001;97:1399-1403) (C) 2001 by The American Society of Hematology. C1 Childrens Hosp Los Angeles, Res Inst, Sect Mol Carcinogenesis, Div Hematol Oncol, Los Angeles, CA 90027 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Groffen, J (reprint author), Childrens Hosp Los Angeles, Res Inst, Sect Mol Carcinogenesis, Div Hematol Oncol, MS 54,4650 Sunset Blvd, Los Angeles, CA 90027 USA. FU NCI NIH HHS [CA47456, CA50248] NR 24 TC 98 Z9 99 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 2001 VL 97 IS 5 BP 1399 EP 1403 DI 10.1182/blood.V97.5.1399 PG 5 WC Hematology SC Hematology GA 404TQ UT WOS:000167117500031 PM 11222386 ER PT J AU Peters, DG Hoover, RR Gerlach, MJ Koh, EY Zhang, HY Choe, K Kirschmeier, P Bishop, WR Daley, GQ AF Peters, DG Hoover, RR Gerlach, MJ Koh, EY Zhang, HY Choe, K Kirschmeier, P Bishop, WR Daley, GQ TI Activity of the farnesyl protein transferase inhibitor SCH66336 against BCR/ABL-induced murine leukemia and primary cells from patients with chronic myeloid leukemia SO BLOOD LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; ABL TYROSINE KINASE; FARNESYLTRANSFERASE INHIBITORS; PHILADELPHIA-CHROMOSOME; ANTITUMOR-ACTIVITY; ADAPTER PROTEIN; RAS PROTEIN; SH2 DOMAIN; TRANSFORMATION; GROWTH AB BCR/ABL, the oncoprotein responsible for chronic myeloid leukemia (CML), transforms hematopoietic cells through both Ras-dependent and -independent mechanisms. Farnesyl protein transferase inhibitors (FTIs) were designed to block mutant Ras signaling, but they also inhibit the growth of transformed cells with wild-type Ras, implying that other farnesylated targets contribute to FTI action. In the current study, the clinical candidate FTI SCH66336 was characterized for its ability to inhibit BCR/ABL transformation. When tested against BCR/ABL-BaF3 cells, a murine cell line that is leukemogenic in mice, SCH66336 potently inhibited soft agar colony formation, slowed proliferation, and sensitized cells to apoptotic stimuli. Quantification of activated guanosine triphosphate (GTP)-bound Ras protein and electrophoretic mobility shift assays for AP-1 DNA binding showed that Ras effector pathways are inhibited by SCH66336. However, SCH66336 was more inhibitory than dominant-negative Ras in assays of soft agar colony formation and cell proliferation, suggesting activity against targets other than Ras. Cell cycle analysis of BCR/ABL-BaF3 cells treated with SCH66336 revealed G2/M blockade, consistent with recent reports that centromeric proteins that regulate the G2/M checkpoint are critical farnesylated targets of FTI action. Mice injected intravenously with BCR/ABL-BaF3 cells developed acute leukemia and died within 4 weeks with massive splenomegaly, elevated white blood cell counts, and anemia. In contrast, nearly all mice treated with SCH66336 survived and have remained disease-free for more than a year. Furthermore, SCH66336 selectively inhibited the hematopoietic colony formation of primary human CML cells. As an oral, nontoxic compound with a mechanism of action distinct from that of ABL tyrosine kinase inhibition, FTI SCH66336 shows promise for the treatment of BCR/ABL-induced leukemia. (Blood, 2001;97: 1404-1412) (C) 2001 by The American Society of Hematology. C1 Whitehead Inst, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Schering Plough Corp, Res Inst, Dept Tumor Biol, Kenilworth, NJ 07033 USA. RP Daley, GQ (reprint author), Whitehead Inst, 9 Cambridge Ctr, Cambridge, MA 02142 USA. FU NCI NIH HHS [CA476418-01] NR 49 TC 150 Z9 152 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 2001 VL 97 IS 5 BP 1404 EP 1412 DI 10.1182/blood.V97.5.1404 PG 9 WC Hematology SC Hematology GA 404TQ UT WOS:000167117500032 PM 11222387 ER PT J AU Tomasson, MH Williams, IR Li, SG Kutok, J Cain, D Gillessen, S Dranoff, G Van Etten, RA Gilliland, DG AF Tomasson, MH Williams, IR Li, SG Kutok, J Cain, D Gillessen, S Dranoff, G Van Etten, RA Gilliland, DG TI Induction of myeloproliferative disease in mice by tyrosine kinase fusion oncogenes does not require granulocyte-macrophage colony-stimulating factor or interleukin-3 SO BLOOD LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; BCR-ABL ONCOGENE; GROWTH-FACTORS; CELL-LINES; GM-CSF; LYMPHOPROLIFERATIVE DISEASE; PHILADELPHIA-CHROMOSOME; AUTOCRINE PRODUCTION; SIGNAL-TRANSDUCTION AB Tyrosine kinase fusion oncogenes that occur as a result of chromosomal translocations have been shown to activate proliferative and antiapoptotic pathways in leukemic cells, but the importance of autocrine and paracrine expression of hematopoietic cytokines in leukemia pathogenesis is not understood. Evidence that leukemic transformation may be, at least in part, cytokine dependent includes data from primary human leukemia cells, cell culture experiments, and murine models of leukemia. This report demonstrates that interleukin (IL)-3 plasma levels are elevated in myeloproliferative disease (MPD) caused by the TEL/ tyrosine kinase fusions TEL/platelet-derived growth factor beta receptor (PDGF betaR), TEL/Janus kinase 2 (JAK2), and TEL/neurotrophin-3 receptor (TRKC). Plasma granulocyte-macrophage colony-stimulating factor (GM-CSF) levels were elevated by TEL/PDGF betaR and TEL/JAK2. However, all of the fusions tested efficiently induced MPD in mice genetically deficient for both GM-CSF and IL-3, demonstrating that these cytokines are not necessary for the development of disease in this model system. Furthermore, in experiments using normal marrow transduced with TEL/PDGF betaR retrovirus mixed with marrow transduced with an enhanced green fluorescent protein (EGFP) retrovirus, the MPD induced in these mice demonstrated minimal stimulation of normal myelopoiesis by the TEL/PDGF betaR-expressing cells. In contrast, recipients of mixed GM-CSF-transduced and EGFP-transduced marrow exhibited significant paracrine expansion of EGFP-expressing cells. Collectively, these data demonstrate that, although cytokine levels are elevated in murine bone marrow transplant models of leukemia using tyrosine kinase fusion oncogenes, GM-CSF and IL-3 are not required for myeloproliferation by any of the oncogenes tested. (Blood, 2001;97:1435-1441) (C) 2001 by The American Society of Hematology. C1 Harvard Univ, Brigham & Womens Hosp,Sch Med, Dana Farber Canc Inst,Harvard Inst Med,Dept Med, Ctr Blood Res,Dept Pathol,Div Hematol, Boston, MA 02115 USA. Div Oncol Serv, Bone Marrow Transplantat Sect, St Louis, MO 63110 USA. Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Tomasson, MH (reprint author), Div Oncol Serv, Bone Marrow Transplantat Sect, 660 S Euclid Ave,Campus Box 8007, St Louis, MO 63110 USA. RI Williams, Ifor/D-3648-2011 OI Williams, Ifor/0000-0002-8810-2911 FU NCI NIH HHS [CA39542, CA66996, CA57593, CA74886, CA81187-01]; NIAMS NIH HHS [AR44628]; NIDDK NIH HHS [DK50654] NR 55 TC 14 Z9 15 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 2001 VL 97 IS 5 BP 1435 EP 1441 DI 10.1182/blood.V97.5.1435 PG 7 WC Hematology SC Hematology GA 404TQ UT WOS:000167117500036 PM 11222391 ER PT J AU Li, SG Gillessen, S Tomasson, MH Dranoff, G Gilliland, DG Van Etten, RA AF Li, SG Gillessen, S Tomasson, MH Dranoff, G Gilliland, DG Van Etten, RA TI Interleukin 3 and granulocyte-macrophage colony-stimulating factor are not required for induction of chronic myeloid leukemia-like myeloproliferative disease in mice by BCR/ABL SO BLOOD LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; BCR-ABL; HEMATOPOIETIC-CELLS; TYROSINE KINASE; LYMPHOPROLIFERATIVE DISEASE; P210; TRANSFORMATION; GENE; TRANSDUCTION; INVOLVEMENT AB Primitive hematopoietic progenitors from some patients with Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML) express aberrant transcripts for interleukin 3 (IL-3) and granulocyte colony-stimulating factor(G-CSF), and exhibit autonomous proliferation in serum-free cultures that is inhibited by anti-IL-3 and anti-IL-3 receptor antibodies. Expression of the product of the Ph chromosome, the BCR/ABL oncogene, in mice by retroviral bone marrow transduction and transplantation induces CML-like leukemia, and some leukemic mice have increased circulating IL-3, and perhaps granulocyte-macrophage colony-stimulating factor (GM-CSF), These observations raise the possibility of autocrine or paracrine cytokine production in the pathogenesis of human CML. Mice with homozygous inactivation of the II-3 gene, the Gm-csf gene, or both, were used to test the requirement for these cytokines for induction of CML-like disease by BCR/ ABL. Neither IL-3 nor GM-CSF was required in donor, recipient, or both for induction of CML-like leukemia by p210 BCR/ABL. Use of novel mice deficient in both IL-3 and GM-CSF demonstrated that the lack of effect on leukemogenesis was not due to redundancy between these hematopoietic growth factors. Analysis of cytokine levels in leukemic mice where either donor or recipient was II-3(-/-) indicated that the increased IL-3 originated from the recipient, suggestive of a host reaction to the disease. These results demonstrate that IL-3 and GM-CSF are not required for BCR/ABL-induced CML-like leukemia in mice and suggest that autocrine production of IL-3 does not play a role in established chronic phase CML in humans. (Blood, 2001;97:1442-1450) (C) 2001 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Inst Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Van Etten, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA81197, CA66996, CA39542, CA57593, CA74886]; NIDDK NIH HHS [DK50654] NR 36 TC 57 Z9 58 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 2001 VL 97 IS 5 BP 1442 EP 1450 DI 10.1182/blood.V97.5.1442 PG 9 WC Hematology SC Hematology GA 404TQ UT WOS:000167117500037 PM 11222392 ER PT J AU Huang, CA Fuchimoto, Y Gleit, ZL Ericsson, T Griesemer, A Scheier-Dolberg, R Melendy, E Kitamura, H Fishman, JA Ferry, JA Harris, NL Patience, C Sachs, DH AF Huang, CA Fuchimoto, Y Gleit, ZL Ericsson, T Griesemer, A Scheier-Dolberg, R Melendy, E Kitamura, H Fishman, JA Ferry, JA Harris, NL Patience, C Sachs, DH TI Posttransplantation lymphoproliferative disease in miniature swine after allogeneic hematopoietic cell transplantation: similarity to human PTLD and association with a porcine gammaherpesvirus SO BLOOD LA English DT Article ID EPSTEIN-BARR-VIRUS; LARGE-ANIMAL-MODEL; MIXED CHIMERISM; CLONAL ANALYSIS; DISORDERS; ANTIBODIES; TOLERANCE; LYMPHOMAS; PIGS AB Posttransplantation lymphoproliferative disease (PTLD) is a major complication of current clinical transplantation regimens. The lack of a reproducible large-animal model of PTLD has limited progress in understanding the pathogenesis of and in developing therapy for this clinically important disease. This study found a high incidence of PTLD in miniature swine undergoing allogeneic hematopoietic stem cell transplantation and characterized this disease in swine. Two days before allogeneic peripheral blood stem cell transplantation, miniature swine were conditioned with thymic irradiation and in vivo T-cell depletion. Animals received cyclosporine daily beginning 1 day before transplantation and continuing for 30 to 60 days. Flow cytometry and histologic examination were performed to determine the cell type involved in lymphoproliferation. Polymerase chain reaction was developed to detect and determine the level of porcine gammaherpesvirus in involved lymph node tissue. PTLD in swine is morphologically and histologically similar to that observed in human allograft recipients. Nine of 21 animals developed a B-cell lymphoproliferation involving peripheral blood (9 of 9), tonsils, and lymph nodes (7 of 9) from 21 to 48 days after transplantation. Six of 9 animals died of PTLD and 3 of 9 recovered after reduction of immunosuppression. A novel porcine gammaherpesvirus was identified in involved tissues. Miniature swine provide a genetically defined large-animal model of PTLD with many characteristics similar to human PTLD. The availability of this reproducible large-animal model of PTLD may facilitate the development and testing of diagnostic and therapeutic approaches for prevention or treatment of PTLD in the clinical setting. (Blood, 2001;97:1467-1473) (C) 2001 by The American Society of Hematology. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Biotransplant Inc, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Infect Dis, Boston, MA 02114 USA. RP Sachs, DH (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 NHLBI NIH HHS [1R01 HL63430-01] NR 29 TC 51 Z9 51 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 MAR 1 PY 2001 VL 97 IS 5 BP 1467 EP 1473 DI 10.1182/blood.V97.5.1467 PG 7 WC Hematology SC Hematology GA 404TQ UT WOS:000167117500040 PM 11222395 ER PT J AU Mitsikostas, DD del Rio, MS AF Mitsikostas, DD del Rio, MS TI Receptor systems mediating c-fos expression within trigeminal nucleus caudalis in animal models of migraine SO BRAIN RESEARCH REVIEWS LA English DT Review DE c-fos; migraine; animal model; pain; 5-HT; glutamate; GABA; neurokinin ID GENE-RELATED PEPTIDE; SUPERIOR SAGITTAL SINUS; METHYL-D-ASPARTATE; CORTICAL SPREADING DEPRESSION; NEUROGENIC DURAL INFLAMMATION; PLASMA-PROTEIN EXTRAVASATION; RAT SPINAL-CORD; HUMAN CEREBRAL-ARTERIES; EXCITATORY AMINO-ACIDS; DORSAL RAPHE NUCLEUS AB In intracranial structures unmyelinated C- and A delta -fibers of the trigeminal nerve transmit pain stimuli from meninges to the trigeminal nucleus caudalis (Sp5C). Peripheral nerve endings surround meningeal vessels (the so-called trigeminovascular system) and contain vasoactive neuropeptides (calcitonin gene-related peptide, substance P and neurokinin A). Activation of the trigeminovascular system promotes a meningeal sterile inflammatory response through the release of neuropeptides by peripheral endings. Orthodromic conduction along trigeminovascular fibers transmits information centrally with induction of immediate early c-fos gene within post-synaptic Sp5C neurons, as a marker of neuronal activity within central nociceptive pathways. In laboratory animals the system is activated by either electrical stimulation of the TG, chemical stimulation of the meninges, electrical or mechanical stimulation of the superior sagittal sinus or by induction of cortical spreading depression. All these techniques induce c-fos within SD5C and are used as a rodent/feline model of vascular headache in humans. Up-to-date there is evidence that at least ten receptors (5-HT1B, 5-HT1D, 5-HT1F, 5-HT2B, NK-1, GABA(A), NMDA, AMPA, class III metabotropic glutamate receptors, and opioids mu receptors) modulate c-fos expression within Sp5C. These receptors represent potential targets for anti-migraine drugs as shown by triptans (5-HT1B/1D/1F) and ergot alkaloids (5-PIT1A1B/1D/1F). This review discusses the importance of c-Sos expression within Sp5C as a marker of cephalic nociception, the different cephalic pain models that induce c-fos within Sp5C, the receptors involved and their potential role as targets for anti-migraine drugs. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Athens Naval Hosp, Dept Neurol, Headache Clin, Athens 11521, Greece. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA USA. RP Mitsikostas, DD (reprint author), Athens Naval Hosp, Dept Neurol, Headache Clin, 70 Dinokratous St, Athens 11521, Greece. NR 189 TC 65 Z9 72 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 J9 BRAIN RES REV JI Brain Res. Rev. PD MAR PY 2001 VL 35 IS 1 BP 20 EP 35 DI 10.1016/S0165-0173(00)00048-5 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 414BC UT WOS:000167645200002 PM 11245884 ER PT J AU Bjerke, RJ Mangione, MP AF Bjerke, RJ Mangione, MP TI Asystole after intravenous neostigmine in a heart transplant recipient SO CANADIAN JOURNAL OF ANAESTHESIA-JOURNAL CANADIEN D ANESTHESIE LA English DT Article ID REINNERVATION AB Purpose: To describe a heart transplant recipient who developed asystole after administration of neostigmine which suggests that surgical dennervation of the heart may not permanently prevent significant responses to anticholinesterases. Clinical features: A 67-yr-old man, I I yr post heart transplant underwent left upper lung lobectomy. He developed asystole after intravenous administration of 4 mg neostigmine with 0.8 mg glycopyrrolate for reversal of the muscle relaxant. He had no history of rate or rhythm abnormalities either prior to or subsequent to the event. Conclusion: When administering anticholinesterase medications to heart transplant patients, despite surgical dennervation, one must be prepared for a possible profound cardiac response. C1 Univ Pittsburgh, Sch Med, Dept Anesthesiol & Crit Care Med, Pittsburgh, PA 15261 USA. RP Bjerke, RJ (reprint author), VA Pittsburgh Hlth care Syst, Anesthesia Serv, Univ Dr C, Pittsburgh, PA 15240 USA. NR 8 TC 16 Z9 17 U1 0 U2 0 PU CANADIAN ANESTHESIOLOGISTS SOC PI TORONTO PA 1 EGLINTON AVE EAST, SUITE 208, TORONTO, ONTARIO M4P 3A1, CANADA SN 0832-610X J9 CAN J ANAESTH JI Can. J. Anaesth.-J. Can. Anesth. PD MAR PY 2001 VL 48 IS 3 BP 305 EP 307 PG 3 WC Anesthesiology SC Anesthesiology GA 411FP UT WOS:000167487700017 PM 11305835 ER PT J AU Chan, AW Loeffler, JS AF Chan, AW Loeffler, JS TI Controversies in the management of patients with brain metastases SO CANCER JOURNAL LA English DT Editorial Material ID RANDOMIZED TRIAL; SINGLE METASTASES; RADIOTHERAPY; RADIOSURGERY; SURGERY C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Loeffler, JS (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St,Cox 302, Boston, MA 02114 USA. NR 9 TC 2 Z9 2 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PONE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. Sci. Am. PD MAR-APR PY 2001 VL 7 IS 2 BP 105 EP 107 PG 3 WC Oncology SC Oncology GA 419TX UT WOS:000167965700005 PM 11324762 ER PT J AU Metz, JM Jones, H Devine, P Hahn, S Glatstein, E AF Metz, JM Jones, H Devine, P Hahn, S Glatstein, E TI Cancer patients use unconventional medical therapies far more frequently than standard history and physical examination suggest SO CANCER JOURNAL LA English DT Article DE alternative medicine; complementary medicine; cancer; neoplasm ID ALTERNATIVE MEDICINE; PROSTATE-CANCER; UNITED-STATES; ACUPUNCTURE; HEPATITIS; CHEMOTHERAPY; COMBINATION; RELAXATION; DISEASE AB BACKGROUND Studies with questionnaires have suggested that many cancer patients utilize unconventional medical therapies (UMT). There are few data evaluating directed questions about the use of UMT. This study was performed to determine if careful directed questioning about UMT reveals a higher rate of utilization compared to standard history and physical examination. MATERIALS AND METHODS A prospective evaluation of 196 consecutive patients presenting for initial consultation at the University of Pennsylvania was performed. Each patient underwent standard history and physical examination, including questions regarding prescription and over-the-counter medications, At the completion of standard questioning, patients were asked an explicit set of directed questions regarding the utilization of UMT. The median age of the patient population was 61 years (range = 28-80 years), Cancer diagnoses included breast (19%), lung (28%), prostate (26%), and other (27%). Females constituted 32% of the patient population. RESULTS Initially, only 13 patients (7%) revealed they were using UMT during a standard history and physical. Evaluation of the remaining 183 patients with directed questioning revealed an additional 66 patients (36%) were utilizing these therapies. Of the 79 patients taking UMT, 84% were identified by directed questioning and 16% by standard history and physical examination (P less than or equal to 0.0005). Forty-one patients (52%) were using greater than or equal to 2 of these therapies (mean = 2.5; range 1-17 therapies). A total of 48 different UMT were used by this patient population. Patients utilizing multivitamin supplementation were significantly more likely to be using an UMT than those who were not (68% vs. 31%; P less than or equal to 0.0001). Females were more likely to use UMT than males (49% vs. 35%; P = 0.08). CONCLUSIONS The addition of explicitly directed questioning to the standard history and physical examination significantly increases the oncologist's ability to identify cancer patients who utilize UMT, Some of these therapies may interact with conventional cancer treatments and/or cause significant side effects; consequently. it is important for oncologists to detect those patients utilizing these therapies. C1 Vet Affairs Med Ctr, Dept Radiat Oncol, Philadelphia, PA USA. Univ Penn, Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA. RP Metz, JM (reprint author), Hosp Univ Penn, Dept Radiat Oncol, 3400 Spruce St,2 Donner, Philadelphia, PA 19104 USA. NR 40 TC 18 Z9 19 U1 4 U2 5 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PONE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. Sci. Am. PD MAR-APR PY 2001 VL 7 IS 2 BP 149 EP 154 PG 6 WC Oncology SC Oncology GA 419TX UT WOS:000167965700011 PM 11324768 ER PT J AU Schink, JC Weller, E Harris, LS Cella, D Gerstner, J Falkson, C Wadler, S AF Schink, JC Weller, E Harris, LS Cella, D Gerstner, J Falkson, C Wadler, S TI Outpatient taxol and carboplatin chemotherapy for suboptimally debulked epithelial carcinoma of the ovary results in improved quality of life: An Eastern Cooperative Oncology Group phase II study (E2E93) SO CANCER JOURNAL LA English DT Article ID OF-LIFE; CANCER; PACLITAXEL AB PURPOSE The combination of a platinum compound and paclitaxel is a standard treatment for ovarian cancer. In this cooperative group trial, paclitaxel and carboplatin were combined in an outpatient schedule to determine the clinical benefit, toxicities, and effect on quality of rife. PATIENTS AND METHODS Women with International Federation of Gynecology and Obstetrics stage ii to IV epithelial ovarian cancer with suboptimal residual disease (> 1 cm) were eligible. Paclitaxel, 150 mg/m(2), was given over 3 hours, followed by carboplatin (area under the curve, 5). This was repeated every 4 weeks for six cycles. Quality of life was assessed using the Functional Assessment of Cancer Therapy-Ovarian Cancer scale. Fifty-nine patients were enrolled, 38 with measurable disease and 21 with evaluable disease. RESULTS The response rate (complete response + partial response) was 72%. The progression-free interval for patients with measurable disease was 17.5 months and for patients with evaluable disease was 11.1 months. Median survivals were 30.1 months (measurable) and 25.7 months (evaluable). Toxicities were modest. Quality-of-life scores improved significantly during therapy, DISCUSSION This regimen is ideal for most women with advanced ovarian cancer because it is convenient and well tolerated, with response and survival comparable to those of more aggressive regimens. Overall quality-of-life scores and physical well-being scores improved throughout this outpatient treatment regimen for most patients. C1 Univ Wisconsin, Ctr Comprehens Canc, Madison, WI 53706 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Evanston NW Hlth Care, Evanston, IL USA. Evanston NW Hlth Care, Chicago, IL USA. Mayo Clin, Rochester, MN USA. Univ Pretoria, ZA-0002 Pretoria, South Africa. Albert Einstein Canc Ctr, Bronx, NY USA. RP Schink, JC (reprint author), Univ Wisconsin, Hosp & Clin, Div Gynecol Oncol, H4-636 CSC,600 Highland Ave, Madison, WI 53792 USA. FU NCI NIH HHS [CA13650, CA23318, CA21076] NR 18 TC 13 Z9 15 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PONE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. Sci. Am. PD MAR-APR PY 2001 VL 7 IS 2 BP 155 EP 164 PG 10 WC Oncology SC Oncology GA 419TX UT WOS:000167965700012 PM 11324769 ER PT J AU Tseng, YH Vicent, D Zhu, JH Niu, YL Adeyinka, A Moyers, JS Watson, PH Kahn, CR AF Tseng, YH Vicent, D Zhu, JH Niu, YL Adeyinka, A Moyers, JS Watson, PH Kahn, CR TI Regulation of growth and tumorigenicity of breast cancer cells by the low molecular weight GTPase Rad and Nm23 SO CANCER RESEARCH LA English DT Article ID NUCLEOSIDE DIPHOSPHATE KINASE; TUMOR-METASTASIS; PROGNOSTIC FACTORS; SKELETAL-MUSCLE; GENE-EXPRESSION; DOWN-REGULATION; PC12 CELLS; RNA LEVELS; FOLLOW-UP; PROTEIN AB Rad is the prototypic member of a family of novel Ras-related GTPases that is normally expressed in heart, skeletal muscle, and lung and that has been shown to exhibit a novel form of hi-directional interaction with the nm23 metastasis suppressor. In the present study, we hale investigated the expression of Rad in normal and neoplastic breast tissues by Western blot and immunohistochemistry and the functional effect of altered Rad expression in breast cancer cell lines. We found that, although Rad is frequently expressed in normal breast tissue (23/30 Rad+ve), expression is usually lost in adjacent invasive carcinoma (8/30 Rad+ve: P < 0.0001). However, where Rad expression persists in a small proportion of tumors, it is associated with higher grade, larger size, and extensive axillar?; nodal involvement (n = 48; P = 0.035, P = 0.016, P = 0.022, respectively). Furthermore, Rad is also highly expressed in a breast cancer cell line with high tumorigenic and metastatic potential (MDA-MB231). To further examine the role of Rad in breast cancer, we stably transfected a Rad-ve breast cancer cell line (MDA-MB435). We observed an increase in growth and marked increased colony formation in soft agar in vitro (P < 0.05) and an increase in tumor growth rate in nude mice (P < 0.05). Moreover. coexpression of nm23 with wild-type Rad inhibited the effect of Rad on growth of these cells in culture and markedly inhibited tumor growth in vivo. Additional transfection studies with mutated Rad cDNAs revealed that the growth-promoting effects of Rad appeared to be mediated through its NH2- and COOH-terminal regions, rather than its GTPase domain, and might involve acceleration of cell cycle transition. These findings suggest that Rad may act as an oncogenic protein in breast tissues and demonstrate a potential mechanism by which interaction between Rad and nm23 may regulate growth and tumorigenicity of breast cancer. C1 Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Res Div, Boston, MA 02215 USA. Univ Manitoba, Dept Pathol, Winnipeg, MB R3E 0W3, Canada. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Res Div, 1 Joslin Pl, Boston, MA 02215 USA. RI Vicent, David/O-2255-2014 OI Vicent, David/0000-0002-6663-0350 FU NIDDK NIH HHS [DK-45935] NR 62 TC 76 Z9 81 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2001 VL 61 IS 5 BP 2071 EP 2079 PG 9 WC Oncology SC Oncology GA 412RL UT WOS:000167568100050 PM 11280768 ER PT J AU Nabors, LB Gillespie, GY Harkins, L King, PH AF Nabors, LB Gillespie, GY Harkins, L King, PH TI HuR, a RNA stability factor, is expressed in malignant brain tumors and binds to adenine- and uridine-rich elements within the 3 ' untranslated regions of cytokine and angiogenic factor mRNAs SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR EXPRESSION; FACTOR MESSENGER-RNA; POSTTRANSCRIPTIONAL REGULATION; DIFFERENTIAL EXPRESSION; DROSOPHILA-MELANOGASTER; SENSORY NEURONOPATHY; DOWN-REGULATION; NERVOUS-SYSTEM; UP-REGULATION; IN-VIVO AB Tumors of the central nervous system (CNS) often have sustained expression of labile genes, including angiogenic growth factors and immunosuppressive cytokines, which promote tumor progression. Stabilization of the RNA transcripts for these genes, such as vascular endothelial growth factor (VEGF), is an important molecular pathway for this upregulation, HuR, a member of the Elav family of RNA-binding proteins, has been implicated in this pathway through its binding to adenine and uridine (AU)-rich stability elements (ARE) located in the 3' untranslated regions (3'-UTRs) of the mRNA, Whereas three of the Elav family members (Hel-N1, HuC, and HuD) are restricted to young and mature neurons, HuR is more broadly expressed, including proliferating cells of the developing CNS, Because RNA stabilization of labile genes may promote tumor growth, we analyzed and compared the expression pattern of HuR in 35 freshly resected and cultured CNS tumors to determine whether there was any correlation with tumor grade or histological type, We found that HuR mRNA was consistently expressed in all of the tumors, regardless of cell origin or degree of malignancy. Using a novel HuR-specific polyclonal antibody, we found that strong HuR protein expression was limited to high-grade malignancies (glioblastoma multiforme and medulloblastoma), Within the glioblastoma multiforme, prominent HuR expression was also detected in perinecrotic areas in which angiogenic growth factors are up-regulated. To further define its role as a potential RNA stabilizer, we analyzed whether HuR could bind to the stability motifs within the 3'-UTRs of cytokines and growth factors linked to brain tumor progression. We used a novel ELISA-based RNA binding assay and focused on the 3'-UTRs of angiogenic factors VEGF, COX-2, and (interleukin) IL-8 as well as the immunomodulating factors IL-6, transforming growth factor (TGF)-beta and tumor necrosis factor (TNF)-alpha as potential RNA ligands, Our results indicated overall a very high binding affinity to these RNA targets. A comparison of these ligands revealed a hierarchy of binding affinities with the angiogenic factors, and TGF-P showing the highest (K-d of 1.8-3.4 nM), and TNF-alpha the lowest (K-d of 18.3 nM). The expression pattern of HuR, coupled with the RNA binding data, strongly suggests a role for this protein in the posttranscriptional regulation of these genes in CNS tumors. C1 Univ Alabama, Dept Neurol, Birmingham, AL 35233 USA. Univ Alabama, Dept Neurosurg, Birmingham, AL 35233 USA. Univ Alabama, Dept Physiol & Biophys, Birmingham, AL 35233 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP King, PH (reprint author), Univ Alabama, Dept Neurol, 1235 Jefferson Tower, Birmingham, AL 35233 USA. FU NCI NIH HHS [CA71933] NR 48 TC 188 Z9 196 U1 3 U2 8 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2001 VL 61 IS 5 BP 2154 EP 2161 PG 8 WC Oncology SC Oncology GA 412RL UT WOS:000167568100062 PM 11280780 ER PT J AU Sun, JX Hemler, ME AF Sun, JX Hemler, ME TI Regulation of MMP-1 and MMP-2 production through CD147/extracellular matrix metalloproteinase inducer interactions SO CANCER RESEARCH LA English DT Article ID COLLAGENASE-STIMULATORY FACTOR; SQUAMOUS-CELL CARCINOMA; BLOOD-BRAIN-BARRIER; IMMUNOGLOBULIN SUPERFAMILY; EXTRACELLULAR-MATRIX; INTERSTITIAL COLLAGENASE; STROMAL EXPRESSION; TUMOR PROGRESSION; IG SUPERFAMILY; MEMBER AB Extracellular matrix metalloproteinase inducer (EMMPRIN: CD147) is a heavily glycosylated protein containing two immunoglobulin superfamily domains. It is enriched on the surface of tumor cells and stimulates the production of matrix metalloproteinases (MMPs) by adjacent stromal cells. Here we use CD147 transfectants and immobilized recombinant CD147-Fc fusion protein to show that CD147/EMMPRIN engages in a homophilic interaction, predominantly through the first immunoglobulin domain. Anti-CD147 antibody 8G6 and recombinant CD147-Fc fusion protein markedly inhibited not only homophilic interaction, but also the production of secreted MMP-2 by breast cancer cell line MDA-435 and the MMP-2-dependent invasion of MDA-435 cells through reconstituted basement-membrane Matrigel. Purified native CD147 induced the production of secreted MMP not only by dermal fibroblasts (MMP-1) but also by MDA-435 cells themselves (MMP-2), suggesting homophilic CD147-binding may occur in the context of both heterotypic and homotypic cell-cell interactions. Purified deglycosylated CD147 failed to induce MMP-1 or MMP-2, but instead antagonized the MMP-1-inducing activity of purified native CD147, Our results suggest that homophilic CD147 interactions may play a key role in MMP-2 production and tumor cell invasion, and that perturbation of this molecule may have potential therapeutic uses in the prevention of MMP-2 and MMP-1-dependent cancer metastasis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA42368] NR 36 TC 280 Z9 340 U1 4 U2 23 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2001 VL 61 IS 5 BP 2276 EP 2281 PG 6 WC Oncology SC Oncology GA 412RL UT WOS:000167568100080 PM 11280798 ER PT J AU Hartsough, MT Clare, SE Mair, M Elkahloun, AG Sgroi, D Osborne, CK Clark, G Steeg, PS AF Hartsough, MT Clare, SE Mair, M Elkahloun, AG Sgroi, D Osborne, CK Clark, G Steeg, PS TI Elevation of breast carcinoma Nm23-H1 metastasis suppressor gene expression and reduced motility by DNA methylation inhibition SO CANCER RESEARCH LA English DT Article ID NM23/NUCLEOSIDE DIPHOSPHATE KINASE; TISSUE GROWTH-FACTOR; CANCER CELL-LINE; MELANOMA-CELLS; RETINOIC ACID; ESTROGEN-RECEPTOR; BASEMENT-MEMBRANE; PROSTATE-CANCER; CPG ISLANDS; IN-VIVO AB We hypothesize that elevation of Nm23-H1 expression in micrometastatic breast cancer cells may inhibit their metastatic colonization and further invasion, and induce differentiation, thus resulting in a clinical benefit. The current study investigated the possible contribution of DNA methylation to the regulation of Nm23-H1 expression, based on the observation that two CpG. islands are present in its promoter. 5-Aza-2'-deoxycytidine (5-Aza-CdR), a DNA methylation inhibitor, increased the Nm23-H1 expression of 5 of 11 human breast carcinoma cell lines in vitro, including 3 of 3 metastatically competent lines. Increased Nm23-H1 expression was accompanied by a reduction in motility in vitro, with minimal effect on proliferation. Both increased Nm23-H1 expression and decreased motility were observed using low (75 nM) concentrations of 5-Aza-CdR, Array analysis of MDA-MB-231 breast carcinoma cells treated with 5-Aza-CdR confirmed the elevation of nm23-H1 mRNA, whereas relatively few other genes exhibited altered expression, Bisulfite sequencing of the two CpG islands in a panel of cell lines and in 20 infiltrating ductal carcinomas revealed that one island (-3090 bp to -3922 bp) exhibited infrequent differential methylation. The data indicate that DNA methylation inhibitors ran directly or indirectly cause both elevation of Nm23-H1 expression and decreased function in one aspect of metastasis, motility. C1 NCI, NIH, Womens Canc Sect, Pathol Lab,Div Clin Sci, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Mol Pathol, Charlestown, MA 02129 USA. Baylor Coll Med, Breast Ctr, Houston, TX 77030 USA. NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA. RP Hartsough, MT (reprint author), NCI, NIH, Womens Canc Sect, Pathol Lab,Div Clin Sci, Bldg 10,Room 2A33, Bethesda, MD 20892 USA. NR 70 TC 67 Z9 77 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2001 VL 61 IS 5 BP 2320 EP 2327 PG 8 WC Oncology SC Oncology GA 412RL UT WOS:000167568100087 PM 11280805 ER PT J AU Berenson, JR Vescio, RA Rosen, LS VonTeichert, JM Woo, M Swift, R Savage, A Givant, E Hupkes, M Harvey, H Lipton, A AF Berenson, JR Vescio, RA Rosen, LS VonTeichert, JM Woo, M Swift, R Savage, A Givant, E Hupkes, M Harvey, H Lipton, A TI A phase I dose-ranging trial of monthly infusions of zoledronic acid for the treatment of osteolytic bone metastases SO CLINICAL CANCER RESEARCH LA English DT Article ID AMINOHYDROXYPROPYLIDENE BISPHOSPHONATE APD; ADVANCED MULTIPLE-MYELOMA; BREAST-CANCER; DOUBLE-BLIND; SKELETAL COMPLICATIONS; PAMIDRONATE TREATMENT; BIOCHEMICAL MARKERS; HYPERCALCEMIA; RESORPTION; MALIGNANCY AB Bisphosphonates are potent inhibitors of bone resorption and provide a therapeutic benefit for patients with bone metastases, Zoledronic acid is a highly potent, nitrogen-containing bisphosphonate, In the present trial, we assessed the safety and tolerability of increasing doses of zoledronic acid and its effects on urinary markers of bone resorption in cancer patients with bane metastases. Fifty-nine cancer patients with bone metastases were enrolled sequentially into one of 8 treatment groups in the core protocol. Each patient received a 5-min i,v, infusion of 0.1, 0.2, 0.4, 0.8, 1.5, 2, 4, or 8 mg zoledronic acid monthly for 3 months. Patients were monitored for clinical findings, adverse events, electrocardiograms, markers of bone resorption, as well as routine hematology, blood chemistries, and urinalysis. Thirty patients who demonstrated a radiographic response to treatment or stable disease in the core protocol were enrolled in a humanitarian extension protocol and continued to receive monthly infusions, Zoledronic acid was well tolerated at all dose levels. Adverse events reported by >10% of patients included skeletal pain, nausea, fatigue, upper respiratory tract infection, constipation, headache, diarrhea, and fever. Three patients in the core protocol and one patient in the extension protocol experienced grade 3 skeletal pain,'flu-like" symptoms, or hypophosphatemia, which were possibly related to treatment; all recovered completely. Adverse events were reported with similar frequency across all of the dosage groups. Zoledronic acid resulted in sustained, dose-dependent decreases in urinary markers of bone resorption, Zoledronic acid was safe and well tolerated and demonstrated potent inhibition of bone resorption. C1 Cedars Sinai Med Ctr, Div Hematol & Oncol, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90073 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. Milton S Hershey Med Ctr, Dept Med, Hershey, PA 17033 USA. RP Berenson, JR (reprint author), Cedars Sinai Med Ctr, Div Hematol & Oncol, Beverly Modular 1,Room 100,8700 Beverly Blvd, Los Angeles, CA 90048 USA. NR 64 TC 64 Z9 64 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 2001 VL 7 IS 3 BP 478 EP 485 PG 8 WC Oncology SC Oncology GA 418GT UT WOS:000167883100006 PM 11297237 ER PT J AU Reilly, CM Oates, JC Sudian, J Crosby, MB Halushka, PV Gilkeson, GS AF Reilly, CM Oates, JC Sudian, J Crosby, MB Halushka, PV Gilkeson, GS TI Prostaglandin J(2) inhibition of mesangial cell iNOS expression SO CLINICAL IMMUNOLOGY LA English DT Article DE lupus; mesangial cell; nitric oxide; PPAR-gamma; prostaglandin J(2) ID NITRIC-OXIDE SYNTHASE; ACTIVATED PROTEIN-KINASE; NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; RECEPTOR-GAMMA; GENE-EXPRESSION; CYCLOPENTENONE PROSTAGLANDINS; TRANSCRIPTIONAL CONTROL; MECHANISMS; P38 AB Mesangial cells from MRL/lpr mice, a model of lupus, overproduce nitric oxide (NO) compared to controls. J series prostaglandins (PG) and thiazolidinediones block LPS stimulation of NO production via the activation of peroxisome proliferator-activator receptor-gamma (PPAR-gamma) in macrophages but utilize an alternative mechanism in microglial cells. We investigated the mechanism by which PGJ(2) inhibits NO production in LPS/IFN-gamma -stimulated MRL/lpr mesangial cells. Our results demonstrated that LPS/IFN-gamma addition to MRL/lpr mesangial cells stimulated MOS activation, expression of p-38 kinase and p44/42 MAPK, and NF-kappaB translocation to the nucleus. Both pioglitazone, a specific PPAR-gamma agonist, and PGJ(2) blocked NO production, iNOS protein expression, and iNOS mRNA transcription. PGJ(2) failed to inhibit nuclear NF-kappaB translocation or p44/42 MAPK or p-38 kinase induction in stimulated mesangial cells. These data suggest that PGJ(2) blocks iNOS expression and subsequent NO production in mesangial cells via a PPAR-gamma -mediated mechanism either by interfering with NF-kappaB transcriptional activity or by an NF-kappaB-independent mechanism. (C) 2001 Academic Press. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29403 USA. Med Univ S Carolina, Dept Pharmacol, Charleston, SC 29403 USA. Ralph H Johnson VAMC, Med Res Serv, Charleston, SC 29403 USA. RP Reilly, CM (reprint author), Med Univ S Carolina, Dept Med, Charleston, SC 29403 USA. FU NIAMS NIH HHS [R01AR45499] NR 34 TC 50 Z9 51 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD MAR PY 2001 VL 98 IS 3 BP 337 EP 345 DI 10.1006/clim.2000.4985 PG 9 WC Immunology SC Immunology GA 410BD UT WOS:000167419400006 PM 11237557 ER PT J AU Hanna, GJ D'Aquila, RT AF Hanna, GJ D'Aquila, RT TI Clinical use of genotypic and phenotypic drug resistance testing to monitor antiretroviral chemotherapy SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROTEASE INHIBITOR THERAPY; LINE PROBE ASSAY; REVERSE-TRANSCRIPTASE; ZIDOVUDINE RESISTANCE; VIROLOGICAL RESPONSE; CONTAINING REGIMEN; SALVAGE THERAPY; HIV-INFECTION; MUTATIONS AB Assays that detect antiretroviral drug resistance in human immunodeficiency virus have recently become available to clinicians. Phenotypic assays measure the drug susceptibility of the virus by determining the concentration of drug that inhibits viral replication in tissue culture. Genotypic assays determine the presence of mutations that are known to confer decreased drug susceptibility. Although each type of assay has specific advantages, limitations associated with these tests often complicate the interpretation of results. Several retrospective clinical trials have suggested that resistance testing may be useful in the assessment of the success of salvage antiretroviral therapy. Prospective, controlled trials have demonstrated that resistance testing improves short-term virological response. Resistance testing is currently recommended to help guide the choice of new drugs for patients after treatment has failed and for pregnant women. Resistance testing should also be considered for treatment-naive patients, to detect transmission of resistant virus. C1 Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. RP D'Aquila, RT (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, 149 13th St, Charlestown, MA 02129 USA. NR 65 TC 68 Z9 73 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 1 PY 2001 VL 32 IS 5 BP 774 EP 782 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 406ED UT WOS:000167201200014 PM 11229846 ER PT J AU Paltiel, AD Goldie, SJ Losina, E Weinstein, MC Seage, GR Kimmel, AD Zhang, H Freedberg, KA AF Paltiel, AD Goldie, SJ Losina, E Weinstein, MC Seage, GR Kimmel, AD Zhang, H Freedberg, KA TI Preevaluation of clinical trial data: The case of preemptive cytomegalovirus therapy in patients with human immunodeficiency virus SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID POLYMERASE-CHAIN-REACTION; PNEUMOCYSTIS-CARINII PNEUMONIA; COST-EFFECTIVENESS; ORAL GANCICLOVIR; CMV DISEASE; HIV-INFECTION; AIDS PATIENTS; PROPHYLAXIS; PREVENTION; RISK AB We developed a mathematical simulation model to anticipate outcomes from an upcoming trial of targeted, preemptive cytomegalovirus (CMV) therapy in high-risk, human immunodeficiency virus (HIV)-infected patients identified by means of CMV polymerase chain reaction screening. We estimated the costs and consequences of CMV prophylaxis in patients with CD4(+) counts less than or equal to 100 cells/muL under various assumptions regarding disease progression, complication rates, drug effects, and costs. Without CMV preemptive therapy, lifetime costs average $44,600 with expected duration of survival of 19.16 quality-adjusted life-months and 213 CMV cases per 1000 patients. Targeted preemptive therapy with orally administered valganciclovir increases costs and duration of survival to $46,900 and 19.63 quality-adjusted life-months, respectively. CMV cases decrease to 174 per 1000 patients. The cost per quality-adjusted life-year gained is $59,000. This result compares favorably with other strategies in end-stage HIV disease but hinges on valganciclovir cost and efficacy assumptions and the absence of minimally effective salvage antiretroviral therapy for HIV. The upcoming trial should resolve the clinical uncertainty surrounding some of these assumptions. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Harvard Univ, Sch Publ Hlth, Ctr Risk Anal, Dept Hlth Policy & Management, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Internal Med, Boston, MA USA. RP Paltiel, AD (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, 60 Coll St, New Haven, CT 06520 USA. FU NIAID NIH HHS [R01 AI042006, U01 AI027659] NR 54 TC 22 Z9 22 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 1 PY 2001 VL 32 IS 5 BP 783 EP 793 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 406ED UT WOS:000167201200015 PM 11229847 ER PT J AU Heffner, JE Hess, D AF Heffner, JE Hess, D TI Tracheostomy management in the chronically ventilated patient SO CLINICS IN CHEST MEDICINE LA English DT Review ID PERCUTANEOUS DILATATIONAL TRACHEOSTOMY; INTENSIVE-CARE UNIT; HYGROSCOPIC CONDENSER HUMIDIFIER; PROLONGED MECHANICAL VENTILATION; SIGNIFICANT TRACHEAL OBSTRUCTION; CRITICALLY ILL PATIENTS; TUBE CUFF PRESSURE; EVERY 48 HOURS; MOISTURE EXCHANGERS; NOSOCOMIAL PNEUMONIA AB Successful management of patients who require long-term ventilatory support requires a skilled approach to airway care. Tracheostomy provides multiple benefits to patient care in addition to provision of airway access for mechanical ventilation. Realization of these benefits, however, depends on knowledge of approaches for promoting speech and nutrition in the intubated patient, providing expert respiratory care, and initiating effective weaning and airway decannulation efforts. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Heffner, JE (reprint author), Med Univ S Carolina, Dept Med, 96 Jonathan Lucas St,Suite 812CSB,POB 250623, Charleston, SC 29425 USA. NR 145 TC 32 Z9 36 U1 3 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-5231 J9 CLIN CHEST MED JI Clin. Chest Med. PD MAR PY 2001 VL 22 IS 1 BP 55 EP + DI 10.1016/S0272-5231(05)70025-3 PG 16 WC Respiratory System SC Respiratory System GA 423KV UT WOS:000168176200005 PM 11315459 ER PT J AU Sweeney, AT Brown, FM AF Sweeney, AT Brown, FM TI Gestational diabetes mellitus SO CLINICS IN LABORATORY MEDICINE LA English DT Review ID IMPAIRED GLUCOSE-TOLERANCE; BIRTH-WEIGHT; NORMAL-PREGNANCY; GLYCEMIC CONTROL; CARBOHYDRATE INTOLERANCE; PREPREGNANCY WEIGHT; PERINATAL MORBIDITY; INSULIN-SECRETION; CESAREAN DELIVERY; C-PEPTIDE AB The diagnostic thresholds for gestational diabetes mellitus were originally defined as two standard deviations above the mean on the 100g 3-hour oral glucose tolerance test. These criteria predicted the mother's future risk of diabetes rather than pregnancy outcomes. The precise threshold at which glucose intolerance adversely affects outcome is unknown and accounts for the controversy in the diagnosis of gestational diabetes mellitus. C1 Harvard Univ, Joslin Diabet Ctr, Sch Med, Dept Med,Sect Endocrinol & Diabet, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02215 USA. RP Brown, FM (reprint author), Harvard Univ, Joslin Diabet Ctr, Sch Med, Dept Med,Sect Endocrinol & Diabet, 1 Joslin Pl, Boston, MA 02115 USA. RI Sandall, Jane/D-4146-2009 OI Sandall, Jane/0000-0003-2000-743X NR 106 TC 4 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD MAR PY 2001 VL 21 IS 1 BP 173 EP + PG 21 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 420VD UT WOS:000168025200010 PM 11321934 ER PT J AU Verfaellie, M Giovanello, KS Keane, MM AF Verfaellie, Mieke Giovanello, Kelly Sullivan Keane, Margaret M. TI Recognition memory in amnesia: Effects of relaxing response criteria SO COGNITIVE AFFECTIVE & BEHAVIORAL NEUROSCIENCE LA English DT Article AB In two experiments, using the remember/know paradigm, we examined whether recognition memory in amnesic patients can be improved by instructing patients to relax their response criterion. Experiment 1 was modeled after a study by Dorfman, Kihlstrom, Cork, and Misiaszek (1995), in which direct instructions to respond more leniently led to an increase in recognition accuracy in patients with ECT-induced amnesia. We failed to extend this finding to patients with global amnesia, but the manipulation was unsuccessful in control subjects as well. In Experiment 2, response criterion was manipulated indirectly by providing information about the alleged base rate of study items on the recognition test. This manipulation led to a criterion shift in control subjects and enhanced discriminability in amnesic patients. Analysis of "remember" and "know" responses suggests that improved accuracy in amnesia was associated with enhanced familiarity-based recognition. C1 [Verfaellie, Mieke; Giovanello, Kelly Sullivan; Keane, Margaret M.] Boston VA Healthcare Syst, Boston, MA USA. [Verfaellie, Mieke; Giovanello, Kelly Sullivan; Keane, Margaret M.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Keane, Margaret M.] Wellesley Coll, Wellesley, MA 02181 USA. RP Verfaellie, M (reprint author), Boston VA Healthcare Syst 151A, Memory Disorders Res Ctr, 150 S Huntington Ave, Boston, MA 02130 USA. EM verf@bu.edu FU NINDS Program Project [NS 26985]; NIMH [57681]; Medical Research Service of the VA Healthcare System FX This research was supported by NINDS Program Project Grant NS 26985 and NIMH Grant 57681 to Boston University and by the Medical Research Service of the VA Healthcare System. Correspondence should be addressed to M. Verfaellie, Memory Disorders Research Center, Boston VA Healthcare System (151A), 150 S. Huntington Ave., Boston, MA 02130 (e-mail: verf@bu.edu). NR 25 TC 20 Z9 20 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-7026 EI 1531-135X J9 COGN AFFECT BEHAV NE JI Cogn. Affect. Behav. Neurosci. PD MAR PY 2001 VL 1 IS 1 BP 3 EP 9 DI 10.3758/CABN.1.1.3 PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA V32LU UT WOS:000208953500002 PM 12467099 ER PT J AU Merchant, A Zacks, CM Wilhelmus, K Durand, M Dohlman, CH AF Merchant, A Zacks, CM Wilhelmus, K Durand, M Dohlman, CH TI Candidal endophthalmitis after keratoplasty SO CORNEA LA English DT Article DE fungal endophthalmitis; Candida albicans; keratoplasty; storage medium; eye banking ID PENETRATING KERATOPLASTY; ALBICANS ENDOPHTHALMITIS; EYE BANKING; CORNEAS; CONTAMINATION; TRANSPLANTATION; BACTERIAL AB Purpose. To report a case of explosive fungal endophthalmitis after penetrating keratoplasty and to review additional published and unpublished cases to consider possible strategies for prevention. Methods. Records of this patient with postkeratoplasty candidal endophthalmitis and previously reported cases of postkeratoplasty candidal endophthalmitis were reviewed. Additional information of 26 unpublished cases was obtained from the Eye Bank Association of America. Results. After standard keratoplasty, the patient developed precipitous endophthalmitis on the second postoperative day. Abundant contamination with Candida was found in the residual donor corneoscleral rim. and Candida albicans was isolated from the aqueous humor of the recipient. Despite therapy with local antimicrobial agents, intraocular amphotericin B, and systemic fluconazole. the patient had a poor outcome with hand-motion visual acuity. Of the 44 collected cases of postkeratoplasty candidal endophthalmitis. 40 (91%) had the same organism cultured from the donor rim or medium. Forty-three donor corneas had been preserved in cold storage medium at 4 degreesC. Of 15 cases in which the outcome was available. 9 (60%) resulted in visual acuity of 20/200 or worse. Conclusion. Case reports confirm the occurrence of donor-to-host transmission of postkeratoplasty candidal endophthalmitis. Despite the low reported incidence, the poor prognosis of the affected eye in the majority of these cases suggests the need for antifungal supplementation of cold preservation media and other preventative strategies. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Cornea Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Baylor Coll Med, Cullen Eye Inst, Houston, TX 77030 USA. Maine Eye Ctr, Portland, ME USA. Aga Khan Univ Hosp, Karachi, Pakistan. RP Dohlman, CH (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Cornea Serv, 243 Charles St, Boston, MA 02114 USA. NR 26 TC 26 Z9 27 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD MAR PY 2001 VL 20 IS 2 BP 226 EP 229 DI 10.1097/00003226-200103000-00026 PG 4 WC Ophthalmology SC Ophthalmology GA 405UL UT WOS:000167178900026 PM 11248837 ER PT J AU Courand, JA Marshall, J Chang, YC King, ME AF Courand, JA Marshall, J Chang, YC King, ME TI Clinical applications of wall-stress analysis in the pediatric intensive care unit SO CRITICAL CARE MEDICINE LA English DT Article DE pediatric; echocardiographic; wall stress; velocity of circumferential shortening; Doppler-derived cardiac index; afterload; contractility; non-invasive; monitoring; pediatric intensive care unit ID STAGE RENAL-DISEASE; DOPPLER DETERMINATION; CARDIAC-OUTPUT; SEPTIC SHOCK; CHILDREN; CONTRACTILITY; MECHANICS; CATHETER; COARCTATION; HYPERTROPHY AB Objective: To determine whether serial, noninvasive assessment of afterload, contractility, and Doppler-derived cardiac output reliably detects variations in cardiac function in unstable pediatric patients. Design: Prospective, blinded clinical trial. Setting: The pediatric intensive care unit at Massachusetts General Hospital. Patients: Fourteen critically ill pediatric patients, Interventions: Pediatric patients meeting criteria for hemodynamic instability underwent serial echocardiograms every 6 hrs until they met exit criteria, generating 75 studies. Measurements and Main Results: Shortening fraction, cardiac index (CI), end-systolic wall stress (ESWS), and corrected Velocity of circumferential shortening (Vcfc) were measured in each patient. Data points were plotted as a stress-velocity relationship, compared with published normal values, then correlated with changes in vital signs and pharmacologic interventions. Fourteen of 16 patients who were enrolled completed the study. A strong negative correlation between ESWS end Vcfc was confirmed (p < .001). As an internal measure of validity, Vcfc had a strong positive correlation with CI measurements (p = .012). An increase in dopamine infusion was associated with a fall in ESWS (p = .02), an increase in Vcfc (p = .03), and an increase in the CI as measured by Doppler (p = .035). The infusion of dopamine above renal perfusion levels moved patients from zones of normal or compensated contractility for afterload on a modified stress-velocity relationship to a zone of high contractility for afterload. Urine output was the only clinical index of cardiac function that had a significant correlation with the echocardiographic indices. Hemodynamically unstable patients followed similar patterns of deterioration and recovery on the modified stress-velocity graph. All surviving patients returned to a normal or compensated zone. Conclusions: Wall-stress analysis of cardiac function is easily and safely performed on mechanically ventilated pediatric patients with the production of consistently high-quality data. For internal validity, Vcfc and CI measurements were correlated and were strongly positive. Wall-stress indices reliably detected patient deterioration, recovery, and response to changes in dopamine infusion. Patients who failed to return to areas of normal or compensated levels of contractility and afterload did poorly in this study. Noninvasive measures of afterload and contractility appear useful for monitoring cardiac function of critically ill children in an intensive care setting. C1 Massachusetts Gen Hosp, Dept Pediat Crit Care Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. RP Courand, JA (reprint author), Massachusetts Gen Hosp, Dept Pediat Crit Care Med, Boston, MA 02114 USA. NR 27 TC 8 Z9 8 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAR PY 2001 VL 29 IS 3 BP 526 EP 533 DI 10.1097/00003246-200103000-00010 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 411WM UT WOS:000167522400008 PM 11373415 ER PT J AU Stoddard, FJ Todres, ID AF Stoddard, FJ Todres, ID TI A new frontier: Posttraumatic stress and its prevention, diagnosis, and treatment SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE stress disorders; intensive care ID INTENSIVE-CARE; DISORDER; CHILDREN; ADOLESCENTS; MEMORY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Stoddard, FJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 20 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAR PY 2001 VL 29 IS 3 BP 687 EP 688 DI 10.1097/00003246-200103000-00050 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 411WM UT WOS:000167522400041 PM 11379543 ER PT J AU Cooper, DKC Keogh, AM AF Cooper, DKC Keogh, AM TI The potential role of xenotransplantation in treating endstage cardiac disease: a summary of the report of the Xenotransplantation Advisory Committee of the International Society for Heart and Lung Transplantation SO CURRENT OPINION IN CARDIOLOGY LA English DT Review ID ENDOGENOUS RETROVIRUS; SENSITIZED PATIENTS; ANTIBODIES; PRIMATES; TRANSMISSION; EXPERIENCE; SWINE AB There is an increasing shortage of human donor hearts for transplantation. One potential solution is using hearts from a suitable animal source, such as the pig. A committee of the International Society for Heart and Lung Transplantation has reviewed the current status of research into xenotransplantation, Furthermore, the committee considered what results in the pig-to-nonhuman primate experimental model would justify a clinical trial of xenotransplantation, and the criteria for selecting patients to be entered in the trial. This review emphasizes initial patient selection issues, although the committee's overall conclusions and recommendations are summarized. Although the current experimental results do not presently justify initiating a clinical trial, the committee concluded that xenotransplantation theoretically has immense potential, and that research in this field should be encouraged and supported. Human cadaveric organ donation will still be of the highest priority for the foreseeable future. Curr Opin Cardiol 2001, 16:105-109 (C) 2001 Lippincott Williams & Wilkins, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. St Vincents Hosp, Dept Cardiol, Sydney, NSW 2010, Australia. 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. NR 23 TC 10 Z9 10 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-4705 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD MAR PY 2001 VL 16 IS 2 BP 105 EP 109 DI 10.1097/00001573-200103000-00005 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 410BA UT WOS:000167419100005 PM 11224641 ER PT J AU Seliger, SL Davis, C Stehman-Breen, C AF Seliger, SL Davis, C Stehman-Breen, C TI Gender and the progression of renal disease SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review ID POLYCYSTIC KIDNEY-DISEASE; COLLAGEN-SYNTHESIS; MESANGIAL CELLS; SEX-HORMONES; DIABETIC NEPHROPATHY; HYPERTENSIVE RATS; BLOOD-PRESSURE; BETA-ESTRADIOL; MESSENGER-RNA; EXPRESSION AB Many studies of chronic renal disease have reported that men have a more rapid progression of renal insufficiency. However, other studies have found no differences between the sexes, and the true effect of sex on chronic renal disease remains a topic of controversy. There is evidence that women with non-diabetic renal diseases experience a slower progression, but in diabetic renal disease, the effect of gender is not yet established. Sex hormones may mediate the effects of gender on chronic renal disease, through alterations in the renin-angiotensin system, reduction in mesangial collagen synthesis, the modification of collagen degradation, and upregulation of nitric oxide synthesis. Curr Opin Nephrol Hypertens 10:219-225. (C) 2001 Lippincott Williams & Wilkins. C1 VA Puget Sound Hlth Care Syst, Renal Unit, Seattle, WA 98108 USA. Univ Washington, Med Ctr, Div Nephrol, Seattle, WA 98195 USA. Univ Washington, Med Ctr, Kidney Pancreas Transplant Program, Seattle, WA 98195 USA. RP Stehman-Breen, C (reprint author), VA Puget Sound Hlth Care Syst, Renal Unit, Mailstop 111A,1660 S Columbian Way, Seattle, WA 98108 USA. NR 42 TC 81 Z9 83 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD MAR PY 2001 VL 10 IS 2 BP 219 EP 225 DI 10.1097/00041552-200103000-00010 PG 7 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 406MF UT WOS:000167219200010 PM 11224697 ER PT J AU Lesser, G Kandiah, K Libow, LS Likourezos, A Breuer, B Marin, D Mohs, R Haroutunian, V Neufeld, R AF Lesser, G Kandiah, K Libow, LS Likourezos, A Breuer, B Marin, D Mohs, R Haroutunian, V Neufeld, R TI Elevated serum total and LDL cholesterol in very old patients with Alzheimer's disease SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Alzheimer's disease; dementia; ApoE; CERAD; neuropathology; serum lipids; LDL cholesterol; nursing home; genetics; cholesterol ID APOLIPOPROTEIN-E POLYMORPHISM; DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY-ARTERY DISEASE; DIFFERENT DIAGNOSTIC-CRITERIA; APOPROTEIN-E POLYMORPHISM; VASCULAR DEMENTIA; BLOOD-PRESSURE; NEUROFIBRILLARY TANGLES; MYOCARDIAL-INFARCTION; MULTIINFARCT DEMENTIA AB The relationships of serum lipids with Alzheimer's disease (AD) and other dementias in very old patients are not clear. All residents of an academic nursing home were studied clinically for dementia and for serum lipids. All those autopsied over a 7.7-year period had apolipoprotein E (apoE) genotyping and detailed neuropathological examination. Those with pathologically defined criteria for AD (n = 84) were compared to all others who also had clinical dementia but did not show AD changes (n = 22). In contrast to most other reports of serum lipids in very old patients with AD, total cholesterol (TC) and low density lipoprotein cholesterol levels were each significantly higher for those with AD. The lipid-AD associations were progressively stronger with increasing pathological certainty of AD diagnosis. These relationships remained significant after adjustment for apoE genotype and for other known risk factors. The lipid-AD associations in a very old cohort, and prior evidence that elevated TC in middle life is a risk factor for later dementia, prompt consideration of factors associated with lipid metabolism in the development of Alzheimer's dementia. Copyright (C) 2001 S. Karger AG, Basel. C1 Jewish Home & Hosp New York, New York, NY 10025 USA. CUNY Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, Bronx, NY USA. RP Lesser, G (reprint author), Jewish Home & Hosp New York, 120 W 106th St, New York, NY 10025 USA. FU NIA NIH HHS [AG-05138, AG-02219] NR 72 TC 51 Z9 58 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PD MAR-APR PY 2001 VL 12 IS 2 BP 138 EP 145 DI 10.1159/000051248 PG 8 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 402UN UT WOS:000167006700013 PM 11173887 ER PT J AU Burglin, TR Ruvkun, G AF Burglin, TR Ruvkun, G TI Regulation of ectodermal and excretory function by the C-elegans POU homeobox gene ceh-6 SO DEVELOPMENT LA English DT Article DE ceh-6; Caenorhabditis elegans; Caenorhabditis briggsae; homeobox gene; POU domain; POU-III family; osmoregulation ID DOMAIN TRANSCRIPTION FACTOR; CAENORHABDITIS-ELEGANS; CELL LINEAGE; EPIDERMAL DIFFERENTIATION; MOLECULAR-CLONING; FACTOR BRN-2; EXPRESSION; PROTEIN; DROSOPHILA; PITUITARY AB Caenorhabditis elegans has three POU homeobox genes, unc-86, ceh-6 and ceh-18.ceh-6 is the ortholog of vertebrate Brn1, Brn2, SCIP/Oct6 and Brn4 and by Cf1a/drifter/ventral veinless, Comparison of C. elegans and C, briggsae CEH-B shows that it is highly conserved. C, elegans has only three POU homeobox genes, while Drosophila has five that fall into four families. Immunofluorescent detection of the CEH-6 protein reveals that it is expressed in particular head and ventral cord neurons, as well as in rectal epithelial cells, and in the excretory cell, which is required for osmoregulation, A deletion of the ceh-6 locus causes 80% embryonic lethality. During morphogenesis, embryos extrude cells in the rectal region of the tail or rupture, indicative of a defect in the rectal epithelial cells that express ceh-6, Those embryos that hatch are sick and develop vacuoles, a phenotype similar to that caused by laser ablation of the excretory cell. A GFP reporter construct expressed in the excretory cell reveals inappropriate canal structures in the ceh-6 null mutant. Members of the POU-III family are expressed in tissues involved in osmoregulation and secretion in a number of species. We propose that one evolutionary conserved function of the POU-III transcription factor class could be the regulation of genes that mediate secretion/osmoregulation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Univ Basel, Biozentrum, Div Cell Biol, CH-4056 Basel, Switzerland. RP Karolinska Inst, Sodertorns Hogskola, Dept Biosci, Alfred Nobels Alle 10,Box 4101, SE-14104 Huddinge, Sweden. EM Thomas.Burglin@biosci.ki.se FU NCRR NIH HHS [5 RO1 RR10082-02] NR 73 TC 33 Z9 40 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 EI 1477-9129 J9 DEVELOPMENT JI Development PD MAR PY 2001 VL 128 IS 5 BP 779 EP 790 PG 12 WC Developmental Biology SC Developmental Biology GA 414JG UT WOS:000167662800015 PM 11171402 ER PT J AU Nielsen, C Murtaugh, LC Chyung, JC Lassar, A Roberts, DJ AF Nielsen, C Murtaugh, LC Chyung, JC Lassar, A Roberts, DJ TI Gizzard formation and the role of Bapx1 SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Bapx1; Nkx3.2; gut; pattern formation; gizzard; stomach; chick; development; Bmp4; Wnt5a ID LEFT-RIGHT ASYMMETRY; HOMEOBOX GENE; SONIC-HEDGEHOG; DROSOPHILA BAGPIPE; MOLECULAR-CLONING; CHICKEN-EMBRYO; AXIAL SKELETON; HOX GENES; EXPRESSION; PITX2 AB The anterior-posterior gut pattern is formed from three broad domains: fore-, mid-, and hindgut that have distinct functional, morphological, and molecular boundaries. The stomach demarcates the posterior boundary of the foregut. Avian stomachs are composed of two chambers: the anterior chamber (proventriculus) and the thick muscular posterior chamber (gizzard). Expression of candidate pattern formation control factors are restricted in the chick stomach regions such that Bmp4 and Wnt5a are not expressed in the gizzard. We previously implicated Bmp4 as controlling growth and differentiation of the gut musculature. Bmp4 is not expressed in the developing gizzard but is expressed in the rest of the gut including the adjacent proventriculus and midgut. Bapx1: (Nkx3.2) is expressed in the gizzard musculature but not in the proventriculus or midgut. We show ectopic expression of Bapx1 in the proventriculus results in a gizzard-like morphology and inhibits the normal proventricular expression of Bmp4 and Wnt5a. Overexpression of a reverse-function Bapx1 construct can result in a small stomach and ectopic extension of Bmp4 and Wnt5a expression into the gizzard. We suggest the role of Bapx1 is to regulate the expression of Bmp4 and Wnt5a to pattern the avian stomach. (C) 2001 Academic Press. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Roberts, DJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. FU NICHD NIH HHS [HD34448] NR 64 TC 26 Z9 26 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAR 1 PY 2001 VL 231 IS 1 BP 164 EP 174 DI 10.1006/dbio.2000.0151 PG 11 WC Developmental Biology SC Developmental Biology GA 407KP UT WOS:000167271000013 PM 11180960 ER PT J AU Zulewski, H Abraham, EJ Gerlach, MJ Daniel, PB Moritz, W Muller, B Vallejo, M Thomas, MK Habener, JF AF Zulewski, H Abraham, EJ Gerlach, MJ Daniel, PB Moritz, W Muller, B Vallejo, M Thomas, MK Habener, JF TI Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes SO DIABETES LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; HOMEODOMAIN PROTEIN IDX-1; INSULIN-PRODUCING CELLS; TRANSCRIPTION FACTORS; DIABETES-MELLITUS; AR42J CELLS; IN-VITRO; LIVER DEVELOPMENT; PROGENITOR CELLS; STELLATE CELLS AB The endocrine cells of the rat pancreatic islets of Langerhans, including insulin-producing beta -cells, turn over every 40-50 days by processes of apoptosis and the proliferation and differentiation of new islet cells (neogenesis) from progenitor epithelial cells located in the pancreatic ducts. However, the administration to rats of islet trophic factors such as glucose or glucagon-like peptide 1 for 48 h results in a doubling of islet cell mass, suggesting that islet progenitor cells may reside within the islets themselves. Here we show that rat and human pancreatic islets contain a heretofore unrecognized distinct population of cells that express the neural stem cell-specific marker nestin. Nestin-positive cells within pancreatic islets express neither the hormones insulin, glucagon, somatostatin, or pancreatic polypeptide nor the markers of vascular endothelium or neurons, such as collagen IV and galanin. Focal regions of nestin-positive cells are also identified in large, small, and centrolobular ducts of the rat pancreas. Nestin-positive cells in the islets and in pancreatic ducts are distinct from ductal epithelium because they do not express the ductal marker cytokeratin 19 (CK19). After their isolation, these nestin-positive cells have an unusually extended proliferative capacity when cultured in vitro (similar to8 months), can be cloned repeatedly, and appear to be multipotential. Upon confluence, they are able to differentiate into cells that express liver and exocrine pancreas markers, such as a-fetoprotein and pancreatic amylase, and display a ductal/endocrine phenotype with expression of CK19, neural-specific cell adhesion molecule, insulin, glucagon, and the pancreas/duodenum specific homeodomain transcription factor, IDX-1. We propose that these nestin-positive islet-derived progenitor (NIP) cells are a distinct population of cells that reside within pancreatic islets and may participate in the neogenesis of islet endocrine cells. The NIP cells that also reside in the pancreatic ducts may be contributors to the established location of islet progenitor cells. The identification of NIP cells within the pancreatic islets themselves suggest possibilities for treatment of diabetes, whereby NIP cells isolated from pancreas biopsies could be expanded ex vivo and transplanted into the donor/recipient. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Lab Mol Endocrinol, Boston, MA 02114 USA. Univ Hosp Geneva, Div Endocrinol & Diabet, Geneva, Switzerland. Univ Zurich Hosp, Dept Surg, CH-8091 Zurich, Switzerland. Univ Basel Hosp, Dept Internal Med, Div Endocrinol Diabetol & Metab, CH-4031 Basel, Switzerland. Super Council Sci Res, Inst Biomed Res, Madrid, Spain. RP Habener, JF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Lab Mol Endocrinol, 55 Fruit St,WEL320, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK 30457, DK 30834, DK 55365] NR 55 TC 563 Z9 701 U1 0 U2 28 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2001 VL 50 IS 3 BP 521 EP 533 DI 10.2337/diabetes.50.3.521 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 407JX UT WOS:000167269400006 PM 11246871 ER PT J AU Koutkia, P Mylonakis, E Rounds, S Erickson, A AF Koutkia, P Mylonakis, E Rounds, S Erickson, A TI Cutaneous leucocytoclastic vasculitis associated with oxacillin SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE oxacillin; leucocytoclastic vasculitis; penicillins; renal failure; vasculitis; bacteremia ID NECROTIZING VASCULITIS AB A 67-year-old man who was treated with oxacillin for one week because of Staphylococcus aureus bacteremia, developed renal failure and diffuse, symmetric, palpable purpuric lesions on his feet. Necrotic blisters were noted on his fingers. Skin biopsies showed findings diagnostic of leucocytoclastic vasculitis. Oxacillin was discontinued and patient was treated with corticosteroids. The rash disappeared after three weeks and renal function returned to normal. Leucocytoclastic vasculitis presents as palpable purpura of the lower extremities often accompanied by abdominal pain, arthralgia, and renal involvement. Etiologic factors or associated disorders include infections, medications, collagen vascular disease and neoplasia. However, in half of the cases no etiologic factor is identified. Usually it is a self-limited disorder, but corticosteroid therapy may be needed in life-threatening cases since early treatment with corticosteroids in severe cases can prevent complications. Oxacillin should be included among the drugs that can cause leucocytoclastic vasculitis. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Boston Univ, Med Ctr, Dept Endocrinol Diabet & Nutr, Boston, MA 02118 USA. Harvard Univ, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA USA. Brown Univ, Vet Affairs Med Ctr, Dept Med, Providence, RI 02912 USA. RP Koutkia, P (reprint author), Boston Univ, Med Ctr, Dept Endocrinol Diabet & Nutr, 88 E Newton St,Evans Bldg,Room 201, Boston, MA 02118 USA. NR 15 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD MAR PY 2001 VL 39 IS 3 BP 191 EP 194 DI 10.1016/S0732-8893(00)00238-8 PG 4 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 431LV UT WOS:000168633500010 PM 11337188 ER PT J AU Stelzner, M Somasundaram, S Kearney, D AF Stelzner, M Somasundaram, S Kearney, D TI A simple method for measuring of intestinal solute transport in mucosal biopsy specimens SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE ileum; bile acids; absorption; sheep; human ID NEGATIVE FEEDBACK-REGULATION; BILE-ACID TRANSPORT; NUTRIENT TRANSPORT; ILEAL; ABSORPTION AB Accurate in vitro measurements of intestinal mucosal solute uptake in humans are often difficult because only small amounts of tissue material are available. We describe a miniaturized everted sleeve method of measuring intestinal solute uptake in endoscopy biopsy samples that combines simplicity, good tissue viability and reproducibility. Biopsies were mounted on a dressmaker needle head stationed immediately over a stirring bar rotating at 1200 rpm. This approach was used to measure taurocholate uptake in sheep and human endoscopy biopsies. Comparison was made to conventional standardized everted sleeve preparations. Na+-dependent uptake rates correlated well among individual sheep (R 0.88, P < 0.05). There was excellent correlation between conventional and biopsy preparations in humans (R-2 0.98; P < 0.05). The biopsy method overestimated diffusional uptake rates in sheep and humans by two to three fold when compared to conventional everted sleeve preparations. We conclude that this method is valuable to measure Na+ dependent solute uptake rates in biopsy samples from human intestine. C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Surg, Surg Serv, Seattle, WA 98108 USA. Univ Washington, Dept Surg, Surg Serv, Seattle, WA 98195 USA. Univ Washington, Dept Med, Surg Serv, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Div Gastroenterol, Seattle, WA USA. RP Stelzner, M (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Surg, Surg Serv, 112,1660 S Columbian Way, Seattle, WA 98108 USA. NR 14 TC 5 Z9 5 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD MAR PY 2001 VL 46 IS 3 BP 451 EP 456 DI 10.1023/A:1005681624873 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 421ZB UT WOS:000168092500001 PM 11318514 ER PT J AU Ehrman, RN Robbins, SJ Cornish, JW AF Ehrman, RN Robbins, SJ Cornish, JW TI Results of a baseline urine test predict levels of cocaine use during treatment SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE cocaine dependence; cocaine use; urine test; treatment outcome ID ADDICTION SEVERITY INDEX; ATTRITION; ABUSERS; ABSTINENCE; FAILURE; ALCOHOL AB Sixty-one cocaine dependent outpatients submitted a single urine sample at least 1 week prior to entry into a 4-week treatment study. Participants were then expected to provide three urine samples per week during the month of treatment. The 61 patients studied here all completed treatment and provided an average of more than 11 of 12 scheduled urine samples. Participants who submitted a cocaine-positive sample prior to treatment provided more positive urine samples during the 4-week trial, were less likely to be completely abstinent during the month, and took longer to reach an initial abstinence criterion of three consecutive cocaine-free urines. Thus, a single pretreatment urine test represents a powerful predictor of subsequent cocaine use. The results suggest that future randomized trials stratify group assignment based on the results of a baseline urine test. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Penn, Dept Psychiat, Treatment Res Ctr, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Beaver Coll, Glenside, PA 19038 USA. RP Ehrman, RN (reprint author), Univ Penn, Dept Psychiat, Treatment Res Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. FU NIDA NIH HHS [DA03008, P50-DA09252-02] NR 19 TC 33 Z9 33 U1 2 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD MAR 1 PY 2001 VL 62 IS 1 BP 1 EP 7 DI 10.1016/S0376-8716(00)00137-X PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 406CB UT WOS:000167196400001 PM 11173162 ER PT J AU Strausbaugh, LJ AF Strausbaugh, LJ TI Emerging health care-associated infections in the geriatric population SO EMERGING INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 4th Decennial International Conference on Nosocomial and Healthcare-Associated Infections in Conjunction with the 10th Annual Meeting of SHEA CY MAR 05-09, 2000 CL ATLANTA, GEORGIA SP SHEA ID RESISTANT ENTEROCOCCUS-FAECIUM; NURSING-HOME; NOSOCOMIAL INFECTIONS; CONTROL PROGRAMS; FACILITIES; OUTBREAK; RISK; PREVENTION; RESIDENTS; DIARRHEA AB The increasing number of persons >65 years of age form a special population at risk for nosocomial and other health care-associated infections. The vulnerability of this age group is related to impaired host defenses such as diminished cell-mediated immunity. Lifestyle considerations. e.g., travel and living arrangements, and residence in nursing homes, can further complicate the clinical picture. The magnitude and diversity of health care-associated infections in the aging population are generating new arenas for prevention and control efforts. C1 Portland VA Med Ctr, Med Serv, Portland, OR 97201 USA. RP Strausbaugh, LJ (reprint author), Portland VA Med Ctr, Med Serv, P-3-ID,3710 SW US Vet Hosp Rd, Portland, OR 97201 USA. NR 35 TC 48 Z9 50 U1 0 U2 2 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD MAR-APR PY 2001 VL 7 IS 2 BP 268 EP 271 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 422HG UT WOS:000168112000024 PM 11294721 ER PT J AU Hooper, DC AF Hooper, DC TI Emerging mechanisms of fluoroquinolone resistance SO EMERGING INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 4th Decennial International Conference on Nosocomial and Healthcare-Associated Infections in Conjunction with the 10th Annual Meeting of SHEA CY MAR 05-09, 2000 CL ATLANTA, GEORGIA SP SHEA ID II DNA TOPOISOMERASES; STAPHYLOCOCCUS-AUREUS; STREPTOCOCCUS-PNEUMONIAE; ESCHERICHIA-COLI; DECREASED SUSCEPTIBILITY; RISK-FACTORS; CIPROFLOXACIN RESISTANCE; ANTIMICROBIAL RESISTANCE; PSEUDOMONAS-AERUGINOSA; NEISSERIA-GONORRHOEAE AB Broad use of fluoroquinolones has been followed by emergence of resistance, which has been due mainly to chromosomal mutations in genes encoding the subunits of the drugs' target enzymes, DNA gyrase and topoisomerase IV, and in genes that affect the expression of diffusion channels in the outer membrane and multidrug-resistance efflux systems. Resistance emerged first in species in which single mutations were sufficient to cause clinically important levels of resistance (e.g., Staphylococcus aureus and Pseudomonas aeruginosa). Subsequently, however, resistance has emerged in bacteria such as Campylobacter jejuni, Escherichia coli, and Neisseria gonorrhoeae, in which multiple mutations are required to generate clinically important resistance. In these circumstances, the additional epidemiologic factors of drug use in animals and human-to-human spread appear to have contributed. Resistance in Streptococcus pneumoniae, which is currently low, will require close monitoring as fluoroquinolones are used more extensively for treating respiratory tract infections. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. RP Hooper, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. NR 36 TC 297 Z9 312 U1 3 U2 23 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD MAR-APR PY 2001 VL 7 IS 2 BP 337 EP 341 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 422HG UT WOS:000168112000039 PM 11294736 ER PT J AU Whalen, PJ Shin, LM McInerney, SC Fischer, H Wright, CI Rauch, SL AF Whalen, Paul J. Shin, Lisa M. McInerney, Sean C. Fischer, Hakan Wright, Christopher I. Rauch, Scott L. TI A Functional MRI Study of Human Amygdala Responses to Facial Expressions of Fear Versus Anger SO EMOTION LA English DT Article AB Functional magnetic resonance imaging (fMRI) of the human brain was used to compare changes in amygdala activity associated with viewing facial expressions of fear and anger. Pictures of human faces bearing expressions of fear or anger, as well as faces with neutral expressions, were presented to 8 healthy participants. The blood oxygen-level dependent (BOLD) fMRI signal within the dorsal amygdala was significantly greater to Fear versus Anger, in a direct contrast. Significant BOLD signal changes in the ventral amygdala were observed in contrasts of Fear versus Neutral expressions and, in a more spatially circumscribed region, to Anger versus Neutral expressions. Thus, activity in the amygdala is greater to fearful facial expressions when contrasted with either neutral or angry faces. Furthermore, directly contrasting fear with angry faces highlighted involvement of the dorsal amygdaloid region. C1 [Whalen, Paul J.] Univ Wisconsin, Waisman Ctr, Dept Psychiat & Psychol, WM Keck Lab Funct Brain Imaging & Behav, Madison, WI 53705 USA. [Shin, Lisa M.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Shin, Lisa M.; McInerney, Sean C.; Wright, Christopher I.; Rauch, Scott L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat Neuroimaging Res Grp, Cambridge, MA 02138 USA. [Shin, Lisa M.; McInerney, Sean C.; Wright, Christopher I.; Rauch, Scott L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nucl Magnet Resonance Ctr, Cambridge, MA 02138 USA. [Fischer, Hakan] Uppsala Univ, PET Ctr, Univ Hosp, Uppsala, Sweden. RP Whalen, PJ (reprint author), Univ Wisconsin, Waisman Ctr, Dept Psychiat & Psychol, WM Keck Lab Funct Brain Imaging & Behav, 1500 Highland Ave,T113, Madison, WI 53705 USA. EM pwhalen@facstaff.wisc.edu FU NIMH NIH HHS [MH-01866, MH-01215] NR 78 TC 395 Z9 397 U1 8 U2 45 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 J9 EMOTION JI Emotion PD MAR PY 2001 VL 1 IS 1 BP 70 EP 83 DI 10.1037/1528-3542.1.1.70 PG 14 WC Psychology, Experimental SC Psychology GA V21RE UT WOS:000208223900007 PM 12894812 ER PT J AU Danila, DC Klibanski, A AF Danila, DC Klibanski, A TI Prolactin secreting pituitary tumors in men SO ENDOCRINOLOGIST LA English DT Review ID LONG-TERM; HYPERPROLACTINEMIC HYPOGONADISM; CLINICAL CHARACTERISTICS; MACROPROLACTINOMAS; ADENOMAS; THERAPY; MALES AB Elevated serum levels of prolactin are identified less frequently in men than in women, in part because in men the recognition of symptoms, including reproductive dysfunction, is delayed. The majority of prolactin secreting tumors in men are macroadenomas, and patients often present with headache and visual field abnormalities as chief complaints. Abnormalities in pulsatile gonadotropin secretion result in hypogonadism, and both sexual and reproductive dysfunctions are commonly present at the time of diagnosis. Serum prolactin levels typically correlate with tumor size. In the absence of other explanations for an elevated prolactin level, such as medication, primary hypothyroidism, or pituitary stalk compression, a prolactin secreting pituitary tumor is the most likely diagnosis. A magnetic resonance imaging scan of the pituitary is critical in the diagnosis of a prolactinoma. Medical management with dopamine agonists is the first line of treatment. Bromocriptine or newer agents, such as cabergoline and quinagolide, normalize prolactin levels and decrease tumor size in the majority of patients, independent of initial tumor size. Overall, approximately 80% of men with prolactinomas will normalize serum prolactin levels with dopamine agonist therapy alone. Adjunctive therapy with testosterone for hypogonadism and sexual dysfunction is often necessary due to permanent gonadotroph destruction in macroadenomas or failure to normalize prolactin levels in both macro and microadenomas. Transsphenoidal surgical resection of the tumor should be used only when dopamine agonist therapy fails or cannot be tolerated. Increased recognition of the syndrome of hypogonadism in men in recent years may lead to earlier diagnosis of prolactin secreting tumors in men. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,Bulfinch 457, Boston, MA 02114 USA. NR 20 TC 7 Z9 7 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD MAR-APR PY 2001 VL 11 IS 2 BP 105 EP 111 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 421NJ UT WOS:000168070200006 ER PT J AU Thomas, MK Lee, JH Rastalsky, N Habener, JF AF Thomas, MK Lee, JH Rastalsky, N Habener, JF TI Hedgehog signaling regulation of homeodomain protein islet duodenum homeobox-1 expression in pancreatic beta-cells SO ENDOCRINOLOGY LA English DT Article ID INSULIN GENE-TRANSCRIPTION; TYPE-2 DIABETES-MELLITUS; LOOP-HELIX PROTEINS; FACTOR-I IPF-1; GLUCOSE-CONCENTRATION; TRANSDUCING HEDGEHOG; CUBITUS INTERRUPTUS; BINDING-PROTEINS; DOMAIN PROTEIN; FACTOR STF-1 AB Insulin gene expression in pancreatic beta -cells is regulated by signals from developmental morphogen proteins known as hedgehogs (Hhs). By analyzing 5'-deletion insulin promoter-reporter constructs in transient transfections of clonal INS-1 beta -cells, we located activating Hh-responsive regions within the rat insulin I promoter that include the glucose-response elements Far (E2) and Flat (A2/A3). Activation of Hh signaling in INS-1 cells by ectopic Hh expression increased (and inhibition of Hh signaling with the Hh-specific inhibitor cyclopamine decreased) transcriptional activation of a multimerized FarFlat enhancer-reporter construct. In DNA-binding studies, nuclear extracts from INS-1 cells activated by ectopic Hh expression increased land extracts from INS-1 cells treated with cyclopamine decreased) protein binding to a radiolabeled FarFlat oligonucleotide probe. An antiserum directed against the transcription factor islet duodenum homeobox-l (IDX-1), a regulator of pancreas development and activator of the insulin gene promoter, attenuated the binding activity of Hh-responsive protein complexes. Nuclear IDX-1 protein levels on Western blots were increased by ectopic Hh expression, thereby providing a mechanism for Hh-mediated regulation of the insulin promoter. Addition of cyclopamine to INS-1 cells decreased IDX-1 messenger RNA expression. In transient transfections of a -4.5-kb mouse IDX-1 promoter-reporter construct, ectopic Hh expression increased (and cyclopamine administration decreased) transcriptional activation of the IDX-1 promoter in a dose-dependent manner. Thus, the IDX-1 gene is a direct regulatory target of Hh signaling in insulin-producing pancreatic beta -cells. We propose that Hh signaling activates the insulin gene promoter indirectly via the direct activation of IDX-1 expression. Because IDX-1 gene expression is essential for insulin gene expression, pancreatic beta -cell development, and normal glucose homeostasis, our findings that Hh signaling regulates IDX-1 expression in the endocrine pancreas suggest possible novel therapeutic approaches for diabetes mellitus. C1 Harvard Univ, Mol Endocrinol Lab, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Howard Hughes Med Inst, Boston, MA 02114 USA. RP Habener, JF (reprint author), Harvard Univ, Mol Endocrinol Lab, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,Wellman Bldg 320, Boston, MA 02114 USA. NR 67 TC 43 Z9 43 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 2001 VL 142 IS 3 BP 1033 EP 1040 DI 10.1210/en.142.3.1033 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 405NT UT WOS:000167166400010 PM 11181516 ER PT J AU Kemp, DM Habener, JF AF Kemp, DM Habener, JF TI Insulinotropic hormone glucagon-like peptide 1 (GLP-1) activation of insulin gene promoter inhibited by p38 mitogen-activated protein kinase SO ENDOCRINOLOGY LA English DT Article ID PANCREATIC BETA-CELLS; CAMP-RESPONSIVE ELEMENT; TRANSCRIPTION FACTOR EXPRESSION; DNA-BINDING ACTIVITY; C-JUN; CYCLIC-AMP; I GENE; GLUCOSE-CONCENTRATION; SIGNAL-TRANSDUCTION; DIABETES-MELLITUS AB The insulin gene promoter contains many transcriptional response elements that predispose the gene to a wide range of regulatory signals. Glucagon-like peptide 1 (GLP-1) stimulates insulin gene transcription by intracellular second messenger cascades leading to direct transcription factor activation or to the up-regulation of insulin promoter specific transcription factors. In these studies, we have identified a novel regulatory signaling mechanism acting on the rat insulin 1 promoter (rINS1) in the INS-1 beta -cell line. In the presence of stimulatory concentrations of GLP-1 (0.1-100 nM) on rINS1 activity, inhibition of p38 mitogen-activated protein kinase (p38 MAPK) using SE 203580 resulted in a marked increase in promoter activity (maximum 3-fold) over GLP-1 alone, as determined by rINS1 promoter-luciferase reporter gene expression. This effect was revealed to be mediated via the cAMP response element (CRE) of rINS 1, because site directed mutagenesis of the CRE motif in rINS1 abolished the in-creased response to SE 203580. Furthermore, inhibition of p38 MAPK uncovered a similar, more pronounced, response in the expression of a generic CRE promoter driven reporter gene. Time course dose-response studies indicate that the p38 MAPK induced inhibitory response may involve expression of immediate early genes (IEGs); maximum repression of rINS 1 activity occurred after 4 h of treatment, comparable with regulatory responses by IEGs. In conclusion, these results demonstrate a novel signaling mechanism whereby p38 MAPK represses rINS1 promoter activity in response to GLP-1, suggesting the involvement of a robust regulatory control by p38 MAPK in insulin gene expression. The relevance of this mechanism may be most apparent during periods of cellular stress in which p38 MAPK activity is stimulated. In this regard, reduced insulin expression levels caused by chronic hyperglycemia (glucotoxicity) and/or hyperlipidemia (lipotoxicity) may be a direct consequence of this mechanism. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst,Lab Mol Endocrinol, Boston, MA 02114 USA. RP Habener, JF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst,Lab Mol Endocrinol, 55 Fruit St,WEL320, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-30834] NR 61 TC 33 Z9 35 U1 0 U2 4 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 2001 VL 142 IS 3 BP 1179 EP 1187 DI 10.1210/en.142.3.1179 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 405NT UT WOS:000167166400027 PM 11181533 ER PT J AU Guo, J Lanske, B Liu, BY Divieti, P Kronenberg, HM Bringhurst, FR AF Guo, J Lanske, B Liu, BY Divieti, P Kronenberg, HM Bringhurst, FR TI Signal-selectivity of parathyroid hormone (PTH)/PTH-related peptide receptor-mediated regulation of differentiation in conditionally immortalized growth-plate chondrocytes SO ENDOCRINOLOGY LA English DT Article ID ENDOCHONDRAL BONE-DEVELOPMENT; COLLAGEN GENE-EXPRESSION; METAPHYSEAL CHONDRODYSPLASIA; TERMINAL DIFFERENTIATION; PROTEOGLYCAN SYNTHESIS; PTH/PTHRP RECEPTOR; MOUSE CHONDROCYTES; PHOSPHOLIPASE-C; INDIAN HEDGEHOG; CARTILAGE AB Type-1 PTH/PTH-related peptide receptors (PTH1Rs), which activate both adenylyl cyclase and phospholipase C (PLC), control endochondral bone development by regulating chondrocyte differentiation. To directly analyze PTH1R function in such cells, we isolated conditionally transformed clonal chondrocytic cell lines from tibial growth plates of neonatal mice heterozygous for PTH1R gene ablation. Among 104 cell lines isolated, messenger RNAs for PTH1R, collagen II, and collagen X were detected in 28%, 90%, and 29%, respectively. These cell lines were morphologically diverse. Some appeared large, rounded, and enveloped by abundant extracellular matrix; whereas others were smaller, flattened, and elongated. Two PTH1R-expressing clones showed similar PTH1R binding and cAMP responsiveness to PTH and PTH-related peptide but disparate morphologic features, characteristic of hypertrophic (hC1-5) or nonhypertrophic (nhC2-27) chondrocytes, respectively. hC1-5 cells expressed messenger RNAs for collagen II and X, alkaline phosphatase (ALP), and matrix GLA protein, whereas nhC2-27 cells expressed collagen II and Indian hedgehog but not collagen X or ALP. In hC1-5 cells, PTH and cAMP analog, but not phorbol ester, inhibited both ALP and mineralization. PTH1R-null hC1-5 subclones were isolated by in vitro selection and then reconstituted by stable transfection with wild-type PTH1Rs or mutant (DSEL) PTH1Rs defective in PLC activation. ALP and mineralization were inhibited similarly via both forms of the receptor. These results indicate that PLC activation is not required for PTH1R regulation of mineralization or ALP in hypertrophic chondrocytes and are consistent with a major role for cAMP in regulating differentiation of hypertrophic chondrocytes. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Guo, J (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-11794] NR 40 TC 20 Z9 20 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAR PY 2001 VL 142 IS 3 BP 1260 EP 1268 DI 10.1210/en.142.3.1260 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 405NT UT WOS:000167166400037 PM 11181543 ER PT J AU Schnitzer, JJ Donahoe, PK AF Schnitzer, JJ Donahoe, PK TI Surgical treatment of congenital adrenal hyperplasia SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article ID MULLERIAN-INHIBITING SUBSTANCE; HUMAN ANDROGEN RECEPTOR; AUTOSOMAL SEX REVERSAL; MIXED GONADAL-DYSGENESIS; SRY-RELATED GENE; DETERMINING REGION; MALE PSEUDOHERMAPHRODITISM; 21-HYDROXYLASE DEFICIENCY; TRUE HERMAPHRODITISM; CAMPOMELIC DYSPLASIA AB This article discusses congenital adrenal hyperplasia (CAH) in the context of normal sex determination and differentiation. Topics include how CAH can be differentiated from other causes of ambiguous genitalia that can produce similar phenotypes, how a rapid diagnosis can be made and early treatment employed to avoid adrenal crisis, the timing of surgery after the child stabilizes, the optimization and use of early surgical correction, and follow-up for anticipated problems that may manifest at adolescence. C1 Massachusetts Gen Hosp, Pediat Surg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Surg Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Schnitzer, JJ (reprint author), Massachusetts Gen Hosp, Pediat Surg Serv, WRN 1159,55 Fruit St, Boston, MA 02114 USA. NR 65 TC 27 Z9 28 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD MAR PY 2001 VL 30 IS 1 BP 137 EP + DI 10.1016/S0889-8529(08)70023-9 PG 20 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 426AT UT WOS:000168327500009 PM 11344932 ER PT J AU Genton, P Bauer, J Duncan, S Taylor, AE Balen, AH Eberle, A Pedersen, B Salas-Puig, X Sauer, MV AF Genton, P Bauer, J Duncan, S Taylor, AE Balen, AH Eberle, A Pedersen, B Salas-Puig, X Sauer, MV TI On the association between valproate and polycystic ovary syndrome SO EPILEPSIA LA English DT Review DE polycystic ovaries; polycystic ovary syndrome; valproate; epilepsy; insulin resistance ID REPRODUCTIVE ENDOCRINE DISORDERS; TEMPORAL-LOBE EPILEPSY; RECEIVING ANTICONVULSANT MEDICATION; IMPAIRED GLUCOSE-TOLERANCE; MALE PATTERN BALDNESS; GROWTH FACTOR-I; PARTIAL SEIZURES; LUTEINIZING-HORMONE; METABOLIC FEATURES; SERUM PROLACTIN AB Recent studies by Isojarvi et al. have raised the issue of an increased incidence of polycystic ovary syndrome (PCOS) in women with epilepsy treated with valproate (VPA) and have proposed replacement with lamotrigine (LTG). Poly cystic ovaries (PCO) are a common finding, with a prevalence >20% in the general population, and are easily detected by pelvic or vaginal ultrasonography, whereas PCOS is comparatively rare: few women with PCO have fully developed PCOS, which includes hirsutism, acne, obesity, hypofertility, hyperandrogenemia, and menstrual disorders. From an extensive re view of the current literature, it appears that there are no reliable data on the actual prevalence of PCOS in normal women and in women with epilepsy. The pathogenesis of PCO is multifactorial, including genetic predisposition and the intervention of environmental factors, among which weight gain and hyper insulinism with insulin resistance may play a part. The roles of central (hypothalamic/pituitary), peripheral. and local ovarian factors are still debated. PCO and PCOS appear to be more frequent in women with epilepsy, but there are no reliable data showing a greater prevalence after VPA. The recent studies by Isojarvi et al. may have been biased by the retrospective selection of patients. To date, there is no reason to contraindicate the use of VPA in women with epilepsy. However, patients should be informed about the risk of weight gain and its consequences. C1 Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Hosp Gen Asturias, E-33006 Oviedo, Spain. Aalborg Sygehus Nord, Aalborg, Denmark. Arkansas Childrens Hosp, Little Rock, AR 72202 USA. Leeds Gen Infirm, Leeds, W Yorkshire, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. Salford Royal Hosp, Salford, Lancs, England. Univ Bonn, Epilepsy Clin, D-5300 Bonn, Germany. Ctr St Paul, F-13009 Marseille, France. RP Genton, P (reprint author), Ctr St Paul, 300 Blvd St Marguerite, F-13009 Marseille, France. NR 102 TC 69 Z9 72 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAR PY 2001 VL 42 IS 3 BP 295 EP 304 DI 10.1046/j.1528-1157.2001.28899.x PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 416NC UT WOS:000167786200001 PM 11442143 ER PT J AU Costantini, LC Cole, D Isacson, O AF Costantini, LC Cole, D Isacson, O TI Immunophilin ligands can prevent progressive dopaminergic degeneration in animal models of Parkinson's disease SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE animal models; FK-binding proteins; mouse; neuroprotection; neurotrophic factors; rat; substantia nigra ID PARTIAL LESION MODEL; NEUROTROPHIC FACTOR; GROWTH-FACTOR; IN-VIVO; INTRASTRIATAL INJECTION; RAT MODEL; NIGROSTRIATAL NEURONS; TYROSINE-HYDROXYLASE; SHORT-TERM; FOLLOW-UP AB Slowing or halting the progressive dopaminergic (DA) degeneration in Parkinson's disease (PD) would delay the onset and development of motor symptoms, prolong the efficacy of pharmacotherapies and decrease drug-induced side-effects. We tested the potential of two orally administered novel immunophilin ligands to protect against DA degeneration in two animal models of PD. First, in an MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model, we compared an immunophilin ligand (V-10,367) documented to bind the immunophilin FKBP12 with V-13,661, which does not bind FKBP12. Both molecules could prevent the loss of striatal DA innervation in a dose-dependent fashion during 10 days of oral administration. Second, to determine whether an immunophilin ligand can protect against progressive and slow DA degeneration typical of PD, an intrastriatal 6-hydroxydopamine-infusion rat model was utilized. Oral treatment with the FKBP12-binding immunophilin ligand began on the day of lesion and continued for 21 days. At this time point, post mortem analyses revealed that the treatment had prevented the progressive loss of DA innervation within the striatum and loss of DA neurons within the substantia nigra, related to functional outcome as measured by rotational behaviour. Notably, DA fibres extending into the area of striatal DA denervation were observed only in rats treated with the immunophilin ligand, indicating neuroprotection or sprouting of spared DA fibres. This is the first demonstration that immunophilin ligands can prevent a slow and progressive DA axonal degeneration and neuronal death in vivo. The effects of orally administered structurally related immunophilin ligands in acute and progressive models of DA degeneration are consistent with the idea that these compounds may have therapeutic value in PD. C1 Harvard Univ, McLean Hosp, Sch Med, Neuroregenerat Lab, Belmont, MA 02178 USA. McLean Hosp, Massachusetts Gen Hosp, Dept Neurol & Psychiat, Belmont, MA 02178 USA. Vertex Pharmaceut Inc, Cambridge, MA USA. RP Isacson, O (reprint author), Harvard Univ, McLean Hosp, Sch Med, Neuroregenerat Lab, 115 Mill St, Belmont, MA 02178 USA. FU NINDS NIH HHS [P50-NS39793] NR 59 TC 42 Z9 45 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAR PY 2001 VL 13 IS 6 BP 1085 EP 1092 DI 10.1046/j.0953-816x.2001.01473.x PG 8 WC Neurosciences SC Neurosciences & Neurology GA 413MF UT WOS:000167615400003 PM 11285005 ER PT J AU Zhang, SL To, C Chen, X Filep, JG Tang, SS Ingelfinger, JR Carriere, S Chen, JSD AF Zhang, SL To, C Chen, X Filep, JG Tang, SS Ingelfinger, JR Carriere, S Chen, JSD TI Effect of renin-angiotensin system blockade on the expression of the angiotensinogen gene and induction of hypertrophy in rat kidney proximal tubular cells SO EXPERIMENTAL NEPHROLOGY LA English DT Article DE hyperglycemia; angiotensinogen; kidney and hypertrophy ID CELLULAR HYPERTROPHY; MESSENGER-RNA; DIABETIC NEPHROPATHY; BETA; TRANSCRIPTION; ANTAGONISTS; SECRETION; RECEPTOR; FEEDBACK; SEQUENCE AB Studies have shown that high levels of glucose and angiotensin II (Ang II) stimulate hypertrophy and the expression of matrix protein genes in mouse proximal tubular cells in vitro. The present study tested the hypothesis that blockade of the renin-angiotensin system (RAS) inhibits the stimulatory effect of high levels of glucose on the expression of the renal angiotensinogen (ANG) gene and the formation of Ang II and subsequently attenuates the induction of hypertrophy in kidney proximal tubular cells. Immortalized rat proximal tubular cells (IRPTC) were cultured in monolayer. The levels of expression of rat ANG and ANG mRNA in the IRPTC were quantified by specific radioimmunoassays for rat ANG (RIA-rANG) and by a reverse-transcription polymerase chain reaction (RT-PCR) assay, respectively. Hypertrophy of IRPTC was analyzed by flow cytometry (FACScan) and cellular protein assay. Our studies showed that losartan (an Ang II (AT(1))-receptor blocker), perindopril and captopril (inhibitors of angiotensin-converting enzyme) blocked the stimulatory effect of a high level of glucose (i.e. 25 mM) on the expression of the rat ANG gene and hypertrophy in IRPTC but not by the Ang II (AT(2))-receptor blocker. Our studies indicate that the blockade of RAS is effective in inhibiting the stimulatory effect of hyperglycemia on the expression of the ANG gene and hypertrophy in IRPTC, supporting the notion that the local formation of intrarenal Ang II may play a role in the development of renal hypertrophy during early diabetes. Copyright (C) 2001 S. Karger AG, Basel. C1 Univ Montreal, Maisonneuve Rosemont Hosp, Res Ctr, Montreal, PQ H1T 2M4, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA USA. Servier Amer, Laval, PQ, Canada. RP Chen, JSD (reprint author), Univ Montreal, Maisonneuve Rosemont Hosp, Res Ctr, 5415 Boul Assompt, Montreal, PQ H1T 2M4, Canada. FU NHLBI NIH HHS [HL-48455]; NIDDK NIH HHS [DK-50836] NR 27 TC 34 Z9 35 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-7782 J9 EXP NEPHROL JI Exp. Nephrol. PD MAR-APR PY 2001 VL 9 IS 2 BP 109 EP 117 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 395PE UT WOS:000166588100006 PM 11150859 ER PT J AU Koka, R Hadlock, TA AF Koka, R Hadlock, TA TI Quantification of functional recovery following rat sciatic nerve transection SO EXPERIMENTAL NEUROLOGY LA English DT Article DE rat sciatic nerve; transection; behavioral testing ID NEUROLOGIC EVALUATION; BLOCKADE; REGENERATION; MICROSPHERES AB Functional recovery following experimental nerve injury has been notoriously difficult to quantify precisely. The current gold standard in the rat sciatic nerve model involves analysis of footprints of the recovering animal, and computation of the sciatic function index (SFI). We performed transection injuries and measured recovery both by walking track analysis and by a newer, simpler, more quantitative test of motor recovery, the extensor postural thrust (EPT). We demonstrate a high correlation between both testing modalities and suggest a role for EPT measurements as an easier, more consistent measure of motor recovery following experimental rat sciatic nerve transection. (C) 2001 Academic Press. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hadlock, TA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. NR 14 TC 53 Z9 57 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAR PY 2001 VL 168 IS 1 BP 192 EP 195 DI 10.1006/exnr.2000.7600 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 406ER UT WOS:000167202400018 PM 11170734 ER PT J AU Tonini, M Spelta, V De Ponti, F De Giorgio, R D'Agostino, G Stanghellini, V Corinaldesi, R Sternini, C Crema, F AF Tonini, M Spelta, V De Ponti, F De Giorgio, R D'Agostino, G Stanghellini, V Corinaldesi, R Sternini, C Crema, F TI Tachykinin-dependent and -independent components of peristalsis in the guinea pig isolated distal colon SO GASTROENTEROLOGY LA English DT Article ID RAT GASTROINTESTINAL-TRACT; CIRCULAR MUSCLE; SMALL-INTESTINE; NK2 RECEPTORS; SUBSTANCE-P; INTERSTITIAL-CELLS; NITRIC-OXIDE; SYNAPTIC TRANSMISSION; MOTILITY REFLEXES; MYENTERIC PLEXUS AB Background & Aims: In-the intestine, tachykinins regulate motility by participating in neuromuscular and neuro-neuronal transmission. The aim of this study was to test the hypothesis that colonic propulsion is regulated by an interplay between tachykinergic and cholinergic transmission. Methods: Propulsion was elicited by intraluminal distention of a thin rubber balloon, which traveled from the oral to the anal end of guinea pig isolated distal colon segments. The overall contribution of endogenous tachyhinins to colonic propulsion was examined by blocking NK1, NK2, and NK3 receptors simultaneously. Results: NK2-receptor blockade by MEN 11420 inhibited propulsion, whereas blockade of NK1 by SR 140333 or of NK3 receptors by SR 142801 had minor effects on motility, Blockade of muscarinic or nicotinic receptors by hyoscine or hexamethonium decelerated peristalsis up to propulsion arrest. In the presence of partial muscarinic receptor blockade, the NK1-receptor antagonist SR 140333 and the NK2-receptor antagonist MEN 11420 markedly inhibited propulsion. Propulsion was also inhibited by the NK3-receptor antagonist SR 142801 in the presence of partial nicotinic receptor blockade. The simultaneous administration of the 3 tachykinin antagonists inhibited propulsion by 50%. Conclusions: This study demonstrates the existence of an interplay between tachykinergic and cholinergic pathways during peristalsis and the importance of endogenous tachykinins acting at multiple receptor sites in the control of colonic propulsion. C1 Univ Pavia, Dept Internal Med & Therapeut, Div Clin & Expt Pharmacol, I-27100 Pavia, Italy. Univ Bologna, Dept Pharmacol, Bologna, Italy. Univ Bologna, Dept Internal Med & Gastroenterol, Bologna, Italy. Univ Pavia, Sch Pharm, Dept Expt & Appl Pharmacol, I-27100 Pavia, Italy. Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Div Digest Dis, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Div Digest Dis, Dept Neurobiol, Los Angeles, CA USA. Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Tonini, M (reprint author), Univ Pavia, Dept Internal Med & Therapeut, Div Clin & Expt Pharmacol, I-27100 Pavia, Italy. OI De Giorgio, Roberto/0000-0003-0867-5873; De Ponti, Fabrizio/0000-0002-0367-9595 FU NIDDK NIH HHS [DK 54155]; PHS HHS [41301] NR 50 TC 38 Z9 38 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAR PY 2001 VL 120 IS 4 BP 938 EP 945 DI 10.1053/gast.2001.22526 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 407ZP UT WOS:000167302300022 PM 11231947 ER PT J AU Lieberman, D AF Lieberman, D TI Colorectal cancer: Not an equal opportunity cancer SO GASTROENTEROLOGY LA English DT Editorial Material ID FECAL OCCULT-BLOOD; COST; COLON; CARE C1 Oregon Hlth Sci Univ, Portland VA Med Ctr, Dept Med, Div Gastroenterol, Portland, OR 97207 USA. RP Lieberman, D (reprint author), Oregon Hlth Sci Univ, Portland VA Med Ctr, Dept Med, Div Gastroenterol, P3-G1,POB 1034, Portland, OR 97207 USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAR PY 2001 VL 120 IS 4 BP 1043 EP 1046 DI 10.1053/gast.2001.23055 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 407ZP UT WOS:000167302300034 PM 11231960 ER PT J AU Schwartz, JL Jordan, R Liber, H Murnane, JP Evans, HH AF Schwartz, JL Jordan, R Liber, H Murnane, JP Evans, HH TI TP53-dependent chromosome instability is associated with transient reductions in telomere length in immortal telomerase-positive cell lines SO GENES CHROMOSOMES & CANCER LA English DT Article ID WILD-TYPE P53; HUMAN FIBROBLASTS; G(1) ARREST; GENOMIC INSTABILITY; SPINDLE CHECKPOINT; GENE AMPLIFICATION; MUTANT P53; CYCLE; SENESCENCE; ABERRATIONS AB Telomere shortening in telomerase-negative somatic cells leads to the activation of the TP53 protein and the elimination of potentially unstable cells. We examined the effect of TP53 gene expression on both telomere metabolism and chromosome stability in immortal, telomerase-positive cell lines. Telomere length, telomerase activity, and chromosome instability were measured in multiple clones isolated from three related human B-lymphoblast cell lines that vary in TP53 expression; TK6 cells express wild-type TP53, WTKI cells overexpress a mutant form of TP53, and NH32 cells express no TP53 protein. Clonal variations in both telomere length and chromosome stability were observed, and shorter telomeres were associated with higher levels of chromosome instability. The shortest telomeres were found in WTKI- and NH32-derived cells, and these cells had 5- to 10-fold higher levels of chromosome instability. The primary marker of instability was the presence of dicentric chromosomes. Aneuploidy and other stable chromosome alterations were also found in clones showing high levels of dicentrics. Polyploidy was found only in WTKI-derived cells. Both telomere length and chromosome instability fluctuated in the different cell populations with time in culture, presumably as unstable cells and cells with short telomeres were eliminated from the growing population. Our results suggest that transient reductions in telomere lengths may be common in immortal cell lines and that these alterations in telomere metabolism can have a profound effect on chromosome stability. (C) 2001 Wiley-Liss. Inc. C1 Univ Washington, Dept Radiat Oncol, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Univ San Francisco, Dept Radiat Oncol, San Francisco, CA 94117 USA. Case Western Reserve Univ, Dept Radiat Oncol, Cleveland, OH 44106 USA. RP Schwartz, JL (reprint author), Univ Washington, Dept Radiat Oncol, Boc 356069, Seattle, WA 98195 USA. FU NCI NIH HHS [CA-73931, CA49696, CA69044] NR 48 TC 19 Z9 21 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAR PY 2001 VL 30 IS 3 BP 236 EP 244 DI 10.1002/1098-2264(2000)9999:9999<::AID-GCC1085>3.0.CO;2-G PG 9 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 400BT UT WOS:000166849300003 PM 11170280 ER PT J AU Allen, DR van Praag, H Ray, J Weaver, Z Winrow, CJ Carter, TA Braquet, R Harrington, E Ried, T Brown, KD Gage, FH Barlow, C AF Allen, DR van Praag, H Ray, J Weaver, Z Winrow, CJ Carter, TA Braquet, R Harrington, E Ried, T Brown, KD Gage, FH Barlow, C TI Ataxia telangiectasia mutated is essential during adult neurogenesis SO GENES & DEVELOPMENT LA English DT Article DE neural progenitor; DNA repair; neuron; oligodendrocyte; astrocyte; running ID ATM-DEPENDENT PHOSPHORYLATION; CENTRAL-NERVOUS-SYSTEM; DOUBLE-STRAND BREAKS; NEURAL STEM-CELLS; DNA-LIGASE-IV; GENE-PRODUCT; DEFICIENT MICE; DENTATE GYRUS; S-PHASE; PROTEIN AB Ataxia telangiectasia (A-T) is an autosomal recessive disease characterized by normal brain development followed by progressive neurodegeneration. The gene mutated in A-T (ATM) is a serine protein kinase implicated in cell cycle regulation and DNA repair. The role of ATM in the brain and the consequences of its loss on neuronal survival remain unclear. We studied the role of ATM in adult neural progenitor cells in vivo and in vitro to define the role of ATM in dividing and postmitotic neural cells from Atm-deficient (Atm(-/-)) mice in a physiologic context. We demonstrate that ATM is an abundant protein in dividing neural progenitor cells but is markedly down-regulated as cells differentiate. In the absence of ATM, neural progenitor cells of the dentate gyrus show abnormally high rates of proliferation and genomic instability. Atm(-/-) cells in vivo, and in cell culture, show a blunted response to environmental stimuli that promote neural progenitor cell proliferation, survival, and differentiation along a neuronal lineage. This study defines a role for ATM during the process of neurogenesis, demonstrates that ATM is required for normal cell fate determination and neuronal survival both in vitro and in vivo, and points to a mechanism for neuronal cell loss in progressive neurodegenerative diseases. C1 Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA. NCI, Dept Genet, Div Clin Sci, NIH, Bethesda, MD 20892 USA. Louisiana State Univ, Med Ctr, Dept Biochem & Mol Biol, New Orleans, LA 70112 USA. Louisiana State Univ, Med Ctr, Stanley S Scott Canc Ctr, New Orleans, LA 70112 USA. Massachusetts Gen Hosp, Mol Oncol Lab, Charlestown, MA 01029 USA. RP Barlow, C (reprint author), Salk Inst Biol Studies, Genet Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. RI Winrow, Christopher/K-1864-2014; van Praag, Henriette/F-3939-2015 OI van Praag, Henriette/0000-0002-5727-434X FU NINDS NIH HHS [N01-NS-6-2348]; PHS HHS [A606088] NR 45 TC 116 Z9 121 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAR 1 PY 2001 VL 15 IS 5 BP 554 EP 566 DI 10.1101/gad.869001 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 410AZ UT WOS:000167419000006 PM 11238376 ER PT J AU Sif, S Saurin, AJ Imbalzano, AN Kingston, RE AF Sif, S Saurin, AJ Imbalzano, AN Kingston, RE TI Purification and characterization of mSin3A-containing Brg1 and hBrm chromatin remodeling complexes SO GENES & DEVELOPMENT LA English DT Article DE chromatin remodeling; ATPase activity; histone deacetylases; Sin3 repressor complex; human SWI/SNF complexes ID YEAST SWI/SNF COMPLEX; SWI-SNF COMPLEX; HISTONE DEACETYLASE; CELL-CYCLE; TRANSCRIPTIONAL REPRESSION; GLUCOCORTICOID RECEPTOR; RETINOBLASTOMA PROTEIN; NUCLEOSOME DISRUPTION; ACTIVATOR BINDING; DNA AB Alteration of nucleosomes by ATP-dependent remodeling complexes represents a critical step in the regulation of transcription. The human SWI/SNF (hSWI/SNF) family is composed of complexes that contain either Brg1 or hBrm as the central ATPase; however, these separate complexes have not been compared functionally. Here we describe the establishment of cell lines that express epitolpe-tagged Brg1 and hBrm and a characterization of the complexes associated with these two ATPases. We show that Brg1 fractionates into two complexes that differ in activity and subunit composition, whereas hBrm is found in one complex with lower activity than the Brg1 complexes. These three complexes can remodel nucleosomal arrays, increase restriction enzyme accessibility, and hydrolyze ATP in a DNA-dependent manner. The three complexes differ markedly in their ability to remodel mononucleosomal core particles. We also show that the hBrm complex and one of the Brg1 complexes contain components of the mammalian Sin3 (mSin3) complex. In addition, we have found that Brg1, hBrm, and BAF155 can interact specifically with mSin3A in vitro, showing a direct association of hSWI/SNF complexes with proteins involved in gene repression. These unexpected functional characteristics indicate that these hSWI/SNF complexes play diverse regulatory roles. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Ohio State Univ, Coll Med, Dept Mol & Cellular Biochem, Columbus, OH 43210 USA. Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01655 USA. RP Sif, S (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. FU NCI NIH HHS [K01 CA089854, 1 K01 CA89854-01]; NIGMS NIH HHS [GM48405, R01 GM048405, R37 GM048405] NR 54 TC 206 Z9 213 U1 1 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAR 1 PY 2001 VL 15 IS 5 BP 603 EP 618 DI 10.1101/gad.872801 PG 16 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 410AZ UT WOS:000167419000010 PM 11238380 ER PT J AU Sarkar, S Thompson, DG Woolf, CJ Hobson, A Aziz, Q AF Sarkar, S Thompson, DG Woolf, CJ Hobson, A Aziz, Q TI Wind-up in the human viscera: Central sensitization contributes to visceral pain SO GUT LA English DT Meeting Abstract C1 Hope Hosp, Dept Gastrointestinal Sci, Salford, Lancs, England. Massachusetts Gen Hosp, Dept Anaesthesia & Critical Care, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD MAR PY 2001 VL 48 SU 1 MA 014 BP A4 EP A4 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 408PN UT WOS:000167334700015 ER PT J AU Lee, CY Rosowski, JJ AF Lee, CY Rosowski, JJ TI Effects of middle-ear static pressure on pars tensa and pars flaccida of gerbil ears SO HEARING RESEARCH LA English DT Article DE tympanic membrane; tympanometry; laser Doppler velocimetry ID SOUND-POWER COLLECTION; TYMPANIC MEMBRANE; MONGOLIAN GERBIL; MERIONES-UNGUICULATUS; AUDITORY PERIPHERY; MECHANICS; TYMPANOMETRY; VOLUME; IMPEDANCE AB It has long been known that static pressure affects middle-ear function and conventional tympanometry uses variations in static pressure for clinical assessment of the middle ear. However, conventional tympanometry treats the entire tympanic membrane as a uniform interface between the external and middle ear and does not differentiate the behavior of the two components of the tympanic membrane, pars tensa and pars flaccida. To analyze separately the different acoustic behavior of these two tympanic membrane components, laser Doppler velocimetry is used to determine the motion of each of these two structures. The velocities of points near the center of p. tensa and p. flaccida in response to the external-ear sound pressure at different middle-ear static pressures were measured in nine gerbil ears. The effect of middle-ear static pressure on the acoustic response of both structures is similar in that nan-zero middle-ear static pressures generally reduce the velocity magnitude of the two membrane components in response to sound stimuli. Middle-ear under-pressures tend to reduce the velocity magnitude more than do middle-ear over-pressures. The acoustic stiffness and inertance of both p. tensa and p. flaccida are altered by static pressure, as shown in our results as changes of transferfunction phase angle. Compared to p. tense, p. flaccida showed larger reductions in the velocity magnitude to small over- and under-pressures near the ambient middle-ear pressure. This higher pressure sensitivity of p. flaccida has been found in all ears and may link the previously proposed middle-ear pressure regulating and the acoustic shunting functions of p. flaccida. We also describe, in both p. tensa and p. flaccida, a frequency dependence of the velocity measurements, hysteresis of velocity magnitude between different directions of pressure sweep and asymmetrical effects of over- and under-pressure on the point velocity. (C) 2001 Published by Elsevier Science B.V. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Natl Taiwan Univ Hosp, Dept Otorhinolaryngol, Taipei, Taiwan. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. MIT, Harvard MIT Div Hlth Sci & Technol, Speech & Hearing Sci Program, Cambridge, MA 02139 USA. RP Rosowski, JJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 38 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD MAR PY 2001 VL 153 IS 1-2 BP 146 EP 163 DI 10.1016/S0378-5955(00)00269-0 PG 18 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 408XR UT WOS:000167352700015 PM 11223305 ER PT J AU Griffiths, RI Rabeneck, L Guzman, G Cromwell, DM Strauss, MJ Robinson, JW Winston, B Li, T Graham, DY AF Griffiths, RI Rabeneck, L Guzman, G Cromwell, DM Strauss, MJ Robinson, JW Winston, B Li, T Graham, DY TI Costs of Managing Helicobacter pylori-infected ulcer patients after initial therapy SO HELICOBACTER LA English DT Article ID DUODENAL-ULCER; UNITED-STATES; ERADICATION; RECURRENCE; DYSPEPSIA; ENDOSCOPY; METRONIDAZOLE; OMEPRAZOLE; MANAGEMENT AB Background. The objective of this research was to evaluate the outcomes and costs of alternative approaches to managing patients previously treated for peptic ulcer disease and Helicobacter pylori infection. Materials and Methods. A decision-analytic model was used to compare (1a) urease breath testing (UBT) for assessment of H. pylori status versus (1b) observation without further testing or treatment, among patients who were symptom-free following initial antimicrobial and antisecretory therapy for endoscopically demonstrated ulcer and H. pylori infection; and (2a) UBT versus (2b) repeat endoscopy with H. pylori testing, and versus (2c) repeat antimicrobial and antisecretory therapy without further testing, among patients who remained symptomatic following initial therapy. Results, Among patients who were symptom free after initial therapy, 6.1% receiving UBT had symptomatic ulcer at one year, compared to 18.2% of those simply observed. The expected first-year cost per symptom-free patient following initial therapy was $591 for UBT compared to $480 for observation. Among patients with persistent symptoms after initial therapy, 21% receiving repeat therapy had symptomatic ulcer at one year, compared to 23.8% receiving repeat endoscopy, and 23.3% receiving UBT. Corresponding medical costs per patient were, respectively, $766, $1787 and $1122. Conclusions. The optimal approach to managing patients following initial treatment for ulcer and H. pylori infection depends on symptom status following initial therapy. For symptomatic patients, the preferred approach is to prescribe a repeat course of antimicrobial and antisecretory therapy. For patients without symptoms following initial therapy, UBT is the preferred approach because it is associated with a threefold lower risk of symptomatic ulcer at one year, although it costs an additional $110 per patient, compared with observation. C1 Project Hope Ctr Hlth Affairs, Bethesda, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Dept Vet Affairs Med Ctr, Houston, TX USA. VA Hlth Serv Res & Dev HSR & D Field Program, Houston, TX USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Covance Hlth Econ & Outcomes Serv Inc, Washington, DC USA. St Marks Hlth Care Fdn, Midvale, UT USA. Kaiser Permanente, Springfield, VA USA. Spring Valley Primary Care, Washington, DC USA. RP Rabeneck, L (reprint author), Vet Affairs Med Ctr, 111D,2002 Holcombe Blvd, Houston, TX 77030 USA. NR 25 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD MAR PY 2001 VL 6 IS 1 BP 66 EP 76 DI 10.1046/j.1523-5378.2001.00008.x PG 11 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 425DG UT WOS:000168272600009 PM 11328368 ER PT J AU Goldberg, SN Gazelle, GS AF Goldberg, SN Gazelle, GS TI Radiofrequency tissue ablation: Physical principles and techniques for increasing coagulation necrosis SO HEPATO-GASTROENTEROLOGY LA English DT Review DE radiofrequency; minimally invasive therapy; tumor ablation ID INTERSTITIAL THERMAL ABLATION; LIVER METASTASES; CARDIAC-ARRHYTHMIAS; CATHETER ABLATION; NEEDLE ELECTRODE; TUMOR ABLATION; BLOOD-FLOW; FOLLOW-UP; IN-VIVO; TEMPERATURE AB Radiofrequency tumor ablation has been demonstrated as a reliable method for creating thermally-induced coagulation necrosis using either a percutaneous approach with image-guidance or direct surgical placement of thin electrodes into tissues to be treated. Early clinical trials with this technology have studied the treatment of hepatic, cerebral, and bony malignancies. The extent of coagulation necrosis induced with conventional monopolar radiofrequency electrodes is dependent on overall energy deposition, the duration of radiofrequency application, and radiofrequency electrode tip length and gauge. This article will discuss these technical considerations with the goal of defining optimal parameters for radiofrequency ablation. Strategies to further increase induced coagulation necrosis including: multiprobe and bipolar arrays, and internally-cooled radiofrequency electrodes, with or without pulsed-radiofrequency or cluster technique will be presented. The development and laboratory results for many of these radiofrequency techniques and potential biophysical limitations to radiofrequency induced coagulation, such as perfusion mediated tissue cooling (vascular flow) will likewise be discussed. C1 Beth Israel Deaconess Med Ctr, Dept Radiol, Minimally Invas Therapeut Lab, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Radiol, DATA Grp, Boston, MA 02114 USA. RP Beth Israel Deaconess Med Ctr, Dept Radiol, Minimally Invas Therapeut Lab, 330 Brookline Ave, Boston, MA 02215 USA. EM sgoldber@caregroup.harvard.edu NR 42 TC 89 Z9 96 U1 0 U2 4 PU H G E UPDATE MEDICAL PUBLISHING S A PI ATHENS PA PO BOX 17257, ATHENS GR-10024, GREECE SN 0172-6390 J9 HEPATO-GASTROENTEROL JI Hepato-Gastroenterol. PD MAR-APR PY 2001 VL 48 IS 38 BP 359 EP 367 PG 9 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 425QU UT WOS:000168303500015 PM 11379309 ER PT J AU Stuyver, LJ Locarnini, SA Lok, A Richman, DD Carman, WF Dienstag, JL Schinazi, RF AF Stuyver, LJ Locarnini, SA Lok, A Richman, DD Carman, WF Dienstag, JL Schinazi, RF CA HEP DART Int Comm TI Nomenclature for antiviral-resistant human hepatitis B virus mutations in the polymerase region SO HEPATOLOGY LA English DT Article ID INDUCED ESCAPE MUTANT; NUCLEOTIDE-SEQUENCE; REVERSE-TRANSCRIPTASE; LIVER-TRANSPLANTATION; PHYLOGENETIC RELATEDNESS; GENETIC CLASSIFICATION; ADEFOVIR DIPIVOXIL; G->A HYPERMUTATION; INFECTED PATIENTS; TYROSINE RESIDUE AB There is currently no universally accepted numbering convention for the antiviral drug-related resistance mutations in the reverse transcriptase (rt) domain of the human hepatitis B virus (HBV) polymerase. The published inconsistencies have resulted from different HBV genotypes. A standardized numbering system for HBV polymerase is proposed. The new system is based on functional observations of HBV surface gene proteins (preS1, preS2, and HBsAg) and on the current convention used for human immunodeficiency virus type 1 (HIV-1) polymerase proteins (protease, rt, and integrase), in which the amino acid numbering restarts at the first codon position of each domain. The HBV polymerase protein can be divided into 4 domains (terminal protein, spacer, rt, ribonuclease H) and each of these can be numbered separately. In this proposal, the HBV rt domain starts with the highly conserved EDWGPCDEHG motif, contains 344 amino acids, and the lamivudine-related resistance mutations are found at amino acid rtL180M (previously amino acid 528, 526, 515, or 525) and rtM204V/I (previously 552, 550, 539, or 549). The new consensus rt domain numbering system is genotype independent and allows investigators to number any previously and newly discovered antiviral-related amino acid change in a standardized manner. C1 Vet Affairs Med Ctr, Decatur, GA 30033 USA. Pharmasset Inc, Tucker, GA USA. Victorian Infect Dis Reference Lab, N Melbourne, Vic, Australia. Univ Michigan, Med Ctr, Ann Arbor, MI USA. San Diego Vet Affairs Med Ctr, La Jolla, CA USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Univ Glasgow, Div Virol, Glasgow, Lanark, Scotland. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Emory Univ, Sch Med, Dept Pediat, Decatur, GA 30033 USA. RP Schinazi, RF (reprint author), Vet Affairs Med Ctr, 1670 Clairmont Rd, Decatur, GA 30033 USA. RI Lok, Anna /B-8292-2009; Schinazi, Raymond/B-6777-2017; OI Niesters, Hubert/0000-0002-1758-0430; Poynard, Thierry/0000-0002-2050-640X; Yang, Shuman/0000-0002-9638-0890 FU NIAID NIH HHS [AI27670, AI388858, AI41980] NR 70 TC 285 Z9 314 U1 0 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAR PY 2001 VL 33 IS 3 BP 751 EP 757 DI 10.1053/jhep.2000.22166 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 407LZ UT WOS:000167274200032 PM 11230757 ER PT J AU Krebs, DE McGibbon, CA Goldvasser, D AF Krebs, DE McGibbon, CA Goldvasser, D TI Analysis of postural perturbation responses SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Article DE ataxia; center-of-pressure (COP); cerebellar rehabilitation; damping; perturbation ID GALVANIC VESTIBULAR STIMULATION; REHABILITATION; BALANCE; STANCE AB People with cerebellar ataxia lack lower limb coordination and dissipate sway motion slowly and inefficiently after a posture perturbation. We report a practical and low-cost "human resonance frequency test" for both laboratory and clinical use to quantify progress in balance and cerebellar rehabilitation. We assumed that the center-of-pressure (COP) oscillation rate of decay following a standing posture perturbation is directly related to resonance frequency; a more rapidly dissipating COP oscillation about the position of equilibrium indicates, by definition, more efficient postural control. We hypothesized that following successful physical rehabilitation, people with cerebellar degeneration will have a faster rate of decay of the COP response to an external perturbation, Because the COP is modulated by a synergy of trunk and lower limb motion strategies, COP decay rate may be a useful measure of lower limb coordination in people with cerebellar ataxia, The method was applied to three subjects with cerebellar ataxia before and after rehabilitation; there was good agreement between the calculated COP decay rate and conventionally used gait stability parameters providing pilot data for this simple approach. C1 Massachusetts Gen Hosp, Biomot Lab, MGH Inst Hlth Profess, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Krebs, DE (reprint author), Massachusetts Gen Hosp, Biomot Lab, MGH Inst Hlth Profess, Boston, MA 02114 USA. FU NIA NIH HHS [R01AG11255]; PHS HHS [H133G60045] NR 17 TC 9 Z9 9 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 1534-4320 J9 IEEE T NEUR SYS REH JI IEEE Trans. Neural Syst. Rehabil. Eng. PD MAR PY 2001 VL 9 IS 1 BP 76 EP 80 DI 10.1109/7333.918279 PG 5 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA 453ZB UT WOS:000169947100010 PM 11482366 ER PT J AU van der Kouwe, AJW Wang, DL Brown, GJ AF van der Kouwe, AJW Wang, DL Brown, GJ TI A comparison of auditory and blind separation techniques for speech segregation SO IEEE TRANSACTIONS ON SPEECH AND AUDIO PROCESSING LA English DT Article DE auditory scene analysis; blind source separation; computational auditory scene analysis (CASA); oscillatory correlation; speech segregation ID INDEPENDENT COMPONENT ANALYSIS; SIGNALS AB A fundamental problem in auditory and speech processing is the segregation of speech from concurrent sounds. This problem has been a focus of study in computational auditory scene analysis (CASA), and it has also been recently investigated from the perspective of blind source separation. Using a standard corpus of voiced speech mixed with interfering sounds, we report a comparison between CASA and blind source separation techniques, which have been developed independently. Our comparison reveals that they perform well under very different conditions, A number of conclusions are drawn with respect to their relative strengths and weaknesses in speech segregation applications as well as in modeling auditory function. C1 Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. RP van der Kouwe, AJW (reprint author), Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. EM dwang@cis.ohio-state.edu OI Brown, Guy/0000-0001-8565-5476 NR 28 TC 23 Z9 23 U1 0 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1063-6676 J9 IEEE T SPEECH AUDI P JI IEEE Trans. Speech Audio Process. PD MAR PY 2001 VL 9 IS 3 BP 189 EP 195 DI 10.1109/89.905993 PG 7 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 407UF UT WOS:000167288600001 ER PT J AU Muder, RR AF Muder, RR TI Frequency of intravenous administration set changes and bacteremia: Defining the risk SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Editorial Material ID INTERVALS; PREVENTION; INFECTIONS; 48-HOUR C1 Vet Affairs Pittsburgh Healthcare Syst, Infect Dis Sect, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Muder, RR (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Infect Dis Sect, Univ Dr C, Pittsburgh, PA 15240 USA. NR 11 TC 3 Z9 3 U1 1 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD MAR PY 2001 VL 22 IS 3 BP 134 EP 135 DI 10.1086/501878 PG 2 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 413MV UT WOS:000167616700002 PM 11310689 ER PT J AU Neuzil, KM Griffin, MR Schaffner, W AF Neuzil, KM Griffin, MR Schaffner, W TI Influenza vaccine: Issues and opportunities SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; IMMUNODEFICIENCY-VIRUS INFECTION; PLACEBO-CONTROLLED TRIAL; HEALTH-CARE WORKERS; LONG-TERM-CARE; YOUNG-CHILDREN; DOUBLE-BLIND; RESPIRATORY-DISEASE; ANTIBODY-RESPONSE; NATURAL INFECTION AB Several recent developments offer opportunities to improve the diagnosis, treatment, and prevention of influenza. Rapid diagnostic tests assist in selecting patients for antiviral therapy and avoid some antibiotic use. The neuraminidase inhibitors now offer therapeutic options with potentially fewer side effects than the traditional drugs, albeit at greater cost. Inactivated influenza vaccine is now recommended annually for all persons aged 50 and older and younger adults and children (aged 6 months and older) who have underlying risk factors for the severe complications of influenza. This includes pregnant women who are in their second or third trimesters during influenza season. C1 Vanderbilt Univ, Sch Med, Dept Prevent Med, Nashville, TN 37232 USA. Univ Washington, Sch Med, Div Infect Dis, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Vanderbilt Univ, Sch Med, Div Gen Internal Med, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Div Infect Dis, Nashville, TN 37232 USA. RP Schaffner, W (reprint author), Vanderbilt Univ, Sch Med, Dept Prevent Med, A-1124 Med Ctr N, Nashville, TN 37232 USA. NR 84 TC 16 Z9 16 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD MAR PY 2001 VL 15 IS 1 BP 123 EP + DI 10.1016/S0891-5520(05)70271-3 PG 20 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 418HY UT WOS:000167885900009 PM 11301811 ER PT J AU Wong, IHN Yeo, W Chan, AT Johnson, PJ AF Wong, IHN Yeo, W Chan, AT Johnson, PJ TI Quantitative correlation of cytokeratin 19 mRNA level in peripheral blood with disease stage and metastasis in breast cancer patients: potential prognostic implications SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE semiquantitative RT-PCR; CK19 mRNA; disease stage; metastasis; survival ID POLYMERASE-CHAIN-REACTION; CIRCULATING TUMOR-CELLS; P15 PROMOTER METHYLATION; REVERSE-TRANSCRIPTASE; MESSENGER-RNA; HEPATOCELLULAR-CARCINOMA; BONE-MARROW; COLORECTAL-CANCER; ANTIGEN NCA; GENE FAMILY AB Mortality among patients with breast cancer (BC) is mainly caused by metastasis. We determined the circulating tumor burden in BC patients by semiquantitative reverse transcription-polymerase chain reaction using carcinoembryonic antigen (CEA) and cytokeratin 19 (CK19) mRNAs as molecular markers. We distinguished the mRNA levels in circulation between BC patients and healthy controls with reference to a BC-derived cell line, SK-BR-3. We prospectively analyzed peripheral, blood samples from 33 BC patients and 26 healthy controls. We found CEA mRNA in 97% of patients and 92% of normal controls, and CK19 mRNA in 72% of patients and 19% of controls. CEA and CK19 mRNAs in normal peripheral blood were most likely derived from illegitimate transcription. In 10 patients, of whom 9 (90%) developed systemic metastases, the upper limit of CK19 mRNA of normal controls was exceeded. As compared with normal controls, significantly elevated CK19 mRNA levels in the patients appeared to originate from circulating malignant BC cells (P < 0.0001). It was clinically significant that the mean CK19 mRNA level increased with advancing disease stage. Of prognostic value, we report for the first time that BC patients with CK19 mRNA elevation had notably shorter (3-year reduction) overall survival than patients with normal CK19 mRNA levels (P = 0.045). Quantification of CK19 mRNA may prove useful for cancer staging, disease monitoring and prognostic assessment among BC patients. C1 Chinese Univ Hong Kong, Prince Wales Hosp, Dept Anat & Cellular Pathol, Shatin, Hong Kong, Peoples R China. Chinese Univ Hong Kong, Prince Wales Hosp, Dept Clin Oncol, Shatin, Hong Kong, Peoples R China. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Wong, IHN (reprint author), Univ Hong Kong, Fac Med, Dept Biochem, Li Shu Fan Bldg,5 Sassoon Rd, Hong Kong, Hong Kong, Peoples R China. NR 31 TC 11 Z9 13 U1 0 U2 2 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAR PY 2001 VL 18 IS 3 BP 633 EP 638 PG 6 WC Oncology SC Oncology GA 402YY UT WOS:000167016800028 PM 11179498 ER PT J AU Lee, AK Schultz, D Renshaw, AA Richie, JP D'Amico, AV AF Lee, AK Schultz, D Renshaw, AA Richie, JP D'Amico, AV TI Optimizing patient selection for prostate monotherapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate cancer; biopsy Gleason score; prostatectomy gleason score; prostate-specific antigen; outcome ID SYSTEMATIC SEXTANT BIOPSIES; RADICAL PROSTATECTOMY; CANCER; ANTIGEN; PREDICTION; CARCINOMA; DISEASE; BRACHYTHERAPY; ULTRASOUND; RADIATION AB Purpose: Patients at low risk for prostate-specific antigen (PSA) failure following definitive local therapy are those with PSA of 10 or less, biopsy Gleason Score of 6 or less, acid 1992 American Joint Committee on Cancer (AJCC) clinical Stage T1c or T2a, However, low-risk patients managed with radical prostatectomy and found to have prostatectomy Gleason score greater than or equal to 3+4 have a less favorable PSA outcome when compared to patients with prostatectomy Gleason score less than or equal to 3+3, This study was performed to determine whether the percentage of positive prostate biopsy cores could predict upgrading from a biopsy Gleason score of 6 or less to a prostatectomy Gleason score greater than or equal to 3+4 in low-risk patients to optimize selection for prostate only radiation therapy. Methods and Materials: Concordance testing of the biopsy Gleason score and the primary and secondary prostatectomy Gleason grades was performed in 427 prostate cancer patients treated with radical prostatectomy and at low risk for PSA failure. Logistic regression multivariable analysis was performed to test the ability of the established prognostic factors and the percentage of positive prostate biopsies (<34%, 34-50%, >50%) to predict for upgrading from biopsy Gleason score of 6 or less prostatectomy Gleason score 3+4, PSA failure-free survival was reported using the actuarial method of Kaplan and Meier and comparisons were made using a log-rank test, Results: Twenty-nine percent of the 427 study patients were upgraded from a biopsy Gleason score of 6 or less to a prostatectomy Gleason score greater than or equal to 3+4, The presence of greater than 50% positive biopsies was the only significant factor for predicting the upgrading from biopsy Gleason score of 6 or less to prostatectomy Gleason score > 3+4 on logistic regression multivariable analysis with the variables treated as continuous and categorical. Specifically, upgrading occurred in 26% vs. 59% of patients with 50% or less vs. greater than 50% positive biopsies, respectively. This translated into a 5-year PSA failure-free survival which was significantly higher (92% vs, 62%,p = 0.00001) for men with 50% or less vs. greater than 50% positive prostate biopsies, respectively. Conclusion: The presence of greater than 50% positive biopsies was associated with higher rates of pathologic upgrading which translated into lower 5-year PSA failure-free survival following radical prostatectomy (RP), Therefore, the percentage of positive biopsies may be useful in optimizing the selection of low-risk patients for prostate only radiation therapy such as external beam radiation or implant monotherapy, (C) 2001 Elsevier Science Inc. C1 Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02215 USA. Millersville Univ, Dept Math, Millersville, PA 17551 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lee, AK (reprint author), Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, 330 Brookline Ave,5th Floor, Boston, MA 02215 USA. NR 22 TC 19 Z9 20 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 1 PY 2001 VL 49 IS 3 BP 673 EP 677 DI 10.1016/S0360-3016(00)01421-8 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 400XK UT WOS:000166897800009 PM 11172948 ER PT J AU Sippel, KC Jain, S Azar, DT AF Sippel, KC Jain, S Azar, DT TI Monovision achieved with excimer laser refractive surgery SO INTERNATIONAL OPHTHALMOLOGY CLINICS LA English DT Article ID BIFOCAL CONTACT-LENSES; PHOTOREFRACTIVE KERATECTOMY; VISUAL-ACUITY; TASK-PERFORMANCE; SUPPRESSION C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Sippel, KC (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY10101] NR 40 TC 19 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-8167 J9 INT OPHTHALMOL CLIN JI Int. Ophthalmol. Clin. PD SPR PY 2001 VL 41 IS 2 BP 91 EP 101 DI 10.1097/00004397-200104000-00009 PG 11 WC Ophthalmology SC Ophthalmology GA 424GM UT WOS:000168224500008 PM 11290924 ER PT J AU Wetzel, RK Sweadner, KJ AF Wetzel, RK Sweadner, KJ TI Immunocytochemical localization of NaK-ATPase isoforms in the rat and mouse ocular ciliary epithelium SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID DIFFERENTIAL GENE-EXPRESSION; ALPHA-SUBUNIT ISOFORMS; PROTEIN-KINASE-C; AQUEOUS-HUMOR; NA,K-ATPASE ALPHA; ADENOSINE TRIPHOSPHATASE; HELA-CELLS; SODIUM; SECRETION; MECHANISM AB PURPOSE. Ion gradients established by NaK-adenosine triphosphatase (ATPase) in the ocular ciliary epithelium (CE) contribute to the production of aqueous humor. Modulation of NaK-ATPase activity in the CE may alter aqueous inflow, aqueous turnover, and intraocular pressure. To understand the role of NAK-ATPase, it is necessary to examine the distribution of NaK-ATPase subunit isoforms within the epithelium. METHODS. Isoform-specific antibodies and scanning laser con focal microscopy were used to localize NaK-ATPase subunit isoforms in the CE of the mouse and rat. RESULTS. The nonpigmented epithelium (NPE) expressed alpha2 and beta3 at very high levels on its basolateral surface, and al and beta2 at much lower levels. The pigmented epithelium (PE) expressed alpha1 and beta1 subunits on its basolateral surface along its entire length, whereas alpha3 was expressed in the pars plana only. The distribution and apparent expression levels of isoforms were similar for mouse and rat, with only minor discrepancies, most likely caused by antibody sensitivity. CONCLUSIONS. The results indicate that sodium pumps in the NPE are primarily composed of alpha2 and beta3, whereas those in the PE are alpha1 and beta1. This specialization in isoform expression implies that NaK-ATPase has distinct physiological functions in the two epithelia and that its activity is likely to be regulated by different mechanisms. C1 Massachusetts Gen Hosp, Lab Membrane Biol, Ctr Neurosci, Charlestown, MA 02129 USA. RP Sweadner, KJ (reprint author), Massachusetts Gen Hosp, Lab Membrane Biol, Ctr Neurosci, 149 13th St,149-6118, Charlestown, MA 02129 USA. EM sweadner@helix.mgh.harvard.edu FU NINDS NIH HHS [5R01 NS27653] NR 34 TC 18 Z9 19 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2001 VL 42 IS 3 BP 763 EP 769 PG 7 WC Ophthalmology SC Ophthalmology GA 406GM UT WOS:000167206600033 PM 11222539 ER PT J AU Xu, QW Qaum, T Adamis, AP AF Xu, QW Qaum, T Adamis, AP TI Sensitive blood-retinal barrier breakdown quantitation using Evans blue SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ENHANCED VASCULAR-PERMEABILITY; MURINE CEREBRAL MALARIA; GUINEA-PIG CONJUNCTIVA; PLASMA LEAKAGE; RAT AIRWAYS; ADHESION; INFLAMMATION; INHIBITION; BRADYKININ; PREVENTION AB PURPOSE. This study investigated whether a nonradioactive dye, Evans blue, can be adapted as a safe alternative to the isotope-dilution method for quantitating blood-retinal barrier breakdown. METHODS. Blood-retinal barrier breakdown was induced in rats with vascular endothelial growth factor (VEGF) or through the induction of diabetes. After allowing Evans blue to circulate in the vasculature, the dye was cleared from the bloodstream with saline, citrate, or citrate-buffered paraformaldehyde, and the efficacies of the perfusion solutions were compared. Extravasated dye was detected at 620 nm and was normalized against the time-averaged Evans blue plasma concentration, the circulation time, and also against wet and dry retina weights. RESULTS. Evans blue leakage from retinas treated with VEGF was 4.0-fold higher than that of contralateral untreated eyes (n = 6 rats, P < 0.05). Retinal Evans blue leakage of eyes from 1-week diabetic animals (n = 11 retinas) was 1.7-fold higher (P < .0.05) than that of nondiabetic controls (n = 10 retinas). Intra-animal, inter-retina weights showed significantly less variability (P < 0.05) with the use of dry weights (11.2%, n = 74 retina pairs) than with wet weights (20.5%, n = 93 retina pairs). CONCLUSIONS. The Evans blue dye technique can be modified to be as sensitive and quantitative as the isotope-dilution method for measuring blood-retinal barrier breakdown. The advantages of the Evans blue technique are its safety, relative simplicity, and economy. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Childrens Hosp,Dept Surg Res, Boston, MA 02114 USA. Affiliated Hosp Jining Med Coll, Dept Ophthalmol, Jining, Shandong, Peoples R China. RP Adamis, AP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY11627, EY12611] NR 32 TC 161 Z9 190 U1 0 U2 8 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2001 VL 42 IS 3 BP 789 EP 794 PG 6 WC Ophthalmology SC Ophthalmology GA 406GM UT WOS:000167206600036 PM 11222542 ER PT J AU Bush, RK Portnoy, JM AF Bush, RK Portnoy, JM TI The role and abatement of fungal allergens in allergic diseases SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE fungi; allergic disease; asthma; environment; exposure; abatement ID NUTRITION EXAMINATION SURVEY; MAJOR ALTERNARIA ALLERGEN; SICK BUILDING SYNDROME; 2ND NATIONAL-HEALTH; SCHOOL-AGE-CHILDREN; DUST MITE; INDOOR AIR; RESIDENTIAL CHARACTERISTICS; ENVIRONMENTAL-FACTORS; RESPIRATORY SYMPTOMS AB Sensitivity to a variety of fungi is known to be a factor in allergic rhinitis and asthma. In this review methods for measuring exposure to fungi in the indoor environment are evaluated. A variety of markers for the presence of fungi are also described in addition to their known relationship to either toxic or adverse immunologic effects. Key studies documenting the clinical effects of different types of fungi are also reviewed, as well as a description of abatement methods that either have been successful or need further investigation. Although many studies have shown an association between exposure to fungi and allergic disease, in many cases a direct cause-and-effect relationship has not been established. Improved knowledge of the epidemiology and mechanisms behind fungal-induced human disease will hopefully establish this causal link and suggest methods for reducing morbidity. C1 Univ Wisconsin, William S Middleton Mem Vet Adm Hosp, Dept Med, Madison, WI 53705 USA. Childrens Mercy Hosp, Sect Allergy Immunol, Kansas City, MO 64108 USA. RP Bush, RK (reprint author), Univ Wisconsin, William S Middleton Mem Vet Adm Hosp, Dept Med, 2500 OVerlook Terrace, Madison, WI 53705 USA. NR 94 TC 78 Z9 81 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAR PY 2001 VL 107 IS 3 SU S BP S430 EP S440 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA 418KR UT WOS:000167891800005 PM 11242604 ER PT J AU Eggleston, PA Bush, RK AF Eggleston, PA Bush, RK TI Environmental allergen avoidance: An overview SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article C1 Univ Wisconsin, William S Middleton Mem Vet Adm Hosp, Dept Med, Madison, WI 53705 USA. Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21218 USA. RP Bush, RK (reprint author), Univ Wisconsin, William S Middleton Mem Vet Adm Hosp, Dept Med, 2500 Overlook Terrace, Madison, WI 53705 USA. NR 0 TC 28 Z9 29 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD MAR PY 2001 VL 107 IS 3 SU S BP S403 EP S405 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 418KR UT WOS:000167891800001 PM 11242600 ER PT J AU Wechsler, H Kelley, K Seibring, M Kuo, M Rigotti, NA AF Wechsler, H Kelley, K Seibring, M Kuo, M Rigotti, NA TI College smoking policies and smoking cessation programs: Results of a survey of college health center directors SO JOURNAL OF AMERICAN COLLEGE HEALTH LA English DT Article DE cessation programs; college students; smoking; smoking policy; tobacco ID STUDENTS AB College students' cigarette smoking rose dramatically during the 1990s. Little is known about what colleges do to address the problem. Health center directors at 393 4-year US col leges provided information (response rate: 65.1%) about college policies addressing smoking and the availability of smoking cessation programs. Of the health center directors surveyed, 85% considered students' smoking a problem; yet only 81% of colleges prohibit smoking in all public areas and only 27% ban smoking in all indoor areas, including students' rooms in dormitories and in private offices. More than 40% of the respondents reported that their schools did not offer smoking cessation programs and that the demand for existing program was low. Colleges need to do more to discourage student tobacco use. Recommended actions include campus-wide no-smoking policies that apply to student residences and identification of new ways of providing smoking prevention and cessation services. C1 Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Cambridge, MA 02138 USA. Childrens Hosp, Ctr Adolescent Subst Abuse Res, Boston, MA 02115 USA. Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Wechsler, H (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, 677 Huntington Ave, Cambridge, MA 02138 USA. NR 16 TC 45 Z9 45 U1 1 U2 3 PU HELDREF PUBLICATIONS PI WASHINGTON PA 1319 EIGHTEENTH ST NW, WASHINGTON, DC 20036-1802 USA SN 0744-8481 J9 J AM COLL HEALTH JI J. Am. Coll. Health PD MAR PY 2001 VL 49 IS 5 BP 205 EP 212 PG 8 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 424MH UT WOS:000168235700002 PM 11337895 ER PT J AU Nahum, R Shifren, JL Chang, YC Leykin, L Isaacson, K Toth, TL AF Nahum, R Shifren, JL Chang, YC Leykin, L Isaacson, K Toth, TL TI Antral follicle assessment as a tool for predicting outcome in IVF - Is it a better predictor than age and FSH? SO JOURNAL OF ASSISTED REPRODUCTION AND GENETICS LA English DT Article DE antral follicle; IVF outcome; pregnancy rate; cancellation rate ID HUMAN MENOPAUSAL GONADOTROPIN; IN-VITRO FERTILIZATION; INVITRO FERTILIZATION; OVARIAN VOLUME; STIMULATION; BASAL; RESERVE; WOMEN AB Purpose: The purpose of this study is to determine if baseline antral follicle assessment may serve as additional information in predicting in vitro fertilization outcome. Methods: Prospective, descriptive preliminary study of in vitro fertilization outcome. From July 1998 to July 1999 224 patients underwent antral follicle assessment (follicle 2-6 mm in diameter) on baseline of the planned, stimulated in vitro fertilization cycle. The outcomes were analyzed with respect to antral follicle assessment (less than or equal to6 or >6), basal cycle day 3 follicle stimulated harmone (less than or equal to 10 or > 10 IU/L) and maternal age (less than or equal to 35 or > 35 years). Results: The clinical pregnancy rate was significantly higher in the group with baseline antral follicle >6 compared to that in the group with antral follicle less than or equal to6 (51% vs. 19%, respectively). Controlling for patient age, and basal follicle stimulated harmone, the pregnancy rate was significantly higher in the group with antral follicle >6 compared to that in the group with antral follicle less than or equal to6. The cancellation rate was significantly increased with advancing maternal age, elevated basal follicle stimulated harmone levels, and baseline antral follicle less than or equal to6. The cancellation rate was significantly higher in the group with antral follicle >6 compared to that in the group with antral follicle greater than or equal to6 (33% vs. 1%, respectively). Conclusions: In vitro fertilization outcome is strongly correlated with both maternal ages, basal cycle, day 3 follicle, stimulated harmone, and antral follicle assessment. Antral follicle assessment was a better predictor of in vitro fertilization outcome than were age or follicle stimulated harmone. Antral follicle assessment may provide a marker for ovarian age that is distinct from chronological age or hormonal markers. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent IVF Unit,Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Toth, TL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent IVF Unit,Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 16 TC 43 Z9 45 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1058-0468 J9 J ASSIST REPROD GEN JI J. Assist. Reprod. Genet. PD MAR PY 2001 VL 18 IS 3 BP 151 EP 155 DI 10.1023/A:1009424407082 PG 5 WC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology SC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology GA 439QD UT WOS:000169127800006 PM 11411430 ER PT J AU Suri-Payer, E Cantor, H AF Suri-Payer, E Cantor, H TI Differential cytokine requirements for regulation of autoimmune gastritis and colitis by CD4(+)CD25(+) T cells SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE autoimmune gastritis; regulatory T Cells; CD25; cytokine; colitis ID IMMUNOLOGICAL SELF-TOLERANCE; NONOBESE DIABETIC MICE; ANTIGEN-PRESENTING CELLS; GROWTH-FACTOR-BETA; INTESTINAL INFLAMMATION; NOD MICE; INTERFERON-GAMMA; SCID MICE; DEFICIENT MICE; IFN-GAMMA AB Murine autoimmune gastritis, induced by neonatal thymectomy or the injection of CD25-depleted lymphocytes into nu/nu recipients, is characterized by an inflammatory infiltrate into the gastric mucose, parietal cell destruction and circulating anti-parietal cell antibodies. Using RAG-2(-/-) mice as recipients, we determined that the induction of disease relies on CD4(+)CD25(-) effector cells and prevention relies on CD4(+)CD25(+) regulatory cells; neither requires participation of CD8 cells or B cells. The severity of gastritis was dependent on the cytokine repertoire of CD4(+)CD25(-) effector T cells. Recipients of IL-4(-/-) T cells developed more severe gastritis and recipients of INF-gamma (-/-) T cells developed milder disease than recipients of wildtype or IL-10(-/-) effector T cells. Gastritis did not develop in the absence of IL-12. Protection from gastritis does not require either IL-4 or IL-10 because CD4(+)CD25(+) cells from IL-4(-/-) or IL-10(-/-) mice completely abrogated the disease process. CD4(+)CD25(+) cells also protected RAG-2(-/-) recipients from colitis and inhibitory activity was partially dependent on IL-10 expression. These findings highlight the critical role of CD4(+)CD25(+) regulatory T cells in protection from several autoimmune syndromes and delineate the differential contribution of IL-10 to CD4(+)CD25(+) Treg activity in the settings of gastritis and colitis. (C) 2001 Academic Press. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Suri-Payer, E (reprint author), Gothenburg Univ, Dept Rheumatol, Sch Med, S-41346 Gothenburg, Sweden. FU NIAID NIH HHS [AI 37562, AI 12184] NR 53 TC 188 Z9 200 U1 0 U2 4 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD MAR PY 2001 VL 16 IS 2 BP 115 EP 123 DI 10.1006/jaut.2000.0473 PG 9 WC Immunology SC Immunology GA 412GR UT WOS:000167547100004 PM 11247637 ER PT J AU Ledoux, WR Hirsch, BE Church, T Caunin, M AF Ledoux, WR Hirsch, BE Church, T Caunin, M TI Pennation angles of the intrinsic muscles of the foot SO JOURNAL OF BIOMECHANICS LA English DT Article DE musculoskeletal modeling; muscle architecture; pennation angle; foot ID MODELS; ARCHITECTURE; LENGTH AB As mathematical models of the musculoskeletal system become increasingly detailed and precise, they require more accurate information about the architectural parameters of the individual muscles. These muscles are typically represented as Hill-type models, which require data on fiber length, physiological cross-sectional area (PCSA) and pennation angle. Most of this information for lower limb muscles has been published, except for data on the pennation angle of the intrinsic muscles of the foot. Each (n = 20) intrinsic muscle of three human feet was dissected free. The dorsal and plantar surfaces were photographed and a digitized color image was imported into Abobe Photoshop(TM). The muscles were divided into "anatomical units". For each anatomical unit (n = 26), a line was drawn along the tendon axis and a number of other lines were drawn along individual muscle fibers. The angle between the tendon line and each fiber line was defined as the pennation angle of that fiber. By visual inspection, an effort was made to take measurements such that they represented the distribution of fibers in various parts of the muscle. Although some individual muscles had higher or lower pennation angles, when averaged for all specimens, the second dorsal interosseous had the smallest pennation angle (6.7 +/- 6.81 degrees) while the abductor digiti minimi had the largest (19.1 +/- 11.19 degrees). Since the cosines of the angles range from 0.9932 to 0.9449, the effect of the pennation angle on the force generated by the muscle was not great. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Temple Univ, Sch Pediat Med, Dept Anat & Cell Biol, Philadelphia, PA 19107 USA. VA Puget Sound Hlth Care Syst, Rehabil Res & Dev Ctr, Seattle, WA 98108 USA. Univ Washington, Dept Orthopaed, Seattle, WA 98195 USA. RP Hirsch, BE (reprint author), Temple Univ, Sch Pediat Med, Dept Anat & Cell Biol, 8th & Race St, Philadelphia, PA 19107 USA. RI Ledoux, William/K-6815-2015 OI Ledoux, William/0000-0003-4982-7714 NR 14 TC 26 Z9 26 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD MAR PY 2001 VL 34 IS 3 BP 399 EP 403 DI 10.1016/S0021-9290(00)00194-9 PG 5 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 411DH UT WOS:000167482500015 PM 11182133 ER PT J AU Clatworthy, MG Ballance, J Brick, GW Chandler, HP Gross, AE AF Clatworthy, MG Ballance, J Brick, GW Chandler, HP Gross, AE TI The use of structural allograft for uncontained defects in revision total knee arthroplasty - A minimum five-year review SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article AB Background: To our knowledge, the medium to long-term outcome after revision knee arthroplasty with structural allograft augmentation for reconstruction of uncontained defects has not been determined. The purpose of the present study was to assess the outcome for patients managed with such a procedure. Methods: We prospectively followed fifty patients who had fifty-two revision knee replacements with sixty-six structural grafts performed at three institutions. Twenty-nine knees (twenty-seven patients) were independently evaluated at a mean of 96.9 months (range, sixty to 189 months) by an investigator who had not been involved in the index procedure. Twelve knees (23%) had a repeat revision at a mean of 70.7 months (range, twenty-six to 157 months). The allograft was retained in two of these patients. Eleven patients died at a mean of ninety-three months (range, sixty-one to 128 months) after the procedure; the structural allograft and implants were intact, and the patients were not awaiting revision at the time of death. Results: Clinical evaluation revealed that the mean modified Hospital for Special Surgery knee score had improved from 32.5 points preoperatively to 75.6 points at the time of the review and the mean range of motion had increased from 60.5 degrees preoperatively to 88.6 degrees. Failure was defined as an increase of less than 20 points in the modified Hospital for Special Surgery knee score at the time of the review or the need for an additional operation related to the allograft. Thirteen knee replacements failed, yielding a 75% success rate. Five knees had graft resorption, resulting in implant loosening. Four knee replacements failed because of infection, and two knees had nonunion between the host bone and the allograft. Two knees (one patient) did not have a 20-point improvement in the knee score. The survival rate of the allografts was 72% (95% confidence interval, 69% to 75%) at ten years. On radiographic analysis, none of the surviving grafts had severe resorption, one had moderate resorption, and two had mild resorption. One knee had a loose tibial component, and three knees had nonprogressive tibial radiolucent lines. All four knees were asymptomatic. Conclusions: Our results demonstrate that allografts used in revision knee replacement in patients with the difficult problem of massive bone loss have an encouraging medium-term rate of survival. C1 Mt Sinai Hosp, Dept Orthopaed Surg, Toronto, ON M5G 1X5, Canada. Brigham & Womens Hosp, Dept Orthopaed, Boston, MA 02120 USA. Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. RP Clatworthy, MG (reprint author), Mt Sinai Hosp, Dept Orthopaed Surg, 600 Univ Ave, Toronto, ON M5G 1X5, Canada. NR 21 TC 102 Z9 112 U1 1 U2 4 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 MAR PY 2001 VL 83A IS 3 BP 404 EP 411 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 411MH UT WOS:000167503500013 PM 11263645 ER PT J AU Whitfield, JF Isaacs, RJ Chakravarthy, B Maclean, S Morley, P Willick, G Divieti, P Bringhurst, FR AF Whitfield, JF Isaacs, RJ Chakravarthy, B Maclean, S Morley, P Willick, G Divieti, P Bringhurst, FR TI Stimulation of protein kinase C activity in cells expressing human parathyroid hormone receptors by C- and N-terminally truncated fragments of parathyroid hormone 1-34 SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE parathyroid hormone; receptors; adenylyl cyclase; protein kinase C ID HUMAN-SKIN FIBROBLASTS; PHOSPHOLIPASE-C; BONE-GROWTH; OVARIECTOMIZED RATS; PTH/PTHRP RECEPTOR; ACTIVATION DOMAIN; ADENYLATE-CYCLASE; ANALOGS; PTH; BINDING AB The parathyroid hormone (PTH) fragment PTH(1-34) stimulates adenylyl cyclase, phospholipase C (PLC), and protein kinase C's (PKCs) in cells that express human, opossum, or rodent type 1 PTH/PTH-related protein (PTHrP) receptors (PTHR1s). Certain carboxyl (C)-terminally truncated fragments of PTH(1-34), such as human PTH(1-31) [hPTH-(1-31)NH2], stimulate adenylyl cyclase but not PKCs in rat osteoblasts or PLC and PKCs in mouse kidney cells. The hPTH(1-31)NH2 peptide does fully stimulate PLC in HKRK B7 porcine renal epithelial cells that express 950,000 transfected hPTHR1s per cell. Amino (N)-terminally truncated fragments, such as bovine PTH(3-34) [bPTH(3-34)1, hPTH(3-34)NH2, and hPTH(13-34), stimulate PKCs in Chinese hamster ovary (CHO) cells expressing transfected rat receptors, opossum kidney cells, and rat osteoblasts, but an intact N terminus is needed to stimulate PLC via human PTHR1s in HKRK B7 cells. We now report that the N-terminally truncated analogs bPTH(3-34)NH2 and hPTH(13-34)OH do activate PKC via human PTHR1s in HKRK B7 cells, although less effectively than hPTH(1-34)NH2 and hPTH(1-31)NH2. Moreover, in a homologous human cell system (normal foreskin fibroblasts), these N-terminally truncated fragments stimulate PKC activity as strongly as hPTH(1-34)NH2 and hPTH(1-31)NH2. Thus, it appears that unlike their opossum and rodent equivalents, hPTHR1s can stimulate both PLC and PKCs when activated by C-terminally truncated fragments of PTH(1-31). Furthermore, hPTHR1s, like the PTHR1s in rat osteoblasts, opossum kidney cells, and rat PTHR1-transfected CHO cells also can stimulate PKC activity by a mechanism that is independent of PLC. The efficiency with which the N-terminally truncated PTH peptides stimulate PKC activity depends on the cellular context in which the PTHR1s are expressed. C1 Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA USA. RP Whitfield, JF (reprint author), Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada. NR 38 TC 22 Z9 23 U1 1 U2 2 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD MAR PY 2001 VL 16 IS 3 BP 441 EP 447 DI 10.1359/jbmr.2001.16.3.441 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 405KC UT WOS:000167157700003 PM 11277261 ER PT J AU Sheridan, R Stoddard, F Querzoli, E AF Sheridan, R Stoddard, F Querzoli, E TI Management of background pain and anxiety in critically burned children requiring protracted mechanical ventilation SO JOURNAL OF BURN CARE & REHABILITATION LA English DT Article AB Optimal control of pain and anxiety is an elusive but important goal in children with protracted critical illness. This review represents an effort to document the doses of background medication required to achieve this goal in a group of children managed under a pain and anxiety protocol that adjusts background infusions to comfort. The course of children with wounds involving at least 10% of the body surface and coincident respiratory failure requiring mechanical ventilation for more than 7 days managed 1 Jan 97 to 31 Dec 98 was reviewed. A pain and anxiety protocol was used, including background infusions of morphine and midazolam. adjusted to comfort. These 28 children had a mean (+/- standard deviation) age of 5.3 +/- 4.6 years, wound size of 48.3 +/- 28.4%, and were intubated for 25.0 +/- 23.9 days. Neuromuscular blocking drugs were administered for 65 of 447 (14.5%) ventilator days. To maintain comfort, drugs were required at doses substantially above standard dosing schemes. The highest daily background infusion of morphine sulfate averaged 0.40 mg/kg/hr +/- 0.24 mg/kg/hr (usual starting dose was 0.05 to 0.1 mg/kg/hr) and was reached 14.1 +/- 12.8 days after admission. The highest daily background infusion of midazolam averaged 0.15 +/- 0.07 mg/kg/hr (usual starting dose was 0.04 mg/kg/hr) and was reached 14.0 +/- 3.8 days after admission. Morphine infusions at extubation averaged 0.22 +/- 0.17 mg/kg/hr and midazolam infusions 0.10 +/- 0.12 mg/kg/hr. All children survived to discharge and there was no perceived morbidity related to these high doses of medication. Children with serious burns and respiratory failure will require high doses of background opiates and benzodiazepines to remain comfortable, because they develop drug tolerance during protracted critical illness. Infusions can be continued at a reduced dose through extubation, do not result in addiction or other apparent morbidity if adjusted to desired level of comfort, and may contribute to a reduced incidence of treatment-related stress disorders. C1 Shriners Burns Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Burns & Trauma, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Sheridan, R (reprint author), Shriners Burns Hosp, 51 Blossom St, Boston, MA 02114 USA. NR 14 TC 19 Z9 19 U1 0 U2 0 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 MAR-APR PY 2001 VL 22 IS 2 BP 150 EP 153 DI 10.1097/00004630-200103000-00012 PG 4 WC Emergency Medicine; Rehabilitation; Surgery SC Emergency Medicine; Rehabilitation; Surgery GA 606TL UT WOS:000178749500010 PM 11302604 ER PT J AU Azar, DT Jain, S Sambursky, R Strauss, L AF Azar, DT Jain, S Sambursky, R Strauss, L TI Microkeratome-assisted posterior keratoplasty SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article; Proceedings Paper CT Symposium on Cataract, IOL and Refractive Surgery CY APR, 1997 CL BOSTON, MASSACHUSETTS ID IN-SITU KERATOMILEUSIS; LAMELLAR KERATOPLASTY; PHOTOREFRACTIVE KERATECTOMY; PENETRATING KERATOPLASTY; SURGICAL TECHNIQUE AB Microkeratome-assisted posterior keratoplasty is a new surgical technique that may be valuable in treating patients with corneal decompensation secondary to endothelial dysfunction. A hinged anterior stromal flap is fashioned in the host cornea using a microkeratome, and the diseased posterior stroma and endothelium are resected. A complementary donor stromal button is prepared using a microkeratome and an artificial anterior chamber. The donor button is transplanted and secured with sutures, and the flap is repositioned. The flap can be lifted later to remove the sutures or to correct residual refractive errors using an excimer laser. This technique may allow the use of infant corneal donor tissue and may improve the outcomes of posterior keratoplasty. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Corneal & Refract Surg Serv, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Johns Hopkins Univ, Wilmer Ophthalmol Inst, Baltimore, MD USA. RP Azar, DT (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Corneal & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. NR 11 TC 32 Z9 41 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD MAR PY 2001 VL 27 IS 3 BP 353 EP 356 DI 10.1016/S0886-3350(00)00778-1 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 413BT UT WOS:000167590600009 PM 11255044 ER PT J AU Dunn, AK Bolay, T Moskowitz, MA Boas, DA AF Dunn, AK Bolay, T Moskowitz, MA Boas, DA TI Dynamic imaging of cerebral blood flow using laser speckle SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE optical imaging; cerebral blood flow; laser speckle; cortical spreading depression; focal cerebral ischemia ID ISCHEMIC PENUMBRA; FUNCTIONAL RECOVERY; DOPPLER FLOWMETRY; ARTERY OCCLUSION; RAT; THRESHOLDS; CORTEX; MICROCIRCULATION; MODEL; PET AB A method for dynamic, high-resolution cerebral blood flow (CBF) imaging is presented in this article. By illuminating the cortex with laser light and imaging the resulting speckle pattern, relative CBF images with tens of microns spatial and millisecond temporal resolution are obtained. The regional CBF changes measured with the speckle technique are validated through direct comparison with conventional laser-Doppler measurements. Using this method, dynamic images of the relative CBF changes during focal cerebral ischemia and cortical spreading depression were obtained along with electrophysiologic recordings. Upon middle cerebral artery (MCA) occlusion, the speckle technique yielded high-resolution images of the residual CBF gradient encompassing the ischemic core, penumbra, oligemic, and normally perfused tissues over a 6 x 4 mm cortical area. Successive speckle images demonstrated a further decrease in residual CBF indicating an expansion of the ischemic zone with finely delineated borders. Dynamic CBF images during cortical spreading depression revealed a 2 to 3 mm area of increased CBF (160% to 250%) that propagated with a velocity of 2 to 3 mm/min. This technique is easy to implement and can be used to monitor the spatial and temporal evolution of CBF changes with high resolution in studies of cerebral pathophysiology. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. RP Dunn, AK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Bldg 149 13th St, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011; Dunn, Andrew/I-9527-2014 FU NINDS NIH HHS [5 P50 NS10828, 1 R29 NS38842 A 01] NR 33 TC 442 Z9 451 U1 6 U2 35 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAR PY 2001 VL 21 IS 3 BP 195 EP 201 PG 7 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 408VJ UT WOS:000167347900002 PM 11295873 ER PT J AU Shimizu, S Nagayama, T Jin, KL Zhu, L Loeffert, JE Watkins, SC Graham, SH Simon, RP AF Shimizu, S Nagayama, T Jin, KL Zhu, L Loeffert, JE Watkins, SC Graham, SH Simon, RP TI bcl-2 antisense treatment prevents induction of tolerance to focal ischemia in the rat brain SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE ischemic tolerance; antisense oligodeoxynucleotides; striatum ID CYTOCHROME-C; GERBIL HIPPOCAMPUS; CEREBRAL-ISCHEMIA; NEURONAL DEATH; CELL-DEATH; EXPRESSION; APOPTOSIS; PROTEIN; MITOCHONDRIA; RNA AB In the rat, 60 minutes of transient ischemia to the middle cerebral artery results in infarction of the caudate putamen. Ischemic preconditioning with 20 minutes of transient focal ischemia produced tolerance (attenuated infarction volume) to 60 minutes of subsequent focal ischemia administered three days, five days, or seven days later. Western blots from tolerant caudate putamen demonstrated increased bcl-2 expression, maximum at 3 days and persisting through 7 days. Immunocytochemical examination found that bcl-2 was expressed in cells with both neuronal and nonneuronal morphology in striatum after preconditioning ischemia. bcl-2 antisense oligodeoxynucleotides (ODNs), bcl-2 sense ODNs, or artificial cerebrospinal fluid (CSF, vehicle) was infused into the lateral ventricle for the 72 hours between the 20-minute ischemic preconditioning and the 60-minute period of ischemia. Antisense ODN treatment reduced expression of bcl-2 in the striatum and blocked the induction of tolerance by preconditioning ischemia. Sense and CSF treatments had no effect on either bcl-2 expression or tolerance. In this model of induced tolerance to focal ischemia, bcl-2 appears to be a major determinant. C1 Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Ctr Biol Imaging, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA 15213 USA. Vet Affairs Pittsburgh Hlth Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Graham, SH (reprint author), Univ Pittsburgh, Dept Neurol, 526 S BST, Pittsburgh, PA 15213 USA. FU NINDS NIH HHS [R01 NS24728, P01 NS35965] NR 34 TC 88 Z9 109 U1 0 U2 0 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 MAR PY 2001 VL 21 IS 3 BP 233 EP 243 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 408VJ UT WOS:000167347900007 PM 11295878 ER PT J AU Greene, RW Ablon, JS AF Greene, RW Ablon, JS TI What does the MTA study tell us about effective psychosocial treatment for ADHD? SO JOURNAL OF CLINICAL CHILD PSYCHOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; MULTIMODAL TREATMENT; SOCIAL DISABILITY; CHILDREN; BEHAVIOR; MODEL; PSYCHOTHERAPY; COMORBIDITY; RATIONALE AB Discussed the initial findings from the recently published, National Institute of Mental Health-sponsored Multimodal Treatment Study (MTA) of attention deficit hyperactivity disorder (ADHD). These findings can be summarized as follows: Medical management alone was found to be significantly more effective for the core symptoms of ADHD as compared to behavioral treatment alone and routine (community) care, and behavioral treatment did not significantly improve outcome when combined with medical treatment In discussing these findings, it is important to be explicit about the research questions the study was and was not designed to answer The MTA study provided useful information regarding the question, "Does a very intensive forms of behavioral treatment deliver greater benefits than the less intensive forms of behavioral treatment investigated in prior studies?" but little insight on the question, "What type of treatment by what type of therapist is most effective in dealing with what specific problems among specific children with ADHD ? " It is suggested that the clearest finding from the MTA study is that the effectiveness of psychosocial intervention for (ADHD) hinges on the degree to which a broad range of treatment ingredients are considered, carefully selected, matched, and tailored to the individual needs of each child with the disorder and implemented and monitored over the long term. C1 Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Harvard Med Sch, Boston, MA 02114 USA. RP Greene, RW (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Harvard Med Sch, ACC725, Boston, MA 02114 USA. NR 62 TC 21 Z9 21 U1 4 U2 7 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0047-228X J9 J CLIN CHILD PSYCHOL JI J. Clin. Child Psychol. PD MAR PY 2001 VL 30 IS 1 BP 114 EP 121 DI 10.1207/S15374424JCCP3001_13 PG 8 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 418MF UT WOS:000167895400012 PM 11294069 ER PT J AU Fryer, JFL Griffiths, PD Fishman, JA Emery, VC Clark, DA AF Fryer, JFL Griffiths, PD Fishman, JA Emery, VC Clark, DA TI Quantitation of porcine cytomegalovirus in pig tissues by PCR SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; PERIPHERAL-BLOOD; HUMAN-CELLS; INFECTION; QUANTIFICATION; RETROVIRUS; ASSAY; LOAD AB A quantitative-competitive PCR for the quantification of porcine cytomegalovirus (PCMV) was developed. The virus was detected in a variety of pig organs (including potential xenotransplant donations),,vith viral loads ranging from <10 to: 97 genome copies/g of DNA. This assay will have significant utility for studying the activation and replication of PCMV and in swine models for allo- and xenotransplantation. C1 UCL, Royal Free & Univ Coll Med Sch, Dept Virol, London NW3 2PF, England. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Infect Dis Program, Boston, MA USA. RP Clark, DA (reprint author), UCL, Royal Free & Univ Coll Med Sch, Dept Virol, Royal Free Campus,Rowland Hill St, London NW3 2PF, England. EM d.clark@rfc.ucl.ac.uk NR 15 TC 23 Z9 24 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 MAR PY 2001 VL 39 IS 3 BP 1155 EP 1156 DI 10.1128/JCM.39.3.1155-1156.2001 PG 2 WC Microbiology SC Microbiology GA 408FY UT WOS:000167316900057 PM 11230447 ER PT J AU Frustaci, S Gherlinzoni, F De Paoli, A Bonetti, M Azzarelli, A Comandone, A Olmi, P Buonadonna, A Pignatti, G Barbieri, E Apice, G Zmerly, H Serraino, D Picci, P AF Frustaci, S Gherlinzoni, F De Paoli, A Bonetti, M Azzarelli, A Comandone, A Olmi, P Buonadonna, A Pignatti, G Barbieri, E Apice, G Zmerly, H Serraino, D Picci, P TI Adjuvant chemotherapy for adult soft tissue sarcomas of the extremities and girdles: Results of the Italian randomized cooperative trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; EUROPEAN ORGANIZATION; LOCAL RECURRENCE; PHASE-II; IFOSFAMIDE; EPIRUBICIN; RADIATION; SURVIVAL AB Purpose: Adjuvant chemotherapy for soft tissue sarcoma is controversial because previous trials reported conflicting results. The present study wets designed with restricted selection criteria and high dose-intensities of the two most active chemotherapeutic agents. Patients and Methods: Patients between 18 and 65 years of age with grade 3 to 4 spindle-cell sarcomas (primary diameter greater than or equal to 5 cm or any size recurrent turner) in extremities or girdles were eligible. Stratification was by primary versus recurrent tumors and by tumor diameter greater than or equal to 10 cm versus less than 10 cm. One hundred four patients were randomized, 51 to the control group and 53 to the treatment group (five cycles of 4'-epidoxorubicin 60 mg/m(2) days 1 and 2 and ifosfamide 1.8 g/m(2) days 1 through 5, with hydration, mesna, and granulocyte colony-stimulating factor). Results: After a median follow-up of 59 months, 60 patients had relapsed and 48 died (28 and 20 in the treatment arm and 32 and 28 in the control arm, respectively). The median disease-free survival (DFS) was 48 months in the treatment group and 16 months in the control group (P = .04); and the median overall survival (QS) was 75 months for treated and 46 months for untreated patients (P = .03). For OS, the absolute benefit deriving from chemotherapy was 13% at 2 years and increased to 19% at 4 years (P = .04). Conclusion: Intensified adjuvant chemotherapy had a positive impact on the DFS and OS of patients with high-risk extremity soft tissue sarcomas at a median follow-up of 59 months. Therefore, our data favor an intensified treatment in similar cases. Although cure is still difficult to achieve, a significant delay in death is worthwhile, also considering the short duration of treatment and the absence of toxic deaths. J Clin Oncol 19:1238-1247. (C) 2001 by American Society of Clinical Oncology. C1 Ctr Riferimento Oncol, Div Med Oncol, Unita Operat Oncol Med & Oncol Radioterap, I-33170 Aviano, PN, Italy. Ctr Riferimento Oncol, Serv Epidemiol, I-33081 Aviano, Italy. Osped Civile, Unita Operat Ortoped, Gorizia, Italy. Ist Nazl Tumori, Unita Operat Chirurg Muscoloscheletr, I-20133 Milan, Italy. Osped Gradenigo, Unita Operat Oncol Med, Turin, Italy. Univ Florence, Div Radioterapia, I-50121 Florence, Italy. Univ Bologna, Ist Radioterapia, Bologna, Italy. Univ Bologna, Ist Ortoped Rizzoli, Lab Ric Oncol, Bologna, Italy. Univ Bologna, Ist Ortoped Rizzoli, Div V, Bologna, Italy. Ist Pascale, Unita Operat Oncol Med B, Naples, Italy. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Frustaci, S (reprint author), Ctr Riferimento Oncol, Div Med Oncol, Unita Operat Oncol Med & Oncol Radioterap, Via Pedemontana Occ 12, I-33170 Aviano, PN, Italy. RI Picci, Piero/J-5979-2016 OI De Paoli, Antonino/0000-0002-9512-8108; Buonadonna, Angela/0000-0002-1930-0308; Picci, Piero/0000-0002-8519-4101 NR 36 TC 319 Z9 335 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2001 VL 19 IS 5 BP 1238 EP 1247 PG 10 WC Oncology SC Oncology GA 408LB UT WOS:000167326700002 PM 11230464 ER PT J AU Kirkwood, JM Ibrahim, J Lowson, DH Aikins, MB Agarwala, SS Collins, K Mascari, R Morrissey, DM Chapman, PB AF Kirkwood, JM Ibrahim, J Lowson, DH Aikins, MB Agarwala, SS Collins, K Mascari, R Morrissey, DM Chapman, PB TI High-dose interferon alfa-2b does mot diminish antibody response to GM2 vaccination in patients with resected melanoma: Results of the multicenter Eastern Cooperative Oncology Group phase II trial E2696 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID GANGLIOSIDE; SURVIVAL AB Purpose: High-dose interferon alfa-2b (IFN alpha 2b) is the only established adjuvant therapy of resectable high-risk melanoma. GM2-KLH/QS-21 (GMK) is a chemically defined vaccine that is one of the best developed of a range of vaccine candidates for melanoma. A single-institution phase III trial conducted at Memorial Hospital served as the impetus for an intergroup adjuvant E1694/S9512/C509801 trial, which recently completed enrollment of 880 patients. To build on the apparent benefit of IFN alpha 2b in resectable high-risk American Joint Committee on Cancer [AJCC) stage IIB or III melanoma, this phase II study was designed to evaluate the combination of GMK and IFN alpha 2b. The E2696 trial was undertaken to evaluate the toxicity and other effects of the established adjuvant high-dose IFN alpha 2b regimen in relation to immune responses to GMK and to evaluate the potential clinical and immunologic effects of the combined therapies, Patients and Methods: This trial enrolled 107 patients with resectable high- or very high-risk melanoma (AJCC stages IIB, III, and IV). Results: The results demonstrate that IFN alpha 2b does not significantly inhibit immunoglobulin M or G serologic responses to the vaccine and that the combination of high-dose IFN alpha 2b and GMK is well tolerated in this patient population. Conclusion: Cox analysis of the results of the combination with IFN alpha 2b show improvement in the relapse-free survival of patients with very high-risk melanoma (including those with resectable M-1, disease). J Clin Oncol 19:1430-1436. (C) 2001 by American Society of Clinical Oncology. C1 Univ Pittsburgh, Med Ctr, Sch Med, Canc Inst,Melanoma Ctr,Dept Med,Div Hematol Oncol, Pittsburgh, PA 15213 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA. Progen Pharmaceut Inc, Tarrytown, NY USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Kirkwood, JM (reprint author), Univ Pittsburgh, Med Ctr, Sch Med, Canc Inst,Melanoma Ctr,Dept Med,Div Hematol Oncol, 200 Lothrop St, Pittsburgh, PA 15213 USA. FU NCI NIH HHS [U10 CA39229-15] NR 10 TC 75 Z9 79 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2001 VL 19 IS 5 BP 1430 EP 1436 PG 7 WC Oncology SC Oncology GA 408LB UT WOS:000167326700026 PM 11230488 ER PT J AU Zhao, YS Verselis, SJ Klar, N Sadowsky, NL Kaelin, CM Smith, B Foretova, L Li, FP AF Zhao, YS Verselis, SJ Klar, N Sadowsky, NL Kaelin, CM Smith, B Foretova, L Li, FP TI Nipple fluid carcinoembryonic antigen and prostate-specific antigen in cancer-bearing and tumor-free breasts SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID DOT-IMMUNOBINDING ASSAY; ASPIRATE FLUID; RISK; DISCHARGE; MARKERS; WOMEN; SERUM; DIAGNOSIS; DISEASE; BENIGN AB Purpose: Mammograms and breast examinations are established methods for early breast cancer detection. Routine mammography screening reduces breast cancer mortality among women ages greater than or equal to 50 years, but additional screening methods are needed. We and others have found high levels of carcinoembryonic antigen (CEA) and prostate-specific antigen (PSA) in nipple aspirate fluids (NAFs), but the usefulness for these biomarkers for early breast cancer detection is unknown. Patients and Method: NAFs from one or both breasts of 388 women were analyzed for CEA, PSA, and albumin levels. The study included 44 women with newly diagnosed invasive breast cancers, 67 women with proliferative breast lesions (duct-al and lobular carcinoma in situ and atypical ductal hyperplasia), and 277 controls without these breast lesions. Analyses were conducted using the log(10)-transformed CEA and PSA levels to normalize the distributions of these tumor markers. Results: Nipple fluid CEAs are significantly higher for cancerous breasts than turner-free breasts (median 1,830 and 1,408 ng/mL, respectively; P <.01). However, at 90% specificity of the assay (CEA = 11,750 ng/mL), the corresponding sensitivity for cancer detection is 32%. CEA levels are not significantly different for breasts with proliferative lesions compared with tumor-free breasts. Nipple fluid PSAs do not differ by turner status. Analyses of NAF albumin-standardized CEAs and PSAs yield similar results. Nipple fluid CEA and PSA titers are correlated in the affected and unaffected breast of women with unilateral lesions. Conclusion: Nipple fluid CEAs are higher for breasts with untreated invasive cancers, but the test sensitivity is low. Nipple fluid PSA titers do not seem to be useful for breast cancer detection. J Clin Oncol 19:1462-1467. (C) 2001 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Faulkner Hosp, Jamaica Plain, MA USA. RP Li, FP (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Smith 201,44 Binney St, Boston, MA 02115 USA. NR 37 TC 39 Z9 43 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2001 VL 19 IS 5 BP 1462 EP 1467 PG 6 WC Oncology SC Oncology GA 408LB UT WOS:000167326700030 PM 11230492 ER PT J AU Schiffer, CA Anderson, KC Bennett, CL Bernstein, S Elting, LS Goldsmith, M Goldstein, M Hume, H McCullough, JJ McIntyre, RE Powell, BL Rainey, JM Rowley, SD Rebulla, P Troner, MB Wagnon, AH AF Schiffer, CA Anderson, KC Bennett, CL Bernstein, S Elting, LS Goldsmith, M Goldstein, M Hume, H McCullough, JJ McIntyre, RE Powell, BL Rainey, JM Rowley, SD Rebulla, P Troner, MB Wagnon, AH CA Amer Soc Clinical Oncology TI Platelet transfusion for patients with cancer: Clinical practice guidelines of the American Society of Clinical Oncology SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID ALLOIMMUNIZED THROMBOCYTOPENIC PATIENTS; WHITE CELL-REDUCTION; BLOOD COMPONENT PREPARATION; INTRAVENOUS GAMMA-GLOBULIN; MARROW TRANSPLANT PATIENTS; ACUTE MYELOID-LEUKEMIA; PACKED RED-CELLS; HLA-ALLOIMMUNIZATION; SINGLE-DONOR; COST-EFFECTIVENESS AB Objective: To determine the most effective, evidence-based approach to the use of platelet transfusions in patients with cancer. Outcomes: Outcomes of interest included prevention of morbidity and mortality from hemorrhage, effects on survival, quality of life, toxicity reduction, and cost effectiveness. Evidence: A complete MedLine search was performed of the past 20 years of the medical literature. Keywords included platelet transfusion, alloimmunization, hemorrhage, threshold and thrombocytopenia. The search was broadened by articles from the bibliographies of selected articles. Values: Levels of evidence and guideline grades were rated by a standard process. More weight was given to studies that tested a hypothesis directly related to one of the primary outcomes in a randomized design. Benefits/Harms/Cost: The possible consequences of different approaches to the use of platelet transfusion were considered in evaluating a preference for one or another technique producing similar outcomes. Cost alone was not a determining factor. Recommendations: Appendix A summarizes the recommendations concerning the choice of particular platelet preparations, the use of prophylactic platelet transfusions, indications for transfusion in selected clinical situations, and the diagnosis, prevention, and management of refractoriness to platelet transfusion. Validation: Five outside reviewers, the ASCO Health Services Research Committee, and the ASCO Board reviewed this document. Sponsor: American Society of Clinical Oncology J Clin Oncol 19:1519-1538. (C) 2001 by American Society of Clinical Oncology. C1 Amer Soc Clin Oncol, Hlth Serv Res Dept, Alexandria, VA 22314 USA. Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. VA Chicago Hlth Care Syst, Chicago, IL USA. SUNY Buffalo, Buffalo, NY 14260 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Rite Passage Canc Project, Newport, RI USA. Harvard Med Sch, Brookline, MA USA. Hop St Justine, Montreal, PQ H3T 1C5, Canada. Univ Minnesota, Minneapolis, MN USA. Venture Co Hematol Oncol Specialists, Oxnard, CA USA. Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. J&M Resources, Lafayette, LA USA. Osped Maggiore, IRCCS, Ctr Transfus & Immunol Trapianti, Milan, Italy. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Oncol Radiat Assoc, Miami, FL USA. Soc Utah Oncologists, Ogden, UT USA. RP Schiffer, CA (reprint author), Amer Soc Clin Oncol, Hlth Serv Res Dept, 1900 Duke St,Suite 200, Alexandria, VA 22314 USA. RI Bennett, Charles/C-2050-2008; Rebulla, Paolo/I-7684-2015 OI Rebulla, Paolo/0000-0002-3875-5754 NR 143 TC 298 Z9 320 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2001 VL 19 IS 5 BP 1519 EP 1538 PG 20 WC Oncology SC Oncology GA 408LB UT WOS:000167326700036 PM 11230498 ER PT J AU Huisman, TAGM Holzmann, D Nadal, D AF Huisman, TAGM Holzmann, D Nadal, D TI MRI of chronic recurrent parotitis in childhood SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE parotitis, recurrent; parotid gland; parotid gland, diseases ID CHILDREN; SIALECTASIS; GLAND AB Purpose: Chronic recurrent parotitis (CRP) is a rare inflammatory disease characterized by multiple episodes of unilateral or bilateral parotid inflammation over a period of years. The objective of this study was to evaluate the parotid glands using MRI during acute inflammation as well as during symptom-free intervals. Method: Twelve children with a history of CRP were included. Four patients were examined during the acute phase and eight children during symptom-free intervals. MR findings were correlated with the clinical status. Results: Two different patterns were identified by MRI: acute inflammation versus chronic inflammation. Contrast enhancement of the parotid gland indicated acute inflammation. Cysts due to chronic inflammation were encountered in children who suffered multiple episodes of inflammation. Conclusion: Our findings suggest that CRP is characterized by recurrent, acute exacerbations of inflammation, resulting in a slowly progressive destruction of the parotid gland. C1 Univ Zurich, Childrens Hosp, Dept Pediat, Div Infect Dis, Zurich, Switzerland. Univ Zurich Hosp, Dept Otorhinolaryngol, CH-8091 Zurich, Switzerland. Univ Zurich Hosp, Inst Diagnost Radiol, CH-8091 Zurich, Switzerland. RP Huisman, TAGM (reprint author), Massachusetts Gen Hosp, MGH NMR Ctr, Bldg 149,13 St,Mailcode 149 2301, Charlestown, MA 02129 USA. NR 17 TC 13 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAR-APR PY 2001 VL 25 IS 2 BP 269 EP 273 DI 10.1097/00004728-200103000-00021 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 411VY UT WOS:000167521000021 PM 11242227 ER PT J AU Reinschmidt, JP Murray, SP Casha, LM Gagliano, RA Tracy, DA Collins, GJ AF Reinschmidt, JP Murray, SP Casha, LM Gagliano, RA Tracy, DA Collins, GJ TI Localization of pulmonary nodules using suture-ligated microcoils SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE lungs, nodules; lungs, biopsies; lungs, neoplasms; computed tomography ID ASSISTED THORACOSCOPIC SURGERY; NEEDLE LOCALIZATION; METHYLENE-BLUE; LUNG NODULES; RESECTION; WIRE; PLACEMENT; HOOKWIRE; SYSTEM AB Percutaneous localization of pulmonary nodules in five patients was performed utilizing suture-ligated embolization microcoils and CT guidance. Each localization was performed prior to video-assisted thoracoscopic wedge resection of the targeted nodules. Each suture-ligated microcoil was placed within 1.0 cm of the targeted pulmonary nodule. The attached suture served as a guide to direct accurate resection of the nodules. This technique is easily performed and provides a reliable alternative to nodule localization prior to thoracoscopic resection. C1 Madigan Army Med Ctr, Dept Diagnost Radiol, Tacoma, WA 98431 USA. Kaweah Delta Hosp, Visalia, CA 93291 USA. Madigan Army Med Ctr, Dept Diagnost Radiol, Ft Lewis, WA USA. Madigan Army Med Ctr, Dept Intervent Radiol, Ft Lewis, WA USA. Madigan Army Med Ctr, Dept Cardiothorac Surg, Ft Lewis, WA USA. Massachusetts Gen Hosp, Dept Intervent Radiol, Boston, MA 02114 USA. Keller Army Community Hosp, Dept Surg, W Point, NY USA. RP Reinschmidt, JP (reprint author), Kaweah Delta Hosp, 400 W Mineral King, Visalia, CA 93291 USA. NR 14 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAR-APR PY 2001 VL 25 IS 2 BP 314 EP 318 DI 10.1097/00004728-200103000-00029 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 411VY UT WOS:000167521000029 PM 11242235 ER PT J AU Zhu, Z Lee, CS Tejeda, KM Giannobile, WV AF Zhu, Z Lee, CS Tejeda, KM Giannobile, WV TI Gene transfer and expression of platelet-derived growth factors modulate periodontal cellular activity SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE gene transfer; platelet-derived growth factor; growth factors; adenovirus; tissue engineering ID DOMINANT-NEGATIVE MUTANTS; ADENOVIRUS VECTORS; MESSENGER-RNA; CELLS; PDGF; REGENERATION; THERAPY; COMBINATION; CULTURE; REPAIR AB Platelet-derived growth factor (PDGF) is a potent stimulator of wound healing. PDGF gene therapy may promote greater periodontal regeneration than local protein application, due to sustained growth factor delivery to the target tissue. This investigation tested the ability of recombinant adenoviruses (rAds) encoding PDGF-A or PDGF-1308 (a PDGF-A dominant-negative mutant that disrupts endogenous PDGF bioactivity) to affect cells derived from the periodontium. Osteoblasts, periodontal ligament fibroblasts, and gingival fibroblasts were transduced with rAds, and gene expression, DNA synthesis, and cell proliferation were evaluated. The results revealed strong message for the PDGF-A gene for 7 days following gene delivery. Ad2/PDGF-A enhanced the mitogenic and proliferative response in all cell types, while Ad2/PDGF-1308 potently inhibited mitogenesis and proliferation. In conclusion, Ad2/PDGF can effectively transduce cells derived from the periodontium and promote biological activity equivalent to PDGF-AA. These studies support the potential use of gene therapy for sustained PDGF release in periodontal tissues. C1 Univ Michigan, Dept Periodont Prevent Geriatr, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Dana Farber Harvard Canc Ctr, Boston, MA USA. Univ Michigan, Ctr Biorestorat Oral Hlth, Ann Arbor, MI 48109 USA. RP Giannobile, WV (reprint author), Univ Michigan, Dept Periodont Prevent Geriatr, 1011 N Univ Ave, Ann Arbor, MI 48109 USA. OI Giannobile, William/0000-0002-7102-9746 FU NIDCR NIH HHS [R01 DE013047, DE 11960, DE 13047, R01 DE013047-02, R29 DE011960, R29 DE011960-03] NR 31 TC 37 Z9 38 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD MAR PY 2001 VL 80 IS 3 BP 892 EP 897 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 473EH UT WOS:000171026700009 PM 11379891 ER PT J AU Pearson, GW Langley, RGB AF Pearson, GW Langley, RGB TI Topical imiquimod SO JOURNAL OF DERMATOLOGICAL TREATMENT LA English DT Article DE cytokine; human papilloma virus; imiquimod; immune response modifier; immunomodulator ID IMMUNE-RESPONSE MODIFIER; EXTERNAL GENITAL WARTS; 5-PERCENT CREAM; PATIENT; DISEASE C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dermatol Clin Invest Unit, Cambridge, MA 02138 USA. RP Langley, RGB (reprint author), Dalhousie Univ, Dept Med, Div Dermatol, QEII Hlth Sci Ctr, Room 4-195,Dickson Bldg, Halifax, NS B3H 2Y6, Canada. NR 18 TC 3 Z9 5 U1 0 U2 0 PU MARTIN DUNITZ LTD PI LONDON PA LIVERY HOUSE, 7-9 PRATT ST, LONDON NW1 0AE, ENGLAND SN 0954-6634 J9 J DERMATOL TREAT JI J. Dermatol. Treat. PD MAR PY 2001 VL 12 IS 1 BP 37 EP 40 DI 10.1080/095466301750163572 PG 4 WC Dermatology SC Dermatology GA 427VD UT WOS:000168425400011 PM 12171687 ER PT J AU Silva, JA Derecho, DV Leong, GB Weinstock, R Ferrari, MM AF Silva, JA Derecho, DV Leong, GB Weinstock, R Ferrari, MM TI A classification of psychological factors leading to violent behavior in posttraumatic stress disorder SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; forensic psychiatry; posttraumatic stress disorder; violence; misidentification of persons; combat addiction; sleep disturbance; dissociation; mens rea; diminished capacity ID POST-TRAUMATIC STRESS; VIETNAM VETERANS; COMBAT VETERANS; SLEEP; DEPRESSION; DISSOCIATION; COMORBIDITY; ANGER; PTSD AB Posttraumatic stress disorder has long been linked to violent behavior. However, the exact nature of that association remains poorly characterized due to the limitations of knowledge in the area of phenomenology, contextual factors, the biology, and the nature of the aggression involved in the disorder. A clear understanding of the genesis of violence in posttraumatic stress disorder can be helpful to those involved in assessing psychiatric-legal issues relevant to the disorder and in its therapeutic management. In this article, we review the potential psychological links between posttraumatic stress disorder secondary to combat exposure and violent behavior and suggest a tentative classification of the main psychological causes of violence in that syndrome. C1 Palo Alto Vet Hlth Care Syst, San Jose, CA 95160 USA. Vet Affairs Palo Alto Hlth Care Syst, Nalt Ctr Posttraumat Stress Disorder, Menlo Pk Div, Palo Alto, CA USA. Western State Hosp, Tacoma, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Greater Los Angeles Vet Healthcare Syst, Los Angeles, CA USA. Kaiser Permanente, Med Grp, Div Child & Adolescent Psychiat, Santa Clara, CA USA. RP Silva, JA (reprint author), Palo Alto Vet Hlth Care Syst, POB 20928, San Jose, CA 95160 USA. NR 66 TC 21 Z9 22 U1 1 U2 6 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD MAR PY 2001 VL 46 IS 2 BP 309 EP 316 PG 8 WC Medicine, Legal SC Legal Medicine GA 451JB UT WOS:000169798000014 PM 11305432 ER PT J AU Fernandez, DL Ring, D Jupiter, JB AF Fernandez, DL Ring, D Jupiter, JB TI Surgical management of delayed union and nonunion of distal radius fractures SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE distal radius; wrist; nonunion; bone graft; internal fixation AB Ten patients with malaligned fractures of the distal radius that demonstrated either delayed healing or the development of an atrophic or synovial nonunion on standard radiographs were treated with surgical realignment, stable internal fixation, and autogenous iliac crest bone grafting. All 10 fractures healed with acceptable radiologic alignment within 3 months of the index procedure. After an average follow-up period of 3 years 6 months (range, 2 years to 8 years 6 months) patients had an average of 105 degrees wrist flexion and extension, 145 degrees forearm rotation, and 73% grip strength compared with the opposite limb. In the treatment of malaligned, ununited fractures of the distal radius, specific techniques and implants must be tailored to the deformity of the distal radius and the shape of the distal fragment. A stable, well-aligned wrist with preservation of at least 50 degrees mobility in flexion and extension was achieved in every patient, but the final result was compromised by associated problems in 3 patients. (J Hand Surg 2001;26A:201-209. Copyright (C) 2001 by the American Society for Surgery of the Hand.). C1 Harvard Univ, Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Dept Orthopaed,Sch Med, Boston, MA 02114 USA. Univ Bern, Dept Orthopaed Surg, Bern, Switzerland. Lindenhof Hosp, Bern, Switzerland. RP Jupiter, JB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Dept Orthopaed,Sch Med, ACC 527,15 Parkman St, Boston, MA 02114 USA. NR 17 TC 29 Z9 29 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAR PY 2001 VL 26A IS 2 BP 201 EP 209 DI 10.1053/jhsu.2001.22917 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 415YT UT WOS:000167751700003 PM 11279565 ER PT J AU Vossen, KM Timothy, NH Manders, EK AF Vossen, KM Timothy, NH Manders, EK TI An unusual presentation of a linear epidermal nevus SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE hand surgery; linear nevus; epidermal nevus; hyperkeratosis ID PRECOCIOUS PUBERTY; SEBACEOUS SYNDROME; PROTEUS SYNDROME AB We report an unusual presentation of a linear epidermal nevus in an adolescent male. Epidermal nevi most commonly appear in infancy and early childhood. They often are found in association with other organ system anomalies. We describe a palmar linear epidermal nevus that caused impairment of the patient's use of his hand. Therapeutic management involved surgical excision of the nevus and reconstruction of the area with a full-thickness skin graft. (J Hand Surg 2001;26A3291-295. Copyright (C) 2001 by the American Society for Surgery of the Hand.). C1 Univ Pittsburgh, Sch Med, Div Plast & Reconstruct Surg, Dept Med, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Div Plast & Reconstruct Surg, Dept Surg, Pittsburgh, PA 15261 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Cambridge, MA 02138 USA. RP Manders, EK (reprint author), Univ Pittsburgh, Sch Med, Div Plast & Reconstruct Surg, Dept Med, 666 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. NR 28 TC 2 Z9 2 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAR PY 2001 VL 26A IS 2 BP 291 EP 295 DI 10.1053/jhsu.2001.20966 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 415YT UT WOS:000167751700014 PM 11279576 ER PT J AU Ostrow, JD Tiribelli, C AF Ostrow, JD Tiribelli, C TI New concepts in bilirubin neurotoxicity and the need for studies at clinically relevant bilirubin concentrations SO JOURNAL OF HEPATOLOGY LA English DT Editorial Material ID RESISTANCE-ASSOCIATED PROTEIN; CHOROID-PLEXUS EPITHELIUM; UNCONJUGATED BILIRUBIN; P-GLYCOPROTEIN; RAT-BRAIN; GUNN RAT; HEREDITARY HYPERBILIRUBINEMIA; NEONATAL HYPERBILIRUBINEMIA; CEREBELLAR HYPOPLASIA; BLOOD-BRAIN C1 Univ Trieste, Dept BBCM, Ctr Studi Fegato, I-34127 Trieste, Italy. Univ Washington, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Seattle Div, GI Hepatol Div, Res Serv, Seattle, WA 98108 USA. RP Tiribelli, C (reprint author), Univ Trieste, Dept BBCM, Ctr Studi Fegato, Via Giorgeri 1, I-34127 Trieste, Italy. NR 48 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD MAR PY 2001 VL 34 IS 3 BP 467 EP 470 DI 10.1016/S0168-8278(00)00051-9 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 421XP UT WOS:000168089100016 PM 11322210 ER PT J AU Xu, WD Smith-Franklin, BA Li, PL Wood, C He, J Du, QJ Bhat, GJ Kankasa, C Katinger, H Cavacini, LA Posner, MR Burton, DR Chou, TC Ruprecht, RM AF Xu, WD Smith-Franklin, BA Li, PL Wood, C He, J Du, QJ Bhat, GJ Kankasa, C Katinger, H Cavacini, LA Posner, MR Burton, DR Chou, TC Ruprecht, RM TI Potent neutralization of primary human immunodeficiency virus clade C isolates with a synergistic combination of human monoclonal antibodies raised against clade B SO JOURNAL OF HUMAN VIROLOGY LA English DT Article DE HIV-1 clade C; neutralization; human neutralizing monoclonal antibodies; passive immunization ID QUANTITATIVE-ANALYSIS; DEVELOPING-WORLD; HIV TYPE-1; SUBTYPE-C; TRANSMISSION; PREVENTION; INFECTION; SEROTYPES; GENERATION; PROTECTION AB Objectives: We investigated the ability of several human neutralizing monoclonal antibodies (mAbs), originally raised against human immunodeficiency virus (HIV) clade B isolates, to neutralize primary clade C isolates as single agents and in combination. tudy Design/Methods: HIV clade C isolates from five different countries were tested for susceptibility to neutralization by anti-clade B mAbs in human peripheral blood mononuclear cells. Monoclonal antibody combinations were evaluated for possible synergy. Results: All 20 primary HIV clade C isolates could be neutralized 97.5% to 100% by a quadruple combination of mAbs IgG1b12. 2G12, 2F5, and 4E10. These mAbs recognized conserved epitopes and were highly synergistic, resulting in strong cross-clade neutralization. Conclusions: In our previous experiment, a synergistic combination of human neutralizing mABs protected all macaque neonates against oral challenge with a simian-human immunodeficiency virus encoding HIV env. Together, our data suggest that passive immunization with currently available anticlade B mAbs could play a role in preventing HIV clade C transmission through breastfeeding. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Univ Nebraska, Sch Biol Sci, Lincoln, NE USA. Univ Teaching Hosp, Lusaka, Zambia. Inst Appl Microbiol, A-1190 Vienna, Austria. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Scripps Res Inst, Dept Immunol & Mol Biol, La Jolla, CA USA. Mem Sloan Kettering Canc Ctr, Biochem Pharmacol Lab, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Preclin Pharmacol Core Facil, New York, NY 10021 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. RI Chou, Ting-Chao/B-4111-2009 OI Chou, Ting-Chao/0000-0002-3340-1594 FU NIAID NIH HHS [R01 AI46177, R01 AI34266, P01 AI48240] NR 32 TC 49 Z9 53 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1090-9508 J9 J HUMAN VIROL JI J. Human Virol. PD MAR-APR PY 2001 VL 4 IS 2 BP 55 EP 61 PG 7 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA 446DL UT WOS:000169497600001 PM 11437315 ER PT J AU Ito, H Kurtz, J Shaffer, J Sykes, M AF Ito, H Kurtz, J Shaffer, J Sykes, M TI CD4 T cell-mediated alloresistance to fully MHC-mismatched allogeneic bone marrow engraftment is dependent on CD40-CD40 ligand interactions, and lasting T cell tolerance is induced by bone marrow transplantation with initial blockade of this pathway SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RENAL-ALLOGRAFT REJECTION; MONOCLONAL-ANTIBODY; HOST DISEASE; IN-VIVO; CD28-DEFICIENT MICE; THYMIC IRRADIATION; CLONAL DELETION; MIXED CHIMERISM; DENDRITIC CELL; CUTTING EDGE AB Costimulatory blockade can he used to promote allogeneic marrow engraftment and tolerance induction, but on its own is not 100% reliable, We sought to determine whether one or the other of the CD4 or CD8 T cell subsets of the recipient was primarily responsible for resistance to allogeneic marrow engraftment in mice receiving costimulatory blockade, and to use this information to develop a more reliable, minimal conditioning regimen for induction of mixed chimerism and transplantation tolerance, We demonstrate that a single anti-CD40 ligand mAb treatment is sufficient to completely overcome CD4 cell-mediated resistance to allogeneic marrow engraftment and rapidly induce CD4 cell tolerance, but does not reliably overcome CD8 CTL-mediated alloresistance, The data suggest that costimulation, which activates alloreactive CTL, is insufficient to activate alloreactive CD4 cells when the CD40 pathway is blocked. The addition of host CD8 T cell depletion to anti-CD40 ligand treatment reliably allows the induction of mixed chimerism and donor-specific skin graft tolerance in 3 Gy-irradiated mice receiving fully MHC-mismatched bone marrow grafts. Thus, despite the existence of multiple costimulatory pathways and pathways of APC activation, our studies demonstrate an absolute dependence on CD40-mediated events for CD4 cell-mediated rejection of allogeneic marrow. Exposure to donor bone marrow allows rapid tolerization of alloreactive CD4 cells when the CD40 pathway is blocked, leading to permanent marrow engraftment and intrathymic tolerization of T cells that develop subsequently. C1 Massachusetts Gen Hosp East, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. RP Sykes, M (reprint author), Massachusetts Gen Hosp East, Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, 13th St,Bldg 149-5102, Boston, MA 02129 USA. FU NHLBI NIH HHS [R01HL49915] NR 75 TC 77 Z9 79 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2001 VL 166 IS 5 BP 2970 EP 2981 PG 12 WC Immunology SC Immunology GA 404RW UT WOS:000167115300010 PM 11207246 ER PT J AU Dao, T Exley, M Mehal, WZ Tahir, SMA Snapper, S Taniguchi, M Balk, SP Crispe, IN AF Dao, T Exley, M Mehal, WZ Tahir, SMA Snapper, S Taniguchi, M Balk, SP Crispe, IN TI Involvement of CD1 in peripheral deletion of T lymphocytes is independent of NK T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IN-VIVO; MONOCLONAL-ANTIBODY; TRANSGENIC MICE; MOUSE CD1; LPR MICE; LIVER; ANTIGEN; ACTIVATION; APOPTOSIS; RECEPTOR AB During peripheral T cell deletion, lymphocytes accumulate in nonlymphoid organs including the liver, a tissue that expresses the nonclassical, MHC-like molecule, CD1. Injection of anti-CD3 Ab results in T cell activation, which in normal mice is followed by peripheral T cell deletion. However, in CD1-deficient mice, the deletion of the activated T cells from the lymph nodes was impaired. This defect in peripheral T cell deletion was accompanied by attenuated accumulation of CD8(+) T cells in the liver. In tetra-parental bone marrow chimeras, expression of CD1 on the T cells themselves was not required for T cell deletion, suggesting a role for CD1 on other tell with which the T cells interact. We tested whether this role was dependent on the Ag receptor-invariant, CD1-reactive subset of NK T cells using two other mutant mouse lines that lack most NK T cells, due to deletion of the genes encoding either beta (2)-microglobolin or the TCR element J alpha 281. However, these mice had no abnormality of peripheral T cell deletion. These findings indicate a novel role for CD1 in T cell deletion, and show that CD1 functions in this process through mechanisms that does not involve the major, TCR-invariant set of NK T cells. C1 Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06510 USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Canc Biol Program, Boston, MA 02215 USA. Massachusetts Gen Hosp, Med Serv, Gastrointestinal Unit, Boston, MA 02116 USA. Chiba Univ, Grad Sch Med, Dept Mol Immunol, Chuo Ku, Chiba, Japan. RP Crispe, IN (reprint author), Univ Rochester, Aab Inst Biomed Res, Ctr Vaccine Biol & Immunol, 601 Elmwood Ave, Rochester, NY 14620 USA. FU NIAID NIH HHS [AI37554, AI42955] NR 53 TC 15 Z9 15 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2001 VL 166 IS 5 BP 3090 EP 3097 PG 8 WC Immunology SC Immunology GA 404RW UT WOS:000167115300024 PM 11207260 ER PT J AU Slavik, JM Lim, DG Burakoff, SJ Hafler, DA AF Slavik, JM Lim, DG Burakoff, SJ Hafler, DA TI Uncoupling p70(s6) kinase activation and proliferation: Rapamycin-resistant proliferation of human CD8(+) T lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID P70 S6 KINASE; MHC CLASS-I; IMMUNOSUPPRESSIVE DRUGS; MAMMALIAN PROTEIN; CELL ACTIVATION; CYCLOSPORINE-A; EXPRESSION; PHOSPHORYLATION; TRANSPLANTATION; STIMULATION AB Rapamycin is a fungal macrolide that inhibits the proliferation of T cells. Studies in both animals and humans have found that rapamycin significantly reduces graft rejection. However, though CD8(+) T cells are involved in graft infiltration and rejection, little is known regarding the effects of rapamycin on CD8+ human T cell responses. In this study, we examined the mechanism of rapamycin-induced inhibition of Ag-driven activation of CD8(+) T cells. Surprisingly, a heterogeneous proliferative response in the presence of rapamycin was observed among different Ag-specific CD8(+) T cell clones; this was also observed in CD8(+) peripheral blood T cells activated with TCR cross-linking ex vivo. Inhibition of T cell proliferation by rapamycin was controlled by both the strength of signal delivered through the Ag receptor as well as the specific costimulatory signals received by the T cell. Rapamycin-resistant proliferation occurred despite inhibition of p70(56) kinase activity. Moreover, rapamycin-resistant proliferation of the CD8(+) T cell clones was blocked by anti-IL-2 Abs, suggesting that while some of the parallel pathways triggered by IL-2R signaling are sensitive to the effects of rapamycin, others account for the Ag-driven rapamycin resistance. These data provide a new framework for examining the specific mechanism of action of rapamycin in human disease. C1 Brigham & Womens Hosp, Ctr Neurol Dis, Lab Mol Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Hafler, DA (reprint author), Brigham & Womens Hosp, Ctr Neurol Dis, Lab Mol Immunol, 77 Av Louis Pasteur, Boston, MA 02115 USA. FU NIAID NIH HHS [R01 AI44447-01, P01 AI39671] NR 41 TC 33 Z9 34 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 2001 VL 166 IS 5 BP 3201 EP 3209 PG 9 WC Immunology SC Immunology GA 404RW UT WOS:000167115300037 PM 11207273 ER PT J AU Sykes, M AF Sykes, M TI Graft-versus-host alloresponses to treat nonlymphohematopoietic tumors: Is there a solid approach? SO JOURNAL OF IMMUNOTHERAPY LA English DT Editorial Material ID BONE-MARROW TRANSPLANTATION; STEM-CELL TRANSPLANTATION; COLONY-STIMULATING FACTOR; CYTOTOXIC T-LYMPHOCYTES; ANTITUMOR IMMUNITY; DENDRITIC CELLS; MYELOGENOUS LEUKEMIA; VACCINATION; IMMUNOTHERAPY; FEASIBILITY C1 Massachusetts Gen Hosp, Boston, MA 02129 USA. RP Sykes, M (reprint author), Massachusetts Gen Hosp, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. NR 29 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 MAR-APR PY 2001 VL 24 IS 2 BP 101 EP 103 DI 10.1097/00002371-200103000-00002 PG 3 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 406CP UT WOS:000167197600002 PM 11265765 ER PT J AU Akasaki, Y Kikuchi, T Homma, S Abe, T Kofe, D Ohno, T AF Akasaki, Y Kikuchi, T Homma, S Abe, T Kofe, D Ohno, T TI Antitumor effect of immunizations with fusions of dendritic and glioma cells in a mouse brain tumor model SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE glioma; dendritic cells; fusions; immunotherapy; interleukin 12 ID IN-VITRO; RECOMBINANT INTERLEUKIN-12; B7 COSTIMULATION; IMMUNITY; ANTIGEN; IL-12; IMMUNOGENICITY; EXPRESSION; REGRESSION; REJECTION AB The authors studied antitumor immunity conferred by fusions of dendritic and glioma cells in a mouse brain tumor model. Previous immunization with fusion cells (FCs) prevented tumor formation on challenge with glioma cells in the flank or in the brain. Efficacy was decreased when studies were performed in mice depleted of CD8(+) cells. In a treatment model, FCs were injected subcutaneously after tumor development in the brain. The administration of FCs alone had limited effects on survival of mice bearing brain tumors. Importantly, however, administration of FCs and recombinant interleukin-12 (rIL-12) remarkably prolonged the survival of mice with brain tumors. Cytotoxic T lymphocyte activity against glioma cells from immunized mice was also stimulated by coadministration of FCs and rIL-12 compared with that obtained with FCs or rIL-12 alone. These data support the therapeutic efficacy of combining FC-based vaccine therapy and rIL-12. C1 Jikei Univ, Sch Med, Inst DNA Med,Dept Oncol, Minato Ku, Tokyo 1058461, Japan. Jikei Univ, Sch Med, Dept Neurosurg, Tokyo 1058461, Japan. Jikei Univ, Sch Med, Dept Internal Med, Tokyo 1058461, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kikuchi, T (reprint author), Jikei Univ, Sch Med, Inst DNA Med,Dept Oncol, Minato Ku, 3-25-8 Nishishinbashi, Tokyo 1058461, Japan. NR 27 TC 92 Z9 101 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 MAR-APR PY 2001 VL 24 IS 2 BP 106 EP 113 DI 10.1097/00002371-200103000-00004 PG 8 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 406CP UT WOS:000167197600004 PM 11265767 ER PT J AU Gulick, RM Smeaton, LM D'Aquila, RT Eron, JJ Currier, JS Gerber, JG Acosta, E Sommadossi, JP Tung, R Snyder, S Kuritzkes, DR Murphy, RL AF Gulick, RM Smeaton, LM D'Aquila, RT Eron, JJ Currier, JS Gerber, JG Acosta, E Sommadossi, JP Tung, R Snyder, S Kuritzkes, DR Murphy, RL CA AIDS Clinical Trails Grp 373 Study TI Indinavir, nevirapine, stavudine, and lamivudine for human immunodeficiency virus-infected, amprenavir- experienced subjects: AIDS Clinical Trials Group protocol 373 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 7th Conference on Retroviruses and Opportunistic Infections CY JAN 29-FEB 03, 2000 CL SAN FRANCISCO, CALIFORNIA ID SAQUINAVIR-CONTAINING REGIMEN; PROTEASE INHIBITOR; RESISTANCE; RITONAVIR; TYPE-1; THERAPY AB This prospective, multicenter, open-label study was designed to determine the antiretroviral activity and safety of a 4-drug regimen: 1000 mg indinavir every 8 h with 200 mg nevirapine, 40 mg stavudine, and 150 mg lamivudine, each given twice daily in amprenavir-experienced subjects. The primary end points of the study were the human immunodeficiency virus (HIV) RNA level and CD4 cell count responses. Fifty-six subjects were enrolled and were changed from amprenavir-containing regimens to the 4-drug regimen. Overall, at week 48, 33 (59%) of 56 subjects had HIV RNA levels <500 copies/mL (intent-to-treat analysis, where missing values equal 500 copies/mL) and CD4 cell counts increased by 94 cells/mm(3) from baseline. Subjects who had previously taken amprenavir combination therapy were more likely to experience virologic failure than those who had taken amprenavir monotherapy (odds ratio, 7.7; P = .0012). In this study, most subjects who had taken amprenavir-based regimens and who changed to a 4-drug regimen achieved subsequent durable virologic suppression. C1 Cornell Univ, Weill Med Coll, Cornell Clin Trials Unit, New York, NY 10021 USA. NYU, Sch Med, New York, NY USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Vertex Pharmaceut, Cambridge, MA USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Univ So Calif, Los Angeles, CA USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Alabama, Birmingham, AL USA. Social & Sci Syst, Rockville, MD USA. Northwestern Univ, Sch Med, Chicago, IL USA. RP Gulick, RM (reprint author), Cornell Univ, Weill Med Coll, Cornell Clin Trials Unit, Box 566,525 E 68th St, New York, NY 10021 USA. OI Murphy, Robert/0000-0003-3936-2052 FU NCRR NIH HHS [RR-00046, RR-00051, RR-00096]; NIAID NIH HHS [AI-38858, AI-27742, AI-27665, AI-25915, AI-32775, AI-25868, AI-27659, AI-27673, AI-32770, AI-46386] NR 25 TC 13 Z9 14 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 MAR 1 PY 2001 VL 183 IS 5 BP 715 EP 721 DI 10.1086/318820 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 399WD UT WOS:000166836500005 PM 11181147 ER PT J AU Musher, DM Phan, HM Baughn, RE AF Musher, DM Phan, HM Baughn, RE TI Protection against bacteremic pneumococcal infection by antibody to pneumolysin SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the Infectious-Diseases-Society-of-America CY SEP 08, 2000 CL NEW ORLEANS, LOUISIANA SP Infect Dis Soc Amer ID STREPTOCOCCUS-PNEUMONIAE; VIRULENCE AB Pneumolysin is an important virulence factor of Streptococcus pneumoniae. This study examined the hypothesis that human antibody to pneumolysin provides protection against pneumococcal infection. At the time of hospital admission, patients with nonbacteremic pneumococcal pneumonia had higher levels of serum anti-pneumolysin IgG than did patients with bacteremic pneumococcal pneumonia or uninfected control subjects. IgG levels rose significantly during convalescence in patients with bacteremic pneumonia, reaching levels observed in nonbacteremic patients. Purified human anti-pneumolysin IgG protected mice against intraperitoneal challenge with S. pneumoniae types 1 or 4 in a dose-related fashion; mice that received anti-pneumolysin IgG had a greater likelihood of surviving challenge and had negative blood cultures. Pneumolysin damages epithelial cells and inhibits phagocytic function of polymorphonuclear leukocytes. One hypothesis that might explain the study results is that, early in infection, IgG to pneumolysin blocks these effects in the alveoli, thereby protecting the host against bacteremic pneumococcal disease. C1 Dept Vet Affairs Med Ctr, Infect Dis Sect, Med Serv, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Dermatol, Houston, TX 77030 USA. RP Musher, DM (reprint author), Dept Vet Affairs Med Ctr, Infect Dis Sect, Med Serv, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 15 TC 49 Z9 50 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 MAR 1 PY 2001 VL 183 IS 5 BP 827 EP 830 DI 10.1086/318833 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 399WD UT WOS:000166836500021 PM 11181163 ER PT J AU Anzueto, A AF Anzueto, A TI Untitled SO JOURNAL OF INTERNATIONAL MEDICAL RESEARCH LA English DT Editorial Material ID CHRONIC-BRONCHITIS; DISEASE C1 Audie L Murphy Mem Vet Hosp, Pulm Dis Sect 3E, San Antonio, TX 78284 USA. RP Anzueto, A (reprint author), Audie L Murphy Mem Vet Hosp, Pulm Dis Sect 3E, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. NR 13 TC 1 Z9 1 U1 0 U2 0 PU CAMBRIDGE MED PUBL PI WORTHING PA WICKER HOUSE, HIGH ST, WORTHING BN11 1DJ, W SUSSEX, ENGLAND SN 0300-0605 J9 J INT MED RES JI J. Int. Med. Res. PD MAR-APR PY 2001 VL 29 IS 2 BP 49 EP 50 PG 2 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 433QU UT WOS:000168771900001 PM 11393348 ER PT J AU Brancaleon, L Bamberg, MP Sakamaki, T Kollias, N AF Brancaleon, L Bamberg, MP Sakamaki, T Kollias, N TI Attenuated total reflection-fourier transform infrared spectroscopy as a possible method to investigate biophysical parameters of stratum corneum in vivo SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE infrared spectroscopy; in vivo spectroscopy; skin hydration ID HUMAN-SKIN; PERMEABILITY BARRIER; WATER-LOSS; SEBACEOUS GLAND; FATTY-ACIDS; SURFACE; LIPIDS; EPIDERMIS; HYDRATION; INVIVO AB We investigated the use of attenuated total reflection-Fourier transform infrared spectroscopy as a method to study differences in the molecular components of human stratum corneum in vivo. These variations as a function of the anatomic site and of the depth into its layered structure are important to understand the biology and physiology of the tissue. In this preliminary study we have investigated spectroscopic changes in 18 healthy individuals. Total reflection-Fourier transform infrared spectroscopy represents a potentially powerful tool to study biophysical properties of surfaces. We observed that, in vivo, biophysical parameters of the stratum corneum (such as hydration, lipid composition, and conformation of the aliphatic chains) are indeed dependent on the anatomic site. As in total reflection-Fourier transform infrared spectroscopy experiments the penetration depth of the evanescent field into the stratum corneum is comparable with the thickness of a layer of corneocytes, this technique can be used to follow the distribution of lipids, water, and proteins as a function of depth into the tissue. We found that, in vivo, these molecular components are non-uniformly distributed, in agreement with the presence of water and lipid reservoirs as observed with ex vivo ultrastructural investigations. Composition and conformational order of lipids are also a function of depth into the stratum corneum. Finally we compared the in vivo superficial hydration measured using the infrared absorption of the OH stretch of water, with the hydration measured using the Skicon hygrometer. Our results indicate that total reflection-Fourier transform infrared spectroscopy might be useful to measure important chemical and biophysical parameters of stratum corneum in vivo. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photochem, Boston, MA USA. RP Brancaleon, L (reprint author), Univ Dundee, Ninewells Hosp & Med Sch, Dept Dermatol, Dundee DD1 9SY, Scotland. RI Brancaleon, Lorenzo/B-5625-2009 NR 45 TC 49 Z9 53 U1 1 U2 6 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAR PY 2001 VL 116 IS 3 BP 380 EP 386 DI 10.1046/j.1523-1747.2001.01262.x PG 7 WC Dermatology SC Dermatology GA 406NN UT WOS:000167222200005 PM 11231311 ER PT J AU Pollak, VE Lorch, JA Means, RT AF Pollak, VE Lorch, JA Means, RT TI Unanticipated favorable effects of correcting iron deficiency in chronic hemodialysis patients SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the American-Society-of-Nephrology CY NOV 01-08, 1999 CL MIAMI, FLORIDA SP Amer Soc Nephrol ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; STAGE RENAL-DISEASE; THERAPY; ANEMIA; NUTRITION; MORTALITY; SUPPLEMENTATION; MORBIDITY; DIALYSIS AB Background: Correction of anemia in hemodialysis patients is seldom completely attained, and the response of parameters other than hemoglobin concentration to anemia correction has not been evaluated in detail, Methods: Laboratory parameters that suggest iron deficiency occurred in 10-15% of 206 recombinant human erythropoietin (rhEPO)-treated patients. Oral iron was given for 9 months and intravenous iron thereafter on a patient-specific basis when iron deficiency was evident. Eighty-seven hemodialysis patients with data for 12 months were followed for another 12 months. A computerized information system enabled data management and analysis. Results: With oral iron, serum ferritin decreased (P<0.001), indicating further iron depletion. With intravenous iron, hemoglobin increased, evidence of iron deficiency decreased, and less rhEPO was needed. Striking macrocytosis appeared. Serum albumin and serum creatinine/kg body weight tan index of muscle mass) increased, while blood pressure decreased, Data were reanalyzed in four mean corpuscular volume (MCV) quartiles and two ferritin subsets at study onset. Iron deficient erythropoiesis (low MCV, mean corpuscular hemoglobin [MCH], and transferrin saturation) was striking in quartile 1; low ferritin was prevalent in all quartiles, With intravenous iron, hemoglobin increased only in quartile 1, the quartile with the greatest decrease (52%) in rhEPO dose. MCV increased in all quartiles (P<0.001), Serum albumin increased in all MCV quartiles and both ferritin subsets, but significant creatinine/kg increase and blood pressure decrease occurred only in the low-ferritin subset. Conclusions: Macrocytosis occurred with intravenous iron replacement. The universal MCV increase suggests unrecognized, inadequately treated, folic acid deficiency unmasked by an adequate iron supply. There was also improved well being, Effects were most clearly evident in patients with deficient iron stores. C1 MIQS Inc, Boulder, CO 80303 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. St Lukes Hosp, Dept Med, New York, NY USA. Columbia Univ, Coll Phys & Surg, New York, NY 10027 USA. Med Univ S Carolina, Div Hematol Oncol, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Pollak, VE (reprint author), MIQS Inc, 5621-D Arapahoe Ave, Boulder, CO 80303 USA. RI Means, Robert/A-4454-2008 NR 37 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 2001 VL 49 IS 2 BP 173 EP 183 DI 10.2310/6650.2001.34044 PG 11 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 405WZ UT WOS:000167184700007 PM 11288758 ER PT J AU Pound, EM Kang, JX Leaf, A AF Pound, EM Kang, JX Leaf, A TI Partitioning of polyunsaturated fatty acids, which prevent cardiac arrhythmias, into phospholipid cell membranes SO JOURNAL OF LIPID RESEARCH LA English DT Article DE eicosapentaenoic acid; docosahexaenoic acid; arachidonic acid; fish oil; sudden cardiac death ID UNILAMELLAR VESICLES; MYOCYTES; ALBUMIN; CURRENTS; DEATH; RATES; DOGS AB It has been demonstrated in animal studies that polyunsaturated fatty acids (PUFA) prevent ischemia-induced malignant ventricular arrhythmias, a major cause of sudden cardiac death in humans, To learn how these PUFA, at low micromolar concentrations, exert their antiarrhythmic activity, we studied their effects in vitro on the contractions of isolated cardiac myocytes and the conductances of their sarcolemmal ion channels, These fatty acids directly stabilize electrically every cardiac myocyte by modulating the conductances of specific ion channels in their sarcolemma, In this study, we determined the molar ratio of PUFA to the moles of phospholipid (PL) in cell membranes to learn if the ratio is so lo rv as to preclude the possibility that the primary site of action of PUFA is on the packing of the membrane FL. [H-3]-arachidonic acid (AA) was used to measure the incorporation of PUFA, and the inorganic phosphorous of the PL was determined as a measure of the moles of PL in the cell membrane. Our results indicate that the mole percent of AA to moles of phospolipid is very low (less than or equal to1.0) at the concentrations that affect myocyte contraction and the conductance of voltage-dependent Na+ and L-type Ca2+ channels in rat cardiomyocytes and in alpha -subunits of human myocardial Na+ channels. In conclusion, it seems highly unlikely that these fatty acids are affecting the packing of PL within cell membranes as their way of modulating changes in cell membrane ion currents and in preventing arrhythmias in our contractility studies. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Leaf, A (reprint author), Massachusetts Gen Hosp E, Bldg 149,Room 4001,13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL62284]; NIDDK NIH HHS [DK38165] NR 21 TC 71 Z9 76 U1 0 U2 3 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD MAR PY 2001 VL 42 IS 3 BP 346 EP 351 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 416XY UT WOS:000167806800004 PM 11254745 ER PT J AU White, AR Huang, XD Jobling, MF Barrow, CJ Beyreuther, K Masters, CL Bush, AI Cappai, R AF White, AR Huang, XD Jobling, MF Barrow, CJ Beyreuther, K Masters, CL Bush, AI Cappai, R TI Homocysteine potentiates copper- and amyloid beta peptide-mediated toxicity in primary neuronal cultures: possible risk factors in the Alzheimer's-type neurodegenerative pathways SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE cell culture; dementia; folate deficiency; neurodegeneration; transition metals ID AMYOTROPHIC-LATERAL-SCLEROSIS; MTT FORMAZAN EXOCYTOSIS; OXIDATIVE STRESS; HYDROGEN-PEROXIDE; PRION-PROTEIN; CORTICAL-NEURONS; A-BETA; GLUTATHIONE DEPLETION; INDUCED NEUROTOXICITY; COGNITIVE IMPAIRMENT AB Oxidative stress may have an important role in the progression of neurodegenerative disorders such as Alzheimer's disease (AD) and prion diseases. Oxidative damage could result from interactions between highly reactive transition metals such as copper (Cu) and endogenous reducing and/or oxidizing molecules in the brain. One such molecule, homocysteine, a thiol-containing amino acid, has previously been shown to modulate Cu toxicity in HeLa and endothelial cells in vitro. Due to a possible link between hyperhomocysteinemia and AD, we examined whether interaction between homocysteine and Cu could potentiate Cu neurotoxicity. Primary mouse neuronal cultures were treated with homocysteine and either Cu (II), Fe (II or III) or Zn (II). Homocysteine was shown to selectively potentiate toxicity from low micromolar concentrations of Cu. The toxicity of homocysteine/Cu coincubation was dependent on the ability of homocysteine to reduce Cu(II) as reflected by the inhibition of toxicity with the Cu(I)-specific chelator, bathocuproine disulphonate. This was supported by data showing that homocysteine reduced Cu (II) more effectively than cysteine or methionine but did not reduce Fe (III) to Fe (II). Homocysteine also generated high levels of hydrogen peroxide in the presence of Cu (II) and promoted A beta /Cu-mediated hydrogen peroxide production and neurotoxicity. The potentiation of metal toxicity did not involve excitotoxicity as ionotropic glutamate receptor antagonists had no effect on neurotoxicity. Homocysteine alone also had no effect on neuronal glutathione levels. These studies suggest that increased copper and/or homocysteine levels in the elderly could promote significant oxidant damage to neurons and may represent additional risk factor pathways which conspire to produce AD or related neurodegenerative conditions. C1 Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. Mental Hlth Res Inst, Parkville, Vic, Australia. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Unit, Charlestown, MA USA. Univ Melbourne, Sch Chem, Parkville, Vic 3052, Australia. Univ Heidelberg, Ctr Mol Biol, D-6900 Heidelberg, Germany. RP White, AR (reprint author), Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia. RI Bush, Ashley/A-1186-2007; White, Anthony/P-5596-2016; OI Bush, Ashley/0000-0001-8259-9069; White, Anthony/0000-0003-1802-9891; Cappai, Roberto/0000-0002-9505-8496 NR 65 TC 175 Z9 184 U1 0 U2 5 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAR PY 2001 VL 76 IS 5 BP 1509 EP 1520 DI 10.1046/j.1471-4159.2001.00178.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 407GX UT WOS:000167264800025 PM 11238735 ER PT J AU Kimchi, EY Kajdasz, S Bacskai, BJ Hyman, BT AF Kimchi, EY Kajdasz, S Bacskai, BJ Hyman, BT TI Analysis of cerebral amyloid angiopathy in a transgenic mouse model of Alzheimer disease using in vivo multiphoton microscopy SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article ID A-BETA; PRECURSOR PROTEIN; ENDOTHELIAL-CELLS; MICE; MUTANT; VASOACTIVITY; DIAGNOSIS AB Transgenic mice overexpressing the human amyloid precursor protein (APPV717F) develop cerebral amyloid angiopathy (CAA) as they age. We have examined the effect of CAA on blood vessels in vivo using multiphoton laser scanning microscopy. We are able to simultaneously detect, in an alive but anesthetized animal, fluorescent angiography of microvessels as well as the presence of amyloid angiopathy in 3-dimensional volumes near the surface of the brain. Analysis revealed dilation of the portions of vessels that were associated with amyloid deposition, even when that amyloid deposition was quite mild. In addition, analysis of the 3-dimensional reconstruction of the relationship between the vasculature and CAA suggest that CAA is initiated close to branch points of vessels. Taken together, these data suggest that CAA has a substantial effect on the physiology of the microvasculature in vivo. C1 Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Lab, Boston, MA 02129 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Alzheimers Dis Res Lab, 149 13th St,CNY 6305, Boston, MA 02129 USA. FU NIA NIH HHS [AG 08487] NR 19 TC 28 Z9 29 U1 0 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAR PY 2001 VL 60 IS 3 BP 274 EP 279 PG 6 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 408BT UT WOS:000167307200005 PM 11245211 ER PT J AU Hinkin, CH Castellon, SA Hardy, DJ Farinpour, R Newton, H Singer, E AF Hinkin, CH Castellon, SA Hardy, DJ Farinpour, R Newton, H Singer, E TI Methylphenidate improves HIV-1-associated cognitive slowing SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the International-Neuropsychological-Society CY FEB, 1999 CL BOSTON, MASSACHUSETTS SP Int Neuropsychol Soc ID HIV-INFECTED INDIVIDUALS; AIDS-RELATED COMPLEX; PARKINSONS-DISEASE; TASK-PERFORMANCE; HOMOSEXUAL MEN; DOPAMINE; IMPAIRMENT; SYSTEM; MEMORY; SPEED AB Sixteen HIV-1 seropositive individuals participated in a single-blind, placebo-controlled, cross-over-design study of the effectiveness of 30 mg/day of methytphenidate (MPH) in the treatment of HIV-associated cognitive slowing. Regression analyses revealed that participants who entered the study with a greater degree of either depressive symptomatology or cognitive slowing tended to demonstrate a better response to MPH on computerized measures of choice and dual-task reaction time. Participants without evidence of cognitive slowing at study entry did not show greater improvement on MPH than on placebo. Contrary to expectation, symptoms of depression did not respond;rd better to MPH than to placebo, regardless of initial symptomatology. Information processing slowing in HIV-I infection therefore appears amenable to pharmacologic intervention with the dopamine agonist MPH. However, results suggest clinicians should consider reserving the use of MPH for patients with more pronounced cognitive and affective deficits. C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. RP Hinkin, CH (reprint author), Univ Calif Los Angeles, Sch Med, Dept Psychiat, 760 Westwood Plaza,Room C8-747, Los Angeles, CA 90024 USA. OI newton, thomas/0000-0002-3198-5901 NR 34 TC 37 Z9 39 U1 0 U2 4 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SPR PY 2001 VL 13 IS 2 BP 248 EP 254 DI 10.1176/appi.neuropsych.13.2.248 PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 432JE UT WOS:000168687800011 PM 11449032 ER PT J AU Baba, H Kohno, T Moore, KA Woolf, CJ AF Baba, H Kohno, T Moore, KA Woolf, CJ TI Direct activation of rat spinal dorsal horn neurons by prostaglandin E2 SO JOURNAL OF NEUROSCIENCE LA English DT Article DE inflammation; central sensitization; prostaglandin E2; EP2 receptor; deep dorsal horn; allodynia; hyperalgesia ID CYCLOOXYGENASE-2 MESSENGER-RNA; SUBSTANTIA-GELATINOSA NEURONS; NONSELECTIVE CATION CHANNELS; INDUCED NEUROPEPTIDE RELEASE; SENSORY NEURONS; PERIPHERAL INFLAMMATION; PROSTANOID RECEPTORS; UNANESTHETIZED RATS; AMINO-ACIDS; CORD SLICES AB Whole-cell patch-clamp and intracellular recording techniques have been used to study the action of prostaglandin E2 (PGE2) on neurons in adult rat transverse spinal cord slices. Bath-applied PGE2 (1-20 muM) induced an inward current or membrane depolarization in the majority of deep dorsal horn neurons (laminas III-VI; 83 of 139 cells), but only in a minority of lamina II neurons (6 of 53 cells). PGE2 alone never elicited spontaneous action potentials; however, it did convert subthreshold EPSPs to suprathreshold, leading to action potential generation. PGE2-induced inward currents were unaffected by perfusion with either a Ca2+-free/high Mg2+ (5 mM) solution or tetrodotoxin (1 muM), indicating a direct postsynaptic action. Both 17-phenyl trinor prostaglandin E2 (an EP1 agonist) and sulprostone (an EP3 agonist) had little effect on membrane current, whereas butaprost methyl ester (an EP2 agonist) mimicked the effect of PGE2. Depolarizing responses to PGE2 were associated with a decrease in input resistance, and the amplitude of inward current was decreased as the holding potential was depolarized. PGE2-induced inward currents were reduced by substitution of extracellular Na+ with N-methyl-D-glucamine and inhibited by flufenamic acid (50-200 muM), which is compatible with activation of a nonselective cation channel. These results suggest that PGE2, acting via an EP2-like receptor, directly depolarizes spinal neurons. Moreover, these findings imply an involvement of spinal cord-generated prostanoids in modulating sensory processing through an alteration in dorsal horn neuronal excitability. C1 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. FU NINDS NIH HHS [NS38253-01] NR 37 TC 147 Z9 153 U1 0 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 1 PY 2001 VL 21 IS 5 BP 1750 EP 1756 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 404YG UT WOS:000167129700036 PM 11222664 ER PT J AU Proctor, SP Heaton, KJ White, RF Wolfe, J AF Proctor, SP Heaton, KJ White, RF Wolfe, J TI Chemical sensitivity and chronic fatigue in Gulf War veterans: A brief report SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID POPULATION-BASED SURVEY; HEALTH; PREVALENCE; SYMPTOMS; STRESS; DEFINITION; ILLNESS; LIFE AB The foci of this brief report are to (1) describe the prevalence of chemical sensitivity (CS) and chronic fatigue (CF) symptomatology and of presumptive multiple CS and CF syndrome diagnoses, and (2) explore the potential overlap between one purported case definition (ie, chronic multi-symptom illness) and these unexplained symptom syndromes in a well-characterized group of Gulf War veterans, The number of subjects with CS and CF symptomatology and presumptive multiple CS and CF syndrome diagnoses was higher in the Gulf War-deployed group compared with a group deployed to Germany during the Gulf War However, the percent differences were not significant when comparing the presumptive diagnoses of multiple CS and CF syndrome. The characteristic differences between the groups and the overlap with chronic multi-symptom illness are also discussed. C1 Boston Environm Hazards Ctr 116B 4, Boston, MA 02130 USA. VA Boston Healthcare Syst, Psychol Serv, Boston, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Univ So Denmark, Dept Environm Med, Odense, Denmark. RP Proctor, SP (reprint author), Boston Environm Hazards Ctr 116B 4, 150 S Huntington Ave, Boston, MA 02130 USA. RI Heaton, Kristin/E-3660-2013 NR 30 TC 13 Z9 14 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD MAR PY 2001 VL 43 IS 3 BP 259 EP 264 DI 10.1097/00043764-200103000-00014 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 414TR UT WOS:000167682700014 PM 11285874 ER PT J AU Castano, FJ Troulis, MJ Glowacki, J Kaban, LB Yates, KE AF Castano, FJ Troulis, MJ Glowacki, J Kaban, LB Yates, KE TI Proliferation of masseter myocytes after distraction osteogenesis of the porcine mandible SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article; Proceedings Paper CT 81st Annual Meeting of the American-Association-of-Oral-and-Maxillofacial-Surgeons CY SEP, 1999 CL BOSTON, MASSACHUSETTS SP Amer Assoc Oral & Maxillofacial Surgeons ID ADVANCEMENT SURGERY; RIGID FIXATION; STABILITY; MUSCLE; RELAPSE; OSTEOTOMIES; RABBITS; GROWTH AB Purpose: Long-term success of distraction osteogenesis depends on the ability of the surrounding soft tissues to tolerate distraction forces and to adapt to the resulting increase in skeletal length and volume. The hypothesis tested in this study was that mandibular elongation by distraction induces myocyte proliferation. Materials and Methods: Unilateral mandibular angle osteotomies were performed in 16 Yucatan minipigs. The hemimandibles were lengthened using semiburied distraction devices (Synthes Maxillofacial, Paoli, PA) with 0-day latency, 1, 2, or 4 mm/d distraction rates, and a neutral fixation period of twice the gap size in days. In 2 additional animals, the dissection anti osteotomies were performed, and distraction devices were placed without activation (sham control). At the end of neutral fixation, tissues were taken from masseter muscle overlying the osteotomy and the equivalent region on the unoperated side (contralateral control). Proliferation of myocytes was estimated using immunol histochemical localization with antibodies against proliferating cell nuclear antigen (PCNA). Results: Muscle overlying the distracted mandible showed 6-fold more PCNA-positive myocytes (16.8% +/- 11.3%) than the contralateral control side (2.8% +/- 1.1%, P < .0001). In the 2 sham-control animals, there was a low index of PCNA-positive myocytes on both the osteotomy (2%, 5%) and the contralateral sides (1%, 2%). Conclusions: The results of this study suggest that distraction of the porcine mandible by the protocol described induces myocyte proliferation in the masseter muscle. A proliferative response may contribute to improved long-term stability of mandibular expansion by distraction osteogenesis. (C) 2001 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Skeletal Biol Res Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Oral & Maxillofacial Surg, Boston, MA USA. Harvard Univ, Sch Dent Med, Boston, MA USA. RP Yates, KE (reprint author), Massachusetts Gen Hosp, Skeletal Biol Res Ctr, 149 13th St, Charlestown, MA 02129 USA. NR 39 TC 30 Z9 32 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAR PY 2001 VL 59 IS 3 BP 302 EP 307 DI 10.1053/joms.2001.21000 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 407BJ UT WOS:000167251300014 PM 11243613 ER PT J AU Peretti, GM Caruso, EM Randolph, MA Zaleske, DJ AF Peretti, GM Caruso, EM Randolph, MA Zaleske, DJ TI Meniscal repair using engineered tissue SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article ID MENISCECTOMY; CARTILAGE; KNEE; MICROVASCULATURE AB In this study, devitalized meniscal tissue pre-seeded with viable cultured chondrocytes was used to repair a bucket-handle incision in meniscal tissue transplanted to nude mice. Lamb knee menisci were devitalized by cyclic freezing and thawing. Chips measuring four by two by one-half millimeters were cut from this devitalized tissue to serve as scaffolds. These chips were then cultured either with or without viable allogeneic lamb chondrocytes. From the inner third of the devitalized meniscal tissue, rectangles were also cut approximately 8 x 6 mm. A 4 mm bucket-handle type incision was made in these blocks. The previously prepared chips either with (experimental group) or without viable chondrocytes (control group) were positioned into the incisions and secured with suture. Further control groups included blocks of devitalized menisci with incisions into which no chips were positioned and either closed with suture or left open with no suture. Specimens were transplanted to subcutaneous pouches of nude mice for 14 weeks. After 14 weeks, seven of eight experimental specimens (chips with viable chondrocytes) demonstrated bridging of the incision assessed by gross inspection and manual distraction. All the control groups were markedly different from the experimental group in that the incision remained grossly visible. Histological analysis was consistent with the differences apparent at the gross level. Only the experimental specimens (chips with viable chondrocytes) with gross bridging demonstrated obliteration of the interface between incision and scaffold. None of the control specimens revealed any cells or tissue filling the incision. Tissue engineering using scaffolds and viable cells may have an application in meniscal repair in vivo. (C) 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Orthopaed Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Plast Surg Res Labs, Boston, MA 02114 USA. Hosp San Raffaele, Dept Orthopaed, I-20132 Milan, Italy. RP Zaleske, DJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Orthopaed Serv, WACC 507,15 Parkman St, Boston, MA 02114 USA. RI Peretti, Giuseppe/K-6358-2016 OI Peretti, Giuseppe/0000-0001-9341-7187 NR 34 TC 36 Z9 37 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0736-0266 J9 J ORTHOPAED RES JI J. Orthop. Res. PD MAR PY 2001 VL 19 IS 2 BP 278 EP 285 DI 10.1016/S0736-0266(00)90010-X PG 8 WC Orthopedics SC Orthopedics GA 429AF UT WOS:000168493300016 PM 11347702 ER PT J AU Casarett, DJ AF Casarett, DJ TI Differences between patients referred to hospice from academic vs. non-academic settings SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE hospice; palliative care; social support; Medicare ID ANTICIPATORY GRIEF; SURVIVAL AB Hospice is designed to provide end-of-life care to patients who are terminally ill. Increasingly, hospices are developing affiliations with academic medical centers. However; little is known about this group of patients, and how their needs may differ from those of the general population of hospice patients. To identify differences between patients referred to an urban, nonprofit hospice from academic vs. non-academic medical centers, a retrospective cohort study of 1, 691 patients admitted to an inpatient and outpatient hospice program was conducted. Admission dates were between January 1997 and January 1999, and data were gathered until discharge or death. The major outcome of interest was the need for nursing interventions at the time of entry into hospice. Patients referred from academic medical centers were younger, had higher incomes, and were less likely to have Medicare or Medicaid. Patients referred from academic medical centers were less likely to have a Do Not Resuscitate order or a living will, and had more medical and nursing needs. Survival analysis revealed no difference in length of stay between patients referred from academic and non-academic medical centers. Patients referred to hospice from academic medical centers have greater needs for nursing and medical care than do patients referred from nan-academic medical centers. The implications of these findings for policy): are discussed, J Pain Symptom Manage 2001; 21:197-203. (C) U.S. Cancer Pain Relief Committee, 2001. C1 Univ Penn, Ctr Bioeth, Inst Aging, Div Geriatr, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Casarett, DJ (reprint author), Univ Penn, Ctr Bioeth, Inst Aging, Div Geriatr, 3615 Chestnut St, Philadelphia, PA 19104 USA. NR 11 TC 9 Z9 9 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD MAR PY 2001 VL 21 IS 3 BP 197 EP 203 DI 10.1016/S0885-3924(00)00260-8 PG 7 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 406NG UT WOS:000167221600007 PM 11239738 ER PT J AU Du, MQ Liu, H Diss, TC Hamoudi, RA Cabecadas, J Dong, HY Harris, N Isaacson, PG AF Du, MQ Liu, H Diss, TC Hamoudi, RA Cabecadas, J Dong, HY Harris, N Isaacson, PG TI KSHV positive germinotropic lymphoma: A new KSHV associated lymphoproliferative disorder SO JOURNAL OF PATHOLOGY LA English DT Meeting Abstract C1 Royal Free & UCL, Sch Med, Dept Histopathol, London, England. Inst Canc Res, Gene Cloning Ctr, Sutton, Surrey, England. Inst Portugues Oncol Francisco Gentil, Serv Anat Patol, Oporto, Portugal. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3417 J9 J PATHOL JI J. Pathol. PD MAR PY 2001 VL 193 SU S BP 18A EP 18A PG 1 WC Oncology; Pathology SC Oncology; Pathology GA 410YV UT WOS:000167469400071 ER PT J AU Spiekermann, GM Walker, WA AF Spiekermann, GM Walker, WA TI Oral tolerance and its role in clinical disease SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Review ID INFLAMMATORY-BOWEL-DISEASE; MYELIN BASIC-PROTEIN; GROWTH-FACTOR-BETA; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; RESTRICTED T-CELLS; DEPENDENT DIABETES-MELLITUS; COLLAGEN-INDUCED ARTHRITIS; MUCOSAL IMMUNE-RESPONSES; MESSENGER-RNA EXPRESSION; SHORT RAGWEED EXTRACT C1 Harvard Univ, Sch Med, Childrens Hosp,Gastrointestinal Cell Biol Lab, Combined Program Pediat Gastroenterol & Nutr, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp,Mucosal Immunol Lab, Combined Program Pediat Gastroenterol & Nutr, Boston, MA USA. RP Walker, WA (reprint author), Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Mucosal Immunol Lab, 149 13th St 1493404, Charlestown, MA 02129 USA. NR 166 TC 29 Z9 39 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 MAR PY 2001 VL 32 IS 3 BP 237 EP 255 DI 10.1097/00005176-200103000-00003 PG 19 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 426GX UT WOS:000168342400003 PM 11345170 ER PT J AU Ding, HF Fisher, DE AF Ding, HF Fisher, DE TI P53, caspase 8, and regulation of apoptosis after ionizing radiation SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE p53; apoptosis; transcription-independent; fadd ID WILD-TYPE P53; CELL-CYCLE ARREST; TRANSCRIPTIONAL ACTIVATION; P53-DEPENDENT APOPTOSIS; P53-MEDIATED APOPTOSIS; RECEPTOR/LIGAND SYSTEM; CANCER-THERAPY; CD95 FAS/APO-1; CYTOCHROME-C; IN-VIVO C1 Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol Hematol, Boston, MA 02115 USA. RP Fisher, DE (reprint author), 44 Binney St, Boston, MA 02115 USA. NR 29 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD MAR-APR PY 2001 VL 23 IS 3 BP 185 EP 188 DI 10.1097/00043426-200103000-00014 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 419LT UT WOS:000167951100012 PM 11305724 ER PT J AU Neuzil, KM AF Neuzil, KM TI Influenza vaccine in children with asthma: Why no progress? SO JOURNAL OF PEDIATRICS LA English DT Editorial Material ID IMPACT; RATES C1 Univ Washington, Sch Med, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Neuzil, KM (reprint author), Univ Washington, Sch Med, 1660 S Columbian Way 111, Seattle, WA 98108 USA. NR 23 TC 16 Z9 16 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAR PY 2001 VL 138 IS 3 BP 301 EP 303 DI 10.1067/mpd.2001.113101 PG 3 WC Pediatrics SC Pediatrics GA 413BZ UT WOS:000167591200001 PM 11241032 ER PT J AU Emerman, CL Cydulka, RK Crain, EF Rowe, BH Radeos, MS Camargo, CA AF Emerman, CL Cydulka, RK Crain, EF Rowe, BH Radeos, MS Camargo, CA CA MARC Investigators TI Prospective multicenter study of relapse after treatment for acute asthma among children presenting to the emergency department SO JOURNAL OF PEDIATRICS LA English DT Article ID ORAL CORTICOSTEROIDS; PEDIATRIC ASTHMA; CONTROLLED TRIAL; PEAK FLOW; MANAGEMENT; RECOVERY; VISITS; SCORE AB Objective: Single-center studies have reported varying relapse rates after treatment of patients with acute asthma, We determined the relapse rate after emergency department (ED) treatment in a cohort of children. Design: This was a prospective inception cohort study performed during 1997-1998. Setting: The study was performed in 44 EDs including both general and pediatric centers. Patients: Children (n = 1184) aged 2 to 17 years who had been admitted to EDs, with acute asthma restricted to 881 patients discharged from the ED. Main results: Two weeks after discharge, families were telephoned to determine relapse. Follow-up data were available for 762 (86%) of the children with a 10% incidence of relapse. On univariate analysis several factors were associated with relapse including current medications and markers of asthma severity. On multivariate analysis the factors associated with relapse were age (OR 1.4 per 5-year increase), use of second-line asthma medications (OR 3.7), exposure to cigarette smoke (OR 0.5), and ED visits within the past year (OR 1.2 per 5 ED visits). Conclusions: The incidence of relapse among children is lower than that observed among adults and varies with age. Other risk factors such as frequent ED visits are likely markers of chronic asthma severity. Further research should focus on ways to decrease the relapse rate among patients at high risk. C1 Metrohlth Med Ctr, Dept Emergency Med, Cleveland, OH 44109 USA. Jacobi Hosp, Div Emergency Med, Bronx, NY USA. Univ Alberta, Div Emergency Med, Edmonton, AB, Canada. Capital Hlth Author, Edmonton, AB, Canada. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA USA. RP Emerman, CL (reprint author), Metrohlth Med Ctr, Dept Emergency Med, 2500 Metrohlth Dr,Room S1-203, Cleveland, OH 44109 USA. FU NHLBI NIH HHS [HL-03533, HL-07427, HL-63253] NR 19 TC 40 Z9 42 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAR PY 2001 VL 138 IS 3 BP 318 EP 324 DI 10.1067/mpd.2001.111320 PG 7 WC Pediatrics SC Pediatrics GA 413BZ UT WOS:000167591200006 PM 11241036 ER PT J AU De Soete, M Mongardini, C Pauwels, M Haffajee, A Socransky, S van Steenberghe, D Quirynen, M AF De Soete, M Mongardini, C Pauwels, M Haffajee, A Socransky, S van Steenberghe, D Quirynen, M TI One-stage full-mouth disinfection. Long-term microbiological results analyzed by checkerboard DNA-DNA hybridization SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE chlorhexidine/therapeutic use; periodontitis/therapy; infection control/drug effects; dental plaque/prevention and control; disinfection/drug effects; disinfection/methods ID EARLY-ONSET PERIODONTITIS; ORAL MUCOUS-MEMBRANES; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; CLINICAL OBSERVATIONS; CHRONIC ADULT; INFECTIONS; TRANSMISSION; COLONIZATION; CALCULUS AB Background: Recent studies reported significant, additional clinical and microbiological improvements when severe adult periodontitis was treated via the one-stage full-mouth (OSFM) disinfection approach, instead of a standard treatment scheme with staged instrumentation per quadrant. The OSFM disinfection involves dealing with the remaining oropharyngeal niches such as tonsils, saliva, tongue, and mucosa. The OSFM disinfection procedure involves scaling and root planing of all pockets within 24 hours in combination with chlorhexidine application to all oropharyngeal niches (chairside and at home for 2 months). This study aimed to compare the microbiological shifts with the OSFM approach versus standard therapy. Methods: Nineteen patients with advanced chronic periodontitis (AP) and 12 patients with early-onset periodontitis (EOP) were randomly assigned to the test and control groups. The control group (9 AP patients, 6 EOP patients) was scaled and root planed, per quadrant, with 2-week intervals. The test group (10 AP patients and 6 EOP patients) underwent OSFM disinfection treatment. At baseline and after 2, 4, and 8 months, pooled subgingival plaque samples were taken from single- and multi-rooted teeth. The presence and levels of 30 subgingival taxa were determined using whole genomic DNA probes and checkerboard DNA-DNA hybridization. Results: Both treatments resulted in important reductions of the pathogenic species up to 8 months after therapy, both for their detection level and frequency. The OSFM disinfection resulted in an additional improvement, especially in the AP group. P. gingivalis and B. forsythus were reduced below detection level. The number of beneficial species remained nearly unchanged. Conclusions: The OSFM disinfection results in supplementary reductions of periodontal pathogens even after 8 months in the treatment of patients with advanced or early-onset periodontitis. C1 Catholic Univ Louvain, Fac Med, Dept Periodontol, Sch Dent Oral Pathol & Maxillofacial Surg, B-3000 Louvain, Belgium. Rega Inst, Microbiol Lab, Res Grp Microbial Adhes, Louvain, Belgium. Forsyth Inst, Dept Periodontol, Boston, MA USA. RP Quirynen, M (reprint author), Catholic Univ Louvain, Fac Med, Dept Periodontol, Sch Dent Oral Pathol & Maxillofacial Surg, Capucijnenvoer 7, B-3000 Louvain, Belgium. NR 30 TC 50 Z9 50 U1 0 U2 2 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD MAR PY 2001 VL 72 IS 3 BP 374 EP 382 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 419KN UT WOS:000167948100013 PM 11327066 ER PT J AU da Cunha, IT Lim, PAC Qureshy, H Henson, H Monga, T Protas, EJ AF da Cunha, IT Lim, PAC Qureshy, H Henson, H Monga, T Protas, EJ TI A comparison of regular rehabilitation and regular rehabilitation with supported treadmill ambulation training for acute stroke patients SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE acute stroke; bike stress test; rehabilitation; supported treadmill ambulation training ID BODY-WEIGHT SUPPORT; NONAMBULATORY HEMIPARETIC PATIENTS; MENTAL-STATE-EXAMINATION; INTERRATER RELIABILITY; GAIT; EXERCISE; SCALE; RECOVERY; CAT AB The purpose of this pilot study was to compare differences in motor recovery between regular rehabilitation (REG), and regular rehabilitation with supported treadmill ambulation training (STAT) using the performance on a bicycle exercise test and the locomotor scale of the Functional Independence Measure (FIM-L). Twelve patients with acute strokes were randomly assigned to either REG or STAT for 2 to 3 weeks. The STAT group received daily gait training utilizing a treadmill with partial support of body weight. After intervention, the STAT group had higher oxygen consumption (11.34 +/- 0.88 vs 8.32 +/- 0.88 ml/kg/min, p=0.039), total workload (58.75 +/- 7.09 vs 45.42 +/- 7.09 watts, p=ns), and total time pedaling the bike (288.91 +/- 30.61 vs 211.42 +/- 30.61 s, p=ns) compared To the REG group. The FIM-L scores were not different for the two groups. This pilot study suggests that the STAT intervention is a promising technique for acute stroke rehabilitation, and that future studies with larger sample sizes are warranted to establish the effectiveness of this intervention. C1 Texas Womans Univ, Sch Phys Therapy, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Houston, TX USA. RP da Cunha, IT (reprint author), Texas Womans Univ, Sch Phys Therapy, 1130 MD Anderson Blvd, Houston, TX 77030 USA. NR 37 TC 44 Z9 46 U1 2 U2 3 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAR-APR PY 2001 VL 38 IS 2 BP 245 EP 255 PG 11 WC Rehabilitation SC Rehabilitation GA 434FK UT WOS:000168804300010 ER PT J AU Li-Yu, J Clayburne, G Sieck, M Beutler, A Rull, M Eisner, E Schumacher, HR AF Li-Yu, J Clayburne, G Sieck, M Beutler, A Rull, M Eisner, E Schumacher, HR TI Treatment of chronic gout. Can we determine when urate stores are depleted enough to prevent attacks of gout? SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE chronic gout; urate crystals; allopurinol; colchicine ID KNEE JOINTS; CRYSTALS; MANAGEMENT; THERAPY AB Objective. To determine if lowering of serum uric acid (SUA) concentrations below 6 mg/dl or longer duration of lowered SUA will result in depletion of urate crystals from the knee joints and prevent further attacks of gout. Methods, A prospective study was initiated 10 years ago at Philadelphia VA Medical Center to attempt to maintain SUA levels of patients with crystal proven gout at < 6.0 mg/dl, We recalled all 57 patients who were available during 1999. Patients were divided into 2 groups: Group A, with SUA still > 6 mg/dl, and Group B, with SUA less than or equal to6 mg/dl. A knee joint aspirate was requested from all asymptomatic Group B patients and many in Group A. Aspirates were examined by polarized light microscopy for identification of crystals. Results. There were no differences between the groups in age, sex, duration of gout, or serum creatinine. Group A (n = 38) had a mean of 6 attacks of gout for the recent year, those with tophi having the most frequent attacks. Among the 16 patients in this group who agreed to knee aspiration, monosodium urate (MSU) crystals were found in 14, although they were asymptomatic at the time. Nineteen patients (Group B) were able to maintain serum urate levels less than or equal to 6 mg/dl for > 12 months. Nearly half of them had no attack of gout for 2 or more years, with a mean of 1 attack in the last year for the whole group. Three patients in whom tophi were found did not have major flares of gout within the past year. Knee joint aspiration was done on 16 asymptomatic patients. Seven (44%) still had MSU crystals present in their knees. Patients in this group who were taking prophylactic colchicine did not differ with respect to the character of synovial fluid from those who had discontinued it for up to several years, although the frequency of attacks was less in those who continued colchicine. Conclusion, A majority of patients were able to deplete urate crystal stores in their knee joint fluids when their SUA levels were kept to less than or equal to6 mg/dl for several years. The mechanisms for persistence in some patients, and whether such crystals have clinical implications, are not known. Patients with chronic gout need serum urate concentrations to be kept low to prevent further attacks. C1 Hosp Univ Penn, Dept Med, Div Rheumatol, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Rheumatol Sect, Philadelphia, PA 19104 USA. RP Li-Yu, J (reprint author), Santo Tomas Univ Hosp, Ctr Bone & Joint, Sect Rheumatol & Clin Immunol, Manila 1008, Philippines. NR 10 TC 120 Z9 125 U1 2 U2 3 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAR PY 2001 VL 28 IS 3 BP 577 EP 580 PG 4 WC Rheumatology SC Rheumatology GA 408KT UT WOS:000167325900022 PM 11296962 ER PT J AU Prinz, P Bailey, S Moe, K Wilkinson, C Scanlan, J AF Prinz, P Bailey, S Moe, K Wilkinson, C Scanlan, J TI Urinary free cortisol and sleep under baseline and stressed conditions in healthy senior women: Effects of estrogen replacement therapy SO JOURNAL OF SLEEP RESEARCH LA English DT Article DE estrogen replacement therapy; hydrocortisone; postmenopause; sleep; stress; women ID CORTICOSTEROID-BINDING GLOBULIN; CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; CIRCADIAN RHYTHMICITY; POSTMENOPAUSAL WOMEN; CATECHOLAMINE RESPONSES; TEMPERATURE RHYTHMS; GENDER DIFFERENCES; PLASMA-CORTISOL; GROWTH-HORMONE AB The purpose of this study was to examine the effects of a mild 24-h stress (indwelling IV catheter) on cortisol and sleep in postmenopausal women, and to evaluate differences due to estrogen replacement therapy (ERT) status. This study, conducted in the General Clinical Research Center at the University of Washington Medical Center, examined sleep, cortisol and sleep-cortisol relationships in both baseline and stress conditions, and compared women on ERT with women not on ERT. Forty-two women (age = 69.6 +/- 6.2 years [SD]), of whom 20 were on ERT, participated. Urinary free cortisol (UFC) levels and sleep polysomnography were measured over both 24-baseline and stress condition. Sleep was impaired in,the stress condition for both groups; mean UFC levels were higher, sleep efficiency and minutes of stages 2, 3 and 4 sleep were reduced, and morning risetime was earlier in the stress than baseline condition. For the combined groups, age-controlled correlations between 24-h UFC and sleep were significant in both conditions: at baseline, UFC levels were associated with earlier time of rising and less REM sleep, and under stress with reduced sleep efficiency, there was reduced minutes of stages 2, 3, 4 sleep, reduced REM sleep, and an earlier risetime. The pattern of negative significant correlations between UFC and sleep/sleep timing remained when plasma estrogen was statistically controlled; however, when groups were examined separately, the significant negative UFC-sleep relationships were confined to the non ERT group. Elevated 24-h UFC is associated with impaired sleep and earlier awakening in older women not on ERT, but not in women on ERT. C1 Univ Washington, Dept Biobehav Nursing & Hlth Syst, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. RP Prinz, P (reprint author), Univ Washington, Dept Biobehav Nursing & Hlth Syst, Box 357266, Seattle, WA 98195 USA. FU NCRR NIH HHS [M01-RR-00037]; NIA NIH HHS [R01-AG-12915]; NINR NIH HHS [NR-04001] NR 51 TC 25 Z9 25 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0962-1105 J9 J SLEEP RES JI J. Sleep Res. PD MAR PY 2001 VL 10 IS 1 BP 19 EP 26 DI 10.1046/j.1365-2869.2001.00236.x PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 417HN UT WOS:000167829700003 PM 11285051 ER PT J AU Clark, HW Masson, CL Delucchi, KL Hall, SM Sees, KL AF Clark, HW Masson, CL Delucchi, KL Hall, SM Sees, KL TI Violent traumatic events and drug abuse severity SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article DE posttraumatic stress disorder; depression; drug abuse severity; violence ID POSTTRAUMATIC-STRESS-DISORDER; SUBSTANCE USE DISORDER; METHADONE-MAINTENANCE; GENERAL-POPULATION; WOMEN; PTSD; DEPENDENCE; VICTIMIZATION; INDIVIDUALS; VALIDITY AB We examined the occurrence of violent traumatic events, DSM-III-R diagnosis of posttraumatic stress disorder (PTSD), and PTSD symptoms, and the relationship of these variables to drug abuse severity. One-hundred fifty opioid-dependent drug abusers who were participants in a randomized trial of two methadone treatment interventions were interviewed using the Diagnostic Interview Schedule, the Addiction Severity Index, and the Beck Depression Inventory. Twenty-nine percent met diagnostic criteria for PTSD. With the exception of rape, no gender differences in the prevalence of violent traumatic events were observed. The occurrence of PTSD-related symptoms was associated with greater drug abuse severity after controlling for gender, depression, and lifetime diagnosis of PTSD. The high rate of PTSD among these methadone patients, the nature of the traumatic events to which they are exposed, and subsequent violence-related psychiatric sequelae have important implications for identification and treatment of PTSD among those seeking drug abuse treatment. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Univ Calif San Francisco, Langley Porter Psychiat Inst, Dept Psychiat, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, Dept Psychiat, San Francisco, CA 94121 USA. RP Clark, HW (reprint author), CSAT, SAMHSA, Rockwall 2,Suite 615,5600 Fishers Lane, Rockville, MD 20857 USA. OI Delucchi, Kevin/0000-0003-2195-9627 FU NIDA NIH HHS [P50 DA09253] NR 36 TC 75 Z9 76 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD MAR PY 2001 VL 20 IS 2 BP 121 EP 127 DI 10.1016/S0740-5472(00)00156-2 PG 7 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 426PM UT WOS:000168357600004 PM 11306214 ER PT J AU Biederman, J Mick, E Faraone, SV Burback, M AF Biederman, J Mick, E Faraone, SV Burback, M TI Patterns of remission and symptom decline in conduct disorder: A four-year prospective study of an ADHD sample SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE symptom remission; symptom decline; conduct disorder; attention-deficit hyperactivity disorder ID DEFICIT HYPERACTIVITY DISORDER; FOLLOW-UP; PSYCHIATRIC STATUS; CHILDREN; BOYS; ADULT; ADOLESCENTS; CHILDHOOD; INTERVIEW; PROBANDS AB Objective: To evaluate systematically the longitudinal course of conduct disorder (CD) in a sample of youths with attention-deficit hyperactivity disorder (ADHD) to determine the effects of a persistent course on outcome. Method: One hundred forty children with ADHD and their nuclear families were assessed at baseline and again at 1 and 4 years. Subjects were examined by means of DSM-III-R-based structured interviews. They were also evaluated for cognitive and social functioning. Persistent (exhibiting symptoms of CD at either follow-up) and desistent (symptoms of CD at neither follow-up) cases were identified. Results: Forty-two percent of CD cases followed a persistent course. Although both persistent and desistent subjects had high rates of antisocial disorders in relatives, increased family conflict and decreased family cohesion were selectively associated with a persistent course. In addition, subjects with persistent symptoms of CD exhibited more impaired ratings on the Aggression and Delinquency subscales of the Child Behavior Checklist, as well as higher rates of bipolar, oppositional defiant, and substance use disorders. Conclusions: These findings suggest that the poor prognosis associated with CD is limited to an identifiable subgroup with a persistent course. C1 Massachusetts Gen Hosp, Dept Psychiat & Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Dept Psychiat & Pediat Psychopharmacol, 15 Parkman St WACC 725, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH41314] NR 33 TC 46 Z9 48 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 2001 VL 40 IS 3 BP 290 EP 298 DI 10.1097/00004583-200103000-00008 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 406DQ UT WOS:000167200000008 PM 11288770 ER PT J AU Daviss, WB Bentivoglio, P Racusin, R Brown, KM Bostic, JQ Wiley, L AF Daviss, WB Bentivoglio, P Racusin, R Brown, KM Bostic, JQ Wiley, L TI Bupropion sustained release in adolescents with comorbid attention-deficit/hyperactivity disorder and depression SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE bupropion sustained release; adolescent; attention-deficit/hyperactivity disorder; depression ID DEFICIT HYPERACTIVITY DISORDER; PAST 10 YEARS; CHILDHOOD; CHILDREN; MOOD AB Objective: To determine whether bupropion sustained release (SR) is effective and well-tolerated in adolescents with comorbid attention-deficit/hyperactivity disorder (ADHD) and depression. Method: Subjects were 24 adolescents (aged 11-16 years old) with ADHD and either major depressive disorder or dysthymic disorder. After a 2-week, single-blind placebo lead-in, subjects were treated for 8+ weeks with bupropion SR at doses flexibly titrated up to 3 mg/kg b.i.d. (mean final doses: 2.2 mg/kg q A.M. and 1.7 mg/kg q P.M.).Outcomes were global improvement in ADHD and depression (clinicianrated), along with changes in depressive symptomatology (parent- and child-rated), ADHD symptomatology (parent- and teacher-rated), and functional impairment (parent-rated). Results: Clinicians rated 14 subjects (58%) responders in both depression and ADHD, 7 (29%) responders in depression only, and 1 (4%) a responder in ADHU only. Compared with post-placebo ratings, final parents' (p <.0005) and children's (p =.016) ratings of depressive symptomatology improved significantly, as did parents' (p <.0005) but not teachers' (p =.080) ratings of ADHD symptomatology. Final ratings of functional impairment improved significantly from enrollment (p <.0005). No subject discontinued medication because of side effects. Conclusions: Bupropion SR may be effective and well-tolerated in adolescents with comorbid ADHD and depressive disorders. However, randomized, placebo-controlled studies are needed. C1 Dartmouth Med Sch, Dept Psychiat, Hanover, NH USA. Massachusetts Gen Hosp, Dept Child Psychiat, Boston, MA 02114 USA. RP Daviss, WB (reprint author), Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA. FU NIMH NIH HHS [K23 MH065375-02, MH56147] NR 28 TC 82 Z9 89 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD MAR PY 2001 VL 40 IS 3 BP 307 EP 314 DI 10.1097/00004583-200103000-00010 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 406DQ UT WOS:000167200000010 PM 11288772 ER PT J AU Mauiyyedi, S Della Pelle, P Saidman, S Collins, AB Pascual, M Tolkoff-Rubin, NE Williams, WW Cosimi, AB Schneeberger, EE Colvin, RB AF Mauiyyedi, S Della Pelle, P Saidman, S Collins, AB Pascual, M Tolkoff-Rubin, NE Williams, WW Cosimi, AB Schneeberger, EE Colvin, RB TI Chronic humoral rejection: Identification of antibody-mediated chronic renal allograft rejection by C4d deposits in peritubular capillaries SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 88th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-27, 1999 CL SAN FRANCISCO, CALIFORNIA SP US & Canadian Acad Pathol ID TRANSPLANTED MOUSE HEARTS; KIDNEY ALLOGRAFTS; CORONARY ATHEROSCLEROSIS; COMPLEMENT ACTIVATION; VASCULAR REJECTION; ENDOTHELIAL-CELLS; HLA ANTIBODIES; IMMUNITY; LESIONS; GLOMERULOPATHY AB The pathogenesis of chronic renal allograft rejection (CR) remains obscure. The hypothesis that a subset of CR is mediated by antidonor antibody was tested by determining whether C4d is deposited in peritubular capillaries (PTC) and whether it correlates with circulating antidonor antibodies. All cases (from January 1, 1990, to July 31, 1999) that met histologic criteria for CR and had frozen tissue (28 biopsies, 10 nephrectomies) were included. Controls were renal allograft biopsies with chronic cyclosporine toxicity (n = 21) or nonspecific interstitial fibrosis (n = 10), and native kidneys with end-stage renal disease (n = 10) or chronic interstitial fibrosis (n = 5). Frozen sections were stained by two-color immunofluorescence for C4d, type TV collagen and Ulex europaeus agglutinin I. Antidonor HLA antibody was sought by panel-reactive antibody analysis and/or donor cross matching in sera within 7 wk of biopsy. Overall, 23 of 38 CR cases (61%) had PTC staining for C4d, compared with 1 of 46 (2%) of controls (P < 0.001). C4d in PTC was localized at the interface of endothelium and basement membrane. Most of the C4d-positive CR tested had antidonor HLA antibody (15 of 17; 88%); none of the C4d-negative CR tested (0 of 8) had antidonor antibody (P < 0.0002). The histology of C4d-positive CR was similar to C4d-negative CR, and l-yr graft survival rates were 62% and 25%, respectively (P = 0.05). Since August 1998, five of six C4d-positive CR cases have been treated with mycophenolate mofetil +/- tacrolimus with a 100% 1-yr graft survival, versus 40% before August 1998 (P < 0.03). These data support the hypothesis that a substantial fraction of CR is mediated by antibody (immunologically active). C4d can be used to separate this group of CR from the nonspecific category of chronic allograft nephropathy and may have the potential to guide successful therapeutic intervention. C1 Massachusetts Gen Hosp, Pathol Unit, Boston, MA 02140 USA. Massachusetts Gen Hosp, Surg Unit, Boston, MA 02140 USA. Massachusetts Gen Hosp, Med Serv Unit, Boston, MA 02140 USA. Massachusetts Gen Hosp, Immunopathol Unit, Boston, MA 02140 USA. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02140 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mauiyyedi, S (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 225, Boston, MA 02140 USA. FU NHLBI NIH HHS [P01-HL18646] NR 43 TC 329 Z9 352 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAR PY 2001 VL 12 IS 3 BP 574 EP 582 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 406NE UT WOS:000167221400019 PM 11181806 ER PT J AU Herring, AH Ibrahim, JG AF Herring, AH Ibrahim, JG TI Likelihood-based methods for missing covariates in the Cox proportional hazards model SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Cox model; EM algorithm; Gibbs sampling; missing at random; Monte Carlo EM algorithm ID GENERALIZED LINEAR-MODELS; CENSORED SURVIVAL-DATA; REGRESSION-MODELS; EM ALGORITHM AB Problems associated with missing covariate data are well known but often ignored. We present a method for estimating the parameters in the Cox proportional hazards model when the missing data are missing at random (MAR) and censoring is noninformative. Due to the computational burden of this method, we introduce an approximation that allows us to use a weighted expectation-maximization (EM) algorithm to estimate the parameters more easily. When the missing covariates are continuous rather than categorical, we implement a Monte Carlo version of the Ehl algorithm along with the Gibbs sampler to obtain parameter estimates. We also give the asymptotic distribution of these estimates. The primary advantage of this method over complete case analysis is that it produces more efficient parameter estimates and corrects for bias in the MAR setting. To motivate the methodology, we present an analysis of a phase III melanoma clinical trial conducted by the Eastern Cooperative Oncology Group. C1 Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Herring, AH (reprint author), Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. NR 25 TC 37 Z9 37 U1 0 U2 3 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 2001 VL 96 IS 453 BP 292 EP 302 DI 10.1198/016214501750332866 PG 11 WC Statistics & Probability SC Mathematics GA 408KU UT WOS:000167326000033 ER PT J AU Schatz, J Craft, S White, D Park, TS Figiel, GS AF Schatz, J Craft, S White, D Park, TS Figiel, GS TI Inhibition of return in children with perinatal brain injury SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE attention; visual processing; cerebral palsy; cognitive ID VISUAL-ATTENTION; EARLY INFANCY AB Inhibition of return is a bias in attention that reduces the likelihood of returning attention to previously viewed locations. This attention bias develops during the first 6 months of life and is putatively mediated by midbrain structures. The present study evaluated the effects of perinatal lesions on the development of inhibition of return. Thirty-three children with perinatal injury resulting in spastic diplegic cerebral palsy were grouped based on magnetic resonance exams. Children with anterior (n = 5), posterior (n = 12), diffuse (n = 8), or no apparent (n = 8) lesions were compared with a group of age-matched children without neurologic injury (n = 39) on an orienting task designed to elicit inhibition of return. Short-delay trials demonstrated grossly intact facilitation of attention for all groups. Long-delay trials that produced inhibition of return in the control and posterior injury groups indicated a disruption of inhibition of return in the groups with anterior and diffuse lesions. The findings are consistent with previous reports that anterior regions are important for the developing attention system, and that bilateral injury can result in unilateral disruption of visual attention. C1 Washington Univ, Dept Psychol, St Louis, MO 63130 USA. Vet Affairs Pugent Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Washington Univ, Sch Med, Dept Neurol & Neurol Surg, St Louis, MO 63110 USA. Washington Univ, Sch Med, St Louis Childrens Hosp, St Louis, MO USA. Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. RP Schatz, J (reprint author), Univ S Carolina, Dept Psychol, Columbia, SC 29208 USA. NR 23 TC 16 Z9 16 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI PORT CHESTER PA 110 MIDLAND AVE, PORT CHESTER, NY 10573-4930 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD MAR PY 2001 VL 7 IS 3 BP 275 EP 284 DI 10.1017/S1355617701733012 PG 10 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 427VA UT WOS:000168425100001 PM 11311028 ER PT J AU Norton, LE Ostergaard, AL AF Norton, LE Ostergaard, AL TI Priming performance in Alzheimer's disease: The role of task sensitivity SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE Alzheimer's disease; priming; implicit memory; picture fragment identification ID EXPLICIT MEMORY; IMPLICIT; DISSOCIATIONS; FREQUENCY; DEMENTIA; DEFICITS; SYSTEMS AB Studies examining implicit memory performance in Alzheimer's disease (AD) have yielded inconsistent findings, with these patients demonstrating impaired performance within some priming studies and intact performance within others. The present study examined the role of task sensitivity in detecting impaired priming in memory-impaired patients. Twelve healthy older adults and 12 AD patients were administered a picture fragment identification test. Task sensitivity was increased by employing stimulus cues expected to produce larger and more variable priming effects than obtained in previous studies. A simple comparison of priming scores revealed that the AD patients demonstrated significantly impaired priming relative to normal control participants. However, further analysis of priming in relation to certain stimulus characteristics revealed that AD patients often demonstrated impaired priming when overall priming effects were large but relatively intact priming when priming effects were small. These findings suggest that the prevention of ceiling effects in control participants may aid in the detection of impaired priming in patient populations. C1 Univ Calif San Diego, Dept Psychiat & Neurosci, San Diego, CA USA. RP Norton, LE (reprint author), Massachusetts Gen Hosp, Psychol Assessment Ctr, 5 Emerson Pl,Suite 105, Boston, MA 02114 USA. FU NIA NIH HHS [5R01 AG06849] NR 22 TC 2 Z9 2 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI PORT CHESTER PA 110 MIDLAND AVE, PORT CHESTER, NY 10573-4930 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD MAR PY 2001 VL 7 IS 3 BP 294 EP 301 DI 10.1017/S1355617701733036 PG 8 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 427VA UT WOS:000168425100003 PM 11311030 ER PT J AU Lebeche, D Kang, ZB Hajjar, R AF Lebeche, D Kang, ZB Hajjar, R TI Candesartan abrogates G protein-coupled receptors agonist-induced MAPK activation and cardiac myocyte hypertrophy SO JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM LA English DT Article DE candesartan; Ang II type 1 receptor blockers; MAP kinases; cardiac hypertrophy ID CONGESTIVE-HEART-FAILURE; NH2-TERMINAL KINASE ACTIVATION; ANGIOTENSIN-II; MECHANICAL-STRESS; CARDIOMYOCYTE HYPERTROPHY; IN-VITRO; ANTAGONIST; CALCINEURIN; CILEXETIL; BLOCKADE AB The renin-angiotensin-aldosterone system (RAAS) has been identified as a major contributor to the development of cardiac hypertrophy and the subsequent transition to heart failure. G protein-coupled receptors agonists such as angiotensin Il (Ang II), endothelin-1 (ET-1) and phenylephrine (PE) have been implicated in hypertrophic responses in ventricular myocytes through the activation of several families of MAP kinases. In this study we examined the effect of candesartan, an Ang II type 1-(AT(1))-receptor antagonist, on cardiac hypertrophy by using cultured neonatal rat cardiomyocytes. Stimulation with Ang II (100 nM), ET-1 (100 nM) or PE (1 muM) induced marked increases in [H-3]Leucine incorporation (greater than or equal to 50%), compatible with enhanced protein synthesis. The addition of candesartan abrogated the increase in [H-3]Leucine incorporation in response not only to Ang II but also to ET-I and PE. To elucidate the mechanisms involved in this antihypertrophic effect of candesartan, we studied the activation of p38-MAPK, extracellular signal-regulated kinases (ERK1/2) and stress-activated protein kinases (SAPKs). Ang II, ET-I and PE increased the phosphorylation levels of ERK1/2, p54(SAPK) and p46(SAPK) and p38 in a time-dependent manner. This activation was completely blocked in the case of Ang II by pretreatment with candesartan. ET-1-induced activation of ERKs, SAPKs and p38 was also partially, but significantly, reduced by candesartan. PE-induced activation of SAPKs, but not ERKs and p38, was also reduced by candesartan. These results suggest that the hypertrophic response to ET-1 and PE, along with Ang II, is dependent upon a functioning AT(1)-receptor and may be mediated by AT(1) activation of the MAP kinases. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02129 USA. RP Hajjar, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, 149 13th St,CNY-4 Room 4215, Boston, MA 02129 USA. NR 33 TC 5 Z9 5 U1 0 U2 0 PU J R A A S LTD PI BIRMINGHAM PA EDGBASTON HOUSE, 3 DUCHESS PLACE, EDGBASTON, BIRMINGHAM B16 8NH, ENGLAND SN 1470-3203 J9 J RENIN-ANGIO-ALDO S JI J. Renin-Angiotensin-Aldosterone Syst. PD MAR PY 2001 VL 2 SU 1 BP S154 EP S161 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 488MB UT WOS:000171938000027 PM 28095237 ER PT J AU Mitchell, JD Mathisen, DJ Wright, CD Wain, JC Donahue, DM Allan, JS Moncure, AC Grillo, HC AF Mitchell, JD Mathisen, DJ Wright, CD Wain, JC Donahue, DM Allan, JS Moncure, AC Grillo, HC TI Resection for bronchogenic carcinoma involving the carina: Long-term results and effect of nodal status on outcome SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Western-Thoracic-Surgical-Association CY JUN 21-24, 2000 CL HAWAII SP Western Thoracic Surg Assoc ID TRACHEAL SLEEVE PNEUMONECTOMY; RESPIRATORY-DISTRESS-SYNDROME; PULMONARY RESECTION; LUNG-CANCER; RECONSTRUCTION; SURVIVAL; MARGIN AB Objective: Bronchogenic carcinoma in close proximity to or involving the carina remains a challenging problem for thoracic surgeons. The operative procedures to allow complete resection are technically demanding and can be associated with significant morbidity and mortality. Little is known about long-term survival data to guide therapy in these patients. Methods: We conducted a single-institution retrospective review. Results: We have performed 60 carinal resections for bronchogenic carcinoma: 18 isolated carinal resections for tumor confined to the carinal or proximal main stem bronchus; 35 carinal pneumonectomies; 5 carinal plus lobar resections, and 2 carinal resections for stump recurrence after prior pneumonectomy. Thirteen patients (22%) had a history of lung or airway surgery. The overall operative mortality was 15%, improved from the first half of the series (20%) to the second half (10%), and varied according to the type of resection performed. Adult respiratory distress syndrome was responsible for 5 early deaths, and all late deaths were related to anastomotic complications. In 34 patients, all lymph nodes were negative for metastatic disease; 15 patients had positive N1 nodes, and 11 patients had positive N2/N3 nodes. Complete follow-up was accomplished in 90%, with a mean follow-up of 59 months. The overall 5-year survival including operative mortality was 42%, with 19 absolute 5-year survivors. Survival was highest after isolated carinal resection (51%). Lymph node involvement had a strong influence on survival: patients without nodal involvement had a 5-year survival of 51%, compared with 32% for patients with N1 disease and 12% for those with N2/N3 disease. Conclusions: This constitutes one of the largest single-institution reports on carinal resection for bronchogenic carcinoma involving the carina. Morbidity and mortality rates are acceptable. The overall survival including operative mortality is 42%. Positive N2/N3 lymph nodes may be a contraindication to surgery because of poor prognosis. C1 Massachusetts Gen Hosp, Gen Thorac Surg Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Mathisen, DJ (reprint author), Massachusetts Gen Hosp, Gen Thorac Surg Unit, Blake Bldg,1570, Boston, MA 02114 USA. NR 23 TC 74 Z9 82 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAR PY 2001 VL 121 IS 3 BP 465 EP 471 DI 10.1067/mtc.2001.112832 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 415KT UT WOS:000167721100011 PM 11241081 ER PT J AU Madihally, SV Toner, M Yarmush, ML Mitchell, RN AF Madihally, SV Toner, M Yarmush, ML Mitchell, RN TI Peripheral blood mononuclear cells exhibit hyercatabolic activity in response to thermal injury correlation with diminished MHC I expression SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE burn injury; protein turnover; skeletal muscle; peripheral blood; splenocytes; lymph nodes; protein synthesis; protein degradation; BALB/c mice; murine model; CD4+/CD8+ratio; f4/80; CD11b and CD19; MHC ID MUSCLE PROTEIN-TURNOVER; BURN INJURY; SKELETAL-MUSCLE; MAJOR INJURY; IMMUNOGLOBULIN-SYNTHESIS; LYMPHOCYTE; INFECTION; METABOLISM; RESISTANCE; TRAUMA AB Background: Muscle wasting is one of the major consequences of severe injury or infection. Although the mechanisms underlying this hypercatabolic state are not completely characterized, it was hypothesized that other cells in the body would be similarly affected, In particular, we sought to determine whether lymphoid cell populations experienced increased protein turnover after burn injury in a fashion analogous to that seen in skeletal muscle, Methods: BALB/c mice received either a 20% total body surface area burn or a control sham treatment, At days 1, 2, and 7 after treatment, skeletal muscle, peripheral blood, spleen, and lymph nodes were harvested from both groups, Protein synthesis and degradation rates were measured using C-14-phenylalanine incorporation and tyrosine release, Lymphocyte subpopulations (CD4 and CD8 T cells, macrophages, and B cells) and expression of major histocompatibility complex I (MHC I) molecules were assessed by flow cytometry. Results:The burn model used in this study resulted in increased skeletal muscle protein turnover in the first 2 days after injury, Protein synthetic and degradation rates of peripheral blood mononuclear cells (PBMNCs) in burned mice also demonstrated comparable changes, but persisted through day 7, Splenocytes showed similar hypercatabolic effects, whereas lymph node cells showed no change. Cell viability analysis confirmed that the observed alterations were not caused by cell death. MHC I expression was depressed in tandem with the increased catabolic rate in PBMNCs. Conclusion: This study demonstrates that various lymphoid populations undergo protein catabolic changes similar to those characteristically observed in skeletal muscle, and these correlated with diminished MHC I expression, Moreover, PBMNCs exhibited prolonged sensitivity to burn injury, of a duration exceeding that observed in skeletal muscles or other lymphoid tissues. C1 Brigham & Womens Hosp, Dept Pathol, Div Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med Surg Serv, Boston, MA 02115 USA. Shriners Hosp Children, Boston, MA USA. RP Mitchell, RN (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Immunol, 221 Longwood Ave,LMRC 515, Boston, MA 02115 USA. RI Madihally, Sundararajan/D-9285-2012 OI Madihally, Sundararajan/0000-0001-7498-5760 NR 51 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD MAR PY 2001 VL 50 IS 3 BP 500 EP 509 DI 10.1097/00005373-200103000-00015 PG 10 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 413UD UT WOS:000167629500026 PM 11265030 ER PT J AU Ryan, ET Calderwood, SB AF Ryan, ET Calderwood, SB TI Cholera vaccines SO JOURNAL OF TRAVEL MEDICINE LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 20-DEC 02, 1999 CL WASHINGTON, D.C. SP Amer Soc Trop Med & Hyg ID LIVE ORAL VACCINES; RECOMBINANT-B-SUBUNIT; SHIGELLA-SONNEI LIPOPOLYSACCHARIDE; SYSTEMIC IMMUNE-RESPONSES; PLACEBO-CONTROLLED TRIAL; SALMONELLA-TYPHI TY21A; ABO BLOOD-GROUPS; FREE MOUSE MODEL; EL-TOR CHOLERA; VIBRIO-CHOLERAE C1 Massachusetts Gen Hosp, Trop & Geog Med Ctr, Travelers Advice & Immunizat Ctr, Div Infect Dis, Boston, MA 02114 USA. RP Ryan, ET (reprint author), Massachusetts Gen Hosp, Trop & Geog Med Ctr, Travelers Advice & Immunizat Ctr, Div Infect Dis, Jackson 504,55 Fruit St, Boston, MA 02114 USA. FU NIAID NIH HHS [R01 AI040725, AI40725, K08 AI01332]; NICHD NIH HHS [HD39165, U01 HD039165] NR 120 TC 10 Z9 10 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1195-1982 J9 J TRAVEL MED JI J. Travel Med. PD MAR-APR PY 2001 VL 8 IS 2 BP 82 EP 91 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 420UH UT WOS:000168023300005 PM 11285167 ER PT J AU Benacerraf, BR AF Benacerraf, BR TI Unilateral cerebral ventriculomegaly - Is one better than two? SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Editorial Material ID SONOGRAPHIC EVALUATION; DILATATION INUTERO; CLINICAL COURSE C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Benacerraf, BR (reprint author), Diagnost Ultrasound Associates, PC, 333 Longwood Ave,Suite 400, Boston, MA 02115 USA. NR 16 TC 3 Z9 3 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD MAR PY 2001 VL 20 IS 3 BP 179 EP 181 PG 3 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 416AG UT WOS:000167755300001 PM 11270520 ER PT J AU Gordon, JA Chudnofsky, CR Hayward, RA AF Gordon, JA Chudnofsky, CR Hayward, RA TI Where health and welfare meet: Social deprivation among patients in the emergency department SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Article ID HOSPITAL EMERGENCY; CARE; SERVICES; PROJECT AB Context. As a safety net provider for many disadvantaged Americans, the emergency department (ED) may be an efficient site not only for providing acute medical care, but also for addressing serious social needs. Objective. To characterize the social needs of ED patients, and to evaluate whether the most disadvantaged patients have connections with the health and welfare system outside the ED. Design. Cross-sectional survey conducted over 24 hours in the fall of 1997. Setting. Three EDs: an urban public reaching hospital, a suburban university hospital, and a semirural community hospital. Participants. Consecutive patients presenting for care, including those transported by ambulance. The survey response rate was 91% (N = 300; urban = 115, suburban = 102, rural = 83). Main Outcome Measure. Index of socioeconomic deprivation described by the US Census Bureau (based on food, housing, and utilities). Results. Of all ED patients, 31% reported one or more serious social deprivations. For example, 13% of urban patients reported not having enough food to eat, and 9% of rural Patients reported disconnection of their gas or electricity (US population averages both less than 3%). While 40% of all patients had no consistent health care outside the ED (less than or equal to1 visit/year), those with higher levels of social deprivation had the least contact with the health care system outside the ED (P < .01). Although those with higher levels of deprivation were more likely to receive public assistance, still almost one-quarter of patients with high-level serial deprivation were not receiving public aid. Conclusion. Many ED patients suffer from fundamental social deprivations that threaten basic health. The most disadvantaged of these patients frequently lack contact with other medical care sires or public assistance networks. Community efforts to address serious social deprivation should include partnerships with the local ED. C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Emergency Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Partners Healthcare Syst, Inst Hlth Policy, Boston, MA 02114 USA. Albert Einstein Med Ctr, Dept Emergency Med, Philadelphia, PA 19141 USA. Univ Michigan Hlth Syst, Dept Vet Affairs, VA Med Ctr, Dept Internal Med, Ann Arbor, MI USA. RP Gordon, JA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St,CLN 115, Boston, MA 02114 USA. NR 24 TC 20 Z9 20 U1 2 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1099-3460 J9 J URBAN HEALTH JI J. Urban Health PD MAR PY 2001 VL 78 IS 1 BP 104 EP 111 DI 10.1093/jurban/78.1.104 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 430XQ UT WOS:000168601100010 PM 11368190 ER PT J AU Niklason, LE Abbott, W Gao, JM Klagges, B Hirschi, KK Ulubayram, K Conroy, N Jones, R AF Niklason, LE Abbott, W Gao, JM Klagges, B Hirschi, KK Ulubayram, K Conroy, N Jones, R TI Morphologic and mechanical characteristics of engineered bovine arteries SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID SMOOTH-MUSCLE CELLS; IN-VITRO; ELASTIN EXPRESSION; VASCULAR WALL; BLOOD-VESSELS; PROLIFERATION; POLYMERS; GRAFTS AB Objective: The ideal small-caliber arterial graft remains elusive despite several decades of intense research. A novel approach to the development of small-caliber arterial prostheses with a biomimetic system for in vitro vessel culture has recently been described. In this study we examined the effects of culture time and tissue culture scaffolding on engineered vessel morphology and function and found that these parameters greatly influence the function of engineered vessels. Methods: This report describes the effects of culture time and scaffold type on vessel morphology cellular differentiation, and vessel mechanical characteristics. Engineered vessels were cultured from bovine aortic smooth muscle cells (SMCs) and endothelial cells that were seeded onto biodegradable polymer scaffolds and cultured under physiologically pulsatile conditions. Engineered vessels were subjected to histologic, ultrastructural, immunocytochemical, and mechanical analyses. Results: Vessel morphology and mechanical characteristics improved as time in culture increased to 8 weeks. SMCs in the engineered vessel wall were organized into a highly lamellar structure, with cells separated by alternating layers of collagen fibrils. Polymer scaffold remnants were present in vessels cultured for 8 weeks, and SMCs that were in proximity to polymer renmants exhibited a dedifferentiated phenotype. Conclusions: These findings aid in the systematic understandings of the effects of in vitro parameters on engineered vessels and will be useful for the translation of vessel culture techniques to human cells for the development of autologous human vascular grafts. C1 Duke Univ, Dept Anesthesiol, Durham, NC 27708 USA. Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesiol, Cambridge, MA USA. Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA. SUNY Buffalo, Sch Med & Biomed Sci, Houston, TX USA. Univ Hacettepe, Dept Pharm, TR-06100 Ankara, Turkey. Georgetown Univ, Washington, DC USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. MIT, Dept Biol, Cambridge, MA 02139 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Niklason, LE (reprint author), Duke Univ, Dept Anesthesiol, Box 90281 Campus, Durham, NC 27708 USA. FU NHLBI NIH HHS [HL-03492, HL-60435] NR 26 TC 165 Z9 168 U1 0 U2 16 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAR PY 2001 VL 33 IS 3 BP 628 EP 638 DI 10.1067/mva.2001.111747 PG 11 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 410JT UT WOS:000167437400027 PM 11241137 ER PT J AU Kolchinsky, P Kiprilov, E Sodroski, J AF Kolchinsky, P Kiprilov, E Sodroski, J TI Increased neutralization sensitivity of CD4-independent human immunodeficiency virus variants SO JOURNAL OF VIROLOGY LA English DT Article ID GP120 ENVELOPE GLYCOPROTEIN; RECOMBINANT SOLUBLE CD4; T-LYMPHOTROPIC RETROVIRUS; HTLV-III/LAV ENVELOPE; TYPE-1 GP120; CONFORMATIONAL-CHANGES; CHEMOKINE RECEPTORS; SYNCYTIUM FORMATION; HIV-1 ENTRY; AIDS VIRUS AB Naturally occurring human immunodeficiency virus (HIV-1) variants require the presence of CD4 and specific chemokine receptors to enter a cell. In the laboratory, HIV-1 variants that are capable of bypassing CD4 and utilizing only the CCR5 chemokine receptor for virus entry have been generated. Here we report that these CD4-independent viruses are significantly more sensitive to neutralization by soluble CD4 and a variety of antibodies. The same amino acid changes in the HIV-1 gp120 envelope glycoprotein determined CD4 independence and neutralization sensitivity. The CD4-independent envelope glycoproteins exhibited higher affinity for antibodies against CD l-induced gp120 epitopes but not other neutralizing ligands. The CD4-independent envelope glycoproteins did not exhibit increased lability relative to the wild-type envelope glycoproteins. The utilization of two receptors apparently allows HIV-1 to maintain a more neutralization-resistant state prior to engaging CD4 on the target cell, explaining the rarity of CD4 independence in wild-type HIV-1. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. FU NIAID NIH HHS [AI24755, AI41851, P30 AI028691, R01 AI031783, R37 AI024755, AI31783, R01 AI041851] NR 96 TC 135 Z9 137 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2001 VL 75 IS 5 BP 2041 EP 2050 DI 10.1128/JVI.75.5.2041-2050.2001 PG 10 WC Virology SC Virology GA 400PQ UT WOS:000166881000002 PM 11160708 ER PT J AU Han, I Harada, S Weaver, D Xue, Y Lane, W Orstavik, S Skalhegg, B Kieff, E AF Han, I Harada, S Weaver, D Xue, Y Lane, W Orstavik, S Skalhegg, B Kieff, E TI EBNA-LP associates with cellular proteins including DNA-PK and HA95 SO JOURNAL OF VIROLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; LYMPHOCYTE GROWTH TRANSFORMATION; SIGNAL-BINDING-PROTEIN; LATENT MEMBRANE PROTEIN-2A; ENCODED NUCLEAR ANTIGEN; HUMAN B-LYMPHOCYTES; J-KAPPA; KILOBASE PAIRS; ACIDIC DOMAIN; T-ANTIGEN AB EBNA-LP-associated proteins were identified by sequencing proteins that immunoprecipitated with Flag epitope-tagged EBNA-LP (FLP) from lymphoblasts in which FLP was stably expressed. The association of EBNA-LP with Hsp70 (72/73) was confirmed, and sequences of DNA-PK catalytic subunit (DNA-PKcs), HA95, Hsp27, prolyl 4-hydroxylase alpha -1 subunit, alpha -tubulin, and beta -tubulin were identified. The fraction of total cellular HA95 that associated with FLP was very high, while progressively lower fractions of the total DNA-PKcs, Hsp70, Hsp 27, alpha -tubulin, and beta -tubulin specifically associated with EBNA-LP as determined by immunoblotting with antibodies to these proteins. EBNA-LP bound to two domains in the DNA-PKcs C terminus and DNA-PKcs associated with the EBNA-LP repeat domain. DNA-PKcs that was bound to EBNA-LP phosphorylated p53 or EBNA-LP in vitro, and the phosphorylation of EBNA-LP was inhibited by Wortmannin, a specific in vitro inhibitor of DNA-PKcs. C1 Harvard Univ, Sch Med, Channing Lab, Boston, MA 02445 USA. Harvard Univ, Ctr Blood Res, Cambridge, MA 02138 USA. Harvard Univ, Microchem Facil, Cambridge, MA 02138 USA. Univ Oslo, Inst Med Biochem, N-0317 Oslo, Norway. RP Kieff, E (reprint author), Harvard Univ, Sch Med, Channing Lab, 181 Longwood Ave, Boston, MA 02445 USA. FU NCI NIH HHS [CA47006, R01 CA047006, R35 CA047006] NR 78 TC 33 Z9 35 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2001 VL 75 IS 5 BP 2475 EP 2481 DI 10.1128/JVI.75.5.2475-2481.2001 PG 7 WC Virology SC Virology GA 400PQ UT WOS:000166881000047 PM 11160753 ER PT J AU Jiang, JJ Shah, AG Hess, MM Verdolini, K Banzali, FM Hanson, DG AF Jiang, JJ Shah, AG Hess, MM Verdolini, K Banzali, FM Hanson, DG TI Vocal fold impact stress analysis SO JOURNAL OF VOICE LA English DT Article DE PGG; impact stress; subglottal pressure; acceleration; vocal nodules; vocal polyps ID PHONATION AB Vocal fold impact stress (force/area) has been implicated a factor possibly contributing to the formation of nodules and polyps. The force of impact of a moving body is related to its acceleration. Since the mass of the folds is relatively constant, one expects impact force to be directly proportional to acceleration. A measure that reflects the relative displacement of the vocal fold is photoglottography (PGG). The velocity and acceleration of the folds are easily obtained by calculating the first and second derivatives of the PGG displacement waveform. This study, therefore, compared the second derivative of the PGG signal with simultaneously measured impact stress in an excised canine larynx model. Global transilumination (PGG) was measured with a subglottic transducer. A miniature force transducer placed in the midline between the vocal folds measured impact stress at the midglottal position. The nine different larynges, there was a positive and linear relationship between the second derivative of PGG and impact stress. The statistically significant results support the hypothesis that the second derivative of PGG may provide a useful noninvasive way to estimate relative vocal fold impact stress. C1 Northwestern Univ, Sch Med, Laryngeal Physiol Lab, Dept Otolaryngol Head & Neck Surg, Chicago, IL 60611 USA. Univ Hamburg, Hamburg, Germany. Harvard Med Sch, Boston, MA USA. Massachusetts Eye & Ear Infirm, Voice & Speech Lab, Boston, MA USA. MGH Inst Hlth Professions, Boston, MA USA. RP Jiang, JJ (reprint author), Northwestern Univ, Sch Med, Laryngeal Physiol Lab, Dept Otolaryngol Head & Neck Surg, Searle Bldg 12-561, 303 E Chicago Ave, Chicago, IL 60611 USA. NR 10 TC 21 Z9 21 U1 1 U2 2 PU SINGULAR PUBLISHING GROUP INC PI SAN DIEGO PA 401 WEST A ST, STE 325, SAN DIEGO, CA 92101-7904 USA SN 0892-1997 J9 J VOICE JI J. Voice PD MAR PY 2001 VL 15 IS 1 BP 4 EP 14 DI 10.1016/S0892-1997(01)00002-9 PG 11 WC Otorhinolaryngology SC Otorhinolaryngology GA 412LE UT WOS:000167555300002 PM 12269634 ER PT J AU Goodman, A Houck, K AF Goodman, A Houck, K TI Anxiety and uncertainty in informed decision making SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Editorial Material ID BREAST-CANCER; WOMEN; RISK C1 Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. RP Goodman, A (reprint author), Massachusetts Gen Hosp, Div Gynecol Oncol, Wang Abmulatory Care Bldg,Suite 237,15 Parkman St, Boston, MA 02114 USA. NR 7 TC 2 Z9 2 U1 1 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PD MAR PY 2001 VL 10 IS 2 BP 93 EP 94 DI 10.1089/152460901300039368 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 415PE UT WOS:000167730900001 PM 11268292 ER PT J AU Friebely, JS Shifren, JL Schiff, I Regestein, QR AF Friebely, JS Shifren, JL Schiff, I Regestein, QR TI Preliminary observations on differing psychological effects of conjugated and esterified estrogen treatments SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Article ID POSTMENOPAUSAL WOMEN; BRAIN; MOOD; 17-BETA-ESTRADIOL; DEPRESSION; PROGESTIN; ANDROGEN; BEHAVIOR; FITNESS AB During a double-blind comparison of menopausal replacement therapy with estrogen alone compared with estrogen plus methyltestosterone (meT), subjects who had been on conjugated equine estrogen (CEE) said they felt better when placed on esterified estrogen (EE). We, therefore, tested whether these estrogen treatments differed in their neuropsychological effects. Subjects were 34 healthy menopausal respondents to advertisements younger than age 66 who were on CEE at baseline. Each was randomized into the EE condition, either immediately after baseline or after they first took EE plus added meT for 8 weeks. We compared neuropsychological measures between these two conditions. Data included cognitive performance test results and symptom self-ratings. Multivariate techniques were used to adjust for the effects of treatment order. Compared with prior CEE treatment, EE treatment was associated with significantly improved scores on the Zung Self-Rated Depression Scale and on Switching Attention Test performance. Further investigation is warranted to determine if different forms of estrogen replacement induce different neuropsycholiogical effects. C1 Massachusetts Gen Hosp, Vincent Ob Gyn Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. RP Schiff, I (reprint author), Massachusetts Gen Hosp, Vincent Ob Gyn Serv, 55 Fruit St,VBK-113, Boston, MA 02114 USA. NR 30 TC 8 Z9 8 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PD MAR PY 2001 VL 10 IS 2 BP 181 EP 187 DI 10.1089/152460901300039548 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 415PE UT WOS:000167730900009 PM 11268301 ER PT J AU Mikota, SK Peddie, L Peddie, J Isaza, R Dunker, F West, G Lindsay, W Larsen, RS Salman, MD Chatterjee, D Payeur, J Whipple, D Thoen, C Davis, DS Sedgwick, C Montali, RJ Ziccardi, M Maslow, J AF Mikota, SK Peddie, L Peddie, J Isaza, R Dunker, F West, G Lindsay, W Larsen, RS Salman, MD Chatterjee, D Payeur, J Whipple, D Thoen, C Davis, DS Sedgwick, C Montali, RJ Ziccardi, M Maslow, J TI Epidemiology and diagnosis of Mycobacterium tuberculosis in captive Asian elephants (Elephas maximus) SO JOURNAL OF ZOO AND WILDLIFE MEDICINE LA English DT Article DE elephant; Elephas maximus; Loxodonta africana; tuberculosis; Mycobacterium tuberculosis; tuberculin test ID RESPIRATORY SPECIMENS; AMPLIFICATION; POLYMORPHISM; INFECTION; ANIMALS; COMPLEX; BOVIS; PCR AB The deaths of two Asian elephants (Elephas maximus) in August 1996 led the United States Department of Agriculture to require the testing and treatment of elephants for tuberculosis. From August 1996 to September 1999, Mycobacterium tuberculosis infection was confirmed by culture in 12 of 118 elephants in six herds. Eight diagnoses were made antemortem on the basis of isolation of M. tuberculosis by culture of trunk wash samples', the remainder (including the initial two) were diagnosed postmortem. We present the case histories, epidemiologic characteristics, diagnostic test results, and therapeutic plans from these six herds. The intradermal tuberculin test, enzyme-linked immunosorbent assay serology, the blood tuberculosis test, and nucleic acid amplification and culture are compared as methods to diagnose M. tuberculosis infection in elephants. C1 Univ Penn, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Infect Dis Sect, Philadelphia, PA 19104 USA. Lincoln Pk Zoo, Chicago, IL 60614 USA. Smithsonian Natl Zool Pk, Washington, DC 20008 USA. Los Angeles Zoo, Los Angeles, CA 90027 USA. Texas A&M Univ, Dept Vet Pathobiol, College Stn, TX 77843 USA. Iowa State Univ Sci & Technol, Coll Vet Med, Dept Microbiol Immunol & Prevent Med, Ames, IA 50011 USA. ARS, Zoonot Dis Res Unit, USDA, Natl Anim Dis Ctr, Ames, IA 50010 USA. Anim & Plant Hlth Inspect Serv, USDA, Natl Vet Serv Labs, Ames, IA 50010 USA. Colorado State Univ, Dept Microbiol, Ft Collins, CO 80523 USA. Colorado State Univ, Coll Vet Med & Biomed Sci, Ctr Vet Epidemiol & Anim Dis Surveillance Syst, Ft Collins, CO 80523 USA. Feld Entertainment, Vienna, VA 22182 USA. San Francisco Zool Gardens, San Francisco, CA 94132 USA. Kansas State Univ, Coll Vet Med, Dept Clin Sci, Manhattan, KS 66506 USA. Audubon Ctr Res Endangered Species, New Orleans, LA 70131 USA. RP Peddie, L (reprint author), 15333 Rains Court, Moorpark, CA 93021 USA. NR 44 TC 52 Z9 56 U1 1 U2 12 PU AMER ASSOC ZOO VETERINARIANS PI YULEE PA 581705 WHITE OAK ROAD, YULEE, FL 32097 USA SN 1042-7260 EI 1937-2825 J9 J ZOO WILDLIFE MED JI J. Zoo Wildl. Med. PD MAR PY 2001 VL 32 IS 1 BP 1 EP 16 PG 16 WC Veterinary Sciences SC Veterinary Sciences GA 478LW UT WOS:000171348500001 PM 12790389 ER PT J AU Mobbs, CV Bray, GA Atkinson, RL Bartke, A Finch, CE Maratos-Flier, E Crawley, JN Nelson, JF AF Mobbs, CV Bray, GA Atkinson, RL Bartke, A Finch, CE Maratos-Flier, E Crawley, JN Nelson, JF TI Neuroendocrine and pharmacological manipulations to assess how caloric restriction increases life span SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article; Proceedings Paper CT Caloric-Restriction-Clinical-Implications-Advisory-Group Meeting CY MAR 08-10, 1999 CL BETHESDA, MARYLAND SP Calor Restrict Clin Implicat Advisory Grp ID MELANIN-CONCENTRATING HORMONE; HYPOTHALAMIC NEUROPEPTIDE-Y; MICE OVEREXPRESSING LEPTIN; GENE-EXPRESSION PROFILE; AGE-RELATED-CHANGES; FOOD RESTRICTION; GROWTH-HORMONE; INFUNDIBULAR NUCLEUS; SYMPATHETIC ACTIVITY; INSULIN SENSITIVITY AB As part of an effort to review current understanding of the mechanisms by which caloric restriction (CR) extends maximum life span, the authors of the present review were requested to develop a list of key issues concerning the potential role of neuroendocrine systems in mediating these effects. It has long been hypothesized that failure of specific neuroendocrine functions during aging leads to key age-related systemic and physiological failures, and more recently it has been postulated that physiological neuroendocrine responses to CR may increase life span. However, although the acute neuroendocrine responses to fasting have been well studied, it is not clear that these responses are necessarily identical to those observed ill response to the chronic moderate (30% to 50% reduction) CR that increases maximum lift: span. Therefore the recommendations of this panel fall into two categories. First, further characterization of neuroendocrine responses to CR over the entire life span is needed. Second, rigorous interventional studies are needed to test the extent to which neuroendocrine responses to CR mediate the effects of CR on life span, or alternatively if CR protects the function of essential neuroendocrine cells whose impairment reduces life span. Complimentary studies using rodent models, nonhuman primates, and humans will be essential to assess the generality of elucidated mechanisms, and to determine if such mechanisms might apply to humans. C1 CUNY Mt Sinai Sch Med, Dept Neurobiol, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Geriatr, New York, NY 10029 USA. Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. Univ Wisconsin, Sch Med, Dept Nutr Sci, Madison, WI 53706 USA. So Illinois Univ, Sch Med, Dept Physiol, Carbondale, IL 62901 USA. Univ So Calif, Andrus Gerontol Ctr, Los Angeles, CA 90089 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Cambridge, MA 02138 USA. NIMH, Sect Behav Neuropharmacol, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. RP Mobbs, CV (reprint author), CUNY Mt Sinai Sch Med, Neurobiol Aging Lab, Box 1639, New York, NY 10029 USA. RI Bartke, Andzej/D-6640-2017 OI Bartke, Andzej/0000-0002-2569-557X NR 83 TC 60 Z9 60 U1 1 U2 4 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAR PY 2001 VL 56 SI SI BP 34 EP 44 PG 11 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 422KX UT WOS:000168118000004 PM 12088210 ER PT J AU Bhandari, BK Feliers, D Duraisamy, S Stewart, JL Gingras, AC Abboud, HE Choudhury, GG Sonenberg, N Kasinath, BS AF Bhandari, BK Feliers, D Duraisamy, S Stewart, JL Gingras, AC Abboud, HE Choudhury, GG Sonenberg, N Kasinath, BS TI Insulin regulation of protein translation repressor 4E-BP1, an eIF4E-binding protein, in renal epithelial cells SO KIDNEY INTERNATIONAL LA English DT Article DE cell signaling; eukaryotic initiation factor 4E binding protein-1; tubular epithelial cells; MAP kinase; protein synthesis; type 2 diabetes; proximal tubule cell ID INITIATION-FACTOR 4E; SMOOTH-MUSCLE CELLS; P70 S6 KINASE; PHAS-I; PHOSPHATIDYLINOSITOL 3-KINASE; SIGNALING PATHWAY; MAP KINASE; PHOSPHORYLATION; RAPAMYCIN; STIMULATION AB Background. Augmented protein translation by insulin involves activation of eukaryotic initiation factor 4E (eIF4E) that follows release of eIF4E from a heterodimeric complex by phosphorylation of its inhibitory binding protein, 4E-BP1. We examined insulin regulation of 4E-BP1 phosphorylation in murine proximal tubular epithelial cells. Methods and Results. Insulin (1 nmol/L) increased de novo protein synthesis by 58 +/- 11% (P < 0.001). Insulin also augmented 4E-BP1 phosphorylation and phosphatidylinositol S-kinase (PI3-kinase) activity in antiphosphotyrosine immunoprecipitates. This could be prevented by PI 3-kinase inhibitors, Wortmannin, and LY294002. Insulin also activated Akt that lies downstream of PI 3-kinase. Rapamycin abrogated 4E-BP1 phosphorylation in response to insulin, suggesting involvement of mammalian target of rapamycin (mTOR), a kinase downstream of Akt. Insulin-stimulated phosphorylation of 4E-BP1 was also inhibited by PD098059, implying involvement of Erk-1/-2 mitogen-activated protein (MAP) kinase. An increase in Erk-1/-2 type MAP kinase activity by insulin was directly confirmed in an immunokinase assay and was found to be PIS-kinase dependent. Conclusions. In proximal tubular epithelial cells, insulin augments 4E-BP1 phosphorylation, which is PI 3-kinase and mTOR dependent. The requirement for Erk-1/-2 MAP kinase activation for 4E-BP1 phosphorylation by insulin suggests a cross-talk between PI 3-kinase and Erk-1/-2-type MAP kinase pathways. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX USA. McGill Univ, Ctr Canc, Dept Biochem, Montreal, PQ H3G 1Y6, Canada. RP Kasinath, BS (reprint author), Univ Texas, Hlth Sci Ctr, Div Nephrol, 7703 Floyd Curl Dr,Mail Code 7882, San Antonio, TX 78229 USA. RI Gingras, Anne-Claude/E-9982-2010 OI Gingras, Anne-Claude/0000-0002-6090-4437 NR 34 TC 53 Z9 54 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAR PY 2001 VL 59 IS 3 BP 866 EP 875 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 410HH UT WOS:000167434200005 PM 11231341 ER PT J AU Jensen, DM AF Jensen, DM TI Clots and spots on ulcers: why and how to treat SO LANGENBECKS ARCHIVES OF SURGERY LA English DT Article DE endoscopy; stigmata; ulcer hemorrhage ID BLEEDING PEPTIC-ULCERS; UPPER GASTROINTESTINAL HEMORRHAGE; ND-YAG LASER; ENDOSCOPIC THERAPY; CONTROLLED TRIAL; HEATER PROBE AB The clinical indication for urgent endoscopy with combined diagnosis and treatment is bleeding severe enough to warrant urgent medical attention, Stigmata of ulcer hemorrhage are utilized as a guide to endoscopic therapy. Active arterial bleeding, nonbleeding visible vessels. and adherent nonbleeding clots are always treated endoscopically. In randomized trials, patients with these "major stigmata" had better outcomes from endoscopic therapies than with medical therapies alone. Flat spots, gray or black sloughs, and clean ulcer bases are not treated endoscopically! since medical therapy alone affords good outcome. The current recommendation is to treat major stigmata of hemorrhage endoscopically for the initial bleeding episode and a second time for rebleeding before considering ulcer surgery;: Clinical presentation and comorbidity and the endoscopic appearance of the ulcer (i,e., stigmata of hemorrhage) of patients with UGI bleeding are used to determine the subsequent level of care (e.g., discharge or ward or intensive care). C1 UCLA CURE Digest Dis Res Ctr, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Jensen, DM (reprint author), UCLA CURE Digest Dis Res Ctr, VA Greater Los Angeles Healthcare Syst, Bldg 115,Room 318,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NCRR NIH HHS [MO1-RR00865]; NIDDK NIH HHS [1K24DK 02650, DK41301]; PHS HHS [R01-33273] NR 19 TC 3 Z9 4 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1435-2443 J9 LANGENBECK ARCH SURG JI Langenbecks Arch. Surg. PD MAR PY 2001 VL 386 IS 2 BP 82 EP 87 DI 10.1007/s004230100217 PG 6 WC Surgery SC Surgery GA 427GR UT WOS:000168396900002 PM 11374052 ER PT J AU Kahn, JB Gliklich, RE Boyev, KP Stewart, MG Metson, RB McKenna, MJ AF Kahn, JB Gliklich, RE Boyev, KP Stewart, MG Metson, RB McKenna, MJ TI Validation of a patient-graded instrument for facial nerve paralysis: The FaCE Scale SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT 103rd Annual Meeting of the American-Laryngological-Rhinological-and-Otological-Society CY MAY 13-18, 2000 CL ORLANDO, FLORIDA SP Amer Laryngol Rhinol & Otol Soc DE facial paralysis; functional status; outcomes; quality of life; instrument ID GRADING SYSTEMS; HOUSE-BRACKMANN; RELIABILITY; RECOVERY; QUALITY; INDEX; LIFE AB Objective: To develop and validate a patient-based instrument to measure both facial impairment and disability, the Facial Clinimetric Evaluation (FaCE) Scale, Study Design: Prospective instrument validation. Methods: Eighty-six patients with a documented history of facial paralysis completed a preliminary, 51-item instrument (alpha FaCE Scale), as well as the previously developed Facial Disability Index (FDI) and the Medical Outcomes Study Short Form 36 Item Questionnaire (SF-36), Two weeks after completing these instruments, 76 patients again completed the alpha FaCE Scale. Forty one of the patients were also evaluated using the House-Brackmann Grading System (HBGS) and the Facial Grading System (FGS), Results: Exploratory principal component factor analysis grouped 15 FaCE Scale items into 6 impairment and disability categories (domains), forming the beta FaCE Scale. Overall, the test-retest reliability of the FaCE Scale was high (Spearman's correlation coefficient (r) = 0.88, P <.01), as were the reliability coefficients of the individual domains (r = 0.81- 0.92, P <.01), The FaCE Scale domains showed appropriate correlation to global visual analogue scale questions posed on the original alpha FaCE Scale (r = 0.65-0.81, P <.01). Overall, the FaCE Scale showed significant correlation with HBGS and FGS scores (r = -0.55 and 0.57, respectively; P <.01). However, not all FaCE Scale domains correlated with the HBGS and FGS scores. Conclusions: A reliable and valid patient-based system to measure impairment and disability in facial paralysis has been developed. This system appears to be better than traditional, physician-graded scales for evaluating quality-of-life issues affected by facial disability. C1 Baylor Coll Med, Bobby R Alford Dept Otorhinolaryngol & Communicat, Houston, TX 77030 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Kahn, JB (reprint author), Baylor Coll Med, Dept Otolaryngol, 1 Baylor Plaza,Box SM 1727, Houston, TX 77030 USA. NR 31 TC 88 Z9 91 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD MAR PY 2001 VL 111 IS 3 BP 387 EP 398 DI 10.1097/00005537-200103000-00005 PG 12 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 410VN UT WOS:000167461900004 PM 11224766 ER PT J AU Armstrong, SA Silverman, LB Ernst, P Sallan, SE Lander, ES Korsmeyer, SJ Golub, TR AF Armstrong, SA Silverman, LB Ernst, P Sallan, SE Lander, ES Korsmeyer, SJ Golub, TR TI The gene expression profile of infant acute lymphoblastic leukemia SO LEUKEMIA LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. MIT, Ctr Genome Res, Whitehead Inst, Boston, MA USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAR PY 2001 VL 15 IS 3 MA O29 BP 489 EP 489 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA 410QT UT WOS:000167451200048 ER PT J AU Nam, CM Zelen, M AF Nam, CM Zelen, M TI Comparing the survival of two groups with an intermediate clinical event SO LIFETIME DATA ANALYSIS LA English DT Article DE clinical trials; intermediate events; semi-Markov processes; score tests; zidovudine ID TRIAL AB Consider a subject entered on a clinical trial in which the major endpoint is a time metric such as death or time to reach a well defined event. During the observational period the subject may experience an intermediate clinical event. The intermediate clinical event may induce a change in the survival distribution. We consider models for the one and two sample problem. The model for the one sample problem enables one to test if the occurrence of the intermediate event changed the survival distribution. This models provides a way of carrying out non-randomized clinical trial to determine if a therapy has benefit. The two sample problem considers testing if the probability distributions, with and without an intermediate event, are the same. Statistical tests are derived using a semi-Markov or a time dependent mixture model. Simulation studies are carried out to compare these new procedures with the log rank, stratified log rank and landmark tests. The new tests appear to have uniformly greater power than these competitor tests. The methods are applied to a randomized clinical trial carried out by the Aids Clinical Trial Group (ACTG) which compared low versus high doses of zidovudine (AZT). C1 Yonsei Univ, Dept Prevent Med & Publ Hlth, Seoul 120749, South Korea. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nam, CM (reprint author), Yonsei Univ, Dept Prevent Med & Publ Hlth, Seoul 120749, South Korea. NR 14 TC 6 Z9 6 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD MAR PY 2001 VL 7 IS 1 BP 5 EP 19 DI 10.1023/A:1009609925212 PG 15 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 401QQ UT WOS:000166940100001 PM 11280847 ER PT J AU Freeman, RB Rohrer, RJ Katz, E Lewis, WD Jenkins, R Cosimi, AB Delmonico, F Friedman, A Lorber, M O'Connor, K Bradley, J AF Freeman, RB Rohrer, RJ Katz, E Lewis, WD Jenkins, R Cosimi, AB Delmonico, F Friedman, A Lorber, M O'Connor, K Bradley, J TI Preliminary results of a liver allocation plan using a continuous medical severity score that de-emphasizes waiting time SO LIVER TRANSPLANTATION LA English DT Article AB Liver allocation remains problematic because current policy prioritizes status 2B or 3 patients by waiting time rather than medical urgency. On February 21, 2000, we implemented a variance to the United Network for Organ Sharing liver allocation policy that redefined status 2A by much more rigid, definable criteria and prioritized status 2B patients by using a continuous medical urgency score based on the Child-Turcotte-Pugh score and other medical conditions. In this system, waiting time is used only to differentiate status 2B candidates with equal medical urgency scores. Comparing the 6-month period (period 1; n = 67) before implementation of this system to the 6-month period after implementation (period 2; n = 75), there was a significant reduction in the number of transplantations performed for patients listed as status 2A (46.3% to 14.7%; P =.002) and an increase in the number of patients listed as status 2B who received transplants (44.8% to 70.7%; P =,10). Most dramatically, there was a 37.1% reduction in overall deaths on the waiting list from 94 deaths in period 1 to 62 deaths in period 2 (P =.005), with the most significant reduction for patients removed from this list at status 2B (52 v 18 patients; P =,04). There were 3 postoperative deaths in each period, with only 1 graft lost in period 2, Status 2B patients with the greatest degree of medical urgency received transplants without multiple peer reviews requesting elevation to 2A status. We conclude that a continuous medical urgency score system allocates donor livers much more fairly to those in medical need and reduces waiting list mortality without sacrificing efficacy. C1 Tufts Univ, Sch Med, New England Med Ctr, Div Transplant Surg, Boston, MA 02111 USA. Univ Massachusetts, Mem Med Ctr, Worcester, MA 01605 USA. Lahey Clin Med Ctr, Burlington, MA 01803 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Yale Univ, Sch Med, Yale New Haven Med Ctr, New Haven, CT USA. New England Organ Bank, Newton, MA USA. RP Freeman, RB (reprint author), Tufts Univ, Sch Med, New England Med Ctr, Div Transplant Surg, Box 40,750 Washington St, Boston, MA 02111 USA. NR 9 TC 48 Z9 51 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD MAR PY 2001 VL 7 IS 3 BP 173 EP 178 DI 10.1053/jlts.2001.22180 PG 6 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 410DN UT WOS:000167424900002 PM 11244156 ER PT J AU Gopal, DV Rabkin, JM Berk, BS Corless, CL Chou, SW Olyaei, A Orloff, SL Rosen, HR AF Gopal, DV Rabkin, JM Berk, BS Corless, CL Chou, SW Olyaei, A Orloff, SL Rosen, HR TI Treatment of progressive hepatitis C recurrence after liver transplantation with combination interferon plus ribavirin SO LIVER TRANSPLANTATION LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Transplantation CY MAY 13-17, 2000 CL CHICAGO, ILLINOIS SP Amer Soc Transplantat ID COLONY-STIMULATING FACTOR; VIRAL-HEPATITIS; VIRUS-INFECTION; THERAPY; RECIPIENTS; ALPHA; PROPHYLAXIS; EFFICACY; TRIAL AB Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) is common, although the majority of cases are mild. A subset of transplant recipients develops progressive allograft injury, including cirrhosis and allograft failure. Minimal data are available on the safety and efficacy of antiviral treatment in this group of patients. The aim of this study is to review our experience in the treatment of moderate to severe HCV recurrence with combination interferon-alpha 2b and ribavirin (IFN/RIB), Between October 1993 and October 1999, a total of 197 patients underwent OLT for HCV-related liver failure. This study describes 12 transplant recipients with moderate to severe recurrence treated with IFN/RIB, All patients met at least 1 of the following inclusion criteria: (1) moderate to severe inflammation (grade III to TV) on allograft biopsy, (2) bridging fibrosis on allograft biopsy, or (3) severe cholestasis attributable solely to HCV recurrence. Two patients had undergone re-OLT for allograft cirrhosis secondary to HCV recurrence and now had evidence of progressive HCV in their second allografts. Appropriate dose reductions of both IFN and RIB, as well as initiation of granulocyte colony-stimulating factor (G-CSF), for marked leukopenia were recorded. IFN/RIB therapy was started GO to 647 days post-OLT, and duration of therapy ranged from 39 to 515 days. Seven patients were administered G-CSF to successfully treat leukopenia. Six of the 12 patients (50%) became HCV RNA negative by polymerase chain reaction. One of these 6 patients (no. 1) was HCV RNA negative at 6 months but chose to discontinue therapy because of intolerable side effects, experienced a relapse, and was HCV RNA positive at 12 months. Two of the remaining 5 patients were HCV RNA negative at 2 and 3 months off therapy. For the entire group, there was a statistically significant decrease in serum biochemical indices assessed at initiation of therapy and 1, 3, and 6 months into therapy. Most patients required dose reductions of both IFN and RIB. Five patients died; 3 patients died of liver-related complications that included severe intrahepatic biliary cholestasis, severe HCV recurrence, and chronic rejection with profound cholestasis. In the subset of HCV-positive liver transplant recipients with moderate to severe recurrence, combination IFN/RIB therapy resulted in complete virological response (serum RNA negative) in 6 of 12 patients (similar to 50%). However, only 1 of 12 patients (8.3%) had sustained virological clearance after cessation of IFN/RIB therapy. Dose reductions of both IFN and RIB were required in most patients. The use of G-CSF (sometimes preemptively) allowed correction of leukopenia and full-dose antiviral therapy. Multicenter trials using combination therapy to identify factors predictive of response are needed in the subset of patients with progressive allograft injury. C1 Oregon Hlth Sci Univ, Div Gastroenterol & Hepatol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Div Infect Dis, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Surg & Liver Transplantat, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. RP Rosen, HR (reprint author), Oregon Hlth Sci Univ, Div Gastroenterol & Hepatol, 3710 SW US Vet Hosp Rd,POB 1034,P3-GI, Portland, OR 97201 USA. NR 38 TC 80 Z9 81 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 MAR PY 2001 VL 7 IS 3 BP 181 EP 190 DI 10.1053/jlts.2001.22447 PG 10 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 410DN UT WOS:000167424900004 PM 11244158 ER PT J AU Mandeville, JB Jenkins, BG Kosofsky, BE Moskowitz, MA Rosen, BR Marota, JJA AF Mandeville, JB Jenkins, BG Kosofsky, BE Moskowitz, MA Rosen, BR Marota, JJA TI Regional sensitivity and coupling of BOLD and CBV changes during stimulation of rat brain SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE CBV; BOLD; MRI; cocaine; rat ID CEREBRAL BLOOD-VOLUME; OXIDATIVE-METABOLISM; FOREPAW STIMULATION; CONTRAST; MRI; OXYGENATION; FMRI; FLOW AB Functional MRI of rat brain was performed at 2 Tesla following intravenous injection of cocaine in order to 1) determine if changes in CBV and changes in BOLD signal were regionally coupled in brain parenchyma, and 2) compare the sensitivities of these imaging methods across different brain structures. Percent changes in CBV and BOLD relaxation rate were spatially and temporally coupled during this graded brain activation. The use of contrast agent increased functional sensitivity in all parenchymal brain structures, with a strong but predictable dependence on the resting-state blood volume fraction. (C) 2001 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Mandeville, JB (reprint author), Massachusetts Gen Hosp, NMR Ctr, Room 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 FU NIDA NIH HHS [DA00384, DA09467] NR 16 TC 87 Z9 92 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD MAR PY 2001 VL 45 IS 3 BP 443 EP 447 DI 10.1002/1522-2594(200103)45:3<443::AID-MRM1058>3.0.CO;2-3 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 405MP UT WOS:000167163800014 PM 11241702 ER PT J AU Reschovsky, J Reed, M Blumenthal, D Landon, B AF Reschovsky, J Reed, M Blumenthal, D Landon, B TI Physicians' assessments of their ability to provide high-quality care in a changing health care system SO MEDICAL CARE LA English DT Article DE managed care; quality of care; clinical autonomy; continuity of care; adequacy of time ID MANAGED-CARE; FINANCIAL INCENTIVES; UNITED-STATES; SATISFACTION; PATIENT; ARRANGEMENTS; TRACKING; OUTCOMES; POLICY; STYLES AB BACKGROUND. With the growth of managed care, there are increasing concerns but inconclusive evidence regarding deterioration in the quality of medical care. OBJECTIVES. TO assess physicians' perceptions of their ability to provide high-quality care and explore what factors, including managed care, affect these perceptions. RESEARCH DESIGN. Bivariate and multivariate analyses of the Community Tracking Study Physician Survey, a cross-sectional, nationally representative telephone survey of 12,385 patient-care physicians conducted in 1997. The response rate was 65%. PARTICIPANTS. Physicians who provide direct patient care for greater than or equal to 20 h/wk, excluding federal employees and those in selected specialties, MEASURES. Level of agreement with 4 statements: 1 regarding overall ability to provide high-quality care and 3 regarding aspects of care delivery associated with quality. RESULTS. Between 21% and 31% of physicians disagreed with the quality statements. Specialists were generally 50% more likely than primary care physicians to express concerns about their ability to provide quality care. Generally, the number of managed care contracts, but not the percent of practice revenue from managed care, was negatively associated with perceived quality. Market-level managed care penetration independently affected physicians' perceptions. Practice setting affected perceptions of quality, with physicians in group settings less likely to express concerns than physicians in solo and P-physician practices. Specific financial incentives and care management tools had limited positive or negative associations with perceived quality. CONCLUSIONS. Managed care involvement is only modestly associated with reduced perceptions of quality among physicians, with some specific tools enhancing perceived quality. Physicians may be able to moderate some negative effects of managed care by altering their practice arrangements. C1 Ctr Studying Hlth Syst Change, Washington, DC 20024 USA. Massachusetts Gen Hosp, Partners HealthCare Syst, Inst Hlth Care Policy, Boston, MA 02114 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med,Dept Hlth Care Policy, Div Gen Med & Primary Care, Boston, MA 02215 USA. RP Reschovsky, J (reprint author), Ctr Studying Hlth Syst Change, 600 Maryland Ave SW,Suite 550, Washington, DC 20024 USA. NR 39 TC 40 Z9 40 U1 2 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 MAR PY 2001 VL 39 IS 3 BP 254 EP 269 DI 10.1097/00005650-200103000-00006 PG 16 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 407PF UT WOS:000167279400006 PM 11242320 ER PT J AU Schnipper, JL Kapoor, WN AF Schnipper, JL Kapoor, WN TI Diagnostic evaluation and management of patients with syncope SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Review ID HEAD-UP TILT; SIGNAL-AVERAGED ELECTROCARDIOGRAM; PLACEBO-CONTROLLED TRIAL; CAROTID-SINUS SYNDROME; NEUROCARDIOGENIC VASOVAGAL SYNCOPE; NEURALLY-MEDIATED SYNCOPE; GENERAL CLINICAL-PRACTICE; COST-EFFECTIVE APPROACH; COLLEGE-OF-CARDIOLOGY; BUNDLE-BRANCH BLOCK AB This article focuses on the evaluation of patients with syncope, a symptom not a disease. Syncope is a transient loss of consciousness associated with loss of postural tone with spontaneous recovery. The authors discuss the utility of an indications for different diagnostic tests, the indications for hospital admission, and the management of patients with certain known causes of syncope, including vasovagal and arrhythmic. C1 Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Kapoor, WN (reprint author), Suite 933 W,MUH,200 Lothrop St, Pittsburgh, PA 15213 USA. EM kapoorwn@msx.upmc.edu NR 120 TC 23 Z9 23 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 EI 1557-9859 J9 MED CLIN N AM JI Med. Clin. N. Am. PD MAR PY 2001 VL 85 IS 2 BP 423 EP + DI 10.1016/S0025-7125(05)70321-7 PG 35 WC Medicine, General & Internal SC General & Internal Medicine GA 405MJ UT WOS:000167163300010 PM 11233954 ER PT J AU Fisher, CM AF Fisher, CM TI If there were no free will SO MEDICAL HYPOTHESES LA English DT Article AB Electrophysiological findings in humans who are performing voluntary acts, indicate that the intention to act, follows brain activity rather than preceding it. This has implications for voluntary behavior and the doctrine of free will. This essay reviews the fields of human behavior, including medicine, in which this new thesis might have far-reaching significance. (C) 2001 Harcourt Publishers Ltd. C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Fisher, CM (reprint author), Massachusetts Gen Hosp, Neurol Serv, Fruit St, Boston, MA 02114 USA. NR 3 TC 2 Z9 2 U1 1 U2 4 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD MAR PY 2001 VL 56 IS 3 BP 364 EP 366 DI 10.1054/mehy.2000.1216 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 424BF UT WOS:000168211700017 PM 11359361 ER PT J AU Taylor, AE AF Taylor, AE TI Should women with premature menopause be screened for FMR-1 mutations? SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID FRAGILE-X PREMUTATIONS; OVARIAN FAILURE C1 Harvard Univ, Sch Med, Reprod Endocrine Unit, Boston, MA USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. RP Taylor, AE (reprint author), Harvard Univ, Sch Med, Reprod Endocrine Unit, Boston, MA USA. NR 12 TC 2 Z9 2 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 MAR-APR PY 2001 VL 8 IS 2 BP 81 EP 83 DI 10.1097/00042192-200103000-00002 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 408RZ UT WOS:000167342600002 PM 11256878 ER PT J AU Anderson, EJ Lavoie, HB Strauss, CC Hubbard, JL Sharpless, JL Hall, JE AF Anderson, EJ Lavoie, HB Strauss, CC Hubbard, JL Sharpless, JL Hall, JE TI Body composition and energy balance: Lack of effect of short-term hormone replacement in postmenopausal women SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID RESTING METABOLIC-RATE; FAT DISTRIBUTION; ESTROGEN REPLACEMENT; FOOD-INTAKE; THERAPY; WEIGHT; EXPENDITURE; MENOPAUSE; SECRETION; MEN AB Postmenopausal women (PMW) commonly believe that hormone replacement (HR) leads to weight gain, and fear of weight gain and/or an actual increase in weight is one of the principle reasons evoked for the discontinuation of HR. However, the potential effects of physiologic HR on body composition have yet to be separated from the effects of lifestyle or aging. Therefore, we examined the effect of short-term hormone replacement and age on alterations in weight, body composition, and energy balance. A prospective study of 28 healthy PMW aged 45 to 55 years (younger PMW, studies completed n = 18) and 70 to 80 years (older PMW, studies completed n = 15) was conducted. The last menstrual period was more than 12 months previously. The women had a body mass index (BMI) less than 30 kg/m(2) and were taking no medication. Subjects were studied at baseline, after 1 month of transdermal estrogen (Estraderm, 50 mug/day) administration (E-2), followed by a further month of transdermal estrogen with progesterone (100 mg per vagina twice daily) for the final 7 days (E-2 + P). Anthropometric measurements and energy assessments were performed at each visit. Physiologic HR was achieved in each subject, and there was no difference between levels achieved in older and younger women. Resting energy expenditure and activity level were positively correlated with fat-free mass (P < .0001), while energy intake was not. Resting energy expenditure was lower in older compared with younger PMW when adjusted for fat-free mass (P < .005). Energy intake was also lower in the older PMW when corrected for fat-free mass (P < .0001); as was activity level (P < .05). There was no effect of hormonal treatment on any of the parameters measured. Changes in weight from baseline for E-2 (0.37 +/- 0.25 and 0.61 +/- 0.27 kg in younger and older) and E-2 + P (0.11 +/- 0.38 and 0.28 +/- 0.31 kg) were not statistically significant. In addition, there was no difference in BMI, fat mass, fat-free mass, total body water, or waist-to-hip ratio (WHR) between groups or with hormonal treatment. In conclusion, short-term transdermal HR is not associated with significant changes in weight or other anthropometric measures in younger or older PMW. These studies confirm the decrease in energy expenditure that occurs with aging, but indicates that there is no effect of HR on resting energy expenditure. Copyright (C) 2001 by W.B. Saunders Company. C1 Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Anderson, EJ (reprint author), Massachusetts Gen Hosp, Gen Clin Res Ctr, MC GRBBA 005,25 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [MO1-RR-01066]; NIA NIH HHS [R01 AG013241, R01-AG-13241]; NICHD NIH HHS [P30- HD-23138] NR 38 TC 13 Z9 13 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD MAR PY 2001 VL 50 IS 3 BP 265 EP 269 DI 10.1053/meta.2001.21015 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 408JK UT WOS:000167322900002 PM 11230776 ER PT J AU Dull, RO Yuan, J Chang, YS Tarbell, J Jain, RK Munn, LL AF Dull, RO Yuan, J Chang, YS Tarbell, J Jain, RK Munn, LL TI Kinetics of placenta growth factor/vascular endothelial growth factor synergy in endothelial hydraulic conductivity and proliferation SO MICROVASCULAR RESEARCH LA English DT Article ID VASCULAR-PERMEABILITY FACTOR; CELL GROWTH; FLT-1; BINDING; FLK-1/KDR; RECEPTORS; KINASE; KDR; IDENTIFICATION; ANGIOGENESIS AB Vascular endothelial growth factor (VEGF) was originally discovered as vascular permeability factor because of its ability to increase microvascular permeability to plasma proteins. Since then, it has been shown to induce proliferation and migration in endothelial cells. Placenta growth factor (PlGF) is a member of the VEGF family of growth factors, but has little or undetectable mitogenic activity on endothelial cells. Intriguingly, however, PlGF was able to potentiate the action of low concentrations of VEGF on endothelial cell growth and macromolecule permeability in vitro. Here we show that PlGF can potentiate the effects of VEGF on the hydraulic conductivity of certain endothelial cells and that the duration of pretreatment with PlGF determines the resulting response. Hydraulic conductivity (Lp) was calculated from the water flux across the monolayer of human umbilical vein endothelial cells (HUVECs) or bovine aortic endothelial cells (BAECs). After 2 h of exposure to VEGF(165), the Lp of BAEC monolayers increased threefold, but the Lp of HUVEC monolayers did not increase. PlGF alone induced a small (63%) increase in Lp in BAECs, but not in HUVECs. BAEC, but not HUVEC, monolayers exposed first to PlGF and then to VEGF exhibited a seven- to eightfold increase in Lp. This enhancement in BAEC Lp could be observed for 4 h after the administration of PlGF. PlGF also potentiated the effect of VEGF on BAEC proliferation. Thus, augmentation of VEGF action by PlGF depends on the duration of PlGF exposure and on the origin of endothelial cells. (C) 2001 Academic Press. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA. Penn State Univ, Dept Chem Engn, University Pk, PA 16802 USA. RP Dull, RO (reprint author), Johns Hopkins Univ, Sch Med, Dept Anesthesia & Crit Care Med, Baltimore, MD 21218 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 24 TC 22 Z9 22 U1 0 U2 2 PU ACADEMIC PRESS INC 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 MAR PY 2001 VL 61 IS 2 BP 203 EP 210 DI 10.1006/mvre.2000.2298 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 413CZ UT WOS:000167593500008 PM 11254400 ER PT J AU Shaffer, DW Dawson, SL Meglan, D Cotin, S Ferrell, M Norbash, A Muller, J AF Shaffer, DW Dawson, SL Meglan, D Cotin, S Ferrell, M Norbash, A Muller, J TI Design principles for the use of simulation as an aid in interventional cardiology training SO MINIMALLY INVASIVE THERAPY & ALLIED TECHNOLOGIES LA English DT Editorial Material DE medicine; simulations; learning; training; education; interventional cardiology AB Learning complex skills through simulation is a goal for training physicians in specialties such as interventional cardiology, where traditional training puts patients at risk. Intuitively, interactive simulation of anatomy, pathology and therapeutic actions should lead to shortening of the learning curve for novice or inexperienced physicians. An accurate recreation of the interactions among anatomy, pathology and therapeutic actions is a necessary, but not sufficient, condition for the development of a simulation-based training system. In addition to real-time graphic interactivity coupled with haptic response, a successful training tool will require features of a 'learning system' such as: an embedded curriculum, functionality that allows rehearsal and practice, hypertext links to educational information, personal archiving, and instructor review and testing capabilities. We describe how such a system might look for the field of interventional cardiology, and suggest that designing a simulation with both technical and pedagogical fidelity is essential in developing simulation-based training systems in any field of medicine. C1 Massachusetts Gen Hosp, Ctr Innovat Minimally Invas Therapy, Boston, MA 02114 USA. RP Shaffer, DW (reprint author), Harvard Univ, Grad Sch Educ, Longfellow Hall Room 325, Cambridge, MA 02138 USA. RI Cotin, Stephane/A-2105-2017 OI Cotin, Stephane/0000-0002-2661-505X NR 30 TC 6 Z9 6 U1 0 U2 0 PU MARTIN DUNITZ LTD PI LONDON PA LIVERY HOUSE, 7-9 PRATT ST, LONDON NW1 0AE, ENGLAND SN 1364-5706 J9 MINIM INVASIV THER JI Minim. Invasive Ther. Allied Technol. PD MAR PY 2001 VL 10 IS 2 BP 75 EP 82 PG 8 WC Surgery SC Surgery GA 477DP UT WOS:000171268100002 ER PT J AU Bruneau, BG Bao, ZZ Fatkin, D Xavier-Neto, J Georgakopoulos, D Maguire, CT Berul, CI Kass, DA Kuroski-de Bold, ML de Bold, AJ Conner, DA Rosenthal, N Cepko, CL Seidman, CE Seidman, JG AF Bruneau, BG Bao, ZZ Fatkin, D Xavier-Neto, J Georgakopoulos, D Maguire, CT Berul, CI Kass, DA Kuroski-de Bold, ML de Bold, AJ Conner, DA Rosenthal, N Cepko, CL Seidman, CE Seidman, JG TI Cardiomyopathy in Irx4-deficient mice is preceded by abnormal ventricular gene expression SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID BHLH TRANSCRIPTION FACTOR; MYOSIN LIGHT CHAIN-2; FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; IROQUOIS HOMEOBOX GENES; NATRIURETIC-FACTOR GENE; HEART DEVELOPMENT; CARDIAC MORPHOGENESIS; XENOPUS HOMOLOG; TRANSGENIC MICE; MOUSE EMBRYOS AB To define the role of Irx4, a member of the Iroquois family of homeobox transcription factors in mammalian heart development and function, we disrupted the murine Irx4 gene. Cardiac morphology in Irx4-deficient mice (designated Irx4(Delta ex2/Delta ex2)) was normal during embryogenesis and in early postnatal life. Adult Irx4(Delta ex2/Delta ex2) mice developed a cardiomyopathy characterized by cardiac hypertrophy and impaired contractile function. Prior to the development of cardiomyopathy, Irx4(Delta ex2/Delta ex2) hearts had abnormal ventricular gene expression: Irx4-deficient embryos exhibited reduced ventricular expression of the basic helix-loop-helix transcription factor eHand (Hand1), increased Irx2 expression, and ventricular induction of an atrial chamber-specific transgene. In neonatal hearts, ventricular expression of atrial natriuretic factor and alpha -skeletal actin was markedly increased. Several weeks subsequent to these changes in embryonic and neonatal gene expression, increased expression of hypertrophic markers BNP and beta -myosin heavy chain accompanied adult-onset cardiac hypertrophy. Cardiac expression of Irx1, Irx2, and Irx5 may partially compensate for loss of Irx4 function. We conclude that Irx4 is not sufficient for ventricular chamber formation but is required far the establishment of some components of a ventricle-specific gene expression program. In the absence of genes under the control of Irx4, ventricular function deteriorates and cardiomyopathy ensues. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. Brigham & Womens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. FMUSP, HC, Inst Coracao, InCor,Lab Genet & Cardiol Mol, BR-05403000 Sao Paulo, Brazil. Johns Hopkins Univ, Baltimore, MD USA. Univ Ottawa, Ottawa Hosp, Inst Heart, Ottawa, ON K1Y 4H9, Canada. RP Seidman, JG (reprint author), Harvard Univ, Sch Med, Dept Genet, 200 Longwood Ave, Boston, MA 02115 USA. EM seidman@rascal.med.harvard.edu OI Bruneau, Benoit/0000-0002-0804-7597 NR 57 TC 88 Z9 91 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 EI 1098-5549 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 2001 VL 21 IS 5 BP 1730 EP 1736 DI 10.1128/MCB.21.5.1730-1736.2001 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 401RU UT WOS:000166942700031 PM 11238910 ER PT J AU Lu, Y Lian, HZ Sharma, P Schreiber-Agus, N Russell, RG Chin, L van der Horst, GTJ Bregman, DB AF Lu, Y Lian, HZ Sharma, P Schreiber-Agus, N Russell, RG Chin, L van der Horst, GTJ Bregman, DB TI Disruption of the Cockayne syndrome B gene impairs spontaneous tumorigenesis in cancer-predisposed Ink4a/ARF knockout mice SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RNA-POLYMERASE-II; NUCLEOTIDE EXCISION-REPAIR; TRANSCRIPTION-COUPLED REPAIR; ARF TUMOR-SUPPRESSOR; GROUP-A GENE; XERODERMA-PIGMENTOSUM; PREFERENTIAL REPAIR; DNA-DAMAGE; P53-INDEPENDENT APOPTOSIS; NUCLEAR ACCUMULATION AB Cells isolated from individuals with Cockayne syndrome (CS) have a defect in transcription-coupled DNA repair, which rapidly corrects certain DNA lesions located on the transcribed strand of active genes. Despite this DNA repair defect, individuals with CS group A (CSA) or group B (CSB) do not exhibit an increased spontaneous or UV-induced cancer rate. In order to investigate the effect of CSB deficiency on spontaneous carcinogenesis, we crossed CSB (-/-) mice with cancer-prone mice lacking the p16(Ink4a)/p19(ARF) tumor suppressor locus. CSB-/- mice are sensitive to UV-induced skin cancer but show no increased rate of spontaneous cancer, CSB-/- Ink4a/ARF(-/-) mice developed 60% fewer tumors than Ink4a/ARF(-/-) animals and demonstrated a longer tumor-free latency time (260 versus 150 days). Moreover, CSB-/- Ink4a/ARF(-/-) mouse embryo fibroblasts (MEFs) exhibited a lower colony formation rate after low-density seeding, a lower rate of H H-Ras-induced transformation, slower proliferation, and a lower mRNA synthesis rate than Ink4a/ARF(-/-) MEFs. CSB-/- Ink4a/ARF(-/-) MEFs were also more sensitive to UV-induced p53 induction and W-induced apoptosis than were Ink4a/ARF(-/-) MEFs, In order to investigate whether the apparent antineoplastic effect of CSB gene disruption was caused by sensitization to genotoxin-induced (p53-mediated) apoptosis or by p53-independent sequelae, we also generated p53(-/-) and CSB-/- p53(-/-) MEFs. The CSB-/- p53(-/-) MEFs demonstrated lower colony formation efficiency, a lower proliferation rate, a lower mRNA synthesis rate, and a higher rate of UV-induced cell death than p53(-/-) MEFs. Collectively, these results indicate that the antineoplastic effect of CSB gene disruption is at least partially p53 independent; it may result from impaired transcription or from apoptosis secondary to environmental or endogenous DNA damage. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Pathol F514A, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Ctr Comprehens Canc, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Inst Anim Studies, Bronx, NY 10461 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Erasmus Univ, Dept Cell Biol & Genet, NL-3000 DR Rotterdam, Netherlands. RP Bregman, DB (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Pathol F514A, 1300 Morris Pk Ave, Bronx, NY 10461 USA. RI van der Horst, Gijsbertus/E-3661-2015 FU NCI NIH HHS [5-P30-CA13330-26, P30 CA013330, R01 CA80171-01]; NIA NIH HHS [AG17242-02, P01 AG017242] NR 62 TC 26 Z9 27 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 2001 VL 21 IS 5 BP 1810 EP 1818 DI 10.1128/MCB.21.5.1810-1818.2001 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 401RU UT WOS:000166942700038 PM 11238917 ER PT J AU Hall, C Nelson, DM Ye, XF Baker, K DeCaprio, JA Seeholzer, S Lipinski, M Adams, PD AF Hall, C Nelson, DM Ye, XF Baker, K DeCaprio, JA Seeholzer, S Lipinski, M Adams, PD TI HIRA, the human homologue of yeast Hir1p and Hir2p, is a novel cyclin-cdk2 substrate whose expression blocks S-phase progression SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HISTONE GENE-TRANSCRIPTION; DNA-BINDING ACTIVITY; CELL-CYCLE; SACCHAROMYCES-CEREVISIAE; DEPENDENT KINASES; DIGEORGE-SYNDROME; NEGATIVE REGULATION; PROTEIN-KINASE; DROSOPHILA-MELANOGASTER; RETINOBLASTOMA PROTEIN AB Substrates of cyclin-edk2 kinases contain two distinct primary sequence motifs: a cyclin-binding RXL motif and one or more phosphoacceptor sites (consensus S/TPXK/R or S/TP). To identify novel cyclin-cdk2 substrates, we searched the database for proteins containing both of these motifs, One such protein is human HIRA, the homologue of two cell cycle-regulated repressors of histone gene expression in Saccharomyces, cerevisiae, Hir1p and Hir2p. Here we demonstrate that human HIRA is an in vivo substrate of a cyclin-cdk2 kinase, First, HIRA bound to and was phosphorylated by cyclin A- and E-cdk2 in vitro in an RXL-dependent manner. Second, HIRA was phosphorylated in vivo on two consensus cyclin-cdk2 phosphoacceptor sites and at least one of these, threonine 555, was phosphorylated by cyclinA-cdk2 in vitro. Third, phosphorylation of HIRA in vivo was blocked by cyclin-cdk2 inhibitor p21(cip1). Fourth, HIRA became phosphorylated on threonine 555 in S phase when cyclin-cdk2 kinases are active. Fifth, HIRA was localized preferentially to the nucleus, where active cyclin A- and E-cdk2 are located. Finally, ectopic expression of HIRA in tells caused arrest in S phase and this is consistent with the notion that it is a cyclin-cdk2 substrate that has a role in control of the cell cycle. C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Inst Gustave Roussy, Villejuif, France. RP Adams, PD (reprint author), Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. FU NCI NIH HHS [R01 CA076120, 1R01 CA76120] NR 65 TC 84 Z9 88 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 2001 VL 21 IS 5 BP 1854 EP 1865 DI 10.1128/MCB.21.5.1854-1865.2001 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 401RU UT WOS:000166942700043 PM 11238922 ER PT J AU Bardeesy, N Bastian, BC Hezel, A Pinkel, D DePinho, RA Chin, L AF Bardeesy, N Bastian, BC Hezel, A Pinkel, D DePinho, RA Chin, L TI Dual inactivation of RB and p53 pathways in RAS-induced melanomas SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ARF TUMOR-SUPPRESSOR; COMPARATIVE GENOMIC HYBRIDIZATION; HUMAN-MALIGNANT MELANOMA; CELL-CYCLE PROGRESSION; C-MYC; CUTANEOUS MELANOMA; P53-DEPENDENT APOPTOSIS; INK4A LOCUS; DNA-BINDING; WILD-TYPE AB The frequent loss of both INK4a and ARF in melanoma raises the question of which INK4a ARF gene product functions to suppress melanoma genesis in vivo. Moreover, the high incidence of INK4a-ARF: inactivation in transformed melanocytes, along with the lack of p53 mutation, implies a cell type-specific role for INK4a-ARF that may not be complemented by other lesions of the RE and p53 pathways. A mouse model of cutaneous melanoma has been generated previously through the combined effects of INK4a(Delta2/3) deficiency (null for INK4a and ARF) and melanocyte-specific expression of activated RAS (tyrosinase-driven H-RAS(V12G), Tyr-RAS). In this study, we made use of this Tyr-RAS allele to determine whether activated RAS can cooperate with p53 loss in melanoma genesis, whether such melanomas are biologically comparable to those arising in INK4a(Delta2/3-/-) mice, and whether tumor-associated mutations emerge in the p16(INK4n)-RB pathway in such melanomas. Here, we report that p53 inactivation can cooperate with activated RAS to promote the development of cutaneous melanomas that are clinically indistinguishable from those arisen on the INK4a(Delta2/3) null background, Genomewide analysis of RAS-induced p53 mutant melanomas by comparative genomic hybridization and candidate gene surveys revealed alterations of key components governing RB-regulated G(1)/S transition, including c-Myc, cyclin D1, cdc25a, and p21(CIPI). Consistent with the profile of c-Myc dysregulation, the reintroduction of p16(INK4a) profoundly reduced the growth of Tyr-RAS INK4a(Delta2/3-/-) tumor cells but had no effect on tumor cells derived from Tyr-RAS p53(-/-) melanomas. Together, these data validate a role for p53 inactivation in melanomagenesis and suggest that both the RE and p53 pathways function to suppress melanocyte transformation in vivo in the mouse. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. RP Chin, L (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [U01 CA084313, U01CA84313-01]; NIAMS NIH HHS [K08AR02104-01] NR 62 TC 113 Z9 116 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAR PY 2001 VL 21 IS 6 BP 2144 EP 2153 DI 10.1128/MCB.21.6.2144-2153.2001 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 426UG UT WOS:000168366300023 PM 11238948 ER PT J AU Leibiger, B Leibiger, IB Moede, T Kemper, S Kulkarni, RN Kahn, CR de Vargas, LM Berggren, PO AF Leibiger, B Leibiger, IB Moede, T Kemper, S Kulkarni, RN Kahn, CR de Vargas, LM Berggren, PO TI Selective insulin signaling through A and B insulin receptors regulates transcription of insulin and glucokinase genes in pancreatic beta cells SO MOLECULAR CELL LA English DT Article ID TYROSINE KINASE DOMAIN; P70 S6 KINASE; 3-KINASE ACTIVATION; PROMOTER; EXPRESSION; PROTEIN; GLUCOSE; VARIANTS; IDENTIFICATION; RESISTANCE AB Insulin signaling is mediated by a complex network of diverging and converging pathways, with alternative proteins and isoforms at almost every step in the process. We show here that insulin activates the transcription of its own gene and that of the 8 cell glucokinase gene (PGK) by different mechanisms. Whereas insulin gene transcription is promoted by signaling through insulin receptor A type (Ex11-), PI3K class la, and p70s6k, insulin stimulates the PGK gene by signaling via insulin receptor B type (Ex11+), PI3K class Ii-like activity, and PKB (c-Akt). Our data provide evidence for selectivity in insulin action via the two isoforms of the insulin receptor, the molecular basis being preferential signaling through different PI3K and protein kinases. C1 Karolinska Inst, Dept Mol Med, Rolf Luft Ctr Diabet Res, S-17176 Stockholm, Sweden. Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. New England Med Ctr, Dept Med, Boston, MA 02111 USA. RP Leibiger, IB (reprint author), Karolinska Inst, Dept Mol Med, Rolf Luft Ctr Diabet Res, S-17176 Stockholm, Sweden. FU NIDDK NIH HHS [DK34928, DK09825-02, DK31036] NR 44 TC 172 Z9 183 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAR PY 2001 VL 7 IS 3 BP 559 EP 570 DI 10.1016/S1097-2765(01)00203-9 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 419UG UT WOS:000167966600011 PM 11463381 ER PT J AU Ukiyama, E Jancso-Radek, A Li, B Milos, L Zhang, W Phillips, NB Morikawa, N King, CY Chan, G Haqq, CM Radek, JT Poulat, F Donahoe, PK Weiss, MA AF Ukiyama, E Jancso-Radek, A Li, B Milos, L Zhang, W Phillips, NB Morikawa, N King, CY Chan, G Haqq, CM Radek, JT Poulat, F Donahoe, PK Weiss, MA TI SRY and architectural gene regulation: The kinetic stability of a bent protein-DNA complex can regulate its transcriptional potency SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID TESTIS-DETERMINING FACTOR; MINOR-GROOVE; BINDING PROPERTIES; CRYSTAL-STRUCTURE; SEX REVERSAL; HMG-DOMAIN; FLUORESCENCE; MECHANISM; MUTATIONS; PRODUCT AB Protein-directed DNA bending is proposed to regulate assembly of higher-order DNA-multiprotein complexes (enhanceosomes and repressosomes). Because transcriptional initiation is a nonequilibrium process, gene expression may be modulated by the lifetime of such complexes. The human testis-determining factor SRY contains a specific DNA-bending motif, the high-mobility group (HMG) box, and is thus proposed to function as an architectural factor. Here, we test the hypothesis that the kinetic stability of a bent HMG box-DNA complex can in itself modulate transcriptional potency. Our studies employ a cotransfection assay in a mammalian gonadal cell line as a model for SRY-dependent transcriptional activation. Whereas sex-reversal mutations impair SRY-dependent gene expression, an activating substitution is identified that enhances SRY's potency by 4-fold. The substitution (I13F in the HMG box; fortuitously occurring in chimpanzees) affects the motif's cantilever side chain, which inserts between base pairs to disrupt base pairing. An aromatic F13 cantilever prolongs the lifetime of the DNA complex to an extent similar to its enhanced function. By contrast, equilibrium properties (specific DNA affinity, specificity, and bending; thermodynamic stability and cellular expression) are essentially unchanged. This correlation between potency and lifetime suggests a mechanism of kinetic control. We propose that a locked DNA bend enables multiple additional rounds of transcriptional initiation per promoter. This model predicts the occurrence of a novel class of clinical variants: bent but unlocked HMG box-DNA complexes with native affinity and decreased lifetime. Aromatic DNA-intercalating agents exhibit analogous kinetic control of transcriptional elongation whereby chemotherapeutic potencies correlate with drug-DNA dissociation rates. C1 Case Western Reserve Univ, Dept Biochem, Cleveland, OH 44106 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. Inst Genet Humaine, CNRS, UPR 1142, F-34396 Montpellier, France. RP Weiss, MA (reprint author), Case Western Reserve Univ, Dept Biochem, 10900 Euclid Ave, Cleveland, OH 44106 USA. RI zhang, wei/A-7015-2011 FU NCI NIH HHS [R01 CA063485, CA-17393, CA-63485] NR 66 TC 24 Z9 25 U1 0 U2 0 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 MAR PY 2001 VL 15 IS 3 BP 363 EP 377 DI 10.1210/me.15.3.363 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 408TB UT WOS:000167342800003 PM 11222738 ER PT J AU Latchman, Y Wood, CR Chernova, T Chaudhary, D Borde, M Chernova, I Iwai, Y Long, AJ Brown, JA Nunes, R Greenfield, EA Bourque, K Boussiotis, VA Carter, LL Carreno, BM Malenkovich, N Nishimura, H Okazaki, T Honjo, T Sharpe, AH Freeman, GJ AF Latchman, Y Wood, CR Chernova, T Chaudhary, D Borde, M Chernova, I Iwai, Y Long, AJ Brown, JA Nunes, R Greenfield, EA Bourque, K Boussiotis, VA Carter, LL Carreno, BM Malenkovich, N Nishimura, H Okazaki, T Honjo, T Sharpe, AH Freeman, GJ TI PD-L2 is a second ligand for PD-I and inhibits T cell activation SO NATURE IMMUNOLOGY LA English DT Article ID INTERFERON-GAMMA; PD-1-DEFICIENT MICE; B7 FAMILY; CTLA-4; EXPRESSION; CD4(+); MEMBER; LEADS; LYMPHOPROLIFERATION; DIFFERENTIATION AB Programmed death I (PD-1)-deficient mice develop a variety of autoimmune-like diseases, which suggests that this immunoinhibitory receptor plays an important role in tolerance. We identify here PD-1 ligand 2 (PD-L2) as a second ligand for PD-1 and compare the function and expression of PD-L1 and PD-L2. Engagement of PD-1 by PD-L2 dramatically inhibits T cell receptor (TCR)-mediated proliferation and cytokine production by CD4(+) T cells,At low antigen concentrations, PD-L2-PD-1 interactions inhibit strong B7-CD28 signals, In contrast, at high antigen concentrations, PD-L2-PD-1 interactions reduce cytokine production but do not inhibit T cell proliferation. PD-L-PD-1 interactions lead to cell cycle arrest in G(0)/G(1) but do not increase cell death. In addition, ligation of PD-1 + TCR leads to rapid phosphorylation of SHP-2, as compared to TCR ligation alone, PD-L expression was up-regulated on antigen-presenting cells by interferon gamma treatment and was also present on some normal tissues and tumor cell lines,Taken together, these studies show overlapping functions of PD-L1 and PD-L2 and indicate a key role for the PD-L-PD-1 pathway in regulating T cell responses. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med,Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Div Immunol Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Wyeth Ayerst Res, Genet Inst, Cambridge, MA 02140 USA. Kyoto Univ, Grad Sch Med, Dept Med Chem, Kyoto 6068501, Japan. RP Freeman, GJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med,Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Honjo, Tasuku/N-4470-2016 FU NIAID NIH HHS [AI38310, AI39671, AI40614] NR 24 TC 1027 Z9 1113 U1 14 U2 92 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAR PY 2001 VL 2 IS 3 BP 261 EP 268 DI 10.1038/85330 PG 8 WC Immunology SC Immunology GA 409YT UT WOS:000167413800020 PM 11224527 ER PT J AU Almind, K Doria, A Kahn, R AF Almind, K Doria, A Kahn, R TI Putting the genes for type II diabetes on the map SO NATURE MEDICINE LA English DT Editorial Material ID MELLITUS GENETICS FUSION; AUTOSOMAL GENOME SCAN; SUSCEPTIBILITY LOCUS; CHROMOSOME 20Q; INSULIN; MUTATIONS; NIDDM; POLYMORPHISM; CAUCASIANS; INCREASE C1 Joslin Diabet Ctr, Boston, MA 02215 USA. RP Almind, K (reprint author), Joslin Diabet Ctr, Boston, MA 02215 USA. EM c.ronal.kahn@joslin.harvard.edu NR 31 TC 70 Z9 76 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 2001 VL 7 IS 3 BP 277 EP 279 DI 10.1038/85405 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 409JK UT WOS:000167380400019 PM 11231616 ER PT J AU Backskai, BJ Kajdasz, ST Christie, RH Carter, C Games, D Seubert, P Schenk, D Hyman, BT AF Backskai, BJ Kajdasz, ST Christie, RH Carter, C Games, D Seubert, P Schenk, D Hyman, BT TI Imaging of amyloid-beta deposits in brains of living mice permits direct observation of clearance of plaques with immunotherapy SO NATURE MEDICINE LA English DT Article ID ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; PEPTIDE; MOUSE; ANTIBODIES; PATHOLOGY; NEURONS C1 Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. Elan Pharmaceut, S San Francisco, CA USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. NR 14 TC 36 Z9 36 U1 0 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD MAR PY 2001 VL 7 IS 3 BP 369 EP 372 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 409JK UT WOS:000167380400046 ER PT J AU Morollo, AA Eck, MJ AF Morollo, AA Eck, MJ TI Structure of the cooperative allosteric anthranilate synthase from Salmonella typhimurium SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID SULFOLOBUS-SOLFATARICUS; IDENTIFICATION; COMPLEX; ASSIGNMENT; PROGRAM; RESIDUE; GENES; SITE AB We have determined the X-ray crystal structure of the cooperative anthranilate synthase heterotetramer from Salmonella typhimurium at 1.9 Angstrom resolution with the allosteric inhibitor L-tryptophan bound to a regulatory site in the TrpE subunit. Tryptophan binding orders a loop that in turn stabilizes the inactive T state of the enzyme by restricting closure of the active site cleft. Comparison with the structure of the unliganded, noncooperative anthranilate synthase heterotetramer from Sulfolobus solfataricus shows that the two homologs have completely different quarternary structures, even though their functional dimer pairs are structurally similar, consistent with differences in the cooperative behavior of the enzymes. The structural model rationalizes mutational and biochemical studies of the enzyme and establishes the structural differences between cooperative and noncooperative anthranilate synthase homologs. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Eck, MJ (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. NR 29 TC 54 Z9 56 U1 0 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD MAR PY 2001 VL 8 IS 3 BP 243 EP 247 DI 10.1038/84988 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 405VB UT WOS:000167180300018 PM 11224570 ER EF