FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Chung, DC Brown, SB Graeme-Cook, F Seto, M Warshaw, AL Jensen, RT Arnold, A AF Chung, DC Brown, SB Graeme-Cook, F Seto, M Warshaw, AL Jensen, RT Arnold, A TI Overexpression of cyclin D1 occurs frequently in human pancreatic endocrine tumors SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID EPIDERMAL GROWTH-FACTOR; SUPPRESSOR GENE; BREAST-CANCER; CELL-CYCLE; NEUROENDOCRINE TUMORS; INCREASED EXPRESSION; ESOPHAGEAL CANCER; TRANSGENIC MICE; PROTEIN; ONCOGENE AB The molecular pathogenesis of human pancreatic endocrine tumors (PETs) is poorly understood. Three independent animal models have pointed to the pivotal role of the G(1)/S cell cycle transition in pancreatic endocrine cell proliferation. We thus hypothesized that the cell cycle regulator cyclin D1 may contribute to the pathogenesis of human PETs. Overexpression of cyclin D1 was identified in 43% of cases, and no correlation was observed with clinical phenotype. The novel observation of frequent overexpression of cyclin D1 suggests that this established oncogene may be implicated in the pathogenesis of human PETs. The absence of detectable alterations in cyclin D1 genomic structure suggests that the mechanism for its oncogenic activation in PETs may be transcriptional or posttranscriptional. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Connecticut, Ctr Hlth, Ctr Mol Med, Farmington, CT 06030 USA. Aichi Canc Ctr, Lab Chemotherapy, Nagoya, Aichi 464, Japan. NIH, Digest Dis Branch, Bethesda, MD 20892 USA. RP Chung, DC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 825,55 Fruit St, Boston, MA 02114 USA. EM d_chung@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK-01410-11] NR 45 TC 59 Z9 59 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2000 VL 85 IS 11 BP 4373 EP 4378 DI 10.1210/jc.85.11.4373 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 402ML UT WOS:000166992000071 PM 11095482 ER PT J AU Warren, JR Farmer, JJ Dewhirst, FE Birkhead, K Zembower, T Peterson, LR Sims, L Bhattacharya, M AF Warren, JR Farmer, JJ Dewhirst, FE Birkhead, K Zembower, T Peterson, LR Sims, L Bhattacharya, M TI Outbreak of nosocomial infections due to extended-spectrum beta-lactamase-producing strains of Enteric Group 137, a new member of the family Enterobacteriaceae closely related to Citrobacter farmeri and Citrobacter amalonaticus SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID KLEBSIELLA-PNEUMONIAE; IDENTIFICATION; RESISTANCE; GENERATION; COMPUTER; BACTERIA AB A member of the Enterobacteriaceae initially identified as Kluyvera cryocrescens by the MicroScan Gram-Negative Combo 13 panel caused an outbreak of nosocomial infections in four patients (pneumonia, n = 2; urinary tract infection, n = 1; wound infection, n = 1) and urinary tract colonization in one patient, When the strains were tested by the Enteric Reference Laboratory of the Centers for Disease Control and Prevention, biochemical results were most compatible with Yersinia intermedia, Kluyvera cryocrescens, and Citrobacter farmeri but identification scores were low and test results were discrepant. However, when the biochemical test profile was plated in the computer database as a new organism, all strains were identified as the organism with high identification scores (0.999968 to 0.999997) and no discrepant test results. By 16S rRNA sequence analysis the organism clustered most closely with, but was distinct from, Citrobacter farmeri and Citrobacter amalonaticus, Based on its unique biochemical profile and rRNA sequence, this organism is designated Enteric Group 137, Restriction endonuclease analysis and taxonomic antibiograms of strains causing the outbreak demonstrated a single clone of Enteric Group 137, and antibiotic susceptibility testing revealed the presence of extended-spectrum beta -lactamase (ESBL) resistance. Enteric Group 137 appears to be a new opportunistic pathogen that can serve as a source of ESBL resistance in the hospital. C1 Northwestern Univ, Sch Med, Dept Pathol, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. Vet Adm Chicago Hlth Care Syst Lakeside Div, Clin Microbiol Lab, Chicago, IL USA. Ctr Dis Control & Prevent, Enter Reference Lab, Foodborne & Diarrheal Dis Lab Sect, Div Bacterial & Mycot Dis,Natl Ctr Infect Dis, Atlanta, GA 30333 USA. Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. RP Warren, JR (reprint author), Northwestern Univ, Sch Med, Dept Pathol, 303 E Chicago Ave, Chicago, IL 60611 USA. NR 22 TC 11 Z9 12 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 2000 VL 38 IS 11 BP 3946 EP 3952 PG 7 WC Microbiology SC Microbiology GA 400VT UT WOS:000166892900007 PM 11060050 ER PT J AU Witt, DJ Kemper, M Stead, A Sillekens, P Ginocchio, CC Espy, MJ Paya, CV Smith, TF Roeles, F Caliendo, AM AF Witt, DJ Kemper, M Stead, A Sillekens, P Ginocchio, CC Espy, MJ Paya, CV Smith, TF Roeles, F Caliendo, AM TI Analytical performance and clinical utility of a nucleic acid sequence-based amplification assay for detection of cytomegalovirus infection SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID TRANSPLANT RECIPIENTS; HIV-1 RNA; EXPRESSION; SPECIMENS; VIRUS; GENE; TUBE AB A nucleic acid sequence-based amplification (NASBA) assay for qualitative detection of human cytomegalovirus (CMV) pp67 mRNA was evaluated in a multicenter study, Negative results were obtained for all specimens from 50 CMV-seronegative and 50 CMV-seropositive low-risk whole-blood donors, No interference with CMV mRNA amplification was observed in the testing of 288 specimens containing various potential interfering substances, nonspecifically reacting substances (including mRNA from other herpesviruses), and three anticoagulants, A total of 95% (50 of 51) of CMV-positive (cell culture- and antigenemia immunofluorescence [AG-IFA]-positive) clinical specimens were positive by the NASBA assay. Results from different operators over multiple testing days were consistent for each of four panel members containing different concentrations of CMV mRNA indicating the reproducibility of the assay. The estimated 95% reliable upper detection limit of the assay was 600 mRNA copies; the lower limit of detection was less than 25 mRNA copies. The clinical utility of the assay was evaluated with longitudinally collected specimens from solid-organ transplant patients (n = 21), A total of 98% (81 of 83) of the specimens from CMV-negative patients were negative by the NASBA assay, while 90% (10 of 11) of patient specimens that were positive by cell culture or AG-IFA were positive by the NASBA assay. Positive NASBA assay results were obtained earlier than AG-IFA or cell culture results for 55% of the patients and at the same time for the remainder of the patients (45%), The overall agreement between the NASBA assay and current reference tests was 86% when active CMV infection was present, These studies indicate that the CMV pp67 mRNA NASBA assay has reproducible and sensitive performance characteristics that should enable more rapid diagnosis of CMV infection. C1 Organon Teknika Corp, Durham, NC 27712 USA. Organon Teknika BV, Boxtel, Netherlands. Sacramento Med Fdn, Sacramento, CA USA. N Shore Univ Hosp, Manhasset, NY 11030 USA. Mayo Clin, Rochester, MN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Witt, DJ (reprint author), Organon Teknika Corp, 100 AKZO Ave, Durham, NC 27712 USA. RI sebastianovitsch, stepan/G-8507-2013 NR 22 TC 20 Z9 22 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 2000 VL 38 IS 11 BP 3994 EP 3999 PG 6 WC Microbiology SC Microbiology GA 400VT UT WOS:000166892900015 PM 11060058 ER PT J AU Tremblay, CL Giguel, F Merrill, DP Wong, JT Rosenberg, E Kalams, S Walker, BD D'Aquila, RT Hirsch, MS AF Tremblay, CL Giguel, F Merrill, DP Wong, JT Rosenberg, E Kalams, S Walker, BD D'Aquila, RT Hirsch, MS TI Marked differences in quantity of infectious human immunodeficiency virus type 1 detected in persons with controlled plasma viremia by a simple enhanced culture method SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID REPLICATION; HIV-1 AB Culture of autologous CD4 lymphocytes from peripheral blood mononuclear cells compared favorably with two other methods for the measurement of cell-associated human immunodeficiency virus type 1 (HIV-1). For subjects with undetectable HIV-1 RNA levels in plasma, there was a 10,000-fold range of cell-associated virus detected. This method provides a simple and reproducible means for monitoring cell-associated HIV-1. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Infect Dis Unit,AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Immunopathol Unit, Boston, MA 02114 USA. RP Hirsch, MS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Infect Dis Unit,AIDS Res Ctr, Gray 5,Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [CA12464]; NIAID NIH HHS [R21 AI040873, U01 AI027659, R01 AI040873, AI40873, AI29193, R01 AI029193] NR 6 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 2000 VL 38 IS 11 BP 4246 EP 4248 PG 3 WC Microbiology SC Microbiology GA 400VT UT WOS:000166892900057 PM 11060100 ER PT J AU Harris, JR AF Harris, JR TI Notes on the Ontario trial in the context of breast-conserving therapy for early-stage breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 20-23, 2000 CL NEW ORLEANS, LOUISIANA SP Amer Soc Clin Oncol ID FOLLOW-UP; RADIOTHERAPY C1 Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. RP Harris, JR (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. NR 10 TC 3 Z9 3 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 NOV 1 PY 2000 VL 18 IS 21 SU S BP 43S EP 44S PG 2 WC Oncology SC Oncology GA 371KL UT WOS:000165178100008 PM 11060325 ER PT J AU Gutierrez, M Chabner, BA Pearson, D Steinberg, SM Jaffe, ES Cheson, BD Fojo, A Wilson, WH AF Gutierrez, M Chabner, BA Pearson, D Steinberg, SM Jaffe, ES Cheson, BD Fojo, A Wilson, WH TI Role of a doxorubicin-containing regimen in relapsed and resistant lymphomas: An 8-year follow-up study of EPOCH SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NON-HODGKINS-LYMPHOMA; BONE-MARROW TRANSPLANTATION; P-GLYCOPROTEIN EXPRESSION; CLINICAL DRUG-RESISTANCE; HIGH-DOSE CHEMOTHERAPY; PHASE-II; ETOPOSIDE; VINCRISTINE; TUMORS; TRIAL AB Purpose: Curative up-front regimens for non-Hodgkin's lymphomas contain doxorubicin, vincristine, and cyclophosphamide, whereas salvage regimens generally contain non-cross-resistant agents. We hypothesized that up-front agents may be highly effective for salvage and developed an infusional regimen based on in vitro evidence of increased efficacy. Patients and Methods: A prospective phase II study of etoposide, vincristine, and doxorubicin over 96 hours with bolus cyclophosphamide and oral prednisone (EPOCH) was performed in 131 patients with relapsed or resistant lymphoma. Results: Seventy-nine percent of patients herd aggressive histologies, 46% were considered high risk by the International Prognostic Index, and 34% herd resistant disease. Eighty-eight percent of patients held received at least four of the agents in EPOCH, and 94% had received doxorubicin. In 125 assessable patients, 29 (24%) achieved complete responses and 60 (50%) achieved partial responses. Among 42 patients with resistant disease, 57% responded, and in 28 patients with relapsed aggressive de novo lymphomas, 89% responded with 54% complete responses. With a median follow-up of 76 months, the overall and event-free survivals (EFS) were 17.5 and 7 months, respectively. In 33 patients with sensitive aggressive disease who did not receive stem-cell transplantation, EFS was 19% at 36 months. Toxicity was primarily hematologic, with an 18% incidence of febrile neutropenia. No clinically significant cardiac toxicity was observed, despite no maximum cumulative doxorubicin dose. Conclusion: EPOCH is highly effective in patients who had previously received most/all of the same drugs and produces durable remissions in curable subtypes. Salvage regimens need not contain non-crossresistant agents, and infusional schedules may partially reverse drug resistance and reduce toxicity. (C) 2000 by American Society of Clinical Oncology. C1 NCI, Med Branch, Div Clin Sci, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wilson, WH (reprint author), NCI, Med Branch, Div Clin Sci, Bldg 10,Room 12N-226,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 34 TC 77 Z9 86 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 NOV 1 PY 2000 VL 18 IS 21 BP 3633 EP 3642 PG 10 WC Oncology SC Oncology GA 370RJ UT WOS:000165135800006 PM 11054436 ER PT J AU Socransky, SS Haffajee, AD Smith, C Duff, GW AF Socransky, SS Haffajee, AD Smith, C Duff, GW TI Microbiological parameters associated with IL-1 gene polymorphisms in periodontitis patients SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE microbiology; bacteria; subgingival plaque; periodontal disease; periodontitis; periodontal; IL-1 genotype ID DNA-DNA HYBRIDIZATION; PORPHYROMONAS-GINGIVALIS; TREPONEMA-DENTICOLA; EPITHELIAL-CELLS; ADULT PERIODONTITIS; SUBGINGIVAL PLAQUE; BACTEROIDES-FORSYTHUS; ORAL BACTERIA; GROWTH; HEALTHY AB Background, aims: Polymorphisms in the cluster of IL-1 genes have been significantly associated with the severity of adult periodontitis. The purpose of this study was to compare microbiological parameters in IL-1 genotype negative and positive adult subjects with a range of periodontitis severities. Method: The study included 108 subjects in good general health. Clinical parameters were recorded at 6 sites/tooth excluding 3rd molars and included: plaque accumulation, gingival erythema, bleeding on probing, suppuration, pocket depth and attachment level. Subgingival plaque samples were collected from the mesiobuccal surface of up to 28 teeth in each subject (mean 25.3) providing a total of 2736 samples. The levels of 40 subgingival taxa were determined in each sample using checkerboard DNA-DNA hybridization. Fingerstick blood samples were collected for IL-1A (+4845) and IL-1B (+3954) genotyping using PCR-based methods. Results: The proportion of IL-1 genotype positive subjects that exhibited mean counts of specific subgingival species above selected thresholds was significantly higher than the proportion of genotype negative subjects. Prominent among species that were detected at higher levels in genotype positive subjects were members of the "red" and "orange" complexes and included: Bacteroides forsythus, Treponema denticola, the Fusobacterium nucleatum subspecies, Fusobacterium periodonticum, Campylobacter gracilis, Campylobacter showae and Streptococcus constellatus. Streptococcus intermedius, Streptococcus gordonii and 3 Capnocytophaga species were also detected more frequently at high numbers in genotype positive subjects. Significantly higher mean counts of B. forsythus, Porphyromonas gingivalis, T. denticola, the F. nucleatum subspecies, F. periodonticum, Campylobacter rectus, C. showae, Eubacterium nodatum, S. constellatus, S. gordonii, and S. intermedius were detected at periodontal pockets >6 nun in subjects who were genotype positive when compared with genotype negative subjects. The increase was due to increased numbers of cells of these species rather than a major shift in proportion. Conclusion: The data suggest that genotype positive subjects more frequently had higher revels of "red" and "orange" complex species that are known to be strongly associated with measures of periodontal inflammation. C1 Forsyth Inst, Dept Periodontol, Boston, MA USA. Univ Sheffield, Div Med & Mol Genet, Sheffield, S Yorkshire, England. RP Socransky, SS (reprint author), Forsyth Inst, Dept Periodontol, Boston, MA USA. FU NIDCR NIH HHS [DE-04881, DE-10977] NR 36 TC 88 Z9 92 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD NOV PY 2000 VL 27 IS 11 BP 810 EP 818 DI 10.1034/j.1600-051x.2000.027011810.x PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 364LL UT WOS:000089893800004 PM 11073323 ER PT J AU Calabrese, JR Suppes, T Bowden, CL Sachs, GS Swann, AC McElroy, SL Kusumakar, V Ascher, JA Earl, NL Greene, PL Monaghan, ET AF Calabrese, JR Suppes, T Bowden, CL Sachs, GS Swann, AC McElroy, SL Kusumakar, V Ascher, JA Earl, NL Greene, PL Monaghan, ET CA Lamictal 614 Study Grp TI A double-blind, placebo-controlled, prophylaxis study of lamotrigine in rapid-cycling bipolar disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 2nd European-Stanley-Foundation Conference on Bipolar Disorder CY AUG, 2000 CL AMSTERDAM, NETHERLANDS SP European Stanley Fdn ID LITHIUM; VALIDITY; MAINTENANCE; DEPRESSION AB Background: Patients with rapid-cycling bipolar disorder are often treatment refractory. This study examined lamotrigine as maintenance monotherapy for rapid-cycling bipolar disorder. Method: Lamotrigine was added to patients' current psychotropic regimens and titrated to clinical effect during an open-label treatment phase. Stabilized patients were tapered off other psychotropics and randomly assigned to lamotrigine or placebo monotherapy for 6 months. Time to additional pharmacotherapy for emerging symptoms was the primary outcome measure. Secondary efficacy measures included survival in study (time to any premature discontinuation), percentage of patients stable without relapse for 6 months, and changes in the Global Assessment Scale and Clinical Global Impressions-Severity scale. Safety was assessed from adverse event, physical examination, and laboratory data. Results: 324 patients with rapid-cycling bipolar disorder (DSM-IV criteria) received open-label lamotrigine, and 182 patients were randomly assigned to the double-blind maintenance phase. The difference between the treatment groups in time to additional pharmacotherapy did not achieve statistical significance in the overall efficiency population. However, survival in study was statistically different between the treatment groups (p = .036). Analyses also indicated a 6-week difference in median survival time favoring lamotrigine. Forty-one percent of lamotrigine patients versus 26% of placebo patients (p = .03) were stable without relapse for 6 months of monotherapy. Lamotrigine was well tolerated; there were no treatment-related changes in laboratory parameters, vial signs, or body weight. No serious rashes occurred. Conclusion: This was the largest and only prospective placebo-controlled study of rapid-cycling bipolar disorder patients to date: results indicate lamotrigine monotherapy is a useful treatment for some patients with rapid-cycling bipolar disorder. C1 Case Western Reserve Univ, Univ Hosp Cleveland, Sch Med, Cleveland, OH 44106 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Bipolar Disorder Clin & Res Program, Dallas, TX USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Massachusetts Gen Hosp, Bipolar Res & Clin, Boston, MA 02114 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, Houston, TX USA. Univ Cincinnati, Coll Med, Biol Psychiat Program, Cincinnati, OH 45221 USA. Dalhousie Univ, Halifax Stanley Ctr, Halifax, NS, Canada. Glaxo Wellcome Res & Dev Ltd, Res Triangle Pk, NC USA. RP Calabrese, JR (reprint author), 11400 Euclid Ave,Suite 200, Cleveland, OH 44106 USA. NR 33 TC 354 Z9 363 U1 3 U2 11 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD NOV PY 2000 VL 61 IS 11 BP 841 EP 850 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 377XK UT WOS:000165551400006 PM 11105737 ER PT J AU Schmidt, ME Fava, M Robinson, JM Judge, R AF Schmidt, ME Fava, M Robinson, JM Judge, R TI The efficacy and safety of a new enteric-coated formulation of fluoxetine given once weekly during the continuation treatment of major depressive disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID THERAPY AB Background: A simple, once-weekly dosing regimen could be a convenient alternative for many patients during long-term treatment of depression. Such a strategy might also be effective for improving medication compliance and the outcome of continuation treatment. The safety and effectiveness of a new formulation of enteric-coated fluoxetine (90 mg) given once weekly was tested during the continuation treatment of major depressive disorder. Method: Patients meeting DSM-IV criteria for major depressive disorder with modified 17-item Hamilton Rating Scale for Depression (HAM-D-17) scores greater than or equal to 18 and Clinical Global Impressions-Severity of Illness scale (CGI-S) scores greater than or equal to 4 were treated 13 weeks with open-label 20 mg/day of fluoxetine in a multicenter U.S. study. Responders (N = 501) were randomly assigned to receive 20 mg of fluoxetine daily, placebo, or 90 mg of enteric-coated fluoxetine weekly for 25 weeks of double-blind continuation treatment. The primary efficacy measure was the percentage of patients who relapsed. Time to relapse was tested over the 25-week continuation period using log-rank analyses of the Kaplan-Meier estimates of relapse rates. Additional analyses of efficacy included comparison of change from baseline to endpoint for the HAM-D-17, CGI-S, and HAM-D-28 subscales by last observation carried forward (LOCF). Safety measures included comparison of treatment-emergent adverse events, both spontaneous and solicited (using the Association for Methodology of Documentation in Psychiatry-Module 5), vital signs, and laboratory measures. Results: Relapse rates for patients assigned to fluoxetine, either 20 mg daily or 90 mg weekly, were significantly lower than for placebo by log-rank analysis and LOCF analyses of secondary efficacy measures. Efficacy did not significantly differ between the 2 active drug groups by these measures. Enteric-coated fluoxetine at a once-weekly dose of 90 mg was well tolerated, and its safety profile was similar to that of daily 20 mg of fluoxetine. Conclusion: The formulation of enteric-coated fluoxetine taken once weekly is effective, safe, and well tolerated for continuation treatment of depression in patients who responded to acute treatment with 20 mg/day of fluoxetine. Monitoring during long-term treatment fur evidence of sustained remission is important regardless of dosing regimen. C1 Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA USA. RP Schmidt, ME (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Drop Code 1730, Indianapolis, IN 46285 USA. RI Schmidt, Mark/I-5052-2016 OI Schmidt, Mark/0000-0003-3417-8977 NR 17 TC 53 Z9 54 U1 1 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD NOV PY 2000 VL 61 IS 11 BP 851 EP 857 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 377XK UT WOS:000165551400007 PM 11105738 ER PT J AU Fava, M Judge, R Hoog, SL Nilsson, ME Koke, SC AF Fava, M Judge, R Hoog, SL Nilsson, ME Koke, SC TI Fluoxetine versus sertraline and paroxetine in major depressive disorder: Changes in weight with long-term treatment SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 152nd Annual Meeting of the American-Psychiatric-Association CY MAY 15-20, 1999 CL WASHINGTON, D.C. SP Amer Psychiat Assoc ID GAIN; ANTIDEPRESSANTS AB Background: The effects of extended selective serotonin reuptake inhibitor (SSRI) treatment on weight are not well characterized. Also unknown is whether different agents have differential effects. To examine these questions, we assessed weight changes in patients randomly assigned to long-term treatment with fluoxetine, sertraline, or paroxetine. Method: Patients (N = 284) with major depressive disorder (DSM-IV) were randomly assigned to double-blind treatment with fluoxetine (N = 92), sertraline, (N = 96), or paroxetine (N = 96) for a total of 26 to 32 weeks. The mean percent change in weight was compared for each group, as was the number of patients who had greater than or equal to 7% weight increase from baseline. Results: Patients (fluoxetine, N = 44; sertraline, N = 48; paroxetine, N = 47) who completed the trial were included in these analyses. Paroxetine-treated patients experienced a significant weight increase, fluoxetine-treated patients had a modest but nonsignificant weight decrease, and patients treated with sertraline had a modest brit nonsignificant weight increase. The number of patients whose weight increased greater than or equal to 7% from baseline was significantly greater For paroxetine treated compared with either fluoxetine-treated or sertraline-treated patients, Conclusion: Risk of weight gain during extended SSRI treatment differs depending on which SSRI is used. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Lilly Res Labs, Indianapolis, IN USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, WAC 812,15 Parkman St, Boston, MA 02114 USA. NR 20 TC 142 Z9 147 U1 2 U2 14 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD NOV PY 2000 VL 61 IS 11 BP 863 EP 867 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 377XK UT WOS:000165551400009 PM 11105740 ER PT J AU O'Craven, KM Kanwisher, N AF O'Craven, KM Kanwisher, N TI Mental imagery of faces and places activates corresponding stimulus-specific brain regions SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID POSITRON-EMISSION TOMOGRAPHY; HUMAN EXTRASTRIATE CORTEX; PRIMARY VISUAL-CORTEX; CEREBRAL BLOOD-FLOW; SELECTIVE ATTENTION; FUNCTIONAL MRI; INDIVIDUAL-DIFFERENCES; MINDS EYE; NEURAL MECHANISMS; FMRI AB What happens in the brain when you conjure up a mental image in your mind's eye? We tested whether the particular regions of excrastriate cortex activated during mental imagery depend on the content of the image. Using functional magnetic resonance imaging (fMRI), we demonstrated selective activation within a region of cortex specialized for face perception during mental imagery of faces, and selective activation within a place-selective cortical region during imagery of places. In a further study, are compared the activation for imagery and perception in these regions, and found greater response magnitudes for perception than for imagery of the same items. Finally, we found that it is possible to determine the content of single cognitive events from an inspection of the fMRI data from individual imagery trials. These Endings strengthen evidence that imagery and perception share common processing mechanisms, and demonstrate that the specific brain regions activated during mental imagery depend on the content of the visual image. C1 Massachusetts Gen Hosp, NMR Ctr, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. RP O'Craven, KM (reprint author), Rotman Res Inst, Baycrest Ctr, 3560 Bathurst St, Toronto, ON M6A 2E1, Canada. NR 75 TC 471 Z9 475 U1 9 U2 49 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD NOV PY 2000 VL 12 IS 6 BP 1013 EP 1023 DI 10.1162/08989290051137549 PG 11 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 390KX UT WOS:000166295200009 PM 11177421 ER PT J AU West, WC Holcomb, PJ AF West, WC Holcomb, PJ TI Imaginal, semantic, and surface-level processing of concrete and abstract words: An electrophysiological investigation SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID INFERIOR PREFRONTAL CORTEX; EVENT-RELATED POTENTIALS; MEDIAL TEMPORAL-LOBE; DUAL-CODING THEORY; BRAIN POTENTIALS; FUNCTIONAL MRI; SCALP DISTRIBUTIONS; FIELD POTENTIALS; LANGUAGE; COMPREHENSION AB Words representing concrete concepts are processed more quickly and efficiently than words representing abstract concepts. Concreteness effects have also been observed in studies using event-related brain potentials (ERPs). The aim of this study was to examine concrete and abstract words using both reaction time (RT) and ERP measurements to determine (1) at what point in the stream of cognitive processing concreteness effects emerge and (2) how different types of cognitive operations influence these concreteness effects. Three groups of subjects performed a sentence verification task in which the final word of each sentence was concrete or abstract. For each group the truthfulness judgment required either (1) image generation, (2) a semantic decision, or (3) evaluation of surface characteristics. Concrete and abstract words produced similar RTs and ERPs in the surface task, suggesting that postlexical semantic processing is necessary to elicit concreteness effects. In both the semantic and imagery tasks, RTs were shorter for concrete than for abstract words. This difference was greatest in the imagery task. Also, in both of these tasks concrete words elicited more negative ERPs than abstract words between 300 and 550 msec (N400). This effect was widespread across the scalp and may reflect activation in a linguistic semantic system common to both concrete and abstract words. ERPs were also more negative for concrete than abstract words between 550 and 800 msec. This effect was more frontally distributed and was most evident in the imagery task. We propose that this later anterior effect represents a distinct ERP component (N700) that is sensitive to the use of mental imagery. The N700 may reflect the access of specific characteristics of the imaged item or activation in a working memory system specific to mental imagery. These results also support the extended dual-coding hypothesis that superior associative connections and the use of mental imagery both contribute to processing advantages for concrete words over abstract words. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Tufts Univ, Medford, MA 02155 USA. RP West, WC (reprint author), Massachusetts Gen Hosp, VBK 827,55 Fruit St, Boston, MA 02114 USA. FU NICHD NIH HHS [HD25889] NR 53 TC 139 Z9 146 U1 4 U2 13 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD NOV PY 2000 VL 12 IS 6 BP 1024 EP 1037 DI 10.1162/08989290051137558 PG 14 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 390KX UT WOS:000166295200010 PM 11177422 ER PT J AU Kihiczak, D Colletti, PM Terk, MR AF Kihiczak, D Colletti, PM Terk, MR TI MRI of destructive Achilles tendon rupture associated with skin ulceration SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE tendons, Achilles; magnetic resonance imaging; ulcers, skin AB We present a case series of the MR findings of destructive tears of the Achilles tendon secondary to overlying soft tissue ulcerations. C1 Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ So Calif, Los Angeles Cty Imaging Sci Ctr, Sch Med, Dept Radiol, Los Angeles, CA USA. RP Kihiczak, D (reprint author), POB 9657,FND 210, Boston, MA 02114 USA. NR 6 TC 4 Z9 4 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD NOV-DEC PY 2000 VL 24 IS 6 BP 900 EP 902 DI 10.1097/00004728-200011000-00016 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 377PM UT WOS:000165522200016 PM 11105710 ER PT J AU Bauman, RA Gell, G AF Bauman, RA Gell, G TI The reality of picture archiving and communication systems (PACS): A survey SO JOURNAL OF DIGITAL IMAGING LA English DT Article DE radiology; computers; picture archiving and communication systems (PACS); digital imaging; survey ID WORLD AB Toward the end of 1997 vendors were succeeding in installing picture, archiving and communication systems (PACS) in larger numbers. It was hard to separate fact from fiction at times. This survey was undertaken by 2 members of the academic community to confirm what was operational, how well the installed systems worked, and what they were doing. Fax questionnaires were sent to nearly 1.000 facilities worldwide to identify PACS of any size in clinical operation on a date certain, February 1. 1998. A total of 177 PACS were identified. Facilities furnished responses during the first survey period from May 1 to November 1. 1998. A second survey, done in February and March of 2000. sought long-term follow-up data. Many systems operated 5 or more types of modalities. Computed tomography (CT) was the most common modality type at 83%, but the distribution of the rest held surprises. There also was an unexpectedly large use of soft copy reading and filmless operation in 1998. Clear trends toward increased use of computed radiography and digital radiography and a significant expansion on the percentage of all of a facility's examinations on the PACS were seen over the 2 years. Satisfaction with original PACS vendors was relatively high. Eighty-nine percent remained with their original vendor. Only 10 sites reported they changed vendors, and 4 facilities said they abandoned their system. The users reported their expectations of the PACS had been met in 81% of cases. Some (65%) declared their systems were cost effective. The most striking response was that 97% of the users would recommend PACS to others. Copyright (C) 2000 by W.B. Saunders Company. C1 Graz Univ, Inst Med Informat Stat & Documentat, A-8010 Graz, Austria. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gell, G (reprint author), Graz Univ, Inst Med Informat Stat & Documentat, Engelgasse 13, A-8010 Graz, Austria. NR 4 TC 18 Z9 19 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0897-1889 J9 J DIGIT IMAGING JI J. Digit. Imaging PD NOV PY 2000 VL 13 IS 4 BP 157 EP 169 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 374UA UT WOS:000165361700002 PM 11110254 ER PT J AU Kumar, AM Nadel, ES Brown, DFM AF Kumar, AM Nadel, ES Brown, DFM TI Hypertensive crisis SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID SYSTEMIC-SCLEROSIS; SCLERODERMA C1 Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Nadel, ES (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 10 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD NOV PY 2000 VL 19 IS 4 BP 369 EP 373 DI 10.1016/S0736-4679(00)00268-7 PG 5 WC Emergency Medicine SC Emergency Medicine GA 372VX UT WOS:000165255700013 PM 11074333 ER PT J AU Tola, VB Chamberlain, S Kostyk, SK Soybel, DI AF Tola, VB Chamberlain, S Kostyk, SK Soybel, DI TI Symptomatic gallstones in patients with spinal cord injury SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE biliary tract disease; gallstones; cholecystitis; paraplegia; quadriplegia ID NATURAL-HISTORY; SILENT GALLSTONES; DECISION-ANALYSIS; RISK FACTOR; DISEASE; CHOLECYSTECTOMY; MANAGEMENT; SURGERY AB Patients with spinal cord injury (SCI) have an increased prevalence of cholelithiasis. The goal of this study was to clarify the presentation and management of symptomatic gallstone disease in patients with SCI. We performed a retrospective study of presentation of gallstone complications in patients with SCI who underwent cholecystectomy for complications of gallstone disease. The West Roxbury Veterans Administration Medical Center SCI registry (605 patients) was searched fur patients who had undergone cholecystectomy more than 1 year after SCI (35 patients). Gallbladder disease profiles for the 35 patients undergoing cholecystectomy for complications of gallstone disease were prepared, including demographics, clinical presentation, diagnostic studies, operative and pathologic findings, and postoperative complications. All patients were white. Thirty-four were male and the mean age was 50 years (range 35 to 65 years). The majority of patients (66%) complained of right upper quadrant abdominal pain, evert those patients with SCI at high (i.e., cervical) levels. Of the 35 patients in our study group, 22 (63%) had biliary colic and chronic cholecystitis, nine (76%) had acute cholecystitis (gangrenous cholecystitis in two), two (6%) had choledocholithiasis symptoms or cholangitis, and two (6%) had gallstone pancreatitis. Major perioperative morbidity occurred in two (6%) of the 35 patients (pulmonary embolus; intra-operative hemorrhage), and there were no deaths. In the great majority of patients with SCI, cholelithiasis presents with chronic pain and not with life-threatening complications. Out findings suggest that presentation is no more acute in patients with SCI than in the general population. Characteristic symp,toms and signs are not necessarily obscured by SCI injury regardless of the level. C1 Vet Adm Med Ctr W Roxbury, Dept Surg, W Roxbury, MA 02132 USA. Vet Adm Med Ctr W Roxbury, Spinal Cord Injury Serv, W Roxbury, MA 02132 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Soybel, DI (reprint author), Vet Adm Med Ctr W Roxbury, Dept Surg, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. NR 16 TC 8 Z9 9 U1 0 U2 1 PU QUALITY MEDICAL PUBLISHING INC PI ST LOUIS PA 11970 BORMAN DR, STE 222, ST LOUIS, MO 63146 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD NOV-DEC PY 2000 VL 4 IS 6 BP 642 EP 647 DI 10.1016/S1091-255X(00)80115-8 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 418XL UT WOS:000167919700014 PM 11307101 ER PT J AU Lam, PYP Breakefield, XO AF Lam, PYP Breakefield, XO TI Hybrid vector designs to control the delivery, fate and expression of transgenes SO JOURNAL OF GENE MEDICINE LA English DT Review DE hybrid viral vector; transgene expression; regulation and site of expression ID ADENOASSOCIATED VIRUS VECTOR; EPSTEIN-BARR-VIRUS; VESICULAR STOMATITIS-VIRUS; SITE-SPECIFIC INTEGRATION; SCAFFOLD ATTACHMENT REGION; INDUCIBLE GENE-EXPRESSION; CELL-SPECIFIC EXPRESSION; CRE-MEDIATED EXCISION; T7 RNA-POLYMERASE; MAMMALIAN-CELLS AB One of the greatest challenges to gene therapy is the targetting of gene delivery selectively to the sites of disease and regulation of transgene expression without adverse effects. Ultimately, the successful realization of these goals is dependent upon improvements in vector design. Over the years, viral vector design has progressed from various types of replication-defective viral mutants to replication-conditioned viruses and, more recently, to 'gutted' and hybrid vectors, which have, respectively, eliminated expression of non-relevant or toxic viral genes and incorporated desired elements of different viruses so as to increase the efficacy of gene delivery in vivo. This review will focus on the different viral and cellular elements which have been incorporated into virus vectors to: improve transduction efficiencies; alter the entry specificity of virions; control the fate of transgenes in the host cells; and regulate transgene expression. Copyright (C) 2000 John Wiley & Sons, Ltd. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Program, Boston, MA 02114 USA. Natl Canc Ctr, Div Cellular & Mol Res, Singapore 169610, Singapore. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp E, Dept Mol Neurogenet, 13th St,Bldg 149, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA69246]; NINDS NIH HHS [NS24279] NR 163 TC 24 Z9 24 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD NOV-DEC PY 2000 VL 2 IS 6 BP 395 EP 408 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 390EW UT WOS:000166283600001 PM 11199260 ER PT J AU Dresselhaus, TR Peabody, JW Lee, M Wang, MM Luck, J AF Dresselhaus, TR Peabody, JW Lee, M Wang, MM Luck, J TI Measuring compliance with preventive care guidelines - Standardized patients, clinical vignettes, and the medical record SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE compliance; preventive cars guidelines; physician practice ID SIMULATED PATIENTS; HEALTH-CARE; PERFORMANCE; QUALITY; RECOMMENDATIONS; INTERNISTS; ADULT AB OBJECTIVE: To determine how accurately preventive cars reported in the medical record reflects actual physician practice or competence. DESIGN:Scoring criteria based on national guidelines were developed for 7 separate items of preventive care. The preventive care provided by randomly selected physicians was measured prospectively for each of the 7 items. Three measurement methods were used for comparison: (1) the abstracted medical record from a standardized patient (SP) visit: (2) explicit reports of physician practice during those visits from the SPs, who were actors trained to present undetected as patients: and (3) physician responses to written case scenarios (vignettes) identical to the SP presentations. SETTING: The general medicine primary care clinics of two university-affiliate VA medical centers. PARTICIPANTS: Twenty randomly selected physicians (10 at each site) from among eligible second- and third-year general internal medicine residents and attending physicians. MEASUREMENTS AND MAIN RESULTS: Physicians saw 160 SPs (8 cases x 20 physicians). Ws calculated the percentage of visits in which each prevention item was recorded in the chart, determined the marginal percentage improvement of SP checklists and vignettes over chart abstraction alone, and compared the three methods using an analysis-of-variance model. Ws found that chart abstraction underestimated overall prevention compliance by 16% (P < .01) compared with SP checklists. Chart abstraction scores were lower than SP checklists for all seven items and lower than vignettes for four items. The marginal percentage improvement of SP checklists and vignettes to performance as measured by chart abstraction was significant for all seven prevention items and raised the overall prevention scores from 46% to 72% (P < .0001). CONCLUSIONS: These data indicate that physicians perform more preventive cars than they report in the medical record. Thus, benchmarks of preventive care by individual physicians and institutions that rely solely on the medical record may be misleading, at best. C1 Inst Global Hlth, San Francisco, CA 94105 USA. Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Sch Med, San Francisco, CA USA. Vet Affairs Ctr Study Healthcare Provider Behav, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RAND Corp, Santa Monica, CA USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Peabody, JW (reprint author), Inst Global Hlth, 74 New Montgomery St,Suite 508, San Francisco, CA 94105 USA. NR 28 TC 82 Z9 82 U1 1 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2000 VL 15 IS 11 BP 782 EP 788 DI 10.1046/j.1525-1497.2000.91007.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 375NJ UT WOS:000165406600004 PM 11119170 ER PT J AU Bagley, J Wu, Y Sachs, DH Iacomini, J AF Bagley, J Wu, Y Sachs, DH Iacomini, J TI Defining the requirements for peptide recognition in gene therapy-induced T cell tolerance SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLASS-I ANTIGEN; MONOCLONAL-ANTIBODIES; MHC MOLECULES; BONE-MARROW; PROLONGATION; DESTRUCTION; ALLOGRAFTS; MICE AB Expression of a retrovirally transduced MHC class I Ag, H-2K(b) (K-b), in bone marrow-derived cells leads to specific prolongation of K-b disparate skin grafts, To examine the extent to which peptides derived from K-b contribute to the induction of tolerance, retroviruses carrying mutant Iib genes designed to enter separate pathways of Ag presentation were constructed Thymectomized and CD8 T cell-depleted mice that had been irradiated and reconstituted with bone marrow cells expressing a secreted form of K-b shelved prolongation of K-b disparate skin graft survival. Skin graft prolongation was not observed when similar experiments were performed using mice that were not CD8 T cell depicted. This suggests that hyporesponsiveness can he induced in CD4T cells, but not CD8 T cells by Ags presented via the exogenous pathway of Ag processing Modest prolongation of skin allografts was observed in mice reconstituted with bone marrow cells transduced with retroviruses carrying a gene encoding a mutant Kb molecule expressed only in the cytoplasm. Prolongation was also observed in similar experiments in mice that were thymectomized and CD4 T cell depleted following complete reconstitution, but not in mice that were reconstituted and then thymectomized and CD8 T cell depleted. Thus, hyporesponsiveness can he induced in a subset of CD8 T cells by recognition of peptides derived from K-b through both the direct and indirect pathways of Ag recognition, while CD4 T cell hyporesponsiveness to MHC class I disparate grafts occurs only through the indirect pathway of Ag recognition. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Iacomini, J (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH East,Bldg 149,13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [R01 AI43619] NR 25 TC 9 Z9 10 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2000 VL 165 IS 9 BP 4842 EP 4847 PG 6 WC Immunology SC Immunology GA 367RV UT WOS:000090076000011 PM 11046007 ER PT J AU McAdam, AJ Chang, TT Lumelsky, AE Greenfield, EA Boussiotis, VA Duke-Cohan, JS Chernova, T Malenkovich, N Jabs, C Kuchroo, VK Ling, V Collins, M Sharpe, AH Freeman, GJ AF McAdam, AJ Chang, TT Lumelsky, AE Greenfield, EA Boussiotis, VA Duke-Cohan, JS Chernova, T Malenkovich, N Jabs, C Kuchroo, VK Ling, V Collins, M Sharpe, AH Freeman, GJ TI Mouse inducible costimulatory molecule (ICOS) expression is enhanced by CD28 costimulation and regulates differentiation of CD4(+) T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CO-STIMULATION; LACKING EXPRESSION; ANTIGEN; TH2; ACTIVATION; B7-1; CD40; IL-4; CD80 AB The inducible costimulatory (ICOS) molecule is expressed by activated T cells and has homology to CD28 and CD152, ICOS binds B7h, a molecule expressed by APC with homology to CD80 and CD86, To investigate regulation of ICOS expression and its role in Th responses we developed anti-mouse ICOS mAbs and ICOS-Ig fusion protein. Little ICOS is expressed by freshly isolated mouse T cells, but ICOS is rapidly up-regulated on most CD4(+) and CD8(+) T cells following stimulation of the TCR, Strikingly, ICOS up-regulation is significantly reduced in the absence of CD80 and CD86 and can be restored by CD28 stimulation, suggesting that CD28-CD80/CD86 interactions may optimize ICOS expression. Interestingly, TCR-transgenic T cells differentiated into Th2 expressed significantly more ICOS than cells differentiated into Th1, We used two methods to investigate the role of ICOS in activation of CD4(+) T cells. First, CD4(+) cells were stimulated with beads coated with anti-CD3 and either B7h-Ig fusion protein or control Ig fusion protein. ICOS stimulation enhanced proliferation of CD4(+) cells and production of IFN-gamma, IL-4, and IL-10, but not IL-2, Second, TCR-transgenic CD4+ T cells were stimulated with peptide and APC in the presence of ICOS-Ig or control Ig, When the ICOS:B7h interaction was blocked by ICOS-Ig, CD4(+) T cells produced more IFN-gamma and less IL-4 and IL-10 than CD4(+) cells differentiated with control Ig, These results demonstrate that ICOS stimulation is important in T cell activation and that ICOS may have a particularly important role in development of Th2 cells. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Genet Inst, Dept Immunol, Cambridge, MA 02140 USA. RP Freeman, GJ (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Duke-Cohan, Jonathan/A-5812-2010 OI Duke-Cohan, Jonathan/0000-0002-9478-9609 FU NIAID NIH HHS [AI38310, AI39671, K08 AI01669] NR 26 TC 285 Z9 301 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2000 VL 165 IS 9 BP 5035 EP 5040 PG 6 WC Immunology SC Immunology GA 367RV UT WOS:000090076000036 PM 11046032 ER PT J AU Cao, HY Mani, I Vincent, R Mugerwa, R Mugyenyi, P Kanki, P Ellner, J Walker, BD AF Cao, HY Mani, I Vincent, R Mugerwa, R Mugyenyi, P Kanki, P Ellner, J Walker, BD TI Cellular immunity to human immunodeficiency virus type 1 (HIV-1) clades: Relevance to HIV-1 vaccine trials in Uganda SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID T-LYMPHOCYTE RESPONSES; INFECTION; CELLS; RECOGNITION; ANTIGENS AB The first prophylactic human immunodeficiency virus type 1 (HIV-1) vaccine trial in Africa, with a clade B immunogen, is currently under way in Uganda, in a region where clades A and D are endemic. The use of a B clade vaccine is based on anticipated cross-recognition of endemic strains of HIV-1 in Uganda, but, in fact, little is known about the cytotoxic T lymphocyte (CTL) responses in that region. Seventeen HIV-1-infected volunteers from Kampala, Uganda, were studied to determine the immune responses elicited by natural infection with local HIV-1 strains. Despite the presence of broad cross-clade recognition, the CTL responses to the infecting viral clade were highest in most people. Recognition of nonendemic clade B antigens was similar to that of the coendemic local clade, and, in some instances, cross-recognition of clade B was greater. Nevertheless, the degree of cross-clade cellular responses we observed lends justification to the use of clade B-based immunogens in the current phase 1 vaccine trial in Uganda. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Joint Clin Res Ctr, Kampala, Uganda. Case Western Reserve Univ, TB Res Unit, Cleveland, OH 44106 USA. RP Cao, HY (reprint author), Massachusetts Gen Hosp E, AIDS Res Ctr, 149 13th St, Charlestown, MA 02129 USA. FU NIAID NIH HHS [AI 43754-02] NR 20 TC 62 Z9 64 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV PY 2000 VL 182 IS 5 BP 1350 EP 1356 DI 10.1086/315868 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 368FA UT WOS:000090106000009 PM 11023458 ER PT J AU Schooley, RT Spino, C Kuritzkes, D Walker, BD Valentine, FT Hirsch, MS Cooney, E Friedland, G Kundu, S Merigan, TC McElrath, MJ Collier, A Plaeger, S Mitsuyasu, R Kahn, J Haslett, P Uherova, P deGruttola, V Chiu, S Zhang, B Jones, G Bell, D Ketter, N Twadell, T Chernoff, D Rosandich, M AF Schooley, RT Spino, C Kuritzkes, D Walker, BD Valentine, FT Hirsch, MS Cooney, E Friedland, G Kundu, S Merigan, TC McElrath, MJ Collier, A Plaeger, S Mitsuyasu, R Kahn, J Haslett, P Uherova, P deGruttola, V Chiu, S Zhang, B Jones, G Bell, D Ketter, N Twadell, T Chernoff, D Rosandich, M CA AIDS Clin Trials Grp 209 214 Study TI Two double-blinded, randomized, comparative trials of 4 human immunodeficiency virus type 1 (HIV-1) envelope vaccines in HIV-1-infected individuals across a spectrum of disease severity: AIDS clinical trials groups 209 and 214 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 4th National Conference on Retroviruses and Opportunistic Infections CY JAN 22-26, 1998 CL CHICAGO, ILLINOIS ID CYTOTOXIC T-LYMPHOCYTES; ANTIRETROVIRAL THERAPY; IMMUNE-RESPONSES; IMMUNOLOGICAL RESPONSES; RECOMBINANT GP120; CELL RESPONSES; INFECTION; IMMUNOGENICITY; SAFETY; VIREMIA AB The potential role of human immunodeficiency virus type 1 (HIV-1)-specific immune responses in controlling viral replication in vivo has stimulated interest in enhancing virus-specific immunity by vaccinating infected individuals with HIV-1 or its components, These studies were undertaken to define patient populations most likely to respond to vaccination, with the induction of novel HIV-1-specific cellular immune responses, and to compare the safety and immunogenicity of several candidate recombinant HIV-1 envelope vaccines and adjuvants, New lymphoproliferative responses (LPRs) developed in <30% of vaccine recipients. LPRs were elicited primarily in study participants with a CD4 cell count >350 cells/mm(3) and were usually strain restricted. Responders tended to be more likely than nonresponders to have an undetectable level of HIV-1 RNA at baseline (P = .067), Induction of new cellular immune responses by HIV-1 envelope vaccines is a function of the immunologic stage of disease and baseline plasma HIV-1 RNA level and exhibits considerable vaccine strain specificity. C1 Univ Colorado, Hlth Sci Ctr, Div Infect Dis, Denver, CO 80262 USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NYU, Sch Med, New York, NY USA. Yale Univ, Sch Med, New Haven, CT USA. Univ Washington, Sch Med, Seattle, WA USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Genentech Inc, S San Francisco, CA 94080 USA. Chiron Corp, Emeryville, CA 94608 USA. Social & Sci Syst, Rockville, MD USA. NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA. RP Schooley, RT (reprint author), Univ Colorado, Hlth Sci Ctr, Div Infect Dis, B-168,4200 E 9th Ave, Denver, CO 80262 USA. FU NIAID NIH HHS [AI-28568, AI-17665, AI-32770] NR 29 TC 33 Z9 34 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV PY 2000 VL 182 IS 5 BP 1357 EP 1364 DI 10.1086/315860 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 368FA UT WOS:000090106000010 PM 11023459 ER PT J AU Benz, EJ AF Benz, EJ TI Edward J. Benz, Jr, MD SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21218 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. Yale Univ, Div Hematol, New Haven, CT 06520 USA. RP Benz, EJ (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD NOV PY 2000 VL 48 IS 6 BP 381 EP 384 PG 4 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 372VF UT WOS:000165254200001 PM 11094857 ER PT J AU Weiler, MD Harris, NS Marcus, DJ Bellinger, D Kosslyn, SM Waber, DP AF Weiler, MD Harris, NS Marcus, DJ Bellinger, D Kosslyn, SM Waber, DP TI Speed of information processing in children referred for learning problems: Performance on a visual filtering test SO JOURNAL OF LEARNING DISABILITIES LA English DT Article ID READING DISABILITIES; CONTRAST SENSITIVITY; PHONOLOGICAL-CORE; DISABLED CHILDREN; SEARCH; DYSLEXIA; PERCEPTION; SUBTYPES; READERS; DISCREPANCY AB Children referred for evaluation of learning impairment (LI, N =100) and a comparison group of nonreferred (NLI, N = 243) children were evaluated on a visual filtering task. The task was designed hierarchically to provide for evaluation of component operations-serial search, parallel search, decision, and response. With each additional processing demand, response times increased disproportionately for the LI group relative to the NLI group. Overall response time reliably predicted academic skills and cognitive ability, but was more strongly related to group membership. Thus, this nonverbal visual task is sensitive to a characteristic of children with learning problems over and above discrete academic and cognitive skills. Children with problems adapting to the demands of schooling may be distinguished by a disproportionate vulnerability to processing load. C1 Childrens Hosp, LDRC, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Childrens Hosp, Neuropsychol Program, Boston, MA 02115 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Weiler, MD (reprint author), Childrens Hosp, LDRC, CA-504,300 Longwood Ave, Boston, MA 02115 USA. FU NICHD NIH HHS [P30-HD18655, P50-HD33803] NR 57 TC 15 Z9 15 U1 0 U2 3 PU PRO-ED INC PI AUSTIN PA 8700 SHOAL CREEK BLVD, AUSTIN, TX 78757-6897 USA SN 0022-2194 J9 J LEARN DISABIL-US JI J. Learn. Disabil. PD NOV-DEC PY 2000 VL 33 IS 6 BP 538 EP 550 DI 10.1177/002221940003300603 PG 13 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 372VU UT WOS:000165255400003 PM 15495396 ER PT J AU Ishii, H Yoshida, M Rosenzweig, A Gimbrone, MA Yasukochi, Y Numano, F AF Ishii, H Yoshida, M Rosenzweig, A Gimbrone, MA Yasukochi, Y Numano, F TI Adenoviral transduction of human E-selectin into isolated, perfused, rat aortic segments: an ex vivo model for studying leukocyte-endothelial interactions SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE adhesion molecule; adenovirus vector; inflammation ID INTERCELLULAR-ADHESION MOLECULE-1; ANTIENDOTHELIAL CELL ANTIBODIES; MEDIATED GENE-TRANSFER; FLOW CONDITIONS; DEFICIENT MICE; IN-VIVO; VASCULAR ENDOTHELIUM; EXPRESSION; ATHEROSCLEROSIS; IDENTIFICATION AB E-selectin, a member of the selectin family of adhesion molecules, is thought to play an important role in leukocyte-endothelial (EC) interactions during inflammation and atherosclerosis, To critically examine the role of E-selectin in leukocyte-EC interactions in the vascular system, we created a recombinant adenoviral vector containing a human E-selectin cDNA (AdRSVE-sel) and examined the effect of AdRSVE-sel in all er vivo vascular model of a rat aortic segment. A segment of abdominal aorta was isolated from a male Sprague-Dawley rat transduced with AdRSVE-sel ex vivo. After 12 h, surface expression of transduced E-selectin in the segment was confirmed by Western blotting and immunohistochemistry using anti-E-selectin mAb, Aortic segments were connected to a perfusion system and the adhesion of human polymorphonuclear neutrophils (PMN), and a human monocytic cell line (THP-I) to the EC surface was studied in the presence of a physiological level of flow (0.85 nl/min, approximate luminal surface shear stress=1.76 dyn/cm(2)). Adhesion of PMN was assessed by scanning electron microscopy and quantified using fluorescently labeled PMN, AdRSVE-sel transduced aortic segments mediated significantly more PMN and THP-1 adhesion than control segments transduced with AdRSVLacZ, Pretreatment of AdRSVE-sel transduced aortic segments with anti-E-selectin mAb inhibited PMN adhesion significantly, as well as THP-1. These data indicate that human E-selectin expressed in rat aortic segments call support the adhesion of human PMN as well as THP-1 under physiological dow conditions. This genetically modified, excised, vascular-segment model provides a useful tool for the study of leukocyte recruitment in the vascular system. C1 Tokyo Med & Dent Univ, Inst Med Res, Dept Mol Genet, Bunkyo Ku, Tokyo 1138510, Japan. Tokyo Med & Dent Univ, Sch Med, Dept Med, Tokyo 1138510, Japan. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol,Vasc Res Div, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02115 USA. RP Yoshida, M (reprint author), Tokyo Med & Dent Univ, Inst Med Res, Dept Mol Genet, Bunkyo Ku, 1-5-45 Yushima Bldg D-621, Tokyo 1138510, Japan. NR 31 TC 5 Z9 5 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV PY 2000 VL 68 IS 5 BP 687 EP 692 PG 6 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 370PQ UT WOS:000165131800014 PM 11073108 ER PT J AU Medh, JD Fry, GL Bowen, SL Ruben, S Wong, H Chappell, DA AF Medh, JD Fry, GL Bowen, SL Ruben, S Wong, H Chappell, DA TI Lipoprotein lipase- and hepatic triglyceride lipase-promoted very low density lipoprotein degradation proceeds via an apolipoprotein E-dependent mechanism SO JOURNAL OF LIPID RESEARCH LA English DT Article DE heparan sulfate proteoglycans; LDL receptors; fibroblasts; apoE knockout mice ID RECEPTOR-RELATED PROTEIN; HEPARAN-SULFATE PROTEOGLYCANS; CELL-SURFACE PROTEOGLYCANS; IN-VITRO; CHYLOMICRON REMNANTS; RICH LIPOPROTEINS; ENHANCED BINDING; ALPHA(2)-MACROGLOBULIN RECEPTOR; HUMAN FIBROBLASTS; TERMINAL DOMAIN AB Apolipoprotein E (apoE) is the primary recognition signal on triglyceride-rich lipoproteins responsible for interacting with low density Lipoprotein (LDL) receptors and LDL receptor-related protein (LRP). It has been shown that lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) promote receptor-mediated uptake and degradation of very low density lipoproteins (VLDL) and remnant particles, possibly by directly binding to lipoprotein receptors. In this study we hare investigated the requirement for apoE in lipase-stimulated VLDL degradation. We compared binding and degradation of normal and apoE-depleted human VLDL and apoE knockout mouse VLDL in human foreskin fibroblasts. Surface binding at 37 degreesC of apoE knockout VLDL was greater than that of normal VLDL by 3- and 40-fold, respectively, in the presence of LPL and HTGL. In spite of the greater stimulation of surface binding, lipase-stimulated degradation of apoE knockout mouse VLDL was significantly lower than that of normal VLDL (30, 30, and 80%, respectively, for control, LPL, and HTGL treatments). In the presence of LPL and HTGL, surface binding of apoE-depleted human VLDL was, respectively, 40 and 200% of normal VLDL whereas degradation was, respectively, 25 and 50% of normal VLDL. LPL and HTGL stimulated degradation of normal VLDL in a dose-dependent manner and by a LDL receptor-mediated pathway. Maximum stimulation (4-fold) was seen in the presence LPL (1 mug/ml) or HTGL (3 mug/ml) in lovastatin-treated cells. On the other hand, degradation of apoE-depleted VLDL was not significantly increased by the presence of lipases even in lovastatin-treated cells. Surface binding of apoE-depleted VLDL to metabolically inactive cells at 4 degreesC was higher in control and HTGL-treated cells, but unchanged in the presence of LPL. Degradation of prebound apoE-depleted VLDL was only 35% as efficient as that of normal VLDL. Surface binding of apoE knockout or apoE-depleted VLDL was to heparin sulfate proteoglycans because it was completely abolished by heparinase treatment. However, apoE appears to be a primary determinant for receptor-mediated VLDL degradation. Our studies suggest that overexpression of LPL or HTGL may not protect against lipoprotein accumulation seen in apoE deficiency. C1 Univ Iowa, Coll Med, Dept Internal Med, Iowa City, IA 52242 USA. W Los Angeles Vet Affairs Med Ctr, Lipid Res Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. RP Medh, JD (reprint author), Univ Iowa, Coll Med, Dept Internal Med, Iowa City, IA 52242 USA. FU NHLBI NIH HHS [P01 HL049264-09, HL49264] NR 70 TC 26 Z9 28 U1 0 U2 0 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 NOV PY 2000 VL 41 IS 11 BP 1858 EP 1871 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 372FC UT WOS:000165222800017 PM 11060356 ER PT J AU Daws, LC Gould, GG Teicher, SD Gerhardt, GA Frazer, S AF Daws, LC Gould, GG Teicher, SD Gerhardt, GA Frazer, S TI 5-HT1B receptor-mediated regulation of serotonin clearance in rat hippocampus in vivo SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE serotonin transporter; 5-HT1B autoreceptor; chronoamperometry; hippocampus; rat ID IN-VIVO; EXTRACELLULAR SEROTONIN; TRANSPORTER FUNCTION; DOPAMINE RELEASE; BRAIN; 5-HYDROXYTRYPTAMINE; ANTAGONISTS; MODULATE; BINDING; PHOSPHORYLATION AB The 5-hydroxytryptamine (5-HT; serotonin) transporter (5-HTT) is important in terminating serotonergic neurotransmission and is a primary target for many psychotherapeutic drugs. Study of the regulation of 5-HTT activity is therefore important in understanding the control of serotonergic neurotransmission. Using highspeed chronoamperometry, we have demonstrated that local application of 5-HT1B antagonists into the CA3 region of the hippocampus prolongs the clearance of 5-HT from extracellular fluid (ECF). In the present study, we demonstrate that the 5-HT1B antagonist cyanopindolol does not produce this effect by increasing release of endogenous 5-HT or by directly binding to the 5-HTT. Dose-response studies showed that the potency of cyanopindolol to inhibit clearance of 5-HT was equivalent to that of the selective 5-HT reuptake inhibitor fluvoxamine. Local application of the 5-HT1A antagonist WAY 100635 did not alter 5-HT clearance, suggesting that the effect of cyanopindolol to prolong clearance is not via a mechanism involving 5-HT1A receptors. Finally, the effect of low doses of cyanopindolol and fluvoxamine to inhibit clearance of 5-HT from ECF was additive. These data are consistent with the hypothesis that activation of terminal 5-HT1B autoreceptors increases 5-HTT activity. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Mem Hosp Div, San Antonio, TX USA. Univ Kentucky, Dept Neurol, Lexington, KY USA. Univ Kentucky, Dept Neurobiol & Anat, Lexington, KY USA. RP Daws, LC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, Mail Code 7764,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM daws@uthscsa.edu OI Gould, Georgianna/0000-0002-5470-8763 FU NIMH NIH HHS [MH01245, MH57001] NR 43 TC 56 Z9 56 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2000 VL 75 IS 5 BP 2113 EP 2122 DI 10.1046/j.1471-4159.2000.0752113.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 365AA UT WOS:000089925200036 PM 11032901 ER PT J AU Tyurin, VA Tyurina, YY Borisenko, GG Sokolova, TV Ritov, VB Quinn, PJ Rose, M Kochanek, P Graham, SH Kagan, VE AF Tyurin, VA Tyurina, YY Borisenko, GG Sokolova, TV Ritov, VB Quinn, PJ Rose, M Kochanek, P Graham, SH Kagan, VE TI Oxidative stress following traumatic brain injury in rats: Quantitation of biomarkers and detection of free radical intermediates SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE traumatic brain injury; oxidative stress; ascorbate; spin traps; thiols; 8-epi-prostaglandin F-2 alpha ID ELECTRON-SPIN-RESONANCE; LIPID-PEROXIDATION; VITAMIN-E; IN-VIVO; CEREBRAL-ISCHEMIA; PHENOXYL RADICALS; MODEL SYSTEMS; HEAD-INJURY; CYCLOOXYGENASE; ASCORBATE AB Oxidative stress may contribute to many pathophysiologic changes that occur after traumatic brain injury. In the current study, contemporary methods of detecting oxidative stress were used in a rodent model of traumatic brain injury. The level of the stable product derived from peroxidation of arachidonyl residues in phospholipids, 8-epi-prostaglandin F-2 alpha, was increased at 6 and 24 h after traumatic brain injury. Furthermore, relative amounts of fluorescent end products of lipid peroxidation in brain extracts were increased at 6 and 24 h after trauma compared with sham-operated controls. The total antioxidant reserves of brain homogenates and water-soluble antioxidant reserves as well as tissue concentrations of ascorbate, GSH, and protein sulfhydryls were reduced after traumatic brain injury. A selective inhibitor of cyclooxygenase-2, SC 58125, prevented depletion of ascorbate and thiols, the two major water-soluble antioxidants in traumatized brain. Electron paramagnetic resonance (EPR) spectroscopy of rat cortex homogenates failed to detect any radical adducts with a spin trap, 5,5-dimethyl-1-pyrroline N-oxide, but did detect ascorbate radical signals. The ascorbate radical EPR signals increased in brain homogenates derived from traumatized brain samples compared with sham-operated controls. These results along with detailed model experiments in vitro indicate that ascorbate is a major antioxidant in brain and that the EPR assay of ascorbate radicals may be used to monitor production of free radicals in brain tissue after traumatic brain injury. C1 Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA 15238 USA. Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Anesthesiol & Crit Care Med, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. VA Pittsburgh Hlth Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. Kings Coll London, Div Life Sci, London W8 7AH, England. Russian Acad Sci, Inst Evolutionary Physiol & Biochem, St Petersburg 196140, Russia. RP Kagan, VE (reprint author), Univ Pittsburgh, Dept Environm & Occupat Hlth, 260 Kappa Dr, Pittsburgh, PA 15238 USA. EM kagan@pitt.edu RI Kochanek, Patrick/D-2371-2015; Quinn, Peter/E-4019-2010; OI Kochanek, Patrick/0000-0002-2627-913X; Tyurin, Vladimir/0000-0002-3474-1697 FU NINDS NIH HHS [NS30318] NR 61 TC 152 Z9 155 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2000 VL 75 IS 5 BP 2178 EP 2189 DI 10.1046/j.1471-4159.2000.0752178.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 365AA UT WOS:000089925200043 PM 11032908 ER PT J AU Schmidt, BL Kearns, G Gordon, N Kaban, LB AF Schmidt, BL Kearns, G Gordon, N Kaban, LB TI A financial analysis of maxillomandibular fixation versus rigid internal fixation for treatment of mandibular fractures SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article; Proceedings Paper CT 79th Annual Meeting of the American-Association-of-Oral-and-Maxillofacial-Surgeons CY SEP 19, 1997 CL SEATTLE, WASHINGTON SP Amer Assoc Oral & Maxillofacial Surgeons ID OSTEOSYNTHESIS AB Purpose: The aim of this study was to compare the cost-effectiveness of mandibular fracture treatment by closed reduction with maxillomandibular fixation (CRF) with open reduction and rigid internal fixation (ORIF). Patients and Methods: This was a retrospective study of 85 patients admitted to the Oral and Maxillofacial Surgery Service at San Francisco General Hospital and treated for mandibular fractures from January 1 to December 31, 1993. The patients were divided into 2 groups: 1) those treated with CRF and 2) those treated with ORIF. The outcome variables were length of hospital stay, duration of anesthesia, and time in operating room. The charge for primary fracture treatment included the fees for the operation and hospitalization without any complications. Within the group of 85 patients treated for mandibular fractures in 1993, 10 patients treated with CRF and 10 patients treated with ORIF were randomly selected, and hospital billing statements were used to estimate the average charge of primary treatment. The average charge to manage a major postoperative infection also was estimated based on the billing statements of 10 randomly selected patients treated in 1993 (5 treated with CRF, 5 with ORIF) who required hospital admission for the management of a complication. The average total charge was computed by using the average charge for primary treatment plus the incidence of postoperative infection multiplied by the average charge for management of that complication. Results: Eighty-Eve patients were included in the study. The average charge for primary treatment was $10,100 for the CRF. group and $28,362 for the ORIF group. The average charge for the inpatient management of a major postoperative infection was $26,671 for the CRF group and $39,213 for the ORIF group. The average total charge for management of a mandible fracture with CRF was $10,927; the total charge for the ORIF group was $34,636. Conclusion: The results of this retrospective study suggest that the use of CRF in the management of mandibular fractures at our institution provides considerable savings over treatment by using ORIF. The use of ORIF should be reserved for patients and fracture types with specific indications. (C) 2000 American Association of Oral and Maxillofacial Surgeons. C1 Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. San Francisco Gen Hosp, Oral & Maxillofacial Surg Serv, San Francisco, CA 94110 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA USA. RP Schmidt, BL (reprint author), Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, 521 Parnassus Ave,C-522, San Francisco, CA 94143 USA. OI Schmidt, Brian/0000-0002-2409-8984 NR 14 TC 21 Z9 21 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD NOV PY 2000 VL 58 IS 11 BP 1206 EP 1210 DI 10.1053/joms.2000.16612 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 369ZJ UT WOS:000165097400002 PM 11078130 ER PT J AU Stubbs, M Zhang, H Vrahas, MS Baratta, RV Zieske, A AF Stubbs, M Zhang, H Vrahas, MS Baratta, RV Zieske, A TI Effect of intraarticular stainless steel implants on the health of the rabbit knee joint: An experimental study SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article DE retrograde nails; internal fixation; metallosis ID SUPRACONDYLAR FEMUR FRACTURES; INTRAMEDULLARY; ARTHROPLASTY AB Objective: This study was designed to investigate the histologic changes to the knee joints of rabbits after insertion of a metal implant in retrograde fashion. Design: Eighteen rabbits had a modified stainless steel screw implanted in one knee, with the other knee serving as a sham-operated control. The animals were killed after two, six, or twelve months. Outcome Measures: The histologic status of the cartilage and synovium were graded by the Modified Mankin and Mima criteria, respectively. Results: At the time of killing, every insertion site was covered by fibrous tissue. Statistical analysis showed no significant differences in histologic scores between implanted and control knees. Conclusions: Insertion of a stable, well-fixed implant results in no deleterious effect to the knee joint. C1 Louisiana State Univ, Hlth Sci Ctr, Dept Orthopaed Surg, Bioengn Lab, New Orleans, LA 70112 USA. Beijing Univ Med Sci, Beijing Jishuitan Hosp, Dept Gen Orthopaed, Beijing, Peoples R China. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Louisiana State Univ, Hlth Sci Ctr, Dept Pathol, New Orleans, LA USA. RP Baratta, RV (reprint author), Louisiana State Univ, Hlth Sci Ctr, Dept Orthopaed Surg, Bioengn Lab, 2025 Gravier St,Suite 400, New Orleans, LA 70112 USA. NR 18 TC 2 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-5339 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD NOV PY 2000 VL 14 IS 8 BP 567 EP 570 DI 10.1097/00005131-200011000-00009 PG 4 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 382XA UT WOS:000165851600009 PM 11149503 ER PT J AU Sprich, S Biederman, J Crawford, MH Mundy, E Faraone, SV AF Sprich, S Biederman, J Crawford, MH Mundy, E Faraone, SV TI Adoptive and biological families of children and adolescents with ADHD SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE adoption; attention-deficit hyperactivity disorder; family study ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DOPAMINE TRANSPORTER GENE; RISK-FACTORS; DRD4 GENE; ASSOCIATION; RECEPTOR; POLYMORPHISM; ADULTS; COMORBIDITY AB Objective: Using an adoption study design, the authors addressed the issue of genetics in attention-deficit hyperactivity disorder (ADHD). Method: This study examined the rates of ADHD and associated disorders in the first-degree adoptive relatives of 25 adopted probands with ADHD and compared them with those of the first-degree biological relatives of 101 nonadopted probands with ADHD and 50 nonadopted, non-ADHD control probands. Results: Six percent of the adoptive parents of adopted ADHD probands had ADHD compared with 18% of the biological parents of nonadopted ADHD probands and 3% of the biological parents of the control probands. Conclusion: Results of this study lend support to the hypothesis that ADHD has a genetic component. C1 Massachusetts Gen Hosp, Cognit Behav Therapy Program, Psychiat Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Child Psychiat Serv, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Inst Psychiat Epidemiol & Genet,Dept Psychiat, Boston, MA 02115 USA. Commonwealth Res Ctr, Boston, MA USA. RP Sprich, S (reprint author), Massachusetts Gen Hosp, Cognit Behav Therapy Program, Psychiat Serv, WACC 812,MGH,15 Parkman St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 NR 43 TC 113 Z9 122 U1 9 U2 33 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 NOV PY 2000 VL 39 IS 11 BP 1432 EP 1437 DI 10.1097/00004583-200011000-00018 PG 6 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 366KK UT WOS:000090004400018 PM 11068899 ER PT J AU Kutner, L Beresin, EV AF Kutner, L Beresin, EV TI Reaching out: Mass media techniques for child and adolescent psychiatrists SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. McLean Hosp, Boston, MA USA. Harvard Univ, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Beresin, EV (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,Bulfinch 449, Boston, MA 02114 USA. NR 4 TC 5 Z9 5 U1 0 U2 0 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 NOV PY 2000 VL 39 IS 11 BP 1452 EP 1454 DI 10.1097/00004583-200011000-00021 PG 3 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 366KK UT WOS:000090004400021 PM 11068902 ER PT J AU Hongcharu, W Baldassano, M Taylor, CR AF Hongcharu, W Baldassano, M Taylor, CR TI Kimura's disease with oral ulcers: Response to pentoxifylline SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID ANGIOLYMPHOID HYPERPLASIA; EOSINOPHILIA; DISTINCTION; CHINESE; THERAPY; SKIN AB We describe a man with Kimura's disease whose presentation included lymphadenopathy and cutaneous nodules, but was most distinctive for painful oral ulcerations. His lesions showed an initially moderate, but ultimately minimal response to monthly triamcinolone injections. With oral pentoxyifylline, he showed resolution of all of his lesions for 14 months. On cessation of his treatment, his disease flared for 3 months. When pentoxyifylline was restarted, his lesions regressed again within 4 weeks. We review the literature on Kimura's disease. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Hongcharu, W (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA. NR 23 TC 17 Z9 23 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD NOV PY 2000 VL 43 IS 5 BP 905 EP 907 DI 10.1067/mjd.2000.101931 PN 2 PG 3 WC Dermatology SC Dermatology GA 370XT UT WOS:000165149100005 PM 11044818 ER PT J AU Huang, PL AF Huang, PL TI Mouse models of nitric oxide synthase deficiency SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID MICE LACKING; VASCULAR-RESPONSE; GENE; DISRUPTION; INJURY; MUTANT AB Knockout mice for each of the three nitric oxide (NO) synthase (NOS) genes have been generated. Their phenotypes reflect the roles of each NOS isoform in physiologic and pathologic processes. This article reviews how neuronal NOS (nNOS) and endothelial NOS (eNOS) knockout mice have contributed to our knowledge of the roles of NO in cerebral ischemia, cardiovascular processes, and the autonomic nervous system. In some instances, the effects of NO produced by one isoform antagonize the effects of NO produced by another isoform. For example, after cerebral ischemia, the nNOS isoform is involved in tissue injury, whereas the eNOS isoform is important in maintaining blood flow. All three isoforms are expressed in the respiratory tract, but only the nNOS isoform appears to be involved in modulating airway responsiveness and only the inducible NOS isoform appears to respond to antigen stimulation. In the cardiovascular system, endothelial NO is important for vascular tone, systolic and diastolic cardiac function, vascular proliferative responses to injury, platelet aggregation, and hemostasis. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Charlestown, MA 02129 USA. RP Huang, PL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Mail Code 149-4201,149 13th St, Charlestown, MA 02129 USA. NR 23 TC 45 Z9 47 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2000 VL 11 IS 11 SU 16 BP S120 EP S123 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 369MU UT WOS:000165070600007 PM 11065342 ER PT J AU Michels, KB Giovannucci, E Joshipura, KJ Rosner, BA Stampfer, MJ Fuchs, CS Colditz, GA Speizer, FE Willett, WC AF Michels, KB Giovannucci, E Joshipura, KJ Rosner, BA Stampfer, MJ Fuchs, CS Colditz, GA Speizer, FE Willett, WC TI Prospective study of fruit and vegetable consumption and incidence of colon and rectal cancers SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; COLORECTAL-CANCER; RISK-FACTORS; UNITED-STATES; DIETARY FIBER; REPRODUCIBILITY; PREVENTION; VALIDITY; DISEASE; WOMEN AB Background: Frequent consumption of fruit and vegetables has been associated with a reduced risk of colorectal cancer in many observational studies. Methods: We prospectively investigated the association between fruit and vegetable consumption and the incidence of colon and rectal cancers in two large cohorts: the Nurses' Health Study (88 764 women) and the Health professionals' Follow-up Study (47 325 men). Diet was assessed and cumulatively updated in 1980, 1984, 1986, and 1990 among women and in 1986 and 1990 among men. The incidence of cancer of the colon and rectum was ascertained up to June or January of 1996, respectively. Relative risk (RR) estimates were calculated with the use of pooled logistic regression models accounting for various potential confounders. All statistical tests were two-sided. Results: With a follow-up including 1743 645 person-years and 937 cases of colon cancer, we found little association of colon cancer incidence with fruit and vegetable consumption. For women and men combined, a difference in fruit and vegetable consumption of one additional serving per day was associated with a covariate-adjusted RR of 1.02 (95% confidence interval [CI] = 0.98-1.05), A difference in vegetable consumption of one additional serving per day was associated with an RR of 1.03 (95% CI = 0.97-1.09). Similar results were obtained for women and men considered separately. A difference in fruit consumption of one additional serving per day was associated with a covariate-adjusted RR for colon cancer of 0.96 (95% CI = 0.89-1.03) among women and 1.08 (95% CI = 1.00-1.16) among men. For rectal cancer (total, 244 cases), a difference in fruit and vegetable consumption of one additional serving per day was associated with an RR of 1.02 (95% CI = 0.95-1.09) in men and women combined. None of these associations was modified by vitamin supplement use or smoking habits. Conclusions: Although fruits and vegetables may confer protection against some chronic diseases, their frequent consumption does not appear to confer protection from colon or rectal cancer. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral Hlth Policy & Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Ctr Canc Prevent, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Michels, KB (reprint author), Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA55075, CA40356] NR 43 TC 244 Z9 253 U1 1 U2 13 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 1 PY 2000 VL 92 IS 21 BP 1740 EP 1752 DI 10.1093/jnci/92.21.1740 PG 13 WC Oncology SC Oncology GA 368HC UT WOS:000090110800011 PM 11058617 ER PT J AU Januzzi, JL Jang, IK AF Januzzi, JL Jang, IK TI Fundamental concepts in the pathobiology of heparin-induced thrombocytopenia SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE heparin; thrombocytopenia; HIT; pathophysiology ID PROFOUND THROMBOCYTOPENIA; ENDOTHELIAL-CELLS; ANTIBODIES; PLATELET-FACTOR-4; MICROPARTICLES; PLATELETS; BINDING; HIT; EXPLANATION; THROMBOSIS AB Heparin-induced thrombocytopenia (HIT) is among the most common causes of drug-related immune-mediated thrombocytopenia. It is a unique syndrome, in that despite the fact that thrombocytopenia is the major laboratory manifestation of HIT, its major complication is a highly morbid (and commonly fatal) thrombotic diathesis, known as the HIT with thrombosis syndrome (HITTS). The pathogenesis of HIT and MITTS has been recently elucidated, and involves an immune response against epitopes within circulating heparin-platelet factor-4 (PF4) complexes. This leads to cross-linking and activation of platelets, increasing the risk for thromboses. Furthermore, significant immunological cross-reactivity occurs between endothelial-cell bound PF4 and the HIT antibody, which may lead to endothelial damage, activation, and hyperplasia. This complex process leads to a hypercoagulable state, which may lead to overt thromboses. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, Bulfinch 105,55 Fruit St, Boston, MA 02114 USA. NR 33 TC 3 Z9 3 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD NOV PY 2000 VL 10 SU 1 BP S7 EP S11 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 399ED UT WOS:000166797600002 ER PT J AU Barry, MJ Williford, WO Fowler, FJ Jones, KM Lepor, H AF Barry, MJ Williford, WO Fowler, FJ Jones, KM Lepor, H TI Filling and voiding symptoms in the American Urological Association symptom index: The value of their distinction in a Veterans Affairs randomized trial of medical therapy in men with a clinical diagnosis of benign prostatic hyperplasia SO JOURNAL OF UROLOGY LA English DT Article DE prostate; urination disorders; prostatic hyperplasia; urinary tract; health status indicators ID URINARY-TRACT SYMPTOMS; FINASTERIDE; VOLUME; SCORE AB Purpose: We used data from a large Veterans Affairs trial of medical therapy for men with benign prostatic hyperplasia to evaluate the value of calculating separate filling and voiding subscores of the American Urological Association (AUA) symptom index. Materials and Methods: We performed factor analysis to assess the psychometric validity of separating the 7 items of the AUA symptom index into filling and voiding subsets. To assess the clinical usefulness of calculating these subscores we correlated them against baseline measurements of symptom interference as well as urodynamic and anatomical measures of disease severity, and used them for predicting the response to medical therapy. Results: Factor analysis confirmed the psychometric validity of separating the AUA symptom index into a 3-item filling and a 4-item voiding subscale. However, calculating filling and voiding subscores did not result in differential correlations with measures of disease interference or severity. It also did not enable us to predict a better symptomatic or uroflowmetry response to medical therapy. Conclusions: Calculating separate filling and voiding subscores of the AUA symptom index is psychometrically valid but not clinically useful. C1 Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. Vet Affairs Med Ctr, Cooperat Studies Program, Coordinating Ctr, Perry Point, MD USA. NYU Med Ctr, New York, NY 10016 USA. Vet Affairs Med Ctr, New York, NY USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. FU AHRQ HHS [HS 08397] NR 15 TC 23 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 2000 VL 164 IS 5 BP 1559 EP 1564 DI 10.1016/S0022-5347(05)67028-0 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 363DT UT WOS:000089820300022 PM 11025704 ER PT J AU Dai, GH Tsukurov, O Orkin, RW Abbott, WM Kamm, RD Gertler, JP AF Dai, GH Tsukurov, O Orkin, RW Abbott, WM Kamm, RD Gertler, JP TI An in vitro cell culture system to study the influence of external pneumatic compression on endothelial function SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 12th Annual Meeting of the American-Venous-Forum CY FEB 03-06, 2000 CL PHOENIX, ARIZONA SP Amer Venous Forum ID DEEP-VEIN THROMBOSIS; TOTAL HIP-REPLACEMENT; INTERMITTENT COMPRESSION; PLASMINOGEN-ACTIVATOR; VENOUS THROMBOSIS; SHEAR-STRESS; FIBRINOLYTIC-ACTIVITY; CYCLIC STRAIN; VASCULAR WALL; PREVENTION AB Purpose: External pneumatic compression (EPC) is an effective means of prophylaxis against deep venous thrombosis. However, its mechanism remains poorly understood. Understanding of the biological consequences of EPC is an important goal for optimizing performance of the EPC-generating device and providing guidance for clinical use. We present a new in vitro cell culture system (Venous Flow Simulator) that simulates blood flow and vessel collapse conditions during EPC, and we examine the influence of these factors on endothelial cell (EC) fibrinolytic activity and vasomotor function. Methods. An in vitro cell culture system was designed to replicate the hemodynamic sheer stress and vessel wall strain associated with induced blood flow during different modes of EPC. Human umbilical vein endothclial cells were cultured in the system and subjected to intermittent flow vessel collapse, or a combination of the two. The biologic response was assessed through, changes in EC morphology and the expression of fibrinolytic factors tissue plasminogen activator, plasminogen activator inhibitor type 1, profibrinolytic receptor (annexin II), and vasomotor factors endothelial nitric oxide synthase and endothelin-1 Results The cells remained attached and viable after being subjected to intermittent pulsatile flow (F) and tube compression (C). In F and F + C, cells aligned in the direction of flow after 6 hours. Northern blot analysis of messenger RNA shows that there is an upregulation of tissue plasminogen activator expression (1.95 +/- 0.19 in F and 2.45 + 0.46 in FC) and endothelial nitric oxide synthase expression (2.08 +/- 0.25 in F and 2.11 +/- 0.21 in FC). Plasminogen activator inhibitor type 1, annexin II, and endothelin 1 show no significant change under any experimental conditions. The results also show that pulsatile flow, more than vessel compression, influences EC morphology and function. Conclusion: Effects on ECs of intermittent flow and vessel collapse, either individually or simultaneously, were simulated with an in vitro system of nerv design. Initial results show that intermittent flow associated with EPC upregulates EC fibrinolytic potential and influences factors altering vasomotor tone. The system will facilitate future studies of EC function during EPC. C1 Massachusetts Gen Hosp, Div Vasc Surg, Vasc Surg Lab, Boston, MA 02114 USA. MIT, Div Bioengn & Environm Hlth, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gertler, JP (reprint author), Massachusetts Gen Hosp, Div Vasc Surg, Vasc Surg Lab, 15 Parkman St,ACC 464, Boston, MA 02114 USA. OI /0000-0002-7232-304X; Dai, Guohao/0000-0001-7346-2685 NR 32 TC 26 Z9 26 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD NOV PY 2000 VL 32 IS 5 BP 977 EP 987 DI 10.1067/mva.2000.110357 PG 11 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 372FM UT WOS:000165223700030 PM 11054230 ER PT J AU Friedman, RS Frankel, FR Xu, Z Lieberman, J AF Friedman, RS Frankel, FR Xu, Z Lieberman, J TI Induction of human immunodeficiency virus (HIV)-specific CD8 T-cell responses by Listeria monocytogenes and a hyperattenuated Listeria strain engineered to express HIV antigens SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNE-RESPONSES; LYMPHOCYTES-T; TYPE-1; GROWTH; VECTOR; INFECTION; VIREMIA; PATHOGENESIS; MACROPHAGES; APOPTOSIS AB Induction of cell-mediated immunity may be essential for an effective AIDS vaccine. Listeria monocytogenes is an attractive bacterial vector to elicit T-cell immunity to human immunodeficiency virus (HIV) because it specifically infects monocytes, key antigen-presenting cells, and because natural infection originates at the mucosa. Immunization with recombinant L. monocytogenes has been shown to protect mice from lymphocytic choriomeningitis virus, influenza virus, and tumor inoculation. L. monocytogenes expressing HIV gag elicits sustained high levels of Gag-specific cytotoxic T lymphocytes (CTLs) in mice. We have examined the ability of Listeria to infect human monocytes and present HIV antigens to CD8 T lymphocytes of HIV-infected donors to induce a secondary T-cell immune response. Using this in vitro vaccination protocol, we show that L. monocytogenes expressing the HIV-1 gag gene efficiently provides a strong stimulus for Gag-specific CTLs in HIV-infected donor peripheral blood mononuclear cells. Listeria expressing Nef also elicits a secondary in vitro anti-Nef CTL response. Since L. monocytogenes is a pathogen, before it can be seriously considered as a human vaccine vector, safety concerns must be addressed. We therefore have produced a highly attenuated strain of L. monocytogenes that requires D-alanine for viability. The recombinant bacteria are attenuated at Least 10(5)-fold. We show that when these hyperattenuated bacteria are engineered to express HIV-1 Gag, they are at least as efficient at stimulating Gag-specific human CTLs in vitro as wild-type recombinants. These results suggest that attenuated Listeria is an attractive candidate vaccine vector to induce T-cell immunity to HIV in humans. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [AI-42509, R01 AI042509] NR 41 TC 36 Z9 39 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 NOV PY 2000 VL 74 IS 21 BP 9987 EP 9993 DI 10.1128/JVI.74.21.9987-9993.2000 PG 7 WC Virology SC Virology GA 363DN UT WOS:000089819900021 PM 11024127 ER PT J AU Brown, AJL Precious, HM Whitcomb, JM Wong, JK Quigg, M Huang, W Daar, ES D'Aquila, RT Keiser, PH Connick, E Hellmann, NS Petropoulos, CJ Richman, DD Little, SJ AF Brown, AJL Precious, HM Whitcomb, JM Wong, JK Quigg, M Huang, W Daar, ES D'Aquila, RT Keiser, PH Connick, E Hellmann, NS Petropoulos, CJ Richman, DD Little, SJ TI Reduced susceptibility of human immunodeficiency virus type 1 (HIV-1) from patients with primary HIV infection to nonnucleoside reverse transcriptase inhibitors is associated with variation at novel amino acid sites SO JOURNAL OF VIROLOGY LA English DT Article ID ZIDOVUDINE RESISTANCE; DRUG SUSCEPTIBILITY; TRANSMISSION; VARIANTS; FAILURE; TREES; DNA AB Recently, significant numbers of individuals with primary human immunodeficiency virus (HN) infection have been found to harbor viral strains with reduced susceptibility to antiretroviral drugs. In one study, HN from 16% of such antiretroviral-naive individuals was shown to have a susceptibility to nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) between 2.5- and 10-fold lower than that of a wild-type control. Mutations in the RT domain that had previously been associated with antiretroviral resistance were not shared by these strains. We have analyzed by logistic regression 46 variable amino acid sites in RT for their effect on susceptibility and have identified two novel sites influencing susceptibility to NNRTIs: amino acids 135 and 283 in RT. Eight different combinations of amino acids at these sites were observed among these patients. These combinations showed a 14-fold range in mean susceptibility to both nevirapine and delavirdine. In vitro mutagenesis of the control strain combined with a phenotypic assay confirmed the significance of amino acid variation at these sites for susceptibility to NNRTIs. C1 Univ Edinburgh, Inst Cell Anim & Populat Biol, Ctr HIV Res, Edinburgh, Midlothian, Scotland. Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. San Diego Vet Affairs Med Ctr, La Jolla, CA USA. ViroLog Inc, S San Francisco, CA USA. Cedars Sinai Burns & Allen Res Inst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Dept Vet Affairs Med Ctr, Denver, CO USA. RP Brown, AJL (reprint author), Univ Calif San Diego, Treatment Ctr, Dept Pathol, 150 W Washington St, San Diego, CA 92103 USA. RI Leigh Brown, Andrew/F-3802-2010 FU NCRR NIH HHS [M01 RR000425]; NIAID NIH HHS [AI 01541, AI 27670, AI 36214, P30 AI036214, R01 AI029193, R01 AI035522, R01 AI040873, R21 AI040873, R37 AI029164, R37 AI035522, U01 AI027670, U01 AI038858, U01 AI041531, U01 AI041536, U01 AI043638] NR 26 TC 45 Z9 46 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 NOV PY 2000 VL 74 IS 22 BP 10269 EP 10273 DI 10.1128/JVI.74.22.10269-10273.2000 PG 5 WC Virology SC Virology GA 367WE UT WOS:000090083800001 PM 11044070 ER PT J AU Wang, SW Kozlowski, PA Schmelz, G Manson, K Wyand, MS Glickman, R Montefiori, D Lifson, JD Johnson, RP Neutra, MR Aldovini, A AF Wang, SW Kozlowski, PA Schmelz, G Manson, K Wyand, MS Glickman, R Montefiori, D Lifson, JD Johnson, RP Neutra, MR Aldovini, A TI Effective induction of simian immunodeficiency virus-specific systemic and mucosal immune responses in primates by vaccination with proviral DNA producing intact but noninfectious virions SO JOURNAL OF VIROLOGY LA English DT Article ID LYMPH-NODE IMMUNIZATION; CYTOTOXIC T-LYMPHOCYTES; FEMALE RHESUS MACAQUES; NONHUMAN-PRIMATES; REVERSE-TRANSCRIPTASE; ANTIBODY-RESPONSES; MONONUCLEAR-CELLS; VAGINAL CHALLENGE; GENITAL-TRACT; SEX WORKERS AB We report a pilot evaluation of a DNA vaccine producing genetically inactivated simian immunodeficiency virus (SIV) particles in primates, with a focus on eliciting mucosal immunity. Our results demonstrate that DNA vaccines can be used to stimulate strong virus-specific mucosal immune responses in primates. The levels of immunoglobulin A (IgA) detected in rectal secretions of macaques that received the DNA vaccine intradermally and at the rectal mucosa were the most striking of all measured immune responses and were higher than usually achieved through natural infection. However, cytotoxic T lymphocyte responses were generally low and sporadically present in different animals. Upon rectal challenge with cloned SIVmac239, resistance to infection was observed, but some animals with high SIV-specific IgA levels in rectal secretions became infected. Our results suggest that high levels of IgA alone are not sufficient to prevent the establishment of chronic infection, although mucosal IgA responses may have a role in reducing the infectivity of the initial viral inoculum. C1 Childrens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Primedica, Worcester, MA USA. Duke Univ, Durham, NC USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, AIDS Vaccine Program,Retroviral Pathogenesis Lab, Frederick, MD USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA USA. RP Aldovini, A (reprint author), Childrens Hosp, Dept Med, Enders 609,300 Longwood Ave, Boston, MA 02115 USA. RI Wang, Shainn-Wei/B-9644-2009 FU NCRR NIH HHS [K26 RR000168, P51 RR000168, RR00168]; NIAID NIH HHS [AI34757, R01 AI041365, R56 AI041365, AI41365] NR 54 TC 52 Z9 56 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2000 VL 74 IS 22 BP 10514 EP 10522 DI 10.1128/JVI.74.22.10514-10522.2000 PG 9 WC Virology SC Virology GA 367WE UT WOS:000090083800027 PM 11044096 ER PT J AU Labonte, JA Patel, T Hofmann, W Sodroski, J AF Labonte, JA Patel, T Hofmann, W Sodroski, J TI Importance of membrane fusion mediated by human immunodeficiency virus envelope glycoproteins for lysis of primary CD4-positive T cells SO JOURNAL OF VIROLOGY LA English DT Article ID HTLV-III/LAV ENVELOPE; HIV-1 ENTRY; LYMPHOCYTE DEPLETION; SYNCYTIUM FORMATION; HUMAN RETROVIRUS; RHESUS-MONKEYS; CD4(+) CELLS; TYPE-1; APOPTOSIS; AIDS AB In established T-cell lines, the membrane-fusing capacity of the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins mediates cytopathic effects, both syncytium formation and single-cell lysis, Furthermore, changes in the HIV-1 envelope glycoproteins are responsible for the increased CD4(+) T cell-depleting ability observed in infected monkeys upon in vivo passage of simian-human immunodeficiency virus (SHIV) chimeras. In this study, a panel of SHIV envelope glycoproteins and their mutant counterparts defective in membrane-fusing capacity were expressed in primary human CD4(+) T cells. Compared with controls, all of the functional HIV-1 envelope glycoproteins induced cell death in primary CD4(+) T-cell cultures, whereas the membrane fusion-defective mutants did not. Death occurred almost exclusively in envelope glycoprotein-expressing cells and not in bystander cells. Under standard culture conditions, most dying cells underwent lysis as single cells. When the cells were cultured at high density to promote syncytium formation, the envelope glycoproteins of the passaged, pathogenic SHIVs induced more syncytia than those of the respective parental SHIV. These results demonstrate that the HIV-1 envelope glycoproteins induce the death of primary CD4(+) T lymphocytes by membrane fusion-dependent processes. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. FU NIAID NIH HHS [AI24755, AI28691, AI33832, P30 AI028691, R01 AI033832, R37 AI024755] NR 52 TC 70 Z9 70 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 NOV PY 2000 VL 74 IS 22 BP 10690 EP 10698 DI 10.1128/JVI.74.22.10690-10698.2000 PG 9 WC Virology SC Virology GA 367WE UT WOS:000090083800044 PM 11044113 ER PT J AU Nicosia, MA Hind, JA Roecker, EB Carnes, M Doyle, J Dengel, GA Robbins, J AF Nicosia, MA Hind, JA Roecker, EB Carnes, M Doyle, J Dengel, GA Robbins, J TI Age effects on the temporal evolution of isometric and swallowing pressure SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID COMPUTED-TOMOGRAPHY; SKELETAL-MUSCLE; ELDERLY MEN; ENDURANCE; VISCOSITY; DYSPHAGIA; VOLUME; FORCE; YOUNG AB Background. The tongue plays a key role in bolus propulsion through the oropharyngeal chamber. In this study, possible age effects on the magnitude and timing of lingual pressure generation were analyzed. Methods. Oral pressure was measured during isometric and swallowing tasks for 10 elderly (mean age = 81 years) and 10 young (mean age = 51 years) subjects. Three trials each of the isometric task and swallows of three different boluses (3 mi semisolid, 3 mi liquid, and 10 mi liquid) were performed by each subject. The timing and magnitude of isometric and swallowing pressure generation along with the pattern of the swallowing pressure waveform were analyzed. Results. Whereas maximum lingual isometric pressures decreased with age (p < .001), no significant age difference was found for swallowing pressure. Time taken to reach peak pressure also was reduced with age in both the isometric task and swallows of liquid boluses (p < .05), while no significant age effect was found for semisolid swallows. Finally, only elderly subjects showed a pattern of liquid swallowing pressure generation in which multiple lingual gestures were required to reach peak pressure (termed "pressure building"), a pattern demonstrated by both young and elderly groups for semisolids. Conclusions. Decreased lingual strength with age combined with unchanging swallowing pressure leads to a decreased "pressure reserve," perhaps leaving older individuals more at risk for dysphagia resulting from insults directly or indirectly to the swallowing system. Additionally, swallowing is generally "slowed" with age, apparently due to both central and peripheral factors, and this change may have an impact on bolus flow outcomes. C1 William S Middleton Mem Vet Hosp, GRECC 11G, Madison, WI 53705 USA. Univ Wisconsin, Inst Aging, Madison, WI USA. Univ Wisconsin, Dept Med, Madison, WI USA. Univ Wisconsin, Dept Biostat, Madison, WI USA. Univ Wisconsin, Dept Surg, Madison, WI USA. RP Nicosia, MA (reprint author), William S Middleton Mem Vet Hosp, GRECC 11G, Madison, WI 53705 USA. FU NIA NIH HHS [TG AG00213]; NINDS NIH HHS [R01 NS24427] NR 35 TC 145 Z9 150 U1 0 U2 6 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 NOV PY 2000 VL 55 IS 11 BP M634 EP M640 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 373WH UT WOS:000165312700010 PM 11078092 ER PT J AU He, CJ Zheng, F Stitt, S Striker, L Hattori, M Vlassara, H AF He, CJ Zheng, F Stitt, S Striker, L Hattori, M Vlassara, H TI Differential expression of renal AGE-receptor genes in NOD mice: Possible role in nonobese diabetic renal disease SO KIDNEY INTERNATIONAL LA English DT Article DE glycoxidation; kidney disease; receptors; diabetic complications; advanced glycation end product ID GLYCATION END-PRODUCTS; GLUCOSE-MODIFIED PROTEINS; GROWTH FACTOR-I; ADVANCED GLYCOSYLATION; ENDOTHELIAL-CELLS; MATRIX SYNTHESIS; MESANGIAL CELLS; UP-REGULATION; IDENTIFICATION; NEPHROPATHY AB Background. Nonobese diabetic mice (NOD) are prone to glomerular pathology, which is accelerated with the onset of diabetes. Advanced glycation end product (AGE) interactions with AGE-receptors (AGE-Rs) in kidneys can contribute to glomerular injury and diabetic nephropathy (DN). The significant elevation in kidney AGE deposits noted in prediabetic NOD mice suggested that delayed AGE turnover in this model may contribute to its propensity toward DN. Methods. To explore whether excess tissue AGE was linked to altered AGE-R status in the kidney, mRNA/protein expression, and of several AGE-Rs [AGE-R1, AGE-R2, AGE-R3, scavenger receptor II (ScR-II), and receptor for AGE (RAGE)], was determined in renal cortex and in mesangial cells (MCs) isolated from ND-, D-NOD, and ILE mice (N = 20 per group). Ligand binding, receptor site number, and affinity were determined in MCs from the same mouse groups. Results. Prediabetic NOD kidney AGE-Ri mRNA and protein level were threefold lower than that of ILE mice (P < 0.01), while AGE-R3 mRNA was enhanced by twofold (P < 0.05) and AGE-R2, RAGE, and ScR-II mRNA remained close to normal (ILE). The onset of diabetes in NOD mice, while enhancing AGE-Ri mRNA expression by approximately twofold, failed to raise it above the normal (ILE) level, despite increases in tissue, and serum AGE. The latter was associated with higher elevation in AGE-R3 (sixfold, P < 0.05), RAGE (twofold, P = NS), and ScR-II mRNA (2.8-fold, P = NS) above control. MCs from prediabetic NOD mice showed a threefold lower level of AGE-Ri mRNA (P < 0.02 vs. ILE) and AGE-R1-protein, and AGE-binding activity (< 40% of control ILE). In contrast, AGE-R3 mRNA was enhanced (twofold), while AGE-R2 showed no change. Cultured ND-NOD MCs displayed only one fourth of the AGE-binding sites/cell present on ILE MCs (1.6 X 10(6) vs. 6.6 X 10(6), P < 0.05), which after the onset of diabetes rose to the normal range (7.0 X 10(6)/ cell), but failed to exceed it. Conclusions. Reduced AGE-Ri gene expression in this strain may contribute to delayed AGE removal from and early AGE deposition in kidney tissues. This may act as a trigger for those AGE-R genes involved in growth-promoting changes, leading to DN in this strain. C1 CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Univ Miami, Sch Med, Miami, FL USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP He, CJ (reprint author), CUNY Mt Sinai Sch Med, Box 1640,1 Gustave L Levy Pl, New York, NY 10029 USA. RI Stitt, Alan/A-9842-2009 FU NIA NIH HHS [AG09453] NR 36 TC 50 Z9 51 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2000 VL 58 IS 5 BP 1931 EP 1940 DI 10.1046/j.1523-1755.2000.00365.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 369CP UT WOS:000090154500011 PM 11044213 ER PT J AU Stehman-Breen, CO Sherrard, DJ Alem, AM Gillen, DL Heckbert, SR Wong, CS Ball, A Weiss, NS AF Stehman-Breen, CO Sherrard, DJ Alem, AM Gillen, DL Heckbert, SR Wong, CS Ball, A Weiss, NS TI Risk factors for hip fracture among patients with end-stage renal disease SO KIDNEY INTERNATIONAL LA English DT Article DE bone disease; dialysis; epidemiology; renal osteodystrophy; USRDS Study Wave 1 ID BONE-MINERAL DENSITY; RACIAL-DIFFERENCES; OSTEOPOROTIC FRACTURES; HEMODIALYSIS-PATIENTS; PHYSICAL-ACTIVITY; OLDER WOMEN; BLACK-WOMEN; WHITE; MEN; OSTEODYSTROPHY AB Background Although bone disease is well described among end-stage renal disease (ESRD) patients, little attention has been paid to the occurrence of fracture. We sought to identify factors that are associated with hip fracture among ESRD patients. Methods. Data from patients who participated in the United States Renal Data System Dialysis Morbidity and Mortality Study Wave 1 were used for this study. Hip fractures occurring among these patients between 1993 and 1996 were identified from Medicare claims data available from the United States Renal Data System. Cox proportional hazards models were used to estimate the risk of hip fracture associated with demographic and medical variables. Results. Of the 4952 patients included in this analysis, 103 sustained a hip fracture. In the multivariate analysis, age (per increasing decade, RR = 1.40, 95% CI 1.20, 1.64), female gender (RR = 2.26, 95% CI 1.48, 3.44), race (blacks compared with whites, RR = 0.58, 95% CI 0.37, 0.91), body mass index (per 1 unit increase, RR 0.89, 95% CI 0.86, 0.93), and the presence of peripheral vascular disease (RR 1.94, 95% CI 1.29, 2.92) were independently associated with hip fracture. Serum intact parathyroid hormone (iPTH), aluminum, diabetes, and bicarbonate levels did not appreciably influence the risk of hip fracture. Conclusions. Demographic and other characteristics that predict risk of hip fracture in the population at large also do so in ESRD patients. However, we could identify no characteristics of ESRD or its treatment that were independently related to hip fracture incidence. C1 Univ Washington, Sch Publ Hlth & Community Med, Div Nephrol, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Childrens Hosp & Med Ctr, Div Pediat Nephrol, Seattle, WA 98195 USA. RP Stehman-Breen, CO (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way,Mailstop 111A, Seattle, WA 98108 USA. FU NIDDK NIH HHS [DK07721-6] NR 42 TC 149 Z9 152 U1 2 U2 3 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2000 VL 58 IS 5 BP 2200 EP 2205 DI 10.1046/j.1523-1755.2000.00394.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 369CP UT WOS:000090154500040 PM 11044242 ER PT J AU Muzaffar, K Collins, SL Labropoulos, N Baker, WH AF Muzaffar, K Collins, SL Labropoulos, N Baker, WH TI A prospective study of the effects of irradiation on the carotid artery 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 carotid artery; head and neck cancer; irradiation ID EXTERNAL CERVICAL IRRADIATION; DISEASE; NECK; HEAD; ATHEROSCLEROSIS; RADIOTHERAPY; THICKNESS; INJURY AB Objectives/Hypothesis: To prospectively assess the effects of irradiation on the carotid artery in patients with head and neck cancer, as a possibly relevant factor in cancer treatment planning. Study Design: Prospective study from a tertiary care academic setting on university (22 patients) and Veterans Affairs (14 patients) hospital patients; 1-year follow-up, including comparison of study data with age-matched and sex-matched control subjects from epidemiological studies, Methods: Thirty-six patients with head and neck cancer who underwent therapeutic neck irradiation were examined by high-resolution ultrasound before and 1 year after treatment. Twelve patients were also studied at 2 years. Measurements included the intima-media thickness (IMT) of the carotid artery wall, the degree of stenosis as estimated from velocity measurements, and the presence and size of plaque. Results: The pretreatment carotid IMT at baseline was 0.68 mm and was comparable to age-matched and sex-matched control subjects. Significant increase in the IMT was observed on both the left (0.67 vs. 0.84 mm) and the right (0.7 vs. 0.87 mm) sides (P < .001) 1 year after irradiation. In 12 patients who completed 24 months of follow-up the carotid IMT continued to significantly increase statistically compared with that at the first year after treatment (left side, 0.79 vs, 0.85 mm, P = .037; right side, 0.79 vs. 0,95 mm, P =, 014), Statistically significant thickening of the carotid wall developed in all 36 patients by 1 year. Two patients experienced post-treatment neurological events and an area of stenosis greater than 75%. Conclusions: Neck. irradiation significantly increases the thickness of the carotid wall during the first year after treatment-on average, 21 times more than in epidemiologically matched control volunteers. This phenomenon should be taken into consideration when planning treatment for the node-negative (NO) neck. C1 Loyola Univ, Ctr Med, Dept Otolaryngol Head & Neck Surg, Maywood, IL 60153 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. RP Muzaffar, K (reprint author), Loyola Univ, Ctr Med, Dept Otolaryngol Head & Neck Surg, Maywood, IL 60153 USA. NR 19 TC 53 Z9 56 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD NOV PY 2000 VL 110 IS 11 BP 1811 EP 1814 DI 10.1097/00005537-200011000-00007 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 371EL UT WOS:000165165200007 PM 11081590 ER PT J AU Weinrieb, RM Van Horn, DHA McLellan, AT Lucey, MR AF Weinrieb, RM Van Horn, DHA McLellan, AT Lucey, MR TI Interpreting the significance of drinking by alcohol-dependent liver transplant patients: Fostering candor is the key to recovery SO LIVER TRANSPLANTATION LA English DT Article ID PSYCHOLOGICAL HEALTH; CIRRHOSIS; DISEASE; RECIDIVISM; RECIPIENTS; SELECTION AB Few studies have examined the value of treating alcohol addiction either before or after liver transplantation. Nevertheless, most liver transplant programs and many insurance companies require 6 months to 1 year of abstinence from alcohol as a condition of eligibility for liver transplantation (the 6-month rule). We believe there are potentially harsh clinical consequences to the implementation of this rule. For example, the natural history of alcohol use disorders often involves brief fallbacks to drinking ("slips"), but when alcoholic liver transplant candidates slip, most are removed from consideration for transplantation or are required to accrue another 6 months of sobriety. Because there is no alternative treatment to liver transplantation for most patients with end-stage liver disease, the 6-month rule could be lethal in some circumstances. In this review, we survey the literature concerning the ability of the 6-month rule to predict drinking by alcoholic patients who undergo liver transplantation and examine its impact on the health consequences of drinking before and after liver transplantation. We believe that fostering candor between the alcoholic patient and the transplant team is the key to recovery from alcoholism. We conclude that it is unethical to force alcoholic liver patients who have resumed alcohol use while waiting for or after transplantation to choose between hiding their drinking to remain suitable candidates for transplantation or risk death by asking for treatment of alcoholism. Consequently, we advocate a flexible approach to clinical decision making for the transplant professional caring for an alcoholic patient who has resumed drinking and provide specific guidelines for patient management. C1 Univ Penn, Treatment Res Ctr, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Weinrieb, RM (reprint author), Univ Penn, Treatment Res Ctr, Sch Med, Dept Med, 3900 Chestnut St, Philadelphia, PA 19104 USA. FU NIAAA NIH HHS [1R01AA12299-01]; NIDA NIH HHS [DA07705] NR 27 TC 53 Z9 53 U1 2 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD NOV PY 2000 VL 6 IS 6 BP 769 EP 776 DI 10.1053/jlts.2000.18497 PG 8 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 374XU UT WOS:000165370800015 PM 11084066 ER PT J AU Rosen, HR AF Rosen, HR TI Retransplantation for hepatitis C: Implications of different policies SO LIVER TRANSPLANTATION LA English DT Article ID LIVER-TRANSPLANTATION AB 1. Approximately 20% of hepatitis C virus (HCV)-positive liver transplant recipients develop evidence of allograft cirrhosis by year 5. 2. The prevalence of HCV infection in patients undergoing retransplantation has significantly increased since 1990. 3. Retransplantation for recurrent HCV is associated with poor long-term survival. 4. Preoperative hyperbilirubinemia (billirubin greater than or equal to5 mg/ dL) and renal failure predict poor outcome after retransplantation. 5. Retransplantation is the only viable option for patients in whom allografts fail because of recurrent HCV disease. C1 Portland State Univ, Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol, Portland, OR 97207 USA. Portland State Univ, Portland Vet Affairs Med Ctr, Liver Transplantat Program, Portland, OR 97207 USA. RP Rosen, HR (reprint author), Portland State Univ, Portland Vet Affairs Med Ctr, Div Gastroenterol Hepatol, 3710 SW US Vet Hosp Rd,POB 1034,P3-GI, Portland, OR 97207 USA. NR 18 TC 14 Z9 14 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 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD NOV PY 2000 VL 6 IS 6 SU 2 BP S41 EP S46 DI 10.1053/jlts.2000.18689 PG 6 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 375WE UT WOS:000165423600008 PM 11084084 ER PT J AU Pearson, ML Lee, JL Chang, BL Elliott, M Kahn, KL Rubenstein, LV AF Pearson, ML Lee, JL Chang, BL Elliott, M Kahn, KL Rubenstein, LV TI Structured implicit review - A new method for monitoring nursing care quality SO MEDICAL CARE LA English DT Review DE nursing care; quality of health care; peer review; implicit review; processes of care ID PROSPECTIVE PAYMENT SYSTEM; DEPRESSED ELDERLY PATIENTS; PEER ASSESSMENTS; MEDICAL-RECORD; HOSPITAL-CARE; RELIABILITY; APPROPRIATENESS; IMPLEMENTATION; JUDGMENTS; EVENTS AB BACKGROUND. Nurses' independent decisions about assessment, treatment, and nursing interventions for hospitalized patients are important determinants of quality of care. Physician peer implicit review of medical records has been central to Medicare quality management and is considered the gold standard far reviewing physician care, but peer implicit review of nursing processes of care has not received similar attention. OBJECTIVE. The objective of this study was to develop and evaluate nurse structured implicit review (SIR) methods. RESEARCH DESIGN. We developed SIR instruments for rating the quality of inpatient nursing care for congestive heart failure (CHF) and cerebrovascular accident (CVA). Nurse reviewers used the SIR form to rate a nationally representative sample of randomly selected medical records for each disease from 297 acute care hospitals in 5 states (collected by the RAND-HCFA Prospective Payment System study). SUBJECTS. The study subjects were elderly Medicare inpatients with CHF (n = 291) or CVA (n = 283). MEASURES. We developed and tested scales reflecting domains of nursing process, evaluated interrater and interitem reliability, and assessed the extent to which items and scales predicted overall ratings of the quality of nursing care. RESULTS. Interrater reliability for 14 of 16 scales (CHF) or 10 of 16 scales (CVA) was greater than or equal to0.40. Interitem reliability was >0.80 for all but 1 scale (both diseases). Functional Assessment, Physical Assessment, and Medication Tracking ratings were the strongest predictors of overall nursing quality ratings (P < 0.001 for each). CONCLUSIONS. Nurse peer review with SIR has adequate interrater and excellent scale reliabilities and can be a valuable tool for assessing nurse performance. C1 RAND Corp, RAND Hlth, Santa Monica, CA 90407 USA. Univ Michigan, Sch Nursing, Undergrad Program, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Nursing, Non Trad Program, Ann Arbor, MI 48109 USA. Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles, Dept Med, Los Angeles, CA USA. RP Pearson, ML (reprint author), RAND Corp, RAND Hlth, POB 2138,1700 Main St, Santa Monica, CA 90407 USA. FU NINR NIH HHS [1-R01-NR-3681-01] NR 69 TC 23 Z9 23 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD NOV PY 2000 VL 38 IS 11 BP 1074 EP 1091 DI 10.1097/00005650-200011000-00003 PG 18 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 368UF UT WOS:000090135400003 PM 11078049 ER PT J AU Harada, ND Chun, A Chiu, V Pakalniskis, A AF Harada, ND Chun, A Chiu, V Pakalniskis, A TI Patterns of rehabilitation utilization after hip fracture in acute hospitals and skilled nursing facilities SO MEDICAL CARE LA English DT Article DE physical therapy; hip fracture ID PROSPECTIVE PAYMENT; RACIAL-DIFFERENCES; ELDERLY PATIENTS; SUBACUTE CARE; MANAGED CARE; OUTCOMES; STROKE; MEDICARE AB BACKGROUND. Hospitalized hip fracture patients may receive physical therapy (PT) in acute and/or postacute settings. Patterns of PT use may vary by patient, clinical, and hospital characteristics. These patterns can be analyzed if the acute and postacute stays are linked. OBJECTIVES. We classified the following patterns of PT use: acute PT only, skilled nursing facility (SNF) PT only, acute and SNF PT, and no PT. For each pattern, we compared (1) characteristics of hip fracture patients, (2) length of stay (LOS), and (3) discharge outcomes. SUBJECTS. The study included 187,990 hospitalized hip fracture patients derived from Medicare administrative data. MEASURES. Dependent variables were PT use patterns, acute hospital and SNF LOS, total episode days of care, and discharge destination. Independent variables were demographic, clinical, and facility characteristics. PT use patterns were also used as independent variables in the LOS and discharge destination models. RESULTS. Patterns of PT use were influenced by demographic and clinical characteristics such as age, race, and surgery type. Similarly, different LOS measures and discharge destinations varied by the PT use patterns. Patients receiving acute PT had longer acute LOSs; however, those patients who were subsequently transferred to SNFs had shorter SNF LOSs and total episode days of care. Patients utilizing PT were more likely to be discharged to home after the acute or SNF stay. CONCLUSIONS. Disparities in PT use exist for subgroups of patients such as the elderly and blacks. Providers should determine the most appropriate setting for initiation of PT to achieve better discharge outcomes with efficient use of resources. C1 Univ Calif Los Angeles, Sch Med, GRECC 11G, VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90073 USA. Cedars Sinai Med Ctr, Resource & Outcomes Management Dept, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Sch Med, Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90048 USA. RP Harada, ND (reprint author), Univ Calif Los Angeles, Sch Med, GRECC 11G, VA Greater Los Angeles Hlth Care Syst, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 38 TC 37 Z9 37 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 NOV PY 2000 VL 38 IS 11 BP 1119 EP 1130 DI 10.1097/00005650-200011000-00006 PG 12 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 368UF UT WOS:000090135400006 PM 11078052 ER PT J AU Dailey, GE Boden, GH Creech, RH Johnson, DG Gleason, RE Kennedy, FP Weinrauch, LA Weir, M D'Elia, JA AF Dailey, GE Boden, GH Creech, RH Johnson, DG Gleason, RE Kennedy, FP Weinrauch, LA Weir, M D'Elia, JA TI Effects of pulsatile intravenous insulin therapy on the progression of diabetic nephropathy SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID METABOLIC CONTROL; KIDNEY-FUNCTION; RENAL-FAILURE; MELLITUS; HYPERGLYCEMIA; PROTEINURIA; EFFICACY; DISEASE; DECLINE AB The purpose of this study was to assess the effects of pulsatile intravenous insulin therapy (PIVIT) on the progression of diabetic nephropathy in patients with type 1 diabetes mellitus (DM). This 18-month multicenter, prospective, controlled study involved 49 type 1 DM patients with nephropathy who were following the Diabetes Control and Complications Trial (DCCT) intensive therapy (IT) regimen. Of these, 26 patients formed the control group (C), which continued on IT, while 23 patients formed the treatment group (T) and underwent, in addition to IT, weekly PIVIT. Blood pressure in all patients was maintained below 140/90 mm Hg on antihypertensive medication, preferentially using angiotensin-converting enzyme (ACE) inhibitors. Ail study patients were seen in the clinic weekly for 18 months, had monthly glycohemoglobin (HbA(1c)), and every 3 months, 24-hour urinary protein excretion and creatinine clearance (CrCl) determinations. The HbA(1c) levels declined from 8.61% +/- 0.33% to 7.68% +/- 0.31% (P = .0028) in the T group and from 9.13% +/- 0.36% to 8.19% +/- 0.33% (P = .0015) in the C group during the study period. CrCl declined significantly in both groups, as expected, but the rate of CrCl decline in the T group (2.21 +/- 1.62 ml/min/yr) was significantly less than in the C group (7.69 +/- 1.88 ml/min/yr, P = .0343). We conclude that when PIVIT is added to IT in type 1 DM patients with overt nephropathy, it appears to markedly reduce the progression of diabetic nephropathy. The effect appears independent of ACE inhibitor therapy, blood pressure, or glycemic control. Copyright (C) 2000 by W.B. Saunders Company. C1 Scripps Clin, San Diego, CA USA. Temple Univ Hosp, Philadelphia, PA 19140 USA. Summit Med Ctr, Nashville, TN USA. Univ Arizona, Med Ctr, Tucson, AZ 85721 USA. Joslin Clin, Boston, MA USA. Mayo Clin, Rochester, MN USA. Mt Auburn Hosp, Cambridge, MA USA. Univ Maryland, Baltimore, MD 21201 USA. RP Dailey, GE (reprint author), Scripps Clin, Div Endocrinol, 10666 N Torrey Pines Rd, La Jolla, CA 92037 USA. OI D'Elia, John/0000-0001-9482-581X; Weinrauch, Larry/0000-0003-1357-9528 NR 28 TC 11 Z9 11 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD NOV PY 2000 VL 49 IS 11 BP 1491 EP 1495 DI 10.1053/meta.2000.17700 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 372EG UT WOS:000165220900021 PM 11092517 ER PT J AU Ueki, K Algenstaedt, P Mauvais-Jarvis, F Kahn, CR AF Ueki, K Algenstaedt, P Mauvais-Jarvis, F Kahn, CR TI Positive and negative regulation of phosphoinositide 3-kinase-dependent signaling pathways by three different gene products of the p85 alpha regulatory subunit SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID INSULIN-RECEPTOR SUBSTRATE-1; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVATION; INDUCED GLUCOSE-TRANSPORT; PROTEIN-KINASE-B; GLYCOGEN-SYNTHASE; 3T3-L1 ADIPOCYTES; SKELETAL-MUSCLE; DNA-SYNTHESIS; STIMULATION; WORTMANNIN AB Phosphoinositide (PI) 3-kinase is a key mediator of insulin-dependent metabolic actions, including stimulation of glucose transport and glycogen synthesis. The gene for the p85 alpha regulatory subunit yields three splicing variants, p85 alpha, AS53/p55 alpha, and p50 alpha. All three have (i) a C-terminal structure consisting of two Src homology 2 domains flanking the p110 catalytic subunit-binding domain and (ii) a unique N-terminal region of 304, 34, and 6 amino acids, respectively. To determine if these regulatory subunits differ in their effects on enzyme activity and signal transduction from insulin receptor substrate (IRS) proteins under physiological conditions, we expressed each regulatory subunit in fully differentiated L6 myotubes using adenovirus-mediated gene transfer with or without coexpression of the p110 alpha catalytic subunit. PI 3-kinase activity associated with p50 alpha was greater than that associated with p85 alpha or AS53, Increasing the level of p85 alpha or AS53, but not p50 alpha, inhibited both phosphotyrosine-associated and p110-associated PI 3-kinase activities. Expression of a p85 alpha mutant lacking the p110-binding site (Delta p85) also inhibited phosphotyrosine-associated PI 3-kinase activity but not p110-associated activity. Insulin stimulation of two kinases downstream from PI-3 kinase, AM and p70 S6 kinase (p70(S6K)), was decreased in cells expressing p85 alpha or AS53 but not in cells expressing p50a. Similar inhibition of PI 3-kinase, Akt, and p70(S6K) was observed, even when p110 alpha was coexpressed with p85 alpha or AS53, Expression of p110 alpha alone dramatically increased glucose transport but decreased glycogen synthase activity. This effect was reduced when p110 alpha was coexpressed with any of the three regulatory subunits. Thus, the three different isoforms of regulatory subunit can relay the signal from IRS proteins to the p110 catalytic subunit with different efficiencies. They also negatively modulate the PI 3-kinase catalytic activity but to different extents, dependent on the unique N-terminal structure of each isoform, These data also suggest the existence of a mechanism by which regulatory subunits modulate the PI 3-kinase-mediated signals, independent of the kinase activity, possibly through subcellular localization of the catalytic subunit or interaction with additional signaling molecules. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK33201, DK55545, R01 DK033201, R01 DK055545] NR 41 TC 101 Z9 103 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2000 VL 20 IS 21 BP 8035 EP 8046 DI 10.1128/MCB.20.21.8035-8046.2000 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 362TK UT WOS:000089794200020 PM 11027274 ER PT J AU Miller, SJ Suthiphongchai, T Zambetti, GP Ewen, ME AF Miller, SJ Suthiphongchai, T Zambetti, GP Ewen, ME TI p53 binds selectively to the 5 ' untranslated region of cdk4, an RNA element necessary and sufficient for transforming growth factor beta- and p53-mediated translational inhibition of cdk4 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CELL-CYCLE ARREST; TGF-BETA; NUCLEIC-ACIDS; PROTEIN; SUPPRESSION; REPRESSION; DOMAIN AB One consequence of transforming growth factor beta (TGF-beta) treatment is inhibition of Cdk4 synthesis, and this is dependent on p53. Here, we show that the 5' untranslated region (UTR) of the cdk4 mRNA is both necessary and sufficient for wild-type p53-dependent TGF-beta -regulated translational inhibition of cdk4. Wild-type p53 bound selectively to the 5' UTR of the cdk4 mRNA and inhibited translation of RNAs that contain this region. RNA binding and translational control are two genetically separable functions of p53, as are specific and nonspecific RNA binding. Moreover, transactivation-defective mutants of p53 retain the ability to regulate cdk4 translation. Our findings suggest that p53 functions as a regulator of translation in response to TGF-beta in vivo. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. St Jude Childrens Res Hosp, Dept Biochem, Memphis, TN 38105 USA. RP Ewen, ME (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM mark_ewen@dfci.harvard.edu FU NCI NIH HHS [5P30CA21765, CA63230, CA65842, P30 CA021765, R01 CA063230, R01 CA065842] NR 27 TC 59 Z9 60 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 NOV PY 2000 VL 20 IS 22 BP 8420 EP 8431 DI 10.1128/MCB.20.22.8420-8431.2000 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 368AH UT WOS:000090094800012 PM 11046139 ER PT J AU Roberts, RG Sheng, M AF Roberts, RG Sheng, M TI Association of dystrophin-related protein 2 (DRP2) with postsynaptic densities in rat brain SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID DUCHENNE MUSCULAR-DYSTROPHY; CENTRAL-NERVOUS-SYSTEM; UTROPHIN-DEFICIENT MICE; BETA-DYSTROBREVIN; SYNAPTIC VESICLES; NONMUSCLE TISSUES; MOUSE; LOCALIZATION; FAMILY; GENE AB The fundamental function of the membrane-associated cytoskeletal proteins dystrophin and utrophin remains unclear. To gain further insights into the dystrophin family of proteins, we have studied dystrophin-related protein 2 (DRP2), whose expression is largely confined to the vertebrate central nervous system. Both human and rat DRP2 are expressed from two alternative but neighboring transcriptional start sites and have simple transcript structures. Antibodies raised against DRP2 detect a characteristic quartet of bands (similar to 100-120 kDa) in Western blots of rat brain. The DRP2 protein is associated with brain membrane fractions and highly enriched in the postsynaptic density. Immunohistochemistry shows DRP2 to be widely distributed in a punctate pattern on neuronal dendrites and in neuropil, with particular concentration in regions of the brain involved in cholinergic synaptic transmission. Given the presence of utrophin in the cholinergic neuromuscular junction, and perturbations of cholinergic transmission in dystrophin-deficient nematodes, our findings may suggest a role for DRP2 in the organization of central cholinergic synapses. C1 Guys Hosp, Div Med & Mol Genet, GKT Med Sch, London SE1 9RT, England. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Roberts, RG (reprint author), Guys Hosp, Div Med & Mol Genet, GKT Med Sch, 8th Floor,Guys Tower, London SE1 9RT, England. RI Roberts, Roland/C-3596-2009; OI Roberts, Roland/0000-0001-6636-1579 NR 42 TC 9 Z9 10 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell Neurosci. PD NOV PY 2000 VL 16 IS 5 BP 674 EP 685 DI 10.1006/mcne.2000.0895 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 378XT UT WOS:000165611200012 PM 11083927 ER PT J AU Stage-Zimmermann, T Schmidt, U Silver, PA AF Stage-Zimmermann, T Schmidt, U Silver, PA TI Factors affecting nuclear export of the 60S ribosomal subunit in vivo SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID MESSENGER-RNA EXPORT; GTPASE-ACTIVATING PROTEIN; YEAST NSR1 PROTEIN; SACCHAROMYCES-CEREVISIAE; PORE COMPLEX; POLY(A)(+) RNA; TRANSPORT FACTORS; BINDING-PROTEIN; IMPORTIN-BETA; KARYOPHERIN-BETA AB In Saccharomyces cerevisiae, the 60S ribosomal subunit assembles in the nucleolus and then is exported to the cytoplasm, where it joins the 40S subunit for translation. Export of the 60S subunit from the nucleus is known to be an energy-dependent and factor-mediated process, but very little is known about the specifics of its transport. To begin to address this problem, an assay was developed to follow the localization of the 60S ribosomal subunit in S, cerevisiae. Ribosomal protein L11b (Rp111b), one of the similar to 45 ribosomal proteins of the 60S subunit, was tagged at its carboxyl terminus with the green fluorescent protein (GFP) to enable visualization of the 60S subunit in living cells. A panel of mutant yeast strains was screened for their accumulation of Rp111b-GFP in the nucleus as an indicator of their involvement in ribosome synthesis and/or transport. This panel included conditional alleles of several rRNA-processing factors, nucleoporins, general transport factors, and karyopherins. As predicted, conditional alleles of rRNA-processing factors that affect 60S ribosomal subunit assembly accumulated Rp111b-GFP in the nucleus. In addition, several of the nucleoporin mutants as well as a few of the karyopherin and transport factor mutants also mislocalized Rp111b-GFP. In particular, deletion of the previously uncharacterized karyopherin KAP120 caused accumulation of Rp111b-GFP in the nucleus, whereas ribosomal protein import was not impaired. Together, these data further define the requirements for ribosomal subunit export and suggest a biological function for KAP120. C1 Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Silver, PA (reprint author), Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. NR 93 TC 108 Z9 114 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2000 VL 11 IS 11 BP 3777 EP 3789 PG 13 WC Cell Biology SC Cell Biology GA 374VM UT WOS:000165365100008 PM 11071906 ER PT J AU Kwon, J Morshead, KB Guyon, JR Kingston, RE Oettinger, MA AF Kwon, J Morshead, KB Guyon, JR Kingston, RE Oettinger, MA TI Histone acetylation and hSWI/SNF remodeling act in concert to stimulate V(D)J cleavage of nucleosomal DNA SO MOLECULAR CELL LA English DT Article ID HUMAN SWI/SNF; CHROMATIN STRUCTURE; IN-VITRO; RECOMBINATION; COMPLEX; PROTEINS; BINDING; HMG1; RAG1; GENE AB The ordered assembly of immunoglobulin and TCR genes by V(D)J recombination depends on the regulated accessibility of individual loci. We show here that the histone tails and intrinsic nucleosome structure pose significant impediments to V(D)J cleavage. However, alterations to nucleosome structure via histone acetylation or by stable hSWI/SNF-dependent remodeling greatly increase the accessibility of nucleosomal DNA to V(D)J cleavage. Moreover, acetylation and hSWI/SNF remodeling can act in concert on an individual nucleosome to achieve levels of V(D)J cleavage approaching those observed on naked DNA. These results are consistent with a model in which regulated recruitment of chromatin modifying activities is involved in mediating the lineage and stage-specific control of V(D)J recombination. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Oettinger, MA (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. FU NCI NIH HHS [T32 CAO9141]; NIGMS NIH HHS [GM48405, GM58026] NR 39 TC 137 Z9 137 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD NOV PY 2000 VL 6 IS 5 BP 1037 EP 1048 DI 10.1016/S1097-2765(00)00102-7 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 376TD UT WOS:000165472100006 PM 11106743 ER PT J AU Cabodi, S Calautti, E Talora, C Kuroki, T Stein, PL Dotto, GP AF Cabodi, S Calautti, E Talora, C Kuroki, T Stein, PL Dotto, GP TI A PKC-eta/Fyn-Dependent pathway leading to keratinocyte growth arrest and differentiation SO MOLECULAR CELL LA English DT Article ID PROTEIN-KINASE-C; SRC FAMILY KINASES; TYROSINE KINASE; FACTOR RECEPTOR; SELECTIVE MODULATION; MUTANT MICE; NPKC-ETA; T-CELLS; PHOSPHORYLATION; EXPRESSION AB Growth control of epithelial cells differs substantially from other cell types. Activation of Fyn, a Src kinase family member, is required for normal keratinocyte differentiation. We report that increased Fyn activity by itself suppresses growth of keratinocytes, but not dermal fibroblasts, through downmodulation of EGF receptor (EGFR) signaling. Protein kinase C-eta has also been implicated in keratinocyte growth/differentiation control. We show that growth suppression of keratinocytes by PKC-eta depends mostly on Fyn. PKC-eta activity is both necessary and sufficient for Fyn activation, PKC-eta and Fyn are found in association, and recombinant PKC-eta directly activates Fyn. Thus, our findings reveal a direct cross talk between PKC-eta and Fyn, which presides over the decision between keratinocyte (epithelial) cell growth and differentiation. C1 Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Univ Turin, Dept Genet Biol & Med Chem, Turin, Italy. Showa Univ, Inst Mol Oncol, Tokyo, Japan. Wistar Inst, Philadelphia, PA 19104 USA. RP Dotto, GP (reprint author), Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RI Kuroki, Toshio/A-9500-2011; OI Kuroki, Toshio/0000-0001-6369-4351; Cabodi, Sara/0000-0003-1248-6549 FU NCI NIH HHS [CA16038, CA73796]; NIAMS NIH HHS [AR39190] NR 39 TC 64 Z9 67 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD NOV PY 2000 VL 6 IS 5 BP 1121 EP 1129 DI 10.1016/S1097-2765(00)00110-6 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 376TD UT WOS:000165472100014 PM 11106751 ER PT J AU Walker, RH Danisi, FO Swope, DM Goodman, RR Germano, IM Brin, MF AF Walker, RH Danisi, FO Swope, DM Goodman, RR Germano, IM Brin, MF TI Intrathecal baclofen for dystonia: Benefits and complications during six years of experience SO MOVEMENT DISORDERS LA English DT Article DE intrathecal baclofen; dystonia ID INTRACTABLE SPINAL SPASTICITY; MULTIPLE-SCLEROSIS CLINICS; GENERALIZED DYSTONIA; CORD SPASTICITY; CEREBRAL-PALSY; INFUSION; SUICIDE; ORIGIN; PATIENT; MANAGEMENT AB Fourteen patients with primary or secondary dystonia received intrathecal baclofen (ITB) through an implanted pump following a trial dose. Patients were selected for ITB trial if they had clinically unsatisfactory responses to oral antidystonic medications, including oral baclofen. Patients were rated using the Burke-Fahn-Marsden rating scale by a blinded rater after the dose of ITB was optimized. Five patients experienced improvement in symptoms as determined by a change in rating scale scores, although only two had a clear clinical benefit. Etiology of dystonia did not determine the efficacy of ITB therapy, as benefit or failure was seen in both primary and secondary dystonia. C1 Mt Sinai Med Ctr, Dept Neurol, New York, NY 10029 USA. Mt Sinai Med Ctr, Dept Neurosurg, New York, NY 10029 USA. Loma Linda Univ, Dept Neurol, Loma Linda, CA 92350 USA. Columbia Univ, Dept Neurol Surg, New York, NY USA. RP Walker, RH (reprint author), Bronx Vet Affairs Med Ctr, Dept Neurol 127, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. FU NCRR NIH HHS [5-MO1-RR00071] NR 52 TC 57 Z9 60 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD NOV PY 2000 VL 15 IS 6 BP 1242 EP 1247 DI 10.1002/1531-8257(200011)15:6<1242::AID-MDS1028>3.0.CO;2-Z PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 372MD UT WOS:000165236700028 PM 11104213 ER PT J AU Ojala, PM Yamamoto, K Castanos-Velez, E Biberfeld, P Korsmeyer, SJ Makela, TP AF Ojala, PM Yamamoto, K Castanos-Velez, E Biberfeld, P Korsmeyer, SJ Makela, TP TI The apoptotic v-cyclin-CDK6 complex phosphorylates and inactivates Bcl-2 SO NATURE CELL BIOLOGY LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; PROTEIN-KINASE; CELL-DEATH; RETINOBLASTOMA PROTEIN; ECTOPIC EXPRESSION; CANCER-CELLS; C-JUN; CYCLIN; VIRUS; SUPPRESSION AB v-cyclin encoded by Kaposi's sarcoma herpesvirus/human herpesvirus 8 (KSHV or HHV8) associates with cellular cyclin-dependent kinase 6 (CDK6) to form a kinase complex that promotes cell-cycle progression, but can also induce apoptosis in cells with high levels of CDK6. Here we show that whereas HHV8-encoded v-Bcl-5 protects against this apoptosis, cellular Bcl-2 has lost its anti-apoptotic potential as a result of an inactivating phosphorylation in its unstructured loop region. Moreover, we identify Bcl-2 as a new substrate for v-cyclin-CDK6 in vitro, and show that it is present in a complex with CDK6 in cell lysates, A Bcl-2 mutant with a S70A S87A double substitution in the loop region is not phosphorylated and provides resistance to apoptosis, indicating that inactivation of Bcl-2 by v-cyclin-CDK6 may be required for the observed apoptosis. Furthermore, the identification of phosphorylated Bcl-2 in HHV8-positive Kaposi's sarcoma indicates that HHV8-mediated interference with host apoptotic signalling pathways may encourage the development of Kaposi's sarcoma. C1 Univ Helsinki, Haartman Inst, Helsinki 00014, Finland. Univ Helsinki, Biocentrum, Helsinki 00014, Finland. Univ Helsinki, Cent Hosp, HUCH Lab Diagnost, Hyks 00029, Finland. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Karolinska Inst Hosp, Dept Pathol & Oncol, Immunopathol Lab, S-17176 Stockholm, Sweden. RP Ojala, PM (reprint author), Univ Helsinki, Haartman Inst, POB 21,Haartmaninkatu 3, Helsinki 00014, Finland. RI makela, tomi/B-3734-2009 OI makela, tomi/0000-0002-4869-8044 NR 50 TC 117 Z9 121 U1 0 U2 5 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD NOV PY 2000 VL 2 IS 11 BP 819 EP 825 DI 10.1038/35041064 PG 7 WC Cell Biology SC Cell Biology GA 371YU UT WOS:000165207500016 PM 11056537 ER PT J AU Fruman, DA Mauvais-Jarvis, F Pollard, DA Yballe, CM Brazil, D Bronson, RT Kahn, CR Cantley, LC AF Fruman, DA Mauvais-Jarvis, F Pollard, DA Yballe, CM Brazil, D Bronson, RT Kahn, CR Cantley, LC TI Hypoglycaemia, liver necrosis and perinatal death in mice lacking all isoforms of phosphoinositide 3-kinase p85 alpha SO NATURE GENETICS LA English DT Article ID INSULIN-RECEPTOR SUBSTRATE-1; PHOSPHATIDYLINOSITOL 3-KINASE; REGULATORY SUBUNIT; DIFFERENTIAL REGULATION; SKELETAL-MUSCLE; RAT-LIVER; IRS-1; STIMULATION; RESISTANCE; TRANSPORT AB Phosphoinositide 3-kinases produce 3'-phosphorylated phosphoinositides that act as second messengers to recruit other signalling proteins to the membrane(1). Pi3ks are activated by many extracellular stimuli and have been implicated in a variety of cellular responses(1). The Pi3k gene family is complex and the physiological roles of different classes and isoforms are not clear. The gene Pik3r1 encodes three proteins (p85 alpha, p55 alpha and p50 alpha) that serve as regulatory subunits of class I-A Pi3ks (ref. 2). Mice lacking only the p85a isoform are viable but display hypoglycaemia and increased insulin sensitivity correlating with upregulation of the p55 alpha and p50 alpha variants(3). Here we report that loss of all protein products of Pik3r1 results in perinatal lethality. We observed, among other abnormalities, extensive hepatocyte necrosis and chylous ascites, We also noted enlarged skeletal muscle fibres, brown fat necrosis and calcification of cardiac tissue. In liver and muscle, loss of the major regulatory isoform caused a great decrease in expression and activity of class I-A Pi3k catalytic subunits: nevertheless, homozygous mice still displayed hypoglycaemia, lower insulin levels and increased glucose tolerance. Our findings reveal that p55 alpha and/or p50 alpha are required for survival, but not for development of hypoglycaemia, in mice lacking p85 alpha. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Signal Transduct, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Tufts Sch Vet Med, Boston, MA USA. RP Cantley, LC (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Signal Transduct, Boston, MA 02215 USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIDDK NIH HHS [DK55545]; NIGMS NIH HHS [GM41890, R01 GM041890] NR 28 TC 193 Z9 197 U1 2 U2 5 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2000 VL 26 IS 3 BP 379 EP 382 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 371JU UT WOS:000165176500034 PM 11062485 ER PT J AU Kurt-Jones, EA Popova, L Kwinn, L Haynes, LM Jones, LP Tripp, RA Walsh, EE Freeman, MW Golenbock, DT Anderson, LJ Finberg, RW AF Kurt-Jones, EA Popova, L Kwinn, L Haynes, LM Jones, LP Tripp, RA Walsh, EE Freeman, MW Golenbock, DT Anderson, LJ Finberg, RW TI Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus SO NATURE IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTOR-2; CELL WALL COMPONENTS; CUTTING EDGE; DROSOPHILA TOLL; HOST-DEFENSE; LIPOPOLYSACCHARIDE; MICE; ACTIVATION; GENE; LPS AB The innate immune system contributes to the earliest phase of the host defense against foreign organisms and has both soluble and cellular pattern recognition receptors for microbial products. Two important members of this receptor group, CD14 and the Toll-like receptor (TLR) pattern recognition receptors, are essential for the innate immune response to components of Gramnegative and Cram-positive bacteria, mycobacteria, spirochetes and yeast. We now find that these receptors function in an antiviral response as well,The innate immune response to the fusion protein of an important respiratory pathogen of humans, respiratory syncytial virus (RSV), was mediated by TLR4 and CD14. RSV persisted longer in the lungs of infected TLR l-deficient mice compared to normal mice,Thus, a common receptor activation pathway can initiate innate immune responses to both bacterial and viral pathogens. C1 Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA. Dana Farber Canc Inst, Dept Adult Oncol, Program Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Ctr Dis Control & Prevent, Div Viral & Rickettsial Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ Rochester, Sch Med & Dent, Rochester, NY USA. Boston Univ, Sch Med, Maxwell Finland Lab Infect Dis, Boston, MA 02118 USA. RP Kurt-Jones, EA (reprint author), Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA. RI Finberg, Robert/E-3323-2010; OI Tripp, Ralph/0000-0002-2924-9956 FU NIAID NIH HHS [R01AI31628, R01AI38515, R01AI39576]; NIDDK NIH HHS [R01DK50305]; NIGMS NIH HHS [R01GM54060] NR 41 TC 1001 Z9 1058 U1 12 U2 57 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 NOV PY 2000 VL 1 IS 5 BP 398 EP 401 DI 10.1038/80833 PG 4 WC Immunology SC Immunology GA 369PL UT WOS:000165076100012 PM 11062499 ER PT J AU Nathan, DG Varmus, HE AF Nathan, DG Varmus, HE TI The National Institutes of Health and clinical research: a progress report SO NATURE MEDICINE LA English DT Editorial Material ID PHYSICIAN-SCIENTISTS C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Nathan, DG (reprint author), Dana Farber Canc Inst, 44 Binney St,Suite 1628, Boston, MA 02115 USA. NR 9 TC 38 Z9 38 U1 0 U2 2 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 NOV PY 2000 VL 6 IS 11 BP 1201 EP 1204 DI 10.1038/81282 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 370GH UT WOS:000165114800013 PM 11062519 ER PT J AU Orkin, SH AF Orkin, SH TI Stem cell alchemy SO NATURE MEDICINE LA English DT Editorial Material ID IN-VIVO; BONE-MARROW; IDENTIFICATION; EXPRESSION; MUSCLE; BRAIN; BLOOD C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,Div Pediat Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,Div Pediat Hematol Oncol, Boston, MA 02115 USA. NR 20 TC 46 Z9 49 U1 0 U2 0 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 NOV PY 2000 VL 6 IS 11 BP 1212 EP 1213 DI 10.1038/81303 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 370GH UT WOS:000165114800018 PM 11062526 ER PT J AU Cheng, T Rodrigues, N Dombkowski, D Stier, S Scadden, DT AF Cheng, T Rodrigues, N Dombkowski, D Stier, S Scadden, DT TI Stem cell repopulation efficiency but not pool size is governed by p27(kip1) SO NATURE MEDICINE LA English DT Article ID GROWTH-FACTOR-BETA; HEMATOPOIETIC PROGENITORS; COMPETITIVE REPOPULATION; MICE LACKING; CYCLE; EXPRESSION; DIFFERENTIATION; MOUSE; INHIBITOR; ASSAY AB Sustained blood cell production requires preservation of a quiescent, multipotential stem cell pool that intermittently gives rise to progenitors with robust proliferative potential. The ability of cells to shift from a highly constrained to a vigorously active proliferative state is critical for maintaining stem cells while providing the responsiveness necessary for host defense. The cy clin-dependent kinase inhibitor (CDKI), p21(cip1/waf1) (p21) dominates stem cell kinetics. Here we report that another CDKI, p27(kip1) (p27), does not affect stem cell number, cell cycling, or self-renewal, but markedly alters progenitor proliferation and pool size. Therefore, distinct CDKIs govern the highly divergent stem and progenitor cell populations. When competitively transplanted, p27-deficient stem cells generate progenitors that eventually dominate blood cell production. Modulating p27 expression in a small number of stem cells may translate into effects on the majority of mature cells, thereby providing a strategy for potentiating the impact of transduced cells in stem cell gene therapy. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. RP Scadden, DT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, AIDS Res Ctr, 149 13th St,Room 5212, Boston, MA 02129 USA. FU NHLBI NIH HHS [HL 44851, HL 55718]; NIAID NIH HHS [AI07387] NR 45 TC 244 Z9 259 U1 1 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 NOV PY 2000 VL 6 IS 11 BP 1235 EP 1240 DI 10.1038/81335 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 370GH UT WOS:000165114800030 PM 11062534 ER PT J AU Gusella, JF MacDonald, ME AF Gusella, JF MacDonald, ME TI Molecular genetics: Unmasking polyglutamine triggers in neurodegenerative disease SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID SPINOCEREBELLAR ATAXIA TYPE-6; MACHADO-JOSEPH DISEASE; CAG REPEAT LENGTH; NEURONAL INTRANUCLEAR INCLUSIONS; BULBAR MUSCULAR-ATROPHY; SCA1 TRANSGENIC MICE; HUNTINGTONS-DISEASE; EXPANDED POLYGLUTAMINE; TRINUCLEOTIDE REPEAT; MUTANT HUNTINGTIN AB Two decades ago, molecular genetic analysis provided a new approach for defining the roots of inherited disorders. This strategy has proved particularly powerful because, with only a description of the inheritance pattern, it can uncover previously unsuspected mechanisms of pathogenesis that are not implicated by known biological pathways or by the disease manifestations. Nowhere has the impact of molecular genetics been more evident than in the dominantly inherited neurodegenerative disorders, where eight unrelated diseases have been revealed to possess the same type of mutation - an expanded polyglutamine encoding sequence - affecting different genes. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. RP Gusella, JF (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. NR 98 TC 255 Z9 262 U1 2 U2 13 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD NOV PY 2000 VL 1 IS 2 BP 109 EP 115 DI 10.1038/35039051 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 381LN UT WOS:000165764500013 PM 11252773 ER PT J AU Shields, DC Avgeropoulos, NG Banik, NL Tyor, WR AF Shields, DC Avgeropoulos, NG Banik, NL Tyor, WR TI Acute multiple sclerosis characterized by extensive mononuclear phagocyte infiltration SO NEUROCHEMICAL RESEARCH LA English DT Article DE multiple sclerosis; mononuclear phagocyte; interferon alpha; tumor necrosis factor alpha ID CALPAIN; DEMYELINATION; DISEASE; CELLS AB In this study, we examine the clinical, neuroradiological, and immunohistochemical findings of a 51 year old white female who died 27 months after onset of acute multiple sclerosis despite treatment with interferon-beta, azathioprine, corticosteroids, and cyclophosphamide. Immunohistochemical studies revealed extensive gliosis and mononuclear phagocyte infiltration with corresponding upregulation of proinflammatory cytokines (eg. IFN-alpha, TNF-alpha). The significance of immunohistochemical findings with respect to clinical presentation is discussed. C1 Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Massachusetts Gen Hosp, Dept Neurol, Brain Tumor Ctr, Boston, MA 02114 USA. RP Tyor, WR (reprint author), Med Univ S Carolina, Dept Neurol, 171 Ashley Ave, Charleston, SC 29425 USA. FU NIDA NIH HHS [DA-11870]; NINDS NIH HHS [NS-38146, NS-31622] NR 15 TC 4 Z9 4 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD NOV PY 2000 VL 25 IS 11 BP 1517 EP 1520 DI 10.1023/A:1007636427861 PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 369DF UT WOS:000090156000009 PM 11071372 ER PT J AU Royall, DR AF Royall, DR TI Executive cognitive impairment: A novel perspective on dementia SO NEUROEPIDEMIOLOGY LA English DT Review DE cognitive impairment, executive; executive function; frontal lobe; aging; dementia, diagnosis ID QUANTITATIVE CEREBRAL ANATOMY; ALZHEIMERS-DISEASE; ELDERLY SUBJECTS; SYNAPSE LOSS; BEHAVIOR; DEPRESSION; DYSCONTROL; SEVERITY; FEATURES AB In 1994 the American Psychiatric Association added impairment of executive control functions (ECF) to its list of cognitive domains that should be considered in the assessment of dementia, This recommendation has not been widely implemented. None the less, there is growing evidence that ECF impairment is common, strongly associated with disability and functional decline, and not well detected by traditional dementia screening tests. This article reviews the implications of ECF for the epidemiology of dementia. The total number of dementia cases may be much greater than previously thought and we are likely to be selectively missing cases with reversible causes of ECF impairment. Copyright (C) 2000 S. Karger AG, Basel. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA. S Texas Vet Hlth Syst Audie L Murphy Div GRECC, Dept Psychiat, San Antonio, TX USA. S Texas Vet Hlth Syst Audie L Murphy Div GRECC, Dept Med, San Antonio, TX USA. S Texas Vet Hlth Syst Audie L Murphy Div GRECC, Dept Pharmacol, San Antonio, TX USA. RP Royall, DR (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 40 TC 72 Z9 77 U1 4 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0251-5350 J9 NEUROEPIDEMIOLOGY JI Neuroepidemiology PD NOV-DEC PY 2000 VL 19 IS 6 BP 293 EP 299 DI 10.1159/000026268 PG 7 WC Public, Environmental & Occupational Health; Clinical Neurology SC Public, Environmental & Occupational Health; Neurosciences & Neurology GA 371UA UT WOS:000165195700002 PM 11060503 ER PT J AU Rosand, J Greenberg, SM AF Rosand, J Greenberg, SM TI Cerebral amyloid angiopathy SO NEUROLOGIST LA English DT Review DE cerebral amyloid angiopathy; intracerebral hemorrhage; apolipoprotein E ID APOLIPOPROTEIN-E EPSILON-2; PRIMARY INTRACEREBRAL HEMORRHAGE; ACUTE MYOCARDIAL-INFARCTION; CENTRAL-NERVOUS-SYSTEM; PARENCHYMAL BRAIN HEMORRHAGES; ONSET ALZHEIMER-DISEASE; PRECURSOR PROTEIN GENE; BETA-PROTEIN; GRANULOMATOUS-ANGIITIS; INTRACRANIAL HEMORRHAGE AB BACKGROUND- Cerebral amyloid angiopathy (CAA) is increasingly recognized as an important cause of lobar intracerebral hemorrhage in the elderly and is the only major form of stroke without effective treatment. It is characterized by deposition of congophilic material in small- to medium-sized blood vessels of the brain and leptomeninges. In the most severe stages of the disease, amyloid deposits cause breakdown of the blood vessel wall with consequent hemorrhage. Presently, definitive diagnosis of CAA-related hemorrhage requires examination of the brain at autopsy. REVIEW SUMMARY- This article reviews the pathology and pathogenesis of CAA. To aid in identifying patients at risk for CAA, the range of clinical presentations is discussed. Particular attention is devoted to lobar intracerebral hemorrhage, the most common and devastating manifestation of CAA. We review recent developments in the epidemiology of CAA, particularly the lessons learned from studies of the apolipoprotein E genotype. We conclude with a discussion of antemortem diagnosis, the differential diagnosis and management of CAA, and future directions for the development of treatments. CONCLUSIONS- CAA will become increasingly common as the population ages. Its presence should be considered in any elderly patient with lobar hemorrhage or dementia. Recognition of CAA is particularly important in the setting of anticoagulant therapy, which places patients with CAA at high risk for intracerebral hemorrhage. Finally, patients with CAA-related hemorrhage are at high risk for recurrent hemorrhage. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 124 TC 8 Z9 9 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1074-7931 J9 NEUROLOGIST JI Neurologist PD NOV PY 2000 VL 6 IS 6 BP 315 EP 325 DI 10.1097/00127893-200006060-00002 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 376WC UT WOS:000165478900002 ER PT J AU Cutrer, FM O'Donnell, A del Rio, MS AF Cutrer, FM O'Donnell, A del Rio, MS TI Functional neuroimaging: Enhanced understanding of migraine pathophysiology SO NEUROLOGY LA English DT Article ID CEREBRAL BLOOD-FLOW; TRANSCRANIAL MAGNETIC STIMULATION; BASILAR ARTERY MIGRAINE; BRAIN ENERGY-METABOLISM; CLASSIC MIGRAINE; SPREADING DEPRESSION; CEREBROVASCULAR REACTIVITY; DOPPLER SONOGRAPHY; OXYGEN-METABOLISM; AURA AB Research into migraine pathophysiology has been hampered by the episodic nature and unpredictable onset of migraine attacks. Recently, newer imaging techniques have been providing noninvasive methods of studying metabolism and hemodynamics in the brains of migraineurs during and between acute attacks. Xe-133 blood flow techniques, transcranial Doppler, and SPECT have all been employed to investigate hemodynamic changes during migraine aura. PET has been useful in the study of migraine without aura, with findings of increased blood flow related to pain in cortical areas and in the medial brainstem. Currently, three functional MRI imaging techniques are being used in migraine research. Diffusion-weighted imaging has shown normal findings in measures of the ability of neurons to maintain osmotic gradients. Studies using perfusion-weighted imaging have shown alterations in relative cerebral blood flow (CBF), relative cerebral blood volume, and mean transit time during migraine visual aura. The blood oxygen level-dependent technique can supply information related to neuronal activation during acute migraine aura. MRS has been used with mixed success to look for evidence of abnormal energy metabolism in the brains of migraineurs. Magnetoencephalography studies support the presence of a spreading depression-like phenomenon in migraine with aura. Two groups have used transcranial magnetic stimulation to assess whether neurons in the occipital cortex are hyperexcitable, predisposing patients to develop aura symptoms. Despite conflicting findings, migraine with visual aura appears to be generally associated with transient decreases in regional CBF. C1 Brigham & Womens Hosp, Massachusetts Gen Hosp, Partners Headdache Ctr, Dept Neurol, Boston, MA USA. Brigham & Womens Hosp, Massachusetts Gen Hosp, Partners Headdache Ctr, Dept Neurosurg, Boston, MA USA. RP Cutrer, FM (reprint author), Massachusetts Gen Hosp, 149 13th St,CNY 6403, Charlestown, MA 02129 USA. NR 63 TC 36 Z9 37 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 2000 VL 55 IS 9 SU 2 BP S36 EP S45 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 373WM UT WOS:000165313100008 PM 11089518 ER PT J AU Fava, M Kendler, KS AF Fava, M Kendler, KS TI Major depressive disorder SO NEURON LA English DT Review ID STRESSFUL LIFE EVENTS; SEROTONIN TRANSPORTER; TOMOGRAPHY C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Dept Psychiat, ACC 812,15 Parkman St, Boston, MA 02114 USA. NR 34 TC 225 Z9 238 U1 8 U2 28 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD NOV PY 2000 VL 28 IS 2 BP 335 EP 341 DI 10.1016/S0896-6273(00)00112-4 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 377CE UT WOS:000165493700008 PM 11144343 ER PT J AU Graybiel, AM Rauch, SL AF Graybiel, AM Rauch, SL TI Toward a neurobiology of obsessive-compulsive disorder SO NEURON LA English DT Review ID NIGROSTRIATAL DOPAMINE SYSTEM; TONICALLY ACTIVE NEURONS; ORBITOFRONTAL CORTEX; BASAL GANGLIA; PRIMATES STRIATUM; PREFRONTAL CORTEX; BEHAVIOR; MOTOR; RESPONSES; CINGULATE C1 MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Graybiel, AM (reprint author), MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA. NR 34 TC 348 Z9 360 U1 9 U2 40 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD NOV PY 2000 VL 28 IS 2 BP 343 EP 347 DI 10.1016/S0896-6273(00)00113-6 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 377CE UT WOS:000165493700009 PM 11144344 ER PT J AU Bello, L Zhang, JP Nikas, DC Strasser, JF Villani, RM Cheresh, DA Carroll, RS Black, PM AF Bello, L Zhang, JP Nikas, DC Strasser, JF Villani, RM Cheresh, DA Carroll, RS Black, PM TI alpha v beta 3 and alpha v beta 5 integrin expression in meningiomas SO NEUROSURGERY LA English DT Article DE angiogenesis; growth factors; integrins; meningiomas ID ENDOTHELIAL GROWTH-FACTOR; EXTRACELLULAR-MATRIX PROTEINS; VASCULAR-PERMEABILITY FACTOR; HUMAN BRAIN-TUMORS; FACTOR RECEPTORS; ALPHA(V)BETA(3) INTEGRIN; BIOLOGICAL-ACTIVITY; ADHESION MOLECULES; CELL ATTACHMENT; ANGIOGENESIS AB OBJECTIVE: Integrins are emerging as alternative receptors capable of mediating several biological functions, such as cell-matrix and cell-cell adhesion, cell migration, signal transduction, and angiogenesis. Two alphav integrins, i.e., alphav beta3 and alphav beta5, play critical roles in mediating these activities, particularly in tumors. No data are available on the expression of these integrins in meningiomas. METHODS: Using Western blot and immunohistochemical analyses with LM609 and PG32, two monoclonal antibodies capable of recognizing the functional integrin heterodimer, we evaluated the expression of alphav beta3 and alphav beta5 integrins in a series of 34 meningiomas of different histological subtypes and grades. We studied their expression in tumor cells and vasculature, as well as the expression of their related angiogenic factors (fibroblast growth factor 2 and vascular endothelial growth factor) and the alphav beta3 ligand vitronectin. RESULTS: alphav beta3 and alphav beta5 integrins were expressed by neoplastic vasculature and cells. alphav beta3 and alphav beta5 expression was associated and correlated with that of their respective growth factors (fibroblast growth factor 2 and vascular endothelial growth factor) and microvessel counts and densities. alphav beta3 was more strongly expressed than alphav beta5 in two cases of histologically benign meningiomas with aggressive clinical behavior. alphav beta3 expression was associated with that of its related ligand vitronectin and was also evident in small vessels of brain tissue closely surrounding meningiomas. CONCLUSION: Our data demonstrate the expression of alphav beta3 and alphav beta5 integrins in meningioma cells and vasculature. Our findings suggest a role for both of these integrins, and particularly alphav beta3, in meningioma angiogenesis. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Neurosurg, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Brain Tumor Lab, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Milan, Osped Maggiore Policlin, IRCCS, Inst Neurosurg, I-20122 Milan, Italy. Scripps Res Inst, Dept Immunol & Vasc Biol, La Jolla, CA USA. CNR, Ctr Mol & Cellular Pharmacol, Dept Pharmacol, I-20133 Milan, Italy. RP Bello, L (reprint author), Univ Milan, Osped Maggiore Policlin, IRCCS, Inst Neurosurg, Via Francesco Sforza 35, I-20122 Milan, Italy. NR 42 TC 29 Z9 31 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD NOV PY 2000 VL 47 IS 5 BP 1185 EP 1195 DI 10.1097/00006123-200011000-00035 PG 11 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 368YE UT WOS:000090144400084 PM 11063113 ER PT J AU Grinspoon, S AF Grinspoon, S TI Measurement and clinical significance of body-composition changes in HIV disease SO NUTRITION LA English DT Editorial Material ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; PLACEBO-CONTROLLED TRIAL; ENERGY-EXPENDITURE; WASTING SYNDROME; VIRUS INFECTION; MEN; WOMEN; AIDS C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B,55 Fruit St, Boston, MA 02114 USA. NR 23 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0899-9007 J9 NUTRITION JI Nutrition PD NOV-DEC PY 2000 VL 16 IS 11-12 BP 1102 EP 1104 DI 10.1016/S0899-9007(00)00444-5 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 382NG UT WOS:000165828700018 PM 11118838 ER PT J AU Suh-Burgmann, EJ Whall-Strojwas, D Chang, YC Hundley, D Goodman, A AF Suh-Burgmann, EJ Whall-Strojwas, D Chang, YC Hundley, D Goodman, A TI Risk factors for cervical stenosis after loop electrocautery excision procedure SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID IN-VITRO FERTILIZATION; INTRAEPITHELIAL NEOPLASIA; CONE BIOPSY; TRANSFORMATION ZONE; EMBRYO-TRANSFER; COLD-KNIFE; SINGLE-VISIT; CONIZATION; DIAGNOSIS; LASER AB Objective: To assess frequency of and identify risk factors for the development of cervical stenosis after loop electrosurgical excision procedure. Methods: We reviewed outpatient charts of women treated by loop excision for cervical dysplasia between August 1996 and January 1998 in the colposcopy clinic at Massachusetts General Hospital. One hundred sixty-four women were evaluated for cervical stenosis during follow-up. Stenosis was considered present if manual dilation was required to allow endocervical sampling with an endocervical currette 3 mm wide. Multivariable analysis with stepwise logistic regression was used to evaluate age, parity, tobacco use, hormonal status, use of oral contraceptives, pathology, previous loop excision, performance of additional endocervical excision, and dimensions of excision specimens as predictors of cervical stenosis. Results: The average age was 32 years. Cervical stenosis occurred in ten of 164 women (6%, 95% CI 3%, 11%). Among factors analyzed, previous loop excision and volume of excision specimen were the only independent predictors of stenosis. Conclusion: Cervical stenosis correlated with history of loop excision and volume of tissue removed, suggesting that women who have second excisions or large excisions should be counseled that their risk of stenosis might be higher. (Obstet Gynecol 2000;96:657-60. (C) 2000 by The American College of Obstetricians and Gynecologists). C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Goodman, A (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 27 TC 31 Z9 40 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2000 VL 96 IS 5 BP 657 EP 660 DI 10.1016/S0029-7844(00)00993-5 PN 1 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 367WK UT WOS:000090084300004 PM 11042296 ER PT J AU Ferrer, RL Sibai, BM Mulrow, CD Chiquette, E Stevens, KR Cornell, J AF Ferrer, RL Sibai, BM Mulrow, CD Chiquette, E Stevens, KR Cornell, J TI Management of mild chronic hypertension during pregnancy: A review SO OBSTETRICS AND GYNECOLOGY LA English DT Review ID LOW-DOSE ASPIRIN; CONVERTING ENZYME-INHIBITORS; RANDOMIZED CONTROLLED TRIAL; HIGH-RISK PREGNANCY; LOW-BIRTH-WEIGHT; LATE FETAL DEATH; ABRUPTIO PLACENTAE; ANTIHYPERTENSIVE TREATMENT; MODERATE HYPERTENSION; MATERNAL HYPERTENSION AB Objective: To conduct a systematic review of evidence relating to management of mild chronic hypertension during pregnancy, including associated risks, benefits, and harms of treatment with antihypertensive agents, nonpharmacologic measures, and aspirin and benefits of various monitoring strategies. Data Sources: Using four broad search strategies, we searched English and non-English-language citations in 16 electronic databases from their inception to February 1999 and consulted relevant textbooks, references, and experts. Study Selection: Reviewers screened 6228 abstracts and found 215 articles that met multiple prespecified patient selection, study population, and design criteria. Tabulation, Integration, and Results: Forty-six studies consistently showed that chronic hypertension triples the risk for perinatal mortality (odds ratio [OR] 3.4; 95% confidence interval [CI] 3.0, 3.7) and doubles the risk for placental abruption (OR 2.1; 95% CI 1.1, 3.9). Thirteen small, randomized controlled trials had inadequate power to rule in or rule out moderate-to-large (20%-50%) benefits of antihypertensive treatment. Possible adverse effects were fetal renal failure when angiotensin-converting enzyme inhibitors are used in the second or third trimester and growth restriction when atenolol is used early in pregnancy. Trials showed that aspirin neither reduces nor increases perinatal and maternal morbidity, but they did not rule out possible small-to moderate beneficial or adverse effects. No studies provide guidance on benefits or consequences of various nonpharmacologic therapies or monitoring strategies. Conclusion: Mild chronic hypertension is associated with increased maternal and fetal risks. Beneficial treatment and monitoring regimens are not clear, but some treatments, such as angiotensin-converting enzyme inhibitors, are best avoided. (Obstet Gynecol 2000;96:849-60. (C) 2000 by The American College of Obstetricians and Gynecologists.). C1 Univ Texas, Hlth Sci Ctr, Dept Family Med, San Antonio, TX USA. Univ Tennessee, Div Obstet & Gynecol, Memphis, TN USA. Univ Texas, Hlth Sci Ctr, Div Gen Med, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Vet Evidence Based Res Disseminat & Implementat C, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Sch Nursing, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Div Geriatr & Gerontol, San Antonio, TX USA. RP Ferrer, RL (reprint author), Audie L Murphy Mem Vet Hosp, 11C,7400 Merton Minter Blvd, San Antonio, TX 78284 USA. RI Ferrer, Robert/A-6854-2009 NR 113 TC 76 Z9 81 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2000 VL 96 IS 5 SU S BP 849 EP 860 DI 10.1016/S0029-7844(00)00938-8 PN 2 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 368QX UT WOS:000090130000030 PM 11094241 ER PT J AU Carlson, RW Anderson, BO Bensinger, W Cox, CE Davidson, NE Edge, SB Farrar, WB Goldstein, LJ Gradishar, WJ Lichter, AS McCormick, B Nabell, LM Reed, EC Silver, SM Smith, ML Somlo, G Theriault, R Ward, JH Winer, EP Wolff, A AF Carlson, RW Anderson, BO Bensinger, W Cox, CE Davidson, NE Edge, SB Farrar, WB Goldstein, LJ Gradishar, WJ Lichter, AS McCormick, B Nabell, LM Reed, EC Silver, SM Smith, ML Somlo, G Theriault, R Ward, JH Winer, EP Wolff, A CA NCCN TI NCCN Practice Guidelines for breast cancer SO ONCOLOGY-NEW YORK LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; SURGICAL-ADJUVANT-BREAST; LYMPH-NODE BIOPSY; FOLLOW-UP; POSTOPERATIVE RADIOTHERAPY; PREMENOPAUSAL WOMEN; BONE METASTASES; SENTINEL-NODE; CHEMOTHERAPY; TAMOXIFEN C1 NCCN, Rockledge, PA 19046 USA. Stanford Hosp & Clin, Palo Alto, CA 94304 USA. Univ Washington, Med Ctr, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ S Florida, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33682 USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. James Canc Hosp, Columbus, OH 43214 USA. Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. Univ Nebraska, Med Ctr, Eppley Canc Ctr, Omaha, NE 68105 USA. City Hope Natl Med Ctr, Los Angeles, CA 90024 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Carlson, RW (reprint author), NCCN, 50 Huntington Pike,Suite 200, Rockledge, PA 19046 USA. OI Wolff, Antonio/0000-0003-3734-1063 NR 45 TC 65 Z9 66 U1 1 U2 5 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 NOV PY 2000 VL 14 IS 11A SU 10 BP 33 EP 49 PG 17 WC Oncology SC Oncology GA 397TP UT WOS:000166713700003 PM 11195418 ER PT J AU O'Donnell, MR Appelbaum, FR Baer, MR Carabasi, MH Coutre, SE Erba, HP Estey, E Glenn, MJ Kraut, EH Maslak, P Millenson, M Miller, CB Saba, HI Stone, R Tallman, MS AF O'Donnell, MR Appelbaum, FR Baer, MR Carabasi, MH Coutre, SE Erba, HP Estey, E Glenn, MJ Kraut, EH Maslak, P Millenson, M Miller, CB Saba, HI Stone, R Tallman, MS CA NCCN TI NCCN Practice Guidelines for acute myelogenous leukemia SO ONCOLOGY-NEW YORK LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; BONE-MARROW TRANSPLANTATION; HIGH-DOSE CYTARABINE; ARSENIC TRIOXIDE; FIRST REMISSION; ONCOLOGY-GROUP; CHEMOTHERAPY; INDUCTION; TRIAL C1 NCCN, Rockledge, PA 19046 USA. City Hope Natl Med Ctr, Los Angeles, CA 90024 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. Stanford Hosp & Clin, Stanford, CA 94305 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Utah, Salt Lake City, UT 84112 USA. Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. James Canc Hosp, Columbus, OH 43201 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Univ S Florida, Inst Res, Tampa, FL 33612 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. RP O'Donnell, MR (reprint author), NCCN, 50 Huntington Pike,Suite 200, Rockledge, PA 19046 USA. NR 22 TC 1 Z9 1 U1 0 U2 2 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 NOV PY 2000 VL 14 IS 11A SU 10 BP 53 EP 61 PG 9 WC Oncology SC Oncology GA 397TP UT WOS:000166713700004 ER PT J AU Baker, LH Bahnson, RR Hanks, GE Huben, RP Kantoff, P Kozlowski, JM Kuettel, M Lange, PH Logothetis, C Pow-Sang, JM Roach, M Sandler, H Scardino, PT Taylor, RJ Urban, DA Walsh, PC Wilson, TG AF Baker, LH Bahnson, RR Hanks, GE Huben, RP Kantoff, P Kozlowski, JM Kuettel, M Lange, PH Logothetis, C Pow-Sang, JM Roach, M Sandler, H Scardino, PT Taylor, RJ Urban, DA Walsh, PC Wilson, TG CA NCCN TI NCCN Practice Guidelines for prostate cancer SO ONCOLOGY-NEW YORK LA English DT Article ID FLUTAMIDE C1 NCCN, Rockledge, PA 19046 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. Ohio State Univ, James Canc Hosp, Columbus, OH 43210 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Univ Washington, Med Ctr, Seattle, WA 98195 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Univ Calif San Francisco, Mt Zion canc Ctr, San Francisco, CA 94143 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Univ Nebraska, Med Ctr, Eppley Canc Ctr, Omaha, NE 68105 USA. Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. City Hope Natl Med Ctr, Los Angeles, CA 90024 USA. RP Baker, LH (reprint author), NCCN, 50 Huntington Pike,Suite 200, Rockledge, PA 19046 USA. NR 8 TC 6 Z9 7 U1 0 U2 1 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD NOV PY 2000 VL 14 IS 11A SU 10 BP 111 EP 119 PG 9 WC Oncology SC Oncology GA 397TP UT WOS:000166713700013 ER PT J AU Mock, V Atkinson, A Barsevick, A Cella, D Cimprich, B Cleeland, C Donnelly, J Eisenberger, MA Escalante, C Hinds, P Jacobsen, PB Kaldor, P Knight, SJ Peterman, A Piper, BF Rugo, H Sabbatini, P Stahl, C AF Mock, V Atkinson, A Barsevick, A Cella, D Cimprich, B Cleeland, C Donnelly, J Eisenberger, MA Escalante, C Hinds, P Jacobsen, PB Kaldor, P Knight, SJ Peterman, A Piper, BF Rugo, H Sabbatini, P Stahl, C CA NCCN TI NCCN Practice Guidelines for cancer-related fatigue SO ONCOLOGY-NEW YORK LA English DT Article ID QUALITY-OF-LIFE; STEM-CELL TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY; BREAST-CANCER; AEROBIC EXERCISE; ADJUVANT CHEMOTHERAPY; HEALTHY-INDIVIDUALS; COMMUNITY ONCOLOGY; THERAPY; INTERVENTION C1 NCCN, Rockledge, PA 19046 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. City Hope Natl Med Ctr, Los Angeles, CA 90024 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Ohio State Univ, James Canc Hosp, Columbus, OH 43210 USA. Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif San Francisco, Med Ctr, San Francisco, CA 94143 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. RP Mock, V (reprint author), NCCN, 50 Huntington Pike,Suite 200, Rockledge, PA 19046 USA. OI Barsevick, Andrea/0000-0003-1829-6826 NR 56 TC 197 Z9 208 U1 1 U2 13 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 NOV PY 2000 VL 14 IS 11A SU 10 BP 151 EP 161 PG 11 WC Oncology SC Oncology GA 397TP UT WOS:000166713700016 PM 11195408 ER PT J AU Forastiere, AA Pfister, DG Ang, K Brockstein, B Colevas, AD Ellenhorn, J Goepfert, H Hicks, WL Hong, WK Kies, MS Lydiatt, W McCaffrey, T Mittal, BB Ridge, JA Schuller, DE Shah, JP Spencer, S Trotti, A Urba, S Weymuller, EA Wheeler, RH Wolf, GT AF Forastiere, AA Pfister, DG Ang, K Brockstein, B Colevas, AD Ellenhorn, J Goepfert, H Hicks, WL Hong, WK Kies, MS Lydiatt, W McCaffrey, T Mittal, BB Ridge, JA Schuller, DE Shah, JP Spencer, S Trotti, A Urba, S Weymuller, EA Wheeler, RH Wolf, GT CA NCCN TI NCCN Practice Guidelines for head and neck cancers SO ONCOLOGY-NEW YORK LA English DT Article ID SQUAMOUS-CELL CARCINOMA; POSTOPERATIVE RADIATION-THERAPY; LOCALLY ADVANCED HEAD; RANDOMIZED TRIAL; ORAL CAVITY; PHASE-III; GLOTTIC CANCER; CONVENTIONAL FRACTIONATION; NASOPHARYNGEAL CARCINOMA; CONCURRENT CHEMOTHERAPY C1 NCCN, Rockledge, PA 19046 USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Northwestern Univ, Evanston Hosp, Evanston, IL 60201 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. City Hope Natl Med Ctr, Los Angeles, CA 90024 USA. New York State Dept Hlth, Roswell Pk Mem Inst, Buffalo, NY 14263 USA. Univ Nebraska, Med Ctr, Eppley Canc Ctr, Omaha, NE 68105 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. Northwestern Univ, Robert H Lurie Comprehens Ctr, Chicago, IL 60611 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Ohio State Univ, James Canc Hosp, Columbus, OH 43210 USA. Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Univ Washington, Med Ctr, Seattle, WA 98195 USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. RP Forastiere, AA (reprint author), NCCN, 50 Huntington Pike,Suite 200, Rockledge, PA 19046 USA. OI Shah, Jatin/0000-0002-6444-6592 NR 70 TC 10 Z9 10 U1 0 U2 0 PU UBM MEDICA PI NORWALK PA 535 CONNECTICUT AVE, STE 300, NORWALK, CT 06854 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD NOV PY 2000 VL 14 IS 11A SU 10 BP 163 EP 194 PG 32 WC Oncology SC Oncology GA 397TP UT WOS:000166713700017 ER PT J AU Engstrom, PF Benson, A Choti, MA Cohen, AM Doroshow, JH Fuchs, C Kiel, K Martin, EW McGinn, C Petrelli, NJ Posey, JA Skibber, JM Venook, A Yeatman, TJ AF Engstrom, PF Benson, A Choti, MA Cohen, AM Doroshow, JH Fuchs, C Kiel, K Martin, EW McGinn, C Petrelli, NJ Posey, JA Skibber, JM Venook, A Yeatman, TJ CA NCCN TI NCCN Practice Guidelines for colorectal cancer SO ONCOLOGY-NEW YORK LA English DT Article ID POSTOPERATIVE RADIATION-THERAPY; RECTAL-CANCER; ADJUVANT THERAPY; COLON-CANCER; SPHINCTER PRESERVATION; FAMILY HISTORY; LOCAL EXCISION; FOLLOW-UP; FLUOROURACIL; CARCINOMA C1 NCCN, Rockledge, PA 19046 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. City Hope Natl Med Ctr, Los Angeles, CA 90024 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Ohio State Univ, James Canc Hosp, Columbus, OH 43210 USA. Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif San Francisco, Med Ctr, San Francisco, CA 94143 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. RP Engstrom, PF (reprint author), NCCN, 50 Huntington Pike,Suite 200, Rockledge, PA 19046 USA. NR 37 TC 2 Z9 2 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 NOV PY 2000 VL 14 IS 11A SU 10 BP 203 EP 212 PG 10 WC Oncology SC Oncology GA 397TP UT WOS:000166713700019 ER PT J AU Czito, BG Willett, CG Clark, JW Del Castillo, CF AF Czito, BG Willett, CG Clark, JW Del Castillo, CF TI Current perspectives on locally advanced pancreatic cancer SO ONCOLOGY-NEW YORK LA English DT Article ID INTRAOPERATIVE RADIATION-THERAPY; RANDOMIZED CONTROLLED TRIAL; EXTERNAL BEAM IRRADIATION; P53 GENE-MUTATIONS; PREOPERATIVE CHEMORADIATION; CONCURRENT RADIATION; PERITONEAL CYTOLOGY; CLINICAL BENEFIT; ADENOCARCINOMA; CARCINOMA AB This year, approximately 40% of the 28,300 patients diagnosed with pancreatic carcinoma in the United States will present with focally advanced disease. Radiotherapeutic approaches are often employed, as these patients have unresectable tumors by virtue of local invasion into the retroperitoneal vessels in the absence of clinically detectable metastases, These treatments include external-beam irradiation with and without fluorouracil (5-FU)-based chemotherapy, intraoperative irradiation, and more recently, external-beam irradiation with new systemic agents, such as gencitabine (Gemzar). C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Czito, BG (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 48 TC 12 Z9 12 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 NOV PY 2000 VL 14 IS 11 BP 1535 EP 1545 PG 11 WC Oncology SC Oncology GA 397AN UT WOS:000166670900006 PM 11125940 ER PT J AU Garber, J AF Garber, J TI Screening for ovarian cancer: What we know, what we need to know - Review SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID BRCA1; RISK C1 Dana Farber Canc Inst, Canc Risk & Prevent Clin, Dept Canc Epidemiol & Control, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Garber, J (reprint author), Dana Farber Canc Inst, Canc Risk & Prevent Clin, Dept Canc Epidemiol & Control, Boston, MA 02115 USA. NR 7 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 NOV PY 2000 VL 14 IS 11 BP 1615 EP 1616 PG 2 WC Oncology SC Oncology GA 397AN UT WOS:000166670900019 ER PT J AU Wick, W Hochberg, F O'Sullivan, J Goessling, A Hughes, A Cher, L AF Wick, W Hochberg, F O'Sullivan, J Goessling, A Hughes, A Cher, L TI L-dopa-resistant parkinsonism syndrome following cerebral radiation therapy for neoplasm SO ONCOLOGY REPORTS LA English DT Article DE parkinsonism; radiation; brain tumor ID SUBSTANTIA NIGRA; DISEASE; INTOXICATION; MECHANISMS; NECROSIS; FEATURES; DEATH AB A bradykinetic form of parkinsonism, unresponsive to levo-dopa therapy developed in four patients two to eight weeks after completion of external beam irradiation (39.2 Gy to 59.4 Gy) of their intracranial neoplasm. In the absence of other causative factors, we relate the movement disorder to radiation-induced changes within the basal ganglia. At post mortem examination one patient had putamenal gliosis and thickened vessels with loss of nigral neurons. C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Austin & Repatriat Ctr, Dept Neurol, Heidelberg, Vic, Australia. Austin & Repatriat Ctr, Dept Oncol, Heidelberg, Vic, Australia. RP Wick, W (reprint author), Univ Tubingen, Dept Neurol, Hoppe Seyler Str 3, D-72076 Tubingen, Germany. RI O'Sullivan, John/C-6119-2013 NR 29 TC 6 Z9 6 U1 0 U2 2 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD NOV-DEC PY 2000 VL 7 IS 6 BP 1367 EP 1370 PG 4 WC Oncology SC Oncology GA 362ZR UT WOS:000089808600035 PM 11032946 ER PT J AU Rajagopal, J Kinane, TB AF Rajagopal, J Kinane, TB TI Is there more to lung development than steroids and surfactant? SO PEDIATRICS LA English DT Article ID PULMONARY C1 Massachusetts Gen Hosp, Pediat Pulm Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kinane, TB (reprint author), Massachusetts Gen Hosp, Pediat Pulm Unit, Vincent Burham Basement,55 Fruit St, Boston, MA 02114 USA. NR 6 TC 3 Z9 3 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2000 VL 106 IS 5 BP 1103 EP 1104 DI 10.1542/peds.106.5.1103 PN 1 PG 2 WC Pediatrics SC Pediatrics GA 369ED UT WOS:000165052300023 PM 11061782 ER PT J AU Kleinman, RE AF Kleinman, RE TI American Academy of Pediatrics recommendations for complementary feeding SO PEDIATRICS LA English DT Article; Proceedings Paper CT Research Priorities in Complementary Feeding: International-Paediatric-Association/European-Society-of-Paediatric-Gast roenterology-Hepatology-and-Nutrition Workshop CY AUG 26-28, 1999 CL CASABLANCA, MOROCCO SP Int Paediatr Assoc, European Soc Paediatr Gastroenterol Hepatol & Nutr C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02114 USA. RP Kleinman, RE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02114 USA. NR 1 TC 21 Z9 22 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2000 VL 106 IS 5 SU S BP 1274 EP 1274 PN 3 PG 1 WC Pediatrics SC Pediatrics GA 369EK UT WOS:000165052900004 PM 11061819 ER PT J AU Kleinman, RE AF Kleinman, RE TI Complementary feeding and neuromuscular development SO PEDIATRICS LA English DT Article; Proceedings Paper CT Research Priorities in Complementary Feeding: International-Paediatric-Association/European-Society-of-Paediatric-Gast roenterology-Hepatology-and-Nutrition Workshop CY AUG 26-28, 1999 CL CASABLANCA, MOROCCO SP Int Paediatr Assoc, European Soc Paediatr Gastroenterol Hepatol & Nutr C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Gastrointestinal & Nutr Unit, Boston, MA 02114 USA. RP Kleinman, RE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Gastrointestinal & Nutr Unit, Boston, MA 02114 USA. NR 1 TC 1 Z9 1 U1 1 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2000 VL 106 IS 5 SU S BP 1279 EP 1279 PN 3 PG 1 WC Pediatrics SC Pediatrics GA 369EK UT WOS:000165052900010 PM 11061825 ER PT J AU Kleinman, RE AF Kleinman, RE TI Complementary feeding and later health SO PEDIATRICS LA English DT Article; Proceedings Paper CT Research Priorities in Complementary Feeding: International-Paediatric-Association/European-Society-of-Paediatric-Gast roenterology-Hepatology-and-Nutrition Workshop CY AUG 26-28, 1999 CL CASABLANCA, MOROCCO SP Int Paediatr Assoc, European Soc Paediatr Gastroenterol Hepatol & Nutr ID DIABETES-MELLITUS; EXPOSURE; LIFE; CELL C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02114 USA. RP Kleinman, RE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat, Boston, MA 02114 USA. NR 14 TC 8 Z9 10 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2000 VL 106 IS 5 SU S BP 1287 EP 1288 PN 3 PG 2 WC Pediatrics SC Pediatrics GA 369EK UT WOS:000165052900019 PM 11061834 ER PT J AU Martinez, V Tache, Y AF Martinez, V Tache, Y TI Bombesin and the brain-gut axis SO PEPTIDES LA English DT Article DE amphibian skin peptides; regulatory peptides; gut function; gastric secretion; gastric motility; hypothalamic nuclei; vague nerve; autonomic pathways ID GASTRIC-ACID SECRETION; CENTRAL-NERVOUS-SYSTEM; DORSAL VAGAL COMPLEX; THYROTROPIN-RELEASING-HORMONE; INTRACISTERNAL BOMBESIN; ADMINISTERED BOMBESIN; MAMMALIAN BOMBESIN; MOTOR NUCLEUS; PARAVENTRICULAR NUCLEUS; RAT-BRAIN AB Bombesin is the first peptide shown to act in the brain to influence gastric function and the most potent peptide to inhibit acid secretion when injected into the cerebrospinal fluid (CSF) in rats and dogs. Bombesin responsive sites include specific hypothalamic nuclei (paraventricular nucleus, preoptic area and anterior hypothalamus), the dorsal vagal complex as well as spinal sites at T9-T10. The antisecretory effect of central bombesin encompasses a variety of endocrine/paracrine (gastrin, histamine) or neuronal stimulants. Bombesin into the CSF induces an integrated gastric response (increase in bicarbonate, and mucus, inhibition of acid, pepsin, vagally mediated contractions) enhancing the resistance of the mucosa to injury through autonomic pathways. The physiological significance of central action of bombesin on gastric function is still to be unraveled. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Univ Calif Los Angeles, Sch Med, CURE Digest Dis Res Ctr,Digest Dis Div, VA Greater Los Angeles Healthcare Syst,Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, Los Angeles, CA 90073 USA. CEU San Pablo, Sch Vet, Dept Physiol, Valencia 46113, Spain. RP Tache, Y (reprint author), Univ Calif Los Angeles, Sch Med, CURE Digest Dis Res Ctr,Digest Dis Div, VA Greater Los Angeles Healthcare Syst,Dept Med, Los Angeles, CA 90073 USA. RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [DK-30110, DK-41301] NR 90 TC 23 Z9 25 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD NOV PY 2000 VL 21 IS 11 BP 1617 EP 1625 DI 10.1016/S0196-9781(00)00293-X PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 379UK UT WOS:000165660800005 PM 11090915 ER PT J AU Bergeron, B AF Bergeron, B TI Your defensive line against hackers SO PHYSICIAN AND SPORTSMEDICINE LA English DT Article 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 0091-3847 J9 PHYSICIAN SPORTSMED JI Physician Sportsmed. PD NOV PY 2000 VL 28 IS 11 BP A40 EP A40 PG 1 WC Primary Health Care; Orthopedics; Sport Sciences SC General & Internal Medicine; Orthopedics; Sport Sciences GA 373JL UT WOS:000165285700014 ER PT J AU Badawi, RD Ferreira, NC Kohlmyer, SG Dahlbom, M Marsden, PK Lewellen, TK AF Badawi, RD Ferreira, NC Kohlmyer, SG Dahlbom, M Marsden, PK Lewellen, TK TI A comparison of normalization effects on three whole-body cylindrical 3D PET systems SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID DETECTOR EFFICIENCY; SCATTER CORRECTION; RETRACTABLE SEPTA; PERFORMANCE; TOMOGRAPH; BRAIN AB Normalization coefficients in three-dimensional positron emission tomography (3D PET) are affected by parameters such as camera geometry and the design and arrangement of the block detectors. In this work, normalization components for three whole-body 3D-capable tomographs (the GE Advance, the Siemens/CTI962/HR+ and the Siemens/CTI 951R) are compared by means of a series of scans using uniform cylindrical and rotating line sources. Where applicable, the manufacturers' normalization methods are validated, and it is shown that these methods can be improved upon by using previously published normalization protocols. Those architectural differences between the three tomographs that affect normalization are discussed with a view to drawing more general conclusions about the effect of machine architecture on normalization. The data presented suggest that uniformity of system response becomes easier to achieve as the uniformity of crystal response within the detector block is improved. C1 Dana Farber Canc Inst, Div Nucl Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Washington, Div Nucl Med, Seattle, WA 98195 USA. CEA, Serv Hosp Frederic Joliot, F-91406 Orsay, France. Univ Coimbra, Fac Med, Serv Biofis, P-3000 Coimbra, Portugal. Univ Calif Los Angeles, Sch Med, Div Nucl Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA. Univ London Kings Coll, Div Radiol Sci & Med Engn, Guys & St Thomas Clin PET Ctr, London WC2R 2LS, England. RP Badawi, RD (reprint author), Dana Farber Canc Inst, Div Nucl Med, 44 Binney St, Boston, MA 02115 USA. RI Tewatia, Dinesh/D-5897-2012; Ferreira, Nuno/B-5687-2014 OI Ferreira, Nuno/0000-0002-8278-5037 FU NCI NIH HHS [CA42593] NR 21 TC 9 Z9 9 U1 0 U2 3 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD NOV PY 2000 VL 45 IS 11 BP 3253 EP 3266 DI 10.1088/0031-9155/45/11/310 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 374KD UT WOS:000165343600010 PM 11098902 ER PT J AU Clarke, JD Volko, SM Ledford, H Ausubel, FM Dong, XN AF Clarke, JD Volko, SM Ledford, H Ausubel, FM Dong, XN TI Roles of salicylic acid, jasmonic acid, and ethylene in cpr-induced resistance in Arabidopsis SO PLANT CELL LA English DT Article ID SYSTEMIC ACQUIRED-RESISTANCE; PLANT-DISEASE-RESISTANCE; TOBACCO MOSAIC-VIRUS; PATHOGENESIS-RELATED PROTEINS; SIGNAL-TRANSDUCTION PATHWAY; DEPENDENT DEFENSE-RESPONSE; RACE-SPECIFIC ELICITORS; FOR-GENE CONCEPT; CELL-DEATH; SUSCEPTIBILITY MUTANTS AB Disease resistance in Arabidopsis is regulated by multiple signal transduction pathways in which salicylic acid (SA), jasmonic acid (JA), and ethylene (ET) function as key signaling molecules. Epistasis analyses were performed between mutants that disrupt these pathways (npr1, eds5, ein2, and jar1) and mutants that constitutively activate these pathways (cpr1, cpr5, and cpr6), allowing exploration of the relationship between the SA- and JA/ET-mediated resistance responses. Two important findings were made. First, the constitutive disease resistance exhibited by cpr1, cpr5, and cpr6 is completely suppressed by the SA-deficient eds5 mutant but is only partially affected by the SA-insensitive npr1 mutant. Moreover, eds5 suppresses the SA-accumulating phenotype of the cpr mutants, whereas npr1 enhances it. These data indicate the existence of an SA-mediated, NPR1-independent resistance response. Second, the ET-insensitive mutation ein2 and the JA-insensitive mutation jar1 suppress the NPR1-independent resistance response exhibited by cpr5 and cpr6. Furthermore, ein2 potentiates SA accumulation in cpr5 and cpr5 npr1 while dampening SA accumulation in cpr6 and cpr6 npr1. These latter results indicate that cpr5 and cpr6 regulate resistance through distinct pathways and that SA-mediated, NPR1-independent resistance works in combination with components of the JA/ET-mediated response pathways. C1 Duke Univ, Dept Biol, Dev Cell & Mol Biol Grp, Durham, NC 27708 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. RP Dong, XN (reprint author), Duke Univ, Dept Biol, Dev Cell & Mol Biol Grp, Durham, NC 27708 USA. FU NIGMS NIH HHS [GM48707, R01 GM048707, R37 GM048707] NR 86 TC 236 Z9 261 U1 2 U2 30 PU AMER SOC PLANT PHYSIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 1040-4651 J9 PLANT CELL JI Plant Cell PD NOV PY 2000 VL 12 IS 11 BP 2175 EP 2190 DI 10.1105/tpc.12.11.2175 PG 16 WC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology SC Biochemistry & Molecular Biology; Plant Sciences; Cell Biology GA 384AM UT WOS:000165916900012 PM 11090217 ER PT J AU Xiao, WY Sheen, J Jang, JC AF Xiao, WY Sheen, J Jang, JC TI The role of hexokinase in plant sugar signal transduction and growth and development SO PLANT MOLECULAR BIOLOGY LA English DT Article DE development; hexokinase; senescence; sugar signaling ID TRANSGENIC TOBACCO PLANTS; YEAST-DERIVED INVERTASE; TISSUE-SPECIFIC EXPRESSION; CELL-WALL INVERTASE; GENE-EXPRESSION; ARABIDOPSIS-THALIANA; CHENOPODIUM-RUBRUM; SACCHAROMYCES-CEREVISIAE; CATABOLITE REPRESSION; APOPLASTIC INVERTASE AB Previous studies have revealed a central role of Arabidopsis thaliana hexokinases (AtHXK1 and AtHXK2) in the glucose repression of photosynthetic genes and early seedling development. However, it remains unclear whether HXK can modulate the expression of diverse sugar-regulated genes. On the basis of the results of analyses of gene expression in HXK transgenic plants, we suggest that three distinct glucose signal transduction pathways exist in plants. The first is an AtHXK1-dependent pathway in which gene expression is correlated with the AtHXK1-mediated signaling function. The second is a glycolysis-dependent pathway that is influenced by the catalytic activity of both AtHXK1 and the heterologous yeast Hxk2. The last is an AtHXK1-independent pathway in which gene expression is independent of AtHXK1. Further investigation of HXK transgenic Arabidopsis discloses a role of HXK in glucose-dependent growth and senescence. In the absence of exogenous glucose, plant growth is limited to the seedling stage with restricted true leaf development even after a 3-week culture on MS medium. In the presence of glucose, however, over-expressing Arabidopsis or yeast HXK in plants results in the repression of growth and true leaf development, and early senescence, while under-expressing AtHXK1 delays the senescence process. These studies reveal multiple glucose signal transduction pathways that control diverse genes and processes that are intimately linked to developmental stages and environmental conditions. C1 Ohio State Univ, Dept Hort & Crop Sci, Columbus, OH 43210 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Jang, JC (reprint author), Ohio State Univ, Dept Hort & Crop Sci, Columbus, OH 43210 USA. NR 54 TC 193 Z9 210 U1 3 U2 49 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-4412 J9 PLANT MOL BIOL JI Plant Mol.Biol. PD NOV PY 2000 VL 44 IS 4 BP 451 EP 461 DI 10.1023/A:1026501430422 PG 11 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA 379GK UT WOS:000165633500002 PM 11197321 ER PT J AU Charanek, AM Carramaschi, FR Curado, JH May, JW AF Charanek, AM Carramaschi, FR Curado, JH May, JW TI Refinements in transverse rectus abdominis myocutaneous flap breast reconstruction: Projection and contour improvements - Discussion SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Editorial Material ID TRAM FLAP C1 Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP May, JW (reprint author), Massachusetts Gen Hosp, Div Plast Surg, 15 Parkman St,Suite 453, Boston, MA 02114 USA. NR 3 TC 1 Z9 1 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 NOV PY 2000 VL 106 IS 6 BP 1273 EP 1275 PG 3 WC Surgery SC Surgery GA 370KD UT WOS:000165121600006 ER PT J AU Bergeron, B AF Bergeron, B TI Your defensive line against hackers 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 NOV PY 2000 VL 108 IS 6 BP A40 EP A40 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 372GM UT WOS:000165226000019 ER PT J AU Bromley, B Shipp, TD Benacerraf, B AF Bromley, B Shipp, TD Benacerraf, B TI Isolated polydactyly: prenatal diagnosis and perinatal outcome SO PRENATAL DIAGNOSIS LA English DT Article DE isolated polydactyly; prenatal diagnosis; ultrasound ID ABNORMALITIES; ACCURACY; FETUS; HANDS AB Our objective was to determine the clinical significance of isolated polydactyly identified on prenatal sonogram. All patients with sonographically detected isolated polydactyly scanned over an Ii-year period were identified from our database. All patients underwent detailed surveys, and follow-up was obtained by review of the medical records and telephone conversations with parents and referring physicians. Thirteen patients with isolated polydactyly were identified. Follow-up was available in 12 patients. Indications for referral included advanced maternal age (2), second-opinion polydactyly (4), family history of polydactyly (1), uncertain dates (5), and growth (1). The gestational ages at the times of sonographic diagnosis ranged from 17.5 to 34 weeks with all but one case being identified before 23 weeks. Prenatal identification included polydactyly of the upper limb (8), lower limb (4), and both upper and lower limbs (1). Postaxial polydactyly was seen in 12 patients and preaxial in one. Polydactyly was confirmed in all 12 cases in which follow-up was available. Karyotypes were normal ill all five fetuses in which amniocentesis was performed. Ten of 12 fetuses were born alive, one died in utero at 34 weeks as a complication of severe pre-eclampsia and one died at term as a result of a cord accident. No surviving neonate had any other identifiable malformation or suspected karyotypic abnormality. In conclusion isolated polydactyly identified by prenatal sonography is associated with good perinatal outcome. Copyright (C) 2000 John Wiley & Sons, Ltd. C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Obstet Gynecol & Radiol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet Gynecol & Radiol, Boston, MA 02115 USA. RP Bromley, B (reprint author), Diagnost Ultrasound Associates, 333 Longwood Ave,Suite 400, Boston, MA 02115 USA. NR 13 TC 5 Z9 5 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD NOV PY 2000 VL 20 IS 11 BP 905 EP 908 DI 10.1002/1097-0223(200011)20:11<905::AID-PD934>3.0.CO;2-N PG 4 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA 378YJ UT WOS:000165613000009 PM 11113893 ER PT J AU Simon, NM Pollack, MH AF Simon, NM Pollack, MH TI The current status of the treatment of panic disorder pharmacotherapy and cognitive-behavioral therapy SO PSYCHIATRIC ANNALS LA English DT Article ID SEROTONIN UPTAKE INHIBITORS; CONTROLLED TRIAL; ANXIETY DISORDERS; DOUBLE-BLIND; COMORBIDITY; IMIPRAMINE; CLONAZEPAM; EFFICACY; PLACEBO; ALPRAZOLAM C1 Massachusetts Gen Hosp, Anxiety Disorders Program, Dept Psychiat, Boston, MA 02114 USA. RP Simon, NM (reprint author), Massachusetts Gen Hosp, Anxiety Disorders Program, Dept Psychiat, Wang ACC 812,15 Parkman St, Boston, MA 02114 USA. NR 39 TC 4 Z9 4 U1 1 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD NOV PY 2000 VL 30 IS 11 BP 689 EP 696 PG 8 WC Psychiatry SC Psychiatry GA 371MR UT WOS:000165183200004 ER PT J AU Dreyer, KJ AF Dreyer, KJ TI Why IHE? SO RADIOGRAPHICS LA English DT Editorial Material DE editorials; Radiological Society of North America, 86th Scientific Assembly and Annual Meeting C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Adv Imaging Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Dreyer, KJ (reprint author), Partners Hlth Care, Zero Emerson,Suite 3E, Boston, MA 02114 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD NOV-DEC PY 2000 VL 20 IS 6 BP 1583 EP 1584 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 481FU UT WOS:000171509900008 PM 11112812 ER PT J AU Schaefer, PW Grant, PE Gonzalez, RG AF Schaefer, PW Grant, PE Gonzalez, RG TI Diffusion-weighted MR imaging of the brain SO RADIOLOGY LA English DT Review DE brain, diffusion; brain, infarction; brain, infection; brain, injuries; brain, ischemia; brain, MR; brain neoplasms; sclerosis, multiple; state of the art ID CREUTZFELDT-JAKOB-DISEASE; ACUTE CEREBRAL-ISCHEMIA; HIGH-RESOLUTION MEASUREMENT; TRACER BOLUS PASSAGES; NORMAL WHITE MATTER; FAST SPIN-ECHO; MAGNETIC-RESONANCE; ACUTE STROKE; MULTIPLE-SCLEROSIS; APPARENT DIFFUSION AB Diffusion-weighted magnetic resonance (MR) imaging provides image contrast that is different from that provided by conventional MR techniques. It is particularly sensitive for detection of acute ischemic stroke and differentiation of acute stroke from other processes that manifest with sudden neurologic deficits. Diffusion-weighted MR imaging also provides adjunctive information for other cerebral diseases including neoplasms, intracranial infections, traumatic brain injury, and demyelinating processes. Because stroke is common and in the differential diagnosis of most acute neurologic events, diffusion-weighted MR imaging should be considered an essential sequence, and its use in most brain MR studies is recommended. C1 Massachusetts Gen Hosp, Neuroradiol Div, Boston, MA 02114 USA. RP Gonzalez, RG (reprint author), Massachusetts Gen Hosp, Neuroradiol Div, GRB 285,Fruit St, Boston, MA 02114 USA. NR 107 TC 547 Z9 602 U1 0 U2 32 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 2000 VL 217 IS 2 BP 331 EP 345 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 367JW UT WOS:000090058800004 PM 11058626 ER PT J AU Schwartz, RB Feske, SK Polak, JF DeGirolami, U Iaia, A Beckner, KM Bravo, SM Klufas, RA Chai, RYC Repke, JT AF Schwartz, RB Feske, SK Polak, JF DeGirolami, U Iaia, A Beckner, KM Bravo, SM Klufas, RA Chai, RYC Repke, JT TI Preeclampsia-eclampsia: Clinical and neuroradiographic correlates and insights into the pathogenesis of hypertensive encephalopathy SO RADIOLOGY LA English DT Article DE brain, abnormalities; brain, MR; hypertension; pregnancy, complications ID CEREBRAL PERFUSION-PRESSURE; DIFFUSION-WEIGHTED MR; MAGNESIUM-SULFATE; WOMEN; MANAGEMENT; SEIZURES; CT; ABNORMALITIES; NEUROTOXICITY; DYSFUNCTION AB PURPOSE: To investigate the clinical parameters that are associated with the development of brain edema of hypertensive encephalopathy in patients with preeclampsia-eclampsia. MATERIALS AND METHODS: Twenty-eight patients with preeclampsia-eclampsia and neurologic symptoms underwent magnetic resonance (MR) imaging. Clinical parameters recorded at the time of MR imaging included serum electrolytes and various indices of hematologic, renal, and hepatic function. Several data were available 1 week prior to the development of neurologic symptoms in 11 patients. Univariate analysis and multivariate logistic regression analyses were performed to study possible associations between these parameters and brain edema at MR imaging. RESULTS: The 20 patients with brain edema at MR imaging had a significantly greater incidence of abnormal red blood cell morphology (14 [82%] of 17 patients vs two [25%] of eight, P < .005) and higher levels of lactic dehydrogenase (LDH) (339 U/L +/- 65 [SD] vs 258 U/L +/- 65, P = .007) than the eight with normal MR imaging findings; multivariate logistic regression analysis showed a strong association with red blood cell morphology only. Moreover, LDH levels were elevated before the development of neurologic abnormalities (P < .05). Blood pressures were not significantly different between groups at any time. CONCLUSION: Brain edema at MR imaging in patients with preeclampsia-eclampsia was associated with abnormalities in endothelial damage markers and not with hypertension level. C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Univ Nebraska, Sch Med, Dept Obstet & Gynecol, Omaha, NE 68198 USA. RP Schwartz, RB (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. NR 41 TC 162 Z9 193 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 2000 VL 217 IS 2 BP 371 EP 376 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 367JW UT WOS:000090058800008 PM 11058630 ER PT J AU Jones, EC Murray, SK Young, RH AF Jones, EC Murray, SK Young, RH TI Cysts and epithelial proliferations of the testicular collecting system (including rete testis) SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Review ID CORD-STROMAL TUMORS; CELL PAPILLARY CYSTADENOMA; TUNICA VAGINALIS TESTIS; ADENOMATOUS HYPERPLASIA; MALIGNANT MESOTHELIOMA; SPERMATIC CORD; UNDESCENDED TESTIS; PAGETOID SPREAD; CLINICOPATHOLOGICAL ANALYSIS; ULTRASTRUCTURAL OBSERVATIONS AB Neoplastic and non-neoplastic proliferations of the testicular collecting system may be a source of diagnostic difficulty as they are rarely encountered and may have an appearance that leads to confusion with lesions arising in adjacent structures. The rete testis and epididymis are the 2 sites that are most likely to give rise to this unusual group of lesions, This article principally, although not exclusively, deals with those lesions that produce an intrascrotal mass. These include benign acquired or developmental cysts such as cystic dysgenesis of the rete testis or acquired cystic transformation of the rete testis, non-neoplastic epithelial proliferations such as adenomatous hyperplasia of the rete testis or cribriform hyperplasia of the epididymis, and benign or malignant neoplasms, Rate testis cystadenoma, including the sertoliform variant, and papillary cystadenoma of the epididymis are examples of benign tumors of the testicular collecting system that must be considered, the latter is the more likely of the 2 to be encountered. Primary carcinoma of either the rete testis or the epididymis is a rare occurrence; these entities are considered in some detail to allow for their recognition and distinction from other tumors that may occur in this region. Our own experience with 18 unpublished cases of lesions of the rate is also present, Copyright (C) 2000 by W.S. Saunders Company. C1 Univ British Columbia, Dept Pathol, Vancouver Hosp & Hlth Sci Ctr, Vancouver, BC V5Z 4E3, Canada. Harvard Univ, Sch Med, James Homer Wright Pathol Labs, Massachusetts Gen Hosp, Boston, MA USA. RP Jones, EC (reprint author), Univ British Columbia, Dept Pathol, Vancouver Hosp & Hlth Sci Ctr, 910 W 10th Ave, Vancouver, BC V5Z 4E3, Canada. NR 130 TC 21 Z9 21 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 0740-2570 J9 SEMIN DIAGN PATHOL JI Semin. Diagn. Pathol. PD NOV PY 2000 VL 17 IS 4 BP 270 EP 293 PG 24 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 394DL UT WOS:000166508700003 PM 11202545 ER PT J AU Henley, JD Ferry, J Ulbright, TM AF Henley, JD Ferry, J Ulbright, TM TI Miscellaneous rare paratesticular tumors SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Review DE ovarian-type tumors; desmoplastic round cell tumor; melanotic neuroectodermal tumor; lymphoma; granulocytic sarcoma; plasma cytoma; paratesticular neoplasms ID ROUND-CELL TUMOR; MELANOTIC NEUROECTODERMAL TUMOR; POLYMERASE CHAIN-REACTION; PARA-TESTICULAR TUMORS; NON-HODGKINS-LYMPHOMA; SPERMATIC CORD; PAPILLARY CYSTADENOMA; GENE FUSION; BORDERLINE MALIGNANCY; EPIDIDYMAL LYMPHOMA AB A few uncommon but distinctive tumors may preferentially involve the paratestis. The 3 unusual tumors that represent the focus of this discussion are the ovarian-type epithelial tumors (OTET), the desmoplastic small round cell tumor (DSRCT), and the melanotic neuroectodermal tumor of infancy (MNTI). The OTETs are testicular homologues of their more common namesake counterparts that arise in the ovary, Most frequent of these are serous tumors of borderline malignancy, with fewer cases of serous carcinomas or other forms of mullerian differentiation. DSRCT is an increasingly recognized, aggressive, "small blue cell" neoplasm with distinctive clinical and pathologic features. These polyphenotypic tumors characteristically, but not invariably, arise in intimate association with the serosal membrane of the peritoneal cavity and harbor a signature translocation-t(11;22)(p13,q12). In the paratestis they often involve the surface of the epididymis, The MNTI is an enigmatic, histologically distinctive, low-grade neoplasm occasionally encountered in the epididymis. Recognition of its features is essential to avoid misdiagnosis as a more aggressive "small blue cell" neoplasm and consequent therapeutic mismanagement, Primary hematopoietic tumors of the paratesticular structures are rare. There appears to be a tendency for young men to have low-grade lymphomas with an indolent course and older patients to develop higher-grade tumors. Plasmacytoma and granulocytic sarcoma of the paratestis are even more rare and are often susceptible to misinterpretation. Finally, metastatic tumors and a variety of other very rare neoplasms are discussed. Copyright (C) 2000 by W,S. Saunders Company. C1 Indiana Univ, Sch Med, Dept Pathol, Indianapolis, IN 46202 USA. Massachusetts Gen Hosp, James Homer Wright Pathol Lab, Boston, MA 02114 USA. RP Henley, JD (reprint author), Indiana Univ Hosp, Dept Pathol & Lab Med, 3465,550 N Univ Blvd, Indianapolis, IN 46202 USA. NR 104 TC 13 Z9 13 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 0740-2570 J9 SEMIN DIAGN PATHOL JI Semin. Diagn. Pathol. PD NOV PY 2000 VL 17 IS 4 BP 319 EP 339 PG 21 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 394DL UT WOS:000166508700006 PM 11202548 ER PT J AU Oliva, E Young, RH AF Oliva, E Young, RH TI Paratesticular tumor-like lesions SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Review DE paratestis; tumor-like lesions ID NECROTIZING GRANULOMATOUS VASCULITIS; CONGENITAL ADRENAL-HYPERPLASIA; TUNICA VAGINALIS TESTIS; ADRENOGENITAL SYNDROME; TESTICULAR-TUMORS; VASITIS NODOSA; 21-HYDROXYLASE DEFICIENCY; EPIDIDYMAL SARCOIDOSIS; FIBROUS PSEUDOTUMOR; NELSONS SYNDROME AB The diverse non-neoplastic lesions that occur in the paratesticular region and may potentially mimic neoplasms are considered. These include some aspects of normal histology such as a cribriform pattern of the epididymis, bizarre nuclear atypia within epididymal epithelial cells and the presence of Leydig cells outside the testicular parenchyma. Inflammatory changes associated with a hydrocele and a variety of granulomatous and nongranulomatous infectious disorders may mimic a neoplasm on gross evaluation, but should be readily distinguished from them microscopically. This is also the case with malakoplakia and sarcoidosis, which rarely form a paratesticular mass. Other lesions considered are changes associated with vasculitis, the recently described entities inflammatory pseudotumor and fibromuscular hyperplasia and the well-known processes sperm granuloma, spermatocele, vasitis nodosa, fibrous pseudotumor, meconium periorchitis, mesothelial hyperplasia, the testicular tumor of the adrenogenital syndrome, sclerosing lipogranuloma, and splenic-gonadal fusion. Features that aid in the microscopic distinction of these lesions from neoplasms are emphasized. Copyright (C) 2000 by W.S. Saunders Company. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Oliva, E (reprint author), Massachusetts Gen Hosp, Dept Pathol, Fruit St, Boston, MA 02114 USA. NR 126 TC 29 Z9 31 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 0740-2570 J9 SEMIN DIAGN PATHOL JI Semin. Diagn. Pathol. PD NOV PY 2000 VL 17 IS 4 BP 340 EP 358 PG 19 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 394DL UT WOS:000166508700007 PM 11202549 ER PT J AU Lee, S McAuliffe, DJ Kodama, T Doukas, AG AF Lee, S McAuliffe, DJ Kodama, T Doukas, AG TI In vivo transdermal delivery using a shock tube SO SHOCK WAVES LA English DT Article DE shock tube; stress waves; shock waves; stratum corneum permeability; transdermal drug delivery ID GENERATED STRESS WAVES; DRUG-DELIVERY; PLASMA-MEMBRANE; PERMEABILIZATION; GRADIENT; CELLS AB A shock tube was utilized for transdermal delivery in fuzzy rats. Rhodamine-B dextran, 10 kDa molecular weight, was used as the probe molecule. Shock waves were generated by a two-stage shock tube. A single shock wave was applied onto the skin to permeabilize the stratum corneum. Subsequently, the dextran solution diffused through the stratum corneum into the epidermis. Fluorescence microscopy of biopsies showed that the dextran was delivered to a depth of 30-60 mum into the skin. Thus, the shock tube could become an inexpensive device for transdermal drug delivery. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. RP Doukas, AG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. OI kodama, tetsuya/0000-0003-4727-9558 NR 29 TC 9 Z9 9 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-1287 J9 SHOCK WAVES JI Shock Waves PD NOV PY 2000 VL 10 IS 5 BP 307 EP 311 DI 10.1007/s001930000059 PG 5 WC Mechanics SC Mechanics GA 376AY UT WOS:000165436800001 ER PT J AU Kohlmeier, RE Cho, CG Bux, RC Guerra, L Rulon, JJ Selby, DM Gulley, ML AF Kohlmeier, RE Cho, CG Bux, RC Guerra, L Rulon, JJ Selby, DM Gulley, ML TI Prothrombin gene mutation uncommon in pulmonary embolism SO SOUTHERN MEDICAL JOURNAL LA English DT Article ID FACTOR-V-LEIDEN; DEEP VENOUS THROMBOSIS; 3'-UNTRANSLATED REGION; GLN MUTATION; VARIANT; ALLELE; PREVALENCE; CARRIERS; RISK; ARG-506 AB Background. Venous thrombosis followed by pulmonary embolism is one of the most common causes of sudden death among middle-aged adults. Several inherited polymorphisms are associated with heightened risk of venous thrombosis, including mutation at position 20210 of the prothrombin gene and mutation at codon 506 of the factor V gene. Methods. We studied mutation prevalence in 67 individuals who died of pulmonary embolism and were autopsied in a medical examiner's facility over a 5-year period. Mutations were identified by polymerase chain reaction followed by allele-specific endonuclease digestion. Results. Traditional risk factors fur pulmonary embolism (eg, immobility, oral contraceptive use, cancer) were identified in 75%. Heterozygous mutation of the prothrombin gene was found in 3/67 (4%), and heterozygous mutation of the factor V gene was identified in 3/66 (4%). No homozygotes or compound heterozygotes were identified. The prevalence of mutation was not significantly different from that of the general population Conclusions. Individuals who die suddenly from pulmonary embolism are not often affected by prothrombin or factor V gene mutations. Therefore, medical examiners need not routinely test for these mutations in individuals who die of pulmonary embolism. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, Bexar Cty Forens Sci Ctr,Wilford Hall Med Ctr, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX USA. RP Gulley, ML (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, Bexar Cty Forens Sci Ctr,Wilford Hall Med Ctr, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 17 TC 5 Z9 5 U1 0 U2 0 PU SOUTHERN MEDICAL ASSN PI BIRMINGHAM PA 35 LAKESHORE DR PO BOX 190088, BIRMINGHAM, AL 35219 USA SN 0038-4348 J9 SOUTHERN MED J JI South.Med.J. PD NOV PY 2000 VL 93 IS 11 BP 1073 EP 1077 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 376AW UT WOS:000165436500005 PM 11095555 ER PT J AU Schollmeier, G Lahr-Eigen, R Lewandrowski, KU AF Schollmeier, G Lahr-Eigen, R Lewandrowski, KU TI Observations on fiber-forming collagens in the anulus fibrosus SO SPINE LA English DT Article DE anulus fibrosus; fiber-forming collagens; immunohistochemistry; monoclonal antibodies; spine histology ID LUMBAR INTERVERTEBRAL DISCS; LOW-BACK-PAIN; ANNULUS FIBROSUS; III COLLAGEN; MONOCLONAL-ANTIBODIES; TENSILE PROPERTIES; TYPE-2 COLLAGENS; TISSUE-SECTIONS; CARTILAGE; IMMUNOLOCALIZATION AB Study Design. The spatial distribution of fiber-forming collagens in the anulus fibrosus was investigated in the complete longitudinal and horizontal sections of human lumbar intervertebral discs of seven individuals. Objectives. To obtain a more detailed structural definition of the anulus fibrosus because structural alterations of its collagen fiber network have been implicated in discal degeneration and other spinal pathologies. Summary of Background Data. Prior biochemical or immunofluorescence studies permitted only limited conclusions concerning the spatial distribution of the fiber-forming collagens in relation to anatomic structures because they were based on intraoperative tissue specimens or performed on incomplete sections of human intervertebral discs. Methods. Complete human intervertebral discs with their adjacent vertebral bodies were fixed, decalcified, and embedded in paraffin. The intervertebral disc and its adjacent structures were reviewed in their entirety on one histologic slide. Monoclonal antibodies against human Types I, II, and III collagen were used for immunohistochemistry. A comparative analysis based on both immunohistochemical and histologic evaluation was performed. Results. Type I collagen was seen abundantly in the outer zone and outer lamellas of the inner zone of the analus fibrosus. On longitudinal sections, the Type I collagen distribution took the shape of a wedge. On horizontal sections, the Type I collagen positive area took the shape of a ring that was wider anteriorly than posteriorly. This suggests that the three-dimensional shape of the Type I collagen-positive tissue in the anulus fibrosus can he described by a donut that is wider anteriorly than posteriorly. Type II collagen was present in the entire inner of the anulus fibrosus, but not in the outer zone. In addition, it Was found in the cartilaginous endplates. Type III collagen showed some codistribution with Type II collagen, particularly in pericellular locations in areas of spondylosis, which was noted at the endplates, vertebral rim, and insertion sites of the anulus fibrosus. Conclusions. These observations on the location of types land II collagen provide a more derailed structural definition of the anulus fibrosus, which may assist in further investigation of discal herniation. C1 Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. Univ Ottawa, Fac Med, Dept Surg, Ottawa, ON K1N 6N5, Canada. St Josefs Hosp, Dept Surg, Potsdam, Germany. RP Lewandrowski, KU (reprint author), Massachusetts Gen Hosp, Orthopaed Res Labs, GRYJ 1124,55 Fruit St, Boston, MA 02114 USA. FU NIAMS NIH HHS [AR 45062] NR 52 TC 26 Z9 27 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD NOV 1 PY 2000 VL 25 IS 21 BP 2736 EP 2741 DI 10.1097/00007632-200011010-00004 PG 6 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 372PU UT WOS:000165243100003 PM 11064517 ER PT J AU Warshaw, AL AF Warshaw, AL TI Pancreas divisum - really SO SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,WHT 506, Boston, MA 02114 USA. NR 4 TC 4 Z9 4 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD NOV PY 2000 VL 128 IS 5 BP 832 EP 833 DI 10.1067/msy.2000.109610 PG 2 WC Surgery SC Surgery GA 370DJ UT WOS:000165107700010 PM 11056447 ER PT J AU Khuri, SF AF Khuri, SF TI Invited commentary: Application of quality improvement to surgical practice - a word of caution SO SURGERY LA English DT Article C1 Harvard Univ, Sch Med, Dept Surg, VA Boston Healthcare Syst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Khuri, SF (reprint author), Vet Adm Med Ctr, Dept Surg, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD NOV PY 2000 VL 128 IS 5 BP 845 EP 846 DI 10.1067/msy.2000.109115 PG 2 WC Surgery SC Surgery GA 370DJ UT WOS:000165107700013 PM 11056450 ER PT J AU Schmidt-Erfurth, U Hasan, T AF Schmidt-Erfurth, U Hasan, T TI Mechanisms of action of photodynamic therapy with verteporfin for the treatment of age-related macular degeneration SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE age-related macular degeneration; benzoporphyrin derivative; mechanisms of action; photodynamic therapy; verteporfin ID EXPERIMENTAL CHOROIDAL NEOVASCULARIZATION; LIPOPROTEIN-DELIVERED BENZOPORPHYRIN; WATER-SOLUBLE PHOTOSENSITIZER; ETHYL ETIOPURPURIN SNET2; ASPARTYL CHLORIN E6; MOUSE-TUMOR MODEL; RING-A BPD; LASER PHOTOCOAGULATION; ENDOTHELIAL-CELLS; HEMATOPORPHYRIN AB Age-related macular degeneration, especially the neovascular form of the disease, is the loading cause of blindness in elderly people in developed countries. Thermal photocoagulation is still the preferred treatment for choroidal neovascularization that does not involve the fovea, but it is suitable for only a small number of patients and it can lead to immediate loss of visual acuity. Photodynamic therapy with use of photochemical light activation of verteporfin as a photosensitizer (verteporfin therapy) has been shown to be effective in treating vascularized tumors, and its potential to treat other conditions involving neovascularization has also been suggested. Preclinical and clinical studies have indicated that verteporfin therapy can be used to treat choroidal neovascularization secondary to age-related macular degeneration effectively and safely. Selective occlusion of choroidal neovasculature by this therapy causes minimal damage to the neurosensory retina and, therefore, does not induce loss of visual acuity. This benefit allows verteporfin therapy to be used in the large proportion of patients who are not eligible for treatment by laser photocoagulation. The mechanistic aspects of the mode of action of light-activated verteporfin are described in this review. (Surv Ophthalmol 45:195-214, 2000. (C) 2000 by Elsevier Science Inc. All rights reserved.). C1 Univ Eye Hosp, Lubeck, Germany. Massachusetts Gen Hosp, Wellman Lab Photomed, Boston, MA 02114 USA. RP Schmidt-Erfurth, U (reprint author), CIBA Vis Ophthalmol, 11460 Johns Creek Pkwy, Atlanta, GA 30097 USA. NR 99 TC 254 Z9 269 U1 3 U2 33 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD NOV-DEC PY 2000 VL 45 IS 3 BP 195 EP 214 DI 10.1016/S0039-6257(00)00158-2 PG 20 WC Ophthalmology SC Ophthalmology GA 389KC UT WOS:000166236300002 PM 11094244 ER PT J AU Li, JZ Xia, YP Bertino, AM Coburn, JP Kuter, DJ AF Li, JZ Xia, YP Bertino, AM Coburn, JP Kuter, DJ TI The mechanism of apoptosis in human platelets during storage SO TRANSFUSION LA English DT Article ID CELL-DEATH; ACTIVATION; CASPASE; NECROSIS; ACCUMULATION; GENERATION; EXPRESSION; CYTOKINES; RESPONSES; PROTEASE AB BACKGROUND: Although it is usually involved only in nucleated cells (NCs), artificially enucleated cells also lose viability by a programmed process of cell death called apoptosis. Because platelets undergo loss of viability during storage, an attempt was made to determine whether platelets contained the apoptotic mechanisms and whether it was activated during platelet storage. STUDY DESIGN AND METHODS: Platelet viability was measured by reduction of a tetrazolium dye (MTS) and annexin V binding. Members of the death receptor, caspase, and Bcl-2 families were detected by RNase protection assay and Western blotting. Caspase 3 activation was measured by enzyme and Western blot assays and by cleavage of gelsolin. RESULTS: After 5 days of storage under standard blood banking conditions, platelets display biochemical signs of apoptosis by losing MTS activity and increasing the amount of phosphatidylserine on their surface. The mRNA and the proenzyme for several members of the caspase, death receptor, and Bcl-2 families are expressed at high levels in platelets. An increase in caspase 3 activity and the amount of the biologically active p17 subunit of active caspase 3 were observed to coincide with the appearance of apoptotic markers during storage. These effects were not due to platelet activation. The caspase 3 substrate, gelsolin, began to undergo proteolysis after 3 to 4 days of storage, and the addition of the caspase inhibitor z-VAD-fmt substantially inhibited this process. CONCLUSION: Platelets contain many of the components of the apoptotic mechanism and show activation of caspase 3 and consequent cleavage of gelsolin during storage, independent of platelet activation. Evaluation of the mechanism of apoptosis in platelets may provide a basis for developing novel strategies to enhance platelet viability during storage. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hematol Oncol Unit, Boston, MA 02114 USA. RP Kuter, DJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hematol Oncol Unit, 100 Blossom St, Boston, MA 02114 USA. NR 35 TC 120 Z9 128 U1 1 U2 6 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD NOV PY 2000 VL 40 IS 11 BP 1320 EP 1329 DI 10.1046/j.1537-2995.2000.40111320.x PG 10 WC Hematology SC Hematology GA 377BT UT WOS:000165492600006 PM 11099659 ER PT J AU Aalfs, JD Kingston, RE AF Aalfs, JD Kingston, RE TI What does 'chromatin remodeling' mean? SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID YEAST SWI/SNF COMPLEX; HISTONE OCTAMER; SACCHAROMYCES-CEREVISIAE; NUCLEOSOMAL DNA; PHO5 PROMOTER; HSP70 GENE; HO GENE; BINDING; ISWI; TRANSCRIPTION AB The regulated alteration of chromatin structure, termed 'chromatin remodeling', can be accomplished by covalent modification of histones or by the action of ATP-dependent remodeling complexes. A variety of mechanisms can be used to remodel chromatin; some act locally on a single nucleosome and others act more broadly. It is critical to establish a direct connection between the remodeling events observed in vivo and the mechanistic capabilities of remodeling complexes in vitro. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Aalfs, JD (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. NR 47 TC 143 Z9 149 U1 1 U2 5 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD NOV PY 2000 VL 25 IS 11 BP 548 EP 555 DI 10.1016/S0968-0004(00)01689-3 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 373BD UT WOS:000165267800011 PM 11084367 ER PT J AU Cheatham, B AF Cheatham, B TI GLUT4 and company: SNAREing roles in insulin-regulated glucose uptake SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID PROTEIN-KINASE-B; 3T3-L1 ADIPOCYTES; PHOSPHATIDYLINOSITOL 3-KINASE; RAT ADIPOCYTES; C-LAMBDA; GLUT4-CONTAINING VESICLES; INTRACELLULAR-TRANSPORT; 3T3L1 ADIPOCYTES; MEMBRANE-FUSION; SKELETAL-MUSCLE AB The primary physiological role of insulin is in glucose homeostasis. This is accomplished through the inhibition of gluconeogenesis in the liver and the stimulation of glucose uptake into insulin-sensitive tissues, such as adipose tissue, skeletal muscle and cardiac muscle. The ability of insulin to stimulate glucose uptake relies on a complex signaling cascade that leads to the translocation of glucose transporter protein 4 (GLUT4) from an intracellular compartment to the plasma membrane, which results in increased glucose uptake. Defects in the ability of insulin to regulate this key metabolic event can lead to insulin resistance and non-insulin-dependent type 2 diabetes mellitus (T2DM). To design effective treatments for diabetes, there have been major efforts to understand the insulin-regulate mechanisms that govern glucose uptake. These have involved defining the components of the insulin signaling network and identifying the molecular machinery that is used to translocate GLUT4. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Cheatham, B (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. NR 63 TC 20 Z9 21 U1 0 U2 3 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD NOV PY 2000 VL 11 IS 9 BP 356 EP 361 DI 10.1016/S1043-2760(00)00308-8 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 365TF UT WOS:000089966000003 PM 11042465 ER PT J AU Bonner-Weir, S AF Bonner-Weir, S TI Life and death of the pancreatic beta cells SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID GROWTH-FACTOR-II; RAT PANCREAS; NEONATAL RAT; ISLET CELLS; ENDOCRINE PANCREAS; OVAL CELLS; PROLIFERATION; EXPRESSION; APOPTOSIS; GLUCOSE AB Pancreatic beta cells are responsible for maintaining the body's glucose levels within a very narrow range; their population is dynamic, with compensatory changes to maintain euglycemia Throughout the lifetime of a mammal, low levels of beta -cell replication and apoptosis are balanced and result in a slowly increasing mass of beta cells. The emphasis in this review is on recent insights on the natural history of the beta cell in a normal pancreas: sources of renewal, survival and changes in differentiation. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Bonner-Weir, S (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. NR 60 TC 186 Z9 199 U1 0 U2 7 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD NOV PY 2000 VL 11 IS 9 BP 375 EP 378 DI 10.1016/S1043-2760(00)00305-2 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 365TF UT WOS:000089966000006 PM 11042468 ER PT J AU Sachs, G Scott, D Weeks, D Melchers, K AF Sachs, G Scott, D Weeks, D Melchers, K TI Gastric habitation by Helicobacter pylori: insights into acid adaptation SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Article ID PROTON MOTIVE FORCE; UREASE ACTIVITY; PH; SURVIVAL C1 VA Greater LA Healthcare Syst, Los Angeles, CA 90073 USA. BYK Gulden Lomberg GmbH, D-7750 Constance, Germany. RP Sachs, G (reprint author), VA Greater LA Healthcare Syst, Bldg 113,Room 314,11310 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 22 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD NOV PY 2000 VL 21 IS 11 BP 413 EP 416 DI 10.1016/S0165-6147(00)01554-6 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 374GD UT WOS:000165336700002 PM 11121568 ER PT J AU Kalish, LA McDougal, WS McKinlay, JB AF Kalish, LA McDougal, WS McKinlay, JB TI Family history and the risk of prostate cancer SO UROLOGY LA English DT Article ID MIDDLE-AGED MEN; BREAST-CANCER; RELATIVES; DISEASE; PROBANDS; SWEDEN; COHORT AB Objectives. Several studies have identified prostate cancer family history as a risk factor for prostate cancer incidence, typically associated with a twofold to fourfold increase in risk. A family history of breast cancer has also been implicated. We investigated the associations between prostate cancer incidence and family histories of prostate and breast cancer, controlling for possible confounding due to environmental factors. Methods. Data from the random sample-based Massachusetts Male Aging Study cohort (1987 to 1997) were used. Incidence rates were calculated as the number of cases per person-year of follow-up. Covariates were adjusted for using Poisson regression. Results. Among 1149 men with an average of 8.7 person-years of follow-up, 57 were diagnosed with prostate cancer, 110 men reported a prostate cancer family history, and 157 reported a breast cancer family history. The age-adjusted relative risk (RR) of prostate cancer incidence associated with prostate cancer family history was 3.29 (95% confidence interval [CI] 1.82 to 5.94]. No evidence of heterogeneity was found across age levels (P = 0.83). Additional adjusting for environmental factors such as smoking, alcohol use, body mass index, physical activity, education, sexually transmitted disease history, diet, and hormone levels yielded a slightly higher RR (3.78, 95% CI 1.96 to 7.28). No association with a family history of breast cancer was evident (RR = 1.18, 95% CI 0.51 to 2.43). Conclusions. We found an association between prostate cancer incidence and a family history of prostate cancer, independent of environmental factors. No association with a family history of breast cancer was evident. UROLOGY 56: 803-806, 2000. (C) 2000, Elsevier Science Inc. C1 New England Res Inst, Watertown, MA 02472 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kalish, LA (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. FU NIDDK NIH HHS [DK-51345, DK-44995] NR 26 TC 29 Z9 30 U1 0 U2 0 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 NOV PY 2000 VL 56 IS 5 BP 803 EP 806 DI 10.1016/S0090-4295(00)00780-9 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 375LK UT WOS:000165400700021 PM 11068306 ER PT J AU Freedland, SJ Dorey, F Aronson, WJ AF Freedland, SJ Dorey, F Aronson, WJ TI Multivariate analysis of race and adverse pathologic findings after radical prostatectomy SO UROLOGY LA English DT Article ID POSITIVE SURGICAL MARGINS; PROGNOSTIC FACTOR; AFRICAN-AMERICAN; CANCER; ANTIGEN; CARCINOMA; WHITE; SPECIMENS; SURVIVAL; STAGE AB Objectives. Adverse pathologic features that predict disease recurrence after radical prostatectomy (RP) include positive surgical margins, non-organ-confined disease, and seminal vesicle invasion. Given that black men have a higher incidence of, and mortality from, prostate cancer compared with white men, we sought to determine whether race was an independent predictor of adverse pathologic findings among men who underwent RP at an equal access health care center. Results from previous studies evaluating whether race predicts positive surgical margins have been conflicting. No prior studies have evaluated whether race is an independent predictor of non-organ-confined disease or seminal vesicle invasion. Methods, A retrospective survey of 274 patients (126 black, 148 white) who underwent RP at the West Los Angeles Veterans Affairs Medical Center between 1991 and 1999 was undertaken. Multivariate analysis was used to determine the preoperative clinical variables that were most significant in predicting positive surgical margins, non-organ-confined disease, and seminal vesicle invasion. The preoperative variables analyzed were race, age, serum prostate-specific antigen, clinical stage, and biopsy Gleason score. Results. No differences in the incidence of positive surgical margins, non-organ-confined disease, or seminal vesicle invasion were found between black and white men undergoing RP. After controlling for the preoperative variables of age, serum prostate-specific antigen level, clinical stage, and biopsy Gleason score, race was not an independent predictor of positive surgical margins, non-organ-confined disease, or seminal vesicle invasion. Conclusions. This is the first study to show that black race was not an independent predictor of non-organ-confined disease or seminal vesicle invasion among patients undergoing RP. Furthermore, race was not an independent predictor of positive surgical margins. UROLOGY 56: 807-811, 2000. (C) 2000, Elsevier Science Inc. C1 Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Biostat, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Vet Affairs Med Ctr Sepulveda, Los Angeles, CA USA. RP Aronson, WJ (reprint author), Univ Calif Los Angeles, Sch Med, Dept Urol, Box 951738, Los Angeles, CA 90095 USA. NR 21 TC 18 Z9 18 U1 0 U2 0 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 NOV PY 2000 VL 56 IS 5 BP 807 EP 811 DI 10.1016/S0090-4295(00)00754-8 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 375LK UT WOS:000165400700022 PM 11068307 ER PT J AU Alwayn, IPJ Appel, JZ Goepfert, C Buhler, L Cooper, DKC Robson, SC AF Alwayn, IPJ Appel, JZ Goepfert, C Buhler, L Cooper, DKC Robson, SC TI Inhibition of platelet aggregation in baboons: therapeutic implications for xenotransplantation SO XENOTRANSPLANTATION LA English DT Article DE baboons; coagulation; eptifibatide; platelet aggregation; rejection; xenotransplantation ID VON-WILLEBRAND-FACTOR; NITRIC-OXIDE; ENDOTHELIAL-CELLS; XENOGRAFT REJECTION; HYPERACUTE REJECTION; THROMBOXANE A(2); RENAL XENOGRAFTS; GPIIB-IIIA; IN-VIVO; THROMBIN AB Activation of endothelial cells and platelet sequestration play major roles in rejection of xenografts. The histopathology of both hyperacute and acute vascular or delayed rejection of vascularized discordant xenografts is characterized by interstitial hemorrhage and intravascular thrombosis. Agents that prevent platelet activation and consequent microthrombus formation have proven beneficial in xenograft rejection but do not fully preclude vascular thrombosis. Recently, several new anti-platelet therapies have undergone extensive clinical testing for atherosclerotic thrombotic vascular disorders; other putative therapies are undergoing pre-clinical evaluation. We have investigated the effect of several of these novel agents on platelet aggregation in baboons in order to screen for future potential in xenograft rejection models. Methods: Drugs tested in these experiments were aurintricarboxylic acid (ATA, von Willebrand Factor-GPIb inhibitor), fucoidin (a selectin-inhibitor), 1-benzylimidazole (1-BI, thromboxane synthase antagonist), prostacyclin (PGI(2), endothelial stabilizer), heparin (thrombin antagonist), nitroprusside sodium or nicotinamide (NPN or NA, both NO-donors), and eptifibatide (EFT, GPIIb/IIIa receptor antagonist). These were infused intravenously to nine baboons. Coagulation parameters and platelet counts were monitored and baboons were observed for adverse side-effects. The efficacy of these agents in inhibiting platelet aggregation was assayed in a platelet aggregometer. Results. Treatment with ATA and fucoidin resulted in complete inhibition of platelet aggregation but also in major perturbation of coagulation parameters. 1-BI and PGI2 had no effect when administered alone, but in combination resulted in moderate inhibition of aggregation without disturbance in PT or PTT. NPN and NA had no substantive effects on platelet aggregation. Heparin resulted in specific inhibition of thrombin-induced platelet aggregation and, as anticipated, was associated with moderate prolongation of PTT. Importantly, EFT caused complete inhibition of platelet aggregation without changes in coagulation. Platelet counts, fibrinogen levels, and fibrinogen degradation products remained within the normal ranges in all experiments. Conclusions: Although excellent inhibition of platelet activation was obtained with ATA and fucoidin, clinical use may be precluded by concomitant disturbances of coagulation. Combinations of heparin and EFT may prove beneficial in preventing the thrombotic disorders associated with xenograft rejection while maintaining adequate hemostatic responses. These agents are to be evaluated in our pig-to-primate xenotransplantation models. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Immunol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. RP Robson, SC (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Immunol, 99 Brookline Ave,Room 370, Boston, MA 02215 USA. NR 62 TC 35 Z9 38 U1 0 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD NOV PY 2000 VL 7 IS 4 BP 247 EP 257 DI 10.1034/j.1399-3089.2000.00965.x PG 11 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 372PH UT WOS:000165242000003 PM 11081759 ER PT J AU Sapirstein, A Bonventre, JV AF Sapirstein, A Bonventre, JV TI Specific physiological roles of cytosolic phospholipase A(2) as defined by gene knockouts SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Review DE cytosolic phospholipase A(2); fertility; stroke; allergy; asthma; macrophage ID ARACHIDONIC-ACID; MAST-CELLS; PROSTAGLANDIN D-2; NUCLEAR-ENVELOPE; MICE DEFICIENT; MOUSE; GENERATION; MECHANISM; ISCHEMIA; BRAIN AB The cytosolic 85 kDa phospholipase A(2) (cPLA(2)) is a unique member of the phospholipase A(2) (PLA(2)) superfamily. Because PLA(2) activity and eicosanoid production are important in normal and pathophysiological states we and the laboratory of Shimizu created a mouse deficient in cPLA(2) (cPLA(2)(-/-) mouse), cPLA(2)(-/-) mice develop normally but the females have severe reproductive defects. cPLA(2)(-/-) mice suffer smaller infarcts and fewer neurological deficits after transient occlusion of the middle cerebral artery and have less injury after administration of a dopaminergic selective neurotoxin. cPLA(2)(-/-) mice have a more rapid recovery from allergen-induced bronchoconstriction and have no airway hyperresponsiveness. Peritoneal macrophages from CPLA(2)(-/-) mice fail to produce prostaglandins, leukotriene B-4 and cysteinyl leukotrienes after stimulation. Bone marrow-derived mast cells from cPLA(2)(-/-) mice fail to produce eicosanoids in either immediate or delayed phase responses. Thus the cPLA(2) knockout mouse has revealed important roles of cPLA(2) in normal fertility, generation of eicosanoids from inflammatory cells, brain injuries and allergic responses. Furthermore the cPLA(2)(-/-) mouse reveals that the many other forms of PLA(2) cannot replace many functions of cPLA(2). The importance of cPLA(2) in inflammation and tissue injury suggests that pharmacological targeting of this enzyme may have important therapeutic benefits. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Crit Care, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Med Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Boston, MA 02115 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Sapirstein, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK39773, DK38452]; NINDS NIH HHS [NS10828] NR 51 TC 127 Z9 133 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 J9 BBA-MOL CELL BIOL L JI BBA-Mol. Cell. Biol. Lipids PD OCT 31 PY 2000 VL 1488 IS 1-2 BP 139 EP 148 DI 10.1016/S1388-1981(00)00116-5 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 377XL UT WOS:000165551500013 PM 11080683 ER PT J AU Yu, GS Hurier, AM Anthony, M Lu, YC Gulick, T AF Yu, GS Hurier, AM Anthony, M Lu, YC Gulick, T TI Cpt-1 gene expression and fatty acid oxidation are regulated by p38 MAP kinase through MEF2 factors SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 24 BP 7 EP 8 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300025 ER PT J AU Chao, W Matsui, T Tao, J Li, L Rosenzweig, A AF Chao, W Matsui, T Tao, J Li, L Rosenzweig, A TI Adenoviral expression of IGF-I reduces infarction after transient cardiac ischemia SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 43 BP 12 EP 12 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300044 ER PT J AU Rubin, SA Iacoviello, M Smith, SE Dey, S Chatterjee, N Said, HM AF Rubin, SA Iacoviello, M Smith, SE Dey, S Chatterjee, N Said, HM TI Characterization and cloning of a specific, carrier-mediated system for pantothenic acid uptake by vascular smooth muscle SO CIRCULATION LA English DT Meeting Abstract C1 VA Greater Los Angeles, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. VA Long Beach, Long Beach, CA USA. Univ Calif Irvine, Long Beach, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 81 BP 19 EP 19 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300082 ER PT J AU Kassiri, Z Zobel, C Hajjar, RJ Molkentin, JD Johns, DC Backx, PH AF Kassiri, Z Zobel, C Hajjar, RJ Molkentin, JD Johns, DC Backx, PH TI Down-regulation of I-to can induce myocyte hypertrophy in neonatal rat ventricular myocytes: Manipulation of K-v1.4 and K-v4.2 genes using adenoviral gene transfer SO CIRCULATION LA English DT Meeting Abstract C1 Toronto Hosp, Toronto, ON M5T 2S8, Canada. Univ Toronto, Toronto, ON, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Cincinnati, OH 45229 USA. Johns Hopkins Univ, Baltimore, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 91 BP 23 EP 23 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300092 ER PT J AU Moroi, M Moons, L Carmeliet, P Collen, D Yamaguchi, T Yasuda, T Gold, HK AF Moroi, M Moons, L Carmeliet, P Collen, D Yamaguchi, T Yasuda, T Gold, HK TI The effects of disruption of plasminogen gene on vascular neointima formation: Analysis by the external vascular cuff-induced neointima formation mouse model SO CIRCULATION LA English DT Meeting Abstract C1 Toho Univ, Sch Med, Tokyo, Japan. Ctr Transgene Technol & Gene Therapy, Leuven, Belgium. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 172 BP 38 EP 38 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300172 ER PT J AU Acosta, JA Hettinga, J Flykiger, R Goldfine, AB Halperin, JA AF Acosta, JA Hettinga, J Flykiger, R Goldfine, AB Halperin, JA TI A novel role of complement in the pathogenesis of diabetic vascular complications SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 230 BP 50 EP 50 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300230 ER PT J AU Lee, KH Roberts, JD Matsui, T Li, L Gianetti, J Bloch, KD Rosenzweig, A AF Lee, KH Roberts, JD Matsui, T Li, L Gianetti, J Bloch, KD Rosenzweig, A TI Inhaled nitric oxide reduces myocardial infarct size after transient ischemia without affecting systemic hemodynamics SO CIRCULATION LA English DT Meeting Abstract C1 Sungkyunkwan Univ, Sch Med, Seoul, South Korea. Massachusetts Gen Hosp, Boston, MA 02114 USA. CNR, Inst Clin Physiol, I-56100 Pisa, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 285 BP 60 EP 61 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300285 ER PT J AU Gerszten, RE Matsui, T Hung, RR Li, L Force, T Rosenzweig, A AF Gerszten, RE Matsui, T Hung, RR Li, L Force, T Rosenzweig, A TI Activation of PI 3-kinase is sufficient to induce adhesion of the monocytic THP-1 cell line under laminar flow conditions in vitro SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Massachusetts Gen Hosp, CV Res Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 314 BP 66 EP 66 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300314 ER PT J AU Way, KJ Li, ZL King, GL AF Way, KJ Li, ZL King, GL TI Role of connective tissue growth factor expression in myocardial fibrosis induced by protein kinase C beta 2 isoform overexpression in the heart SO CIRCULATION 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 LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 333 BP 70 EP 70 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300332 ER PT J AU Diwan, A Dibbs, ZI Gao, F Nemoto, S Defreitas, G Sivasubramanian, N Carabello, BA Mann, DL AF Diwan, A Dibbs, ZI Gao, F Nemoto, S Defreitas, G Sivasubramanian, N Carabello, BA Mann, DL TI Cardiac restricted overexpression of membrane bound tumor necrosis factor provokes a hypertrophic cardiac phenotype SO CIRCULATION LA English DT Meeting Abstract C1 Winters Ctr Heart Failure Res, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Houston VAMC, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 338 BP 71 EP 71 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300337 ER PT J AU Nemoto, ST Vallejo, JG Defreitas, G Knuefermann, P Carabello, BA AF Nemoto, ST Vallejo, JG Defreitas, G Knuefermann, P Carabello, BA TI Role of gene deletion of the toll-like receptor-4 (TLR-4) in lipopolysaccharide (LPS)-induced left ventricular dysfunction SO CIRCULATION LA English DT Meeting Abstract C1 Houston VAMC, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 355 BP 74 EP 74 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300354 ER PT J AU Biswas, KS Thatte, HS Najjar, SF Rhee, JH Birjiniuk, V Crittenden, MD Khuri, SF AF Biswas, KS Thatte, HS Najjar, SF Rhee, JH Birjiniuk, V Crittenden, MD Khuri, SF TI Multiphoton imaging of endothelial nitric oxide synthase-caveolin regulation in human saphenous vein SO CIRCULATION LA English DT Meeting Abstract C1 Boston VAMC, W Roxbury, MA USA. Brigham & Womens Hosp, W Roxbury, MA USA. Harvard Univ, Sch Med, W Roxbury, MA USA. VA Boston Healthcare Syst, W Roxbury, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 618 BP 128 EP 128 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300616 ER PT J AU Schneider, JW Birjiniuk, V Rocco, TP Crovello, C Carraway, KL Decaprio, J Schwab, MH Lai, C AF Schneider, JW Birjiniuk, V Rocco, TP Crovello, C Carraway, KL Decaprio, J Schwab, MH Lai, C TI A potential mechanism for herceptin cardiomyopathy through abnormal ErbB2-mediated cytoskeletal signaling SO CIRCULATION LA English DT Meeting Abstract C1 VA Boston Healthcare Syst, W Roxbury, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Scripps Res Inst, La Jolla, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 631 BP 131 EP 131 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300629 ER PT J AU Haq, SE Tao, JZ Michael, A Rosenzweig, A Force, T AF Haq, SE Tao, JZ Michael, A Rosenzweig, A Force, T TI Pressure-overload hypertrophy in cPLA2 knockout mice SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 645 BP 134 EP 134 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300643 ER PT J AU Haq, SE Choukroun, G Lee, KH Ranu, H Vayssier-Taussat, M Boecker, W Woodgett, J Molkentin, JD Michael, A Force, T AF Haq, SE Choukroun, G Lee, KH Ranu, H Vayssier-Taussat, M Boecker, W Woodgett, J Molkentin, JD Michael, A Force, T TI Glycogen synthase kinase-3 a negative regulator of hypertrophy SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Ontario Canc Inst, Toronto, ON M4X 1K9, Canada. Childrens Hosp, Cincinnati, OH 45229 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 678 BP 140 EP 140 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300676 ER PT J AU Matsui, T Tao, JZ Del Monte, F Franke, TF Hajjar, RJ Rosenzweig, A AF Matsui, T Tao, JZ Del Monte, F Franke, TF Hajjar, RJ Rosenzweig, A TI Akt activation preserves cardiac function and prevents injury after transient cardiac ischemia in vivo SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Columbia Univ, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 793 BP 165 EP 165 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300791 ER PT J AU Hung, RR Gerszten, RE Matsui, T Franke, TF Rosenzweig, A AF Hung, RR Gerszten, RE Matsui, T Franke, TF Rosenzweig, A TI Activation of AKT in endothelial cells increases adhesion molecule expression but inhibits leukocyte adhesion under laminar flow conditions SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Columbia Univ, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 841 BP 174 EP 174 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300839 ER PT J AU Kuhlencordt, PJ Guyrko, R Kaprielian, R Guerero, L Crosbie, M Han, F Picard, MH Huang, PL AF Kuhlencordt, PJ Guyrko, R Kaprielian, R Guerero, L Crosbie, M Han, F Picard, MH Huang, PL TI Coronary and accelerated aortic atherosclerosis, intramyocardial fibrosis and heart failure in ApoE/eNOS double knockout mice. SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 849 BP 176 EP 176 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300846 ER PT J AU Patton, KK Niimura, H Soults, J McKenna, WJ Maron, BJ Seidman, JG Seidman, CE AF Patton, KK Niimura, H Soults, J McKenna, WJ Maron, BJ Seidman, JG Seidman, CE TI Sarcomere protein gene mutations: A frequent cause of elderly-onset hypertrophic cardiomyopathy. SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Kagoshima Univ, Kagoshima 890, Japan. HHMI, Boston, MA USA. Univ London St Georges Hosp, Sch Med, London SW17 0RE, England. Minneapolis Heart Inst, Minneapolis, MN USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RI Patton, Kristen/A-5626-2008; Niimura, Hideshi/H-1814-2012; McKenna, William/C-3243-2008; OI McKenna, William/0000-0001-7994-2460; Patton, Kristen K./0000-0002-9034-6966 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 861 BP 178 EP 178 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300858 ER PT J AU Beckman, JA Goldfine, AB Garrett, L Gordon, MB Creager, MA AF Beckman, JA Goldfine, AB Garrett, L Gordon, MB Creager, MA TI Protein kinase C inhibition potentiates vasodilation in hyperglycemia in healthy humans SO CIRCULATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 910 BP 188 EP 188 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300907 ER PT J AU Xiao, YF Ke, QG Wang, SY Yang, YK Wang, GK Morgan, JP Leaf, A AF Xiao, YF Ke, QG Wang, SY Yang, YK Wang, GK Morgan, JP Leaf, A TI Different molecular determinants of cocaine and n-3 fatty acid block of the human cardiac Na+ channel SO CIRCULATION LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA USA. SUNY Albany, Albany, NY 12222 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 936 BP 193 EP 193 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300933 ER PT J AU Scherrer-Crosbie, M Ullrich, R Bloch, KD Nakajima, H Aretz, HT Lindsey, ML Vancon, AC Lee, RT Zapol, WM Picard, MH AF Scherrer-Crosbie, M Ullrich, R Bloch, KD Nakajima, H Aretz, HT Lindsey, ML Vancon, AC Lee, RT Zapol, WM Picard, MH TI Nitric oxide synthase 3 limits left ventricular remodeling after myocardial infarction in mice. SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 947 BP 195 EP 195 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072300944 ER PT J AU Li, L Matsui, T Wu, JC Tao, JZ Picard, MH Rosenzweig, A AF Li, L Matsui, T Wu, JC Tao, JZ Picard, MH Rosenzweig, A TI Phenotypic spectrum caused by transgenic overexpression of activated AKT in the heart SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1079 BP 222 EP 223 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301076 ER PT J AU Nozaki, N Nemoto, S Defreitas, G Engel, DJ Baumgarten, G Sivasubramanian, N Carballo, E Blackshear, PJ Carabello, BA Mann, DL AF Nozaki, N Nemoto, S Defreitas, G Engel, DJ Baumgarten, G Sivasubramanian, N Carballo, E Blackshear, PJ Carabello, BA Mann, DL TI Hemodynamic overload induced myocardial cytokine gene regulation occurs through a novel mechanism that involves tristetraprolin SO CIRCULATION LA English DT Meeting Abstract C1 Winters Ctr Heart Failure Res, Houston, TX USA. Houston VAMC, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1081 BP 223 EP 223 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301078 ER PT J AU Ammer, R Keane, DTJ Aretz, HT Ruskin, JN AF Ammer, R Keane, DTJ Aretz, HT Ruskin, JN TI Persistent atrial fibrillation induces apoptosis in atrial and ventricular myocytes in goats SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1173 BP 241 EP 241 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301169 ER PT J AU Chen, HC Bouchie, JL Perez, AS Clermont, AC Feener, EP AF Chen, HC Bouchie, JL Perez, AS Clermont, AC Feener, EP TI Role of the AT1 receptor and stress-activated kinase pathway in the regulation of PAI-1 expression in vascular smooth muscle cells. SO CIRCULATION LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1264 BP 258 EP 258 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301259 ER PT J AU Haq, SE Choukroun, G Grazette, L Lim, H Tymitz, KM Del Monte, F Gwathmey, JK Michael, A Molkentin, JD Force, T AF Haq, SE Choukroun, G Grazette, L Lim, H Tymitz, KM Del Monte, F Gwathmey, JK Michael, A Molkentin, JD Force, T TI Differential regulation of the signaling pathways of the MAPKs, calcineurin and AKT in the failing human heart SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Cincinnati, OH 45229 USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1418 BP 289 EP 290 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301412 ER PT J AU Durante, W Peyton, PJ Schafer, AI AF Durante, W Peyton, PJ Schafer, AI TI Heme oxygenase-1 is an autocrine inhibitor of vascular smooth muscle cell growth SO CIRCULATION LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1457 BP 298 EP 298 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301451 ER PT J AU Bloch, DB Nakajima, A Gulick, T Filippov, G Bloch, KD AF Bloch, DB Nakajima, A Gulick, T Filippov, G Bloch, KD TI Pac, a novel cytokine-induced transcriptional co-activator of peroxisome proliferator-activated receptor alpha (PPAR alpha). SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1493 BP 305 EP 305 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301488 ER PT J AU Brooks, WW Conrad, CH AF Brooks, WW Conrad, CH TI Spironolactone alters cardiac extracellular matrix composition SO CIRCULATION LA English DT Meeting Abstract C1 Boston VA Healthcare Syst, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1531 BP 312 EP 312 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301526 ER PT J AU McQuillan, BM Picard, MH Leavitt, M Weyman, AE AF McQuillan, BM Picard, MH Leavitt, M Weyman, AE TI Age-related increases in pulmonary artery systolic pressure among echocardiographic normal subjects SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1776 BP 363 EP 363 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301771 ER PT J AU Weyman, AE Gardin, JM Davidoff, R Ryan, T Sutton, MS Weissman, NJ AF Weyman, AE Gardin, JM Davidoff, R Ryan, T Sutton, MS Weissman, NJ TI Echocardiographic evaluation of pulmonary artery pressure (PASP) with clinical correlates in adults SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Irvine, Irvine, CA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Penn, Philadelphia, PA 19104 USA. Washington Hosp Ctr, Washington, DC 20010 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1773 BP 363 EP 363 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301768 ER PT J AU Friedman, PL Stevenson, WG Tchou, PJ Wharton, JM Keane, DTJ Skanes, A Dubuc, M AF Friedman, PL Stevenson, WG Tchou, PJ Wharton, JM Keane, DTJ Skanes, A Dubuc, M TI Reversible cryomapping of the slow pathway during catheter cryoablation of atrioventricular nodal reentrant supraventricular tachycardia SO CIRCULATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Duke Univ, Med Ctr, Durham, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. London Hlth Sci Ctr, London, ON, Canada. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1795 BP 368 EP 368 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301790 ER PT J AU Ichinose, F Sapirstein, A Ullrich, R Zapol, WM Bloch, KD AF Ichinose, F Sapirstein, A Ullrich, R Zapol, WM Bloch, KD TI Impairment of hypoxic pulmonary vasoconstriction by endotoxemia requires 5-lipoxygenase in mice SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1810 BP 371 EP 371 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301805 ER PT J AU Maki, JH Wilson, GJ Lauffer, RB Weisskoff, RM Yuan, C AF Maki, JH Wilson, GJ Lauffer, RB Weisskoff, RM Yuan, C TI Vessel wall enhancement with MS-325 facilitates plaque detection and characterization SO CIRCULATION LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Epix Med Inc, Cambridge, MA USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1832 BP 375 EP 375 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301827 ER PT J AU Januzzi, JL Sabatine, MS Choi, J Abernethy, WB Isselbacher, EM AF Januzzi, JL Sabatine, MS Choi, J Abernethy, WB Isselbacher, EM TI Refractory hypertension after type B aortic dissection is not due to renal artery compromise and does not predict adverse outcome. SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1954 BP 401 EP 402 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301949 ER PT J AU Januzzi, JL Sabatine, MS Evangellsta, A Bruckman, D Fattori, R Oh, JK Moore, AG Malouf, J Sechtem, U Llover, A Deutsch, HJ Gilon, D AF Januzzi, JL Sabatine, MS Evangellsta, A Bruckman, D Fattori, R Oh, JK Moore, AG Malouf, J Sechtem, U Llover, A Deutsch, HJ Gilon, D TI Iatrogenic aortic dissection - Results from the International Registry of Aortic Dissection (IRAD) SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Michigan, Coordinating Ctr IRAD, Ann Arbor, MI 48109 USA. Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1952 BP 401 EP 401 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301947 ER PT J AU Bitondo, JM Daggett, WM AF Bitondo, JM Daggett, WM TI Endoscopic vs. open saphenous vein harvest: A comparison of post-operative wound complications SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1957 BP 402 EP 402 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301952 ER PT J AU Thatte, HS Biswas, KS Najjar, SF Rhee, JH Birjiniuk, V Crittenden, MD Khuri, SF Michel, T AF Thatte, HS Biswas, KS Najjar, SF Rhee, JH Birjiniuk, V Crittenden, MD Khuri, SF Michel, T TI Multi-photon microscopy in the evaluation of human saphenous vein and the development of a new preservation solution SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Boston VAMC, Brigham & Womens Hosp, W Roxbury, MA USA. Boston VA Med Ctr, W Roxbury, MA USA. VA Boston Healthcare Syst, W Roxbury, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1955 BP 402 EP 402 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301950 ER PT J AU Jang, IK Bouma, BE Kang, DH Moon, YC Park, SJ Park, SW Seung, KB Choi, KB Shishkov, M Schelndorf, K Aretz, HT Tearney, GJ AF Jang, IK Bouma, BE Kang, DH Moon, YC Park, SJ Park, SW Seung, KB Choi, KB Shishkov, M Schelndorf, K Aretz, HT Tearney, GJ TI Identification of different coronary plaque types in living patients using optical coherence tomography SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Asan Med Ctr, Seoul, South Korea. St Marys Hosp, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 1997 BP 410 EP 411 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301992 ER PT J AU Bozkurt, B Geraci, JM Knowlton, AA AF Bozkurt, B Geraci, JM Knowlton, AA TI Spironolactone use in heart failure: Spiraling out of control? SO CIRCULATION LA English DT Meeting Abstract C1 Baylor Coll Med, VAMC, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 2002 BP 412 EP 412 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072301997 ER PT J AU Kubota, T Miyagishima, M Alvarez, RJ Kormos, RL Rosenblum, WD Semigran, MJ Dec, GW Holubkov, R McTiernan, CF Feldman, AM McNamara, DM AF Kubota, T Miyagishima, M Alvarez, RJ Kormos, RL Rosenblum, WD Semigran, MJ Dec, GW Holubkov, R McTiernan, CF Feldman, AM McNamara, DM TI Expression of proinflammatory cytokines in the failing human heart: Comparison of recent-onset and end-stage cardiomyopathy SO CIRCULATION LA English DT Meeting Abstract C1 Kyushu Univ, Grad Sch Med Sci, Fukuoka 812, Japan. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Ohio State Univ, Med Ctr, Columbus, OH 43210 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 2015 BP 414 EP 414 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302010 ER PT J AU McNamara, DM Starling, R Dec, GW Loh, E Torre-Amione, G Tokarczyk, TR Janosko, KM Holubkov, R AF McNamara, DM Starling, R Dec, GW Loh, E Torre-Amione, G Tokarczyk, TR Janosko, KM Holubkov, R TI Plasma cytokines in acute cardiomyopathy: Evolution over time, correlations with functional studies, and potential role in recovery SO CIRCULATION LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Penn, Philadelphia, PA 19104 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 2020 BP 415 EP 415 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302015 ER PT J AU Jafari, B Chindhuchao, N Hales, CA Quinn, DA AF Jafari, B Chindhuchao, N Hales, CA Quinn, DA TI N-acetylcysteine effects as an anti-oxidant on lung stretch: A possible protective agent in ventilator induced lung injury SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 2077 BP 427 EP 427 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302072 ER PT J AU Hylek, EM Regan, S Hughes, RA Go, AS Henault, LE Singer, DE AF Hylek, EM Regan, S Hughes, RA Go, AS Henault, LE Singer, DE TI Effect of age on maintenance warfarin dose among outpatients with an international normalized ratio (INR) target intensity of 2-3 SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Kaiser Permanente, San Francisco, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 2083 BP 428 EP 428 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302078 ER PT J AU Del Monte, F Williams, E Gwathmey, JK Rosenzweig, A Lewandowski, ED Hajjar, RJ AF Del Monte, F Williams, E Gwathmey, JK Rosenzweig, A Lewandowski, ED Hajjar, RJ TI Improvement in survival and metabolism following gene transfer of SERCA2a in aortic-banded rats in transition to heart failure SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Boston Univ, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 2203 BP 452 EP 453 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302198 ER PT J AU McQuillan, BM Picard, MH Leavitt, M Weyman, AE AF McQuillan, BM Picard, MH Leavitt, M Weyman, AE TI Lack of change in average pulmonary artery systolic pressures in echocardiographic normal subjects despite increased recording sensitivity: A decades' experience SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI McQuillan, Brendan/B-8271-2013 OI McQuillan, Brendan/0000-0002-2130-8114 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 2222 BP 456 EP 457 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302217 ER PT J AU Jaffer, FA O'Donnell, CJ Kissinger, KV Chan, SK Botnar, RM Edelman, RR Manning, WJ AF Jaffer, FA O'Donnell, CJ Kissinger, KV Chan, SK Botnar, RM Edelman, RR Manning, WJ TI MRI assessment of aortic atherosclerosis in an asymptomatic population: The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RI Botnar, Rene/E-6875-2012 OI Botnar, Rene/0000-0003-2811-2509 NR 0 TC 7 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 2228 BP 458 EP 458 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302223 ER PT J AU Chan, SK Jaffer, FA Botnar, RM Kissinger, KV Goepfert, L Manning, WJ AF Chan, SK Jaffer, FA Botnar, RM Kissinger, KV Goepfert, L Manning, WJ TI MRI aortic atherosclerosis reproducibility project SO CIRCULATION LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Botnar, Rene/E-6875-2012 OI Botnar, Rene/0000-0003-2811-2509 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 2238 BP 460 EP 460 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302233 ER PT J AU Jang, IK Tearney, GJ Kang, DH Moon, YC Park, SJ Park, SW Seung, KB Houser, SL Shishkov, M Pomerantsev, E Aretz, HT Bouma, BE AF Jang, IK Tearney, GJ Kang, DH Moon, YC Park, SJ Park, SW Seung, KB Houser, SL Shishkov, M Pomerantsev, E Aretz, HT Bouma, BE TI Comparison of optical coherence tomography and intravascular ultrasound for detection of coronary plaques with large lipid-core in living patients. SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Asan Med Ctr, Seoul, South Korea. St Marys Hosp, Seoul, South Korea. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 2474 BP 509 EP 509 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302468 ER PT J AU Carroll, DL Rankin, SH AF Carroll, DL Rankin, SH TI Changes in and satisfaction with physical functioning after myocardial infarction: The influence of gender in the elderly SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 2484 BP 511 EP 511 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302478 ER PT J AU Nagurney, JT Brown, DFM Chae, CU Chang, YC Cranmer, HH Chung, WG Dan, L Fisher, J Grossman, SA Tedrow, U Lewandrowski, KB Jang, IK AF Nagurney, JT Brown, DFM Chae, CU Chang, YC Cranmer, HH Chung, WG Dan, L Fisher, J Grossman, SA Tedrow, U Lewandrowski, KB Jang, IK TI A comparison of five cardiac markers for acute coronary syndrome SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Affiliated Emergency Med Residency, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 2526 BP 519 EP 520 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302520 ER PT J AU Tawakol, AA Fischman, AJ Creager, MA Gewirtz, H AF Tawakol, AA Fischman, AJ Creager, MA Gewirtz, H TI Role of nitric oxide in regulation of basal myocardial blood flow in normal humans. SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 2651 BP 545 EP 545 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302645 ER PT J AU Bouma, BE Tearney, GJ Shishkov, M Kang, DH Houser, SL Schlendorf, KH Aretz, HT Moon, YC Park, SJ Park, SW Seung, KB Jang, IK AF Bouma, BE Tearney, GJ Shishkov, M Kang, DH Houser, SL Schlendorf, KH Aretz, HT Moon, YC Park, SJ Park, SW Seung, KB Jang, IK TI Optical coherence tomography imaging of stents in living human patients SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Asan Med Ctr, Seoul, South Korea. St Marys Hosp, Seoul, South Korea. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 2661 BP 547 EP 547 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302655 ER PT J AU Semigran, MJ Lopez-Cuellar, J Zapol, WM Bloch, KD Palacios, IF AF Semigran, MJ Lopez-Cuellar, J Zapol, WM Bloch, KD Palacios, IF TI Vasodilation with inhaled nitric oxide identifies mitral stenosis patients with severe pulmonary hypertension likely to benefit from percutaneous mitral valvotomy SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 2679 BP 551 EP 551 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302673 ER PT J AU Leon, MN Harrell, LC Mahdi, NA Simosa, HF Palacios, IF AF Leon, MN Harrell, LC Mahdi, NA Simosa, HF Palacios, IF TI Immediate and long-term results of percutaneous mitral balloon valvuloplasty (PMV) in patients with echocardiographic scores 9-11. SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 2682 BP 552 EP 552 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302676 ER PT J AU Newton-Cheh, CH Larson, MG Benjamin, EJ Caunt, D D'Agostino, RB O'Donnell, CJ AF Newton-Cheh, CH Larson, MG Benjamin, EJ Caunt, D D'Agostino, RB O'Donnell, CJ TI The QT interval is a heritable quantitative trait with evidence for linkage to chromosome 3 in a genome-wide scan: The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Framingham Heart Dis Epidemiol Study, Framingham, MA 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 2835 BP 584 EP 585 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072302829 ER PT J AU Myers, J Jones, JW Oesterle, S Burkhoff, D AF Myers, J Jones, JW Oesterle, S Burkhoff, D TI Transmyocardial and percutaneous laser revascularization do not induce silent ischemia as assessed by exercise testing SO CIRCULATION LA English DT Meeting Abstract C1 Vet Affairs Med Ctr, Palo Alto, CA 94304 USA. Univ Missouri, Columbia, MO USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Columbia Univ, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 3135 BP 646 EP 646 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303127 ER PT J AU Singh, JP Larson, MG O'Donnell, CJ Tsuji, H Caunt, D Levy, D AF Singh, JP Larson, MG O'Donnell, CJ Tsuji, H Caunt, D Levy, D TI Genome scan linkage results for heart rate variability: The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. NHLBI, Framingham Heart Dis Epidemiol Study, 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 OCT 31 PY 2000 VL 102 IS 18 SU S MA 3306 BP 684 EP 684 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303298 ER PT J AU Singh, JP Evans, JC Tsuji, H Benjamin, EJ AF Singh, JP Evans, JC Tsuji, H Benjamin, EJ TI Is reduced heart rate variability associated with new onset atrial fibrillation? Insights from the Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Kansai Med Univ, Osaka, Japan. Framingham Heart Dis Epidemiol Study, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 3307 BP 684 EP 684 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303299 ER PT J AU Delmonte, F Harding, SE Rosenzweig, A Gwathmey, JK Hajjar, RJ AF Delmonte, F Harding, SE Rosenzweig, A Gwathmey, JK Hajjar, RJ TI Improvement in contractile function in isolated failing human ventricular cardiac myocytes by gene transfer of antisense phospholamban SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Univ London Imperial Coll Sci Technol & Med, London, England. Boston Univ, Boston, MA 02215 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 3485 BP 720 EP 721 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303477 ER PT J AU Schlendorf, KH Houser, SL Bouma, BE Koroshetz, WJ Tearney, GJ AF Schlendorf, KH Houser, SL Bouma, BE Koroshetz, WJ Tearney, GJ TI Imaging of carotid arteries with optical coherence tomography and correlation with histology SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 3527 BP 729 EP 729 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303519 ER PT J AU Klugherz, BD Llanos, G Lieuallen, W Kopia, GA Papandreou, G Narayanan, P Levengood, T Sasseen, BM Adelman, S Carter, AJ Falotico, R Wilensky, RL AF Klugherz, BD Llanos, G Lieuallen, W Kopia, GA Papandreou, G Narayanan, P Levengood, T Sasseen, BM Adelman, S Carter, AJ Falotico, R Wilensky, RL TI Intramural kinetics of sirolimus eluted from an intracoronary stent SO CIRCULATION LA English DT Meeting Abstract C1 Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Cordis Corp, Warren, NJ USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. Wyeth Ayerst, Malvern, PA USA. Stanford Univ, Palo Alto, CA 94304 USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 3 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 3544 BP 733 EP 733 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303536 ER PT J AU Okura, Y Dec, GW Hare, JM Berry, GR Tazelaar, HD Cooper, LT AF Okura, Y Dec, GW Hare, JM Berry, GR Tazelaar, HD Cooper, LT TI A multicenter registry comparison of cardiac sarcoidosis and idiopathic giant-cell myocarditis. SO CIRCULATION LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Hosp, Baltimore, MD 21287 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 3807 BP 788 EP 788 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303799 ER PT J AU Inglessis, I Chow, CM Rudski, L Zapol, WM Bloch, KD Semigran, MJ AF Inglessis, I Chow, CM Rudski, L Zapol, WM Bloch, KD Semigran, MJ TI Inhaled nitric oxide improves hemodynamics and right to left shunting in patients with right ventricular infarction SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. McGill Univ, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 3834 BP 794 EP 794 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303826 ER PT J AU Go, AS Hylek, EM Phillips, KA Henault, LE Selby, JV Ruskin, JN Singer, DE AF Go, AS Hylek, EM Phillips, KA Henault, LE Selby, JV Ruskin, JN Singer, DE TI Prevalence & predictors of antiarrhythmic drug use among 13,428 atrial fibrillation patients: The ATRIA study SO CIRCULATION LA English DT Meeting Abstract C1 Kaiser Permanente, Oakland, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Kaiser Permanente Med Care Program N Calif, Oakland, CA USA. Kaiser Permanente, Div Res, Oakland, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 3872 BP 802 EP 802 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072303864 ER PT J AU O'Donnell, CJ Larson, MG Jaffer, FA Kissinger, KV Levy, D Manning, WJ AF O'Donnell, CJ Larson, MG Jaffer, FA Kissinger, KV Levy, D Manning, WJ TI Aortic atherosclerosis detected by MRI is associated with contemporaneous and longitudinal risk factors: The Framingham Heart Study (FHS) SO CIRCULATION LA English DT Meeting Abstract C1 Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 4019 BP 836 EP 836 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072304010 ER PT J AU Philbin, EF McCullough, PA Di Salvo, TG Dec, GW Jenkins, PL Weaver, WD AF Philbin, EF McCullough, PA Di Salvo, TG Dec, GW Jenkins, PL Weaver, WD TI Socioeconomic status is an important determinant of use of invasive strategies after myocardial infarction in hospitals with cardiac surgery SO CIRCULATION LA English DT Meeting Abstract C1 Albany Med Coll, Albany, NY 12208 USA. Henry Ford Hlth Syst, Detroit, MI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Bassett Healthcare, Cooperstown, NY USA. Henry Ford Hosp, Detroit, MI 48202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 4035 BP 840 EP 840 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072304026 ER PT J AU Rumsfeld, JS Magid, DJ O'Brien, MM Plomondon, ME Parsons, LS Spertus, JA Every, NR Sales, AE AF Rumsfeld, JS Magid, DJ O'Brien, MM Plomondon, ME Parsons, LS Spertus, JA Every, NR Sales, AE TI Predictors of quality of life following acute coronary syndromes SO CIRCULATION LA English DT Meeting Abstract C1 Denver VA Med Ctr, Denver, CO USA. Colorado Permanente Med Grp, Denver, CO USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. RI Sales, Anne/D-9678-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 4080 BP 849 EP 849 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072304071 ER PT J AU Beinart, SC Sales, AE Parsons, LS Spertus, JA Caldwell, DM Every, NR AF Beinart, SC Sales, AE Parsons, LS Spertus, JA Caldwell, DM Every, NR TI Predictors of treatment satisfaction after admission for AMI and unstable angina SO CIRCULATION LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Missouri, Kansas City, MS USA. RI Sales, Anne/D-9678-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 4083 BP 850 EP 850 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072304074 ER PT J AU Fong, PP Sales, AE Parsons, LS Spertus, JA Caldwell, DM Every, NR AF Fong, PP Sales, AE Parsons, LS Spertus, JA Caldwell, DM Every, NR TI Functional status in veterans after discharge for unstable angina pectoris versus acute myocardial infarction SO CIRCULATION LA English DT Meeting Abstract C1 Univ Washington, VA Puget Sound Hlth Care, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Missouri, Kansas City, MO 64110 USA. RI Sales, Anne/D-9678-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 4088 BP 851 EP 851 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072304079 ER PT J AU Oliveria, SA Lapuerta, P McCarthy, BD Whyte, JL Asch, SM L'Italien, GJ AF Oliveria, SA Lapuerta, P McCarthy, BD Whyte, JL Asch, SM L'Italien, GJ TI Physician knowledge and barriers to the effective management of uncontrolled hypertension SO CIRCULATION LA English DT Meeting Abstract C1 Columbia Univ, Weill Med Coll, New York, NY USA. Bristol Myers Squibb Co, Princeton, NJ USA. Henry Ford Hlth Syst, Detroit, MI USA. VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 SU S MA 4108 BP 855 EP 855 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 367QE UT WOS:000090072304099 ER PT J AU Moreno, PR Murcia, AM Palacios, IF Leon, MN Bernardi, VH Fuster, V Fallon, JT AF Moreno, PR Murcia, AM Palacios, IF Leon, MN Bernardi, VH Fuster, V Fallon, JT TI Coronary composition and macrophage infiltration in atherectomy specimens from patients with diabetes mellitus SO CIRCULATION LA English DT Article DE atherosclerosis; coronary disease; diabetes mellitus; plaque ID ACUTE MYOCARDIAL-INFARCTION; HUMAN ATHEROSCLEROTIC PLAQUES; UNSTABLE ANGINA; TISSUE FACTOR; THROMBOGENICITY; RUPTURE; ANGIOPLASTY; DISRUPTION; THROMBOSIS; RESTENOSIS AB Background-Lipid-rich, inflamed atherosclerotic lesions are associated with plaque rupture and thrombosis,; which are the most important causes of death in patients with diabetes mellitus. This study was designed to quantify Lipid composition and macrophage infiltration in the coronary lesions of patients with diabetes mellitus, Methods and Results-A total of 47 coronary atherectomy specimens from patients with diabetes mellitus were examined and compared with 48 atherectomy specimens from patients without diabetes. Plaque composition was characterized by trichrome staining. Macrophage infiltration was characterized by immunostaining. Clinical and demographic data were similar in both groups. The percentage of total area occupied by lipid-rich atheroma was larger; in specimens from patients with diabetes (7+/-2%) than in specimens from patients without diabetes (2+/-1%; P=0.01); and the percentage of total area occupied by macrophages was larger in specimens from patients with diabetes (22+/-3%) than in specimens from patients without diabetes (12+/-1%; P=0.003). The incidence of thrombus was also higher in specimens from patients with diabetes than in specimens from patients without diabetes (62% versus 40%; P=0.04). Plaque composition, macrophage infiltration, and thrombus were similar in lesions from diabetic patients treated with insulin compared with lesions from patients treated with sulfonylureas or diet. Conclusions-Coronary tissue from patients with diabetes exhibits a larger content of lipid-rich atheroma, macrophage infiltration, and subsequent thrombosis than tissue from patients without diabetes. These differences suggest an increased vulnerability for coronary thrombosis in patients with diabetes mellitus. C1 Univ Kentucky, Gill Heart Inst, Lexington, KY USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Unit, Boston, MA USA. CUNY Mt Sinai Sch Med, Cardiovasc Inst, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Pathol, New York, NY 10029 USA. Mt Sinai Med Ctr, Dept Internal Med, Miami, FL USA. Excelsitas Med Ctr, Buenos Aires, DF, Argentina. RP Moreno, PR (reprint author), VA Med Ctr, 111B-CDD, Lexington, KY 40511 USA. RI Fuster, Valentin/H-4319-2015 OI Fuster, Valentin/0000-0002-9043-9986 NR 25 TC 222 Z9 232 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 BP 2180 EP 2184 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 368GM UT WOS:000090109400013 PM 11056089 ER PT J AU Slawsky, MT Colucci, WS Gottlieb, SS Greenberg, BH Haeusslein, E Hare, J Hutchins, S Leier, CV LeJemtel, TH Loh, E Nicklas, J Ogilby, D Singh, BN Smith, W AF Slawsky, MT Colucci, WS Gottlieb, SS Greenberg, BH Haeusslein, E Hare, J Hutchins, S Leier, CV LeJemtel, TH Loh, E Nicklas, J Ogilby, D Singh, BN Smith, W CA Study Investigators TI Acute hemodynamic and clinical effects of levosimendan in patients with severe heart failure SO CIRCULATION LA English DT Article DE heart failure; inotropic agents; vasodilation; calcium ID MEDIATED CALCIUM SENSITIZATION; POSITIVE INOTROPIC AGENTS; TROPONIN-C; MYOCARDIAL-CONTRACTILITY; ISOMETRIC TENSION; CA2+ SENSITIZER; RELAXATION; DOGS AB Background-We determined the short-term hemodynamic and clinical effects of levosimendan, a novel calcium-sensitizing agent, in patients with decompensated heart failure. Methods and Results-One hundred forty-six patients with New York Heart Association functional class III or IV heart failure (mean left ventricular ejection fraction 21+/-1%) who had a pulmonary capillary wedge pressure greater than or equal to 15 mm Kg and a cardiac index less than or equal to2.5 L.min(-1).m(-2) were enrolled in a multicenter, double-blind, placebo-controlled study and randomized 2:1 to intravenous infusion of levosimendan or placebo. Drug infusions were uptitrated over 4 hours from an initial infusion rate of 0.1 mug.kg(-1).min(-1) to a maximum rate of 0.4 mug.kg(-1).min(-1) and maintained at the maximal tolerated infusion rate for an additional 2 hours. Levosimendan caused dose-dependent increases in stroke volume and cardiac index be,inning with the lowest infusion rate and achieving maximal increases in stroke volume and cardiac index of 28% and 39%, respectively. Heart rate increased modestly (8%) at the maximal infusion rate and was not increased at the 2 lowest infusion rates. Levosimendan caused dose-dependent decreases in pulmonary capillary wedge, right atrial, pulmonary arterial, and mean arterial pressures. Levosimendan appeared to improve dyspnea and fatigue, as assessed by the patient and physician, and was not associated with a significant increase in adverse events. Conclusions-Levosimendan caused rapid dose-dependent improvement in hemodynamic function in patients with decompensated heart Failure. These hemodynamic effects appeared to be accompanied by symptom improvement and were not associated with a significant increase in the number of adverse events. Levosimendan may be of value in the short-term management of patients with decompensated heart failure. C1 Boston Univ, Med Ctr, Cardiovasc Med Sect, Boston, MA 02118 USA. Boston Univ, Med Ctr, Cardiomyopathy Program, Boston, MA 02118 USA. VA Boston Healthcare Syst, Boston, MA USA. Univ Maryland, Baltimore, MD 21201 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Calif Pacific Med Ctr, San Francisco, CA 94115 USA. Johns Hopkins Hosp, Baltimore, MD 21287 USA. Cardiol Consultants, Little Rock, AR USA. Ohio State Univ, Columbus, OH 43210 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Univ Michigan Hosp, Ann Arbor, MI 48109 USA. Presbyterian Univ, Penn Med Ctr, Philadelphia, PA USA. W Los Angeles VA Med Ctr, Los Angeles, CA USA. Louisiana Cardiovasc Res Ctr, New Orleans, LA USA. RP Colucci, WS (reprint author), Boston Univ, Med Ctr, Cardiovasc Sect, 88 E Newton St, Boston, MA 02118 USA. NR 25 TC 264 Z9 282 U1 0 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 BP 2222 EP 2227 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 368GM UT WOS:000090109400020 PM 11056096 ER PT J AU Hsia, J Simon, JA Lin, F Applegate, WB Vogt, MT Hunninghake, D Carr, M AF Hsia, J Simon, JA Lin, F Applegate, WB Vogt, MT Hunninghake, D Carr, M CA HERS Investigators TI Peripheral arterial disease in randomized trial of estrogen with progestin in women with coronary heart disease - The heart and estrogen/progestin replacement study SO CIRCULATION LA English DT Article DE hormones; peripheral vascular disease; coronary disease; women ID POSTMENOPAUSAL WOMEN; INTERMITTENT CLAUDICATION; CAROTID ATHEROSCLEROSIS; MYOCARDIAL-INFARCTION; DOUBLE-BLIND; THERAPY; PRAVASTATIN; PROGRESSION; LOVASTATIN; CHOLESTEROL AB Background-Postmenopausal estrogen use has been associated with reduced carotid atherosclerosis in observational studies, but this relationship has not been confirmed in a clinical trial. The impact of estrogen on atherosclerotic disease in other peripheral arteries is unknown. Methods and Results-Postmenopausal women with coronary heart disease (CHD) and an intact uterus (n=2763)were randomly assigned to conjugated equine estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) daily or to placebo in a secondary CHD prevention trial. This analysis focuses on incident peripheral arterial procedures and deaths in the 2 treatment groups; peripheral vascular disease was a predefined secondary outcome. During a mean of 4.1 years of follow-up, 311 peripheral arterial events were reported in 213 women, an annual incidence of 2.9%. The number of women who had peripheral arterial events was 99 among those assigned to active estrogen/progestin and 114 among those assigned to placebo, a nonsignificant difference (relative hazard 0.87, 95% CI 0.66 to 1.14), In the placebo group, hypertension and diabetes mellitus were independently associated with higher rates of peripheral arterial events, and plasma HDL cholesterol and body mass index were associated with lower rates of peripheral arterial events. In the estrogen/progestin group, current smoking and diabetes ware independent predictors of peripheral arterial events. Incident peripheral arterial disease was not a significant predictor of coronary, cardiovascular, or total mortality. Conclusions-Treatment with oral conjugated estrogen plus medroxyprogesterone acetate was not associated with a significant reduction in incident peripheral arterial events in postmenopausal women with preexisting CHD. C1 George Washington Univ, Dept Med, Washington, DC 20052 USA. San Francisco VA Med Ctr, Dept Gen Internal Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Wake Forest Univ, Dept Med, Winston Salem, NC 27109 USA. Univ Pittsburgh, Sch Med, Dept Orthopaed Surg, Pittsburgh, PA 15261 USA. Univ Minnesota, Heart Dis Prevent Clin, Minneapolis, MN USA. San Francisco VA Med Ctr, Dept Gen Internal Med, San Francisco, CA USA. RP Hsia, J (reprint author), 2150 Penn Ave NW 4-414, Washington, DC 20037 USA. NR 27 TC 44 Z9 45 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 31 PY 2000 VL 102 IS 18 BP 2228 EP 2232 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 368GM UT WOS:000090109400021 PM 11056097 ER PT J AU Liedtke, W Choe, Y Marti-Renom, MA Bell, AM Denis, CS Sali, A Hudspeth, AJ Friedman, JM Heller, S AF Liedtke, W Choe, Y Marti-Renom, MA Bell, AM Denis, CS Sali, A Hudspeth, AJ Friedman, JM Heller, S TI Vanilloid receptor-related osmotically activated channel (VR-OAC), a candidate vertebrate osmoreceptor SO CELL LA English DT Article ID CAENORHABDITIS-ELEGANS; LAMINA TERMINALIS; CAPSAICIN-RECEPTOR; ION-CHANNEL; SENSITIVITY; NEURONS; RAT; MECHANOTRANSDUCTION; IDENTIFICATION; TRANSDUCTION AB The detection of osmotic stimuli is essential for all organisms, yet few osmoreceptive proteins are known, none of them in vertebrates. By employing a candidate-gene approach based on genes encoding members of the TRP superfamily of ion channels, we cloned cDNAs encoding the vanilloid receptor-related osmotically activated channel (VR-OAC) from the rat, mouse, human, and chicken. This novel cation-selective channel is gated by exposure to hypotonicity within the physiological range. In the central nervous system, the channel is expressed in neurons of the circumventricular organs, neurosensory cells responsive to systemic osmotic pressure. The channel also occurs in other neurosensory cells, including inner-ear hair cells, sensory neurons, and Merkel cells. C1 Rockefeller Univ, Mol Genet Lab, New York, NY 10021 USA. Rockefeller Univ, Lab Sensory Neurosci, New York, NY 10021 USA. Rockefeller Univ, Lab Mol Biophys, New York, NY 10021 USA. Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. RP Heller, S (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. RI Marti-Renom, Marc/A-1836-2010; Liedtke, Wolfgang/G-4633-2011 OI Marti-Renom, Marc/0000-0002-0151-4279; FU Howard Hughes Medical Institute; NIDCD NIH HHS [DC00317, F32 DC000317, R01 DC000241, R01 DC000241-26]; NIDDK NIH HHS [DK41096, R01 DK041096, R01 DK041096-18]; NIGMS NIH HHS [GM54762, R01 GM054762, R01 GM054762-13, R29 GM054762] NR 43 TC 681 Z9 729 U1 6 U2 23 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 27 PY 2000 VL 103 IS 3 BP 525 EP 535 DI 10.1016/S0092-8674(00)00143-4 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 368YB UT WOS:000090144100017 PM 11081638 ER PT J AU Farzan, M Vasilieva, N Schnitzler, CE Chung, S Robinson, J Gerard, NP Gerard, C Choe, H Sodroski, J AF Farzan, M Vasilieva, N Schnitzler, CE Chung, S Robinson, J Gerard, NP Gerard, C Choe, H Sodroski, J TI A tyrosine-sulfated peptide based on the N terminus of CCR5 interacts with a CD4-enhanced epitope of the HIV-1 gp120 envelope glycoprotein and inhibits HIV-1 entry SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CD4 BINDING-SITE; GENETIC RESTRICTION; INFECTION; RECEPTOR; CORECEPTOR; ANTIBODY; 7-TRANSMEMBRANE; INDIVIDUALS; AIDS AB The sequential association of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 with CD4 and a seven-transmembrane segment coreceptor such as CC RB or CXCR4 initiates entry of the virus into its target cell. The N terminus of CCR5, which contains several sulfated tyrosines, plays a critical role in the CD4-dependent association of gp120 with CCR5 and in viral entry. Here we demonstrate that a tyrosine-sulfated peptide based on the N terminus of CCR5, but not its unsulfated analogue, inhibits infection of macrophages and peripheral blood mononuclear cells by CCR5-dependent, but not CXCR4-dependent, HIV-1 isolates. The sulfated peptide also inhibited the association of CCR5-expressing cells with gp120-soluble CD4 complexes and, less efficiently, with MIP-1 alpha. Moreover, this peptide inhibited the precipitation of gp120 by 48d and 23e antibodies, which recognize CD4-inducible gp120 epitopes, but not by several other antibodies that recognize proximal epitopes, The ability of the sulfated peptide to block 48d association with gp120 was dependent in part on seven tropism-determining residues in the third variable (V3) and fourth conserved (C4) domains of gp120, These data underscore the important role of the N-terminal sulfate moieties of CCR5 in the entry of R5 HIV-1 isolates and Localize a critical contact between gp120 and CCR5. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Sch Publ Hlth, Dept Canc Biol, Boston, MA 02115 USA. Childrens Hosp, Dept Pediat, Perlmutter Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Hosp, Dept Med, Boston, MA 02115 USA. Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70112 USA. RP Farzan, M (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 4 Binney St, Boston, MA 02115 USA. RI Schnitzler, Christine/G-8733-2013 FU NIAID NIH HHS [AI28691, R01 AI043891, AI41851, AI43891] NR 38 TC 118 Z9 124 U1 0 U2 9 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 OCT 27 PY 2000 VL 275 IS 43 BP 33516 EP 33521 DI 10.1074/jbc.M007228200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 368EK UT WOS:000090104600048 PM 10938094 ER PT J AU Keller, SM Adak, S Wagner, H Herskovic, A Komaki, R Brooks, BJ Perry, MC Livingston, RB Johnson, DH AF Keller, SM Adak, S Wagner, H Herskovic, A Komaki, R Brooks, BJ Perry, MC Livingston, RB Johnson, DH CA Eastern Cooperative Oncology Grp TI A randomized trial of postoperative adjuvant therapy in patients with completely resected stage II or IIIa non-small-cell lung cancer. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CHEMOTHERAPY; RADIOTHERAPY; CARCINOMA; CISPLATIN; TABLES AB Background: We conducted a randomized trial to determine whether combination chemotherapy plus thoracic radiotherapy is superior to thoracic radiotherapy alone in prolonging survival and preventing local recurrence in patients with completely resected stage II or IIIa non-small-cell lung cancer. Methods: After surgical staging and resection of the tumor (usually by lobectomy or pneumonectomy), the patients were randomly assigned to receive either four 28-day cycles of cisplatin (60 mg per square meter of body-surface area intravenously on day 1) and etoposide (120 mg per square meter intravenously on days 1, 2, and 3) administered concurrently with radiotherapy (a total of 50.4 Gy, given in 28 daily fractions) or radiotherapy alone (a total of 50.4 Gy, given in 28 daily fractions). Results: Of the 488 patients who were enrolled in the study, 242 were assigned to receive radiotherapy alone and 246 were assigned to receive chemotherapy and radiotherapy. The median duration of follow-up was 44 months. Treatment-associated mortality was 1.2 percent in the group given radiotherapy alone and 1.6 percent in the group given chemotherapy and radiotherapy. The median survival was 39 months in the group given radiotherapy and 38 months in the group given chemotherapy and radiotherapy (P= 0.56 by the log-rank test). The relative likelihood of survival among patients assigned to receive chemotherapy and radiotherapy, as compared with those assigned to receive radiotherapy alone, was 0.93 (95 percent confidence interval, 0.74 to 1.18). Intrathoracic disease recurred within the radiation field in 30 of 234 patients (13 percent) in the group given radiotherapy and in 28 of 236 patients (12 percent) in the group given chemotherapy and radiotherapy (P=0.84); data on recurrence were not available for 18 patients. Conclusions: As compared with radiotherapy alone, adjuvant radiotherapy and chemotherapy with cisplatin and etoposide does not decrease the risk of intrathoracic recurrence or prolong survival in patients with completely resected stage II or IIIa non-small-cell lung cancer. C1 Beth Israel Med Ctr, Dept Surg, New York, NY 10003 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA USA. H Lee Moffitt Canc Ctr, Dept Radiat Oncol, Tampa, FL USA. Oakwood Hosp, Dept Radiat Oncol, Detroit, MI USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. Alton Ochsner Med Fdn & Ochsner Clin, Div Med Oncol, Baton Rouge, LA USA. Univ Missouri, Ellis Fischer Canc Ctr, Div Hematol & Med Oncol, Columbia, MO USA. Univ Washington, Div Med Oncol, Seattle, WA 98195 USA. Vanderbilt Univ, Div Med Oncol, Nashville, TN USA. RP Keller, SM (reprint author), Beth Israel Med Ctr, Dept Surg, 1st Ave & 16th St, New York, NY 10003 USA. RI Johnson, David/A-7437-2009 FU NCI NIH HHS [CA120046, CA23318, CA31946] NR 23 TC 274 Z9 291 U1 1 U2 6 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 OCT 26 PY 2000 VL 343 IS 17 BP 1217 EP 1222 DI 10.1056/NEJM200010263431703 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 366PQ UT WOS:000090014100003 PM 11071672 ER PT J AU Nasser, SM Pitman, MB Pilch, BZ Faquin, WC AF Nasser, SM Pitman, MB Pilch, BZ Faquin, WC TI Fine-needle aspiration biopsy of papillary thyroid carcinoma - Diagnostic utility of cytokeratin 19 immunostaining SO CANCER CYTOPATHOLOGY LA English DT Article DE cytology; fine-needle aspiration biopsy; papillary carcinoma; cytokeratin (CK) 19; thyroid; immunocytochemistry ID INTERMEDIATE FILAMENT PROTEINS; FOLLICULAR VARIANT; EXPRESSION; EXPERIENCE; LESIONS; TUMORS; GLAND; PATTERN; KERATIN; BENIGN AB BACKGROUND. Papillary thyroid carcinoma is the most common malignant neoplasm of the thyroid gland, and fine-needle aspiration biopsy (FNAB) often is the initial diagnostic method used in its detection. Prior studies have shown that immunohistochemical staining for various cytokeratins in general, and cytokeratin 19 (CK19) in particular, can be applied as an ancillary technique for diagnosing papillary thyroid carcinoma in histologic specimens. In the current study the authors assessed the diagnostic utility of CK19 to detect papillary carcinoma effectively in cytologic preparations of thyroid FNABs. METHODS. Immunocytochemical staining with CK19 was performed on cytologic aspirates from 37 papillary thyroid carcinomas and 36 other lesions of the thyroid (14 follicular adenomas, 10 multinodular goiters, 5 cases of Hashimoto thyroiditis, 6 oncocytic [Hurthle cell] neoplasms, and 1 follicular carcinoma). All cases included in the study had a corresponding histopathology specimen. RESULTS. Positive immunocytochemical reactivity for CK19 was identified in 34 of 37 papillary carcinomas and in 1 of 36 other thyroid lesions (sensitivity of 92% and specificity of 97%). Although the strongest reactivity was obtained in methanol fixed thin layer preparations, the antibody also was effective in detecting papillary carcinoma in alcohol fixed and air-dried smears. The single false-positive case was a follicular adenoma with focal areas of papillary hyperplasia. AU other aspirates including those from cases of Hashimoto thyroiditis, multinodular goiter, follicular adenoma, oncocytic neoplasms, and follicular carcinoma were negative. CONCLUSIONS. CK19 is an effective, highly sensitive, and specific ancillary tool for the diagnosis of papillary carcinoma in thyroid FNABs. Cancer (Cancer Cytopathol) 2000;90:307-11. (C) 2000 American Cancer Society. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Faquin, WC (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. NR 21 TC 32 Z9 37 U1 1 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2000 VL 90 IS 5 BP 307 EP 311 DI 10.1002/1097-0142(20001025)90:5<307::AID-CNCR7>3.0.CO;2-N PG 5 WC Oncology; Pathology SC Oncology; Pathology GA 365DW UT WOS:000089934000007 PM 11038428 ER PT J AU Ayanian, JZ Weissman, JS Schneider, EC Ginsburg, JA Zaslavsky, AM AF Ayanian, JZ Weissman, JS Schneider, EC Ginsburg, JA Zaslavsky, AM TI Unmet health needs of uninsured adults in the United States SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID DISEASE RISK-FACTORS; FECAL-OCCULT-BLOOD; COLORECTAL-CANCER; MULTIPLE IMPUTATION; INSURANCE STATUS; CARE; ACCESS; US; RELIABILITY; POPULATION AB Context In 1998, 33 million US adults aged 18 to 64 years lacked health insurance. Determining the unmet health needs of this population may aid efforts to improve access to care. Objective To compare nationally representative estimates of the unmet health needs of uninsured and insured adults, particularly among persons with major health risks. Design and setting Random household telephone survey conducted in all 50 states and the District of Columbia through the Behavioral Risk Factor Surveillance System. Participants A total of 105 764 adults aged 18 to 64 years in 1997 and 117364 in 1998, classified as long-term (greater than or equal to 1 year) uninsured (9.7%), short-term (<1 year) uninsured (4.3 %), or insured (86.0%). Main Outcome Measures Adjusted proportions of participants who could not see a physician when needed due to cost in the past year, had not had a routine checkup within 2 years, and had not received clinically indicated preventive services, compared by insurance status. Results Long-term- and short-term-uninsured adults were more likely than insured adults to report that they could not see a physician when needed due to cost (26.8%, 21.7%, and 8.2%, respectively), especially among those in poor health (69.1 %, 51.9%, and 21.8%) or fair health (48.8%, 42.4%, and 15.7%) (P<.001). Long-term-uninsured adults in general were much more likely than short-term-uninsured and insured adults not to have had a routine checkup in the last 2 years (42.8%, 22.3%, and 17.8%, respectively) and among smokers, obese individuals, binge drinkers, and people with hypertension, elevated cholesterol, diabetes, or human immunodeficiency virus risk factors (P<.001), Deficits in cancer screening, cardiovascular risk reduction, and diabetes care were most pronounced among long-term-uninsured adults. Conclusions In our study, long-term-uninsured adults reported much greater unmet health needs than insured adults. Providing insurance to improve access to care for long-term-uninsured adults, particularly those with major health risks, could have substantial clinical benefits. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Gen Med & Primary Care, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, Boston, MA USA. Harvard Univ, Sch Med, Dept Hlth Policy & Management, Boston, MA USA. Amer Soc Internal Med, Amer Coll Phys, Washington, DC USA. RP Ayanian, JZ (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. OI Schneider, Eric/0000-0002-1132-5084 NR 83 TC 420 Z9 422 U1 2 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 25 PY 2000 VL 284 IS 16 BP 2061 EP 2069 DI 10.1001/jama.284.16.2061 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 364QA UT WOS:000089902100026 PM 11042754 ER PT J AU Bauer, MP Bridgham, JT Langenau, DM Johnson, AL Goetz, FW AF Bauer, MP Bridgham, JT Langenau, DM Johnson, AL Goetz, FW TI Conservation of steroidogenic acute regulatory (StAR) protein structure and expression in vertebrates SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE StAR-related proteins; expression; amino acid sequences ID TROUT SALVELINUS-FONTINALIS; LIPOID ADRENAL-HYPERPLASIA; MESSENGER-RIBONUCLEIC-ACID; LEYDIG TUMOR-CELLS; GRANULOSA-CELLS; HEN; HORMONE; STIMULATION; ENZYMES; TISSUE AB Complementary DNAs for the open reading frames of the chicken, Xenopus and zebrafish StAR homologs were cloned along with a partial cDNA of the zebrafish homolog to MLN64, a StAR-related protein. A comparison of the amino acid sequences of piscine. amphibian, avian and mammalian StARs, indicates strong conservation of the protein across divergent vertebrate groups. On Northern blots probed with species specific StAR cDNAs, expression of StAR transcripts was observed in the ovary and adrenal of chicken, and the ovary, testis, kidney and head of zebrafish. The expression of StAR mRNA in various compartments of the hen ovary was consistent with the results of past studies on steroidogenesis; expression was first observed in follicles selected into the preovulatory hierarchy and was greatest in the largest preovulatory Follicle. The expression of StAR mRNA was also consistent with aromatase expression in zebrafish ovaries. The conserved deduced protein sequence and expression pattern of StAR transcripts in chicken and zebrafish tissues, strongly suggest that StAR is also involved in the regulation of steroidogenesis in nonmammalian vertebrates. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Goetz, FW (reprint author), Univ Notre Dame, Dept Biol Sci, POB 369, Notre Dame, IN 46556 USA. NR 30 TC 66 Z9 73 U1 1 U2 9 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD OCT 25 PY 2000 VL 168 IS 1-2 BP 119 EP 125 DI 10.1016/S0303-7207(00)00316-6 PG 7 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 369JK UT WOS:000165062000012 PM 11064158 ER PT J AU Lai, EC Jankovic, J Krauss, JK Ondo, WG Grossman, RG AF Lai, EC Jankovic, J Krauss, JK Ondo, WG Grossman, RG TI Long-term efficacy of posteroventral pallidotomy in the treatment of Parkinson's disease SO NEUROLOGY LA English DT Article AB The authors describe results of unilateral posteroventral pallidotomy (PVP) in 89 patients with PD. At 3 months after surgery, 81.9% of the patients reported marked or moderate improvement in their parkinsonian symptoms. Postoperative Unified PD Rating Scale "off" state mean total motor score improved by 35.5% and the mean activities of daily living score by 33.7% (p < 0,001). Improvements in parkinsonian symptoms were maintained in both "off" and "on" states in 62 patients at 12 months after PW and in 41 patients who were followed for 18 months or longer (mean 26.6 months). C1 Houston Vet Affairs Med Ctr, Houston, TX USA. Baylor Coll Med, Methodist Hosp, Dept Neurol, Houston, TX 77030 USA. Baylor Coll Med, Methodist Hosp, Dept Neurosurg, Houston, TX 77030 USA. RP Lai, EC (reprint author), Baylor Coll Med, Dept Neurol, 6550 Fannin,Suite 1801, Houston, TX 77030 USA. NR 10 TC 35 Z9 36 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 24 PY 2000 VL 55 IS 8 BP 1218 EP 1222 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 366PB UT WOS:000090012800027 PM 11071505 ER PT J AU Holt, JR Corey, DP AF Holt, JR Corey, DP TI Two mechanisms for transducer adaptation in vertebrate hair cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT National Academy of Sciences Colloquium on Auditory Neuroscience - Development, Transduction, and Integration CY MAY 19-21, 2000 CL IRVINE, CALIFORNIA SP Natl Acad Sci ID MYOSIN-I-BETA; MECHANOELECTRICAL-TRANSDUCTION; BULLFROGS SACCULUS; INNER-EAR; TIP LINKS; FUNCTIONAL EXPRESSION; BLOCK ADAPTATION; ACTIN-FILAMENTS; STEREOCILIA; BUNDLE AB Deflection of the hair bundle atop a sensory hair cell modulates the open probability of mechanosensitive ion channels. In response to sustained deflections, hair cells adapt. Two fundamentally distinct models have been proposed to explain transducer adaptation. Both models support the notion that channel open probability is modulated by calcium that enters via the transduction channels, Both also suggest that the primary effect of adaptation is to shift the deflection-response [I(X)] relationship in the direction of the applied stimulus, thus maintaining hair bundle sensitivity. The models differ in several respects. They operate on different time scales: the faster on the order of a few milliseconds or less and the slower on the order of 10 ms or more. The model proposed to explain fast adaptation suggests that calcium enters and binds at or near the transduction channels to stabilize a closed conformation. The:model proposed to explain the slower adaptation suggests that adaptation is mediated by an active, force-generating process that regulates the effective stimulus applied to the transduction channels, Here we discuss the evidence in support of each model and consider the possibility that both may function to varying degrees in hair cells of different species and sensory organs. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Neurobiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Holt, JR (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Neurobiol, Wellman 414, Boston, MA 02114 USA. OI Corey, David/0000-0003-4497-6016 NR 55 TC 75 Z9 81 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 24 PY 2000 VL 97 IS 22 BP 11730 EP 11735 DI 10.1073/pnas.97.22.11730 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 367PQ UT WOS:000090071000012 PM 11050202 ER PT J AU O'Brien, SP Seipel, K Medley, QG Bronson, R Segal, R Streuli, M AF O'Brien, SP Seipel, K Medley, QG Bronson, R Segal, R Streuli, M TI Skeletal muscle deformity and neuronal disorder in Trio exchange factor-deficient mouse embryos SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gene targeting; embryonic lethality; Rac; mouse development ID PERONEAL MUSCULAR-ATROPHY; FACTOR DOMAINS; MYOGENIN GENE; RHO-GTPASE; IN-VIVO; PROTEINS; FAMILY; KINASE; CYTOSKELETON; MYOTUBES AB Dbl-homology guanine nucleotide exchange factors (DH-GEFs) regulate actin cytoskeletal reorganization, cell adhesion, and gene transcription via activation of Rho GTPases, However, little is known about the physiological role of mammalian DH-GEFs during development, The DH-GEF family member Trio is of particular interest because it is a multifunctional protein possessing two GEF domains, as well as a protein serine/threonine kinase domain, and trio-like genes in Caenorhabditis elegans and Drosophila were shown to function in neural migration and axon guidance. To determine the role of Trio during mammalian development, we generated a mouse trio loss-of-function mutation (trio(-/-)). Trio function is essential during late embryonic development as genotype analysis indicated that trio(-/-) embryos died between embryonic day (E)-15.5 and birth, or shortly thereafter. In the trio(-/-) embryos, primary skeletal myofibers were relatively normal at E14.5; but by E18.5 highly unusual spherical myofibers accumulated. Trio deficiency may cause a defect in secondary myogenesis. as the appearance of the abnormal trio(-/-) skeletal myofibers temporally coincided with the onset of secondary myogenesis, and smaller secondary myofibers located adjacent to the primary myofibers were absent. The proliferation of trio(-/-) secondary myoblasts appeared normal, suggesting that Trio may regulate secondary myoblast alignment or fusion. trio(-/-) embryos also displayed, aberrant organization in several regions within the brain, including the hippocampal formation and olfactory bulb. We thus conclude that Trio is essential for late embryonic development, and that Trio functions in fetal skeletal muscle formation and in the organization of neural tissues. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Tufts Univ, Sch Vet Med, Boston, MA 02111 USA. RP Streuli, M (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 38 TC 107 Z9 108 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 24 PY 2000 VL 97 IS 22 BP 12074 EP 12078 DI 10.1073/pnas.97.22.12074 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 367PQ UT WOS:000090071000067 PM 11050238 ER PT J AU Hirschhorn, JN Sklar, P Lindblad-Toh, K Lim, YM Ruiz-Gutierrez, M Bolk, S Langhorst, B Schaffner, S Winchester, E Lander, ES AF Hirschhorn, JN Sklar, P Lindblad-Toh, K Lim, YM Ruiz-Gutierrez, M Bolk, S Langhorst, B Schaffner, S Winchester, E Lander, ES TI SBE-TAGS: An array-based method for efficient single-nucleotide polymorphism genotyping SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID OLIGONUCLEOTIDE ARRAYS; GENETIC INFORMATION; GENOME; SCALE; ASSAY; TOOL AB Generating human single-nucleotide polymorphisms (SNPs) is no longer a rate-limiting step for genetic studies of disease. The number of SNPs in public databases already exceeds 200,000, and the total is expected to exceed 1,000,000 within a year. Rather, progress is limited by the inability to genotype large numbers of SNPs. Current genotyping methods are suitable for studying individual loci or at most a handful at a time. Here, we describe a method for parallel genotyping of SNPs, called single base extension-tag array on glass slides, SEE-TAGS. The principle is as follows. SNPs are genotyped by single base extension (SBE), using bifunctional primers carrying a unique sequence tag in addition to a locus-specific sequence. Because each locus has a distinct tag, the genotyping reactions can be performed in a highly multiplexed fashion, and the resulting product can then be "demultiplexed" by hybridization to the reverse complements of the sequence tags arrayed on a glass slide. SEE-TAGS is simple and inexpensive because of the high degree of multiplexing and the use of an easily generated, generic tag array. The method is also highly accurate: we genotyped over 100 SNPs, obtaining over 5,000 genotypes, with approximately 99% accuracy. C1 MIT, Whitehead Inst Biomed Res, Ctr Genome Res, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Lander, ES (reprint author), MIT, Whitehead Inst Biomed Res, Ctr Genome Res, 1 Kendall Sq,Bldg 300, Cambridge, MA 02139 USA. RI Schaffner, Stephen/D-1189-2011 NR 24 TC 137 Z9 149 U1 0 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 24 PY 2000 VL 97 IS 22 BP 12164 EP 12169 DI 10.1073/pnas.210394597 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 367PQ UT WOS:000090071000083 PM 11035790 ER PT J AU Butte, AJ Tamayo, P Slonim, D Golub, TR Kohane, IS AF Butte, AJ Tamayo, P Slonim, D Golub, TR Kohane, IS TI Discovering functional relationships between RNA expression and chemotherapeutic susceptibility using relevance networks SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN CANCER-CELLS; L-PLASTIN; GENE-EXPRESSION; PATTERNS; 14-3-3-ZETA; ACTIVATION; DISPLAY AB In an-effort to find gene regulatory networks and clusters of genes that affect cancer susceptibility to anticancer agents, we joined a database with baseline expression levels of 7,245 genes measured by using microarrays in 60 cancer cell lines, to a database with the amounts of 5,084 anticancer agents needed to inhibit growth of those same cell lines. Comprehensive pair-wise correlations were calculated between gene expression and measures of agent susceptibility. Associations weaker than a threshold strength were removed, leaving networks of highly correlated genes and agents called-relevance networks. Hypotheses for potential single-gene determinants of anticancer agent susceptibility were constructed. The effect of random chance in the large number of calculations performed:was empirically determined by repeated random permutation testing; only associations stronger than those seen in multiply permuted data were used in clustering. We discuss the advantages of this methodology over alternative approaches, such as phylogenetic-type tree clustering and self-organizing maps. C1 Childrens Hosp, Informat Program, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Butte, AJ (reprint author), Childrens Hosp, Informat Program, 300 Longwood Ave, Boston, MA 02115 USA. RI Kohane, Isaac Kohane/K-3716-2012 OI Kohane, Isaac Kohane/0000-0003-2192-5160 FU NLM NIH HHS [5T15 LM07092-07, R01 LM06587-01, T15 LM007092] NR 27 TC 334 Z9 344 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 24 PY 2000 VL 97 IS 22 BP 12182 EP 12186 DI 10.1073/pnas.220392197 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 367PQ UT WOS:000090071000086 PM 11027309 ER PT J AU Ristow, M Pfister, MF Yee, AJ Schubert, M Michael, L Zhang, CY Ueki, K Michael, MD Lowell, BB Kahn, CR AF Ristow, M Pfister, MF Yee, AJ Schubert, M Michael, L Zhang, CY Ueki, K Michael, MD Lowell, BB Kahn, CR TI Frataxin activates mitochondrial energy conversion and oxidative phosphorylation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRIPLET-REPEAT EXPANSION; RAT-LIVER MITOCHONDRIA; FRIEDREICHS-ATAXIA; IN-VIVO; PYRIDINE-NUCLEOTIDES; INSULIN-RESISTANCE; IRON ACCUMULATION; HOMOLOG; PROTEIN; CELLS AB lFriedreich's ataxia (FA) is an autosomal recessive disease caused by decreased expression of the mitochondrial protein frataxin, The biological function of frataxin is unclear. The homologue of frataxin in yeast, YFH1, is required for cellular respiration and was suggested to regulate mitochondrial iron homeostasis. Patients suffering from FA exhibit decreased ATP production in skeletal muscle, We now demonstrate that overexpression of frataxin in mammalian cells causes a Ca2+-induced up-regulation of tricarboxylic acid cycle flux and respiration, which, in turn, leads to an increased mitochondrial membrane potential (Delta Psim) and results in an elevated cellular ATP content. Thus, frataxin appears to be a key activator of mitochondrial energy conversion and oxidative phosphorylation. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol & Metab, Boston, MA 02215 USA. RP Ristow, M (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. EM michael.ristow@uni-koeln.de; c.ronald.kahn@joslin.harvard.edu RI Schubert, Markus/F-5150-2010; Ristow, Michael/O-9858-2014 OI Ristow, Michael/0000-0003-2109-2453 FU NIDDK NIH HHS [DK 45935, R01 DK045935] NR 55 TC 137 Z9 141 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 24 PY 2000 VL 97 IS 22 BP 12239 EP 12243 DI 10.1073/pnas.220403797 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 367PQ UT WOS:000090071000096 PM 11035806 ER PT J AU Lee, CA Silva, M Siber, AM Kelly, AJ Galyov, E McCormick, BA AF Lee, CA Silva, M Siber, AM Kelly, AJ Galyov, E McCormick, BA TI A secreted Salmonella protein induces a proinflammatory response in epithelial cells, which promotes neutrophil migration SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NF-KAPPA-B; INTESTINAL EPITHELIUM; NUCLEAR RESPONSES; BACTERIAL ENTRY; PEYERS-PATCHES; HOST-CELL; TYPHIMURIUM; INVASION; DUBLIN; VIRULENCE AB In response to Salmonella typhimurium, the intestinal epithelium generates an intense inflammatory response consisting largely of polymorphonuclear leukocytes (neutrophils, PMN) migrating toward and ultimately across the epithelial monolayer into the intestinal lumen. It has been shown that bacterial-epithelial cell interactions elicit the production of inflammatory regulators that promote transepithelial PMN migration. Although S. typhimurium can enter intestinal epithelial cells, bacterial internalization is not required for the signaling mechanisms that induce PMN movement. Here, we sought to determine which S, typhimurium factors and intestinal epithelial signaling pathways elicit the production of PMN chemoattractants by enterocytes. Our results suggest that S. typhimurium activates a protein kinase C-dependent signal transduction pathway that orchestrates transepithelial PMN movement. We show that the type ill effector protein, SipA, is not only necessary but is sufficient to induce this proinflammatory response in epithelial cells. Our results force us to reconsider the long-held view that Salmonella effector proteins must be directly delivered into host cells from bacterial cells. C1 Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Inst Anim Hlth, Compton RG20 7NN, Berks, England. RP McCormick, BA (reprint author), Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK50989] NR 51 TC 128 Z9 129 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 24 PY 2000 VL 97 IS 22 BP 12283 EP 12288 DI 10.1073/pnas.97.22.12283 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 367PQ UT WOS:000090071000104 PM 11050248 ER PT J AU Fernandez, A Grumbach, K Goitein, L Vranizan, K Osmond, DH Bindman, AB AF Fernandez, A Grumbach, K Goitein, L Vranizan, K Osmond, DH Bindman, AB TI Friend or foe? How primary care physicians perceive hospitalists SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID INTERNAL-MEDICINE; SYSTEM; EXPERIENCE; PATIENT; MODEL AB Background: increased use of hospitalists is redefining the role of primary care physicians. Whether primary care physicians welcome this transition is unknown. We examined primary care physicians' perceptions of how hospitalists affect their practices, their patient relationships, and overall patient care. Methods: A mailed survey of randomly selected general internists, general pediatricians, and family practitioners with experience with hospitalists practicing in California. Main Outcome Measures: Physicians' self-reports of hospitalists' effects on quality of patient care and on their own practices. Results: Seven hundred eight physicians were eligible for this study, and there was a 74% response rate. Of the 524 physicians who responded, 34% were internists, 38% were family practitioners, and 29% were pediatricians. Of the 524 respondents, 335 (64%) had hospitalists available to them and 120 (23%) were required to use hospitalists for all admissions. Physicians perceived hospitalists as increasing (41%) or not changing (44%) the overall quality of care and perceived their practice style differences as neutral or beneficial. Twenty-eight percent of primary care physicians believed that the quality of the physician-patient relationship decreased; 69% reported that hospitalists did not affect their income; 53% believed that hospitalists decreased their workload; and 50% believed that hospitalists increased practice satisfaction. In a multivariate model predicting physician perceptions, internists, physicians who attributed loss of income to hospitalists, and physicians in mandatory hospitalist systems viewed hospitalists less favorably. Conclusions: Practicing primary care physicians have generally favorable perceptions of hospitalists' effect on patients and on their own practice satisfaction, especially in voluntary hospitalist systems that decrease the workload of primary care physicians and do not threaten their income. Primary care physicians, particularly internists, are less accepting of mandatory hospitalist systems. C1 San Francisco Gen Hosp, Primary Care Res Ctr, San Francisco, CA 94110 USA. San Francisco Gen Hosp, Div Gen Internal Med, San Francisco, CA 94110 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Community & Family Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biostat & Epidemiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Calif Hlth Workforce Studies, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Fernandez, A (reprint author), San Francisco Gen Hosp, Primary Care Res Ctr, Bldg 90,Ward 95,1001 Potrero Ave, San Francisco, CA 94110 USA. RI Grumbach, Kevin/L-9222-2016 FU AHRQ HHS [R03HS09557-01] NR 18 TC 28 Z9 28 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 23 PY 2000 VL 160 IS 19 BP 2902 EP 2908 DI 10.1001/archinte.160.19.2902 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 365ZL UT WOS:000089980300003 PM 11041896 ER PT J AU Brand, JG AF Brand, JG TI Within reach of an end to unnecessary bitterness? SO LANCET LA English DT Editorial Material ID TASTE; GUSTDUCIN C1 Monell Chem Senses Ctr, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Philadelphia, PA 19104 USA. RP Brand, JG (reprint author), Monell Chem Senses Ctr, 3500 Market St, Philadelphia, PA 19104 USA. RI Marion-Poll, Frederic/D-8882-2011 OI Marion-Poll, Frederic/0000-0001-6824-0180 NR 20 TC 8 Z9 8 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD OCT 21 PY 2000 VL 356 IS 9239 BP 1371 EP 1372 DI 10.1016/S0140-6736(00)02836-1 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 365XQ UT WOS:000089976100005 PM 11052575 ER PT J AU Vallee, JP AF Vallee, JP TI Complete coloscopy for colorectal cancer screening? SO PRESSE MEDICALE LA French DT Editorial Material C1 Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Div Gastroenterol, Portland, OR 97207 USA. RP Vallee, JP (reprint author), Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Div Gastroenterol, P-3-GI,POB 1034, Portland, OR 97207 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSON EDITEUR PI PARIS 06 PA 120 BLVD SAINT-GERMAIN, 75280 PARIS 06, FRANCE SN 0755-4982 J9 PRESSE MED JI Presse Med. PD OCT 21 PY 2000 VL 29 IS 31 BP 1707 EP 1707 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 368ZH UT WOS:000090147000008 PM 11094616 ER PT J AU Tarazi, FI Zhang, KH Baldessarini, RJ AF Tarazi, FI Zhang, KH Baldessarini, RJ TI Effects of nigrostriatal dopamine denervation on ionotropic glutamate receptors in rat caudate-putamen SO BRAIN RESEARCH LA English DT Article DE autoradiography; caudate-putamen; glutamate receptors; 6-hydroxydopamine; Parkinson's disease ID MONOAMINE-DEPLETED RATS; NUCLEUS-ACCUMBENS-SEPTI; MEDIAL FOREBRAIN-BUNDLE; D-ASPARTATE RECEPTORS; METHYL-D-ASPARTATE; BASAL GANGLIA; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; STRIATUM; AMPA AB Changes in ionotropic glutamate NMDA, AMPA and KA receptor binding in rat caudate-putamen were examined by quantitative in vitro receptor autoradiography 5 weeks after lesioning nigrostriatal dopaminergic projections. In this animal model of Parkinson's disease, density of binding in caudate-putamen increased at KA, but not NMDA or AMPA receptors. The findings indicate that nigrostriatal dopamine denervation can selectively enhance KA receptor levels in rat basal ganglia, suggest that KA receptors contribute to the pathophysiology of Parkinson's disease, and may suggest innovative treatments. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Tarazi, FI (reprint author), Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. FU NIMH NIH HHS [MH-47370, MH-34006] NR 22 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 20 PY 2000 VL 881 IS 1 BP 69 EP 72 DI 10.1016/S0006-8993(00)02812-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 366ZQ UT WOS:000090036500009 PM 11033095 ER PT J AU Skiba, NP Hopp, JA Arshavsky, VY AF Skiba, NP Hopp, JA Arshavsky, VY TI The effector enzyme regulates the duration of G protein signaling in vertebrate photoreceptors by increasing the affinity between transducin and RGS protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTPASE ACCELERATING PROTEIN; CGMP PHOSPHODIESTERASE; INHIBITORY SUBUNIT; ROD PHOTORECEPTORS; TRANSITION-STATE; TARGET ENZYME; GAMMA-SUBUNIT; IN-VIVO; HYDROLYSIS; BINDING AB The photoreceptor-specific G protein transducin acts as a molecular switch, stimulating the activity of its downstream effector in its GTP-bound form and inactivating the effector upon GTP hydrolysis, This activity makes the rate of transducin GTPase an essential factor in determining the duration of photoresponse in vertebrate rods and cones. In photoreceptors, the slow intrinsic rate of transducin GTPase is accelerated by the complex of the ninth member of the regulators of G protein signaling family with the long splice variant of type 5 G protein beta subunit (RGS9-G beta 5L). However, physiologically rapid GTPase is observed only when transducin forms a complex with its effector, the gamma subunit of cGMP phosphodiesterase (PDE gamma), In this study, we addressed the mechanism by which PDE gamma regulates the rate of transducin GTPase, We found that RGS9-G beta 5L alone has a significant ability to activate transducin GTPase, but its affinity for transducin is low. PDEy acts by enhancing the affinity between activated transducin and RGS9-G beta 5L by more than 15-fold, which is evident both from kinetic measurements of transducin GTPase rate and from protein binding assays with immobilized transducin. Furthermore, our data indicate that a single RGS9-G beta 5L molecule is capable of accelerating the GTPase activity of similar to 100 transducin molecules/s. This rate is faster than the rates reported previously for any RGS protein and is sufficient for timely photoreceptor recovery in both rod and cone photoreceptors. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Howe Lab Ophthalmol, Boston, MA 02114 USA. RP Arshavsky, VY (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Howe Lab Ophthalmol, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY-12859] NR 37 TC 55 Z9 55 U1 1 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 OCT 20 PY 2000 VL 275 IS 42 BP 32716 EP 32720 DI 10.1074/jbc.C000413200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 366KD UT WOS:000090003800048 PM 10973941 ER PT J AU Rebeck, GW AF Rebeck, GW TI Confirmation of the genetic association of interleukin-1A with early onset sporadic Alzheimer's disease SO NEUROSCIENCE LETTERS LA English DT Article DE interleukin-1A; Alzheimer's disease; polymorphism ID PROTEIN-PRECURSOR; APOLIPOPROTEIN-E AB An association between altered risk of Alzheimer's disease (AD) and the interleukin-1A (IL-1A) gene was recently reported in two independent studies. Here, the IL-1A polymorphism was analyzed in a third population of 247 AD ;patients and 187 control individuals. In support of the published findings, the IL-1A 2/2 genotype was associated with an increased risk of early onset AD (odds ratio of 3.1, P = 0.02). Clinically, the IL-1A 2/2 genotype was associated with an earlier age of onset, but not with a change in the rate of progression of AD. (C) 2000 Elsevier Science Ireland Ltd. Ail rights reserved. C1 Massachusetts Gen Hosp, Alzheimer Res Unit, Charlestown, MA 02129 USA. RP Rebeck, GW (reprint author), Massachusetts Gen Hosp, Alzheimer Res Unit, 149 13th St, Charlestown, MA 02129 USA. FU NCHM CDC HHS [HM31862]; NIA NIH HHS [AG05134, AG14473] NR 12 TC 78 Z9 85 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD OCT 20 PY 2000 VL 293 IS 1 BP 75 EP 77 DI 10.1016/S0304-3940(00)01487-7 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 363HK UT WOS:000089829500020 PM 11065142 ER PT J AU Barouch, DH Santra, S Schmitz, JE Kuroda, MJ Fu, TM Wagner, W Bilska, M Craiu, A Zheng, XX Krivulka, GR Beaudry, K Lifton, MA Nickerson, CE Trigona, WL Punt, K Freed, DC Guan, LM Dubey, S Casimiro, D Simon, A Davies, ME Chastain, M Strom, TB Gelman, RS Montefiori, DC Lewis, MG Emini, EA Shiver, JW Letvin, NL AF Barouch, DH Santra, S Schmitz, JE Kuroda, MJ Fu, TM Wagner, W Bilska, M Craiu, A Zheng, XX Krivulka, GR Beaudry, K Lifton, MA Nickerson, CE Trigona, WL Punt, K Freed, DC Guan, LM Dubey, S Casimiro, D Simon, A Davies, ME Chastain, M Strom, TB Gelman, RS Montefiori, DC Lewis, MG Emini, EA Shiver, JW Letvin, NL TI Control of viremia and prevention of clinical AIDS in rhesus monkeys by cytokine-augmented DNA vaccination SO SCIENCE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-LYMPHOCYTES; IMMUNE-RESPONSES; CELL RESPONSES; DISEASE PROGRESSION; PROTECTION; INFECTION; MACAQUES; PROTEIN; HIV-1 AB With accumulating evidence indicating the importance of cytotoxic T Lymphocytes (CTLs) in containing human immunodeficiency virus-1 (HIV-1) replication in infected individuals, strategies are being pursued to elicit virus-specific CTLs with prototype HIV-1 vaccines. Here, we report the protective efficacy of vaccine-elicited immune responses against a pathogenic SHIV-89.6P challenge in rhesus monkeys. Immune responses were elicited by DNA vaccines expressing SIVmac239 Gag and HIV-1 89.6P Env, augmented by the administration of the purified fusion protein IL-2/Ig, consisting of interleukin-2 (IL-2) and the Fc portion of immunoglobulin G (IgG), or a plasmid encoding IL-2/Ig. After SHIV-89.6P infection, sham-vaccinated monkeys developed weak CTL responses, rapid Loss of CD4(+) T cells, no virus-specific CD4(+) T cell responses, high setpoint viral loads, significant clinical disease progression, and death in half of the animals by day 140 after challenge. in contrast, all monkeys that received the DNA vaccines augmented with IL-2/Ig were infected, but demonstrated potent secondary CTL responses, stable CD4(+) T cell counts, preserved virus-specific CD4(+) T cell responses, Low to undetectable setpoint viral Loads, and no evidence of clinical disease or mortality by day 140 after challenge. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Merck Res Labs, W Point, PA 19486 USA. So Res Inst, Frederick, MD 21701 USA. Duke Univ, Med Ctr, Durham, NC 27710 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Barouch, DH (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, 330 Brookline Ave, Boston, MA 02215 USA. FU NCI NIH HHS [CA-50139, R01 CA050139]; NIAID NIH HHS [AI-65301, P01 AI041521, AI-85343] NR 41 TC 753 Z9 768 U1 0 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 20 PY 2000 VL 290 IS 5491 BP 486 EP 492 DI 10.1126/science.290.5491.486 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 365HN UT WOS:000089946000042 PM 11039923 ER PT J AU Schwartz, GG AF Schwartz, GG TI Exploring new strategies for the management of acute coronary syndromes SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT Symposium on New Directions in the Understanding and Management of Acute Coronary Syndromes CY MAR 24, 2000 CL TORONTO, CANADA ID ACUTE MYOCARDIAL-INFARCTION; GLUCOSE-INSULIN-POTASSIUM; RANDOMIZED TRIAL; UNSTABLE ANGINA; THERAPY; REPERFUSION; DISEASE; ATHEROSCLEROSIS; ATORVASTATIN; ENDOTHELIUM AB Patients who present today with an acute coronary syndrome face a substantially lower risk of death, recurrent myocardial infarction, or severe ischemia than patients did a decade ago. Researchers are pursuing new strategies to further improve the outcomes of patients with acute coronary syndromes. These strategies may be grouped into 3 paradigms: (1) restoration and maintenance of coronary flow at the site of culprit lesion; (2) reduction of infarct size, reperfusion injury, and postischemic dysfunction; (3) stabilization of the coronary arterial wall and its interaction with the bloodstream to reduce recurrent ischemic events. The last approach encompasses strategies to alter the underlying vascular patho-physiology that leads to plaque instability and coronary thrombosis. Investigation into each of these paradigms may yield new strategies that will be incorporated into standard clinical management of acute coronary syndromes in coming years. With so many mechanistically different approaches to the management of acute coronary syndromes, clinicians have reason for optimism that continued progress will further reduce the morbidity and mortality associated with acute coronary syndromes and the likelihood of their recurrence, (C) 2000 by Excerpta Medica, Inc. C1 Univ Colorado, Hlth Sci Ctr, Denver Vet Affairs Med Ctr, Cardiol Sect 111B, Denver, CO 80220 USA. RP Schwartz, GG (reprint author), Univ Colorado, Hlth Sci Ctr, Denver Vet Affairs Med Ctr, Cardiol Sect 111B, 1055 Clermont St, Denver, CO 80220 USA. NR 36 TC 3 Z9 3 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 19 PY 2000 VL 86 IS 8B SI SI BP 44J EP 49J PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 372BU UT WOS:000165214400012 PM 11081448 ER PT J AU Greene, MF AF Greene, MF TI Oral hypoglycemic drugs for gestational diabetes SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID INSULIN C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Greene, MF (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 10 TC 27 Z9 27 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 19 PY 2000 VL 343 IS 16 BP 1178 EP 1179 DI 10.1056/NEJM200010193431608 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 364FY UT WOS:000089882800008 PM 11036125 ER PT J AU Canhoto, AJ Chestukhin, A Litovchick, L DeCaprio, JA AF Canhoto, AJ Chestukhin, A Litovchick, L DeCaprio, JA TI Phosphorylation of the retinoblastoma-related protein p130 in growth-arrested cells SO ONCOGENE LA English DT Article DE p130; G0; growth arrest; pRb ID LARGE-T-ANTIGEN; PHOSPHOAMINO ACID ANALYSIS; LAYER CELLULOSE PLATES; PRB-RELATED PROTEINS; GENE-PRODUCT; SUSCEPTIBILITY GENE; TRANSCRIPTIONAL REPRESSOR; FUNCTIONAL INACTIVATION; TUMOR-SUPPRESSOR; FAMILY PROTEINS AB The retinoblastoma family of proteins including pRB, p107 and p130 undergoes cell cycle dependent phosphorylation during the mid-G1 to S phase transition. This phosphorylation is dependent upon the activity of cyclin D/cdk4. In contrast to pRB and p107, p130 is phosphorylated during G0 and the early GT phase of the cell cycle, We observed that p130 is specifically phosphorylated on serine and threonine residues in T98G cells arrested in G0 by serum deprivation or density arrest. Identification of the phospho-serine and phosphothreonine residues revealed that most were clustered within a short co-linear region unique to p130, defined as the Loop, Deletion of the Loop region resulted in a change in the phosphorylation status of p130 under growth arrest conditions. Notably, deletion of the Loop did not affect the ability of p130 to bind to E2F-4 or SV40 Large T antigen, to induce growth arrest in Saos-2 cells, and to become hyperphosphorylated during the proliferative phase of the cell cycle. p130 undergoes specific G0 phosphorylation in a manner that distinguishes it from pRB and p107. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP DeCaprio, JA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Mayer 457,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [2T32CA09361, 5T32CA09031, R01-CA63113] NR 61 TC 37 Z9 39 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 19 PY 2000 VL 19 IS 44 BP 5116 EP 5122 DI 10.1038/sj.onc.1203893 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 365CD UT WOS:000089930100010 PM 11042701 ER PT J AU Frazier, AL Colditz, GA Fuchs, CS Kuntz, KM AF Frazier, AL Colditz, GA Fuchs, CS Kuntz, KM TI Cost-effectiveness of screening for colorectal cancer in the general population SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID FECAL OCCULT-BLOOD; LARGE BOWEL; UNRESECTED POLYPS; LARGE-INTESTINE; COLON; RISK; COLONOSCOPY; SIGMOIDOSCOPY; PREVALENCE; RECURRENCE AB Context A recent expert panel recommended that persons at average risk of colorectal cancer (CRC) begin screening for CRC at age 50 years using 1 of several strategies. However, many aspects of different CRC screening strategies remain uncertain. Objective To assess the consequences, costs, and cost-effectiveness of CRC screening in average-risk individuals. Design Cost-effectiveness analysis from a societal perspective using a Markov model. Subjects Hypothetical subjects representative of the 50-year-old US population at average risk for CRC. Setting Simulated clinical practice in the United States. Main Outcome Measures Discounted lifetime costs, life expectancy, and incremental cost-effectiveness (CE) ratio, compared used 22 different CRC screening strategies, including those recommended by the expert panel. Results In 1 base-case analysis, compliance was assumed to be 60% with the initial screen and 80% with follow-up or surveillance colonoscopy. The most effective strategy for white men was annual rehydrated fecal occult blood testing (FOBT) plus sigmoidoscopy (followed by colonoscopy if either a low- or high-risk polyp was found) every 5 years from age 50 to 85 years, which resulted in a 60% reduction in cancer incidence and an 80% reduction in CRC mortality compared with no screening, and an incremental CE ratio of $92 900 per year of life gained compared with annual unrehydrated FOBT plus sigmoidoscopy every 5 years. In a base-case analysis in which compliance with screening and follow-up is assumed to be 100%, screening more often than every 10 years was prohibitively expensive; annual rehydrated FOBT plus sigmoidoscopy every 5 years had an incremental CE ratio of $489 900 per life-year gained compared with the same strategy every 10 years. Other strategies recommended by the expert panel were either less effective or cost more per year of life gained than the alternatives. Colonoscopy every 10 years was less effective than the combination of annual FOBI plus sigmoidoscopy every 5 years. However, a single colonoscopy at age 55 years achieves nearly half of the reduction in CRC mortality obtainable with clolonoscopy every 10 years. Because of increased life expectancy among white women and increased cancer mortality among blacks, CRC screening was even more cost-effective in these groups than in white men. Conclusions Screening for CRC, even in the setting of imperfect compliance, significantly reduces CRC mortality at rests comparable to other cancer screening procedures. However, compliance rates significantly affect the incremental CE ratios. In this model of CRC, 60% compliance with an every 5-year schedule of screening was roughly equivalent to 100% compliance with an every 10-year schedule. Mathematical modeling used to inform clinical guidelines needs to take into account expected compliance rates. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 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. RP Frazier, AL (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU AHRQ HHS [HS07038]; NCI NIH HHS [5 K07 CA62252-03]; NIDDK NIH HHS [T32DK07703] NR 54 TC 403 Z9 412 U1 2 U2 20 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 18 PY 2000 VL 284 IS 15 BP 1954 EP 1961 DI 10.1001/jama.284.15.1954 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 362JC UT WOS:000089774000028 PM 11035892 ER PT J AU Galper, SR Lee, SJ Tao, ML Troyan, S Kaelin, CM Harris, JR Weeks, JC AF Galper, SR Lee, SJ Tao, ML Troyan, S Kaelin, CM Harris, JR Weeks, JC TI Patient preferences for axillary dissection in the management of early-stage breast cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID LYMPH-NODE DISSECTION; SENTINEL LYMPHADENECTOMY; PSYCHOLOGICAL MORBIDITY; CONSERVATIVE SURGERY; DECISION INSTRUMENT; RADIATION-THERAPY; ARM; COMPLICATIONS; CHEMOTHERAPY; RADIOTHERAPY AB Background: Recent data on the value of adjuvant therapy in lymph node-negative breast cancer and promising early data on less invasive strategies for managing the axilla have raised questions about the appropriate role of axillary lymph node dissection (ALND) in the management of early-stage breast cancer. We sought to evaluate how women weigh potential benefits of ALND-prognostic information, enhanced local control, and tailored therapy-against the risks of long-term morbidity that are associated with the procedure. Methods: We used hypothetical scenarios to survey 82 randomly selected women with invasive breast cancer who had been treated with ALND and 62 women at risk for invasive breast cancer by virtue of a history of ductal carcinoma in situ (DCIS) who had not undergone ALND, Results: Women in both the invasive cancer and the DCIS groups required substantial improvements in local control of the cancer (5% and 15%, respectively) and overall survival (3% and 10%, respectively) before they would opt for this procedure. Women with invasive cancer would choose ALND if it had only a 1% chance of altering treatment recommendations, whereas DCIS subjects required a 25% chance. Sixty-eight percent and 29% of women in the invasive cancer and DCIS groups, respectively, would accepted a 40% risk of arm dysfunction to gain prognostic information that would not change treatment. Conclusions: For most subjects treated previously for invasive breast cancer and almost half those at risk of the disease, the potential benefits of ALND, particularly the value of prognostic information, were sufficient to outweigh the risks of morbidity, However, women varied considerably in their preferences, highlighting the need to tailor decisions regarding management of the axilla to individual patients' values. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Weeks, JC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 44 TC 13 Z9 13 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 18 PY 2000 VL 92 IS 20 BP 1681 EP 1687 DI 10.1093/jnci/92.20.1681 PG 7 WC Oncology SC Oncology GA 363HW UT WOS:000089830600013 PM 11036114 ER PT J AU Ho, CY Lever, HM DeSanctis, R Farver, CF Seidman, JG Seidman, CE AF Ho, CY Lever, HM DeSanctis, R Farver, CF Seidman, JG Seidman, CE TI Homozygous mutation in cardiac troponin T - Implications for hypertrophic cardiomyopathy SO CIRCULATION LA English DT Article DE cardiomyopathy; cardiac troponin T; genetics ID HEAVY-CHAIN GENE; BINDING PROTEIN-C; MISSENSE MUTATION; PROGNOSTIC IMPLICATIONS; CLINICAL EXPRESSION; ALPHA-TROPOMYOSIN; MYOSIN; DISEASE AB Background-Mutations in the gene that encode cardiac troponin T (cTnT) account for approximate to 15% of cases of familial hypertrophic cardiomyopathy (HCM). These mutations are associated with a particularly severe form of HCM characterized by a high incidence of sudden death and a poor overall prognosis, despite subclinical or mild left ventricular hypertrophy. Methods and Results-We evaluated a family with HCM and multiple occurrences of sudden death in children. DNA samples were isolated from peripheral blood or paraffin-embedded tissue, and all protein-encoding exons of the cTnT gene were sequenced. A mutation was identified in exon 11 and is predicted to substitute a phenylalanine-for-serine mutation at residue 179 (Ser(179)Phe) in cTnT. Both parents and 3 of 4 surviving and clinically unaffected children were heterozygous for this mutation; another clinically unaffected child did not carry the mutation. Genetic analysis of DNA from a child who died suddenly at age 17 years demonstrated he was homozygous for this mutation. A review of his echocardiogram revealed profound left and right ventricular hypertrophy. Conclusions-An homozygous Ser(179)Phe mutation in cTnT causes a severe form of HCM characterized by striking morphological abnormalities and juvenile lethality. In contrast, the natural history of the heterozygous mutation is benign. These studies emphasize the relevance of genetic diagnosis in hypertrophic cardiomyopathy and provide a new perspective on the clinical consequences of troponin T mutations. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Seidman, CE (reprint author), Harvard Univ, Sch Med, Dept Genet, Alpert Bldg,200 Longwood Ave, Boston, MA 02115 USA. NR 28 TC 96 Z9 99 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 17 PY 2000 VL 102 IS 16 BP 1950 EP 1955 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 363UW UT WOS:000089856000016 PM 11034944 ER PT J AU Choo, J Gretler, DD Gold, HK AF Choo, J Gretler, DD Gold, HK TI Platelet aggregation inhibition with single and double bolus regimens of eptifibatide (Integrilin). SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract C1 COR Therapeut Inc, S San Francisco, CA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 16 PY 2000 VL 86 IS 8A SI SI MA 177 BP 71I EP 71I PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 373CB UT WOS:000165269800177 ER PT J AU Ali, NM Raizner, AE Schulz, DG Zymek, P Kaluza, GL AF Ali, NM Raizner, AE Schulz, DG Zymek, P Kaluza, GL TI The effects of intravascular beta-radiation with P-32 in stent injured porcine peripheral arteries. SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract C1 Baylor Coll Med, Methodist Hosp, Houston, TX 77030 USA. Baylor Coll Med, VA Med Ctr, Cardiol Sect, Dept Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 16 PY 2000 VL 86 IS 8A SI SI MA 326 BP 123I EP 123I PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 373CB UT WOS:000165269800322 ER PT J AU Kaluza, GL Zymek, P Schulz, DG Raizner, AE Ali, NM AF Kaluza, GL Zymek, P Schulz, DG Raizner, AE Ali, NM CA Methodist Hosp VA Med Ctr TI Is "Geographic miss" the mechanism of edge effect after intracoronary radiation? A histologic study. SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract C1 Baylor Coll Med, Methodist Hosp, Houston, TX 77030 USA. Baylor Coll Med, VA Med Ctr, Cardiol Sect, Dept Med, Houston, TX 77030 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 16 PY 2000 VL 86 IS 8A SI SI MA 334 BP 126I EP 126I PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 373CB UT WOS:000165269800330 ER PT J AU Koch, M Murrell, JR Hunter, DD Olson, PF Jin, W Keene, DR Brunken, WJ Burgeson, RE AF Koch, M Murrell, JR Hunter, DD Olson, PF Jin, W Keene, DR Brunken, WJ Burgeson, RE TI A novel member of the netrin family, beta-netrin, shares homology with the beta chain of laminin: Identification, expression, and functional characterization SO JOURNAL OF CELL BIOLOGY LA English DT Article DE axon guidance; kidney; olfactory bulb; vasculature; brain ID COLORECTAL-CANCER DCC; C-ELEGANS; CHEMOATTRACTANT NETRIN-1; CAENORHABDITIS-ELEGANS; ZEBRAFISH EMBRYO; NERVOUS-SYSTEM; GUIDANCE CUES; UNC-6; AXONS; MIGRATIONS AB The netrins are a family of laminin-related molecules. Here, we characterize a new member of the family, beta -netrin. beta -Netrin is homologous to the NH2 terminus of laminin chain short arms; it contains a laminin-like domain VI and 3.5 laminin EGF repeats and a netrin C domain. Unlike other netrins, this new netrin is more related to the laminin beta chains, thus, its name beta -netrin. An initial analysis of the tissue distribution revealed that kidney, heart, ovary, retina, and the olfactory bulb were tissues of high expression. We have expressed the molecule in a eukaryotic cell expression system and made antibodies to the expressed product. Both in situ hybridization and immunohistochemistry were used to describe the cellular source of beta -netrin and where beta -netrin is deposited. beta -Netrin is a basement membrane component; it is present in the basement membranes of the vasculature, kidney, and ovaries. In addition, beta -netrin is expressed in a limited set of fiber tracts within the brain, including the lateral olfactory tract and the vomeronasal nerve. Functional studies were performed and show that beta -netrin promotes neurite elongation from olfactory bulb explants. Together, these data suggest that beta -netrin is important in neural, kidney, and vascular development. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Tufts Univ, Sch Med, Dept Neurosci, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Anat & Cell Biol, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA. Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. Shriners Hosp Children, Portland, OR 97201 USA. RP CBRC, MGH E Bldg 149, Charlestown, MA 02129 USA. EM bob.burgeson@cbrc2.mgh.harvard.edu FU NEI NIH HHS [R01EY12037]; NIAMS NIH HHS [R37AR35689]; NINDS NIH HHS [R01 NS039502, R01 NS039502-03, R01NS39502] NR 51 TC 115 Z9 124 U1 0 U2 8 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA SN 0021-9525 EI 1540-8140 J9 J CELL BIOL JI J. Cell Biol. PD OCT 16 PY 2000 VL 151 IS 2 BP 221 EP 234 DI 10.1083/jcb.151.2.221 PG 14 WC Cell Biology SC Cell Biology GA 365JT UT WOS:000089948700006 PM 11038171 ER PT J AU Cariappa, A Liou, HC Horwitz, BH Pillai, S AF Cariappa, A Liou, HC Horwitz, BH Pillai, S TI Nuclear factor kappa B is required for the development of marginal zone B lymphocytes SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE transcription factors; lymphocyte development; recombination activating gene-2(-/-) mice; peripheral B cells; Bruton's tyrosine kinase ID CELL-CYCLE PROGRESSION; NECROSIS-FACTOR FAMILY; C-H TRANSCRIPTION; PROLIFERATIVE RESPONSES; IMMUNE-RESPONSES; MICE LACKING; DEFECTS; REL; DEFICIENT; ACTIVATION AB Although immunoglobulin (Ig)M(hi)IgD(lo/-)CD21(hi) marginal zone B cells represent a significant proportion of naive peripheral splenic B lymphocytes, few of the genes that regulate their development have been identified. This subset of peripheral B cells fails to emerge in mice that lack nuclear factor (NF)-kappa Bp50. Less drastic reductions in marginal zone B cell. numbers are also seen in the spleens of recombination activating gene (Rag)-2(-/-) mice reconstituted with NF-kappa Bp65(-/-) fetal liver cells and in c-Rel(-/-) mice. In contrast, steady-state levels of IgD(hi) splenic follicular B cells are not significantly reduced in the absence of NF-kappa Bp50, NF-kappa Bp65, or c-Rel. Reconstitution of B cells in Rag-2(-/-) mice with a mixture of p50(-/-)/p65(-/-) fetal liver cells and Rag-2(-/-) bone marrow cells revealed that the generation of marginal zone B cells requires the expression of NF-kappaB in developing B cells, as opposed to supporting cells. C1 Harvard Univ, Ctr Canc, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. CUNY, Coll Med, Dept Med, Div Immunol, New York, NY 10021 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Pillai, S (reprint author), Harvard Univ, Ctr Canc, Massachusetts Gen Hosp, Sch Med, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA69618]; NIAID NIH HHS [R01 AI033507, AI33507] NR 30 TC 123 Z9 126 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 16 PY 2000 VL 192 IS 8 BP 1175 EP 1182 DI 10.1084/jem.192.8.1175 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 366BA UT WOS:000089983900011 PM 11034607 ER PT J AU Wang, XB Chen, DF Niu, TH Wang, ZX Wang, LH Ryan, L Smith, T Christiani, DC Zuckerman, B Xu, XP AF Wang, XB Chen, DF Niu, TH Wang, ZX Wang, LH Ryan, L Smith, T Christiani, DC Zuckerman, B Xu, XP TI Genetic susceptibility to benzene and shortened gestation: Evidence of gene-environment interaction SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE benzene; cytochrome P-450CYP1A1; environmental exposure; genes; genetic predisposition to disease; gestational age; glutathione transferase ID S-TRANSFERASE-THETA; LUNG-CANCER; HOMOZYGOUS DELETION; PRETERM DELIVERY; EXPOSURE; RISK; POLYMORPHISMS; GENOTYPES; SOLVENTS; ENZYMES AB This study investigated whether the association between low level benzene exposure and shortened gestation is modified by two susceptibility genes, CYP1A1 and GSTT1. This report includes 542 (302 nonexposed, 240 benzene-exposed) nonsmoking and nondrinking mothers of singleton live births at Beijing Yanshan Petrochemical Corporation between June 1995 and June 1997. Epidemiologic and clinical data and blood samples were obtained from mothers. Multiple linear regression models were used to estimate the associations of benzene exposure and genetic susceptibility with gestational age, adjusting for maternal age, education, parity, stress, passive smoking, prepregnancy weight and height, and infant's sex. Without consideration of genotype, benzene exposure was associated with a decrease in mean gestational age of 0.29 (standard error (SE), 0.12) week. When stratified by the maternal CYP1A1 genotype, the estimated decrease was 0.54 (SE, 0.12) week for the AA group, which was significantly greater (p = 0.003) than that for the Aa/aa group, which showed no decrease in gestational age. When both CYP1A1 and GSTT1 were considered, the greatest decrease was found among exposed mothers with the CYP1A1 AA-GSTT1 absent group (0.79 (SE, 0.25) week) and the CYP1A1 AA-GSTT1 present group (0.50 (SE, 0.22) week). Among the nonexposed, genetic susceptibility alone did not confer a significant adverse effect. This study provides evidence of gene-environment interaction and supports further assessment of the role of genetic susceptibility in the evaluation of reproductive toxins. C1 Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. Boston Med Ctr, Boston, MA USA. Beijing Med Univ, Ctr Ecogenet & Reprod Hlth, Beijing, Peoples R China. Harvard Univ, Sch Publ Hlth, Program Populat Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. RP Wang, XB (reprint author), Boston Univ, Sch Med, Dept Pediat, Matern 4,818 Harrison Ave, Boston, MA 02118 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 FU NICHD NIH HHS [1R01 HD32505-01]; NIEHS NIH HHS [1R01 ES08337-01]; NIOSH CDC HHS [1R01 OH03027] NR 38 TC 47 Z9 53 U1 2 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 15 PY 2000 VL 152 IS 8 BP 693 EP 700 DI 10.1093/aje/152.8.693 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 364RK UT WOS:000089906500001 PM 11052546 ER PT J AU Saint, S Wiese, J Amory, JK Bernstein, ML Patel, UD Zemencuk, JK Bernstein, SJ Lipsky, BA Hofer, TP AF Saint, S Wiese, J Amory, JK Bernstein, ML Patel, UD Zemencuk, JK Bernstein, SJ Lipsky, BA Hofer, TP TI Are physicians aware of which of their patients have indwelling urinary catheters? SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID NURSING-HOME PATIENTS; TRACT INFECTION; NOSOCOMIAL INFECTIONS; UNITED-STATES; BACTERIURIA AB PURPOSE: Although infections associated with indwelling urinary catheters are common, costly, and morbid, the use of these catheters is unnecessary in more than one-third of patients. We sought to assess whether attending physicians, medical residents, and medical students are aware if their hospitalized patients have an indwelling urinary catheter, and whether physician awareness is associated with appropriate use of these catheters. METHODS: The physicians and medical students responsible for patients admitted to the medical services at four university-affiliated hospitals were given a list of the patients on their service. For each patient, the provider was asked: "As of yesterday afternoon, did this patient have an indwelling urethral catheter?" Respondents' answers were compared with the results of examining the patient. RESULTS: Among 288 physicians and students on 56 medical teams, 256 (89%) completed the survey. Of 469 patients, 117 (25%) had an indwelling catheter. There were a total of 319 provider-patient observations among these 117 patients. Over all, providers were unaware of catheterization for 88 (28%) of the 319 provider-patient observations. Unawareness rates by level of training were 21% for students, 22% for interns, 27% for residents, and 38% for attending physicians (P = 0.06). Catheter use was inappropriate in 36 (31%) of the 117 patients with a catheter. Providers were unaware of catheter use for 44 (41%) of the 108 provider-patient observations of patients who were inappropriately catheterized. Catheterization was more Likely to be appropriate if respondents were aware of the catheter (odds ratio = 3.7; 95% confidence interval, 2.1 to 6.7, P<0.001). CONCLUSION: Physicians are commonly unaware that their patients have an indwelling urinary catheter. Inappropriate catheters are more often "forgotten" than appropriate ones. System-wide interventions aimed at discontinuing unnecessary catheterization seem warranted. Am J Med. 2000;109: 476-480. (C) 2000 by Excerpta Medica, Inc. C1 Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA 94143 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Vet Affairs Ann Arbor Healthcare Syst, Vet Affairs Ctr Practice Management & Outcomes, Ann Arbor, MI USA. Vet Affairs Puget Sound Hlth Care Syst, Primary & Specialty Med Care, Seattle, WA USA. RP Saint, S (reprint author), Univ Michigan Hlth Syst, Taubman Ctr 3116, Box 0376,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 23 TC 126 Z9 126 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT 15 PY 2000 VL 109 IS 6 BP 476 EP 480 DI 10.1016/S0002-9343(00)00531-3 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 367JC UT WOS:000090057100006 PM 11042237 ER PT J AU Gage, BF Fihn, SD White, RH AF Gage, BF Fihn, SD White, RH TI Management and dosing of warfarin therapy SO AMERICAN JOURNAL OF MEDICINE LA English DT Review ID ORAL ANTICOAGULANT-THERAPY; FRESH-FROZEN PLASMA; EXCESSIVE ANTICOAGULATION; VITAMIN-K; RANDOMIZED TRIAL; DECISION-SUPPORT; SUBCUTANEOUS VITAMIN-K-1; OUTPATIENT THERAPY; SELF-MANAGEMENT; STEADY-STATE AB When initiating warfarin therapy, clinicians should avoid loading doses-that can raise the International Normalized Ratio (INR) excessively; instead, warfarin should be initiated with a 5-mg dose (or 2 to 4 mg in the very elderly). With a 5-mg initial dose, the INR will not rise appreciably in the first 24 hours, except in rare patients who will ultimately require a very small daily dose (0.5 to 2.0 mg). Adjusting a steady-slate warfarin dose depends on the measured INR values and clinical factors: the dose does not need to be adjusted for a single INR that is slightly out of range, and most changes should alter the total weekly dose by 5% to 20%. The INR should be monitored frequently (eg, 2 to 4 times per week) immediately after initiation of warfarin; subsequently, the interval between INR tests can be lengthened gradually (up to a maximum of 4 to 6 weeks) in patients with Stable INR values. Patients who have an elevated INR will need more frequent testing and may also require vitamin K1. For example, a nonbleeding patient with an INR of 9 can be given low-dose vitamin K1 (eg, 2.5 mg phytonadione, by mouth). Patients who have an excessive INR with clinically important bleeding require clotting factors leg, fresh-frozen plasma) as well as vitamin K1. Am J Med. 2000;109:481-488. (C) 2000 by Excerpta Medica, Inc. C1 Washington Univ, Sch Med, Div Gen Med Sci, St Louis, MO 63110 USA. Univ Washington, Div Gen Internal Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Calif Davis, Div Gen Med, 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 [HS10133] NR 105 TC 83 Z9 84 U1 2 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT 15 PY 2000 VL 109 IS 6 BP 481 EP 488 DI 10.1016/S0002-9343(00)00545-3 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 367JC UT WOS:000090057100007 PM 11042238 ER PT J AU Kistler, JP Furie, KL AF Kistler, JP Furie, KL TI Patent foremen ovale diameter and embolic stroke: A part of the puzzle? SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID CEREBRAL VASCULAR-DISEASE; ATHEROTHROMBOSIS; THERAPY C1 Massachusetts Gen Hosp, Serv Neurol, Boston, MA 02114 USA. RP Kistler, JP (reprint author), Massachusetts Gen Hosp, Serv Neurol, 32 Fruit St,VBK 802, Boston, MA 02114 USA. NR 14 TC 6 Z9 7 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT 15 PY 2000 VL 109 IS 6 BP 506 EP 507 DI 10.1016/S0002-9343(00)00599-4 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 367JC UT WOS:000090057100014 PM 11042246 ER PT J AU Chen, HY Ishii, A Wong, WK Chen, LB Lo, SH AF Chen, HY Ishii, A Wong, WK Chen, LB Lo, SH TI Molecular characterization of human tensin SO BIOCHEMICAL JOURNAL LA English DT Article DE calpain; focal adhesion; glutamine repeat ID FOCAL ADHESION KINASE; NEURONAL INTRANUCLEAR INCLUSIONS; SMOOTH-MUSCLE; SIGNAL-TRANSDUCTION; BINDING PROTEIN; CELL-LINES; TYROSINE PHOSPHORYLATION; EXTRACELLULAR-MATRIX; EXPRESSION; CALPAIN AB Tensin is a focal-adhesion molecule that binds to actin filaments and interacts with phosphotyrosine-containing proteins. To analyse tensin's function in mammals, we have cloned tensin cDNAs from human and cow. The isolated approx. 7.7-kb human cDNA contains an open reading frame encoding 1735 amino acid residues. The amino acid sequence of human tensin shares 60%; identity with chicken tensin, and contains all the structural features described previously in chicken tensin. This includes the actin-binding domains, the Src homology domain 2, and the region similar to a tumour suppressor, PTEN. Two major differences between human and chicken tensin are (i) the lack of the first 54 residues present in chicken tensin, and (ii) the addition of 34- and 38-residue inserts in human and bovine tensin. In addition, our interspecies sequencing data have uncovered the presence of a glutamine/CAG repeat that appears to have expanded in the course of evolution. Northern-blot analysis reveals a 10-kb message in most of the human tissues examined. An additional 9-kb message is detected in heart and skeletal muscles. The molecular mass predicted from the human cDNA is 185 kDa, although both endogenous and recombinant human tensin migrate as 220-kDa proteins on SDS/PAGE. The discrepancy is due to the unusually low electrophoretic mobility of the central region of the tensin polypeptide (residues 306-981). A survey of human prostate and breast cancer cell lines by Western-blot analysis shows a lack of tensin expression in most cancer cell lines, whereas these lines express considerable amounts of focal-adhesion molecules such as talin and focal-adhesion kinase. Finally, tensin is rapidly cleaved by a focal-adhesion protease, calpain II. Incubation of cells with a calpain inhibitor, MDL, prevented tensin cleavage and induced morphological change in these cells, suggesting that cleavage of tensin and other focal-adhesion constituents by calpain disrupts maintenance of normal cell shape. C1 Univ Calif Davis, Dept Orthopaed Surg, Ctr Tissue Regenerat & Repair, Sacramento, CA 95817 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lo, SH (reprint author), Univ Calif Davis, Dept Orthopaed Surg, Ctr Tissue Regenerat & Repair, 4635 2nd Ave, Sacramento, CA 95817 USA. NR 44 TC 49 Z9 51 U1 1 U2 4 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD OCT 15 PY 2000 VL 351 BP 403 EP 411 DI 10.1042/0264-6021:3510403 PN 2 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 369RD UT WOS:000165080000014 PM 11023826 ER PT J AU Zhang, P Zhang, XB Iwama, A Yu, CN Smith, KA Mueller, BU Narravula, S Torbett, BE Orkin, SH Tenen, DG AF Zhang, P Zhang, XB Iwama, A Yu, CN Smith, KA Mueller, BU Narravula, S Torbett, BE Orkin, SH Tenen, DG TI PU.1 inhibits GATA-1 function and erythroid differentiation by blocking GATA-1 DNA binding SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR GATA-1; MURINE ERYTHROLEUKEMIA-CELLS; MEGAKARYOCYTIC DIFFERENTIATION; ZINC-FINGER; MYELOID DEVELOPMENT; MAMMALIAN-CELLS; GENE-EXPRESSION; CD11B PROMOTER; PROTEIN; ACTIVATION AB The lineage-specific transcription factors GATA-1 and PU.1 can physically interact to inhibit each other's function, but the mechanism of repression of GATA-1 function by PU,I has not been elucidated. Both the N terminus and the C terminus of PU.1 can physically interact with the C-terminal zinc finger of GATA-1. It is demonstrated that the PU.1 N terminus, but not the C terminus, is required for inhibiting GATA-1 function. Induced overexpression of PU.1 in K562 erythroleukemia cells blocks hemin-induced erythroid differentiation. In this system, PU.1 does not affect the expression of GATA-1 messenger RNA, protein, or nuclear localization. However, GATA-1 DNA binding decreases dramatically. By means of electrophoretic mobility shift assays with purified proteins, it is demonstrated that the N-terminal 70 amino acids of PU.1 can specifically block GATA-1 DNA binding. In addition, PU.1 had a similar effect in the G1ER cell line, in which the GATA-1 null erythroid cell line G1E has been transduced with a GATA-1-estrogen receptor fusion gene, which is directly dependent on induction of the GATA-1 fusion protein to effect erythroid maturation. Consistent with in vitro binding assays, overexpression of PU,I blocked DNA binding of the GATA-1 fusion protein as well as GATA-1-mediated erythroid differentiation of these G1ER cells. These results demonstrate a novel mechanism by which function of a lineage-specific transcription factor is inhibited by another lineage-restricted factor through direct protein-protein interactions. These findings contribute to understanding how protein-protein interactions participate in hematopoietic differentiation and leukemogenesis, (C) 2000 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Inst Med, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Scripps Res Inst, Dept Immunol & Mol & Expt Med, La Jolla, CA USA. RP Tenen, DG (reprint author), Harvard Univ, Sch Med, Inst Med, Div Hematol Oncol, Rm 954,77 Ave Louis Pasteur, Boston, MA 02115 USA. FU NCI NIH HHS [CA41456]; NIDDK NIH HHS [DK659381] NR 51 TC 226 Z9 233 U1 0 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 2000 VL 96 IS 8 BP 2641 EP 2648 PG 8 WC Hematology SC Hematology GA 366KA UT WOS:000090003500001 PM 11023493 ER PT J AU Sackstein, R Dimitroff, CJ AF Sackstein, R Dimitroff, CJ TI A hematopoietic cell L-selectin ligand that is distinct from PSGL-1 and displays N-glycan-dependent binding activity SO BLOOD LA English DT Article ID HIGH-ENDOTHELIAL VENULES; P-SELECTIN; GLYCOPROTEIN LIGAND-1; MONOCLONAL-ANTIBODY; ADHESION MOLECULE-1; CD34(+) CELLS; BONE-MARROW; FLAVOBACTERIUM-MENINGOSEPTICUM; LINKED OLIGOSACCHARIDES; HYDRODYNAMIC SHEAR AB Human hematopoietic progenitor cells express L-selectin and also express PSGL-1, a ligand for all selectins, Using a shear-based adhesion assay, a hematopoietic cell L-selectin ligand (HCLL) that is expressed on the hematopoietic cell line KG1a and on normal human hematopoietic progenitors was previously identified. To characterize the structural biology of HCLL and to define its relationship to PSGL-1, the effects of chemical and enzymatic treatments on HCLL activity of KG1a cells and membrane preparations were analyzed. Protease digestions and chemical treatments of KG1a cells and membranes indicated that HCLL is an integral membrane glycoprotein, Glycosidase digestions of membrane protein preparations and metabolic treatments of KG1a cells with glycosylation processing modifiers revealed that L-selectin binding determinants on HCLL are sialofucosylated structures presented on complex-type N-glycans. Adhesion assays and biochemical studies showed that this glycoprotein is also expressed on circulating blasts in native acute leukemias. HCLL is distinguishable from PSGL-1: (1) KG1a cells sorted for PSGL-1 expression had equivalent HCLL activity; (2) anti-PSGL-1 blocking antibodies and proteases known to eliminate L-selectin binding to PSGL-1 had no effect on HCLL binding activity of KG1a cells; (3) blasts from native leukemias with low expression of PSGL-1 and CD34 display high HCLL activity; and (4) despite high level expression of PSGL-1, HCLL activity was absent on HL60 cells. These data provide first evidence of a naturally expressed membrane L-selectin ligand expressing binding determinant(s) on an N-linked glycoconjugate. This novel ligand may help mediate L-selectin-dependent cell-cell adhesive interactions within the cytoarchitecture of the bone marrow microenvironment, (C) 2000 by The American Society of Hematology. C1 Massachusetts Gen Hosp, Dept Med, Bone Marrow Transplant Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. Harvard Univ, Sch Med, Skin Dis Res Ctr, Boston, MA USA. RP Sackstein, R (reprint author), Harvard Univ, Inst Med, 77 Ave Louis Pasteur,Rm 671, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL60528] NR 69 TC 40 Z9 41 U1 0 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 2000 VL 96 IS 8 BP 2765 EP 2774 PG 10 WC Hematology SC Hematology GA 366KA UT WOS:000090003500018 PM 11023510 ER PT J AU D'Amico, AV Wu, YH Chen, MH Nash, M Renshaw, AA Richie, JP AF D'Amico, AV Wu, YH Chen, MH Nash, M Renshaw, AA Richie, JP TI Pathologic findings and prostate specific antigen outcome after radical prostatectomy for patients diagnosed on the basis of a single microscopic focus of prostate carcinoma with a Gleason score <= 7 SO CANCER LA English DT Article DE prostate carcinoma; prostate specific antigen; detection; radical prostatectomy; outcome ID RADIATION-THERAPY; CLINICAL-SIGNIFICANCE; REPEAT SEXTANT; CANCER; DISEASE; BIOPSIES; MEN; FAILURE AB BACKGROUND, Whether patients who are diagnosed on the basis of a single microscopic focus of prostate carcinoma with a Gleason score less than or equal to 7 (micro PC) have potentially life-threatening disease if they are not treated is unknown. METHODS. Pathologic findings and prostate specific antigen (PSA) outcome after radical prostatectomy (RP) for men who were diagnosed with micro PC were determined. Of 917 patients who were managed with RP during 1989-1999 at the Brigham and Women's Hospital, 66 patients (7%) were diagnosed on the basis of micro PC. Pathologic stage, tumor grade, tumor volume, margin status, and PSA outcome were investigated and are reported. Estimates of PSA outcome were calculated using the actuarial method of Kaplan and Meier. Pairwise comparisons were made using the log rank test. RESULTS. The finding of micro PC at biopsy was associated with macroscopic disease (involving at least half of a single lobe) in 92% of the patients in this series. Although these men had favorable pathologic findings (94% had organ confined disease, 89% had negative tumor margins, and 79% had a prostatectomy Gleason score less than or equal to 6), approximately 10% of the patients failed biochemically within 5 years after RP. CONCLUSIONS. The finding of micro PC at biopsy should not be used as a surrogate for clinically insignificant disease. Cancer 2000;89:1810-7, (C) 2000 American Cancer Society. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Worcester Polytech Inst, Dept Math Sci, Worcester, MA 01609 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, L2 Level,75 Francis St, Boston, MA 02115 USA. NR 23 TC 28 Z9 28 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 2000 VL 89 IS 8 BP 1810 EP 1817 DI 10.1002/1097-0142(20001015)89:8<1810::AID-CNCR22>3.0.CO;2-9 PG 8 WC Oncology SC Oncology GA 363MG UT WOS:000089811100022 PM 11042577 ER PT J AU Smith, MR Kaufman, D Oh, W Guerin, K Seiden, M Makatsoris, T Manola, J Kantoff, PW AF Smith, MR Kaufman, D Oh, W Guerin, K Seiden, M Makatsoris, T Manola, J Kantoff, PW TI Vinorelbine and estramustine in androgen-independent metastatic prostate cancer - A phase II study SO CANCER LA English DT Article DE prostatatic neoplasms; androgen-independent; vinorelbine; estramustine ID ORAL ESTRAMUSTINE; DOCETAXEL TAXOTERE; PHOSPHATE; TRIAL; PACLITAXEL; CARCINOMA; ETOPOSIDE; PAIN AB BACKGROUND. The aim of this study was to determine the safety and activity of vinorelbine in combination with estramustine in men with androgen-independent metastatic prostate cancer. METHODS. Twenty-five men with androgen-independent metastatic prostate cancer were treated with the combination of vinorelbine and estramustine. Vinorelbine 25 mg/m(2) was administered by intravenous bolus on Days 1 and 8. Estramustine 140 mg was administered three times a day by mouth on Days 1 through 14. Treatment was repeated every 21 days. RESULTS. A total of 132 cycles of treatment were administered. The median number of cycles per patient was 5 (range: 1-16). Mild Grade 1 or 2 gastrointestinal toxicity and fatigue were the most common adverse effects. Hematologic toxicity was minimal. Treatment resulted in a sustained > 50% decrease in serum prostate-specific antigen (PSA) in 6 of 25 patients (24% of patients; 95% confidence interval (CI) 9-45%). The median duration of PSA response was 10 weeks (range: 3-39 weeks). Of the five men with bidimensionally measurable disease, none achieved a complete or partial response. There were no documented improvements in post-treatment bone scans. Median overall survival time was 14.1 months. CONCLUSIONS. The combination of vinorelbine and estramustine is a well-tolerated and modestly active regimen in men with androgen-independent metastatic prostate cancer. Cancer 2000;89:1824-8. (C) 2000 American Cancer Society. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Cox 640,100 Blossom St, Boston, MA 02114 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 18 TC 24 Z9 25 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 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 2000 VL 89 IS 8 BP 1824 EP 1828 DI 10.1002/1097-0142(20001015)89:8<1824::AID-CNCR24>3.0.CO;2-R PG 5 WC Oncology SC Oncology GA 363MG UT WOS:000089811100024 PM 11042579 ER PT J AU Loh, ML Samson, Y Motte, E Moreau, LA Dalton, V Waters, S Sallan, SE Gilliland, DG AF Loh, ML Samson, Y Motte, E Moreau, LA Dalton, V Waters, S Sallan, SE Gilliland, DG TI Translocation (2;8)(p12;q24) associated with a cryptic t(12;21)(p13;q22) TEL/AML1 gene rearrangement in a child with acute lymphoblastic leukemia SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID CELL-SURFACE; FUSION; CANCER; T(12-21); FIXATION; COMMON; TEL; DNA AB We report a case of childhood acute lymphoblastic leukemia with the simultaneous occurrence of a t(2:8)(p12;q24) typically associated with mature B cell or Burkitt leukemia, and a t(12;21)(p13; q22) exclusively associated with pre-B cell ALL. The lymphoblasts were characterized as L2 morphology by the French-American-British classification. However, there were atypical morpho logic findings for L2 ALL, including vacuolization in some cells. The lymphoblasts were periodic acid-Schiff positive and myeloperoxidase negative. Immunophenotypic analysis revealed that the majority of lymphoblasts were TdT+. CD10+, CD19+, CD20-. and cytoplasmic mu+ These features were consistent with an immature pre-B cell leukemia phenotype with some characteristics of a mature B-cell leukemia. A t(2;8)(p12;q24)(p12;q24), characteristic of mature B-cell leukemia or Burkitt type leukemia, was detected by conventional cytogenetics with no other cytogenetic abnormalities. However, diagnostic peripheral blood and bone marrow specimens demonstrated simultaneous occurrence of a cryptic t(12;21)(p13:q22) by both FISH and RT-PCR. The simultaneous occurrence of these translocations in a pediatric patient have implications for the pathogenesis of leukemias with t(2;8)(p12;q24) as well as 1(12;21)(p12;q22). Analysis of additional cases of leukemia with translocations involving the MYC locus on 8q24 will be required to determine the frequency of association with the cryptic t(12;21)(p13;22), and the prognostic significance of the simultaneous occurrence of the translocations. (C) 2000 Elsevier Science Inc. FLU rights reserved. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. Laval Univ Hosp, Laval, PQ, Canada. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Cytogenet, Boston, MA 02115 USA. RP Gilliland, DG (reprint author), Univ Calif San Francisco, Div Pediat Hematol Oncol, San Francisco, CA 94143 USA. FU NCI NIH HHS [CA68484, K23CA80915-01] NR 21 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD OCT 15 PY 2000 VL 122 IS 2 BP 79 EP 82 DI 10.1016/S0165-4608(00)00293-4 PG 4 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 379AB UT WOS:000165617800003 PM 11106815 ER PT J AU Shiao, T Iwahashi, M Fortune, J Quattrochi, L Bowman, S Wick, M Qadri, I Simon, FR AF Shiao, T Iwahashi, M Fortune, J Quattrochi, L Bowman, S Wick, M Qadri, I Simon, FR TI Structural and functional characterization of liver cell-specific activity of the human sodium/taurocholate cotransporter SO GENOMICS LA English DT Article ID BILE-ACID COTRANSPORTER; HEPATOCYTE NUCLEAR FACTOR-6; BINDING-PROTEIN ISOFORMS; RNA POLYMERASE-II; RAT-LIVER; GENE-EXPRESSION; TRANSCRIPTION FACTORS; PROMOTER REGION; TAUROCHOLATE TRANSPORT; MOLECULAR-CLONING AB Bile salts are rapidly removed from the circulation by the liver-specific sodium/taurocholate cotransporter (SLC10A1), To understand factors controlling its liver-specific expression, we isolated human SLC10A1 from a YAC chromosomal clone. SLC10A1 spans similar to 23 kb distributed over five exons, The major transcription start site is at 299 bp, and a minor start site is at 395 bp from the translational start site. A 1.2-kb portion of the 5' flanking region was sequenced and shown. to contain a number of liver-enriched elements, but no TATA box. Using secreted alkaline phosphatase reporter constructs liver-specific expression was examined. Transient transfection demonstrated that SLC10A1 promoter expression was selectively expressed eightfold in FAO and rat hepatocytes, while deletion mutants demonstrated liver-specific expression in a region extending from -5 to +198 bp, which contained putative sites for C/EBP and HNF3, Mutations of the C/EBP site resulted in loss of 77% of transcriptional activity. Cotransfection of C/EBP, but not other putative liver-enriched binding factors, increased SLC10A1 promoter activity. Electrophoretic mobility shift assays demonstrated specific protein-DNA interactions that involved C/EBP alpha and beta, These studies demonstrate that the TATA-less human SLC10A1 promoter exhibits liver-specific activity and its regulatory elements contain binding sites for C/EBP, which contributes specifically to its transcriptional regulation, (C) 2000 Academic Press. C1 Univ Colorado, Hlth Sci Ctr, Dept Med B145, Denver, CO 80262 USA. Denver Vet Affiars Med Ctr, Denver, CO 80262 USA. RP Simon, FR (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Med B145, 4200 E 9th Ave, Denver, CO 80262 USA. RI Qadri, Ishtiaq/I-6889-2013 FU NCI NIH HHS [CA46934]; NIDDK NIH HHS [R01 DK-15851] NR 55 TC 20 Z9 20 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 OCT 15 PY 2000 VL 69 IS 2 BP 203 EP 213 DI 10.1006/geno.2000.6329 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 368KT UT WOS:000090116700006 PM 11031103 ER PT J AU Pratt, JC Igras, VE Maeda, H Baksh, S Gelfand, EW Burakoff, SJ Neel, BG Gu, HH AF Pratt, JC Igras, VE Maeda, H Baksh, S Gelfand, EW Burakoff, SJ Neel, BG Gu, HH TI Cutting edge: Gab2 mediates an inhibitory phosphatidylinositol 3 '-kinase pathway in T cell antigen receptor signaling SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PLECKSTRIN HOMOLOGY DOMAIN; PHOSPHOINOSITIDE 3-KINASE; TRANSCRIPTIONAL REGULATION; INTERLEUKIN-2 GENE; PROTEIN; ACTIVATION; CYTOKINE; WORTMANNIN; REVEALS; KINASE AB Phosphatidylinositol 3'-kinase (PI3K) is a key component of multiple signaling pathways, where it typically promotes survival, proliferation, and/or adhesion. Here, we show that in TCR signaling, the scaffolding adapter Gab2 delivers an inhibitory signal via PI3K. Overexpression of Gab2 in T cell lines inhibits TCR-evoked activation of the IL-2 promoter, blocking NF-AT- and NF-kappa B-directed transcription. Inhibition is abrogated by mutating the Gab2 p85-binding sites, by treatment with PI3K inhibitors or by cotransfection of phosphatase homolog of tensin, Our findings provide the first evidence of a negative function for a scaffolding adapter in T cells and identify Gab2/PI3K-containing complexes as novel regulators of TCR signaling. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Canc Biol Program, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Natl Jewish Med & Res Ctr, Dept Pediat, Div Cell Biol, Denver, CO 80206 USA. RP Gu, HH (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Canc Biol Program, 77 Ave Louis Pasteur,HIM 1043, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA66600]; NIDDK NIH HHS [P01 DK50654, R01 DK50693] NR 20 TC 50 Z9 52 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 2000 VL 165 IS 8 BP 4158 EP 4163 PG 6 WC Immunology SC Immunology GA 362BK UT WOS:000089758600002 PM 11035047 ER PT J AU Moore, KJ Andersson, LP Ingalls, RR Monks, BG Li, R Arnaout, MA Golenbock, DT Freeman, MW AF Moore, KJ Andersson, LP Ingalls, RR Monks, BG Li, R Arnaout, MA Golenbock, DT Freeman, MW TI Divergent response to LPS and bacteria in CD14-deficient murine macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTOR-2; GRAM-NEGATIVE BACTERIA; BORRELIA-BURGDORFERI LIPOPROTEINS; PATTERN-RECOGNITION RECEPTOR; CUTTING EDGE; STAPHYLOCOCCUS-AUREUS; COMPLEMENT RECEPTOR; SIGNAL-TRANSDUCTION; LEUKOCYTE INTEGRINS; MEMBRANE-PROTEINS AB Gram-negative bacteria and the LPS constituent of their outer membranes stimulate the release of inflammatory mediators believed to be responsible for the clinical manifestations of septic shock. The GPI-linked membrane protein, CD14, initiates the signaling cascade responsible for the induction of this inflammatory response by LPS, In this paper, we report the generation and characterization of CD14-null mice in which the entire coding region of CD14 was deleted. As expected, LPS failed to elicit TNF-alpha and IL-6 production in macrophages taken from these animals, and this loss in responsiveness is associated with impaired activation of both the NF-kappa B and the c-Jun N-terminal mitogen-activated protein kinase pathways. The binding and uptake of heat-killed Escherichia coli, measured by FAGS analysis, did not differ between CD14-null and wild-type macrophages. However, in contrast to the findings with LPS, whole E, coli stimulated similar levels of TNF-alpha release from CD14-null and wild-type macrophages at a dose of 10 bioparticles per cell, This effect was dose dependent, and at lower bacterial concentrations CD14-deficient macrophages produced significantly less TNF-alpha than wild type. Approximately half of this CD14-independent response appeared to be mediated by CD11b/CD18, as demonstrated by receptor blockade using neutrophil inhibitory factor, An inhibitor of phagocytosis, cytochalasin B, abrogated the induction of TNF-alpha in CD14-deficient macrophages by E, coli, These data indicate that CD14 is essential far macrophage responses to free LPS, whereas other receptors, including CD11b/CD18, can compensate for the loss of CD14 in response to whole bacteria. C1 Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Med Ctr, Dept Med, Maxwell Finland Lab Infect Dis, Boston, MA 02118 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Leukocyte Biol & Inflammat Program, Boston, MA 02114 USA. RP Freeman, MW (reprint author), Massachusetts Gen Hosp, Lipid Metab Unit, 55 Fruit St,GRJ1328, Boston, MA 02114 USA. RI Monks, Brian/B-8362-2015 OI Monks, Brian/0000-0003-4008-3093 FU NIAID NIH HHS [U19AI3815]; NIDDK NIH HHS [DK50305]; NIGMS NIH HHS [R01GM54060] NR 50 TC 164 Z9 170 U1 2 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 2000 VL 165 IS 8 BP 4272 EP 4280 PG 9 WC Immunology SC Immunology GA 362BK UT WOS:000089758600016 PM 11035061 ER PT J AU Melian, A Watts, GFM Shamshiev, A De Libero, G Clatworthy, A Vincent, M Brenner, MB Behar, S Niazi, K Modlin, RL Almo, S Ostrov, D Nathenson, SG Porcelli, SA AF Melian, A Watts, GFM Shamshiev, A De Libero, G Clatworthy, A Vincent, M Brenner, MB Behar, S Niazi, K Modlin, RL Almo, S Ostrov, D Nathenson, SG Porcelli, SA TI Molecular recognition of human CD1b antigen complexes: Evidence for a common pattern of interaction with alpha beta TCRs SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL RECEPTOR; MHC CLASS-II; PRESENTING MOLECULES; CRYSTAL-STRUCTURE; LIPID ANTIGENS; LYMPHOCYTES-T; PEPTIDE; FAMILY; EXPRESSION; SPECIFICITY AB Ag-specific T fell. recognition is mediated through direct interaction of clonotypic TCRs with complexes formed between Ag-presenting molecules and their bound ligands, Although characterized in substantial detail for class I and class II: MHC encoded molecules, the molecular interactions responsible for TCR recognition of the CD1 lipid and glycolipid Ag-presenting molecules are not yet well. understood. Using a panel of epitope-specific Abs and site-specific mutants of the CD1b molecule, we showed that TCR interactions occur on the membrane distal aspects of the CD1b molecule over the alpha 1 and alpha 2 domain helices, The location of residues on CD1b important for this interaction suggested that TCRs bind in a diagonal orientation relative to the longitudinal axes of the alpha helices, The data point to a model in which TCR interaction extends over the opening of the putative Ag-binding groove, making multiple direct contacts with both alpha helices and bound Ag, Although reminiscent of TCR interaction with MHC class I,our data also pointed to significant differences between the TCR interactions with CD1 and MHC encoded Ag-presenting molecules, indicating that Ag receptor binding must be modified to accommodate the unique molecular structure of the CD1b molecule and the unusual Ags it presents. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA 02115 USA. Univ Basel Hosp, Dept Res, CH-4031 Basel, Switzerland. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Univ Calif Los Angeles, Div Dermatol, Dept Med, Med Ctr, Los Angeles, CA 90095 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Biochem, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. RP Porcelli, SA (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, 1300 Morris Pk Ave,Room 416,Forchheimer Bldg, Bronx, NY 10461 USA. RI Modlin, Robert/M-7941-2014 OI Modlin, Robert/0000-0003-4720-031X FU NIAID NIH HHS [AI40135, AI45889, K11AI013858] NR 42 TC 44 Z9 45 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 2000 VL 165 IS 8 BP 4494 EP 4504 PG 11 WC Immunology SC Immunology GA 362BK UT WOS:000089758600044 PM 11035089 ER PT J AU Flores, AI Mallon, BS Matsui, T Ogawa, W Rosenzweig, A Okamoto, T Macklin, WB AF Flores, AI Mallon, BS Matsui, T Ogawa, W Rosenzweig, A Okamoto, T Macklin, WB TI Akt-mediated survival of oligodendrocytes induced by neuregulins SO JOURNAL OF NEUROSCIENCE LA English DT Article DE oligodendrocyte; survival; Akt; neuregulin; multiple sclerosis; apoptosis ID PROTEIN-KINASE-B; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; DIFFERENTIATION FACTOR ISOFORMS; CILIARY NEUROTROPHIC FACTOR; TUMOR-NECROSIS-FACTOR; MULTIPLE-SCLEROSIS; GROWTH-FACTOR; PHOSPHATIDYLINOSITOL 3-KINASE; CELL-SURVIVAL; IN-VITRO AB Neuregulins have been implicated in a number of events in cells in the oligodendrocyte lineage, including enhanced survival, mitosis, migration, and differentiation. At least two signaling pathways have been shown to be involved in neuregulin signaling: the phosphatidylinositol (PI)-3 kinase and the mitogen-activated protein kinase pathways. In the present studies, we examined the signaling pathway involved in the survival function of heregulin, focusing on heregulin-induced changes in Akt activity in cultured glial cells, and the consequences of Akt activation in cells in the oligodendrocyte lineage. Heregulin binds erbB receptors, and in our studies, primary cultures of both oligodendrocyte progenitor cells and differentiating oligodendrocytes expressed erbB2, erbB3, and erbB4 receptors. In C6 glioma cells and primary cultures of oligodendrocytes, heregulin induced time- and dose-dependent Akt phosphorylation at Ser(473) in a wortmannin-sensitive manner. To investigate further the signaling pathway for heregulin in glial cells, BAD was overexpressed in C6 glioma cells. In these cells, heregulin induced phosphorylation of BAD at Ser(136). Apoptosis of oligodendrocyte progenitor cells induced by growth factor deprivation was effectively blocked by heregulin in a wortmannin-sensitive manner. Overexpression of dominant negative Akt but not of wild-type Akt by adenoviral gene transfer in primary cultures of both oligodendrocytes and their progenitors induced significant apoptosis through activation of the caspase cascade. The present data suggest that the survival function of heregulin is mediated through the PI-3 kinase/ Akt pathway in cells in the oligodendrocyte lineage and that the Akt pathway may be quite important for survival of cells in this lineage. C1 Cleveland Clin Fdn, Dept Neurosci NC30, Lerner Res Inst, Cleveland, OH 44195 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02139 USA. Kobe Univ, Sch Med, Dept Internal Med 2, Chuo Ku, Kobe, Hyogo 6500017, Japan. RP Macklin, WB (reprint author), Cleveland Clin Fdn, Dept Neurosci NC30, Lerner Res Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA. FU NIMH NIH HHS [R29-MH56036]; NINDS NIH HHS [NS25304] NR 74 TC 120 Z9 122 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 15 PY 2000 VL 20 IS 20 BP 7622 EP 7630 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 361ZC UT WOS:000089753300019 PM 11027222 ER PT J AU Bonetti, M Gelber, RD AF Bonetti, M Gelber, RD TI A graphical method to assess treatment-covariate interactions using the Cox model on subsets of the data SO STATISTICS IN MEDICINE LA English DT Article ID COUNTING-PROCESSES; SPLINES; CANCER AB We introduce the subpopulation treatment effect pattern plot (STEPP) method, designed to facilitate the interpretation of estimates of treatment effect derived from different but potentially overlapping subsets of clinical trial data. In particular, we consider sequences of subpopulations defined with respect to a covariate, and obtain confidence bands for the collection of treatment effects (here obtained from the Cox proportional hazards model) associated with the sequences. The method is aimed at determining whether the magnitude of the treatment effect changes as a function of the values of the covariate. We apply STEPP to a breast cancer clinical trial data set to evaluate the treatment effect as a function of the oestrogen receptor content of the primary tumour. Copyright (C) 2000 John Wiley & Sons, Ltd. C1 Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Bonetti, M (reprint author), Dana Farber Canc Inst, Dept Biostat Sci, 44 Binney St, Boston, MA 02115 USA. OI Bonetti, Marco/0000-0003-2304-4180 FU NCI NIH HHS [CA-06516, CA-75362] NR 16 TC 107 Z9 107 U1 0 U2 8 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 OCT 15 PY 2000 VL 19 IS 19 BP 2595 EP 2609 DI 10.1002/1097-0258(20001015)19:19<2595::AID-SIM562>3.0.CO;2-M PG 15 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 358AF UT WOS:000089534500001 PM 10986536 ER PT J AU Datta, R Oki, E Endo, K Biedermann, V Ren, J Kufe, D AF Datta, R Oki, E Endo, K Biedermann, V Ren, J Kufe, D TI XIAP regulates DNA damage-induced apoptosis downstream of caspase-9 cleavage SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYTOCHROME-C RELEASE; PROTEIN-KINASE; LEUKEMIA-CELLS; ACTIVATION; MITOCHONDRIA; INHIBITORS; INDUCTION; PATHWAY; DEATH; IAP AB The IAP (inhibitor of apoptosis) family of anti-apoptotic proteins regulates programmed cell death. Of the six known human IAP-related proteins, XIAP is the most potent inhibitor. To study the mechanistic effects of XIAP on DNA damage-induced apoptosis, we prepared U-937 cells that stably overexpress XIAP. The results demonstrate that XIAP inhibits apoptosis induced by 1-[beta-D-arabinofuranosyl]cytosine (ara-C) and other genotoxic agents. XIAP had no detectable effect on ara-C-induced release of mitochondrial cytochrome c and attenuated cleavage of procaspase-9. In addition, we show that ara-C induces the association of XIAP with the cleaved fragments of caspase-9 and thereby inhibition of caspase-9 activity. The results also demonstrate that ara-C induces cleavage of procaspase-3 by a caspase-8-dependent mechanism and that XIAP inhibits caspase-3 activity. These results demonstrate that XIAP functions downstream of procaspase-9 cleavage as an inhibitor of both proteolytically processed caspase-9 and -3 in the cellular response to genotoxic stress. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Datta, R (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA29431]; NIGMS NIH HHS [GM58200] NR 40 TC 76 Z9 80 U1 0 U2 2 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 OCT 13 PY 2000 VL 275 IS 41 BP 31733 EP 31738 DI 10.1074/jbc.M910231199 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 363VT UT WOS:000089858900028 PM 10930419 ER PT J AU Hayne, C Tzivion, G Luo, ZJ AF Hayne, C Tzivion, G Luo, ZJ TI Raf-1/MEK/MAPK pathway is necessary for the G(2)/M transition induced by nocodazole SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; SPINDLE ASSEMBLY CHECKPOINT; XENOPUS EGG EXTRACTS; CELL-CYCLE; MAP KINASE; M-PHASE; RAF-1 ACTIVATION; 3T3 CELLS; RAS; PHOSPHORYLATION AB The dynamic balance between polymerization and depolymerization of microtubules is critical for cells to enter and exit mitosis, and drugs that disrupt this balance, such as taxol, colchicine, and nocodazole, arrest the cell cycle in mitosis. Although the Raf/MEK/MAPK pathway can be activated by these drugs, its role in mitosis has not been addressed. Here, we characterize activation of Raf/MEK/MAPK by nocodazole when mitosis is induced. We find that at early time points (up to 3 h) in nocodazole induction, Raf/MEK/MAPK is activated, and inhibition of MAPK activation by a MEK inhibitor, PD98059 or U0126, reduces the number of cells entering mitosis by creating a block at G(2). At later time points and in mitosis, activation of MEK/MAPK is severely inhibited, even though Raf-l activity remains high and can be further increased by growth factor. This inhibition is reversed when cells are released from metaphase and enter G(0)/G(1) phase. In addition, we find that binding of Raf-1 to 14-3-3 is progressively induced by nocodazole, reaching a maximum in mitosis, and that this binding is necessary to maintain mitotic Raf-l activity. Our present study indicates that activation of the Raf/MEK/MAPK pathway is necessary for the G(2)/M progression. C1 Boston Univ, Sch Med, Evans Dept Med, Endocrinol Sect,Diabet & Metab Res Unit, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. RP Luo, ZJ (reprint author), Boston Univ, Sch Med, Evans Dept Med, Endocrinol Sect,Diabet & Metab Res Unit, 650 Albany St,Rm 820, Boston, MA 02118 USA. RI Tzivion, Guri/D-8954-2011 FU NIGMS NIH HHS [GM 57959] NR 50 TC 79 Z9 80 U1 0 U2 2 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 OCT 13 PY 2000 VL 275 IS 41 BP 31876 EP 31882 DI 10.1074/jbc.M002766200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 363VT UT WOS:000089858900047 PM 10884385 ER PT J AU Sun, M Goldin, E Stahl, S Falardeau, JL Kennedy, JC Acierno, JS Bove, C Kaneski, CR Nagle, J Bromley, MC Colman, M Schiffmann, R Slaugenhaupt, SA AF Sun, M Goldin, E Stahl, S Falardeau, JL Kennedy, JC Acierno, JS Bove, C Kaneski, CR Nagle, J Bromley, MC Colman, M Schiffmann, R Slaugenhaupt, SA TI Mucolipidosis type IV is caused by mutations in a gene encoding a novel transient receptor potential channel SO HUMAN MOLECULAR GENETICS LA English DT Article ID ABNORMAL TRANSPORT; SKIN FIBROBLASTS; VARIANT AB Mucolipidosis type IV (MLIV) is a developmental neurodegenerative disorder characterized by severe neurologic and ophthalmologic abnormalities, The MLIV gene, ML4 (MCOLN1), has recently been localized to chromosome 19p13.2-13.3 by genetic linkage. Here we report the cloning of a novel transient receptor potential cation channel gene and show that this gene is mutated in patients with the disorder, ML4 encodes a protein, which we propose to call mucolipin, which has six predicted transmembrane domains and is a member of the polycystin II subfamily of the Drosophila transient receptor potential gene family. The role of a potential receptor-stimulated cation channel defect in the pathogenesis of mucolipidosis IV is discussed. C1 NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, DNA Sequencing Facil, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Harvard Inst Human Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. RP Sun, M (reprint author), NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. OI Kaneski, Christine/0000-0003-1453-2502 FU NINDS NIH HHS [R01-NS39995] NR 20 TC 210 Z9 223 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 12 PY 2000 VL 9 IS 17 BP 2471 EP 2478 DI 10.1093/hmg/9.17.2471 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 367KZ UT WOS:000090061400001 PM 11030752 ER PT J AU Burstein, HJ Winer, EP AF Burstein, HJ Winer, EP TI Primary care - Primary care for survivors of breast cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID ESTROGEN REPLACEMENT THERAPY; QUALITY-OF-LIFE; SURGICAL-ADJUVANT-BREAST; BONE-MINERAL DENSITY; LYMPH-NODE DISSECTION; BOWEL-PROJECT P-1; FOLLOW-UP CARE; RADIATION-THERAPY; ENDOMETRIAL CANCER; CONTRALATERAL BREAST C1 Dana Farber Canc Inst, Breast Oncol Ctr, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, Breast Oncol Ctr, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 124 TC 135 Z9 135 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 OCT 12 PY 2000 VL 343 IS 15 BP 1086 EP 1094 DI 10.1056/NEJM200010123431506 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 362FA UT WOS:000089766900006 PM 11027744 ER PT J AU Larson, VD Williams, DW Henderson, WG Luethke, LE Beck, LB Noffsinger, D Wilson, RH Dobie, RA Haskell, GB Bratt, GW Shanks, JE Stelmachowicz, P Studebaker, GA Boysen, AE Donahue, A Canalis, R Fausti, SA Rappaport, BZ AF Larson, VD Williams, DW Henderson, WG Luethke, LE Beck, LB Noffsinger, D Wilson, RH Dobie, RA Haskell, GB Bratt, GW Shanks, JE Stelmachowicz, P Studebaker, GA Boysen, AE Donahue, A Canalis, R Fausti, SA Rappaport, BZ CA NIDCD VA Hearing Aid Clin Trial Gr TI Efficacy of 3 commonly used hearing aid circuits - A crossover trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID COMPRESSION; IMPAIRMENT; BENEFIT; PERFORMANCE; PROFILE; QUALITY; GAIN; LIFE AB Context Numerous studies have demonstrated that hearing aids provide significant benefit for a wide range of sensorineural hearing loss, but no carefully controlled, multicenter clinical trials comparing hearing aid efficacy have been conducted. Objective To compare the benefits provided to patients with sensorineural hearing loss by 3 commonly used hearing aid circuits. Design Double-blind, 3-period, 3-treatment crossover trial conducted from May 1996 to February 1998. Setting Eight audiology laboratories at Department of Veterans Affairs medical centers across the United States. Patients A sample of 360 patients with bilateral sensorineural hearing loss (mean age, 67.2 years; 57% male, 78.6% white). Intervention Patients were randomly assigned to 1 of 6 sequences of linear peak clipper (PC), compression limiter (CL), and wide dynamic range compressor (WDRC) hearing aid circuits. All patients wore each of the 3 bearing aids, which were installed in identical casements, for 3 months, Main Outcome Measures Results of tests of speech recognition, sound quality, and subjective hearing aid benefit, administered at baseline and after each 3-month intervention with and without a hearing aid. At the end of the experiment, patients ranked the 3 hearing aid circuits. Results Each circuit markedly improved speech recognition, with greater improvement observed for soft and conversationally loud speech (all 52-dB and 62-dB conditions, P less than or equal to .001). All 3 circuits significantly reduced the frequency of problems encountered in verbal communication. Some test results suggested that CL and WDRC circuits provided a significantly better listening experience than PC circuits in word recognition (P = .002), loudness (P = .003), overall liking (P = .001), aversiveness of environmental sounds (P = .02), and distortion (P = .02). In the rank-order ratings, patients preferred the CL hearing aid circuits more frequently (41.6%) than the WDRC (29.8%) and the PC (28.6%) (P = .001 for CL vs both WDRC and PC). Conclusions Each circuit provided significant benefit in quiet and noisy listening situations. The CL and WDRC circuits appeared to provide superior benefits compared with the PC, although the differences between them were much less than the differences between the aided vs unaided conditions. C1 Dept Vet Affairs Med Ctr, Washington, DC USA. Hines VA Cooperat Studies Program, Coordinating Ctr, Hines, IL USA. Natl Inst Deafness & Other Commun Disorders, Bethesda, MD USA. Greater Los Angeles VA Hlth Care Syst, Los Angeles, CA USA. Dept Vet Affairs Med Ctr, Mt Home, TN USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Dept Vet Affairs Med Ctr, Iowa City, IA 52242 USA. Dept Vet Affairs Med Ctr, Nashville, TN 37212 USA. Dept Vet Affairs Med Ctr, Long Beach, CA USA. Boys Town Natl Res Hosp, Omaha, NE 68131 USA. Univ Memphis, Memphis, TN 38152 USA. Univ Calif Los Angeles, Harborview Med Ctr, Los Angeles, CA USA. Dept Vet Affairs Med Ctr, Portland, OR USA. Dept Vet Affairs Med Ctr, Albuquerque, NM USA. RP Larson, VD (reprint author), Howard Leight Ind, 7828 Waterville Rd, San Diego, CA 92154 USA. OI dobie, robert/0000-0003-3833-1772 NR 35 TC 47 Z9 49 U1 2 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 11 PY 2000 VL 284 IS 14 BP 1806 EP 1813 DI 10.1001/jama.284.14.1806 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 359PW UT WOS:000089622100032 PM 11025833 ER PT J AU Rosand, J Hylek, EM O'Donnell, HC Greenberg, SM AF Rosand, J Hylek, EM O'Donnell, HC Greenberg, SM TI Warfarin-associated hemorrhage and cerebral amyloid angiopathy - A genetic and pathologic study SO NEUROLOGY LA English DT Article ID APOLIPOPROTEIN-E EPSILON-2; RISK-FACTORS; INTRACEREBRAL HEMORRHAGE; INTRACRANIAL HEMORRHAGE; ATRIAL-FIBRILLATION; ALZHEIMERS-DISEASE; HIGH-FREQUENCY; ALLELE; ANTICOAGULATION; OUTPATIENTS AB Background: Intracerebral hemorrhage (ICH) is the most feared complication of warfarin therapy. The pathogenesis of this often-fatal complication remains obscure. Cerebral amyloid angiopathy (CAA) is a major cause of spontaneous lobar hemorrhage in the elderly and is associated with specific alleles of the APOE gene. Objective: To assess the role of CAA in warfarin-associated ICH. Methods: Clinical characteristics and APOE genotype were compared between 41 patients with warfarin-related ICH (from a cohort of 59 consecutive patients aged greater than or equal to 65 years with supratentorial ICH on warfarin) and 66 randomly selected individuals aged greater than or equal to 65 years without ICH taking warfarin. In addition, all neuropathologic specimens from ICH patients were reviewed for the presence and severity of CAA. Results: Hemorrhages tended to be in the lobar regions of the brain, and most (76%) occurred with an international normalized ratio of less than or equal to 3.0. The APOE epsilon 2 allele was overrepresented among patients with warfarin-associated lobar hemorrhage (allele frequency 0.13 versus 0.04 in control subjects; p = 0.031). After controlling for other variables associated with ICH, carriers of the epsilon 2 allele had an OR of 3.8 (95% CI, 1.0 to 14.6) for lobar ICH. CAA was pathologically diagnosed as the cause of lobar hemorrhage in 7 of 11 patients with available tissue samples. Conclusions: CAA is an important cause of warfarin-associated lobar ICH in the elderly. Although diagnosis of CAA before hemorrhage is not yet possible, these data offer hope that future patients at high risk for hemorrhage may be identified before initiation of warfarin therapy. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Greenberg, SM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Wang ACC 836, Boston, MA 02114 USA. FU NIA NIH HHS [AG00725] NR 33 TC 167 Z9 170 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 10 PY 2000 VL 55 IS 7 BP 947 EP 951 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 360ZD UT WOS:000089696500009 PM 11061249 ER PT J AU Karlawish, JHT Klocinski, JL Merz, J Clark, CM Asch, DA AF Karlawish, JHT Klocinski, JL Merz, J Clark, CM Asch, DA TI Caregivers' preferences for the treatment of patients with Alzheimer's disease SO NEUROLOGY LA English DT Article ID CONTROLLED TRIAL; DECISIONS; DEMENTIA; OUTCOMES; DRUGS; TRANSPLANTATION; RISKS AB Objectives: To learn caregivers' preferences for the treatment of AD with a disease-slowing therapy, and to identify relationships between these preferences and the characteristics of caregivers and patients. Methods: A structured interview with 40 caregivers of patients with AD. Preferences were measured for an AD-slowing medicine with the benefits of a gain in survival and a delay to nursing home placement (NHP), and risks of three degrees of severity of GI bleeding. Results: Using a six-point scale ranging from "not at all important" to "extremely important," the median rating of the importance of survival as a treatment benefit was "very important" and of a delay to NHP was "extremely important." Fifty-five percent of the caregivers identified a benefit more important than these two benefits. Qualitative data showed that caregivers' reasons for these preferences featured the importance of patient quality of life, and the preservation of patient cognition and function. Bivariate analyses showed that increasing importance of the benefit of survival was related to higher assessments of the patient's health and quality of life, and lower ratings of the caregiver's experience of burden. In order to slow disease progression by 1 year, 25/38 (66%) of caregivers would accept some risk of death from gastrointestinal bleeding. Regression models showed that risk tolerance was higher among caregivers who were working, adult children caring for early stage patients or from families with an history of dementia. Conclusions: Caregivers generally are willing to tolerate notable amounts of risk to slow AD progression. Factors that describe the caregiver's experience and perception of the patient and the patient-caregiver relationship influence how they want to treat the disease. This information may be useful for decisions about how to study and prescribe AD treatments. C1 Univ Penn, Inst Aging, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA. Philadelphia Vet Affairs Med Ctr, Dept Sociol, Philadelphia, PA USA. Philadelphia Vet Affairs Med Ctr, Dept Mol & Cellular Engn, Philadelphia, PA USA. Philadelphia Vet Affairs Med Ctr, Dept Neurol, Philadelphia, PA USA. Univ Penn, Alzheimers Dis Ctr, Philadelphia, PA 19104 USA. Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. RP Karlawish, JHT (reprint author), Univ Penn, Inst Aging, 3615 Chestnut St, Philadelphia, PA 19104 USA. FU NHGRI NIH HHS [R01-HG01765]; NIA NIH HHS [AG-01024, K01-AG00931] NR 36 TC 43 Z9 46 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 10 PY 2000 VL 55 IS 7 BP 1008 EP 1014 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 360ZD UT WOS:000089696500020 PM 11061260 ER PT J AU Chaudhuri, S Cariappa, A Tang, M Bell, D Haber, DA Isselbacher, KJ Finkelstein, D Forcione, D Pillai, S AF Chaudhuri, S Cariappa, A Tang, M Bell, D Haber, DA Isselbacher, KJ Finkelstein, D Forcione, D Pillai, S TI Genetic susceptibility to breast cancer: HLA DQB*03032 and HLA DRB1*11 may represent protective alleles SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CYTOLYTIC T-LYMPHOCYTES; CERVICAL-CARCINOMA; BRCA1 MUTATIONS; CROHNS-DISEASE; HUMAN-MELANOMA; RISK; DQ; ASSOCIATIONS; INDIVIDUALS; LINKAGE AB Tumors are believed to emerge only when immune surveillance fails. We wished to ascertain whether the failure to inherit putative protective alleles of HLA class II genes is linked to the development of breast cancer. We molecularly typed HLA DPB1, DQB1, DRB1, and DRB3 alleles in 176 Caucasian women diagnosed with early-onset breast cancer and in 215 ethnically matched controls. HLA DQB*03032 was identified in 7% of controls but in no patients with early-onset breast cancer (P = 0.0001). HLA DRB1*11 alleles were also significantly overrepresented (P < 0.0001) in controls (16.3%) as compared with patients with early-onset breast cancer (3.5%). HLA DQB*03032 and HLA DRB1*11 alleles may have a protective role in human breast cancer. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Pillai, S (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 32 TC 41 Z9 44 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 10 PY 2000 VL 97 IS 21 BP 11451 EP 11454 DI 10.1073/pnas.97.21.11451 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 363GA UT WOS:000089825700060 PM 11027344 ER PT J AU Glynn, RJ Chae, CU Guralnik, JM Taylor, JO Hennekens, CH AF Glynn, RJ Chae, CU Guralnik, JM Taylor, JO Hennekens, CH TI Pulse pressure and mortality in older people SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; DIASTOLIC BLOOD-PRESSURE; MYOCARDIAL-INFARCTION; PREDICTING RISK; ARTERIAL DISTENSIBILITY; SYSTOLIC HYPERTENSION; NORMOTENSIVE SUBJECTS; AORTIC COMPLIANCE; RANDOMIZED TRIAL; LOADING SEQUENCE AB Background: In older people, observational data are unclear concerning the relationships of systolic and diastolic blood pressure with cardiovascular and total mortality. We examined which combinations of systolic, diastolic, pulse, and mean arterial pressure best predict total and cardiovascular mortality in older adults. Methods: In 1981, the National Institute on Aging initiated its population-based Established Populations for Epidemiologic Studies of the Elderly in 3 communities. At baseline, 9431 participants, aged 65 to 102 years, had blood pressure measurements, along with measures of medical history, use of medications, disability, and physical function. During an average follow-up of 10.6 years among survivors, 4528 participants died, 2304 of cardiovascular causes. Results: In age- and sex-adjusted survival analyses, the lowest overall death rate occurred among those with systolic pressure less than 130 mm Hg and diastolic pressure 80 to 89 mm Hg; relative to this group, the highest death rate occurred in those with systolic pressure of 160 mm Hg or more and diastolic pressure less than 70 mm Hg (relative risk, 1.90; 95% confidence interval, 1.47-2.46). Both low diastolic pressure and elevated systolic pressure independently predicted increases in cardiovascular (P<.001) and total(P<.001) mortality. Pulse pressure correlated strongly with systolic pressure (R=0.82) but was a slightly stronger predictor of both cardiovascular and total mortality. ln a model containing pulse pressure and other potentially confounding variables, diastolic pressure (P=.88) and mean arterial pressure (P=.11) had no significant association with mortality. Conclusions: Pulse pressure appears to be the best single measure of blood pressure in predicting mortality in older people and helps explain apparently discrepant results for low diastolic blood pressure. C1 Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. E Boston Neighborhood Hlth Ctr, E Boston, MA USA. Univ Miami, Sch Med, Dept Epidemiol & Publ Hlth Med, Miami, FL USA. RP Glynn, RJ (reprint author), Brigham & Womens Hosp, Div Prevent Med, Dept Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. FU NIA NIH HHS [AG02107] NR 70 TC 146 Z9 162 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 9 PY 2000 VL 160 IS 18 BP 2765 EP 2772 DI 10.1001/archinte.160.18.2765 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 357XQ UT WOS:000089527600007 PM 11025786 ER PT J AU Mahoney, JE Palta, M Johnson, J Jalaluddin, M Gray, S Park, S Sager, M AF Mahoney, JE Palta, M Johnson, J Jalaluddin, M Gray, S Park, S Sager, M TI Temporal association between hospitalization and rate of falls after discharge SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 51st Annual Scientific Meeting of the Gerontological-Society-of-America CY NOV 20-24, 1998 CL PHILADELPHIA, PENNSYLVANIA SP Gerontol Soc Amer ID ELDERLY PATIENTS; BED REST; RISK-FACTORS; DELIRIUM; COMMUNITY; HOME; POPULATION; PREDICTORS; ILLNESS; PEOPLE AB Background: Evidence suggests that acute illness and hospitalization may increase the risk for falls. Objective: To evaluate the rate of falls, and associated risk factors, for 90 days following hospital discharge. Methods: We consecutively enrolled 311 patients, aged 65 years and older, discharged from the hospital after an acute medical illness and receiving home-nursing services. Patients were assessed within 5 days of discharge for prehospital and current functioning by self-report, and balance, vision, cognition, and delirium by objective measures. Patients were followed up weekly for 13 weeks for falls, injuries, and health care use. Results: The rate of falls was significantly higher in the first 2 weeks after hospitalization (8.0 per 1000 person-days) compared with 3 months later (1.7 per 1000 person-days) (P=.002). Fall-related injuries accounted for 15% of all hospitalizations in the first month after discharge. Independent prehospital risk factors significantly associated with falls included dependency in activities of daily living, use of a standard walker, 2 or more falls, and more hospitalizations in the year prior. Posthospital risk factors included use of a tertiary amine tricyclic antidepressant, probable delirium, and poorer balance, while use of a cane was protective. Conclusions: The rate of falls is substantially increased in the first month after medical hospitalization, and is an important cause of injury and morbidity. Posthospital risk factors may be potentially modifiable. Efforts to assess and modify risk factors should be integral to the hospital and posthospital care of older adults (those aged greater than or equal to 65 years). C1 Univ Wisconsin, Sch Med, Dept Med, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Dept Prevent Med, Madison, WI USA. William S Middleton Mem Vet Hosp, Ctr Geriatr Res Educ & Clin, Madison, WI USA. Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA. New England Ctr Integrat Hlth, Lyme, NH USA. SmithKline Beecham Pharmaceut, Philadelphia, PA USA. Univ Washington, Sch Pharm, Seattle, WA 98195 USA. RP Mahoney, JE (reprint author), Univ Wisconsin, Sch Med, Dept Med, 2870 Univ Ave,Suite 100, Madison, WI 53705 USA. FU NIA NIH HHS [K08AG00623, K08AG00808-01] NR 47 TC 56 Z9 59 U1 2 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 OCT 9 PY 2000 VL 160 IS 18 BP 2788 EP 2795 DI 10.1001/archinte.160.18.2788 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 357XQ UT WOS:000089527600010 PM 11025789 ER PT J AU Scholz, VH Flaherty, AW Kraft, E Keltner, JR Kwong, KK Chen, YI Rosen, BR Jenkins, BG AF Scholz, VH Flaherty, AW Kraft, E Keltner, JR Kwong, KK Chen, YI Rosen, BR Jenkins, BG TI Laterality, somatotopy and reproducibility of the basal ganglia and motor cortex during motor tasks SO BRAIN RESEARCH LA English DT Article DE functional magnetic resonance imaging; striatum; putamen; motor control; laterality; extrapyramidal system; inhibition ID SACCADIC EYE-MOVEMENTS; MONKEY; ASYMMETRY; BRAIN; PROJECTIONS; HANDEDNESS; LOCATION; PUTAMEN; HUMANS; SYSTEM AB We investigated the basal ganglia, motor cortex area 4, and supplementary motor area (SMA) using functional magnetic resonance imaging (fMRI) and five motor tasks: switching between finger and toe movements, writing, finger tapping, pronation/supination, and saccadic eye movements. We found reliable activation in the caudate nucleus and putamen in single subjects without the need for inter-subject averaging. Percent signal changes in basal ::anglia were smaller by a factor of three than those in SMA or motor cortex (1% vs. 2.5-3%). There was a definite foot-dorsal, hand-ventral basal ganglia somatotopy, similar to prior data from primates. Saccadic eye movements activated the caudate nucleus significantly more than the other tasks did. Unilateral movements produced bilateral activation in the striatum even when motor cortex activation was unilateral. Surprisingly, bilateral performance of the tasks led, on average, to consistently smaller basal ganglia activation than did unilateral performance (P<0.001), suggesting less inhibition of contralateral movements during bilateral tasks. Moreover, there was a striking dominance pattern in basal ganglia motor activation: the left basal ganglia were more active than the right for right handers, regardless of the hand used. This lateralization appears much stronger than that previously reported for motor cortex. Comparisons of inter-subject and intra-subject reproducibility indicated a much larger variability in basal ganglia and SMA compared to motor cortex, in spite of similar percent signal changes in the latter two structures. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Dept Radiol, MGH NMR Ctr, Charlestown, MA 02119 USA. Harvard Univ, Sch Med, Charlestown, MA 02119 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02119 USA. Univ Munich, Klinikum Grosshadern, Dept Diagnost Radiol, D-8000 Munich, Germany. RP Jenkins, BG (reprint author), Massachusetts Gen Hosp, Dept Radiol, MGH NMR Ctr, Charlestown, MA 02119 USA. NR 31 TC 76 Z9 80 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 6 PY 2000 VL 879 IS 1-2 BP 204 EP 215 DI 10.1016/S0006-8993(00)02749-9 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 362DG UT WOS:000089762900027 PM 11011024 ER PT J AU Dhe-Paganon, S Shigeta, R Chi, YI Ristow, M Shoelson, SE AF Dhe-Paganon, S Shigeta, R Chi, YI Ristow, M Shoelson, SE TI Crystal structure of human frataxin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MITOCHONDRIAL PROCESSING PEPTIDASE; FRIEDREICHS-ATAXIA; YEAST; IRON; MATURATION; HOMOLOG; ASSOCIATION; DEFICIENCY; DNA AB Friedreich's ataxia, an autosomal recessive neurodegenerative disorder characterized by progressive gait and limb ataxia, cardiomyopathy, and diabetes mellitus, is caused by decreased frataxin production or function. The structure of human frataxin, which we have determined at 1.8-Angstrom resolution, reveals a novel protein fold. A five-stranded, antiparallel beta sheet provides a flat platform, which supports a pair of parallel alpha helices, to form a compact arp sandwich. A cluster of 12 acidic residues from the first helix and the first strand of the large sheet form a contiguous anionic surface on the protein. The overall protein structure and the anionic patch are conserved in eukaryotes, including animals, plants, and yeast, and in prokaryotes. Additional conserved residues create an extended 1008-Angstrom(2) patch on a distinct surface of the protein. Side chains of disease-associated mutations either contribute to the anionic patch, help create the second conserved surface, or point toward frataxin's hydrophobic core. These structural findings predict potential modes of protein-protein and protein-iron binding. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Univ Cologne, Dept Internal Med 2, D-50931 Cologne, Germany. RP Shoelson, SE (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. RI Ristow, Michael/O-9858-2014 OI Ristow, Michael/0000-0003-2109-2453 FU NIDDK NIH HHS [DK07260, DK4312] NR 30 TC 130 Z9 134 U1 0 U2 2 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 OCT 6 PY 2000 VL 275 IS 40 BP 30753 EP 30756 DI 10.1074/jbc.C000407200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 362DE UT WOS:000089762700003 PM 10900192 ER PT J AU Li, XG Multon, MC Henin, Y Schweighoffer, F Venot, C Josef, J Zhou, CH LaVecchio, J Stuckert, P Raab, M Mhashilkar, A Tocque, B Marasco, WA AF Li, XG Multon, MC Henin, Y Schweighoffer, F Venot, C Josef, J Zhou, CH LaVecchio, J Stuckert, P Raab, M Mhashilkar, A Tocque, B Marasco, WA TI Grb3-3 is up-regulated in HIV-1-infected T-cells and can potentiate cell activation through NFATc SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; TRANSCRIPTION FACTOR NFAT1; NF-KAPPA-B; SIGNAL-TRANSDUCTION; TAT PROTEIN; HIV-1 INFECTION; CYCLOSPORINE-A; CD28 RECEPTOR; KINASE; PATHWAY AB The MAPK pathway is required for T-cell activation; however, its role in modulating T-cell function following human immunodeficiency virus type 1 (HIV-1) infection is poorly understood. In this report, we investigated whether Grb3-3, an isoform of the Grb2 (growth factor receptor-bound protein-2) adaptor molecule that is associated with the MAPK pathway, could be involved. We found that Grb3-3, but not its isoform Grb2, is markedly up-regulated in CD4(+) peripheral blood mononuclear cells derived from either in vitro HIV-1-infected cultures or HIV-1-infected human subjects. Analysis of HIV-1 gene products indicated that Tat and Nef, both of which have been implicated in modulating T-cell function, can independently induce expression of Grb3-3. By using NFAT/AP-1, AP-1, or NFAT reporter assays, we found that Grb3-3 can potentiate NFAT (but not AP-1) promoter activity in Jurkat T-cells upon engagement of the T-cell receptor and CD28 co-receptor. In addition, potentiation of NFAT by Grb3-3 is substantially suppressed by MEKK1, a kinase that may play an important role in retaining NFAT in the cytoplasm, and by cyclosporin A. Finally, we also found that Grb3-3 potentiates HIV-1 long terminal (LTR) repeat promoter activity following T-cell receptor stimulation, an effect that can be largely suppressed by cyclosporin A. Taken together, this study indicates that Grb3-3 is a cellular factor that can be up-regulated by HIV-1. In addition, Grb3-3 can also function as a positive factor for T-cell activation and, in doing so, may aid in establishing an intracellular environment that can optimally support HIV-1 replication. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Aventis Pharma Inc, F-94403 Vitry Sur Seine, France. Exonhit Therapeut, F-75013 Paris, France. RP Marasco, WA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. FU NCI NIH HHS [CA06516]; NIAID NIH HHS [AI41954, AI28785] NR 57 TC 12 Z9 12 U1 0 U2 2 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 OCT 6 PY 2000 VL 275 IS 40 BP 30925 EP 30933 DI 10.1074/jbc.M005535200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 362DE UT WOS:000089762700029 PM 10906142 ER PT J AU Mao, CG Xu, RJ Bielawska, A Szulc, ZM Obeid, LM AF Mao, CG Xu, RJ Bielawska, A Szulc, ZM Obeid, LM TI Cloning and characterization of a Saccharomyces cerevisiae alkaline ceramidase with specificity for dihydroceramide SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STRESS-RESPONSE; SPHINGOLIPIDS; IDENTIFICATION; PROLIFERATION; METABOLISM; GROWTH AB In a previous study, we reported that the Saccharomyces cerevisiae gene YPC1 encodes an alkaline ceramidase with a dual activity, catalyzing both hydrolysis and synthesis of yeast ceramide (Mao, C., Xu, R., Bielawska, A., and Obeid, L., M., (2000) J. Biol. Chem. 275, 6876-6884). In this study, we have identified a YPC1 homologue in S. cerevisiae that also encodes an alkaline ceramidase, We show that these two ceramidases have different substrate specificity, such that YPC1p preferentially hydrolyzes phytoceramide, whereas the new ceramidase YDC1p hydrolyzes dihydroceramide preferentially and phytoceramide only slightly. Neither enzyme hydrolyzes unsaturated mammalian-type ceramide. In contrast to YPC1p, YDC1p had only minor in vitro reverse activity of catalyzing dihydroceramide formation from a free fatty acid and dihydrosphingosine and no activity with phytosphingosine, Overexpression of YDC1p had no reverse activity in non-stressed yeast cells, but like YPC1p suppressed the inhibition of growth by fumonisin B1 albeit more modestly. Deletion of YDC1 and YPC1 or both did not apparently affect growth, suggesting neither gene is essential, However, the Delta ydc1 deletion mutant but not the Delta ypc1 deletion mutant was sensitive to heat stress, indicating a role for dihydroceramide but not phytoceramide in heat stress responses, and suggesting that the two enzymes have distinct physiological functions. C1 Ralph H Johnson Vet Affairs Hosp, Div Gen Internal Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem, Charleston, SC 29425 USA. RP Obeid, LM (reprint author), Ralph H Johnson Vet Affairs Hosp, Div Gen Internal Med, 114 Doughty St,Rm 604 STB,POB 250779, Charleston, SC 29425 USA. OI obeid, lina/0000-0002-0734-0847 FU NIA NIH HHS [AG16583, AG12467] NR 28 TC 103 Z9 105 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 OCT 6 PY 2000 VL 275 IS 40 BP 31369 EP 31378 DI 10.1074/jbc.M003683200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 362DE UT WOS:000089762700088 PM 10900202 ER PT J AU Santana, MA Pedraza-Alva, G Olivares-Zavaleta, N Madrid-Marina, V Horejsi, V Burakoff, SJ Rosenstein, Y AF Santana, MA Pedraza-Alva, G Olivares-Zavaleta, N Madrid-Marina, V Horejsi, V Burakoff, SJ Rosenstein, Y TI CD43-mediated signals induce DNA binding activity of AP-1, NF-AT, and NF kappa B transcription factors in human T lymphocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID WISKOTT-ALDRICH SYNDROME; CELL ACTIVATION; PROTEIN-KINASE; NUCLEAR FACTOR; SURFACE SIALOGLYCOPROTEIN; CD43 LEUKOSIALIN; GENE-EXPRESSION; CYCLOSPORINE-A; CROSS-LINKING; IL-2 GENE AB Although numerous reports document a role for CD43 in T cell signaling, the direct participation of this molecule in cell activation has been questioned. In this study we show that CD43 ligation on human normal peripheral T cells was sufficient to induce interleukin-2, CD69, and CD40-L gene expression, without requiring signals provided by additional receptor molecules. This response was partially inhibited by cyclosporin A and staurosporine, suggesting the participation of both the Ca2+ and the protein kinase C pathways in CD43 signaling. Consistent with the transient CD43-dependent intracellular Ca2+ peaks reported by others, signals generated through the CD43 molecule resulted in the induction of NF-AT DNA binding activity. CD43-dependent signals resulted also in AP-1 and NF kappa B activation, probably as a result of protein kinase C involvement. AP-1 complexes bound to the AP-1 sequence contained c-Jun, and those bound to the NF-AT-AP-1 composite site contained c-Jun and Fos. NF kappa B complexes containing p65 could be found as early as 1 h after CD43 crosslinking, suggesting that CD43 participates in early events of T cell activation. The induction of the interleukin-a, CD69, and CD-40L genes and the participation of AP-1, NF-AT, and NF kappa B in the CD43-mediated signaling cascade implicate an important role for this molecule in the regulation of gene expression and cell function. C1 Univ Nacl Autonoma Mexico, Inst Biotecnol, Cuernavaca 62250, Morelos, Mexico. Inst Nacl Salud Publ, Ctr Invest Enfermedades Infecciosas, Dept Inmunol Viral, Cuernavaca 62508, Morelos, Mexico. Acad Sci Czech Republ, Inst Mol Genet, CR-14220 Prague, Czech Republic. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Rosenstein, Y (reprint author), Univ Nacl Autonoma Mexico, Inst Biotecnol, Apartado Postal 510-3, Cuernavaca 62250, Morelos, Mexico. RI Horejsi, Vaclav/G-3113-2014 NR 69 TC 39 Z9 39 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 OCT 6 PY 2000 VL 275 IS 40 BP 31460 EP 31468 DI 10.1074/jbc.M005231200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 362DE UT WOS:000089762700100 PM 10908570 ER PT J AU Wolkow, CA Kimura, KD Lee, MS Ruvkun, G AF Wolkow, CA Kimura, KD Lee, MS Ruvkun, G TI Regulation of C-elegans life-span by insulinlike signaling in the nervous system SO SCIENCE LA English DT Article ID AGE-1 PI3 KINASE; CAENORHABDITIS-ELEGANS; GENE-EXPRESSION; TRANSCRIPTION FACTOR; OXIDATIVE STRESS; METABOLIC-RATE; LONGEVITY; DIAPAUSE; RECEPTOR; DAF-2 AB An insulinlike signaling pathway controls Caenorhabditis elegans aging. metabolism, and development. Mutations in the daf-2 insulin receptor-like gene or the downstream age-1 phosphoinositide 3-kinase gene extend adult life-span by two- to threefold. To identify tissues where this pathway regulates aging and metabolism, we restored daf-2 pathway signaling to only neurons, muscle, or intestine. Insulinlike signaling in neurons alone was sufficient to specify wild-type life-span, but muscle or intestinal signaling was not. However, restoring daf-2 pathway signaling to muscle rescued metabolic defects, thus decoupling regulation of life-span and metabolism. These findings point to the nervous system as a central regulator of animal longevity. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Nagoya Univ, Div Biol Sci, Nagoya, Aichi 4648602, Japan. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. OI Kimura, Koutarou/0000-0002-3359-1578 FU NIA NIH HHS [AG14161] NR 27 TC 428 Z9 451 U1 4 U2 34 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 6 PY 2000 VL 290 IS 5489 BP 147 EP 150 DI 10.1126/science.290.5489.147 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 361LP UT WOS:000089724800055 PM 11021802 ER PT J AU Valverde, P AF Valverde, P TI Cloning, expression, and mapping of hWW45, a novel human WW domain-containing gene SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE WW domain; cDNA cloning; gene expression; developmental biology; chromosome mapping; coiled-coil ID YES-ASSOCIATED PROTEIN; IDENTIFICATION; DATABASE; BINDING; LOCALIZATION; INTERACTS; SEARCH; MOTIFS; MODULE; CELLS AB WW domain-containing proteins are found in all eukaryotes and play an important role in the regulation of a wide variety of cellular functions such as protein degradation, transcription, and RNA splicing. The cloning and characterization of a novel human WW domain-containing gene, hWW45, which encodes a protein of approximately 45 kDa consisting of 2 WW domains and a coiled-coil region is reported here. The murine homologue cDNA, mWW45, displays a different 3'-untranslated region and predicts a protein identity of 93% to hWW45. Northern blot and RT-PCR analysis demonstrated that both mWW45 and hWW45 transcripts are ubiquitously expressed in adult tissues. The mouse embryonic expression is first seen at 7 days post coitum in Northern blot analysis of whole embryos. Chromosomal localization by radiation hybrid mapping revealed that hWW45 is localized at chromosome 14, 10.31cR from the marker D14S269. (C) 2000 Academic Press. C1 Forsyth Inst, Harvard Forsyth Dept Oral Biol, Boston, MA 02115 USA. RP Forsyth Inst, Harvard Forsyth Dept Oral Biol, 140 Fenway, Boston, MA 02115 USA. EM pvalverde@forsyth.org RI Valverde, Paloma/A-9897-2008 NR 39 TC 19 Z9 22 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 5 PY 2000 VL 276 IS 3 BP 990 EP 998 DI 10.1006/bbrc.2000.3582 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 362TL UT WOS:000089794300029 PM 11027580 ER PT J AU Lissy, NA Davis, PK Irwin, M Kaelin, WG Dowdy, SF AF Lissy, NA Davis, PK Irwin, M Kaelin, WG Dowdy, SF TI A common E2F-1 and p73 pathway mediates cell death induced by TCR activation SO NATURE LA English DT Article ID PERIPHERAL T-LYMPHOCYTES; LI-FRAUMENI; APOPTOSIS; P53; EXPRESSION; PROTEINS; GENE; MICE; COMPLEXITY; INDUCTION AB Strong stimulation of the T-cell receptor (TCR) on cycling peripheral T cells causes their apoptosis by a process called TCR-activation-induced cell death (TCR-AICD)(1-3). TCR-AICD occurs from a late G1 phase cell-cycle check point(4) independently of the 'tumour suppressor' protein p53 (refs 5, 6). Disruption of the gene for the E2F-1 transcription factor(7,8), an inducer of apoptosis(9-11), causes significant increases in T-cell number and splenomegaly(12-15). Here we show that T cells undergoing TCR-AICD induce the p53-related gene p73, another mediator of apoptosis(16), which is hypermethylated in lymphomas(17,18). Introducing a dominant-negative E2F-1 protein or a dominant-negative p73 protein into T cells protects them from TCR-mediated apoptosis, whereas dominant-negative E2F-2, E2F-4 or p53 does not. Furthermore, E2F-1-null or p73-null primary T cells do not undergo TCR-mediated apoptosis either. We conclude that TCR-AICD occurs from a late G1 cell-cycle checkpoint that is dependent on both E2F-1 and p73 activities. These observations indicate that, unlike p53, p73 serves to integrate receptor-mediated apoptotic stimuli. C1 Washington Univ, Sch Med, Dept Pathol, Howard Hughes Med Inst, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Med, Howard Hughes Med Inst, St Louis, MO 63110 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Dowdy, SF (reprint author), Washington Univ, Sch Med, Dept Pathol, Howard Hughes Med Inst, St Louis, MO 63110 USA. NR 30 TC 265 Z9 268 U1 0 U2 3 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 5 PY 2000 VL 407 IS 6804 BP 642 EP 645 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 362HP UT WOS:000089772800050 PM 11034214 ER PT J AU Irwin, M Marin, MC Phillips, AC Seelan, RS Smith, DI Liu, WG Flores, ER Tsai, KY Jacks, T Vousden, KH Kaelin, WG AF Irwin, M Marin, MC Phillips, AC Seelan, RS Smith, DI Liu, WG Flores, ER Tsai, KY Jacks, T Vousden, KH Kaelin, WG TI Role for the p53 homologue p73 in E2F-1-induced apoptosis SO NATURE LA English DT Article ID P53-INDEPENDENT APOPTOSIS; LI-FRAUMENI; DNA-BINDING; IN-VIVO; E2F-1; FAMILY; OVEREXPRESSION; PROTEIN; DOMAIN; CELLS AB The transcription factor E2F-1 induces both cell-cycle progression and, in certain settings, apoptosis. E2F-1 uses both p53-dependent and p53-independent pathways to kill cells(1-8). The p53-dependent pathway involves the induction by E2F-1 of the human tumour-suppressor protein p14ARF, which neutralizes HDM2 (human homologue of MDM2) and thereby stabilizes the p53 protein(9). Here we show that E2F-1 induces the transcription of the p53 homologue p73. Disruption of p73 function inhibited E2F-1-induced apoptosis in p53-defective tumour cells and in p53(-/-) mouse embryo fibroblasts. We conclude that activation of p73 provides a means for E2F-1 to induce death in the absence of p53. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. NCI, Regulat Cell Growth Lab, FCRDC, Frederick, MD 21702 USA. Mayo Clin & Mayo Fdn, Mayo Med Sch, Dept Lab Med & Pathol, Rochester, MN 55905 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. Howard Hughes Med Inst, Chevy Chase, MD 20185 USA. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Marin Vieira, Maria del Carmen/B-8108-2015 OI Marin Vieira, Maria del Carmen/0000-0002-7149-287X NR 29 TC 481 Z9 491 U1 4 U2 18 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 5 PY 2000 VL 407 IS 6804 BP 645 EP 648 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 362HP UT WOS:000089772800051 PM 11034215 ER PT J AU von Andrian, UH Mackay, CR AF von Andrian, UH Mackay, CR TI Advances in immunology: T-cell function and migration - Two sides of the same coin SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID HIGH ENDOTHELIAL VENULES; LEUKOCYTE ADHESION DEFICIENCY; CHEMOKINE RECEPTOR EXPRESSION; SECONDARY LYMPHOID ORGANS; P-SELECTIN; RHEUMATOID-ARTHRITIS; T-HELPER-2 CELLS; DENDRITIC CELLS; EOSINOPHIL CHEMOATTRACTANT; PHYSIOLOGICAL FLOW C1 Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, Boston, MA 02115 USA. Garvan Inst Med Res, Darlinghurst, NSW, Australia. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. RI Mackay, Charles/A-9673-2008; von Andrian, Ulrich/A-5775-2008 OI Mackay, Charles/0000-0002-6338-7340; NR 109 TC 879 Z9 897 U1 6 U2 44 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 OCT 5 PY 2000 VL 343 IS 14 BP 1020 EP 1033 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 359PU UT WOS:000089619900007 PM 11018170 ER PT J AU McLellan, AT Lewis, DC O'Brien, CP Kleber, HD AF McLellan, AT Lewis, DC O'Brien, CP Kleber, HD TI Drug dependence, a chronic medical illness - Implications for treatment, insurance, and outcomes evaluation SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CEREBRAL BLOOD-FLOW; OUT-OF-TREATMENT; DSM-III-R; FOLLOW-UP; ALCOHOL DEPENDENCE; COCAINE ABUSERS; DIABETES-MELLITUS; FEMALE TWINS; BRAIN; CARE AB The effects of drug dependence on social systems has helped shape the generally held view that drug dependence is primarily a social problem, not a health problem. In turn, medical approaches to prevention and treatment are lacking, We examined evidence that drug (including alcohol) dependence is a chronic medical illness. A literature review compared the diagnoses, heritability, etiology (genetic and environmental factors), pathophysiology, and response to treatments (adherence and relapse) of drug dependence vs type 2 diabetes mellitus, hypertension, and asthma, Genetic heritability, personal choice, and environmental factors are comparably involved in the etiology and course of all of these disorders. Drug dependence produces significant and lasting changes in brain chemistry and function. Effective medications are available for treating nicotine, alcohol, and opiate dependence but not stimulant or marijuana dependence, Medication adherence and relapse rates are similar across these illnesses. Drug dependence generally has been treated as if it were an acute illness, Review results suggest that long-term care strategies of medication management and continued monitoring produce lasting benefits. Drug dependence should be insured, treated, and evaluated like other chronic illnesses. C1 Treatment Res Inst, Philadelphia, PA 19106 USA. Vet Affairs Med Ctr, Penn VA Ctr Studies Addict, Philadelphia, PA USA. Univ Penn, Philadelphia, PA 19104 USA. Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. Columbia Univ, Natl Ctr Addict & Subst Abuse, New York, NY USA. RP McLellan, AT (reprint author), Treatment Res Inst, 150 S Independence Mall W,Suite 600, Philadelphia, PA 19106 USA. NR 91 TC 981 Z9 998 U1 22 U2 142 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 4 PY 2000 VL 284 IS 13 BP 1689 EP 1695 DI 10.1001/jama.284.13.1689 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 357KY UT WOS:000089501900030 PM 11015800 ER PT J AU Emanuel, EJ Fairclough, D Clarridge, BC Blum, D Bruera, E Penley, WC Schnipper, LE Mayer, RJ AF Emanuel, EJ Fairclough, D Clarridge, BC Blum, D Bruera, E Penley, WC Schnipper, LE Mayer, RJ TI Attitudes and practices of US oncologists regarding euthanasia and physician-assisted suicide SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID WASHINGTON-STATE; REQUESTS; DEATH AB Background: The practices of euthanasia and physician-assisted suicide remain controversial. Objective: To achieve better understanding of attitudes and practices regarding euthanasia and physician-assisted suicide in the context of end-of-life care. Design: Cohort study. Setting: United States. Participants: 3299 oncologists who are members of the American Society of Clinical Oncology. Measurements: Responses to survey questions on attitudes toward euthanasia and physician-assisted suicide for a terminally ill patient with prostate cancer who has unremitting pain, requests for and performance of euthanasia and physician-assisted suicide, and sociodemographic characteristics. Results: Of U.S. oncologists surveyed, 22.5% supported the use of physician-assisted suicide for a terminally ill patient with unremitting pain and 6.5% supported euthanasia Oncologists who were reluctant to increase the dose of intravenous morphine for terminally ill patients in excruciating pain (odds ratio [OR], 0.61 [95% CI, 0.48 to 0.77]) and had sufficient time to talk to dying patients about end-of-life care issues (OR, 0.79 [CI, 0.71 to 0.87]) were less likely to support euthanasia or physician-assisted suicide. During their career, 3.7% of surveyed oncologists had performed euthanasia and 10.8% had performed physician-assisted suicide. Oncologists who were reluctant to increase the morphine dose for patients in excruciating pain (OR, 0.58 [CI, 0.43 to 0.79]) and those who believed that they had received adequate training in end-of-life care (OR, 0.86 [CI, 0.79 to 0.95]) were less likely to have performed euthanasia or physician-assisted suicide. Oncologists who reported not being able to obtain all the care that a dying patient needed were more likely to have performed euthanasia (P = 0.001). Conclusions: Requests for euthanasia and physician-assisted suicide are likely to decrease as training in end-of-life care improves and the ability of physicians to provide this care to their patients is enhanced. C1 Dana Farber Canc Inst, Dept Med Adult Oncol, Boston, MA 02115 USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. AMC Canc Res Ctr, Denver, CO USA. Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Canc Care Inc, New York, NY USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Baptist Hosp, Nashville, TN USA. RP Mayer, RJ (reprint author), Dana Farber Canc Inst, Dept Med Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 17 TC 91 Z9 91 U1 1 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 OCT 3 PY 2000 VL 133 IS 7 BP 527 EP 532 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 360QG UT WOS:000089678300004 PM 11015165 ER PT J AU Blostein, MD Rigby, AC Furie, BC Furie, B Gilbert, G AF Blostein, MD Rigby, AC Furie, BC Furie, B Gilbert, G TI Amphipathic helices support function of blood coagulation factor IXa SO BIOCHEMISTRY LA English DT Article ID GAMMA-CARBOXYGLUTAMIC ACID; PHOSPHOLIPID-BINDING SITE; FACTOR-X ACTIVATION; FACTOR-VIII; MEMBRANE-BINDING; C2 DOMAIN; DODECYLPHOSPHOCHOLINE MICELLES; NMR-SPECTROSCOPY; MOLECULAR-BASIS; ENZYME COMPLEX AB Blood coagulation factor IXa gains proteolytic efficiency upon binding to a phospholipid membrane. We have found that an amphipathic, membrane-binding peptide from the C2 domain of factor VIII, fVIII(2303-23), enhances proteolytic efficiency of factor IXa in the absence of phospholipid membranes. This enhancement is the result of a reduction in the K-M for the substrate, factor X, with little effect on the k(cat). Enhanced function requires interaction of the gamma-carbortyglutamic acid (Gla) domains of factor IXa and factor X since (i) a synthetic peptide comprising the Gla domain of factor IXa and antibodies directed to the Gla domain of factor IXa inhibit this acceleration, (ii) the acceleration is Ca(II) dependent, and (iii) conversion of Gla-domainless factor X is not affected by the presence of fVIII(2303-23) The effect of fVIII(2303-23) on factor IXa parallels the enhanced function produced by phosphatidylserine-containing bilayers, and fVIII(2303-23) does not further enhance function of factor IXa when phospholipid vesicles are present. The critical feature of fVIII(2303-23) is apparently its amphipathic helix-forming structure [Gilbert, G. E., and Baleja, J. D. (1995) Biochemistry 34, 3022-3031] because other alpha-helical peptides such as a homologous peptide from the C2 domain of factor V and melittin have similar effects. Diastereomeric analogues of fVIII(2303-23) and melittin, which have reduced helical content, do not support factor IXa activity. A truncated peptide of fVIII(2303-23) with three C-terminal residues deleted retains alpha-helical content but loses capacity to enhance factor X cleavage, suggesting that a minimum length of alpha-helix is required. Although these results probably do not illuminate the physiologic function of the factor VIII peptide corresponding to fVIII(2303-23), they demonstrate a novel, membrane-mimetic role of amphipathic helical peptides in supporting function of factor IXa. C1 Beth Israel Deaconess Med Ctr, Ctr Hemostasis & Thrombosis Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, VA Boston Healthcare Syst,Dept Med, Boston, MA 02215 USA. RP Gilbert, G (reprint author), VA Hosp, 1400 VFW Pkwy, Boston, MA 02132 USA. FU NHLBI NIH HHS [P01 HL 42443] NR 44 TC 11 Z9 12 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 3 PY 2000 VL 39 IS 39 BP 12000 EP 12006 DI 10.1021/bi000655c PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 360XW UT WOS:000089693500020 PM 11009614 ER PT J AU Haq, S Choukroun, G Kang, ZB Ranu, H Matsui, T Rosenzweig, A Molkentin, JD Alessandrini, A Woodgett, J Hajjar, R Michael, A Force, T AF Haq, S Choukroun, G Kang, ZB Ranu, H Matsui, T Rosenzweig, A Molkentin, JD Alessandrini, A Woodgett, J Hajjar, R Michael, A Force, T TI Glycogen synthase kinase-3 beta is a negative regulator of cardiomyocyte hypertrophy SO JOURNAL OF CELL BIOLOGY LA English DT Article DE heart; nuclear factor of activated T cells; adenovirus; endothelin-1; protein kinase B ID PROTEIN-KINASE-B; BETA-CATENIN; C-JUN; CARDIAC-HYPERTROPHY; INTACT-CELLS; NF-ATC; ACTIVATION; CALCINEURIN; PHOSPHORYLATION; PATHWAY AB Hypertrophy is a basic cellular response to a variety of stressors and growth factors, and has been best characterized in myocytes, Pathologic hypertrophy of cardiac myocytes leads to heart failure, a major cause of death and disability in the developed world. Several cytosolic signaling pathways have been identified that transduce prohypertrophic signals, but to date, little work has focused on signaling pathways that might negatively regulate hypertrophy, Herein, we report that glycogen synthase kinase-3 beta (GSK-3 beta), a protein kinase previously implicated in processes as diverse as development and tumorigenesis. is inactivated by hypertrophic stimuli via a phosphoinositide 3-kinase-dependent protein kinase that phosphorylates GSK-3 beta on ser 9, Using adenovirus-mediated gene transfer of GSK-3 beta containing a ser 9 to alanine mutation, which prevents inactivation by hypertrophic stimuli, we demonstrate that inactivation of GSK-3 beta is required for cardiomyocytes to undergo hypertrophy, Furthermore, our data suggest that GSK-3 beta regulates the hypertrophic response, at least in part, by modulating the nuclear/cytoplasmic partitioning of a member of the nuclear factor of activated T cells family of transcription factors. The identification of GSK-3 beta as a transducer of antihypertrophic signals suggests that novel therapeutic strategies to treat hypertrophic diseases of the heart could be designed that target components of the GSK-3 pathway. C1 Massachusetts Gen Hosp, Div Cardiol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02129 USA. Childrens Hosp, Dept Mol Cardiol, Cincinnati, OH 45229 USA. Univ Cincinnati, Cincinnati, OH 45229 USA. Ontario Canc Inst, Toronto, ON M5G 2M9, Canada. Princess Margaret Hosp, Toronto, ON M5G 2M9, Canada. RP Force, T (reprint author), Massachusetts Gen Hosp, Div Cardiol, E 149 13th St,Suite 4002, Charlestown, MA 02129 USA. RI Woodgett, Jim/F-1087-2010; OI Woodgett, Jim/0000-0003-3731-5797; Force, Thomas/0000-0002-0450-8659 FU NHLBI NIH HHS [HL61688, HL59521, R01 HL059521, R01 HL061557, R01 HL061688]; NIDDK NIH HHS [DK50282] NR 53 TC 280 Z9 286 U1 0 U2 10 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD OCT 2 PY 2000 VL 151 IS 1 BP 117 EP 129 DI 10.1083/jcb.151.1.117 PG 13 WC Cell Biology SC Cell Biology GA 361DM UT WOS:000089707400010 PM 11018058 ER PT J AU Freeman, GJ Long, AJ Iwai, Y Bourque, K Chernova, T Nishimura, H Fitz, LJ Malenkovich, N Okazaki, T Byrne, MC Horton, HF Fouser, L Carter, L Ling, V Bowman, MR Carreno, BM Collins, M Wood, CR Honjo, T AF Freeman, GJ Long, AJ Iwai, Y Bourque, K Chernova, T Nishimura, H Fitz, LJ Malenkovich, N Okazaki, T Byrne, MC Horton, HF Fouser, L Carter, L Ling, V Bowman, MR Carreno, BM Collins, M Wood, CR Honjo, T TI Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE binding; proliferation inhibition; cytokine secretion inhibition; tissue expression; peripheral tolerance ID CELL CO-STIMULATION; T-CELLS; EXPRESSION; CTLA-4; CD28; INDUCTION; IMMUNORECEPTOR; SECRETION; SURFACE; LIGAND AB PD-1 is an immunoinhibitory receptor expressed by activated T cells, B cells, and myeloid cells. Mice deficient in PD-1 exhibit a breakdown of peripheral tolerance and demonstrate multiple autoimmune features. We report here that the ligand of PD-1 (PD-LI) is a member of the B7 gene family. Engagement of PD-1 by PD-L1 leads to the inhibition of T cell rcceptor-mediated lymphocyte proliferation and cytokine secretion. In addition, PD-1 signaling can inhibit at least suboptimal levels of CD28-mediated costimulation. PD-L1 is expressed by antigen-presenting cells, including human peripheral blood monocytes stimulated with interferon gamma, and activated human and murine dendritic cells. In addition, PD-L1 is expressed in nonlymphoid tissues such as heart and lung. The relative levels of inhibitory PD-L1 and costimulatory B7-1/B7-2 signals on antigen-presenting cells may determine the extent of T cell activation and consequently the threshold between tolerance and autoimmunity. PD-L1 expression on nonlymphoid tissues and its potential interaction with PD-1 may subsequently determine the extent of immune responses at sites of inflammation. C1 Kyoto Univ, Dept Med Chem, Grad Sch Med, Kyoto 6068501, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Wyeth Ayerst Res, Inst Genet, Cambridge, MA 02140 USA. RP Honjo, T (reprint author), Kyoto Univ, Dept Med Chem, Grad Sch Med, Kyoto 6068501, Japan. RI Honjo, Tasuku/N-4470-2016 FU NCI NIH HHS [CA84500, R01 CA084500]; NIAID NIH HHS [AI39671, AI41584, P01 AI039671] NR 28 TC 1530 Z9 1643 U1 14 U2 102 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 2 PY 2000 VL 192 IS 7 BP 1027 EP 1034 DI 10.1084/jem.192.7.1027 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 361QD UT WOS:000089733000010 PM 11015443 ER PT J AU Izikson, L Klein, RS Charo, IF Weiner, HL Luster, AD AF Izikson, L Klein, RS Charo, IF Weiner, HL Luster, AD TI Resistance to experimental autoimmune encephalomyelitis in mice lacking the CC chemokine receptor (CCR)2 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE receptors, chemokine; chemokines; macrophages; encephalomyelitis; cytokines ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; MULTIPLE-SCLEROSIS LESIONS; BETA-CHEMOKINES; CYTOKINE RESPONSES; EXPRESSION; CELLS; EXTRAVASATION; RECRUITMENT; PROTEIN-1 AB Monocyte recruitment to the central nervous system (CNS) is a necessary step in the development of pathologic inflammatory lesions in experimental autoimmune encephalomyelitis (EAE), a murine model of multiple sclerosis. Monocyte chemoattractant protein (MCP)-1, a potent agonist for directed monocyte migration, has been implicated in the pathogenesis of EAE. Here we report that deficiency in CC chemokine receptor (CCR)2, the receptor for MCP-1, confers resistance to EAE. induced with a peptide derived from myelin oligodendrocyte glycoprotein peptide 35-55 (MOGp35-55). CCR2(-/-) mice immunized with MOGp35-55 failed to develop mononuclear cell inflammatory infiltrates in the CNS and failed to increase CNS levels of the chemokines RANTES (regulated on activation, normal T cell expressed and secreted), MCP-1, and interferon (IFN)-inducible protein 10 (IP-10) as well the chemokine receptors CCR1, CCR2, and CCR5. Additionally, T cells from CCR2(-/-) immunized mice showed decreased antigen-induced proliferation and production of IFN-gamma compared with wild-type immunized controls, suggesting that CCR2 enhances the T helper cell type 1 immune response in EAE. These data indicate that CCR2 Flays a necessary and nonredundant role in the pathogenesis of EAE. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol,Ctr Immunol & Inf, Boston, MA 02114 USA. Univ Calif San Francisco, Gladstone Inst, San Francisco, CA 94141 USA. RP Luster, AD (reprint author), Massachusetts Gen Hosp E, Bldg 149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [R01CA69212, R01 CA069212]; NIAID NIH HHS [R01 AI043458, R01AI43458]; NIDA NIH HHS [KO8DA00522, Z01 DA000522] NR 26 TC 406 Z9 416 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 2 PY 2000 VL 192 IS 7 BP 1075 EP 1080 DI 10.1084/jem.192.7.1075 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 361QD UT WOS:000089733000015 PM 11015448 ER PT J AU Samuel, S Shaffer, K AF Samuel, S Shaffer, K TI Profile of medical student teaching in radiology: Teaching methods, staff participation, and rewards SO ACADEMIC RADIOLOGY LA English DT Article DE education; radiology; medical student education ID ANATOMY; EDUCATION; CHALLENGES; UNIVERSITY; PHYSICIANS; SYSTEM AB Rationale and Objectives. The purpose of this study was to collect demographic information about radiology departments and rewards for teaching activities, as well as the impact of new digital imaging methods on teaching. Materials and Methods. Two surveys were conducted of directors of medical school clerkships in radiology. The initial survey focused on numbers of staff and students, courses taught, and perception of rewards fur teaching. The fellow-up survey more specifically addressed teaching methods. Results. Sixty-nine (50%) of the initial surveys sent to 139 departments and 46 (39% of a total of 119) of the follow-up surveys were returned. Clerkship directors spent an average of 9 hours per week teaching and performing administrative tasks, with most given no additional time off. Eighty-four percent of departments provide either no or insignificant rewards for teaching. Many departments have integrated the use of computers in teaching, and most have computers that students use during the radiology course. At the same time, digital imaging and picture archiving and communication systems (PACS) are used, or will be used within 1 year, in most departments. Conclusion. Clerkship directors receive Little compensation in terms of time and rewards for medical student teaching. Teaching methods are evolving in response to the increasing use of computers, digital imaging, and PACS for at least part of the workload in most radiology departments. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Shaffer, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, 44 Binney St, Boston, MA 02115 USA. NR 20 TC 22 Z9 22 U1 0 U2 2 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD OCT PY 2000 VL 7 IS 10 BP 868 EP 874 DI 10.1016/S1076-6332(00)80634-0 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 361NQ UT WOS:000089729500009 PM 11048883 ER PT J AU Foster, CS Havrlikova, K Baltatzis, S Christen, WG Merayo-Lloves, J AF Foster, CS Havrlikova, K Baltatzis, S Christen, WG Merayo-Lloves, J TI Secondary glaucoma in patients with juvenile rheumatoid arthritis-associated iridocyclitis SO ACTA OPHTHALMOLOGICA SCANDINAVICA LA English DT Article DE juvenile rheumatoid arthritis; uveitis; glaucoma; iritis and iridocyclitis ID UVEITIS; CHILDREN AB Purpose: The prevalence and management of glaucoma were evaluated in patients with juvenile rheumatoid arthritis (JRA)-associated iridocyclitis. Methods: The records of 69 patients with JRA-associated iridocyclitis were reviewed. Results: Twenty-nine (42%) of these patients had secondary glaucoma or ocular hypertension. Glaucoma was controlled with topical treatment in only 7 of the 41 affected eyes (17%); systemic carbonic anhydrase inhibitor therapy resulted in control of another 8 eyes. Surgery controlled all but one of the remainder. Conclusion: Glaucoma is a common complication of JRA-associated iridocyclitis. It results from prolonged, inadequately treated intraocular inflammation and in some instances, from steroid use. Medical and surgical therapy for the glaucoma associated with JRA-uveitis is challenging and incompletely effective. We suspect that a more aggressive approach to the treatment of JRA-associated uveitis, earlier in the course of the disease may reduce this vision robbing contribution to the process. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 17 TC 43 Z9 45 U1 0 U2 0 PU SCRIPTOR PUBLISHER PI HVIDOVRE PA SOVANGSVEJ 1-5, DK-2650 HVIDOVRE, DENMARK SN 1395-3907 J9 ACTA OPHTHALMOL SCAN JI Acta Ophthalmol. Scand. PD OCT PY 2000 VL 78 IS 5 BP 576 EP 579 DI 10.1034/j.1600-0420.2000.078005576.x PG 4 WC Ophthalmology SC Ophthalmology GA 356FJ UT WOS:000089433100018 PM 11037918 ER PT J AU Palevsky, PM Washington, MS Stevenson, JA Rohay, JM Dyer, NJ Lockett, R Perry, SB AF Palevsky, PM Washington, MS Stevenson, JA Rohay, JM Dyer, NJ Lockett, R Perry, SB TI Improving compliance with the dialysis prescription as a strategy to increase the delivered dose of hemodialysis: An ESRD Network 4 quality improvement project SO ADVANCES IN RENAL REPLACEMENT THERAPY LA English DT Article DE hemodialysis; ESRD; adequacy of dialysis; quality improvement ID UNITED-STATES; PREDICTORS; MORTALITY; SURVIVAL; ADEQUACY AB Delivery of an inadequate dose of hemodialysis is associated with a significant increase in the relative risk of both hospitalization and death. We hypothesized that noncompliance with the dialysis prescription, defined as failure to achieve the prescribed blood flow, failure to dialyze for the prescribed duration, or failure to use the prescribed dialyzer, was a significant factor in patients not achieving a urea reduction ratio (URR) of greater than or equal to0.65. We identified the 29 dialysis facilities in ESRD Network 4 that had the lowest average URR and/or lowest percent of patients with a URR greater than or equal to0.65 based on quarterly data reports. Each facility was surveyed by review of all dialysis treatment sheets from a single week by network staff to evaluate for noncompliance with the dialysis prescription. Facility-specific data were reported back to each facility. Each facility was required to develop a facility-specific quality improvement plan after receiving intensive education on the quality improvement process. After 9 months the facilities were resurveyed. Although the compliance with the dialysis prescription decreased from 54.0% to 53.6% (P = .026), the delivered URR increased from 0.679 +/- 0.072 to 0.688 +/- 0.070 (P = .026) with an increase in the percentage of patients with a URR greater than or equal to0.65 from 69.7% to 75% (P = .0096). Kt/V increased from 1.37 +/- 0.26 to 1.41 +/- 0.27 (P = .0001). Analysis of the process changes instituted by the individual facilities showed an increase in the prescribed dose of dialysis. Thus, although the process goal of improved compliance with the dialysis prescription was not achieved, the outcome goal of an increased delivered dose of dialysis was met through an alternative process change of an augmented dialysis prescription. (C) 2000 by the National Kidney Foundation, Inc. C1 ESRD Network 4, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Palevsky, PM (reprint author), ESRD Network 4, 200 Lothrop St, Pittsburgh, PA 15213 USA. FU PHS HHS [500-97-E022] NR 17 TC 9 Z9 9 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1073-4449 J9 ADV RENAL REPLACE TH JI Adv. Renal Replace. Ther. PD OCT PY 2000 VL 7 IS 4 SU 1 BP S21 EP S30 DI 10.1053/jarr.2000.18429 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 368JD UT WOS:000090113100004 PM 11053583 ER PT J AU Palevsky, PM Washington, MS Stevenson, JA Rohay, JM Dyer, NJ Lockett, R Perry, SB AF Palevsky, PM Washington, MS Stevenson, JA Rohay, JM Dyer, NJ Lockett, R Perry, SB TI Barriers to the delivery of adequate hemodialysis in ESRD Network 4 SO ADVANCES IN RENAL REPLACEMENT THERAPY LA English DT Article DE hemodialysis; ESRD; adequacy of dialysis ID UNITED-STATES; DIALYSIS; PRESCRIPTION; PREDICTORS; SURVIVAL AB Dialysis dose has been established as a determinant of morbidity and mortality in chronic hemodialysis patients. To identify remediable barriers to the delivery of adequate hemodialysis, we examined factors that affected adherence to prescribed dialysis dose. End-Stage Renal Disease (ESRD) Network 4 facilities that fell into the lowest quintile in measures of dialysis adequacy were studied. At the time of this study, Network 4 was composed of 178 dialysis facilities in Delaware and Pennsylvania. Those 29 facilities had an average delivered urea reduction ratio (URR) of <0.67 and/or 71% of patients with a URR of 0.65. (The mean URR value of Network 4 was 0.699 with a compliance ratio of 80%.) Dialysis treatment sheets were reviewed for all patients in the 29 facilities for all treatments during a calendar week. Predialysis and postdialysis blood urea nitrogen (BUN) values from 1 treatment during this week were used to calculate URR and Kt/V. A total of 1,339 patients with a mean age of 61.9 15.1 years and a mean duration of ESRD of 3.4 +/- 3.3 years were dialyzed in the 29 units. Mean prescribed duration of dialysis (T) was 219 +/- 26 min. with a mean blood flow rate (BFR) of 393 +/- 62 mL/min. Concordance between the prescribed and delivered T (-5 min), DFP (-50 mL/min), and hemodialyzer were assessed, by patient, for each treatment (Tx). Characteristics of a delivered Kt/V 4 < 1.2 were duration <4 hours, BFR < 350 mL/min, patient weight > 100 kg, and delivered BFR 50 mL/min less than prescribed BFR. Multivariate analysis of the relationship between delivered dose of dialysis and patients and treatment characteristics identified black race, male gender, and younger age as demographic factors associated with low delivered dose. potential remediable barriers identified by this analysis included reduced treatment time (>10%) and use of catheters for angioaccess. These data suggest components of the dialysis process that might be targeted in future quality improvement projects to improve the adequacy of dialysis delivery. (C) 2000 by the National Kidney Foundation, Inc. C1 ESRD Network 4, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Palevsky, PM (reprint author), ESRD Network 4, 200 Lothrop St, Pittsburgh, PA 15213 USA. FU PHS HHS [500-97-E022] NR 15 TC 12 Z9 12 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 1073-4449 J9 ADV RENAL REPLACE TH JI Adv. Renal Replace. Ther. PD OCT PY 2000 VL 7 IS 4 SU 1 BP S11 EP S20 DI 10.1053/jarr/2000.18428 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 368JD UT WOS:000090113100003 PM 11053582 ER PT J AU Laposata, M Kabakibi, A Walden, MP Cluette-Brown, JE Nanji, AA Refaai, MA Werner, J Nanji, AA AF Laposata, M Kabakibi, A Walden, MP Cluette-Brown, JE Nanji, AA Refaai, MA Werner, J Nanji, AA TI Differences in the fatty acid composition of fatty acid ethyl esters in organs and their secretions SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol; ethanol; alcohol abuse; ethanol metabolism ID NONOXIDATIVE METABOLITES; ETHANOL; BLOOD; BINDING; CELLS AB Background: Fatty acid ethyl esters (FAEE) are nonoxidative ethanol metabolites that have been shown to be long term markers of ethanol intake and have been implicated as mediators of ethanol-induced cell injury. Previous studies have indicated that the fatty acid composition of the FAEE found in the plasma of human subjects after ethanol ingestion is predominantly ethyl palmitate and ethyl oleate. This raised the possibility that there is some selectivity toward the fatty acid used for FAEE to be exported from the liver into the blood. Methods: To address the hypothesis that the fatty acid composition of FAEE secreted from organs, such as the liver and pancreas, differs from the fatty acid composition of FAEE in the organs, this study was performed using rats that received ethanol by intra-arterial infusion. Results: It was found that the fatty acids in FAEE differed significantly in plasma versus liver, bile versus liver, and pancreatic secretions versus pancreas. Conclusions: These results indicate that organs selectively export certain FAEE species. C1 Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Clin Labs, Room 235 Gray Bldg, Boston, MA 02114 USA. NR 16 TC 10 Z9 10 U1 0 U2 2 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 OCT PY 2000 VL 24 IS 10 BP 1488 EP 1491 PG 4 WC Substance Abuse SC Substance Abuse GA 364GL UT WOS:000089884000004 PM 11045855 ER PT J AU Januzzi, JL Hahn, SS Chae, CU Giugliano, R Lewandrowski, K Theroux, P Jang, IK AF Januzzi, JL Hahn, SS Chae, CU Giugliano, R Lewandrowski, K Theroux, P Jang, IK TI Effects of tirofiban plus heparin versus heparin alone on troponin I levels in patients with acute coronary syndromes SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; UNSTABLE ANGINA; PROGNOSTIC VALUE; T LEVELS; RISK; DEATH; THROMBOSIS; DISEASE AB Elevated serum troponins following an acute coronary syndrome (ACS) predict a poor clinical outcome. Glycoprotein (GP) IIb/IIIa inhibitors reduce adverse clinical outcomes in patients with ACS, although their effect on serum troponin I (Tnl) in this setting has not been described. We therefore studied the effects of the GP IIb/IIIa inhibitor tirofiban on serum Tnl levels in a group of patients in the Platelet Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms trial. Serial blood samples were obtained in 53 patients receiving the combination therapy of tirofiban/heparin and in 52 receiving heparin alone, and were analyzed for baseline, peek, and mean concentrations of Tnl. Baseline Tnl levels were not different between the combination therapy and heparin-only groups (1.6 +/- 3.0 vs 3.1 +/- 6.7 ng/ml, p = 0.15). The peak Tnl level wets significantly lower in the combination therapy group than in the heparin group (5.2 +/- 8.3 vs 15.5 +/- 29.1 ng/ml, p = 0.017), and mean levels over the initial 24-hour period were also significantly lower in the combination therapy group (3.2 +/- 5.0 vs 8.5 +/- 14.8 ng/ml, p = 0.016). In univariate analysis, combination therapy was associated with lower Tnl levels, whereas in a multivariate model, the lower peak and mean Tnl levels as a consequence of tirofiban/heparin compared with heparin monotherapy remained significant (:peak, p = 0.029; mean, p = 0.035). Among patients with negative Tnl at baseline, treatment with the combination of tirofiban/heparin compared with heparin monotherapy still resulted in significantly lower peak (2.5 +/- 5.4 vs 14.6 +/- 32.8 ng/ml, p = 0.024) and mean (1.2 +/- 2.6 vs 6.9 +/- 15.8 ng/ml, p = 0.029) Tnl levels. In patients with ACS, therapy with the combination of tirofiban and heparin (compared with heparin treatment alone) resulted in lower serum Tnl levels, suggesting reduced myocardial injury. (C) 2000 by Excerpta Medico, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. RP Jang, IK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Bulfinch 105,55 Fruit St, Boston, MA 02114 USA. NR 22 TC 19 Z9 23 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 1 PY 2000 VL 86 IS 7 BP 713 EP 717 DI 10.1016/S0002-9149(00)01068-7 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 357XG UT WOS:000089526500001 PM 11018188 ER PT J AU Mora, S Stafford, RS Pasternak, RC AF Mora, S Stafford, RS Pasternak, RC TI Certain cardiac risk factors predict risk factor interventions and influence communication between physicians and patients SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIOVASCULAR-DISEASE; PRIMARY-CARE; CHOLESTEROL; MANAGEMENT; AGREEMENT AB The low rate of risk factor treatment suggests that preventive strategies are not being applied uniformly.(1-7) Previous data from the 1991 to 1992 National Ambulatory Medical Care Surveys suggests that patterns of cholesterol management may be influenced by nonclinical patient characteristics.(8) Identification of patient characteristics that act as barriers to effective risk factor management may aid in targeting specific patient populations and facilitate the more widespread application of prevention measures. In the present study, we examined whether certain clinical conditions can predict which patients get cardiovascular risk factor interventions, and we analyzed how physicians and patients report these interventions in an effort to understand better how they communicate about prevention activities. C1 Massachusetts Gen Hosp, Inst Hlth Policy, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gen Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Mora, S (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, Dept Med, 852 GRB,55 Fruit St, Boston, MA 02114 USA. NR 17 TC 1 Z9 1 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 1 PY 2000 VL 86 IS 7 BP 783 EP + DI 10.1016/S0002-9149(00)01082-1 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 357XG UT WOS:000089526500015 PM 11018202 ER PT J AU Corcoran, C Anderson, EJ Burrows, B Stanley, T Walsh, M Poulos, AM Grinspoon, S AF Corcoran, C Anderson, EJ Burrows, B Stanley, T Walsh, M Poulos, AM Grinspoon, S TI Comparison of total body potassium with other techniques for measuring lean body mass in men and women with AIDS wasting SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE HIV; body composition; lean body mass; wasting; fat mass; total body potassium; bioelectrical impedance analysis; fat-free mass; AIDS; dual-energy X-ray absorptiometry; skinfold-thickness measurement ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; BIOELECTRICAL-IMPEDANCE ANALYSIS; X-RAY ABSORPTIOMETRY; CROSS-VALIDATION; SEX AB Background: Lean body mass is an important predictor of survival and functional status in patients with AIDS wasting. The bias between different techniques for assessing body composition in AIDS wasting is not known. Design: We compared total body potassium (TBK) with fat-free mass (FFM) determined by dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), and skinfold-thickness measurement (SKF) in 132 patients (63 men, 69 women) with AIDS wasting (weight < 90% of ideal body weight, or weight loss > 10% of original, or both). None of the subjects exhibited clinical lipodystrophy. Comparisons were made by using different BIA equations. Results: Lean body mass determined by DXA was highly correlated with TBK in men (r = 0.79, P < 0.0001) and women (r = 0.84, P < 0.0001). FFMBIA and FFMDXA were significantly different (P < 0.01 in men and P < 0.0001 in women). The difference between FFMDXA and FFMBIA was significantly greater with greater weight and body fat, particularly in HIV-infected women (r = -0.39, P = 0.001 for weight; r = -0.60, P < 0.0001 for fat). The comparability of FFM and fat mass determined by DXA and BIA was dependent on the specific BIA equation used. Among men, no single BIA equation was more highly predictive of fat mass and FFM in comparison with DXA. Conclusions: The differences between DXA, BIA, and SKF in the determination of fat mass and FFM are significant in patients with AIDS wasting, BIA overestimates FFM compared with DXA in those with greater body fat. Standard BIA equations may not accurately estimate FFM and fat mass in men and women with AIDS wasting. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. Boston VA Med Ctr, Dept Radiol, Boston, MA USA. Boston Univ, Med Ctr, Boston, MA USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. FU NCRR NIH HHS [MO1RR01066]; NIDDK NIH HHS [R01DK49302, F32DK09218] NR 24 TC 30 Z9 31 U1 0 U2 1 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 2000 VL 72 IS 4 BP 1053 EP 1058 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 357JF UT WOS:000089494200025 PM 11010951 ER PT J AU Selby, DM Kohlmeier, RE Cho, CG Bux, R Gulley, ML AF Selby, DM Kohlmeier, RE Cho, CG Bux, R Gulley, ML TI Prothrombin gene mutation is uncommon in victims of fatal pulmonary embolism. SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract C1 Wilford Hall USAF Med Ctr, San Antonio, TX 78236 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Bexar Cty Forens Sci Ctr, San Antonio, TX USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD OCT PY 2000 VL 114 IS 4 MA 77 BP 654 EP 655 PG 2 WC Pathology SC Pathology GA 357ZX UT WOS:000089533700089 ER PT J AU Ofman, JJ Lewin, K Ramers, C Ippoliti, A Lieberman, D Weinstein, W AF Ofman, JJ Lewin, K Ramers, C Ippoliti, A Lieberman, D Weinstein, W TI The economic impact of the diagnosis of dysplasia in Barrett's esophagus SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID HIGH-GRADE DYSPLASIA; EARLY ADENOCARCINOMA; ENDOSCOPIC BIOPSY; SURVEILLANCE; DISEASE AB OBJECTIVE: Cost-effective strategies for identifying patients with Barrett's esophagus who are most likely to develop cancer have not been developed. Surveillance endoscopy is currently used, and we hypothesized that more frequent surveillance intervals would identify patients with "transient positive" diagnoses of dysplasia-dysplasia found on one examination but not on subsequent ones. Our aim was to explore the potential economic impact of transient positive diagnoses of dysplasia on alternative surveillance strategies over a IO-yr period. METHODS: Data were derived from a 2-yr randomized, prospective study comparing omeprazole to ranitidine in 95 patients with Barrett's esophagus. A transient positive diagnosis of dysplasia was defined as a patient who was diagnosed with dysplasia during the study period but whose 24-month biopsies revealed no dysplasia. We calculated the number of transient positive diagnoses of dysplasia and modeled the potential economic impact of a diagnosis of dysplasia over a 10-yr period. RESULTS: Thirty patients (31%) had at least one reading of dysplasia during the study period. Nineteen patients (20%) had a transient positive diagnosis of dysplasia. During the study period, no cancers were found. A surveillance strategy of every other year and every 6 months for dysplasia would result in 1072 endoscopies over a 10-yr period at a discounted cost of $1,587,184. A total of 61% of endoscopies would be because of transient positive diagnoses of dysplasia. A strategy of yearly surveillance and every 6 months for dysplasia would result in 1404 endoscopies at a discounted cost of $2,096,733, of which 28% would result from transient positive diagnoses of dysplasia. The discounted incremental costs of more frequent surveillance in this cohort of patients over 10 yr is $509,549. CONCLUSIONS: Based on current practice strategies, transient positive diagnoses of dysplasia account for 28-61% of endoscopies in Barrett's surveillance programs. This analysis suggests that the endoscopy workload and costs associated with surveillance could be substantially reduced if patients with transient positive diagnoses of dysplasia reverted to usual surveillance after two negative examinations. (Am J Gastroenterol 2000;95:2946-2952. (C) 2000 by Am. Coll. of Gastroenterology). C1 Cedars Sinai Hlth Syst, Dept Med, Los Angeles, CA USA. Cedars Sinai Hlth Syst, Dept Hlth Serv Res, Los Angeles, CA USA. Zynx Hlth Inc, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Pathol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, CURE, Los Angeles, CA 90024 USA. Portland Vet Affairs Med Ctr, Dept Med, Portland, OR USA. RP Ofman, JJ (reprint author), 9100 Wishire Blvd,Suite 655 E, Beverly Hills, CA 90212 USA. NR 21 TC 24 Z9 24 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2000 VL 95 IS 10 BP 2946 EP 2952 DI 10.1016/S0002-9270(00)02002-5 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 364JC UT WOS:000089888400042 PM 11051373 ER PT J AU Funke, B Pandita, RK Madnani, D Shoemaker, C Schuler, T Brown, MC Van De Water, T Schorle, H Adams, J Morrow, B AF Funke, B Pandita, RK Madnani, D Shoemaker, C Schuler, T Brown, MC Van De Water, T Schorle, H Adams, J Morrow, B TI Identification of a novel locus for hearing impairment on chromosome 22q11, a region associated with congenital anomaly disorders. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Albert Einstein Coll Med, Bronx, NY 10467 USA. ITG, Forschungszentrum Karlsruhe, Eggenstein Leopoldshafen, Germany. Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RI Schorle, Hubert/M-5001-2016 OI Schorle, Hubert/0000-0001-8272-0076 NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 17 BP 13 EP 13 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700019 ER PT J AU Schneider, KA Recklitis, C Harvey, J Casey, E Danziger, K Garber, J Diller, L AF Schneider, KA Recklitis, C Harvey, J Casey, E Danziger, K Garber, J Diller, L TI Integrating genetic counseling into the care of long-term survivors of childhood cancer: A model program. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Genet Hlth Inc, San Mateo, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 118 BP 32 EP 32 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700119 ER PT J AU Hirschhom, JN Altshuler, D Lindgren, CM Klannemark, M Daly, M Vohl, MC Nemesh, J Lane, C Bolk, S Hudson, TJ Groop, L Lander, ES AF Hirschhom, JN Altshuler, D Lindgren, CM Klannemark, M Daly, M Vohl, MC Nemesh, J Lane, C Bolk, S Hudson, TJ Groop, L Lander, ES TI Large-scale candidate gene association studies of type 2 diabetes. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Whitehead Inst, Cambridge, MA 02142 USA. MIT, Ctr Genome Res, Cambridge, MA 02139 USA. Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Lund, Malmo, Sweden. McGill Univ, Montreal, PQ, Canada. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 0 TC 0 Z9 0 U1 1 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 195 BP 49 EP 49 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700196 ER PT J AU Wang, Y TenHave, T Lynch, HT Brunet, JS Narod, SA Garber, JE Godwin, AK Daly, MB Rebbeck, TR AF Wang, Y TenHave, T Lynch, HT Brunet, JS Narod, SA Garber, JE Godwin, AK Daly, MB Rebbeck, TR TI Effect of hierarchical clustered sampling in multicenter, family-based studies: Example of reproductive history and breast cancer risk in BRCA1 mutation carriers. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. Creighton Univ, Omaha, NE 68178 USA. Womens Coll Hosp, Toronto, ON M5S 1B2, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 223 BP 53 EP 53 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700222 ER PT J AU Weber, BL Punzalan, C Eisen, A Lynch, HT Narod, SA Garber, JE Isaacs, C Daly, MB Neuhausen, SL Rebbeck, TR AF Weber, BL Punzalan, C Eisen, A Lynch, HT Narod, SA Garber, JE Isaacs, C Daly, MB Neuhausen, SL Rebbeck, TR TI Ovarian cancer risk reduction after bilateral prophylactic oophorectomy (BPO) in BRCA1 and BRCA2 mutation carriers. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. Creighton Univ, Omaha, NE 68178 USA. Womens Coll Hosp, Toronto, ON M5S 1B2, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Georgetown Univ, Washington, DC USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Utah, Salt Lake City, UT USA. NR 0 TC 19 Z9 20 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 251 BP 59 EP 59 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700252 ER PT J AU Chen, Z Karimi, K Zhang, D Rivolta, M MacDonald, R Holley, M Corwin, J Corey, D AF Chen, Z Karimi, K Zhang, D Rivolta, M MacDonald, R Holley, M Corwin, J Corey, D TI Gene expression analysis of developing mouse utricle by oligonucleotide array and implication in deafness gene identification. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Univ Virginia, Sch Med, Dept Otolaryngol HNS, Charlottesville, VA 22908 USA. Univ Virginia, Sch Med, Dept Neurosci, Charlottesville, VA 22908 USA. Howard Hughes Med Inst, Coconut Grove, FL 33133 USA. Univ Bristol, Sch Med Sci, Dept Physiol, Bristol BS8 1TD, Avon, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 883 BP 168 EP 168 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700884 ER PT J AU Robertson, NG Lin, JS Heller, S Resendes, BL Weremowicz, S Denis, CS Bell, AM Adams, JC Hudspeth, AJ Morton, CC AF Robertson, NG Lin, JS Heller, S Resendes, BL Weremowicz, S Denis, CS Bell, AM Adams, JC Hudspeth, AJ Morton, CC TI Identification and characterization of a novel cochlear gene, OTOR, and localization of its encoded protein, otoraplin. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Rockefeller Univ, Lab Sensory Neurosci, New York, NY 10021 USA. Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 928 BP 176 EP 176 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700931 ER PT J AU Leyne, M Mull, J Gill, SP Cuajungco, MP Karbott, C Johnson, B Robbins, CM Makalowska, I Pinkett, HW Maayan, C Axelrod, FB Blumenfeld, A Brownstein, M Gusella, JF Slaugenhaupt, SA AF Leyne, M Mull, J Gill, SP Cuajungco, MP Karbott, C Johnson, B Robbins, CM Makalowska, I Pinkett, HW Maayan, C Axelrod, FB Blumenfeld, A Brownstein, M Gusella, JF Slaugenhaupt, SA TI Analysis and complete genomic sequence of the refined 178 kb Familiar Dysautonomia candidate region on chromosome 9q31. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Harvard Inst Human Genet, Boston, MA USA. Natl Inst Hlth, Bethesda, MD USA. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. NYU, Med Ctr, New York, NY 10016 USA. RI Brownstein, Michael/B-8609-2009; Cuajungco, Math/B-2647-2008 OI Cuajungco, Math/0000-0003-0749-9564 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 990 BP 186 EP 186 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400700992 ER PT J AU Lemyre, E Bruns, GAP Gusella, JF Korf, BR Herrick, SR Ligon, AH Lewis, J Maas, RL MacDonald, ME Michelson, AM Quade, BJ Morton, CC AF Lemyre, E Bruns, GAP Gusella, JF Korf, BR Herrick, SR Ligon, AH Lewis, J Maas, RL MacDonald, ME Michelson, AM Quade, BJ Morton, CC TI Developmental Genome Anatomy Project: Two breakpoints localized in BAC clones. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Childrens Hosp, Boston, MA 02115 USA. Howard Hughes Med Inst, Coconut Grove, FL 33133 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1413 BP 259 EP 259 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701416 ER PT J AU Breedveld, GJ Srinidhi, L de Vries, BBA Percy, AK Dure, LS Ippel, E MacDonald, ME Heutink, P AF Breedveld, GJ Srinidhi, L de Vries, BBA Percy, AK Dure, LS Ippel, E MacDonald, ME Heutink, P TI Benign heredtitary chorea maps to chromosome 14q and evidence for genetic heterogeneity. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Erasmus Univ, Dept Clin Genet, NL-3000 DR Rotterdam, Netherlands. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Univ Alabama, Div Pediat Neurol, Birmingham, AL USA. Univ Alabama, Dept Pediat, Birmingham, AL USA. Acad Hosp Utrecht, Dept Clin Genet, Utrecht, Netherlands. RI Dure, Leon/B-3243-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1663 BP 301 EP 301 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701664 ER PT J AU Fernandez, MJ Raskind, WH Wolff, J Matsushita, M Lipe, H Bird, TD AF Fernandez, MJ Raskind, WH Wolff, J Matsushita, M Lipe, H Bird, TD TI Benign hereditary chorea with suggestive linkage to 14q: confirmation of a diagnostic entity and narrowing the critical region. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. Univ Washington, Sch Med, Dept Psychiat, Seattle, WA USA. Geriatr Res Serv, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1664 BP 302 EP 302 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701665 ER PT J AU Sugimoto, Y Morita, R Amano, K Fong, CYG Shah, PU Castroviejo, IP Khan, S Delgado-Escueta, AV Yamakawa, K AF Sugimoto, Y Morita, R Amano, K Fong, CYG Shah, PU Castroviejo, IP Khan, S Delgado-Escueta, AV Yamakawa, K TI Childhood absence epilepsy in 8q24: Refinement of candidate region and construction of physical map. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 RIKEN, Brain Sci Inst, Neurogenet Lab, Wako, Saitama, Japan. Univ Calif Los Angeles, Sch Med, Epilepsy Genom Lab, Comprehensive Epilepsy Program, Los Angeles, CA USA. W Los Angeles DVA Med Ctr, Los Angeles, CA USA. Univ Hosp La Paz, Madrid, Spain. Riyadh Armed Forces Hosp, Dept Neurosci, Riyadh, Saudi Arabia. RI Yamakawa, Kazuhiro/N-5050-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1669 BP 302 EP 302 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701670 ER PT J AU He, B Liu, L Osterholm, AM Berg, T Tuomilehto, J Pitkaniemi, J Rogus, J Krolewski, A Tryggvason, K AF He, B Liu, L Osterholm, AM Berg, T Tuomilehto, J Pitkaniemi, J Rogus, J Krolewski, A Tryggvason, K TI Mapping genes for nephropathy in IDDM: Linkage analyses of eight typed chromosomes (2, 4, 6, 10, 12, 16, 20 and 22). SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Karolinska Inst, MBB, S-10401 Stockholm, Sweden. Natl Lab Publ Hlth, Helsinki, Finland. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1719 BP 311 EP 311 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701722 ER PT J AU Willett, CJ Jacoby, LB Kaufman, D MacCollin, M AF Willett, CJ Jacoby, LB Kaufman, D MacCollin, M TI Refining the candidate region for schwannomatosis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1731 BP 313 EP 313 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701734 ER PT J AU Siddique, T Schmidt, S Hosler, B Hung, WY Chen, W Thierry, A Siddique, N Bradford, Y Haines, JL Pericak-Vance, MA Brown, RH AF Siddique, T Schmidt, S Hosler, B Hung, WY Chen, W Thierry, A Siddique, N Bradford, Y Haines, JL Pericak-Vance, MA Brown, RH TI The SOD1 gene is not involved in sporadic amyotrophic lateral sclerosis. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Northwestern Univ, Sch Med, Chicago, IL USA. Duke Univ, Med Ctr, Durham, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1746 BP 315 EP 315 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701745 ER PT J AU Zareparsi, S Kaye, J Camicioli, R Gancher, S Nutt, J Payami, H AF Zareparsi, S Kaye, J Camicioli, R Gancher, S Nutt, J Payami, H TI Genetic analysis of onset age of Parkinson's disease: Apolipoprotein E. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Kaiser Permanente, Portland, OR USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1900 BP 341 EP 341 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701899 ER PT J AU Kosaki, K Kikuchi, T Yoshihashi, H Kosaki, R Suzuki, T Smith, R Matsuo, N AF Kosaki, K Kikuchi, T Yoshihashi, H Kosaki, R Suzuki, T Smith, R Matsuo, N TI Russell-Silver syndrome as a phenotype resulting from defects in the IGF1R axis: the ligand IGF2, its receptor IGF1R, or the signaling modulator GRB10. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Keio Univ, Sch Med, Dept Pediat, Tokyo, Japan. Niigata Univ, Sch Med, Dept Pediat, Niigata, Japan. Keio Univ, Ctr Hlth, Tokyo, Japan. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 1932 BP 347 EP 347 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400701933 ER PT J AU Auerbach, W Hurlbert, MS Hilditch-Maguire, P Wadghiri, YZ Wheeler, VC Cohen, SI Joyner, AL MacDonald, ME Turnbull, DH AF Auerbach, W Hurlbert, MS Hilditch-Maguire, P Wadghiri, YZ Wheeler, VC Cohen, SI Joyner, AL MacDonald, ME Turnbull, DH TI Progressive neurological disease in mice expressing reduced amounts of huntingtin with 20 and 111 glutamine repeat. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Howard Hughes Med Inst, Coconut Grove, FL 33133 USA. NYU, Sch Med, Dept Radiol, New York, NY 10016 USA. NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA. NYU, Sch Med, Dept Physiol, New York, NY 10016 USA. NYU, Sch Med, Dept Neurosci, New York, NY USA. Massachusetts Gen Hosp East, Mol Neurogenet Unit, Charlestown, MA USA. RI Wadghiri, Youssef/E-6848-2016 OI Wadghiri, Youssef/0000-0001-7175-9397 NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2038 BP 364 EP 364 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400702037 ER PT J AU Acierno, JS Falardeau, J Kennedy, JC Leyne, M Bromley, MC Colman, M Sun, M Bove, C Bach, G Ashworth, L Schiripo, T Ma, S Helbling, LA Goldin, E Schiffmann, R Slaugenhaupt, SA AF Acierno, JS Falardeau, J Kennedy, JC Leyne, M Bromley, MC Colman, M Sun, M Bove, C Bach, G Ashworth, L Schiripo, T Ma, S Helbling, LA Goldin, E Schiffmann, R Slaugenhaupt, SA TI Precise genetic mapping and haplotype analysis of the Mucolipidosis IV candidate region on human chromosome 19p13.2-13.3. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Harvard Inst Human Genet, Boston, MA USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. Hadassah Univ Hosp, Dept Human Genet, IL-91120 Jerusalem, Israel. Univ Calif Lawrence Livermore Natl Lab, Ctr Human Genome, Livermore, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2150 BP 384 EP 384 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400702151 ER PT J AU Kluwe, L Mautner, V Xin, W Jacoby, LB Willett, CJ MacCollin, M AF Kluwe, L Mautner, V Xin, W Jacoby, LB Willett, CJ MacCollin, M TI Molecular determination of somatic mosaicism in typical NF2 patients. SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Meeting Abstract C1 Univ Hamburg Hosp, D-2000 Hamburg, Germany. Gen Hosp Ochsenzoll, Hamburg, Germany. Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2000 VL 67 IS 4 SU 2 MA 2254 BP 401 EP 401 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 355TA UT WOS:000089400702254 ER PT J AU Larkin, EK Smith, TJ Stayner, L Rosner, B Speizer, FE Garshick, E AF Larkin, EK Smith, TJ Stayner, L Rosner, B Speizer, FE Garshick, E TI Diesel exhaust exposure and lung cancer: Adjustment for the effect of smoking in a retrospective cohort study SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE confounding; diesel exhaust; lung cancer; railroad workers; smoking ID RAILROAD WORKERS; BETA-CAROTENE; RISK; MORTALITY; VALIDITY; WOMEN; MEN AB Background The extent that cigarette smoking may confound the relationship between diesel exhaust exposure and lung cancer was assessed in a retrospective cohort study of 55,395 U.S. railroad workers followed from 1959 to 1976. Methods The relative risk (RR) of lung cancer due to diesel exhaust was indirectly adjusted using job-specific smoking data from a case-control study Of railroad workers who died between 1981-1982 and from a survey of 514 living workers from an active railroad in 1982. Adjustment factors were developed based on the distribution of job specific smoking rates. Results The unadjusted RR for lung cancer was 1.58 (95% CI = 1.14-2.20)for workers aged 40-44 in 1959, who experienced the longest possible duration of exposure, and the smoking adjusted RR was 1.44 (1.01-2.05). Conclusions After considering differences in smoking rates between workers exposed and unexposed to diesel exhaust in a relatively large blue-collar cohort, there were still elevated risks of lung cancer in workers in jobs with diesel exhaust exposure. Published 2000 Wiley-Liss, Inc. C1 VA Boston Hlth Care Syst, Med & Res Serv, Boston, MA 02132 USA. Harvard Univ, Sch Publ Hlth, Dept Occupat Hlth, Boston, MA 02115 USA. NIOSH, Cincinnati, OH 45226 USA. Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Garshick, E (reprint author), VA Boston Hlth Care Syst, Med & Res Serv, 1400 UFW Pkwy, Boston, MA 02132 USA. NR 32 TC 17 Z9 18 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD OCT PY 2000 VL 38 IS 4 BP 399 EP 409 DI 10.1002/1097-0274(200010)38:4<399::AID-AJIM5>3.0.CO;2-D PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 351DT UT WOS:000089143100005 PM 10982980 ER PT J AU Wong, CS Gipson, DS Gillen, DL Emerson, S Koepsell, T Sherrard, DJ Watkins, SL Stehman-Breen, C AF Wong, CS Gipson, DS Gillen, DL Emerson, S Koepsell, T Sherrard, DJ Watkins, SL Stehman-Breen, C TI Anthropometric measures and risk of death in children with end-stage renal disease SO AMERICAN JOURNAL OF KIDNEY DISEASES 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 DE pediatric; growth; body mass index (BMI); survival ID GROWTH-FACTOR-I; CHRONIC PERITONEAL-DIALYSIS; HEMODIALYSIS-PATIENTS; IGF-I; DILATED CARDIOMYOPATHY; TRANSPLANT RECIPIENTS; KIDNEY-TRANSPLANT; HORMONE TREATMENT; MORTALITY; FAILURE AB We evaluated the association between anthropometric measurements and death among pediatric patients with end-stage renal disease (ESRD) using data from the Pediatric Growth and Development Special Study (PGDSS) from the US Renal Data System. Height, growth velocity, and body mass index (BMI) were used for the analysis of 1,949 patients in the PGDSS. To standardize these measurements, SD scores (SDSs) were calculated using population data from the Third National Health and Nutrition Examination Survey. Using Cox proportional hazards models, we assessed the association between anthropometric measures and death, controlling for demographic factors and stratifying by age. Multivariate analysis showed that each decrease by 1 SDS in height was associated with a 14% increase in risk for death (adjusted relative risk [aRR], 1.14; 95% confidence interval [CI], 1.02 to 1.27; P = 0.017). For each 1 SDS decrease in growth velocity among patients in our sample, the risk for death increased by 12% (aRR, 1.12; 95% CI, 1.00 to 1.25; P = 0.043). There was a statistically significant ill-shaped association between BMI and death (P = 0.001), with relatively low and high BMIs associated with an increased risk for death. In children with ESRD, growth delay and extremes in BMI are associated with an increased risk for mortality. (C) 2000 by the National Kidney Foundation, Inc. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Childrens Hosp & Reg Med Ctr, Div Nephrol, Seattle, WA 98108 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. Univ N Carolina, Sch Med, Div Nephrol, Chapel Hill, NC 27599 USA. RP Stehman-Breen, C (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [TDK 07662-08] NR 55 TC 96 Z9 103 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD OCT PY 2000 VL 36 IS 4 BP 811 EP 819 DI 10.1053/ajkd.2000.17674 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 358HJ UT WOS:000089552300020 PM 11007685 ER PT J AU Getchell, WS Larsen, GC Morris, CD McAnulty, JH AF Getchell, WS Larsen, GC Morris, CD McAnulty, JH TI A comparison of medicare fee-for-service and a group-model HMO in the inpatient management and long-term survival of elderly individuals with syncope SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID HEALTH MAINTENANCE ORGANIZATION; HOSPITALIZED-PATIENTS; DIAGNOSING SYNCOPE; CHRONICALLY ILL; PRIMARY-CARE; OUTCOMES; MORTALITY; SPECIALTY; INSURANCE; IMPACT AB Objective: To compare the management and survival of elderly patients hospitalized with syncope in 2 healthcare delivery systems. Study Design: Retrospective cohort. Patients and Methods: Using hospitalization records from Medicare and a group-model health maintenance organization (HMO) in Oregon, we identified individuals with an admission or discharge diagnosis of syncope between 1992 and 1994, Among patients 65 years or older (median age = 79 years), we randomly selected a sample of the standard Medicare patients (primarily fee-for-service; n = 473) and all of the group-model HMO patients (n = 583). Use of inpatient testing and consultation was ascertained by chart review; all-cause mortality was obtained from the National Death Index. Results: Median diagnostic testing and consultation costs were the same (P = .35) in the standard Medicare population ($643) and the HMO population ($619), although the use of specific tests differed. More cardiovascular syncope was identified in the Medicare population (23% vs 18%; P = .02). Inpatient, 30-day, 1-year, and 4-year mortality rates were higher in the Medicare population (1.7%, 3.8%, 16.7%, and 50.6% respectively) than in the HMO population (0.7%, 1.5 %, 13.2%, and 41.8%). After adjusting for age, gender, comorbidity, diagnostic testing, and administrative factors, the relative risk (RR) of dying was lower for group-model HMO patients (RR = 0.74; 95% confidence interval = 0.60, 0.91) than for standard Medicare patients (RR = 1.0). Conclusions: The inpatient management of these elderly patients with syncope was similar in the group-model HMO and standard Medicare settings, but survival was better for the individuals in the HMO. The reason for the differential survival is not obvious and warrants additional study. C1 Portland Vet Affairs Med Ctr, Cardiol Sect, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Div Cardiol, Dept Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Div Cardiol, Div Med Informat & Outcomes Res, Portland, OR 97201 USA. RP Getchell, WS (reprint author), Portland Vet Affairs Med Ctr, Cardiol Sect, P3-CARD,3710 SW US Vet Hosp Dr, Portland, OR 97207 USA. FU AHRQ HHS [T32 HS00069] NR 39 TC 3 Z9 3 U1 1 U2 1 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 OCT PY 2000 VL 6 IS 10 BP 1089 EP 1098 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 365EK UT WOS:000089935300001 PM 11184665 ER PT J AU Good, CB Fultz, SL Trilli, L Etchason, J AF Good, CB Fultz, SL Trilli, L Etchason, J TI Therapeutic substitution of cimetidine for nizatidine was not associated with an increase in healthcare utilization SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID H-2-RECEPTOR ANTAGONISTS; CLINICAL DIFFERENCES; DRUGS; COSTS AB Objective: To examine changes in healthcare utilization resulting from a formulary switch to cimetidine from nizatidine at the Veterans Affairs Pittsburgh Healthcare System, Study Design: A retrospective analysis of administrative and clinical data 6 months before and 6 months after the therapeutic substitution, Methods: The 704 patients who were switched from nizatidine to cimetidine were included in the study. Administrative data included total and primary care clinic visits, emergency room visits, gastrointestinal (CI)-related radiological studies, and CI endoscopic procedures, Discharge summaries were examined, and rates of total and CI-related hospitalizations were calculated, Results: There was no evidence of increased utilization of healthcare resources during the 6 months after the formulary switch. Estimated monthly pharmaceutical savings for the Veterans Affairs Pittsburgh Healthcare System were $7260, Conclusions: A formulary switch from nizatidine to cimetidine can be accomplished at significant pharmaceutical cost savings, and this retrospective study suggests that this can be done without increasing other aspects of healthcare resource utilization. C1 Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Div Gen Med, Pittsburgh, PA USA. Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA USA. Kerr L White Inst Hlth Serv Res, Atlanta, GA USA. RP Good, CB (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Univ Dr C, Pittsburgh, PA 15240 USA. NR 16 TC 4 Z9 4 U1 1 U2 1 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 OCT PY 2000 VL 6 IS 10 BP 1141 EP 1146 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 365EK UT WOS:000089935300005 PM 11184669 ER PT J AU Fine, MJ Pratt, HM Obrosky, DS Lave, JR McIntosh, LJ Singer, DE Coley, CM Kapoor, WN AF Fine, MJ Pratt, HM Obrosky, DS Lave, JR McIntosh, LJ Singer, DE Coley, CM Kapoor, WN TI Relation between length of hospital stay and costs of care for patients with community-acquired pneumonia SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID OUTCOMES AB PURPOSE: Patients with pneumonia often remain hospitalized after becoming clinically stable, without demonstrated benefits on outcome. The purposes of this study were to assess the relation between length of hospital stay and daily medical care costs and to estimate the potential cost savings associated with a reduced length of stay for patients with pneumonia. SUBJECTS AND METHODS: As part of a prospective study of adults hospitalized with community-acquired pneumonia at a community hospital and two university teaching hospitals, daily medical care costs were estimated by multiplying individual charges by department-specific cost-to-charge ratios obtained from each hospital's Medicare cost reports. RESULTS: The median total cost of hospitalization for all 982 inpatients was $5,942, with a median daily cost of $836, including $491 (59%) for room and $345 (41%) for non-room costs. Average daily non-room costs were 282% greater on the first hospital day, 59% greater on the second day, and 19% greater on the third day than the average daily cost throughout the hospitalization (all P < 0.05), and were 14% to 72% lower on the last 3 days of hospitalization. Average daily room costs remained relatively constant throughout the hospital stay, with the exception of the day of discharge. A projected mean savings of $680 was associated with a 1-day reduction in length of stay. CONCLUSIONS: Despite institutional differences in total costs, patterns of daily resource use throughout hospitalization were similar at all institutions. A 1-day reduction in length of stay might yield substantial cost-savings. (C) 2000 by Excerpta Medica, Inc. C1 Univ Pittsburgh, Grad Sch Publ Hlth, Div Gen Internal Med, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Ctr Res Hlth Care, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Serv Adm, Pittsburgh, PA USA. Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fine, MJ (reprint author), Montefiore Univ Hosp, 3 East,Room 820,200 Lothrop St, Pittsburgh, PA 15213 USA. FU AHRQ HHS [R01 HS06468] NR 15 TC 95 Z9 97 U1 0 U2 4 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT 1 PY 2000 VL 109 IS 5 BP 378 EP 385 DI 10.1016/S0002-9343(00)00500-3 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 360QE UT WOS:000089678100005 PM 11020394 ER PT J AU Siegel, RE AF Siegel, RE TI How long a stay in the hospital is needed for patients with community-acquired pneumonia? SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID LOW-RISK PATIENTS; ANTIMICROBIAL THERAPY; MEDICAL OUTCOMES; ELDERLY PATIENTS; ANTIBIOTICS; DISCHARGE; CARE C1 Bronx Vet Affairs Med Ctr, Intens Care Unit, Crit Care Ctr, Bronx, NY 10468 USA. Mt Sinai Sch Med, New York, NY USA. RP Siegel, RE (reprint author), Bronx Vet Affairs Med Ctr, Intens Care Unit, Crit Care Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. NR 15 TC 6 Z9 7 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT 1 PY 2000 VL 109 IS 5 BP 434 EP 436 DI 10.1016/S0002-9343(00)00525-8 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 360QE UT WOS:000089678100013 PM 11020402 ER PT J AU Jabs, DA Rosenbaum, JT Foster, CS Holland, GN Jaffe, GJ Louie, JS Nussenblatt, RB Stiehm, ER Tessler, H Van Gelder, RN Whitcup, SM Yocum, D AF Jabs, DA Rosenbaum, JT Foster, CS Holland, GN Jaffe, GJ Louie, JS Nussenblatt, RB Stiehm, ER Tessler, H Van Gelder, RN Whitcup, SM Yocum, D TI Guidelines for the use of immunosuppressive drugs in patients with ocular inflammatory disorders: Recommendations of an expert panel SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Review ID RHEUMATOID-ARTHRITIS PATIENTS; BEHCETS-DISEASE; REFRACTORY UVEITIS; WEGENERS GRANULOMATOSIS; MULTIFOCAL CHOROIDITIS; POSTERIOR UVEITIS; RANDOMIZED TRIAL; CYCLOSPORINE-A; MASKED TRIAL; CLINICAL PHARMACOKINETICS AB PURPOSE: To provide recommendations for the use of immunosuppressive drugs in the treatment of patients with ocular inflammatory disorders. PARTICIPANTS: A 12-person panel of physicians with expertise in ophthalmologic, pediatric, and rheumatologic disease, in research, and in the use of immunosuppressive drugs in patient care. EVIDENCE: Published clinical study results. Recommendations were rated according to the quality and strength of available evidence. PROCESS: The panel was convened in September of 1999 and met regularly through May 2000. Subgroups of the panel summarized and presented available information on specific topics to the full panel; recommendations and ratings were determined by group consensus. CONCLUSIONS: Although corticosteroids represent one of the mainstays in the management: of patients with ocular inflammation, in many patients, the severity of the disease, the presence of corticosteroid side effects, or the requirement for doses of systemic corticosteroids highly likely to result in corticosteroid complications supports the rationale for immunosuppressive drugs (for example, antimetabolites, T-cell inhibitors, and alkylating agents) being used in the management of these patients. Because of the potential for side effects, treatment must be individualized and regular monitoring performed. With careful use of immunosuppressive drugs for treatment of ocular inflammatory disorders, many patients will benefit from them either with better control of the ocular inflammation or with a decrease in corticosteroid side effects. (C) 2000 by Elsevier Science Inc. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Oregon Hlth Sci Univ, Casey Eye Inst, Dept Ophthalmol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Casey Eye Inst, Dept Med, Portland, OR 97201 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. Univ Calif Los Angeles, Jules Stein Eye Inst, Dept Ophthalmol, Los Angeles, CA 90024 USA. Duke Univ, Ctr Eye, Durham, NC USA. Harbor Univ Calif Los Angeles, Med Ctr, Dept Med, Los Angeles, CA USA. NEI, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. Univ Illinois, Eye & Ear Infirm, Chicago, IL 60612 USA. Washington Univ, Dept Ophthalmol & Visual Sci, St Louis, MO USA. Univ Arizona, Hlth Sci Ctr, Dept Med, Tucson, AZ USA. RP Jabs, DA (reprint author), 550 N Broadway,Suite 700, Baltimore, MD 21205 USA. NR 122 TC 347 Z9 370 U1 3 U2 7 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 OCT PY 2000 VL 130 IS 4 BP 492 EP 513 DI 10.1016/S0002-9394(00)00659-0 PG 22 WC Ophthalmology SC Ophthalmology GA 362BV UT WOS:000089759500012 PM 11024423 ER PT J AU Moromizato, Y Stechschulte, S Miyamoto, K Murata, T Tsujikawa, A Joussen, AM Adamis, AP AF Moromizato, Y Stechschulte, S Miyamoto, K Murata, T Tsujikawa, A Joussen, AM Adamis, AP TI CD18 and ICAM-1-dependent corneal neovascularization and inflammation after limbal injury SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; INTERCELLULAR-ADHESION MOLECULE-1; VASCULAR-PERMEABILITY FACTOR; ANGIOGENESIS; EXPRESSION; CELLS; MICE AB Extensive Limbal injury is a leading cause of irreversible blindness. The destruction of corneal limbal stem cells often results in corneal neovascularization and an optically inferior epithelium, Previous work has shown that the neovascularization after limbal injury is vascular endothelial growth factor (VEGF)-dependent, with much of the VEGF emanating from the inflammatory cells that invade the cornea, Using a relevant mouse model of limbal injury, we examined the role of CD18 and intercellular adhesion molecule-1 (ICAM-1) in limbal injury-induced neovascularization, The results show that CD18- and ICAM-1-deficient mice developed 35% (n = 5,P = 0.003) and 36% (n = 5, P = 0.002) less neovascularization than strain-specific normal controls, respectively. The corneal neutrophil counts mere similarly reduced by 51% (n = 5, P < 0.003) and 46% (n = 5, P < 0.006), respectively, When VEGF mRNA levels mere analyzed, they were reduced by 66% (n = 3, P = 0.004) and 48% Of = 3,p = 0.024), respectively, Taken together, these data identify CD-18 and ICAM-1 as mediators of the inflammatory and VEGF-dependent corneal neovascularization that follows limbal injury. The targeting of CD18 and ICAM-1 may prove useful in the treatment of inflammation-associated neovascularization in the cornea and elsewhere. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Childrens Hosp, Sch Med, Surg Res Lab, Boston, MA 02115 USA. RP Adamis, AP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY 11627, R01 EY 12611] NR 18 TC 45 Z9 53 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 2000 VL 157 IS 4 BP 1277 EP 1281 DI 10.1016/S0002-9440(10)64643-3 PG 5 WC Pathology SC Pathology GA 362CN UT WOS:000089761200025 PM 11021832 ER PT J AU Zhang, BX Yeh, CK Hymer, TK Lifschitz, MD Katz, MS AF Zhang, BX Yeh, CK Hymer, TK Lifschitz, MD Katz, MS TI EGF inhibits muscarinic receptor-mediated calcium signaling in a human salivary cell line SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE carbachol; signal transduction; protein kinase C; mitogen-activated protein kinase; epidermal growth factor ID PROTEIN-KINASE-C; EPIDERMAL GROWTH-FACTOR; INOSITOL TRISPHOSPHATE RECEPTOR; INTRACELLULAR CALCIUM; ACINAR-CELLS; CA2+ ENTRY; ACTIVATION; PHOSPHORYLATION; STIMULATION; EXPRESSION AB The effects of epidermal growth factor (EGF) on intracellular calcium ([Ca2+](i)) responses to the muscarinic agonist carbachol were studied in a human salivary cell line (HSY). Carbachol (10(-4) M)-stimulated [Ca2+](i) mobilization was inhibited by 40% after 48-h treatment with 5 X 10(-10) M EGF. EGF also reduced carbachol-induced [Ca2+](i) in Ca2+-free medium and Ca2+ influx following repletion of extracellular Ca2+. Under Ca2+-free conditions, thapsigargin, an inhibitor of Ca2+ uptake to internal stores, induced similar [Ca2+](i) signals in control and EGF-treated cells, indicating that internal Ca2+ stores were unaffected by EGF; however, in cells exposed to thapsigargin, Ca2+ influx following Ca2+ repletion was reduced by EGF. Muscarinic receptor density, assessed by binding of the muscarinic receptor antagonist L-[benzilic-4,4'-(HCN)-H-3]quinuclidinyl benzilate ([H-3]QNB), was decreased by 20% after EGF treatment. Inhibition of the carbachol response by EGF was not altered by phorbol ester-induced downregulation of protein kinase C (PKC) but was enhanced upon PKC activation by a diacylglycerol analog. Phosphorylation of mitogen-activated protein kinase (MAP kinase) and inhibition of the carbachol response by EGF were both blocked by the MAP kinase pathway inhibitor PD-98059. The results suggest that EGF decreases carbachol-induced Ca2+ release from internal stores and also exerts a direct inhibitory action on Ca2+ influx. A decline in muscarinic receptor density may contribute to EGF inhibition of carbachol responsiveness. The inhibitory effect of EGF is mediated by the MAP kinase pathway and is potentiated by a distinct modulatory cascade involving activation of PKC. EGF may play a physiological role in regulating muscarinic receptor-stimulated salivary secretion. C1 S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr 182, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Med Res Serv, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Dent Diagnost Sci, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. RP Katz, MS (reprint author), S Texas Vet Hlth Care Syst, Audie L Murphy Div, Geriatr Res Educ & Clin Ctr 182, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NIDCR NIH HHS [DE10756] NR 45 TC 7 Z9 7 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD OCT PY 2000 VL 279 IS 4 BP C1024 EP C1033 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 356YR UT WOS:000089472200016 PM 11003583 ER PT J AU Zaninovic, V Gukovskaya, AS Gukovsky, I Mouria, M Pandol, SJ AF Zaninovic, V Gukovskaya, AS Gukovsky, I Mouria, M Pandol, SJ TI Cerulein upregulates ICAM-1 in pancreatic acinar cells, which mediates neutrophil adhesion to these cells SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE intercellular adhesion molecule-1; cholecystokinin; nuclear; factor-kappa B; inflammatory response; pancreatitis ID NF-KAPPA-B; CYTOKINE-INDUCED EXPRESSION; NECROSIS-FACTOR-ALPHA; MOLECULE-1 ICAM-1; NECROTIZING PANCREATITIS; TRANSCRIPTION FACTORS; REGULATORY ELEMENTS; EPITHELIAL-CELL; GENE-EXPRESSION; CYTOSKELETON AB Neutrophil infiltration into the pancreas is a key event in pancreatitis. Here we show that intercellular adhesion molecule-1 (ICAM-1), which regulates neutrophil adhesion, is present on rat pancreatic acinar cells, is upregulated by a hormone (cerulein) and mediates direct binding of neutrophils to acinar cells. ICAM-1 was upregulated in pancreas of rats with experimental pancreatitis induced by supramaximal doses of cerulein. Furthermore, cerulein time and dose dependently stimulated expression of ICAM-1 mRNA and protein in isolated pancreatic acinar cells. Inhibitory analysis showed that activation of transcription factor nuclear factor-kappa B (NF-kappa B) was involved in ICAM-1 upregulation by cerulein, but NF-kappa B did not mediate basal expression of ICAM-1 mRNA in acinar cells. With an adhesion assay, we found that neutrophils bind to isolated pancreatic acinar cells and that cerulein upregulates the extent of adhesion. Neutralizing ICAM-1 antibody blocked neutrophil binding to both control and cerulein-stimulated acinar cells, suggesting ICAM-1 involvement in this adhesion. Thus the acinar cell is capable of targeting neutrophils to its surface, a process that may be important for inflammatory and cell death responses in pancreatitis and other pancreatic disorders. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. RP Gukovskaya, AS (reprint author), W Los Angeles Vet Affairs Med Ctr, Bldg 258,Rm 340,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM agukovsk@ucla.edu NR 46 TC 60 Z9 62 U1 0 U2 2 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 OCT PY 2000 VL 279 IS 4 BP G666 EP G676 PG 11 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 358CG UT WOS:000089539200003 PM 11005752 ER PT J AU Tian, W Zhang, Z Cohen, DM AF Tian, W Zhang, Z Cohen, DM TI MAPK signaling and the kidney SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Review DE urea; tubule; mesangial; extracellular signal-regulated kinase; stress-activated protein kinase; c-Jun NH(2) -terminal kinase; p38; mitogen-activated protein kinase ID ACTIVATED PROTEIN-KINASE; RAT MESANGIAL CELLS; JUN NH2-TERMINAL KINASE; N-TERMINAL KINASE; GLOMERULAR EPITHELIAL-CELLS; CYTOSOLIC PHOSPHOLIPASE A(2); PROMOTES CELLULAR GROWTH; LOW-DENSITY-LIPOPROTEIN; HIGH GLUCOSE CONDITIONS; PROXIMAL TUBULAR CELLS AB Following an overview of the biochemistry of mitogen-activated protein kinase (MAPK) pathways, the relevance of these signaling events to specific models of renal cell function and pathophysiology, both in vitro and in vivo, will be emphasized. In in vitro model systems, events activating the principal MAPK families [extracellular signal-regulated and c-Jun NH(2)-terminal kinase and p38] have been best characterized in mesangial and tubular epithelial cell culture systems and include peptide mitogens, cytokines, lipid mediators, and physical stressors. Several in vivo models of proliferative or toxic renal injury are also associated with aberrant MAPK regulation. It is anticipated that elucidation of downstream effector signaling mechanisms and a clearer understanding of the immediate and remote upstream activating pathways, when applied to these highly clinically relevant model systems, will ultimately provide much greater insight into the basis for specificity now seemingly absent from these signaling events. C1 Oregon Hlth Sci Univ, Div Nephrol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Div Mol Med, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. RP Cohen, DM (reprint author), Oregon Hlth Sci Univ, Div Nephrol, Portland, OR 97201 USA. EM cohend@ohsu.edu RI Zhang, Zheng/J-2388-2014 OI Zhang, Zheng/0000-0003-2497-0362 FU NIDDK NIH HHS [DK52494] NR 173 TC 110 Z9 129 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD OCT PY 2000 VL 279 IS 4 BP F593 EP F604 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 356EF UT WOS:000089430800001 PM 10997909 ER PT J AU Steudel, W Kirmse, M Weimann, J Ullrich, R Hromi, J Zapol, WM AF Steudel, W Kirmse, M Weimann, J Ullrich, R Hromi, J Zapol, WM TI Exhaled nitric oxide production by nitric oxide synthase-deficient mice SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT International Conference of the American-Thoracic-Society CY APR 23-28, 1999 CL SAN DIEGO, CALIFORNIA SP Amer Thoracic Soc ID NASAL-MUCOSA; BIOLOGICAL-SYSTEMS; ASTHMATIC-PATIENTS; RESPIRATORY-TRACT; PARANASAL SINUSES; GUINEA-PIGS; EXPRESSION; AIRWAYS; HUMANS; AIR AB Nitric oxide (NO) is produced in the nasal cavities, airways, and lungs and is exhaled by normal animals and humans. Although increased exhaled NO concentrations in airway inflammation have been associated with increased airway expression of nitric oxide synthase 2 (NOS 2), it is uncertain which NOS isoform is responsible for baseline levels of exhaled NO. We therefore studied wild-type mice and mice with a congenital deficiency of NOS 1, NOS 2, or NOS 3. By studying a closed chamber in which the exhaled gas of a group of mice was collected, gaseous NO production rates were measured. Wild-type mice exhaled 362 +/- 35 x 10(-15) mol g(-1) min(-1) NO (mean +/- SE, n = 16 groups of five mice), NOS 1-deficient mice exhaled 592 +/- 74 x 10(-15) mol g(-1) min(-1) NO (n = 15 groups, p < 0.05 versus wild-type and NOS 2-deficient mice), NOS 2-deficient mice 330 +/- 74 x 10(-15) mol g(-1) min(-1) NO (n = 14 groups) and NOS 3-deficient mice 766 +/- 101 x 10(-15) mol g(-1) min(-1) NO (n = 16 groups, p < 0.001 versus wild-type and NOS 2-deficient mice). Pharmacological NOS inhibition with L-NAME decreased (p < 0.05) the exhaled NO production rate of wild-type and NOS 3-deficient but not of NOS 2-deficient mice. L-Arginine administration increased exhaled NO production rate in all but NOS 2-deficient mice. Absence of NOS 1 or 3 is associated with increased murine exhaled NO production rates. Since NOS 2-deficient mice were the only genotype to lack substrate- and inhibitor-regulated changes of NO exhalation, we suggest that NOS 2 is an important isoform contributing to exhaled NO exhalation in healthy mice. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Zapol, WM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 32 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL 42397] NR 44 TC 26 Z9 26 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 OCT PY 2000 VL 162 IS 4 BP 1262 EP 1267 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 364RD UT WOS:000089905900012 PM 11029328 ER PT J AU Gottlieb, DJ Yao, Q Redline, S Ali, T Mahowald, MW AF Gottlieb, DJ Yao, Q Redline, S Ali, T Mahowald, MW CA Sleep Heart Hlth Study Res Grp TI Does snoring predict sleepiness independently of apnea and hypopnea frequency? SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID EXCESSIVE DAYTIME SLEEPINESS; POSITIVE AIRWAY PRESSURE; APNEA/HYPOPNEA SYNDROME; VEHICLE ACCIDENTS; BLOOD-PRESSURE; HEART HEALTH; SCALE; FRAGMENTATION; ADULTS; RELIABILITY AB Obstructive apneas and hypopneas during sleep are a well recognized cause of excessive daytime sleepiness. Snoring is also associated with excess sleepiness, although it is not known whether this reflects an independent effect of snoring or whether snoring is simply a marker for obstructive sleep apnea. To further explore the relation of snoring to sleepiness, we conducted a cross-sectional cohort study of community-dwelling adults participating in the Sleep Heart Health Study. The study sample comprises 2737 men and 3,040 women with a mean age of 64 (SD 11) yr. Sleepiness was quantified using the Epworth Sleepiness Scale (ESS). Snoring history was obtained via a self-completion questionnaire. The respiratory disturbance index (RDI), defined as the number of apneas plus hypopneas per hour of sleep, was measured during in-home polysomnography. The ESS score increased progressively with increasing RDI, from a mean of 7.1 (4.2) in subjects with RDI < 1.5 to 8.8 (4.8) in subjects with RDI greater than or equal to 15 (p < 0.001). A progressive increase in ESS score was also seen across five categories of snoring frequency, from 6.4 (4.2) in current nonsnorers to 9.3 (4.8) in subjects who snored six to seven nights per week (p < 0.001). The prevalence of excessive daytime sleepiness, defined as an ESS score greater than or equal to 11, increased from 15% in never-snorers to 39% in those who snored six to seven nights per week. The relation of snoring to sleepiness was seen at all levels of RDI, with no significant change in the relation of snoring to ESS score after adjustment for RDI in multivariate models. The effects of snoring and RDI on sleepiness were little affected by adjustment for age, sex, race, body mass index, or questionnaire evidence of insufficient sleep time or nocturnal leg jerks or cramps. We conclude that both snoring and RDI are independently associated with excess sleepiness in community-dwelling, middle-aged and older adults. C1 Boston Univ, Sch Med, Ctr Pulm, Dept Med, Boston, MA 02118 USA. VA Boston Healthcare Syst, Boston, MA USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA. Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, Oklahoma City, OK USA. Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA. RP Gottlieb, DJ (reprint author), Boston Univ, Sch Med, Ctr Pulm, Dept Med, 715 Albany St,R-304, Boston, MA 02118 USA. FU NHLBI NIH HHS [U01HL53938, U01HL53940, U01HL53941] NR 39 TC 108 Z9 115 U1 2 U2 5 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT PY 2000 VL 162 IS 4 BP 1512 EP 1517 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 364RD UT WOS:000089905900054 PM 11029370 ER PT J AU Cooper, RA Eilers, DB AF Cooper, RA Eilers, DB TI Mammographic findings in basal cell carcinoma of the male nipple SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 Loyola Univ, Med Ctr, Dept Radiol, Maywood, IL 60153 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dermatol Sect, Dept Internal Med, Hines, IL 60141 USA. RP Cooper, RA (reprint author), Loyola Univ, Med Ctr, Dept Radiol, 2160 S 1st Ave, Maywood, IL 60153 USA. NR 8 TC 8 Z9 8 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2000 VL 175 IS 4 BP 1065 EP 1066 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 357GQ UT WOS:000089490500026 PM 11000166 ER PT J AU Park, JJ Sun, DQ Quade, BJ Flynn, C Sheets, EE Yang, A McKeon, F Crum, CP AF Park, JJ Sun, DQ Quade, BJ Flynn, C Sheets, EE Yang, A McKeon, F Crum, CP TI Stratified mucin-producing intraepithelial lesions of the cervix - Adenosquamous or columnar cell neoplasia? SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE cervical intraepithelial neoplasia; cervix neoplasms; adenocarcinoma in situ; p63 ID UTERINE CERVIX; CARCINOMA; EXPRESSION AB BACKGROUND: Squamous (CIN) and glandular (ACIS) intraepithelial lesions often coexist in the same cervical specimen. However, a less common and little studied Variant consists of a stratified epithelium resembling CIN in which conspicuous mucin production is present (Stratified Mucin-producing Intraepithelial LEsions (SMILE). This report describes the phenotypic characteristics of the SMILE, its associated lesions, and its immunophenotype. METHODS: Eighteen SMILEs were identified by the presence of conspicuous cytoplasmic clearing or vacuoles in lesions otherwise resembling CIN. The morphologic spectrum of SMILEs was detailed; including associated intraepithelial and invasive cervical neoplasms. In addition, selected cases were stained for mucicarmine. markers of squamous cell/reserve cell differentiation (keratin-14 and p63), and proliferative activity (Mib-1). RESULTS: Stratified neoplastic epithelial cells with a high Mib-1 index and a rounded or lobular contour at the epithelial-stromal interface characterized SMILEs. In contrast to CIN, in which mucin droplets are confined to surface cells, mucin was present throughout the epithelium, varying from indistinct cytoplasmic clearing to discrete vacuoles. SMILEs were distinguished from benign metaplasia by nuclear hyperchromasia and a high Mib-1 index. All but three coexisted with either a squamous (CIN) or glandular (ACIS) precursor lesion. Nine of nine coexisting invasive carcinomas contained glandular, adenosquamous differentiation. or both. SMILEs stained negative fur keratin-14 and variably for p63. When present, staining with p63 was confined to basal areas of SMILEs and was absent in areas of columnar differentiation. CONCLUSIONS: SMILEs are unusual cervical intraepithelial lesions best classified as variants of endocervical columnar cell neoplasia based on immunophenotype. The distribution and immunophenotype of SMILEs are consistent with a neoplasm arising in reserve cells in the transformation zone. The coexistence of a wide spectrum of intraepithelial and invasive cell phenotypes suggests that SMILEs are a marker for phenotypic instability, emphasizing the importance of identifying SMILEs and ensuring a complete examination of specimens containing this unusual precursor lesion. C1 Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. RP Crum, CP (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, 75 Francis St, Boston, MA 02115 USA. NR 20 TC 55 Z9 61 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 OCT PY 2000 VL 24 IS 10 BP 1414 EP 1419 DI 10.1097/00000478-200010000-00012 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 360XZ UT WOS:000089693800012 PM 11023104 ER PT J AU Sutcliffe, DG Murphy, CM Maslow, A Uppington, J Shorten, GD AF Sutcliffe, DG Murphy, CM Maslow, A Uppington, J Shorten, GD TI A comparison of antagonism of rocuronium-induced neuromuscular blockade during sevoflurane and isoflurane anaesthesia SO ANAESTHESIA LA English DT Article DE anaesthetic agents, isoflurane, sevoflurane neuromuscular blocking agent, rocuronium ID INTRAVENOUS ANESTHESIA; SPONTANEOUS-RECOVERY; TRAIN-OF-4 FADE; VECURONIUM; REVERSAL; NEOSTIGMINE; ATRACURIUM; PANCURONIUM; EDROPHONIUM; DESFLURANE AB Volatile anaesthetic agents potentiate neuromuscular blocking agents and retard their rate of reversal. We hypothesised that there was a difference in the rate of reversal of rocuronium-induced neuromuscular blockade based on the selection of inhalation agent. Thirty-eight patients undergoing elective surgical procedures received either sevoflurane or isoflurane, by random allocation. Neuromuscular blockade was induced using rocuronium 0.6 mg.kg(-1) followed by continuous intravenous infusion to maintain 90% suppression of the single twitch response. Upon completion of surgery, the rocuronium infusion was discontinued, neostigmine 50 mug.kg(-1) and glycopyrrolate 10 mug.kg(-1) were administered. Times from reversal to T-1 = 25, 50 and 60% and train-of-four ratio = 0.6 were recorded. The mean (SD) times to train-of-four ratio = 0.6 in the isoflurane and sevoflurane groups were 327 (132) and 351 (127) s, respectively. The mean (SD) times to single twitch response T-1 = 25, 50 and 60% in the isoflurane group were 81 (33), 161 (59) and 245 (84) s, respectively and in the sevoflurane group were 95 (35), 203 (88) and 252 (127) s, respectively. It is concluded that reversal of rocuronium-induced neuromuscular blockade is similar during isoflurane and sevoflurane anaesthesia. C1 Cork Univ Hosp, Cork, Ireland. Natl Univ Ireland Univ Coll Cork, Cork, Ireland. Beth Israel Deaconess Med Ctr, Dept Anaesthesia & Crit Care, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Shorten, GD (reprint author), Cork Univ Hosp, Cork, Ireland. NR 22 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0003-2409 J9 ANAESTHESIA JI Anaesthesia PD OCT PY 2000 VL 55 IS 10 BP 960 EP 964 DI 10.1046/j.1365-2044.2000.01526.x PG 5 WC Anesthesiology SC Anesthesiology GA 368TB UT WOS:000090132700005 PM 11012490 ER PT J AU Zhang, ZQ Yu, J Stanton, RC AF Zhang, ZQ Yu, J Stanton, RC TI A method for determination of pyridine nucleotides using a single extract SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE pyridine nucleotides; spectrophotometry-NADPH; NADP(+) ID PERFORMANCE LIQUID-CHROMATOGRAPHY; RED BLOOD-CELLS AB Intracellular redox levels play an important role in physiology and pathophysiology. The principal intracellular reductant is NADPH, which is required for both the proper activity of the entire antioxidant system and important prooxidant enzymes such as nitric oxide synthase and NADPH oxidase. Thus an easy and accurate measurement of NADPH is very desirable. The method described in this paper is based on the fact that NADH and NADPH (not NAD(+) and NADP(+)) affect absorbance at 340 nm. A single cell extract is separated into three aliquots (A(1), A(2), and A(3)). A(1) is untreated and the absorbance at 340 nm is measured. A(2) is treated with an enzyme that converts all of the NADP(+) to NADPH and then the absorbance at 340 nm is measured. A(2) is treated with an enzyme that converts all of the NADPH to NADP(+) and then the absorbance at 340 nm is measured. A(1) - A(3) is the NADPH content and A(2) - A(1) is the NADP(+) content of the extract. Using this method, we have obtained full recovery of all added nucleotides from cell extracts, thus making the method suitable for the quick determination of NADP(+) and NADPH in living cells. We conclude that this method for the measurement of NADP(+) and NADPH is rapid, simple, accurate, and reliable. (C) 2000 Academic Press. C1 Joslin Diabet Ctr, Div Renal, Boston, MA 02215 USA. Joslin Diabet Ctr, Dept Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Stanton, RC (reprint author), Joslin Diabet Ctr, Div Renal, Boston, MA 02215 USA. NR 19 TC 83 Z9 86 U1 1 U2 12 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD OCT 1 PY 2000 VL 285 IS 1 BP 163 EP 167 DI 10.1006/abio.2000.4701 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 360VD UT WOS:000089687300020 PM 10998277 ER PT J AU Abdi, S Vilassova, N Decosterd, I Feroz, N Borsook, D AF Abdi, S Vilassova, N Decosterd, I Feroz, N Borsook, D TI The effects of KRN5500, a spicamycin derivative, on neuropathic and nociceptive pain models in rats SO ANESTHESIA AND ANALGESIA LA English DT Article ID PERIPHERAL NEUROPATHY; AXONAL-TRANSPORT; VINCRISTINE; NERVE; HYPERALGESIA; NEURONS AB We studied the effects of a spicamycin derivative, KRN5500, on two animal models of neuropathic pain (Chung and Bennett models) and a nociceptive pain model by using Complete Freund's adjuvant. After the establishment of mechanical allodynia by using the previously mentioned models, a single intraperitoneal injection of KRN5500 produced significant attenuation of mechanical allodynia in both neuropathic pain models. However, this effect was not observed in rats that had a nociceptive injury (Complete Freund's adjuvant). Furthermore, this experimental drug did not alter the mechanical pain threshold (by using von Frey filament test) on normal, uninjured rats. We have demonstrated that KRN5500 may have value in the treatment of neuropathic pain. C1 Massachusetts Gen Hosp, Ctr Funct Pain Neuroimaging & Therapy Res, Dept Radiol & Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Funct Pain Neuroimaging & Therapy Res, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. RP Borsook, D (reprint author), Massachusetts Gen Hosp, Ctr Funct Pain Neuroimaging & Therapy Res, Dept Radiol & Neurol, Bldg 149,13th St,Mail Code 2301, Charlestown, MA 02129 USA. NR 21 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD OCT PY 2000 VL 91 IS 4 BP 955 EP 959 DI 10.1097/00000539-200010000-00035 PG 5 WC Anesthesiology SC Anesthesiology GA 357LT UT WOS:000089503700035 PM 11004056 ER PT J AU He, YL Ueyama, H Tashiro, C Mashimo, T Yoshiya, I AF He, YL Ueyama, H Tashiro, C Mashimo, T Yoshiya, I TI Pulmonary disposition of propofol in surgical patients SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Anesthesiologists CY OCT 17-21, 1998 CL ORLANDO, FLORIDA SP Amer Soc Anesthesiol DE extrahepatic metabolism; pharmacokinetics ID INDOCYANINE GREEN; HUMAN-LUNG; PULSE-SPECTROPHOTOMETRY; LIVER-TRANSPLANTATION; BLOOD COMPONENTS; DISPERSION MODEL; DRUG DISPOSITION; PROTEIN-BINDING; PASS UPTAKE; PHARMACOKINETICS AB Background: The lungs have been mentioned as a possible site contributing to the extrahepatic clearance of propofol, The objective of the present study was to clarify the pulmonary disposition of propofol directly in human lungs by Investigating both the frrst-pass uptake and pulmonary extraction at pseudo-steady state. Methods: Nine patients were enrolled in the first-pass uptake study. Propofol (5 mg) and indocyanine green (ICG; 15 mg) were simultaneously administered via a central venous catheter within 1 s, and sequential arterial blood samples were obtained from the radial artery at 1-s intervals up to 45 s, Eleven patients were included in the infusion study, and propofol was infused via the jugular vein at a rate of 50 mu g.kg(-1).min(-1). Blood samples were simultaneously collected from pulmonary and radial arteries up to 60 min. Results: A pronounced difference in the dilution curves between propofol and ICG was observed, and 28.4 +/- 11.6% (mean +/- SD) of propofol was taken up during the single passage through the human lung. The mean pulmonary transit time of propofol (31.3 +/- 6.0 s) was significantly longer than that of ICG (22.4 +/- 2.7 s; P < 0.01), indicating that some of the propofol trapped by lungs returned to the circulation by back diffusion. In the constant infusion study, no significant differences were observed with the plasma concentrations of propofol between pulmonary and radial arteries except for that at 2 min. The area under the curve of pulmonary and radial arterial concentration curves to 60 min were 59.1 +/- 14.8 and 56.8 +/- 12.5 mu g.ml(-1).min(-1), respectively, No significant difference was observed with the area under the curve, suggesting that metabolism was not involved in the pulmonary uptake in human lungs. Conclusions: Most of the propofol that undergoes pulmonary uptake during the first pass was released back to the circulation by back diffusion. Metabolism was not involved in the pulmonary uptake in human lungs. C1 Hyogo Coll Med, Dept Anesthesiol, Nishinomiya, Hyogo, Japan. Osaka Univ, Sch Med, Dept Anesthesiol, Suita, Osaka 565, Japan. RP He, YL (reprint author), Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care, 55 Fruit St, Boston, MA 02114 USA. NR 36 TC 36 Z9 38 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD OCT PY 2000 VL 93 IS 4 BP 986 EP 991 DI 10.1097/00000542-200010000-00019 PG 6 WC Anesthesiology SC Anesthesiology GA 360MN UT WOS:000089671900014 PM 11020751 ER PT J AU Orcel, P Krane, SM AF Orcel, P Krane, SM TI Secondary osteoporoses and glucocorticoid-induced osteoporosis. SO ANNALES DE MEDECINE INTERNE LA French DT Article DE secondary osteoporosis; glucocorticoid-induced osteoporosis ID BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; RHEUMATOID-ARTHRITIS; ORAL CORTICOSTEROIDS; LONGITUDINAL CHANGES; THYROID-HORMONE; HIP FRACTURE; MECHANISMS; THERAPY; TURNOVER AB In order to assess properly the diagnosis of osteoporosis, a short clinical investigation is required to address potential causes for bone loss. Osteoporosis used to be suspected in a patient with vertebral demineralization, but nowadays it is often diagnosed in a patient with a low bone mass on a screening dual-energy X-ray absorptiometry (DEXA). In this setting, it is important for the clinician to look for secondary osteoporosis, especially in men in whom secondary osteoporosis is more frequent than in women, before discussing any specific therapy. The major causes are longterm glucocorticoid therapy, endocrine (hypogonadism, primary hyperparathyroidism, hyperthyroidism), or digestive diseases. C1 Hop Lariboisiere, Ctr Viggo Petersen, Fdn Rhumatol, F-75475 Paris 10, France. Massachusetts Gen Hosp, Arthritis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Orcel, P (reprint author), Hop Lariboisiere, Ctr Viggo Petersen, Fdn Rhumatol, 6 Rue Guy Patin, F-75475 Paris 10, France. EM philippe.orcel@lrb.ap-hop-paris.fr NR 33 TC 3 Z9 3 U1 0 U2 0 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0003-410X J9 ANN MED INTERNE JI Ann. Med. Interne PD OCT PY 2000 VL 151 IS 6 BP 497 EP 503 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 382MH UT WOS:000165826500009 PM 11104930 ER PT J AU Lum, G AF Lum, G TI How effective are screening tests for microalbuminuria in random urine specimens? SO ANNALS OF CLINICAL AND LABORATORY SCIENCE LA English DT Article DE albuminuria; microalbuminuria; proteinuria; diabetic nephropathy; urine screening tests ID DIABETIC-PATIENTS; NEPHROPATHY; MANAGEMENT AB The effectiveness of four urine screening tests-microalbumin (MAlb), total protein (TProt), total protein/creatinine ratio (TProt/Cr R), and dipstick (DPalb) test fur albumin-were evaluated For the detection of MAlb in random urine specimens. The following criteria were used to assess the effectiveness of each urine screening test: 100% specificity (no false positive results); cost effectiveness; rapidity and ease of performing the screening test; and increased laboratory efficiency. A "gold standard" for presence of MAlb in random urine samples was defined as a microalbumin/creatinine ratio (MAlb/Cr R) of greater than or equal to 30 mg/g. The least costly urine screening test was the DPalb, which, if assigned a value of 1.0, allowed a cost ranking order for the screening tests-DPalb (1.0) < urine TProt (1.03) < urine TProt/Cr R (2.1) < urine MAlb (7.0). Two hundred urine samples from diabetic inpatients and outpatients were tested. Only two screening tests-MAlb and DPalb-achieved 100% specificity without increasing laboratory costs (small net savings), whereas the other two screening tests-TProt and TProt/Cr R-only achieved 100% specificity with increased laboratory costs. Theoretical prevalence rate analysis showed that urine MAlb screening would be effective at all prevalence rates for overt nephropathy. TProt and DPalb urine screening testing would be most effective in populations with prevalence rates of greater than or equal to 15% for overt nephropathy. The TProt/Cr R ratio would only be effective in populations with prevalence rates of greater than or equal to 30%. Of the four urine screening tests, only DPalb would significantly streamline the process of measuring urine MAlb. The dipstick test is inexpensive, easy and rapid to perform, does not delay measuring the ratio, since there is no wait for the screening test result, and can be used by referring laboratories to screen urine specimens before they are submitted to a central laboratory, thereby reducing laboratory workload. C1 VA Boston Healthcare Syst, W Roxbury Div, Pathol & Lab Med Serv, Boston, MA 02132 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Lum, G (reprint author), VA Boston Healthcare Syst, W Roxbury Div, Pathol & Lab Med Serv, 1400 VFW Pkwy, Boston, MA 02132 USA. NR 7 TC 9 Z9 9 U1 0 U2 2 PU INST CLINICAL SCIENCE INC PI PHILADELPHIA PA 1833 DELANCEY PLACE, PHILADELPHIA, PA 19103 USA SN 0091-7370 J9 ANN CLIN LAB SCI JI Ann. Clin. Lab. Sci. PD OCT PY 2000 VL 30 IS 4 BP 406 EP 411 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 363WA UT WOS:000089859600009 PM 11045765 ER PT J AU Sankar, R Shin, D Mazarati, AM Liu, HT Katsumori, H Lezama, R Wasterlain, CG AF Sankar, R Shin, D Mazarati, AM Liu, HT Katsumori, H Lezama, R Wasterlain, CG TI Epileptogenesis after status epilepticus reflects age- and model-dependent plasticity SO ANNALS OF NEUROLOGY LA English DT Article ID SUSTAINING STATUS EPILEPTICUS; PAIRED-PULSE INHIBITION; INDUCED NEURONAL INJURY; TEMPORAL-LOBE EPILEPSY; DENTATE GYRUS; RAT-BRAIN; C-FOS; FEBRILE SEIZURES; SYNAPTIC REORGANIZATION; ELECTRICAL-STIMULATION AB Although epilepsy often begins in childhood, factors that contribute to the development of epilepsy as a consequence of status epilepticus (SE) during early development are poorly understood. We investigated animal models in which seizure-induced epileptogenicity could be studied. Rats undergoing self-sustaining SE induced by perforant path stimulation (PPS) at the ages of postnatal day 21 (P21) and P35 were compared with those subjected to SE by lithium and pilocarpine (LiPC). Although only one animal subjected to PPS at P21 developed chronic spontaneous seizures by several months of observation, all the animals subjected to PPS at P35 became epileptic. In the LiPC model, however, most of the rat pups subjected to SE at P21 became epileptic. Animals with spontaneous seizures showed increased inhibition in the dentate gyrus, a characteristic of the epileptic brain, with evidence of mossy fiber synaptic reorganization. Examination of circuit recruitment by c-Jun immunohistochemistry showed activation restricted to the hippocampus in P21 animals subjected to PPS, although extensive activation of hippocampal and extrahippocampal structures was seen in pups subjected to PPS-induced self-sustaining SE at P35 or LiPC SE at P21. These results demonstrate that the appearance of epilepsy as a consequence of SE is influenced by the type of insult as well as by age-dependent circuit recruitment. C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Neurol Serv, Sepulveda, CA USA. RP Sankar, R (reprint author), Univ Calif Los Angeles, Sch Med, Dept Neurol, 22-474 MDCC,Box 951752, Los Angeles, CA 90095 USA. FU NINDS NIH HHS [NS01792, NS13515] NR 51 TC 97 Z9 99 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD OCT PY 2000 VL 48 IS 4 BP 580 EP 589 DI 10.1002/1531-8249(200010)48:4<580::AID-ANA4>3.0.CO;2-B PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 360DD UT WOS:000089650400004 PM 11026441 ER PT J AU Heaton, JT Kobler, JB Goldstein, EA McMahon, TA Barry, DT Hillman, RE AF Heaton, JT Kobler, JB Goldstein, EA McMahon, TA Barry, DT Hillman, RE TI Recurrent laryngeal nerve transposition in guinea pigs SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE alaryngeal speech; artificial larynx; laryngectomy; larynx; prosthesis; recurrent laryngeal nerve ID MYOSIN ATPASE; MUSCLES; REINNERVATION; FIBERS; RAT AB Improved control of prosthetic voice aids for laryngectomees might be possible to obtain with residual laryngeal motor nerve signals. We were able to recover motor signals from the recurrent laryngeal nerve (RLN) by transposing it into the ipsilateral denervated stemohyoid muscle (SH) in 8 guinea pigs. Reinnervation was monitored by electromyographic recordings from surface and intramuscular needle electrodes in awake animals. Within 4 to 14 weeks after surgery, all animals demonstrated laryngeal-like motor activity in the reinnervated SH, including activity during respiration, sniffing, swallowing, and/or vocalizing. After 3 to 6 months, the animals were reanesthetized, and nerve stimulation and section experiments confirmed the RLN as the source of reinnervation in all cases. In several animals, activity of the RLN-innervated SH was demonstrated to be correlated with that of contralateral laryngeal muscles. Histochemical analysis of the SH indicated a unilateral transformation from mostly fatigable to mostly fatigue-resistant fiber types ipsilateral to the RLN transposition, a phenotype more typical of laryngeal muscles. Thus, RLN transposition at the time of laryngectomy may be a method for salvaging laryngeal control signals that could be used to control prosthetic voice devices. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Univ, Dept Engn & Appl Sci, Cambridge, MA 02138 USA. NASA, Lyndon B Johnson Space Ctr, Houston, TX 77058 USA. RP Heaton, JT (reprint author), Massachusetts Eye & Ear Infirm, Voice & Speech Lab, 243 Charles St, Boston, MA 02114 USA. NR 25 TC 8 Z9 10 U1 1 U2 1 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD OCT PY 2000 VL 109 IS 10 BP 972 EP 980 PN 1 PG 9 WC Otorhinolaryngology SC Otorhinolaryngology GA 363FP UT WOS:000089824700012 PM 11051439 ER PT J AU Grillo, HC AF Grillo, HC TI Stents and sense SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material ID TRACHEAL; STENOSIS; TUBE C1 Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02144 USA. RP Grillo, HC (reprint author), Massachusetts Gen Hosp, Dept Thorac Surg, 55 Fruit St, Boston, MA 02144 USA. NR 9 TC 15 Z9 16 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 OCT PY 2000 VL 70 IS 4 BP 1142 EP 1142 DI 10.1016/S0003-4975(00)01796-3 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 365AE UT WOS:000089925600002 PM 11081858 ER PT J AU Grover, FL Edwards, FH AF Grover, FL Edwards, FH TI Similarity between the STS and New York State databases for valvular heart disease SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 Univ Colorado, Hlth Sci Ctr, Div Cardiothorac Surg C310, Denver, CO 80262 USA. Denver VA Med Ctr, Surg Serv, Denver, CO USA. Univ Florida, Div Cardiothorac Surg, Jacksonville, FL USA. RP Grover, FL (reprint author), Univ Colorado, Hlth Sci Ctr, Div Cardiothorac Surg C310, 4200 E 9th Ave, Denver, CO 80262 USA. NR 3 TC 14 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 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD OCT PY 2000 VL 70 IS 4 BP 1143 EP 1144 DI 10.1016/S0003-4975(00)02168-8 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 365AE UT WOS:000089925600003 PM 11081859 ER PT J AU Mathes, DW Yaremchuk, MJ Isselbacher, EM Madsen, JC AF Mathes, DW Yaremchuk, MJ Isselbacher, EM Madsen, JC TI Successful in situ treatment of an infected ascending aortic graft SO ANNALS OF THORACIC SURGERY LA English DT Article ID MANAGEMENT; TRANSPOSITION; PROSTHESIS; OMENTUM; ARCH AB Infection of an ascending aortic prosthesis is a grave complication associated with a high mortality. In most cases, extraanatomic bypass and removal of the infected vascular graft are not possible. Furthermore, the standard approach to this problem, which includes excision and replacement or debridement and repair of infected thoracic aortic grafts, carries a high early mortality. We report the successful treatment of this life-threatening complication using a conservative strategy in which the aortic prosthesis was salvaged by in situ disinfection followed by coverage with tissue naps. (C) 2000 by The Society of Thoracic Surgeons. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA 02114 USA. RP Madsen, JC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Cardiol, 55 Fruit St,EDR 105, Boston, MA 02114 USA. OI Mathes, David/0000-0003-4388-1373 NR 12 TC 15 Z9 15 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 OCT PY 2000 VL 70 IS 4 BP 1410 EP 1412 DI 10.1016/S0003-4975(00)01964-0 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 365AE UT WOS:000089925600069 PM 11081915 ER PT J AU Kirkpatrick, WR McAtee, RK Fothergill, AW Rinaldi, MG Patterson, TF AF Kirkpatrick, WR McAtee, RK Fothergill, AW Rinaldi, MG Patterson, TF TI Efficacy of voriconazole in a guinea pig model of disseminated invasive aspergillosis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IN-VITRO ACTIVITIES; AMPHOTERICIN-B; ITRACONAZOLE; FUMIGATUS; UK-109,496; SUSCEPTIBILITIES; FLUCONAZOLE; INFECTION; CANDIDA; FUNGI AB Voriconazole (VRC) was evaluated in an immunosuppressed-guinea pig model of invasive aspergillosis. VRC was more effective than amphotericin B or similar doses of itraconazole in the clearance of Aspergillus from tissues. VRC treatment regimens improved survival and significantly reduced tissue colony counts compared with those of controls. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX 78284 USA. RP Kirkpatrick, WR (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, Mail Code 7881,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 21 TC 57 Z9 60 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 2000 VL 44 IS 10 BP 2865 EP 2868 DI 10.1128/AAC.44.10.2865-2868.2000 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 355TK UT WOS:000089402300047 PM 10991875 ER PT J AU Wolozin, B Kellman, W Ruosseau, P Celesia, GG Siegel, G AF Wolozin, B Kellman, W Ruosseau, P Celesia, GG Siegel, G TI Decreased prevalence of Alzheimer disease associated with 3-hydroxy-3-methyglutaryl coenzyme A reductase inhibitors SO ARCHIVES OF NEUROLOGY LA English DT Article ID APOLIPOPROTEIN-E; TOTAL CHOLESTEROL; PROTEIN; TRANSPORT; ALLELE; ONSET; AGE AB Context: Increasing evidence suggests that cholesterol plays a role in the pathophysiology of Alzheimer disease (AD). For instance, an elevated serum cholesterol level has been shown to be a risk factor for AD. Objective: To determine whether patients taking 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), which are a group of medicines that inhibit the synthesis of cholesterol, have a lower prevalence of probable AD. Design: The experiment uses a cross-sectional analysis comparing the prevalence of probable AD in 3 groups of patients from hospital records: the entire population, patients receiving 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (hereafter referred to as the statins), and patients receiving medications used to treat hypertension or cardiovascular disease. Patients: The subjects studied were those included in the computer databases of 3 different hospitals for the years October 1, 1996, through August 31, 1998. Main Outcome Measures: Diagnosis of probable AD. Results: We find that the prevalence of probable AD in the cohort taking statins during the study interval is 60% to 73% (P<.001) lower than the total patient population or compared with patients taking other medications typically used in the treatment of hypertension or cardiovascular disease. Conclusions: There is a lower prevalence of diagnosed probable AD in patients taking 2 different 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors-lovastatin and pravastatin. While one cannot infer causative mechanisms based on these data, this study reveals an interesting association in the data, which warrants further study. C1 Loyola Univ, Med Ctr, Dept Pharmacol, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Neurol, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Biochem, Maywood, IL 60153 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Neurol, Hines, IL 60141 USA. Carl T Hayden Vet Affairs Med Ctr, Dept Geriatr & Extended Care Med, Phoenix, AZ USA. RP Wolozin, B (reprint author), Loyola Univ, Med Ctr, Dept Pharmacol, Bldg 102,Room 3634,2160 S 1st Ave, Maywood, IL 60153 USA. OI Wolozin, Benjamin/0000-0003-2068-1475 NR 17 TC 1047 Z9 1085 U1 1 U2 15 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 OCT PY 2000 VL 57 IS 10 BP 1439 EP 1443 DI 10.1001/archneur.57.10.1439 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 363EB UT WOS:000089821200005 PM 11030795 ER PT J AU Arevalo-Silva, CA Cao, YL Vacanti, M Weng, YL Vacanti, CA Eavey, RD AF Arevalo-Silva, CA Cao, YL Vacanti, M Weng, YL Vacanti, CA Eavey, RD TI Influence of growth factors on tissue-engineered pediatric elastic cartilage SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT 14th Annual Meeting of the American-Society-of-Pediatric-Otolaryngology CY APR 24-29, 1999 CL PALM DESERT, CALIFORNIA SP Amer Soc Pediatr Otolaryngol ID POLYMER-CELL CONSTRUCT; ARTICULAR CHONDROCYTES; FACTOR-BETA; HUMAN EAR; TRANSPLANTATION; RECONSTRUCTION; SHAPE AB Objective: To investigate the influence of growth factors on tissue-engineered pediatric human elastic cartilage relative to potential clinical application. Design: Controlled study. Subjects: Eleven children ranging in age from 5 to 15 years provided auricular elastic cartilage specimens measuring approximately 1 x 1 X 0.2 cm and weighing approximately 100 mg. Interventions: Three million chondrocytes were plated into 4 groups of Ham F-12 culture medium: group I, Ham F-12 culture medium only; no growth factors (control group); group 2, Ham F-12 culture medium and basic fibroblast growth factor; group 3, Ham F-12 culture medium and transforming growth actor beta; nd group 4,Ham F-12 culture medium and a combination of both growth factors. At 3 weeks, the cells were harvested and mixed with a copolymer gel of polyethylene glycol and polypropylene oxide (Pluronic F-127). The cell solution was injected subcutaneously into athymic mice. The constructs were harvested at up to 22 weeks of in vivo culture and histologically analyzed. Results: The average number of cells generated in vitro was as follows: group 1, 12 million, group 2, 40 million; group 3, 7 million; and group 4, 35 million. Group 2 in vivo gross specimens were the largest and : heaviest. Histologically, the control group and the basic fibroblast growth factor group (groups 1 and 2) exhibited characteristics compatible with normal auricular cartilage; groups 3 and 4 demonstrated cellular disorganization and moderate to severe fibrous tissue infiltration. Conclusions: Basic fibroblast growth factor demonstrates the greatest positive influence on the in vitro and in vivo growth of engineered pediatric human auricular cartilage. The results suggest that basic fibroblast growth factor-has the potential for clinical application in which a goal will be to generate a large volume of tissue-engineered cartilage from a small donor specimen in a short period of time and of a quality similar to native human elastic cartilage. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Univ Massachusetts, Med Ctr, Dept Anesthesiol, Ctr Tissue Engn, Boston, MA 02114 USA. Univ Massachusetts, Med Ctr, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Eavey, RD (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 18 TC 26 Z9 30 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD OCT PY 2000 VL 126 IS 10 BP 1234 EP 1238 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 362RE UT WOS:000089791400006 PM 11031410 ER PT J AU Burns, SP Little, JW Hussey, JL Lyman, P Lakshminarayanan, S AF Burns, SP Little, JW Hussey, JL Lyman, P Lakshminarayanan, S TI Sleep apnea syndrome in chronic spinal cord injury: Associated factors and treatment SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Spinal-Injury-Association CY APR 18-22, 1999 CL ATLANTA, GEORGIA SP Amer Spinal Injury Assoc DE rehabilitation; sleep apnea syndromes; spinal cord injuries ID POSITIVE AIRWAY PRESSURE; PULMONARY-HYPERTENSION; DAYTIME SLEEPINESS; RISK-FACTORS; SCALE; DISTURBANCES; TETRAPLEGIA; POPULATION; ACCIDENTS; HYPOPNEA AB Objective: To determine the prevalence of sleep apnea in a sample of persons with chronic spinal cord injury (SCI) of varying injury levels and degrees of impairment. Design: Cross-sectional study. Setting: Inpatient SCI rehabilitation unit. Participants: Twenty men with SCI (motor complete and incomplete; American Spinal Injury Association classes A-D) of at least 1 year's duration, randomly selected from patients with SCI undergoing elective hospitalization. Main Outcome Measures: Apnea index, determined by sleep study (including chest wall movement, airflow, oxygen saturation), and daytime sleepiness, determined by Epworth sleepiness score. Results: Eight subjects (40%) had sleep apnea, manifested by elevated apnea index (mean +/- SD, 17.1 +/- 6-9) and excessive daytime sleepiness. Sleep apnea was commonly diagnosed in motor-incomplete injuries. A trend (p = .07) existed toward a greater prevalence of sleep apnea with tetraplegia. Age and body mass index were not associated with sleep apnea. Conclusion: The prevalence of sleep apnea in men with chronic SCI admitted for nonrespiratory elective hospitalization is high relative to the general population. C1 Vet Affairs Puget Sound Hlth Care Syst, Pulm Serv, Seattle, WA 98108 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Spinal Cord Injury Serv, Seattle, WA 98108 USA. RP Burns, SP (reprint author), VA Puget Sound Hlth Care Syst, SCI Serv 128, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 42 TC 45 Z9 46 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD OCT PY 2000 VL 81 IS 10 BP 1334 EP 1339 DI 10.1053/apmr.2000.9398 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 360WA UT WOS:000089689300003 PM 11030498 ER PT J AU Chen, HC Bouchie, JL Perez, AS Clermont, AC Izumo, S Hampe, J Feener, DP AF Chen, HC Bouchie, JL Perez, AS Clermont, AC Izumo, S Hampe, J Feener, DP TI Role of the angiotensin AT(1) receptor in rat aortic and cardiac PAI-1 gene expression SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE angiotensin II; plasminogen activator inhibitor; hypertension; aorta; vascular smooth muscle cells ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; SMOOTH-MUSCLE CELLS; SPONTANEOUSLY HYPERTENSIVE RATS; CONVERTING ENZYME-INHIBITION; ENDOTHELIAL-CELLS; IMPAIRED FIBRINOLYSIS; SYSTEM; TYPE-1; INDUCTION; ENALAPRIL AB Although the renin-angiotensin system has been implicated in increasing plasminogen activator inhibitor-1 (PAI-1) expression, the role of the angiotensin type 1 (AT(1)) receptor is controversial. This report examines the effects of angiotensin peptides, angiotensin-converting enzyme inhibition, and AT(1) antagonism on rat aortic and cardiac PAI-1 gene expression, In vitro, angiotensin (Ang) I, Ang II, and angiotensin Arg(2)-Phe(8) (Ang III) were potent agonists of PAI-1 mRNA expression in rat aortic smooth muscle cells (RASMCs), and stimulation of PAI-1 by these peptides was blocked by the AT(1) antagonist candesartan. Angiotensin Val(3)-Phe(8) (Ang IV) and angiotensin Asp(1)-Pro(7) (Ang [1-7]) did not affect PAI-1 expression in RASMCs. In neonatal rat cardiomyocytes, Ang II increased PAI-1 mRNA expression by 4-fold (P<0.01), and this response was completely blocked by AT(1) receptor antagonism. Continuous intrajugular infusion of Ang II into Sprague-Dawley rats for 3 hours increased aortic and cardiac PAI-1 mRNA expression by 17- and 9 fold, respectively, and these Ang II responses were completely blocked by coinfusion with candesartan. Aortic and cardiac PAI-1 expressions were compared in spontaneously hypertensive rats and Wistar-Kyoto rats. PAI-1 expression in the aorta and heart from spontaneously hypertensive rats was 5.8-fold and 2-fold higher, respectively, than in control Wistar-Kyoto rats (P<0.05), Candesartan treatment for 1 week reduced aortic and cardiac PAI-1 expression in spontaneously hypertensive rats by 94% and 72%, respectively (P<0.05), but did not affect vascular PAI-1 levels in Wistar-Kyoto rats. These results demonstrate a role for the AT(1) receptor in mediating the effects of Ang II, on aortic and cardiac PAI-1 gene expression. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Feener, DP (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [P30 DK036836, DK 36836, DK 48358] NR 39 TC 40 Z9 47 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD OCT PY 2000 VL 20 IS 10 BP 2297 EP 2302 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 368GY UT WOS:000090110400022 PM 11031218 ER PT J AU Choi, HK Seeger, JD Kuntz, KM AF Choi, HK Seeger, JD Kuntz, KM TI A cost-effectiveness analysis of treatment options for patients with methotrexate-resistant rheumatoid arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID THERAPY; HYDROXYCHLOROQUINE; SULFASALAZINE; CYCLOSPORINE; IMPROVEMENT; COMBINATION; ETANERCEPT; IMPACT; MODEL; TRIAL AB Objective. Recently, new treatment options for rheumatoid arthritis (RA) patients with an inadequate response to methotrexate (MTX) have become available. Given the wide variability in efficacy and costs among these different treatment options, we sought to determine their cost-effectiveness (CE) in order to guide policy in different cost-constrained settings. Methods. We performed a CE analysis comparing 6 treatment options for patients with MTX-resistant RA: 1) etanercept + MTX, 2) etanercept monotherapy, 3) cyclosporine + MTX, 4) triple therapy (hydroxychloroquine, sulfasalazine, and MTX), 5) continuation of MTX monotherapy, and 6) no second-line agent. A decision model was used with a time horizon of 6 months. We used 2 measures of effectiveness based on published clinical trial data: the American College of Rheumatology 20% response criteria (ACR 20); and a weighted average of proportions of patients achieving responses of ACR 70, ACR 50, and ACR 20 (ACR 70 weighted response [ACR 70WR]). Incremental CE ratios were calculated as the additional cost per patient achieving either outcome, compared with the next least expensive option. To help interpret CE relative to these RA-specific outcomes, we conducted a separate, "reference" CE analysis of MTX use in MTX-naive RA patients, using the same outcomes. Results. In our reference analysis, MTX therapy for MTX-naive RA cost $1,100 per ACR 20 outcome and $1,500 per ACR 70WR, compared with no second-line agent. In our base-case analysis with either outcome, MTX continuation, cyclosporine + MTX, and etanercept monotherapy cost more, but either were not more efficacious or had a higher incremental CE ratio than the next most expensive option (i.e., they were dominated). Therefore, these options were not cost-effective. The least expensive option, triple therapy, cost 1.3 times more per patient with ACR 20 outcome ($1,500/ACR 20) and 2.1 times more per ACR 70WR ($3,100/ACR 70WR) than MTX therapy for MTX-naive RA. The most efficacious option, the combination of etanercept and MTX, cost 38 times more per patient with ACR 20 outcome ($4,600/ACR 20) and 23 times more per ACR 70WR ($34,800/ACR 70WR) than MTX therapy for MTX-naive RA. Overall, the results of extensive sensitivity analyses did not substantially affect these results. Conclusion. Our analysis indicates that if 15 mg/week MTX is cost-effective for achieving ACR 20 or ACR 70WR in MTX-naive RA over a 6-month period, then most likely so is triple therapy in MTX-resistant RA. Whether etanercept + MTX is cost-effective depends on whether $34,800/ACR 70WR (or $42,600/ACR 20) over a 6-month period is considered acceptable. C1 Massachusetts Gen Hosp, Arthrit Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Choi, HK (reprint author), Massachusetts Gen Hosp, Arthrit Unit, Bulfinch 165,Fruit St, Boston, MA 02114 USA. NR 29 TC 77 Z9 81 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD OCT PY 2000 VL 43 IS 10 BP 2316 EP 2327 DI 10.1002/1529-0131(200010)43:10<2316::AID-ANR20>3.0.CO;2-6 PG 12 WC Rheumatology SC Rheumatology GA 362BC UT WOS:000089757900020 PM 11037892 ER PT J AU Fraser, PA Lu, LY Ding, WZ Najundaswamy, SN Chen, DF Uko, G Tonks, S AF Fraser, PA Lu, LY Ding, WZ Najundaswamy, SN Chen, DF Uko, G Tonks, S TI HLA-B44031;DRB1*1503 and other sub-Saharan African major histocompatibility complex haplotypes in African Americans and Afro-Caribbeans carry C4A gene deletions: implications for ethnicity-specific lupus susceptibility genes SO ARTHRITIS AND RHEUMATISM LA English DT Article ID REVISED CRITERIA; HLA ANTIGENS; ERYTHEMATOSUS; CLASSIFICATION; ASSOCIATIONS; DEFICIENCY C1 Ctr Blood Res, Boston, MA 02115 USA. Inst Mol Med, Oxford, England. RP Fraser, PA (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NIEHS NIH HHS [ES-10295] NR 21 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD OCT PY 2000 VL 43 IS 10 BP 2378 EP 2379 DI 10.1002/1529-0131(200010)43:10<2378::AID-ANR27>3.0.CO;2-2 PG 2 WC Rheumatology SC Rheumatology GA 362BC UT WOS:000089757900027 PM 11037899 ER PT J AU Fineberg, MS Zarins, B Sherman, OH AF Fineberg, MS Zarins, B Sherman, OH TI Practical considerations in anterior cruciate ligament replacement surgery SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article DE anterior cruciate ligament reconstruction; endoscopic method; anatomy; radiography; tunnel placement; graft-tunnel mismatch; screw divergence ID TIBIAL TUNNEL PLACEMENT; INTERFERENCE SCREW DIVERGENCE; ACL RECONSTRUCTION; RADIOGRAPHIC EVALUATION; GRAFT IMPINGEMENT; FIXATION; ATTACHMENTS; STRENGTH; INVITRO; ANGLES AB The endoscopic method of anterior cruciate ligament (ACL) reconstruction using a patellar tendon graft that is secured with interference screws is a commonly performed procedure. It has many potential pitfalls, the majority of which are secondary to technical errors. Prevention of errors starts with a full knowledge of normal ACL anatomy and any discrepancies with the size and shape of the graft substitute. Accurate tibial and femoral tunnel placement is essential and involves using consistent intra-articular landmarks and achieving specific radiographic criteria. Accurate tunnel placement minimizes graft excursion and impingement against the roof of the intercondylar notch. This will result in maximum knee stability and motion. Much has been written about the principles of graft-tunnel mismatch and interference screw-bone plug divergence. The clinical implications of these potential sources of error remain somewhat controversial and are discussed in this article. C1 SUNY Buffalo, Sports Med Inst, Dept Orthopaed Surg, Sports Med Serv, Buffalo, NY 14214 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Sports Med Serv, Boston, MA 02114 USA. NYU, Hosp Joint Dis, Dept Orthopaed Surg, Sports Med Serv, New York, NY USA. RP Fineberg, MS (reprint author), SUNY Buffalo, Sports Med Inst, Dept Orthopaed Surg, Sports Med Serv, 160 Farber Hall,3435 Main St, Buffalo, NY 14214 USA. EM msfdoc@AOL.com OI sherman, orrin/0000-0002-1646-5174 NR 45 TC 31 Z9 32 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD OCT PY 2000 VL 16 IS 7 BP 715 EP 724 DI 10.1053/jars.2000.8951 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 360XB UT WOS:000089691700005 PM 11027755 ER PT J AU Yip-Schneider, MT Miao, WY Lin, A Barnard, DS Tzivion, G Marshall, MS AF Yip-Schneider, MT Miao, WY Lin, A Barnard, DS Tzivion, G Marshall, MS TI Regulation of the Raf-1 kinase domain by phosphorylation and 14-3-3 association SO BIOCHEMICAL JOURNAL LA English DT Article DE CR3; Raf; serine 338 ID SIGNAL-TRANSDUCTION; 14-3-3-PROTEINS ASSOCIATE; SERINE PHOSPHORYLATION; ACTIVATES RAF-1; GROWTH-FACTORS; IN-VITRO; RAS; PROTEINS; PATHWAY; CELLS AB The Raf-1 kinase domain is kept in an inactive state by the N-terminal regulatory domain. Activation of the kinase domain occurs following release from the N-terminal repression and possible catalytic upregulation. To distinguish the regulatory mechanisms that directly influence the catalytic activity of the enzyme from those which act through the inhibitory domain, the catalytic domain of Raf-1 (CR3) was expressed in COS-7 cells. The role of phosphorylation in the direct regulation of this domain was determined by substituting non-phosphorylatable amino acids for known serine and tyrosine phosphorylation sites. The intrinsic activity of each mutant protein was determined as well as stimulation by v-Src and phorbol esters. Both v-Src and phorbol esters were potent activators of CR3, requiring the serine 338/339 (p21-activated protein kinase, Pak) and tyrosine 340/341 (Src) phosphorylation sites for full stimulation of CR3. In contrast, loss of the serine 497/499 protein kinase C phosphorylation sites had little effect on CR3 activation by either v-Src or phorbol esters. Loss of serine 621, a 14-3-3 adaptor-protein-binding site, prevented activation of CR3 by v-Src or phorbol esters and partially decreased the high basal activity of the kinase fragment. When co-expressed in COS-7 cells, 14-3-3 associated strongly with full-length Raf-1, weakly with wild-type CR3 and not at all with the A621 and D621 CR3 mutants. The role of 14-3-3 in maintaining the activity of the catalytic domain of Raf-1 was investigated further by performing peptide-competition studies with wild-type CR3, wild-type CR3 and v-Src or constitutively active CR3 (CR3[YY340/341DD]). In each case, incubation of the proteins with a phosphoserine-621 Raf-1 peptide, which we show displaced Raf-1 and CR3[YY340/341DD] from 14-3-3, was found to substantially reduce catalytic activity. Taken together, our results support a model of Raf regulation in which the activity of the Raf-1 catalytic domain is directly upregulated by phosphorylation, following relief of inhibition by the N-terminal regulatory domain upon Ras-GTP binding. Moreover, the presence of serine 621 in the free catalytic fragment is required for full CR3 activation by stimulatory factors, and the continuous presence of 14-3-3 at this site is necessary for retaining activity once the kinase is activated. C1 Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Diabet Res Lab, Boston, MA 02114 USA. Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA. Millennium Pharmaceut Inc, Cambridge, MA 02142 USA. Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA. RP Marshall, MS (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Drop Code 1543, Indianapolis, IN 46285 USA. RI Tzivion, Guri/D-8954-2011; OI Yip-Schneider, Michele/0000-0001-7569-7971 NR 40 TC 67 Z9 72 U1 1 U2 2 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD OCT 1 PY 2000 VL 351 BP 151 EP 159 DI 10.1042/0264-6021:3510151 PN 1 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 364RW UT WOS:000089907600017 PM 10998357 ER PT J AU Fitzsimmons, TJ Gukovsky, I McRoberts, JA Rodriguez, E Lai, FA Pandol, SJ AF Fitzsimmons, TJ Gukovsky, I McRoberts, JA Rodriguez, E Lai, FA Pandol, SJ TI Multiple isoforms of the ryanodine receptor are expressed in rat pancreatic acinar cells SO BIOCHEMICAL JOURNAL LA English DT Article DE calcium-induced calcium release; intracellular calcium store; palmitoyl-coenzyme A ID MUSCLE SARCOPLASMIC-RETICULUM; CALCIUM RELEASE CHANNEL; SKELETAL-MUSCLE; CA2+ RELEASE; EXOCRINE PANCREAS; MOLECULAR-CLONING; COENZYME-A; OSCILLATIONS; CDNA; PROPAGATION AB Regulation of cytosolic Ca2+ is important for a variety of cell functions. The ryanodine receptor (RyR) is a Ca2+ channel that conducts Ca2+ from internal pools to the cytoplasm. To demonstrate the presence of the RyR in the pancreatic acinar cell, we performed reverse transcriptase (RT)-PCR, Western blot, immunocytochemistry and microscopic Ca2+-release measurements on these cells. RT-PCR showed the presence of mRNA for RyR isoforms 1, 2 and 3 in both rat pancreas and dispersed pancreatic acini. Furthermore, mRNA expression for RyR isoforms 1 and 2 was demonstrated by RT-PCR in individual pancreatic acinar cells selected under the microscope. Western-blot analysis of acinar cell immunoprecipitates, using antibodies against RyR1 and RyR2, showed a high-molecular-mass (> 250 kDa) protein band that was much less intense when immunoprecipitated in the presence of RyR peptide. Functionally, permeablized acinar cells stimulated with the RyR activator, palmitoyl-CoA, released Ca2+ from both basolateral and apical regions. These data show that pancreatic acinar cells express multiple isoforms of the RyR and that there are functional receptors throughout the cell. C1 Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, W Los Angeles, CA 90073 USA. Univ Wales Coll Med, Cardiff CF4 4XN, S Glam, Wales. RP McRoberts, JA (reprint author), Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, W Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK 33010] NR 34 TC 47 Z9 48 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD OCT 1 PY 2000 VL 351 BP 265 EP 271 DI 10.1042/0264-6021:3510265 PN 1 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 364RW UT WOS:000089907600030 PM 10998370 ER PT J AU Reboul, J Roger, MG Vidal, M AF Reboul, J Roger, MG Vidal, M TI Cloning of ORFeomes SO BIOFUTUR LA French DT Article C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. RP Reboul, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, 44 Binney St,Smith Bldg 848, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0294-3506 J9 BIOFUTUR JI Biofutur PD OCT PY 2000 IS 204 BP A3 EP A6 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 370BG UT WOS:000165101800004 ER PT J AU Roger, MG Vidal, M Vincent, S AF Roger, MG Vidal, M Vincent, S TI Discovering drugs with an inverse yeast two-hybrid system SO BIOFUTUR LA French DT Article ID PROTEIN-PROTEIN INTERACTIONS; PHOSPHATASE; 2-HYBRID; TARGETS C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. RP Roger, MG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, 44 Binney St,Smith Bldg 848, Boston, MA 02115 USA. NR 15 TC 0 Z9 0 U1 0 U2 1 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0294-3506 J9 BIOFUTUR JI Biofutur PD OCT PY 2000 IS 204 BP A7 EP A9 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 370BG UT WOS:000165101800005 ER PT J AU Heckers, S Curran, T Goff, D Rauch, SL Fischman, AJ Alpert, NM Schacter, DL AF Heckers, S Curran, T Goff, D Rauch, SL Fischman, AJ Alpert, NM Schacter, DL TI Abnormalities in the thalamus and prefrontal cortex during episodic object recognition in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE positron emission tomography; cognitive deficits; memory; pulvinar ID POSITRON-EMISSION TOMOGRAPHY; IMPLICIT MEMORY; BRAIN ACTIVITY; ATTENTION; RETRIEVAL; PET; ACTIVATION; TASK; MRI; HIPPOCAMPUS AB Background: Many patients with schizophrenia demonstrate memory deficits. We studied patterns of brain activity during episodic recognition of new and previously seen three-dimensional objects. Methods: We used 150 positron emission tomography to study regional cerebral bloodflow in eight normal subjects and nine patients with schizophrenia during a visual object recognition task, Results: In comparison with control subjects, patients with schizophrenia showed less regional cerebral blood flow increases in the pulvinar region of the right thalamus and the right prefrontal cortex during the recognition of new objects and significantly greater left prefrontal cortex regional cerebral blood flow increases during the recognition of previously seen objects. Patients with schizophrenia exhibited alarm rates to new objects similar to those of control subjects, but significantly lower recognition rates for previously seen objects. Conclusions: Schizophrenia is associated with attenuated right thalamic and right prefrontal activation during the recognition of novel visual stimuli and with increased left prefrontal cortical activation during impaired episodic recognition of previously seen visual stimuli. This study provides further evidence for abnormal thalamic and prefrontal cortex function in schizophrenia, (C) 2000 Society of Biological Psychiatry. C1 Massachusetts Gen Hosp E, Dept Psychiat, Psychot Disorders Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Psychiat, Psychiat Neuroimaging Res Grp, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Positron Emiss Tomog Lab, Charlestown, MA 02129 USA. Case Western Reserve Univ, Dept Psychol, Cleveland, OH 44106 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Heckers, S (reprint author), Massachusetts Gen Hosp E, Dept Psychiat, Psychot Disorders Unit, CNY-9132,Bldg 149,13th St, Charlestown, MA 02129 USA. RI Heckers, Stephan/F-3051-2010; OI Heckers, Stephan/0000-0003-3601-9910; Schacter, Daniel/0000-0002-2460-6061 FU NIMH NIH HHS [K23MH01763-01] NR 41 TC 70 Z9 71 U1 5 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 1 PY 2000 VL 48 IS 7 BP 651 EP 657 DI 10.1016/S0006-3223(00)00919-7 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 365LQ UT WOS:000089953100003 PM 11032976 ER PT J AU Morikawa, N Clarke, TR Novina, CD Watanabe, K Haqq, C Weiss, M Roy, AL Donahoe, PK AF Morikawa, N Clarke, TR Novina, CD Watanabe, K Haqq, C Weiss, M Roy, AL Donahoe, PK TI Human Mullerian-inhibiting substance promoter contains a functional TFII-I-binding initiator SO BIOLOGY OF REPRODUCTION LA English DT Article DE developmental biology; gene regulation; granulosa cells; Mullerian ducts; Sertoli cells ID RNA-POLYMERASE-II; TRANSCRIPTION FACTOR USF; V-BETA PROMOTER; TATA-LESS; COLONY GROWTH; GENE PROMOTER; START SITE; HORMONE; ELEMENT; EXPRESSION AB Mullerian-inhibiting substance (MIS) plays an essential role in mammalian male sexual development; thus, it is important to determine how the tightly regulated expression of the MIS gene is transcriptionally controlled. Transcription of eukaryotic genes is dependent on regulatory elements in the enhancer and one or both distinct elements in the core promoter: the TATA box, and the initiator (Inr) element. Because the human MIS gene does not contain a consensus TATA and has not been reported to contain an Inr element, we hypothesized that the initiator region of the core promoter was essential for promoter activity. Transient transfection assays were conducted using an immortalized Embryonic Day 14.5 male rat urogenital ridge cell line (CH34) that expresses low levels of MIS. These studies revealed that promoter activity is dependent on the region around the start site (-6 to +10) but not on the nonconsensus TATA region. Electrophoretic mobility shift assays demonstrated that the human MIS initiator sequence forms a specific DNA-protein complex with CH34 cell nuclear extract, HeLa cell nuclear extract, and purified TFII-I. This complex could be blocked or supershifted by the addition of antibodies directed against TFII-I. These data suggest that the human MIS gene contains a functional initiator that is specifically recognized by TFII-I. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Pediat Surg Res Labs, Boston, MA 02114 USA. Tufts Univ, Sch Med, Sackler Sch Grad Studies, Div Immunol, Boston, MA 02111 USA. Tufts Univ, Sch Med, Sackler Sch Grad Studies, Dept Pathol, Boston, MA 02111 USA. Univ Chicago, Chicago, IL 60637 USA. RP Donahoe, PK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Pediat Surg Res Labs, Warren 10,32 Fruit St, Boston, MA 02114 USA. NR 64 TC 15 Z9 16 U1 0 U2 0 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 OCT PY 2000 VL 63 IS 4 BP 1075 EP 1083 DI 10.1095/biolreprod63.4.1075 PG 9 WC Reproductive Biology SC Reproductive Biology GA 357GC UT WOS:000089489300016 PM 10993829 ER PT J AU Kodama, T Hamblin, MR Doukas, AG AF Kodama, T Hamblin, MR Doukas, AG TI Cytoplasmic molecular delivery with shock waves: Importance of impulse SO BIOPHYSICAL JOURNAL LA English DT Article ID RIBOSOME-INACTIVATING PROTEINS; ERYTHROCYTE MEMBRANE GHOSTS; RED-BLOOD-CELLS; GENE-THERAPY; IN-VITRO; PIEZOELECTRIC LITHOTRIPTER; INTERSTITIAL DIFFUSION; PLASMA-MEMBRANE; LEUKEMIA-CELLS; STRESS WAVES AB Cell permeabilization using shock waves may be a way of introducing macromolecules and small polar molecules into the cytoplasm, and may have applications in gene therapy and anticancer drug delivery. The pressure profile of a shock wave indicates its energy content, and shock-wave propagation in tissue is associated with cellular displacement, leading to the development of cell deformation. In the present study, three different shock-wave sources were investigated; argon fluoride excimer laser, ruby laser, and shock tube. The duration of the pressure pulse of the shock tube was 100 times longer than the lasers. The uptake of two fluorophores, calcein (molecular weight: 622) and fluorescein isothiocyanate-dextran (molecular weight: 71,600), into HL-60 human promyelocytic leukemia cells was investigated. The intracellular fluorescence was measured by a spectrofluorometer, and the cells were examined by confocal fluorescence microscopy. A single shock wave generated by the shock tube delivered both fluorophores into approximately 50% of the cells (p < 0.01), whereas shock waves from the lasers did not. The cell survival fraction was >0.95. Confocal microscopy showed that, in the case of calcein, there was a uniform fluorescence throughout the cell, whereas, in the case of FITC-dextran, the fluorescence was sometimes in the nucleus acid at other times not. We conclude that the impulse of the shock wave (i.e., the pressure integrated over time), rather than the peak pressure, was a dominant factor for causing fluorophore uptake into living cells, and that shock waves might have changed the permeability of the nuclear membrane and transferred molecules directly into the nucleus. C1 Massachusetts Gen Hosp, Harvard Med Sch, Dept Dermatol, Wellman Labs Photomed, Boston, MA 02114 USA. RP Kodama, T (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Dept Dermatol, Wellman Labs Photomed, 55 Fruit St,WEL 224, Boston, MA 02114 USA. OI kodama, tetsuya/0000-0003-4727-9558; Hamblin, Michael/0000-0001-6431-4605 NR 65 TC 106 Z9 107 U1 0 U2 16 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD OCT PY 2000 VL 79 IS 4 BP 1821 EP 1832 PG 12 WC Biophysics SC Biophysics GA 360VL UT WOS:000089688000013 PM 11023888 ER PT J AU Tallman, MS Neuberg, D Bennett, JM Francois, CJ Paletta, E Wiernik, PH Dewald, G Cassileth, PA Oken, MM Rowe, JM AF Tallman, MS Neuberg, D Bennett, JM Francois, CJ Paletta, E Wiernik, PH Dewald, G Cassileth, PA Oken, MM Rowe, JM TI Acute megakaryocytic leukemia: the Eastern Cooperative Oncology Group experience SO BLOOD LA English DT Article ID ACUTE MEGAKARYOBLASTIC LEUKEMIA; ACUTE MYELOID-LEUKEMIA; BONE-MARROW TRANSPLANTATION; TRANSIENT MYELOPROLIFERATIVE DISORDER; ACUTE MYELOGENOUS LEUKEMIA; ACUTE MYELOFIBROSIS; DOWNS-SYNDROME; ULTRACYTOCHEMICAL DIFFERENCES; MALIGNANT MYELOSCLEROSIS; PLATELET-PEROXIDASE AB Acute megakaryocytic leukemia (AMegL) is a rare subtype of acute myeloid leukemia (AML) evolving from primitive megakaryoblasts. Because of its rarity and the lack of precise diagnostic criteria in the past, few series of adults treated with contemporary therapy have been reported. Twenty among 1649 (1.2%) patients with newly diagnosed AML entered on Eastern Cooperative Oncology Group (ECOG) trials between 1984 and 1997 were found to have AMegL. The median age was 42.5 years (range 18-70). Marrow fibrosis, usually extensive, was present in the bone marrow. Of the 8 patients who had cytogenetic studies performed, abnormalities of chromosome 3 were the most frequent. The most consistent immunophenotypic finding was absence of myeloperoxidase in blast cells from 5 patients. In the most typical 3 cases, the leukemic cells were positive for one to 2 platelet-specific antigens in addition to lacking myeloperoxidase or an antigen consistent with a lymphoid leukemia. Myeloid antigens other than myeloperoxidase and selected T-cell antigens (CD7 and/or CD2) were frequently expressed. Induction therapy included an anthracycline and cytarabine in all cases. Complete remission (CR) was achieved in 10 of 20 patients (50%). Two patients remain alive, one in CR at 160+ months. Resistant disease was the cause of induction failure in all but 3 patients. The median CR duration was 10.6 months (range 1-160+ months). The median survival for all patients was 10.4 months (range 1-160+ months). Although half of the patients achieved CR, the longterm outcome is extremely poor, primarily attributable to resistant disease. New therapeutic strategies are needed. (Blood. 2000;96:2405-2411). (C) 2000 by The American Society of Hematology. C1 Northwestern Univ, Sch Med, Robert H Lurie Canc Ctr, Dept Med,Div Hematol Oncol, Chicago, IL 60611 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Our Lady Mercy Med Ctr, Bronx, NY USA. Mayo Clin, Cytogenet Lab, Rochester, MN USA. Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL 33152 USA. Virginia Piper Canc Inst, Minneapolis, MN USA. Technion Israel Inst Technol, Rambam Med Ctr, Haifa, Israel. Eastern Cooperat Oncol Grp, Brookline, MA USA. RP Tallman, MS (reprint author), Northwestern Univ, Sch Med, Robert H Lurie Canc Ctr, Dept Med,Div Hematol Oncol, 676 N St Clair St,850, Chicago, IL 60611 USA. NR 71 TC 84 Z9 89 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 2000 VL 96 IS 7 BP 2405 EP 2411 PG 7 WC Hematology SC Hematology GA 358HL UT WOS:000089552500015 PM 11001891 ER PT J AU Waters, GS Caplan, D Dufault, C AF Waters, GS Caplan, D Dufault, C TI The relationship between working memory capacity and online sentence processing efficiency in patients with DAT SO BRAIN AND LANGUAGE LA English DT Article ID COMPREHENSION C1 Boston Univ, Dept Commun Disorders, Boston, MA 02215 USA. Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. RP Waters, GS (reprint author), Boston Univ, Dept Commun Disorders, 635 Commonwealth Ave, Boston, MA 02215 USA. NR 3 TC 0 Z9 0 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT 1 PY 2000 VL 74 IS 3 BP 332 EP 334 PG 3 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 358FH UT WOS:000089547200007 ER PT J AU Fitzpatrick, PM Connor, LT Obler, LK Spiro, A AF Fitzpatrick, PM Connor, LT Obler, LK Spiro, A TI Long-term recovery of naming and word finding in narrative discourse in aphasia SO BRAIN AND LANGUAGE LA English DT Article ID PERFORMANCE C1 Boston Univ, Sch Med, Harold Goodglass Aphasia Res Ctr, Boston, MA 02118 USA. VA Boston Healthcare Syst, Speech Pathol & Audio Serv, Boston, MA USA. CUNY, Grad Ctr, New York, NY USA. VA Boston Healthcare Syst, Normat Aging Study, Boston, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. RP Fitzpatrick, PM (reprint author), Boston Univ, Sch Med, Harold Goodglass Aphasia Res Ctr, Boston, MA 02118 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT 1 PY 2000 VL 74 IS 3 BP 395 EP 397 PG 3 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 358FH UT WOS:000089547200026 ER PT J AU Caplan, D Vijayan, S Kuperberg, G West, C Waters, G Greve, D Dale, AM AF Caplan, D Vijayan, S Kuperberg, G West, C Waters, G Greve, D Dale, AM TI Localization of syntactic processing in sentence comprehension by event-related fMRI SO BRAIN AND LANGUAGE LA English DT Article C1 Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. Boston Univ, Dept Commun Disorders, Boston, MA 02215 USA. Massachusetts Gen Hosp, Neuroimaging Ctr, Boston, MA 02114 USA. RP Caplan, D (reprint author), Massachusetts Gen Hosp, Neuropsychol Lab, Vincent Burnham 827,Fruit St, Boston, MA 02114 USA. NR 8 TC 1 Z9 1 U1 2 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT 1 PY 2000 VL 74 IS 3 BP 400 EP 402 PG 3 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 358FH UT WOS:000089547200028 ER PT J AU Brodsky, MB McNeil, MR Park, GH Fossett, TRD Timm, NH Doyle, PJ AF Brodsky, MB McNeil, MR Park, GH Fossett, TRD Timm, NH Doyle, PJ TI Serial-position effects for information unit production: The role of memory in the RAPP story retell procedure for normals and persons with aphasia SO BRAIN AND LANGUAGE LA English DT Article C1 Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Educ Psychol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Otolaryngol, Pittsburgh, PA 15260 USA. VA Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Aphasia Rehabil Res Lab & Clin, Pittsburgh, PA USA. RP Brodsky, MB (reprint author), Univ Pittsburgh, 4033 Forbes Tower, Pittsburgh, PA 15260 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT 1 PY 2000 VL 74 IS 3 BP 494 EP 498 PG 5 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 358FH UT WOS:000089547200058 ER PT J AU Abdi, S Lee, DH Park, SK Chung, JM AF Abdi, S Lee, DH Park, SK Chung, JM TI Lack of pre-emptive analgesic effects of local anaesthetics on neuropathic pain SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE anaesthetics local, bupivacaine; anaesthetics local, lignocaine; pain, neuropathic; rats ID PERIPHERAL MONONEUROPATHY; ANESTHESIA; TRIAL; RATS AB We investigated the significance of pre-emptive analgesia using a well-known model of neuropathic pain in rats. Lignocaine, bupivacaine or saline was applied locally to the left L5-L6 spinal nerve before or 4 days after nerve injury. Mechanical allodynia was then evaluated before and after injury. Pre- and post-injury treatment with local anaesthetics both resulted in a two- to threefold increase in the pain threshold, as manifested by a significant increase in von Frey measurements. However, this effect lasted only 24 h. Our study in rats questions the beneficial effect of a single dose of local anaesthetic as pre-emptive analgesia. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,Clin 3, Boston, MA 02114 USA. Univ Texas, Med Branch, Dept Anat, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Neurosci, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Physiol, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Biophys, Galveston, TX 77555 USA. RP Abdi, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care,Clin 3, 32 Fruit St, Boston, MA 02114 USA. FU NINDS NIH HHS [NS 11255, NS 31680] NR 7 TC 11 Z9 11 U1 0 U2 0 PU PROF SCI PUBL PI LONDON PA TAVISTOCK HOUSE EAST, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD OCT PY 2000 VL 85 IS 4 BP 620 EP 623 DI 10.1093/bja/85.4.620 PG 4 WC Anesthesiology SC Anesthesiology GA 360QX UT WOS:000089679700021 PM 11064624 ER PT J AU Sieff, CA Nisbet-Brown, E Nathan, DG AF Sieff, CA Nisbet-Brown, E Nathan, DG TI Congenital bone marrow failure syndromes SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE haematopoiesis; congenital; gene; bone marrow failure ID DIAMOND-BLACKFAN-ANEMIA; COLONY-STIMULATING-FACTOR; GROUP-C GENE; UMBILICAL-CORD BLOOD; ADENOSINE-DEAMINASE ACTIVITY; RIBOSOMAL-PROTEIN S19; NECROSIS-FACTOR-ALPHA; GROUP-A GENE; FANCONI-ANEMIA; FACTOR-RECEPTOR C1 Harvard Univ, Childrens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Pediat Hematol & Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Paediat, Boston, MA 02115 USA. RP Sieff, CA (reprint author), Dana Farber Canc Inst, Div Pediat Hematol & Oncol M613, 44 Binney St, Boston, MA 02115 USA. RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 NR 137 TC 21 Z9 21 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2000 VL 111 IS 1 BP 30 EP 42 DI 10.1046/j.1365-2141.2000.02263.x PG 13 WC Hematology SC Hematology GA 377KA UT WOS:000165511700005 PM 11091180 ER PT J AU Hersh, WR Crabtree, MK Hickam, DH Sacherek, L Rose, L Friedman, CP AF Hersh, WR Crabtree, MK Hickam, DH Sacherek, L Rose, L Friedman, CP TI Factors associated with successful answering of clinical questions using an information retrieval system SO BULLETIN OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID FRAMEWORK; RELEVANCE; STUDENTS AB Objectives: Despite the growing use of online databases by clinicians, there has been very little research documenting how effectively they are used. This study assessed the ability of medical and nurse-practitioner students to answer clinical questions using an information retrieval system. It also attempted to identify the demographic, experience, cognitive, personality, search mechanics, and user-satisfaction factors associated with successful use of a retrieval system. Methods: Twenty-nine students completed questionnaires of clinical and computer experience as well as tests of cognitive abilities and personality type. They were then administered three clinical questions to answer in a medical library setting using the MEDLINE database and electronic and print full-text resources. Results: Medical students were able to answer more questions correctly than nurse-practitioner students before and after searching, but both had comparable improvements in the number of correct questions before and after searching. Successful ability to answer questions was also associated with having experience in literature searching and higher standardized test-score percentiles. Conclusions: Medical and nurse-practitioner students obtained comparable benefits in the ability to answer clinical questions from use of the information retrieval system. Future research must examine strategies that improve successful search and retrieval of clinical questions posed by clinicians in practice. C1 Oregon Hlth Sci Univ, Div Med Informat & Outcomes Res, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Sch Nursing, Portland, OR 97201 USA. Portland VA Med Ctr, Hlth Serv Res & Dev, Portland, OR USA. Univ Pittsburgh, Ctr Biomed Informat, Pittsburgh, PA USA. RP Hersh, WR (reprint author), Oregon Hlth Sci Univ, Div Med Informat & Outcomes Res, 3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. OI Hersh, William/0000-0002-4114-5148 FU NLM NIH HHS [LM-06311] NR 27 TC 36 Z9 36 U1 0 U2 2 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 0025-7338 J9 B MED LIBR ASSOC JI Bull. Med. Libr. Assoc. PD OCT PY 2000 VL 88 IS 4 BP 323 EP 331 PG 9 WC Information Science & Library Science SC Information Science & Library Science GA 530JT UT WOS:000174355100004 PM 11055299 ER PT J AU Bristow, RE Duska, LR Lambrou, NC Fishman, EK O'Neill, MJ Trimble, EL Montz, FJ AF Bristow, RE Duska, LR Lambrou, NC Fishman, EK O'Neill, MJ Trimble, EL Montz, FJ TI A model for predicting surgical outcome in patients with advanced ovarian carcinoma using computed tomography SO CANCER LA English DT Article DE ovarian carcinoma; computed tomography; cytoreductive surgery ID PRIMARY CYTOREDUCTIVE SURGERY; DEBULKING SURGERY; FREE INTERVAL; CANCER; SURVIVAL; CT AB BACKGROUND. A reliable model for predicting the outcome of primary cytoreductive surgery may be a useful tool in the clinical management of patients with advanced epithelial ovarian carcinoma. METHODS. Forty-one women with a preoperative computed tomographic (CT) scan of the abdomen and pelvis and a histologic diagnosis of Stage III or IV epithelial ovarian carcinoma following primary surgery performed by one of nine gynecologic oncologists were identified from tumor registry databases. All CT scans were analyzed retrospectively using a panel of 25 radiographic features without knowledge of the operative findings. Patient demographics, surgical findings and outcome, Gynecologic Oncology Group performance status, and pre-operative serum CA125 values were collected from patient medical records. Residual disease measuring less than or equal to 1 cm in maximal diameter was considered an optimal surgical result. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each radiographic feature and clinical characteristic. Based on statistical probability of each factor predicting cytoreductive outcome, 13 radiographic features, in addition to performance status, were selected for inclusion in the final model. Each parameter was assigned a numeric value based on the strength of statistical association, and a total Predictive Index score was tabulated for each patient. Receiver operating characteristic (ROC) curve analysis was used to assess the ability of the model to predict surgical outcome. Statistical significance was evaluated using the Fisher exact test. RESULTS. Twenty of 41 patients (48.8%) underwent optimal cytoreduction to less than or equal to 1 cm residual disease. CT features of peritoneal thickening, peritoneal implants (greater than or equal to 2 cm), bowel mesentery involvement (greater than or equal to 2 cm), suprarenal paraaortic lymph nodes (greater than or equal to 1 cm), omental extension (spleen, stomach, or lesser sac), and pelvic sidewall involvement and/or hydroureter were most strongly associated with surgical outcome. Using the Predictive Index scores, a receiver operating characteristic curve was generated with an area under the curve = 0.969 +/- 0.023. In the final model, a Predictive Index score greater than or equal to 4 had the highest overall accuracy at 92.7% and identified patients undergoing suboptimal surgery with a sensitivity of 100% (21/21). The specificity, or ability to identify patients undergoing optimal surgery, was 85.0% (17/20). The PPV of a Predictive Index score greater than or equal to 4 was 87.5% (21/24), and the NPV was 100%. The ability of this model to correctly predict surgical outcome was statistically significant (P < 0.001). CONCLUSIONS. In this model, a Predictive Index score greater than or equal to 4 demonstrated high sensitivity, specificity, PPV, and NPV, and was highly accurate in identifying patients with advanced epithelial ovarian carcinoma unlikely to undergo optimal primary cytoreductive surgery. The Predictive Index model may have clinical utility in guiding the management of patients with ovarian carcinoma. Cancer 2000;89: 1532-40. (C) 2000 American Cancer Society. C1 Johns Hopkins Med Inst, Dept Obstet & Gynecol, Kelly Gynecol Oncol Serv, Baltimore, MD 21287 USA. Johns Hopkins Med Inst, Dept Radiol, Baltimore, MD 21287 USA. Massachusetts Gen Hosp, Div Gynecol Oncol, Vincent Obstet & Gynecol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Bristow, RE (reprint author), Johns Hopkins Med Inst, Dept Obstet & Gynecol, Kelly Gynecol Oncol Serv, 600 N Wolfe St,Phipps 248, Baltimore, MD 21287 USA. NR 18 TC 168 Z9 171 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 0008-543X J9 CANCER JI Cancer PD OCT 1 PY 2000 VL 89 IS 7 BP 1532 EP 1540 DI 10.1002/1097-0142(20001001)89:7<1532::AID-CNCR17>3.0.CO;2-A PG 9 WC Oncology SC Oncology GA 355WJ UT WOS:000089411300017 PM 11013368 ER PT J AU Blahd, WH AF Blahd, WH TI Benedict Cassen: The father of body organ imaging - Historical vignette SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS LA English DT Biographical-Item AB The invention of the radioisotope scanner by Benedict Cassen was seminal to the development of body organ imaging. Cassen assembled the first automated scanning system in 1950. It was a motor-driven scintillation detector coupled to a printer. The scanner was used to image the thyroid gland after the administration of radioiodine. Later, with the development of organ-specific radiopharmaceuticals the scanner was widely used during the late 50s until the early 70s to image the body organs. C1 Vet Adm Greater Los Angeles Healthcare Syst, Nucl Med Sect 115, Imaging Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Blahd, WH (reprint author), Vet Adm Greater Los Angeles Healthcare Syst, Nucl Med Sect 115, Imaging Serv, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1084-9785 J9 CANCER BIOTHER RADIO JI Cancer Biother. Radiopharm. PD OCT PY 2000 VL 15 IS 5 BP 423 EP 429 DI 10.1089/cbr.2000.15.423 PG 7 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging GA 376AP UT WOS:000165435900001 PM 11155815 ER PT J AU Supko, JG Lynch, TJ Clark, JW Fram, R Allen, LF Velagapudi, R Kufe, DW Eder, JP AF Supko, JG Lynch, TJ Clark, JW Fram, R Allen, LF Velagapudi, R Kufe, DW Eder, JP TI A phase I clinical and pharmacokinetic study of the dolastatin analogue cemadotin administered as a 5-day continuous intravenous infusion SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE cemadotin; dolastatin; chemotherapy; clinical trials; pharmacokinetics ID ANTINEOPLASTIC AGENTS; SOLID TUMORS; CELL-LINES; CANCER; PRODUCTS; LU103793; TUBULIN; TRIAL AB Purpose: The dolastatins are a class of naturally occurring cytotoxic peptides which function by inhibiting microtubule assembly and tubulin polymerization. Cemadotin is a synthetic analogue of dolastatin 15 with potent antiproliferative and preclinical antitumor activity. This report describes a phase I study to evaluate the administration of cemadotin to adult cancer patients by a 5-day continuous intravenous (CIV) infusion. Methods: All patients had histologically confirmed refractory solid tumors. The dose was escalated from an initial level of 2.5 mg/m(2) (0.5 mg/m(2) daily) according to a modified Fibonacci algorithm. A minimum of three patients was evaluated at each dose level until the maximum tolerated dose (MTD) was established. Treatment was repeated every 21 days until patients were removed from the study due to toxicity or disease progression. Drug-related toxicities were evaluated and graded by the U.S. National Cancer Institute's Common Toxicity Criteria. A radioimmunoassay (RIA) that detected both the parent drug and its metabolites with an intact N-terminal region of the molecule was used for pharmacokinetic studies. Results. Twenty heavily pretreated patients received a total of 40 courses of cemadotin over five dose levels ranging from 2.5 to 17.5 mg/m(2). Reversible dose-related neutropenia was the principal dose-limiting toxicity and 12.5 mg/m(2) was established as the MTD. Nonhematologic toxicities attributed to the drug were moderate, and there was no evidence of the cardiovascular toxicity noted in the prior phase I studies of cemadotin given IV as a 5-min injection or 24-h infusion. There were no objective antitumor responses. rime courses of the cemadotin RIA equivalent concentration in whole blood were defined in 14 patients during the first cycle of therapy. The RIA-detectable species exhibited apparent first-order pharmacokinetics across the entire range,of doses. The mean +/- SD of the observed steady-state blood concentration at the 12.5 mg/m(2) MTD was: 282 +/- 7 nM (n = 3). Blood levels decayed monoexponentially following the end of the infusion, with a mean half-life of 13.2 +/- 4.3 h (n = 14) in all patients. Mean values (n = 14) of the total blood clearance and apparent volume of distribution at steady state were 0.52 +/- 0.09 l/h/m(2) and 9.9 +/- 3.3 l/m(2), respectively. Conclusions: The cardiotoxic effects of cemadotin were completely avoided by administering it as a 120-h CIV infusion. Thus, cardiovascular toxicity appears to be associated with the magnitude of the peak blood levels of the parent drug or its metabolites, whereas myelotoxicity is related to the duration of time that blood levels exceed a threshold concentration. Nevertheless, the data acquired during the extensive clinical experience with cemadotin requires careful examination to assess whether advancing this compound into disease-oriented efficacy studies is merited. C1 Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02114 USA. Knoll Pharmaceut Co, Parsippany, NJ 07054 USA. RP Eder, JP (reprint author), Dana Farber Canc Inst, Div Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 27 TC 20 Z9 23 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD OCT PY 2000 VL 46 IS 4 BP 319 EP 328 DI 10.1007/s002800000152 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 361RY UT WOS:000089738400009 PM 11052630 ER PT J AU Fan, R Wu, MT Miller, D Wain, JC Kelsey, KT Wiencke, JK Christiani, DC AF Fan, R Wu, MT Miller, D Wain, JC Kelsey, KT Wiencke, JK Christiani, DC TI The p53 codon 72 polymorphism and lung cancer risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENE; SUSCEPTIBILITY AB The p53 tumor suppressor gene frequently is mutated in many forms of human carcinomas. A common polymorphism occurs at codon 72 of exon 4, with two alleles encoding either arginine (CGC) or proline (CCC), This p53 polymorphism reportedly is associated with lung cancer susceptibility. However, not all investigations have been consistent, and this hypothesized association remains controversial. We tested the hypothesis that the Pro/Pro genotype is associated with increased lung cancer risk in a large case-control study of lung cancer that included 482 cases and 510 controls from the Massachusetts General Hospital in Boston, Massachusetts. DNA from peripheral blood samples was examined by PCR-RFLP, Pro/Pro homozygotes were found more frequently in adenocarcinomas (cases, 16.4%; controls, 12.0%; P = 0.03). The prevalence of the Pro/Pro homozygous genotype increased in frequency with increasing pack-years of smoking. The combined susceptible genotype homozygous Pro/Pro and heterozygous Arg/Pro was associated with a 1.45-fold higher risk of adenocarcinoma compared with Arg/Arg genotype (95% confidence interval = 1.01-2.06; P = 0.04) after adjustment for relevant variables. Lung adenocarcinoma risk increased with the presence of one or both variant alleles across smoking strata, In addition, at each level of smoking (except nonsmoker and light smoker), the risk associated with smoking was higher for the population with the combined variant (Arg/Pro + Pro/Pro) genotype, The risk for the combined genotype was associated with tobacco exposure status, In conclusion, the codon 72 germ-line polymorphism (Arg/Pro) of the common tumor suppressor gene p53 contributes to heritable susceptibility for smoke-induced lung adenocarcinoma, The modifications by p53 polymorphism and pack-years resulted in an increased risk of the susceptible genotype to lung adenocarcinoma, The p53 gene may modulate the response to environment carcinogens and thereby affect the risk of developing lung adenocarcinoma. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Canc Cell Biol, Boston, MA 02115 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 Med,Pulm & Crit Care Unit, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, 665 Huntington Ave, Boston, MA 02115 USA. RI Kelsey, Karl/I-1252-2014 FU NCI NIH HHS [CA74386]; NIEHS NIH HHS [ES/CA06409, ES8357] NR 30 TC 156 Z9 170 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2000 VL 9 IS 10 BP 1037 EP 1042 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 364TP UT WOS:000089909300005 PM 11045785 ER PT J AU Lee, CG Heijn, M di Tomaso, E Griffon-Etienne, G Ancukiewicz, M Koike, C Park, KR Ferrara, N Jain, RK Suit, HD Boucher, Y AF Lee, CG Heijn, M di Tomaso, E Griffon-Etienne, G Ancukiewicz, M Koike, C Park, KR Ferrara, N Jain, RK Suit, HD Boucher, Y TI Anti-vascular endothelial growth factor treatment augments tumor radiation response under normoxic or hypoxic conditions SO CANCER RESEARCH LA English DT Article ID FACTOR-NEUTRALIZING ANTIBODY; IONIZING-RADIATION; BLOOD-VESSELS; INTERSTITIAL HYPERTENSION; MONOCLONAL-ANTIBODY; SOLID TUMORS; ANGIOGENESIS; ANTITUMOR; ANGIOSTATIN; APOPTOSIS AB Recent studies in experimental animals have shown that combining antiangiogenic therapy with radiation can enhance tumor response, Whether this enhancement is mainly attributable to angiogenesis inhibition, endothelial cell radiosensitivity, tumor cell apoptosis, or a decrease in the number of hypoxic cells (improved oxygenation) is not known. We designed this study to discern the role of tumor oxygenation. We chose an anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibody (mAb) which has a known target, human VEGF, We also measured interstitial fluid pressure (IFP) to test the hypothesis that the decreased vascular permeability induced by the anti-VEGF mAb can lower IFP, The effect of anti-VEGF mAb on vascular density, partial oxygen tension (pO(2)), and apoptosis was also measured. Athymic NCr/Sed nu/nu mice bearing 6-mm xenograft of the human glioblastoma multiforme (U87), or colon adenocarcinoma (LS174T) were treated with anti-VEGF mAb injected i,p, on alternate days for a total of six injections at a dosage of 100 mu g/injection/mouse. For combined anti-VEGF and radiation, single radiation doses were given under normal blood flow (20 and 30 Gy) or clamped hypoxic conditions (30 and 40 Gy) 24 h after the sixth injection of mAb, The inhibition of the growth of U87 and LS174T tumors by the anti-VEGF mAb was associated with a significant reduction in tumor vascular density and a relatively small increase in the number of apoptotic cells. Compared with size-matched controls, IFP decreased by 74% in LS174T, and 73% in U87 in mice treated with anti-VEGF mAb, After antibody treatment pO(2) increased significantly in U87, but did not change in LS174T tumors. Combined treatment induced in U87 tumors a tumor-growth delay (TGD) which was greater than additive; in LS174T except for the 40-Gy hypoxic group, the effect was only additive. In both U87 and LS174T the TGD induced by the antibody was independent of oxygen levels in the tumor at the time of radiation, The fact that the increase in TGD occurred under both normoxic and hypoxic conditions suggests that anti-VEGF mAb treatment can compensate for the resistance to radiation induced by hypoxia. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA. Genentech Inc, Dept Cardiovasc Res, S San Francisco, CA 94080 USA. RP Suit, HD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA. FU NCI NIH HHS [R37-CA-13111, R35-CA-56591] NR 33 TC 467 Z9 491 U1 0 U2 18 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2000 VL 60 IS 19 BP 5565 EP 5570 PG 6 WC Oncology SC Oncology GA 362HG UT WOS:000089772100042 PM 11034104 ER PT J AU Wong, P Lau, KW Lim, YL Oesterle, SN AF Wong, P Lau, KW Lim, YL Oesterle, SN TI Stent placement for non-STRESS/BENESTENT lesions: A critical review SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Review DE stent; small vessels; long lesions; bifurcation lesions; ostial lesions; left main lesions; saphenous vein graft; chronic total occlusion; acute myocardial infarction ID ACUTE MYOCARDIAL-INFARCTION; CHRONIC TOTAL OCCLUSIONS; LUMINAL CORONARY ANGIOPLASTY; ANGIOGRAPHIC FOLLOW-UP; SAPHENOUS-VEIN GRAFTS; PALMAZ-SCHATZ STENT; BALLOON ANGIOPLASTY; BYPASS GRAFTS; CLINICAL OUTCOMES; MULTICENTER EXPERIENCE AB Stenting lesions with favorable characteristics as required for inclusion in the STRESS/ BENESTENT trials have yielded superior results to that of PTCA alone. Results for less favorable lesions such as in small vessels, diffuse disease, ostial disease, and saphenous vein grafts are less well established. This review seeks to analyze available data for stent placement in this subset of non-STRESS/BENESTENT lesions. Cathet. Cardiovasc. Intervent. 51:223-233, 2000. (C) 2000 Wiley-Liss, Inc. C1 Natl Heart Ctr, Dept Cardiol, Singapore, Singapore. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. RP Wong, P (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,Bulfinch 105, Boston, MA 02114 USA. NR 101 TC 17 Z9 17 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD OCT PY 2000 VL 51 IS 2 BP 223 EP 233 DI 10.1002/1522-726X(200010)51:2<223::AID-CCD21>3.0.CO;2-F PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 359XE UT WOS:000089636700021 PM 11025583 ER PT J AU Tartier, L McCarey, YL Biaglow, JE Kochevar, IE Held, KD AF Tartier, L McCarey, YL Biaglow, JE Kochevar, IE Held, KD TI Apoptosis induced by dithiothreitol in HL-60 cells shows early activation of caspase 3 and is independent of mitochondria SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE dithiothreitol; apoptosis; caspases; mitochondria; HL-60 cells ID PERMEABILITY TRANSITION PORE; RADICAL-MEDIATED TOXICITY; CONTAINING RADIOPROTECTOR DITHIOTHREITOL; RADIATION-INDUCED APOPTOSIS; CYTOCHROME-C RELEASE; HYDROGEN-PEROXIDE; MAMMALIAN-CELLS; HYDROXYL RADICALS; DNA FRAGMENTATION; IN-VIVO AB Previous studies have shown that under certain conditions some thiol-containing compounds can cause apoptosis in a number of different cell lines. Herein, we investigated the apoptotic pathways in HL-60 cells triggered by dithiothreitol (DTT), used as a model thiol compound, and tested the hypothesis that thiols Cause apoptosis via production of hydrogen peroxide (H2O2) during thiol oxidation, The results show that, unlike H2O2, DTT does not induce apoptosis via a mitochondrial pathway. Th is is demonstrated by the absence of early cytochrome c release from mitochondria into the cytosol, the lack of mitochondrial membrane depolarization at early times, and the minor role of caspase 9 in DTT-induced apoptosis, The first caspase activity detectable in DTT treated cells is caspase 3, which is increased significantly 1-2 h after the start of DTT treatment. This was shown by following the cleavage of both a natural substrate, DFF-45/ICAD, and a synthetic fluorescent substrate, z-DEVD-AFC. Cleavage of substrates of caspases 2 and 8, known as initiator caspases, does not start until 3-4 h after DTT exposure,well after caspase 3 has become active and at a time when apoptosis is in late stages, as shown by the occurrence of DNA fragmentation to oligonucleosomal-sized pieces. Although oxidizing DTT can produce H2O2, data presented here indicate that DTT-induced apoptosis is not mediated by production of H2O2 and occurs via a novel pathway that involves activation of caspase 3 at early stages, prior to activation of the common 'initiator' caspases 2, 8 and 9. C1 Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med,Lab Mol & Cellular Radiat Biol, Boston, MA 02114 USA. Harvard Univ, Dept Dermatol, Massachusetts Gen Hosp, Sch Med,Wellman Labs Photomed, Boston, MA 02114 USA. Univ Penn, Div Oncol Res, Philadelphia, PA 19104 USA. RP Held, KD (reprint author), Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med,Lab Mol & Cellular Radiat Biol, COX 302,Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [CA63997, CA44982]; NIGMS NIH HHS [GM30755] NR 62 TC 30 Z9 30 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD OCT PY 2000 VL 7 IS 10 BP 1002 EP 1010 DI 10.1038/sj.cdd.4400726 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 360FF UT WOS:000089655200018 PM 11279547 ER PT J AU Asea, AA Calderwood, SK AF Asea, AA Calderwood, SK TI HSP70 binds to the cell surface of monocytes and induces cytokine expression. SO CELL STRESS & CHAPERONES LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL STRESS SOC INTERNATIONAL PI STORRS PA UNIV CONNECTICUT, DEPT M C B, 75 NORTH EAGLEVILLE RD, U-44, STORRS, CT 06269-3044 USA SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD OCT PY 2000 VL 5 IS 4 BP 374 EP 374 PG 1 WC Cell Biology SC Cell Biology GA 361RM UT WOS:000089737100016 ER PT J AU Young, VB Schauer, DB AF Young, VB Schauer, DB TI Cytolethal distending toxin: A bacterial toxin which disrupts the eukaryotic cell cycle SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article; Proceedings Paper CT Symposium on the Mechanisms of Action of Chytotoxic Agents held at the 219th National Meeting of the American-Chemical-Society CY MAR 29, 2000 CL SAN FRANCISCO, CALIFORNIA SP Amer Chem Soc, Div Chem Toxicol ID HAEMOPHILUS-DUCREYI; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; CAMPYLOBACTER-JEJUNI; T-CELLS; GENES; IDENTIFICATION; EXPRESSION; CYTOTOXIN; DIVISION; PROTEIN C1 MIT, DCM, BEH, Cambridge, MA 02139 USA. MIT, Div Bioengn & Environm Hlth, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Med, Infect Dis Unit, Boston, MA 02114 USA. RP Schauer, DB (reprint author), MIT, DCM, BEH, Room 56-787, Cambridge, MA 02139 USA. RI Young, Vincent/B-3179-2009 OI Young, Vincent/0000-0003-3687-2364 NR 27 TC 5 Z9 5 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD OCT PY 2000 VL 13 IS 10 BP 936 EP 939 DI 10.1021/tx000091d PG 4 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 366MK UT WOS:000090009000002 PM 11080036 ER PT J AU Furuta, GT Ackerman, SJ Varga, J Spiess, AM Wang, MY Wershil, BK AF Furuta, GT Ackerman, SJ Varga, J Spiess, AM Wang, MY Wershil, BK TI Eosinophil granule-derived major basic protein induces IL-8 expression in human intestinal myofibroblasts SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE eosinophil IL-8; major basic protein; gastrointestinal; fibroblast ID GROWTH-FACTOR-BETA; INFLAMMATORY BOWEL-DISEASE; COLONY-STIMULATING FACTOR; CATIONIC PROTEIN; AIRWAY HYPERRESPONSIVENESS; DNA-SYNTHESIS; MAST-CELLS; FIBROBLASTS; ACTIVATION; RELEASE AB Eosinophil infiltration occurs in a variety of allergic and inflammatory diseases, The release of preformed mediators From eosinophils may contribute to inflammatory responses. We investigated the ability of eosinophil-derived major basic protein and eosinophil-derived neurotoxin to stimulate production of IL-8 from intestinal myofibroblasts. Intestinal myofibroblasts (18-Co cells) were incubated with major basic protein, eosinophil-derived neurotoxin, or a synthetic analogue of major basic protein, poly-L-arginine. Immunoreactive IL-g was measured by ELISA and IL-8 mRNA levels were analysed by Northern blot or reverse transcription-polymerase chain assay. Major basic protein induced IL-8 mRNA production and release of significant levels of IL-8 immunoreactive protein. By contrast, eosinophil-derived neurotoxin stimulated little IL-8 release. The induction of IL-8 mRNA by poly-L-arginine was significantly inhibited by actinomycin D. These findings demonstrate a novel interaction between eosinophils and intestinal fibroblasts that may be involved in the pathogenesis of diseases associated with tissue eosinophilia. C1 Childrens Hosp, Div Pediat Gastroenterol & Nutr, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Div Expt Pathol, Boston, MA 02215 USA. Univ Illinois, Coll Med, Dept Med, Rheumatol Sect, Chicago, IL USA. Univ Illinois, Coll Med, Dept Biochem & Mol Biol, Chicago, IL USA. SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. RP Furuta, GT (reprint author), Childrens Hosp, Div Pediat Gastroenterol & Nutr, Combined Program Pediat Gastroenterol & Nutr, 300 Longwood Ave,Hunnewell Ground Floor, Boston, MA 02115 USA. FU NIAID NIH HHS [R01 AI025230]; NIAMS NIH HHS [R01 AR042309]; NIDDK NIH HHS [DK40561, DK46819, P01 DK033506, DK33506, P30 DK040561, R01 DK046819] NR 45 TC 14 Z9 14 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD OCT PY 2000 VL 122 IS 1 BP 35 EP 40 DI 10.1046/j.1365-2249.2000.01337.x PG 6 WC Immunology SC Immunology GA 363DE UT WOS:000089818900007 PM 11012615 ER PT J AU Fiorentino, M Altimari, A D'Errico, A Cukor, B Barozzi, C Loda, M Grigioni, WF AF Fiorentino, M Altimari, A D'Errico, A Cukor, B Barozzi, C Loda, M Grigioni, WF TI Acquired expression of p27 is a favorable prognostic indicator in patients with hepatocellular carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID DEPENDENT-KINASE INHIBITOR; CELL LUNG-CANCER; BREAST-CANCER; P27(KIP1) GENE; MICE LACKING; CDK ACTIVITY; CYCLE; ADENOCARCINOMA; LOCALIZATION; HYPERPLASIA AB The p27 cyclin-dependent kinase inhibitor is a negative regulator of cell-cycle progression. In many human epithelial malignancies, decreased expression of p27 correlates with high grade, early recurrence, and poor prognosis. To evaluate the prognostic significance of p27 in hepatocellular carcinoma (HCC), we studied 54 HCCs along with corresponding nontumoral tissue. Immunohistochemistry (IHC) and Western blot (WB) analysis before and after immunoprecipitation with Cdk2 were performed on paraffin-embedded tissues and protein homogenates, respectively, to compare localization and expression of the p27 protein and to determine the total and active (Cdk2-bound) fractions of p27, Correlations were analyzed between IHC-assessed levels of p27, survival, and major clinical and pathological variables, IHC revealed no p27 expression in the majority of hepatocytes from normal and cirrhotic Liver, whereas 14 HCCs (26%) were high p27 expressers (>50% positive cells), 26 (48%) low expressers (<50% positive cells), and 14 (26%) negative. High IHC signals of p27 correlated with Cdk2-bound p27 as assessed by immunoprecipitation-WB; by contrast, WE alone displayed similar levels of p27 protein in all normal and tumoral samples, High IHC p27 expression correlated with prolonged survival (P = 0.027), whereas the presence of cirrhosis was associated with poor outcome (P = 0.029), We conclude that with respect to their nonneoplastic counterparts, a subset of HCCs acquire significant p27 expression and that high expression of p27 is a favorable independent prognostic parameter for HCC. C1 Univ Bologna, Dept Hematol Oncol, Inst Oncol F Addarii, Pathol Unit, I-40138 Bologna, Italy. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Grigioni, WF (reprint author), Univ Bologna, Dept Hematol Oncol, Inst Oncol F Addarii, Pathol Unit, Viale Ercolani 4-2, I-40138 Bologna, Italy. NR 46 TC 60 Z9 65 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT PY 2000 VL 6 IS 10 BP 3966 EP 3972 PG 7 WC Oncology SC Oncology GA 365CV UT WOS:000089931600025 PM 11051245 ER PT J AU Goldvasser, D McGibbon, CA Krebs, DE AF Goldvasser, D McGibbon, CA Krebs, DE TI Vestibular rehabilitation outcomes: velocity trajectory analysis of repeated bench stepping SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE vestibular rehabilitation; high curvature analysis; stepping; center of gravity; stability ID VESTIBULOOCULAR REFLEX; DYNAMIC BALANCE; GAIT INITIATION; STABILITY; POSTURE AB Objectives: To quantify vestibular rehabilitation (VR) outcomes in patients with vestibulospinal reflex pathology (VSP) using a new technique, high curvature analysis (HCA), that measures space trajectory stability. Methods: Twelve patients with VSP and 10 healthy controls performed a repeated stepping task in a motion analysis laboratory. Patients with VSP were tested before and after a 12 week VR program. Three dimensional whole body center of gravity (CG) was captured during repeated bench stepping trials (step up forward/step down backward), and the resulting horizontal plane CG velocity trajectories were analyzed using HCA. Results: VSP patients were significantly less stable than healthy subjects prior to VR (P = 0.022), but these differences disappeared following VR (P = 0.148). The stability of the VSP patients during the stepping task at 3 months increased significantly from baseline values (P = 0.013). Conclusions: Evaluating the efficacy of VR requires analysis techniques that are sensitive to changes in stability. We conclude that HCA can be used for assessing improvements in CG stability of VSP patients while performing a repeated bench stepping activity. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Biomot Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Orthoped, Boston, MA USA. RP Goldvasser, D (reprint author), Massachusetts Gen Hosp, Biomot Lab, 40 Parkman St, Boston, MA 02114 USA. FU NIA NIH HHS [R01-AG11255] NR 22 TC 6 Z9 6 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD OCT PY 2000 VL 111 IS 10 BP 1838 EP 1842 DI 10.1016/S1388-2457(00)00387-4 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 365KU UT WOS:000089951100017 PM 11018500 ER PT J AU Dodds, MWJ Yeh, CK Johnson, DA AF Dodds, MWJ Yeh, CK Johnson, DA TI Salivary alterations in type 2 (non-insulin-dependent) diabetes mellitus and hypertension SO COMMUNITY DENTISTRY AND ORAL EPIDEMIOLOGY LA English DT Article DE diabetes mellitus; non-insulin-dependent; hypertension; saliva; salivary glands; salivary proteins ID AUTONOMIC NERVOUS-SYSTEM; FLOW-RATE; HUMAN MYELOPEROXIDASE; HIV-1 INFECTION; GLAND FUNCTION; PAROTID-GLAND; WHOLE SALIVA; LACTOFERRIN; PROTEINS; DISEASES AB Objectives: The aim of this study was to determine whether saliva output and composition are altered in type 2 diabetes mellitus by comparison with a healthy, non-medicated control group, and also a roup of hypertensives. Methods: From a community-dwelling cohort of Mexican American and European American subjects enrolled in the OH:SALSA oral aging study, we identified 233 subjects with type 2 diabetes mellitus, 227 with hypertension, and 240 healthy control subjects. We collected unstimulated whole (UW) and submandibular/ sublingual (US) saliva, as well as stimulated parotid (SP) and submandibular/ sublingual (SS) saliva. Flow rates were determined, yeast carriage was assayed in UW saliva, and SP and SS saliva samples were analyzed for protein composition. ELISA was used to determine concentrations of an array of specific protein components, with both antimicrobial and other activities. Results: Both diabetic and hypertensive subjects had reduced output of both stimulated and unstimulated submandibular/sublingual saliva. 30% of the diabetic subjects had high oral yeast counts (greater than or equal to 1000 cfu/mL) compared with 17% of the healthy subjects and 20% of the hypertensives. Significant increases in the concentrations of a number of the protein components were found in the diabetic subjects, specifically, SP lactsferrin, myeloperoxidase (MPO), and salivary peroxidase (SPO), as well as SS total protein, albumin, lactoferrin and secretory IgA. Conclusions: The pattern of decreased flow rates and increased protein concentrations were similar, but consisitently greater in diabetics than hypertensives, suggesting that disease-specific mechanisms may be responsible. Diabetics may be more prone to oral dryness and infections than non-diabetics. C1 Univ Texas, Hlth Sci Ctr, Dept Community Dent, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Dent Diagnost Sci, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. RP Dodds, MWJ (reprint author), Univ Texas, Hlth Sci Ctr, Dept Community Dent, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NIDCR NIH HHS [DE10756] NR 57 TC 54 Z9 58 U1 1 U2 7 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0301-5661 J9 COMMUNITY DENT ORAL JI Community Dentist. Oral Epidemiol. PD OCT PY 2000 VL 28 IS 5 BP 373 EP 381 DI 10.1034/j.1600-0528.2000.028005373.x PG 9 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 356KC UT WOS:000089441600007 PM 11014514 ER PT J AU Suarez-Almazor, ME Belseck, E Homik, J Dorgan, M Ramos-Remus, C AF Suarez-Almazor, ME Belseck, E Homik, J Dorgan, M Ramos-Remus, C TI Identifying clinical trials in the medical literature with electronic databases: MEDLINE alone is not enough SO CONTROLLED CLINICAL TRIALS LA English DT Article DE MEDLINE; EMBASE; on-line databases; clinical trials; rheumatic diseases ID RANDOMIZED CONTROLLED TRIALS; BIBLIOGRAPHIC DATABASES; BIOMEDICAL DATABASES; LITERATURE SEARCHES; PERFORMANCE; RETRIEVAL; RELEVANT; QUALITY; CARE AB The objective of this study was to compare the performance of MEDLINE and EMBASE for the identification of articles regarding controlled clinical trials (CCTs) published in English and related to selected topics: rheumatoid arthritis (RA), osteoporosis (OP), and low back pain (LBP). MEDLINE and EMBASE were searched for literature published in 1988 and 1994. The initial selection of papers was then reviewed to confirm that the articles were about CCTs and to assess the quality of the studies. Selected journals were also hand searched to identify CCTs not retrieved by either database. Overall, 4111 different references were reviewed (2253 for RA, 978 for OF, and 880 for LBP); 3418 (83%) of the papers were in English. EMBASE retrieved 78% more references than MEDLINE (2895 versus 1625). Overall, 1217 (30%) of the papers were retrieved by both databases. Two hundred forty-three papers were about CCTs. Two-thirds of these were retrieved by both databases, and one-third by only one. An additional 16 CCTs not retrieved by either database were identified through hand searching. Taking these into account, EMBASE retrieved 16% more CCTs than MEDLINE (220 versus 188); the EMBASE search identified 85% of the CCTs compared to 73% by MEDLINE. No significant differences were observed in the mean quality scores and sample size of the CCTs missed by MEDLINE compared to those missed by EMBASE. Our findings suggest that the use of MEDLINE alone to identify CCTs is inadequate. The use of two or more databases and hand searching of selected journals are needed to perform a comprehensive searches. (C) Elsevier Science Inc. 2000. C1 Baylor Coll Med, Houston, TX 77030 USA. Univ Alberta, Dept Publ Hlth Sci, Edmonton, AB T6G 2M7, Canada. Inst Mexicano Seguro Social, Guadalajara, Jalisco, Mexico. RP Suarez-Almazor, ME (reprint author), Vet Affairs Med Ctr 152, Hlth Serv Res, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 29 TC 94 Z9 95 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD OCT PY 2000 VL 21 IS 5 BP 476 EP 487 DI 10.1016/S0197-2456(00)00067-2 PG 12 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 361AH UT WOS:000089699200005 PM 11018564 ER PT J AU Hickey, RW Ferimer, H Alexander, HL Garman, RH Callaway, CW Hicks, S Safar, P Graham, SH Kochanek, PM AF Hickey, RW Ferimer, H Alexander, HL Garman, RH Callaway, CW Hicks, S Safar, P Graham, SH Kochanek, PM TI Delayed, spontaneous hypothermia reduces neuronal damage after asphyxial cardiac arrest in rats SO CRITICAL CARE MEDICINE LA English DT Article DE cerebral ischemia; temperature; hypothermia; rat; cardiac arrest; postischemic hypothermia; resuscitation; neuronal damage; cardiopulmonary resuscitation; neuroprotection ID MODERATE HYPOTHERMIA; POSTISCHEMIC HYPOTHERMIA; CEREBRAL RESUSCITATION; BRAIN TEMPERATURE; CARDIOPULMONARY-RESUSCITATION; INJURY; ISCHEMIA; DOGS; MINUTES; GERBIL AB Objective: Core temperature is reduced spontaneously after asphyxial cardiac arrest in rats. To determine whether spontaneous hypothermia influences neurologic damage after asphyxial arrest, we compared neurologic outcome in rats permitted to develop spontaneous hypothermia vs. rats managed with controlled normothermia. Interventions Male Sprague-Dawley rats were asphyxiated for 8 mins and resuscitated. After extubation, a cohort of rats was managed with controlled normothermia (CN) by placement in a servo-controlled incubator set to maintain rectal temperature at 37.4 degrees C for 48 hrs. CN rats were compared with permissive hypothermia (PH) rats that were returned to an ambient temperature environment after extubation. Rats were killed at either 72 hrs (PH72hr, n = 14; CN72hr, n = 9) or 6 wks (PH6wk, n = 6, CN6wk, n = 6) after resuscitation. PH72 rats were historic controls for the CN72 rats, whereas PH6 and CN6 rats were randomized and studied contemporaneously. Measurements: A clinical neurodeficit score (NDS) was determined daily. A pathologist blinded to group scored 40 hematoxylin and eosin-stained brain regions for damage by using a 5-point scale (0 = none, 5 = severe). Quantitative analysis of CA1 hippocampus injury was performed by counting normal-appearing neurons in a defined subsection of CA1. Main Results: Mean rectal temperatures measured in the PH6wk rats (n = 6) were 36.9, 34.8, 35.5, 36.7, and 37.4 degrees C at 2, 8, 12, 24, and 36 hrs, respectively. Mortality rate (before termination) was lower in PH compared with CN (0/20 vs. 7/15; p < .005). PH demonstrated a more favorable progression of NDS (p = .04) and less weight loss (P < .005) compared with CN. Median histopathology scores were lower (less damage) in PH72hr vs. CN72hr for temporal cortex (0 vs. 2.5), parietal cortex (0 vs. 2), thalamus (0 vs. 3), CA1 hippocampus (1.5 vs. 4.5), CA2 hippocampus (0 vs. 3.5), subiculum (0 vs. 4), and cerebellar Purkinje cell layer (2 vs. 4) (all p < .05). There was almost complete loss of normal-appearing CA1 neurons in CN72hr rats (6 +/- 2 [mean +/- SD] normal neurons compared with 109 +/- 12 in naive controls). In contrast, PH72hr rats demonstrated marked protection (97 +/- 23 normal-appearing neurons) that was still evident, although attenuated, at 6 wks (42 +/- 24 normal-appearing neurons, PH6wk). Conclusion: Rats resuscitated from asphyxial cardiac arrest develop delayed, mild to moderate, prolonged hypothermia that is neuroprotective. C1 Univ Pittsburgh, Childrens Hosp Pittsburgh, Dept Pediat, Div Pediat Emergency Med, Pittsburgh, PA 15213 USA. Mercy Hosp, Dept Pediat, Pittsburgh, PA USA. Univ Pittsburgh, Safar Ctr Resuscitat Res, Pittsburgh, PA 15260 USA. Consultants Vet Pathol Inc, Murrysville, PA USA. Univ Pittsburgh, Vet Affairs Pittsburgh Hlth Syst, Ctr Geriatr Res Educ & Clin, Dept Emergency Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Vet Affairs Pittsburgh Hlth Syst, Ctr Geriatr Res Educ & Clin, Dept Neurol, Pittsburgh, PA 15260 USA. RP Hickey, RW (reprint author), Univ Pittsburgh, Childrens Hosp Pittsburgh, Dept Pediat, Div Pediat Emergency Med, 3705 5th Ave, Pittsburgh, PA 15213 USA. RI Kochanek, Patrick/D-2371-2015 OI Kochanek, Patrick/0000-0002-2627-913X NR 41 TC 72 Z9 79 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 OCT PY 2000 VL 28 IS 10 BP 3511 EP 3516 DI 10.1097/00003246-200010000-00027 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 365CT UT WOS:000089931400020 PM 11057809 ER PT J AU Hemler, ME Rutishauser, U AF Hemler, ME Rutishauser, U TI Cell-to-cell contact and extracellular matrix - Editorial overview SO CURRENT OPINION IN CELL BIOLOGY LA English DT Article C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Program Cellular Biochem & Biophys, New York, NY 10021 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, 44 Binney St,Room M613, Boston, MA 02115 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD OCT PY 2000 VL 12 IS 5 BP 539 EP 541 DI 10.1016/S0955-0674(00)00128-9 PG 3 WC Cell Biology SC Cell Biology GA 352FL UT WOS:000089203800001 ER PT J AU Mach, N Dranoff, G AF Mach, N Dranoff, G TI Cytokine-secreting tumor cell vaccines SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID COLONY-STIMULATING-FACTOR; AUTOLOGOUS MELANOMA-CELLS; T-LYMPHOCYTE RESPONSE; CLINICAL-PHASE-I; GENE-THERAPY; METASTATIC MELANOMA; DENDRITIC CELLS; PROTECTIVE IMMUNITY; ANTITUMOR IMMUNITY; MALIGNANT-MELANOMA AB Modification of the tumor microenvironment with gene transfer techniques stimulates two immune mechanisms that effectuate tumor destruction. One involves improved tumor-antigen presentation for the development of specific cellular and humoral immunity. The second involves compromise of the tumor vasculature by soluble factors and leukocytes. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Dranoff, G (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Dana 510E,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA74886] NR 56 TC 88 Z9 94 U1 1 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 2000 VL 12 IS 5 BP 571 EP 575 DI 10.1016/S0952-7915(00)00144-8 PG 5 WC Immunology SC Immunology GA 351EC UT WOS:000089144000014 PM 11007361 ER PT J AU Bobryshev, YV AF Bobryshev, YV TI Dendritic cells and their involvement in atherosclerosis SO CURRENT OPINION IN LIPIDOLOGY LA English DT Review ID RECEPTOR-MEDIATED ENDOCYTOSIS; ANTIGEN-PRESENTING FUNCTION; HUMAN ARTERIAL INTIMA; ATHERO-PRONE AREAS; LANGERHANS CELLS; DEVELOPMENTAL REGULATION; CONTACTING INTERACTIONS; LYMPHOID-TISSUE; CUTTING EDGE; S100 PROTEIN AB Dendritic cells constitute a unique family of cells able to induce primary immune responses. Over the past decade, immunologists have been increasingly preoccupied with dendritic cells and dendritic cells are now seen as a panacea for vaccine development, tumour immunotherapy and a host of other immunological applications. The recent finding of dendritic cells accumulating in atherosclerotic lesions should stimulate investigation of their contributions to atherogenesis and their potential use in anti-atherosclerosis therapies. Curr Opin Lipidol 11:511-517. (C) 2000 Lippincott Williams & Wilkins. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metab Unit, Boston, MA 02114 USA. St Vincents Hosp, Professorial Surg Unit, Sydney, NSW 2010, Australia. RP Bobryshev, YV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lipid Metab Unit, 55 Fruit St,Jackson 1328, Boston, MA 02114 USA. RI Bobryshev, Yuri/J-2838-2013 FU NIDDK NIH HHS [5PO1 DK 50305-10] NR 71 TC 64 Z9 68 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0957-9672 J9 CURR OPIN LIPIDOL JI Curr. Opin. Lipidology PD OCT PY 2000 VL 11 IS 5 BP 511 EP 517 DI 10.1097/00041433-200010000-00009 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Peripheral Vascular Disease SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Cardiovascular System & Cardiology GA 362DX UT WOS:000089764300009 PM 11048894 ER PT J AU Christian, M Yeung, L Williams, R Lapinski, P Moy, R AF Christian, M Yeung, L Williams, R Lapinski, P Moy, R TI Conscious sedation in dermatologic surgery SO DERMATOLOGIC SURGERY LA English DT Review ID ANESTHESIA; ALFENTANIL; PROPOFOL; FENTANYL C1 Univ Texas, SW Med Ctr, Dept Dermatol, Dallas, TX 75235 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Christian, M (reprint author), Univ Texas, SW Med Ctr, Dept Dermatol, 5323 Harry Hines Blvd, Dallas, TX 75235 USA. NR 30 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD OCT PY 2000 VL 26 IS 10 BP 923 EP 928 DI 10.1046/j.1524-4725.2000.026010923.x PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA 362RA UT WOS:000089791000005 PM 11050494 ER PT J AU Roberts, DJ AF Roberts, DJ TI Molecular mechanisms of development of the gastrointestinal tract SO DEVELOPMENTAL DYNAMICS LA English DT Review DE development; gut; gastrointestine; embryo; chick; Hox; Gremlin; Shh; Nkx; Bmp; Wnt; Hnf; GATA; pattern formation; endoderm; mesoderm; epithelial-mesenchymal interaction; differentiation; polarization ID EPITHELIAL-MESENCHYMAL INTERACTIONS; LEFT-RIGHT ASYMMETRY; HELIX TRANSCRIPTION FACTOR; ENHANCER-BINDING PROTEIN; HEART TUBE FORMATION; HOX GENE-EXPRESSION; SONIC-HEDGEHOG; MOUSE EMBRYO; PEPSINOGEN GENE; VENTRAL MORPHOGENESIS AB The gut offers a complex but rich organ system to study visceral pattern formation, The gut is an early evolutionary advance. Data supports that the molecular controls of gut pattern formation are be conserved across species. The gut develops in a stereotyped manner in many different species, by using a basic mechanism of development, the epithelial-mesenchymal interaction. Signaling between the endoderm and mesoderm is essential for normal gut development. The signaling molecules involved are just being described and include factors known to be critical in embryonic development of other systems. The gut has four major patterned axes: anterior-posterior (AP), dorsal-ventral (DV), left-right (LR), and radial (RAD). The molecular pathways used to control pattern in each of these axes are the subject of this review. Major advances in the understanding of AP and LR axis formation in the gut have been described within the past few years, RAD and DV axes are now hot topics for investigation. Despite advances in these areas of gut development, basic events remain poorly understood. Discovery of specific factors that control gut pattern formation may provide a template for the study of pattern formation in other visceral/organ systems. (C) 2000 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol,Div Womens & Perinatal Pathol, Boston, MA 02114 USA. RP Roberts, DJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, 55 Blossom St WRN 225, Boston, MA 02114 USA. NR 106 TC 131 Z9 133 U1 3 U2 7 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD OCT PY 2000 VL 219 IS 2 BP 109 EP 120 DI 10.1002/1097-0177(2000)9999:9999<::AID-DVDY1047>3.3.CO;2-Y PG 12 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 359TL UT WOS:000089628100001 PM 11002332 ER PT J AU Hussain, MA Daniel, PB Habener, JF AF Hussain, MA Daniel, PB Habener, JF TI Glucagon stimulates expression of the inducible cAMP early repressor and suppresses insulin gene expression in pancreatic beta-cells SO DIABETES LA English DT Article ID ELEMENT-BINDING PROTEIN; RESPONSE ELEMENT; CELLULAR PROLIFERATION; SERTOLI CELLS; FACTOR CREB; I GENE; TRANSCRIPTION; KINASE; RECEPTOR; ICER AB The hormone glucagon is secreted by the alpha-cells of the endocrine pancreas (islets of Langerhans) during fasting and is essential for the maintenance of blood glucose levels by stimulation of hepatic glucose output. Excessive production and secretion of glucagon by the alpha-cells of the islets is a common accompaniment to diabetes. The resulting hyperglucagonemia stimulates hepatic glucose production, thereby contributing to hyperglycemia of diabetes. The reduced insulin secretion in diabetes and resultant failure to suppress glucagon secretion by intra-islet paracrine mechanisms is believed to cause the hypersecretion of glucagon. Here, we report the discovery of a new mechanism by which glucagon suppresses insulin secretion. We show that glucagon, but not glucagon-like peptide 1 (GLP-1), or pituitary adenylyl cyclase-activating peptide (PACAP) specifically induces the expression of the transcriptional repressor inducible cAMP early repressor (ICER) in pancreatic beta-cells, resulting in a repression of the transcriptional expression of the insulin gene. Remarkably, glucagon, GLP-1, and PACAP all stimulate the formation of cAMP to a comparable extent in rat pancreatic islets, but only glucagon activates the expression of ICER and represses insulin gene transcription in beta-cells. These findings lead us to propose that hyperglucagonemia may additionally aggravate the diabetic phenotype via a suppression of insulin gene expression mediated by the transcriptional repressor ICER. C1 Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. Howard Hughes Med Inst, Coconut Grove, FL 33133 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Habener, JF (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, 5 Fruit St,WEL320, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-30834] NR 54 TC 33 Z9 33 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2000 VL 49 IS 10 BP 1681 EP 1690 DI 10.2337/diabetes.49.10.1681 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 357QZ UT WOS:000089513500009 PM 11016452 ER PT J AU Levin, SR Coburn, JW Abraira, C Henderson, WG Colwell, JA Emanuele, NV Nuttall, FQ Sawin, CT Comstock, JP Silbert, CK AF Levin, SR Coburn, JW Abraira, C Henderson, WG Colwell, JA Emanuele, NV Nuttall, FQ Sawin, CT Comstock, JP Silbert, CK CA Vet Affairs Cooperative Study Glyc TI Effect of intensive glycemic control on microalbuminuria in type 2 diabetes SO DIABETES CARE LA English DT Article ID VA CSDM; FEASIBILITY TRIAL; CREATININE CLEARANCE; NIDDM PATIENTS; HEART-DISEASE; COMPLICATIONS; MELLITUS; INSULIN; PROGRESSION; THERAPY AB OBJECTIVE - Microalbuminuria can reflect the progress of microvascular complications and may be predictive of macrovascular disease in type 2 diabetes. The effect of intensive glycemic control on microalbuminuria in patients in the U.S. who have had type 2 diabetes for several years has not previously been evaluated. RESEARCH DESIGN AND METHODS - We randomly assigned 153 male patients to either intensive treatment (INT) (goal HbA(1c) 7.1%) or to standard treatment (ST) (goal HbA(1c) 9.1% P = 0.001), and data were obtained during a 2-year period. Mean duration of known diabetes was 8 years, mean age of the patients was 60 years, and patients were well matched at baseline. We obtained 3-h urine samples for each patient at baseline and annually and defined microalbuminuria as an albumin:creatinine ratio of 0.03-030. All patients were treated with insulin and received instructions regarding diet and exercise. Hypertension and dyslipidemia were treated with similar goals in each group. RESULTS - A total of 38% of patients had microalbuminuria at entry and were evenly assigned to both treatment groups. INT retarded the progression of microalbuminuria during the 2-year period: the changes in albumin:creatinine ratio from baseline to 2 years of INT versus ST were 0.045 vs. 0.141, respectively (P = 0.046). Retardation of progressive urinary albumin excretion was most pronounced in those patients who entered the study with microalbuminuria and were randomized to INT. Patients entering with microalbuminuria had a deterioration in creatinine clearance at 2 years regardless of the intensity of glycemic control. In the group entering without microalbuminuria, the subgroup receiving ST had a lower percentage of patients with a macrovascular event (17%) than the subgroup receiving INT (36%) (P = 0.03). Use of ACE inhibitors or calcium-channel blockers was similarly distributed among the groups. CONCLUSIONS - Intensive glycemic control retards microalbuminuria in patients who have had type 2 diabetes for several years but may not lessen the progressive deterioration of glomerular function. Increases in macrovascular event rates in the subgroup entering without albuminuria who received INT remain unexplained but could reflect early worsening, as observed with microvascular disease in the Diabetes Control and Complications Trial. C1 W Los Angeles Vet Affairs Med Ctr, Vet Affairs Greater Los Angeles Healthcare Syst, Med Serv 111K, Los Angeles, CA 90073 USA. Edward Hines Jr Vet Adm Med Ctr, Hines, IL USA. Minneapolis Vet Affairs Med Ctr, Minneapolis, MN USA. Boston Vet Affairs Med Ctr, Boston, MA USA. Charleston Vet Affairs Med Ctr, Charleston, SC USA. Houston Vet Affairs Med Ctr, Houston, TX USA. RP Levin, SR (reprint author), W Los Angeles Vet Affairs Med Ctr, Vet Affairs Greater Los Angeles Healthcare Syst, Med Serv 111K, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 43 TC 53 Z9 57 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2000 VL 23 IS 10 BP 1478 EP 1485 DI 10.2337/diacare.23.10.1478 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 357RB UT WOS:000089513700007 PM 11023140 ER PT J AU Kahn, SE Andrikopoulos, S Verchere, CB Wang, F Hull, RL Vidal, J AF Kahn, SE Andrikopoulos, S Verchere, CB Wang, F Hull, RL Vidal, J TI Oophorectomy promotes islet amyloid formation in a transgenic mouse model of Type II diabetes SO DIABETOLOGIA LA English DT Article DE islet amyloid; islet amyloid polypeptide; amylin; oophorectomy; oestrogen; glucose tolerance; diabetes; Alzheimer's disease ID POLYPEPTIDE; MICE AB Aims/hypothesis. In Type II (non-insulin-dependent) diabetes mellitus, amyloid depletes islet mass. We previously found that 81% of male human islet amyloid polypeptide (IAPP) transgenic mice but only 11% of female mice developed islet amyloid, suggesting that either testosterone promotes or ovarian products protect against amyloid deposition. Methods. We did a bilateral oophorectomy or sham procedure in female human IAPP transgenic mice (n = 11 and n = 8, respectively) and in female non-transgenic mice (n = 7 and n = 9, respectively) at 6-8 weeks of age. Animals were followed for 1 year on a 9 % fat (w/w) diet. Before we killed them we measured, fasting plasma human IAPP and did an intraperitoneal glucose tolerance test. Pancreatic content of IAPP and immunoreactive insulin (IRI) were estimated and pancreata were analysed for islet amyloid. Results. No amyloid was detected in either the sham-operated transgenic mice or, as expected, in both groups of non-transgenic mice. In strong contrast, 7 of 11 (64%) oophorectomized mice developed islet amyloid (p < 0.05). Amyloid deposition in the oophorectomized transgenic mice was not associated with any differences in incremental body weight, fasting human IAPP concentrations or glucose tolerance between the groups. Furthermore, pancreatic content of mouse IAPP, human IAPP and immunoreactive insulin did not differ between groups. Conclusion/interpretation. Oophorectomy is associated with an enhancement of islet amyloid formation in the absence of changes in glucose tolerance, circulating IAPP or pancreatic content of IRI, mouse or human IAPP. Thus, the early stages of islet amyloidogenesis seem to be independent of glucose tolerance, with ovarian products having a protective role. C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Washington, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA 98195 USA. RP Kahn, SE (reprint author), VA Puget Sound Hlth Care Syst, 151,1660 S Columbian Way, Seattle, WA 98108 USA. OI Kahn, Steven/0000-0001-7307-9002; Hull, Rebecca/0000-0001-9690-4087 FU NIDDK NIH HHS [DK-17047, DK-50703] NR 10 TC 18 Z9 18 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD OCT PY 2000 VL 43 IS 10 BP 1309 EP 1312 DI 10.1007/s001250051527 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 365BD UT WOS:000089927800013 PM 11079750 ER PT J AU Gorelik, Y Damron-Rodriguez, J Funderburk, B Solomon, DH AF Gorelik, Y Damron-Rodriguez, J Funderburk, B Solomon, DH TI Undergraduate interest in aging: Is it affected by contact with older adults? SO EDUCATIONAL GERONTOLOGY LA English DT Article ID NURSING-STUDENTS ATTITUDES; SOCIAL-WORK STUDENTS; MEDICAL-STUDENTS; GERONTOLOGICAL EDUCATION; GERIATRIC EDUCATION; PHYSICAL THERAPY; ELDERLY PEOPLE; KNOWLEDGE; PREFERENCES; PERCEPTIONS AB Undergraduate student interest in aging was examined in, elation to age, gender; and contact with older adults. Interest in aging is conceived of along a continuum, ranging from initial interest-taking an aging course-to substantial interest as evidenced by academic and career interest. Undergraduate students who have taken an aging course (n = 189) and a stratified, random comparison group (n = 261) self-assessed their interest in aging. Background information, including the frequency and duration of contact with older family and non-family individuals, individuals, was reported. Being female (p < 001) and having frequent contact with older family members (p < .01) significantly explains initial interest in aging. Initial interest in aging (i.e., taking an aging course) significantly contributes to substantial interest in aging (p < .0001) i.e., taking more aging courses, majoring in gerontology, working or planning to work with older adults. Contact with older adults positively affects undergraduate interest in aging. Interest in aging proceeds along a continuum, from preceding factors to initial interest in aging and then to substantial interest in aging. Aging courses and opportunities for interaction with older adults should be offered at the undergraduate level. C1 Univ Calif Los Angeles, Sch Publ Policy & Social Res, VA Geriat Res Educ & Clin Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Damron-Rodriguez, J (reprint author), VA Greater Los Angeles Healthcare Syst, 11G,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 42 TC 22 Z9 22 U1 0 U2 4 PU HEMISPHERE PUBL CORP PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 USA SN 0360-1277 J9 EDUC GERONTOL JI Educ. Gerontol. PD OCT-NOV PY 2000 VL 26 IS 7 BP 623 EP 638 DI 10.1080/03601270050200626 PG 16 WC Education & Educational Research; Gerontology SC Education & Educational Research; Geriatrics & Gerontology GA 380BL UT WOS:000165678400002 ER PT J AU Lewis, JT Dayanandan, B Habener, JF Kieffer, TJ AF Lewis, JT Dayanandan, B Habener, JF Kieffer, TJ TI Glucose-dependent insulinotropic polypeptide confers early phase insulin release to oral glucose in rats: Demonstration by a receptor antagonist SO ENDOCRINOLOGY LA English DT Article ID GASTRIC-INHIBITORY POLYPEPTIDE; GLUCAGON-LIKE PEPTIDE-1; PHYSIOLOGICAL INCRETIN; FUNCTIONAL EXPRESSION; ENDOCRINE PANCREAS; GIP; SECRETION; HORMONE; PLASMA; MICE AB A novel GIP receptor antagonist was developed to evaluate the acute role of glucose-dependent insulinotropic polypeptide (GIP) in the insulin response to oral glucose in rats. Antisera to an extracellular epitope of the GIP receptor (GIPR) detected immunoreactive GIPR on rat pancreatic beta-cells. Purified GIPR antibody (GIPR Ab) specifically displaced GIP binding to the receptor and blocked GIP-mediated increases in intracellular cAMP. When delivered to rats by ip injection, GIPR Ab had a half-life of approximately 4 days. Treatment with GIPR Ab (1 mu g/g BW) blocked the potentiation of glucose-stimulated insulin secretion by GIP (60 pmol) but not glucagon-like peptide-1 (GLP-1, 60 pmol) in anesthetized rats. The insulin response to oral glucose was delayed in conscious unrestrained rats that were pretreated with GIPR Ab. Plasma insulin levels were similar to 35% lower at 10 min in GIPR Ab treated animals compared with controls. As a result, the glucose excursion was greater in the GIPR Ab treated group. Fasting plasma glucose levels were not altered by GIPR Ab. We conclude that release of GIP following oral glucose may act as an anticipatory signal to pancreatic beta-cells to promote rapid release of insulin for glucose disposal. C1 Univ Alberta, Heritage Med Res Ctr 370, Dept Physiol, Edmonton, AB T6G 2S2, Canada. Univ Alberta, Heritage Med Res Ctr 370, Dept Med, Edmonton, AB T6G 2S2, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Lab Mol Endocrinol, Boston, MA 02114 USA. RP Kieffer, TJ (reprint author), Univ Alberta, Heritage Med Res Ctr 370, Dept Physiol, Edmonton, AB T6G 2S2, Canada. EM tim.kieffer@ualberta.ca NR 53 TC 69 Z9 74 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 2000 VL 141 IS 10 BP 3710 EP 3716 DI 10.1210/en.141.10.3710 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 355PV UT WOS:000089394800023 PM 11014226 ER PT J AU Gatti, JJ Dobeck, JM Smith, C White, RR Socransky, SS Skobe, Z AF Gatti, JJ Dobeck, JM Smith, C White, RR Socransky, SS Skobe, Z TI Bacteria of asymptomatic periradicular endodontic lesions identified by DNA-DNA hybridization SO ENDODONTICS & DENTAL TRAUMATOLOGY LA English DT Article DE apical periodontitis; bacteria; DNA-probes; endodontic infection ID ROOT-CANAL INFECTIONS; PERIAPICAL LESIONS; PERIODONTITIS; TEETH AB Possible inclusion of contaminant bacteria during surgery has been problematic in studies of periradicular lesions of endodontic origin. Therefore, in this study, two different surgical techniques were compared. A second problem is that some difficult to cultivate species may not be detected using bacteriological methods. Molecular techniques may resolve this problem. DNA-DNA hybridization technology has the additional advantage that DNA is not amplified. The purpose of this investigation was to determine if bacteria from periradicular endodontic lesions could be identified using DNA-DNA hybridization. A full thickness intrasulcular mucoperiosteal (IS) flap (n=20) or a submarginal (SM) flap (n=16) was reflected in patients with asymptomatic apical periodontitis. DNA was extracted and incubated with 40 digoxigeninlabeled whole genomic probes. Bacterial DNA was detected in all 36 lesions. Seven probes were negative for all lesions. In patients with sinus tract communication, in teeth lacking intact full coverage crowns, and in patients with a history of trauma, 4-13 probes provided positive signals. Seven probes were positive in lesions obtained by the IS, but not the SM technique. Two probes were in samples obtained with the SM technique, but not the IS. Only Bacteroides forsythus and Actinomyces naeslundii genospecies 2 were present in large numbers using either the IS or the SM technique. The SM flap technique, in combination with DNA-DNA hybridization, appeared to provide excellent data pertaining to periradicular bacteria. These results supported other studies that provide evidence of a bacterial presence and persistence in periradicular lesions. C1 Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA. RP Skobe, Z (reprint author), Forsyth Inst, Dept Biomineralizat, 140 Fenway, Boston, MA 02115 USA. NR 30 TC 31 Z9 31 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0109-2502 J9 ENDOD DENT TRAUMATOL JI Endod. Dent. Traumatol. PD OCT PY 2000 VL 16 IS 5 BP 197 EP 204 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 359JN UT WOS:000089607900002 PM 11202882 ER PT J AU Brand, S Poneros, JM Bouma, BE Tearney, GJ Compton, CC Nishioka, NS AF Brand, S Poneros, JM Bouma, BE Tearney, GJ Compton, CC Nishioka, NS TI Optical coherence tomography in the gastrointestinal tract SO ENDOSCOPY LA English DT Review ID ENDOSCOPIC FLUORESCENCE DETECTION; BARRETTS-ESOPHAGUS; DYSPLASIA; BIOPSY; ADENOCARCINOMA; LIGHT; SKIN AB Optical coherence tomography (OCT) is a high-resolution, cross-sectional optical imaging technique that allows in situ imaging of tissue by measuring back-reflected light, OCT provides images in real time with a resolution approaching that of conventional histopathology; but without the need for tissue removal. OCT imaging can be performed endoscopically to visualize gastrointestinal tissue using a fiberoptic catheter passed through the instrument channel of a conventional endoscope. The resolution of OCT allows visualization of the different layers of gastrointestinal epithelium and the differentiation of Barrett's epithelium from normal gastric and squamous mucosa, OCT has also been used to image esophageal adenocarcinoma and colonic polyps. Recent developments include Doppler OCT, spectroscopic OCT, and ultrahigh-resolution OCT, which can visualize nuclei within single tells, Although still in its infancy as a clinical tool, OCT currently provides high-resolution images over the same imaging depth as conventional mucosal biopsy, and may Drove to be a useful and minimally invasive technique for evaluating gastrointestinal tissue, particularly for early neoplastic changes. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, BAR-703,50 Blossom St, Boston, MA 02114 USA. EM brand@wlp.mgh.harvard.edu NR 49 TC 72 Z9 74 U1 0 U2 5 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X EI 1438-8812 J9 ENDOSCOPY JI Endoscopy PD OCT PY 2000 VL 32 IS 10 BP 796 EP 803 DI 10.1055/s-2000-7714 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 362JJ UT WOS:000089774600010 PM 11068841 ER PT J AU Roselle, GA Danko, LH Kralovic, SM Simbartl, LA Kizer, KW AF Roselle, GA Danko, LH Kralovic, SM Simbartl, LA Kizer, KW TI Tuberculosis in the veterans healthcare system: a six-year review and evaluation of programme effectiveness SO EPIDEMIOLOGY AND INFECTION LA English DT Review ID RESISTANT TUBERCULOSIS AB The Department of Veterans Affairs operates a large, centrally administered health care system consisting of 173 hospitals and 4 free standing outpatient clinics nationwide with approximately 945 115 hospital discharges, 24.2 million outpatient visits, and 2.86 million persons served annually over the time frame of the review. The purpose of the study was to define whether such a system could effect timely change in the incidence of tuberculosis (TB) using centralized programme planning and flexible field implementation. A retrospective review of the number of newly diagnosed cases of active TB treated at veterans health care facilities between 1 October 1990 and 30 September 1997 was determined by using a standardized annual case census. Intervention included implementation of the must current guidelines for the prevention of transmission of TB in the community and hospital setting, including administrative and engineering controls and a change in personal protective equipment. Centrally directed programme guidance, education, and funding were provided for field use in health care facilities of widely varying size and complexity. The numbers of total reported cases of TB decreased significantly (P < 0.001) throughout the veterans health care system (nationally and regionally), with the case rate decreasing at a rate significantly greater than that seen in the USA as a whole (P < 0.0001). TB associated with multi-drug resistance (isoniazid and rifampin) and HIV coinfection also significantly decreased over the study period. Therefore, a large, centrally administered health care system can effectively combat a re-emerging infectious disease and may also demonstrate a successful outcome greater than seen in other, perhaps less organized health care settings. C1 US Dept Vet Affairs, Vet Hlth Adm Headquarters, Washington, DC USA. Vet Adm Med Ctr, Cincinnati, OH 45220 USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Univ Cincinnati, Inst Hlth Policy & Hlth Serv Res, Cincinnati, OH USA. RP Roselle, GA (reprint author), Vet Adm Med Ctr, 3200 Vine St, Cincinnati, OH 45220 USA. NR 30 TC 1 Z9 1 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI PORT CHESTER PA 110 MIDLAND AVE, PORT CHESTER, NY 10573-4930 USA SN 0950-2688 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD OCT PY 2000 VL 125 IS 2 BP 315 EP 323 DI 10.1017/S0950268899004409 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 422BE UT WOS:000168097400010 PM 11117955 ER PT J AU DeMaria, MA Casto, M O'Connell, M Johnson, RP Rosenzweig, M AF DeMaria, MA Casto, M O'Connell, M Johnson, RP Rosenzweig, M TI Characterization of lymphocyte subsets in rhesus macaques during the first year of life SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article DE lymphocyte; macaque; neonate ID VIRUS TYPE-1 INFECTION; T-CELLS; NATURAL-KILLER; HIV-INFECTION; PEDIATRIC AIDS; IMMUNODEFICIENCY; CHILDREN; SUBPOPULATIONS; PATHOGENESIS; INFANTS AB Establishing reliable phenotypic data sets from the analysis of peripheral blood lymphocytes of normal animals is required to assess disease states. The rhesus macaque animal model is well established with respect to adult animals, but limited data are available that characterizes lymphocyte subsets in normal neonates. To address this, we used four-color flow cytometric analysis to follow phenotypic changes in 29 normal rhesus animals through their first ten months of life. From birth to 44 wk of age, the white cell count and absolute lymphocyte count were both elevated compared to adults. CD4 + cells constituted over 80% of all T cells at birth, a percentage that declined gradually over the first 12 wk of life, coincidental with increases in the percentages of CD8 + T cells, CD3-8 + natural killer cells and CD20 + B cells. This difference in relative frequency of CD4 and CD8 results in a significant skewing of CD4:CD8 ratio from 0.7:1 in adults to 3.5:1 in neonates. In addition, the predominant population of T lymphocytes consisted of CD45RA + CD62L + naive cells. This subset continues to be the predominant phenotype for at least the first year of age. After birth the expression of activation markers (CD25) increased particularly on CD4 + T cells, although these levels generally reached a frequency similar to that observed in adults between 12 and 20 weeks after birth. These results are similar to those seen in humans and further confirm the reliability of the rhesus macaque animal model to study human diseases. C1 Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Primate Med, Southborough, MA 01772 USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Div Pathol, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. RP Rosenzweig, M (reprint author), Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Immunol, 1 Pine Hill Dr, Southborough, MA 01772 USA. FU NCRR NIH HHS [RR00168]; NIAID NIH HHS [R29 AI39423] NR 29 TC 30 Z9 30 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD OCT PY 2000 VL 65 IS 4 BP 245 EP 257 DI 10.1034/j.1600-0609.2000.065004245.x PG 13 WC Hematology SC Hematology GA 362NW UT WOS:000089784900004 PM 11073165 ER PT J AU Leenders, H Whitfield, S Benoist, C Mathis, D AF Leenders, H Whitfield, S Benoist, C Mathis, D TI Role of the forkhead transcription family member, FKHR, in thymocyte differentiation SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE transcription factor; T cell differentiation; thymus ID WINGED-HELIX PROTEIN; ACTIVATION DOMAINS; MAMMALIAN-CELLS; FUSION PROTEIN; KINASE-B; T-CELLS; EXPRESSION; GENE; THYMUS; ENHANCER AB While performing a large-scale analysis of mRNA transcripts in the murine thymus, our attention was drawn to the forkhead family transcription factor FKHR. Here we demonstrate that FKHR is expressed in thymocytes, most prominently in those that are undergoing positive selection. Interestingly, FKHR transcripts show a highly regionalized pattern of expression, concentrated in the innermost areas of the medulla. We define the FKHR binding site as (G/C)(A/C)N(G/a)T(A/c)AA(T/c)A(T/g)(T/g)(G/c), a sequence found in the regulatory elements of many genes, including certain that encode molecules crucial for thymocyte differentiation. To study the function of FKHR, we engineered mice expressing a dominant-negative mutant specifically in T cells in a tetracycline-regulatable fashion. In these animals, T cell differentiation appeared quite normal; however, total thymocyte numbers were decreased, owing to reductions in all four of the CD4/CD8 subsets, and incorporation of the thymidine analogue bromo-deoxyuridine was increased, again in all four subsets. These data suggest that, in thymocytes, FKHR may be involved in cell survival and/or cycling. C1 ULP, Inst Genet & Biol Mol & Cellulaire, CNRS, INSERM, Illkirch, France. RP Benoist, C (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. NR 39 TC 47 Z9 50 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 2000 VL 30 IS 10 BP 2980 EP 2990 DI 10.1002/1521-4141(200010)30:10<2980::AID-IMMU2980>3.0.CO;2-9 PG 11 WC Immunology SC Immunology GA 365YN UT WOS:000089978200029 PM 11069081 ER PT J AU Aoki, Y Huang, ZH Thomas, SS Bhide, PG Huang, I Moskowitz, MA Reeves, SA AF Aoki, Y Huang, ZH Thomas, SS Bhide, PG Huang, I Moskowitz, MA Reeves, SA TI Increased susceptibility to ischemia-induced brain damage in transgenic mice overexpressing a dominant negative form of SHP2 SO FASEB JOURNAL LA English DT Article DE protein tyrosine phosphatase; cell survival; cerebral ischemia; neuron ID PROTEIN-TYROSINE-PHOSPHATASE; FOCAL CEREBRAL-ISCHEMIA; TRANSIENT FOREBRAIN ISCHEMIA; NERVE GROWTH-FACTOR; REACTIVE ASTROCYTES; PROGENITOR CELLS; MESSENGER-RNA; RAT-BRAIN; DIFFERENTIAL REGULATION; SIGNAL-TRANSDUCTION AB Cell culture studies have established SH2 domain-containing protein tyrosine phosphatase-2 (SHP2) as an important factor in growth factor and cytokine-activated signaling pathways. However, the significance of SHP2 in the mammalian central nervous system (CNS) is not known since early embryonic lethality occurs in shp2 null mice. To bypass this embryonic lethality, transgenic animals containing a catalytically inactive mutant of SHP2 (SHP2-CS) under the control of a nestin intron II/thymidiue kinase minimal promoter were generated. In the developing CNS of these animals, although high-level transgene expression was detected in the neuroepithelium, there was no obvious abnormality in progenitor cell proliferation or migration. In the adult brain, high-level transgene expression was detected in the subventricular zone, rostral migratory stream, dentate gyrus of hippocampus, and cerebellum. Because SHP2 function is Likely important in cell survival pathways, we used a focal cerebral ischemia model to examined whether SHP2 is important during CNS injury. Ischemia-induced damage and neuronal death was found to be significantly greater in nestin-SHP2-CS mice than in wildtype littermates. These findings indicate that SHP2 is a required factor in signaling pathway(s) important for neuronal survival. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, CNS Signaling Lab, Charlestown, MA 02129 USA. RP Reeves, SA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, CNS Signaling Lab, 149 13th St, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 FU NINDS NIH HHS [R01NS3599601] NR 52 TC 36 Z9 39 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 OCT PY 2000 VL 14 IS 13 BP 1965 EP 1973 DI 10.1096/fj.00-0105com PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 359WE UT WOS:000089634400015 PM 11023980 ER PT J AU Janosch, P Kieser, A Eulitz, M Lovric, J Sauer, G Reichert, M Gounari, F Buscher, D Baccarini, M Mischak, H Kolch, W AF Janosch, P Kieser, A Eulitz, M Lovric, J Sauer, G Reichert, M Gounari, F Buscher, D Baccarini, M Mischak, H Kolch, W TI The Raf-1 kinase associates with vimentin kinases and regulates the structure of vimentin filaments SO FASEB JOURNAL LA English DT Article DE Raf; phosphorylation; cytoskeleton; casein kinase 2 ID DEPENDENT PROTEIN-KINASE; NIH 3T3 CELLS; INTERMEDIATE FILAMENTS; SIGNAL-TRANSDUCTION; IN-VITRO; V-RAF; PLASMA-MEMBRANE; PHOSPHORYLATION; ACTIVATION; DIFFERENTIATION AB Using immobilized GST-Raf-1 as bait, we have isolated the intermediate filament protein vimentin as a Raf-1-associated protein. Vimentin coimmunoprecipitated and colocalized with Raf-1 in fibroblasts, Vimentin was not a Raf-1 substrate, but was phosphorylated by Raf-1-associated vimentin kinases, We provide evidence for at least two Raf-1-associated vimentin kinases and identified one as casein kinase 2. They are regulated by Raf-1, since the activation status of Raf-1 correlated with the phosphorylation of vimentin. Vimentin phosphorylation by Raf-1 preparations interfered with its polymerization in vitro. A subset of tryptic vimentin phosphopeptides induced by Raf-1. in vitro matched the vimentin phosphopeptides isolated from v-raf-transfected cells labeled with orthophosphoric acid, indicating that Raf-1 also induces vimentin phosphorylation in intact cells. In NIH 3T3 fibroblasts, the selective activation of an estrogen-regulated Raf-1 mutant induced a rearrangement and depolymerization of the reticular vimentin scaffold similar to the changes elicited by serum treatment. The rearrangement of the vimentin network occurred independently of the MEK/ERK pathway. These data identify a new branch point in Raf-1 signaling, which links Raf-1 to changes in the cytoskeletal architecture. C1 Beatson Inst Canc Res, Glasgow G61 1BD, Lanark, Scotland. GSF Forschungszentrum Umwelt & Gesundheit, Inst Klin Mol Biol & Tumorgenet, D-81377 Munich, Germany. Univ Lausanne, Inst Biochem, CH-1066 Epalinges, Switzerland. Dana Farber Canc Inst, Boston, MA 02115 USA. Salk Inst Biol Studies, La Jolla, CA 92037 USA. Vienna Bioctr, Inst Microbiol & Genet, A-1030 Vienna, Austria. Med Hsch Hannover, Dept Nephrol, D-30625 Hannover, Germany. RP Janosch, P (reprint author), Beatson Inst Canc Res, Garscube Estate,Switchback Rd, Glasgow G61 1BD, Lanark, Scotland. RI Mischak, Harald/E-8685-2011; Baccarini, Manuela/B-6481-2014; Kieser, Arnd/M-4616-2014; OI Baccarini, Manuela/0000-0002-3033-391X; Kieser, Arnd/0000-0003-0783-1950; Kolch, Walter/0000-0001-5777-5016 NR 71 TC 43 Z9 44 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 OCT PY 2000 VL 14 IS 13 BP 2008 EP 2021 DI 10.1096/fj.99-0883com PG 14 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 359WE UT WOS:000089634400020 PM 11023985 ER PT J AU Hasko, G Kuhel, DG Chen, JF Schwarzschild, MA Deitch, EA Mabley, JG Marton, A Szabo, C AF Hasko, G Kuhel, DG Chen, JF Schwarzschild, MA Deitch, EA Mabley, JG Marton, A Szabo, C TI Adenosine inhibits IL-12 and TNF-alpha production via adenosine A(2a) receptor-dependent and independent mechanisms SO FASEB JOURNAL LA English DT Article DE inflammatory mediators; cytokines; T lymphocytes; inflammation ID INTERFERON-GAMMA PRODUCTION; ACTIVATED PROTEIN-KINASE; NECROSIS-FACTOR-ALPHA; A(3) RECEPTORS; SIGNAL-TRANSDUCTION; INDUCED ARTHRITIS; ENDOTOXEMIC MICE; HUMAN MONOCYTES; INTERLEUKIN-12; CYTOKINE AB Interleukin 12 (IL-12) is a crucial cytokine in the regulation of T helper 1 vs. T helper 2 immune responses. In the present study, we investigated the effect of the endogenous purine nucleoside adenosine on the production of IL-12, In mouse macrophages, adenosine suppressed 12,12 production. Although the order of potency of adenosine receptor agonists suggested the involvement of A(2a) receptors, data obtained with A(2a) receptor-deficient mice showed that the adenosine suppression of IL-12 and even TNF-alpha production is only partly mediated by A(2a) receptor ligation. Studies with adenosine receptor antagonists or the adenosine uptake blocker dipyridamole showed that adenosine released endogenously also decreases IL-12. Although adenosine increases IL-10 production, the inhibition of IL-12 production is independent of the increased IL-10. The mechanism of action of adenosine was not associated with alterations of the activation of the p38 and p42/p44 mitogen-activated protein kinases or the phosphorylation of the c-Jun terminal kinase. Adenosine failed to affect steady-state levels of either IL-12 p35 or p40 mRNA, but augmented IL-10 mRNA levels. In summary, adenosine inhibits IL-12 production via various adenosine receptors. These results support the notion that adenosine-based therapies might be useful in certain autoimmune and/or inflammatory diseases. C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. Inotek Corp, Beverly, MA 01915 USA. Massachusetts Gen Hosp, Dept Neurol, Mol Neurobiol Lab, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Hasko, G (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, 185 S Orange Ave, Newark, NJ 07103 USA. RI Mabley, Jon/D-2296-2010 FU NIAMS NIH HHS [1R43AR46167-01]; NIGMS NIH HHS [1R43GM59560-01, R29GM54773] NR 56 TC 283 Z9 290 U1 0 U2 16 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 OCT PY 2000 VL 14 IS 13 BP 2065 EP 2074 DI 10.1096/fj.99-0508com PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 359WE UT WOS:000089634400026 PM 11023991 ER PT J AU Anawalt, BD Herbst, KL Matsumoto, AM Mulders, TMT Coelingh-Bennink, HJT Bremner, WJ AF Anawalt, BD Herbst, KL Matsumoto, AM Mulders, TMT Coelingh-Bennink, HJT Bremner, WJ TI Desogestrel plus testosterone effectively suppresses spermatogenesis but also causes modest weight gain and high-density lipoprotein suppression SO FERTILITY AND STERILITY LA English DT Article DE male hormonal contraception; spermatogenesis; oligoazoospermia; azoospermia; testosterone; gonadotropins; desogestrel ID MALE CONTRACEPTION; LEVONORGESTREL; GONADOTROPIN; CHOLESTEROL; ENANTHATE AB Objective: To test the hypothesis that oral desogestrel (DSG) plus testosterone would uniformly and rapidly suppress sperm concentrations in young men as effectively as levonorgestrel (LNG) plus testosterone and cause less high-density lipoprotein (HDL) suppression and weight gain. Design: Single-blind, randomized trial. Setting: VA Puget Sound and University of Washington, Seattle, Washington. Patient(s): Twenty-four healthy young men, aged 20-49. Intervention(s): Subjects were randomized to three groups of men who were administered 6 months of therapy with oral DSG plus im testosterone enanthate: 150 mu g of DSG plus 50 mu g of testosterone (DSG 150-T 50), 150 mu g of DSG plus 100 mg of testosterone (DSG 150-T 100) or 300 mu g of DSG plus 100 mg of testosterone (DSG 300-T 100). We compared these three groups to two groups of historical controls of 100 mg of im testosterone alone or 150 mu g of oral LNG plus 100 mg of im testosterone (LNG 125-T 100 group) enrolled in similar studies. Main Outcome Measure(s): Suppression of sperm counts to severe oligoazoospermia (sperm counts <1 X 10(6)/mL) and azoospermia, weight gain, and serum high-density cholesterol (HDL) suppression. Result(s): Azoospermia was achieved in all eight men receiving DSG 150-T 100 and seven of the right men in the DSG 300-T 100 group. DSG 150 or 300 plus T 100 suppressed spermatogenesis as effectively as LNG 125-T 100 and more effectively than DSG 150-T 100 or testosterone alone. All groups tended to gain weight compared with their baseline, but the weight gain was greatest land statistically significant) in the DSG 150-T 100, DSG 300-T 100, and LNG 125-T 100 groups. Serum HDL levels were modestly suppressed in all groups, and this effect was greatest in the DSG 300-T 100 and LNG 125-T 100 groups. Conclusion(s): The combination of DSG plus testosterone is a very effective regimen for suppression of spermatogenesis and has acceptably low side effects. (Fertil Steril (R) 2000;74:707-14. (C) 2000 by American Society for Reproductive Medicine.). C1 Univ Washington, Dept Med, Populat Ctr Res Reprod, Seattle, WA USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. NV Organon, Oss, Netherlands. RP Anawalt, BD (reprint author), S-111 VAPSHCS,1660 S Columbian Way, Seattle, WA 98108 USA. FU NICHD NIH HHS [HD 12629] NR 19 TC 51 Z9 51 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2000 VL 74 IS 4 BP 707 EP 714 DI 10.1016/S0015-0282(00)01490-4 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 362KY UT WOS:000089778200019 PM 11020511 ER PT J AU Bogdanov, M Brown, RH Matson, W Smart, R Hayden, D O'Donnell, H Beal, MF Cudkowicz, M AF Bogdanov, M Brown, RH Matson, W Smart, R Hayden, D O'Donnell, H Beal, MF Cudkowicz, M TI Increased oxidative damage to DNA in ALS patients SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE amyotrophic lateral sclerosis; 8-hydroxy-2 '-deoxyguanosine; DNA; cerebrospinal fluid; plasma; urine; free radicals ID AMYOTROPHIC-LATERAL-SCLEROSIS; AGE-DEPENDENT INCREASES; MOTOR-NEURON DISEASE; SUPEROXIDE-DISMUTASE; CEREBROSPINAL-FLUID; IN-VIVO; PROTEIN; MUTANT; MODEL; 8-HYDROXYDEOXYGUANOSINE AB Although the cause of amyotrophic lateral sclerosis (ALS) is unknown, substantial evidence indicates that oxidative toxicity is associated with neuronal death in this disease. We examined levels of a well-established marker of oxidative damage to DNA, 8-hydroxy-2'-deoxyguanosine (8OH2'dG) in plasma, urine, and cerebrospinal fluid (CSF) at a single time point from subjects with ALS, other neurological diseases, or no known disorders. We also measured the rate of change of 8OH2'dG levels in plasma and urine from ALS and in urine from control subjects over 9 months and examined the relationship to disease severity. In each fluid, 8OH2'dG levels were significantly elevated in the ALS group as compared to control subjects. In all subjects, the plasma and CSF 8OH2'dG levels increased with age, providing further evidence for a role of oxidative damage in normal aging. Plasma and urine sOH2'dG levels increased significantly with time in the ALS group only. The rate of increase in urine 8OH2'dG levels with time was significantly correlated with disease severity. These findings are consistent with the hypothesis that oxidative pathology accompanies the neurodegenerative process in ALS and suggest that 8OH2'dG may provide a useful tool for monitoring therapeutic interventions in this disease. (C) 2000 Elsevier Science Inc. C1 Massachusetts Gen Hosp, Neurochem Lab, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Serv Neurol, New York, NY USA. Harvard Univ, Sch Med, Boston, MA USA. Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. ESA Inc, Chelmsford, MA USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Clin Trial Unit, Boston, MA USA. RP Cudkowicz, M (reprint author), Massachusetts Gen Hosp, Neurochem Lab, Neurol Serv, 15 Parkman St,WAC 836, Boston, MA 02114 USA. FU NIA NIH HHS [P01AG12292]; NINDS NIH HHS [R01NS36640, R01NS37912] NR 37 TC 170 Z9 177 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD OCT 1 PY 2000 VL 29 IS 7 BP 652 EP 658 DI 10.1016/S0891-5849(00)00349-X PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 367VR UT WOS:000090082600008 PM 11033417 ER PT J AU Mizoguchi, A Mizoguchi, E Saubermann, LJ Higaki, K Blumberg, RS Bhan, AK AF Mizoguchi, A Mizoguchi, E Saubermann, LJ Higaki, K Blumberg, RS Bhan, AK TI Limited CD4 T-cell diversity associated with colitis ire T-cell receptor alpha mutant mice requires a T helper 2 environment SO GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT 97th Annual Meeting of the American-Gastroenterological-Association, Digestive Disease Week CY MAY 10-16, 1997 CL WASHINGTON, D.C. SP Amer Gastroenterol Assoc ID INFLAMMATORY-BOWEL-DISEASE; CHAIN-DEFICIENT MICE; BETA-CHAIN; ANTIGEN RECEPTOR; AUTOIMMUNE ENCEPHALOMYELITIS; AUTOANTIBODY PRODUCTION; ULCERATIVE-COLITIS; TRANSGENIC MICE; IN-VIVO; TCR AB Background & Aims: T-cell receptor alpha mutant (TCR alpha(-/-)) mice spontaneously develop chronic colitis mediated by CD4(+) TCR alpha(-)beta(+) T cells, The aim of this study was to analyze the mechanisms of expansion of these cells by characterization of the TCR beta repertoire. Methods: TCR beta repertoire was analyzed by reverse-transcription polymerase chain reaction/Southern blot and DNA sequencing. Clonality of T cells was examined in the lymphoid tissues and colons of TCR alpha(-/-) mice and interleukin 4-deficient TCR alpha(-/-) mice, In addition, an in vitro culture system using syngeneic colonic epithelial cells as antigens was used. Results: The clonal expansion of a restricted subset of V beta 8.2(+) T cells was characterized by conservation of a single negatively charged amino acid residue in the second position of the complementarity-determining region 3 (CDR3), These T cells were observed in the diseased colon and appendix (cecal patch) of TCR alpha(-/-) mice, but not germfree TCR alpha(-/-) mice. Culture of polyclonal T cells from young TCR alpha(-/-) mice with colonic epithelial cells under T helper 2 conditions resulted in the survival of V beta 8.2(+) T cells characterized by the same CDR3 pattern. In addition, the transfer of the cultivated T cells induced mild colitis in recombination-activating gene 1 mutant mice. Conclusions: In the TCR alpha(-/-) mice, the development of colitis is associated with the presence of a restricted diversity of V beta 8.2(+) T-cell subsets characterized by a specific TCR motif, The limited diversity of lamina propria T cells that are derived from naive T cells expanded by reacting with luminal bacterial antigens is likely caused by the survival of these T cells after stimulation with self-antigens in the presence of a T helper 2 environment. C1 Massachusetts Gen Hosp, Dept Pathol, Immunopathol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Div Gastroenterol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Bhan, AK (reprint author), Massachusetts Gen Hosp, Dept Pathol, Immunopathol Unit, Cox 521,100 Blossom St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK47677, DK44319, DK51362] NR 62 TC 27 Z9 30 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2000 VL 119 IS 4 BP 983 EP 995 DI 10.1053/gast.2000.18153 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 363RF UT WOS:000089847800014 PM 11040185 ER PT J AU Schellingerhout, D Rainov, NG Breakefield, XO Weissleder, R AF Schellingerhout, D Rainov, NG Breakefield, XO Weissleder, R TI Quantitation of HSV mass distribution in a rodent brain tumor model SO GENE THERAPY LA English DT Article DE gene transfer; gene therapy; herpes simplex virus; imaging ID HERPES-SIMPLEX VIRUS; GREEN FLUORESCENT PROTEIN; GENE-THERAPY; IN-VIVO; SOLID TUMORS; BRADYKININ AGONIST; AMPLICON VECTORS; EXPRESSION; RMP-7; PERMEABILITY AB A number of different viral vectors have been used for gene therapy of tumors, with many more under construction, ultimately designed to improve tumor targeting and transduction efficiency. It has become apparent that insufficient viral delivery can be a key limitation to treatment efficacy. We have studied the in vivo mass distribution of a herpes simplex virus type 1 (HSV) vector, hrR3, by radiolabeling it with In-111-oxine. The virus was administered to intracerebral 9L glioma bearing Fisher (F-344) rats by intracarotid and intratumoral injection. The blood half-life of the virus was 1 min (fast component, 10% contribution) and 180 min (slow component, 90% contribution). Approximately 20% of activity had been excreted by 24 h. With intracarotid injection, the fetal amount of virus that accumulated in tumor was 0.10 +/- 0.07% of the injected dose (ID)/g at 1 h and 0.19 +/- 0.01% ID/g at 24 h. By comparison, co-injection of RMP-7, a synthetic bradykinin analog, with the virus, resulted in slightly increased tumor delivery of 0. 17 +/- 0.10% ID/g (P 0.05) at 1 h. The 1 h organ distribution after intra-arterial injection (%ID/organ) was as follows: liver 27.3 +/- 2.86%, lung 2.10 +/- 0.68% and kidney 1.78 +/- 1.60% with lesser amounts in other organs. When virus was injected directly into the tumor, 71% of virus remained in tumor at 24 h (590 +/- 212 %ID/g, consistent with the small tumor mass containing most of the virus) with the following distribution regions: tumor > border zone > normal brain (99.40:1). These studies are the first quantitative mass distribution studies of HSV vectors in an experimental brain tumor model. Localization and quantitation of viral accumulation in vivo will enable detailed analysis of viral and organ interactions critical for advancing the therapeutic use of vectors. C1 Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [P01CA48729, P01CA69246]; NINDS NIH HHS [R01NS35258] NR 46 TC 40 Z9 42 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD OCT PY 2000 VL 7 IS 19 BP 1648 EP 1655 DI 10.1038/sj.gt.3301272 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 362GL UT WOS:000089770200005 PM 11083473 ER PT J AU Kadam, S McAlpine, GS Phelan, ML Kingston, RE Jones, KA Emerson, BM AF Kadam, S McAlpine, GS Phelan, ML Kingston, RE Jones, KA Emerson, BM TI Functional selectivity of recombinant mammalian SWI/SNF subunits SO GENES & DEVELOPMENT LA English DT Article DE SWI/SNF; zinc fingers; chromatin; transcription; EKLF; beta-globin ID CHROMATIN REMODELING COMPLEX; SWI-SNF COMPLEX; TRANSCRIPTION FACTOR GATA-1; BETA-GLOBIN PROMOTER; IN-VITRO; HIV-1 ENHANCER; HISTONE ACETYLTRANSFERASE; GLUCOCORTICOID RECEPTOR; PARTIALLY REDUNDANT; BINDING PROTEIN AB The SWI/SNF family of chromatin-remodeling complexes plays a key role in facilitating the binding of specific transcription factors to nucleosomal DNA in diverse organisms from yeast to man. Yet the process by which SWI/SNF and other chromatin-remodeling complexes activate specific subsets of genes is poorly understood. We show that mammalian SWI/SNF regulates transcription from chromatin-assembled genes in a factor-specific manner in vitro. The DNA-binding domains (DBDs) of several zinc finger proteins, including EKLF, interact directly with SWI/SNE to generate DNase I hypersensitivity within the chromatin-assembled beta-globin promoter. Interestingly, we find that two SWI/SNE subunits (BRG1 and BAF155) are necessary and sufficient for targeted chromatin remodeling and transcriptional activation by EKLF in vitro. Remodeling is achieved with only the BRG1-BAF155 minimal complex and the EKLE zinc finger DBD, whereas transcription requires, in addition, an activation domain. In contrast, the BRG1-BAF155 complex does not interact or function with two unrelated transcription factors, TFE3 and NP-kappa B. We conclude that specific domains of certain transcription factors differentially target SWI/SNF complexes to chromatin in a gene-selective manner and that individual SWI/SNF subunits play unique roles in transcription factor-directed nucleosome remodeling. C1 Salk Inst Biol Studies, Regulatory Biol Lab, La Jolla, CA 92037 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Emerson, BM (reprint author), Salk Inst Biol Studies, Regulatory Biol Lab, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. NR 56 TC 167 Z9 173 U1 1 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD OCT 1 PY 2000 VL 14 IS 19 BP 2441 EP 2451 DI 10.1101/gad.828000 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 362EJ UT WOS:000089765400004 PM 11018012 ER PT J AU Firth, L Manchester, J Lorenzen, JA Baron, M Perkins, LA AF Firth, L Manchester, J Lorenzen, JA Baron, M Perkins, LA TI Identification of genomic regions that interact with a viable allele of the Drosophila protein tyrosine phosphatase corkscrew SO GENETICS LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAY; GROWTH-FACTOR RECEPTOR; CELL FATE DECISIONS; EGF RECEPTOR; EYE DEVELOPMENT; EMBRYONIC MESODERM; NEGATIVE REGULATOR; DOMAIN PROTEIN; MAP KINASE; TORSO RTK AB Signaling by receptor tyrosine kinases (RTKs) is critical for a multitude of developmental decisions and processes. Among the molecules known to transduce the RTK-generated signal is the nonreceptor protein tryosine phosphatase Corkscrew (Cs iv). Previously, Csw has been demonstrated to function throughout the Drosophila life cycle and, among the RTKs tested, Csw is essential in the Torso, Sevenless, EGF, and Breathless/FGF RTK pathways. While the biochemical function of Csw remains to be unambiguously elucidated, current evidence suggests that Csw plays more than one role during transduction of the RTK signal and, further, the molecular mechanism of Csw function differs depending upon the RTK in question. The isolation and characterization of a new, spontaneously arising, viable allele of csw, csw(lf) has allowed us to undertake a genetic approach to identify loci required for Csw function. The rough eye and wing vein gap phenotypes exhibited by adult flies homo- or hemizygous for csw(lf) has provided a sensitized background from which we have screened a collection of second and third chromosome deficiencies to identify 33 intervals that enhance and 21 intervals that suppress these phenotypes. We have identified intervals encoding known positive mediators of RTK signaling, e.g., drk, dos, Egfr; E(Egfr)B56, pnt, Ras1, rolled/MAPK: sina, spen, Src64B, Star, Su(Raf)3C, and vein, as well as known negative mediators of RTK signaling, e.g., aos, ed, net, Src42A, sty, and su(ve). Of particular interest are the 5 lethal enhancing intervals and 14 suppressing intervals for which no candidate genes have been identified. C1 Harvard Univ, Pediat Surg Res Labs, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Univ Manchester, Dept Biol Sci, Manchester M13 9PT, Lancs, England. RP Perkins, LA (reprint author), Harvard Univ, Pediat Surg Res Labs, Massachusetts Gen Hosp, Sch Med, Warren 10,32 Fruit St, Boston, MA 02114 USA. FU NIGMS NIH HHS [F32GM17901] NR 74 TC 13 Z9 13 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD OCT PY 2000 VL 156 IS 2 BP 733 EP 748 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 362EZ UT WOS:000089766800023 PM 11014820 ER PT J AU Jackson, SA Cheng, ZK Wang, ML Goodman, HM Jiang, JM AF Jackson, SA Cheng, ZK Wang, ML Goodman, HM Jiang, JM TI Comparative fluorescence in situ hybridization mapping of a 431-kb Arabidopsis thaliana bacterial artificial chromosome contig reveals the role of chromosomal duplications in the expansion of the Brassica rapa genome SO GENETICS LA English DT Article ID FLOWERING TIME; GENE-CLUSTER; MAIZE GENOME; REGIONS; SORGHUM; TOMATO; RICE; ORGANIZATION; SEQUENCE; NAPUS AB Comparative genome studies are important contributors to our understanding of genome evolution. Most comparative genome studies in plants have been based on genetic mapping of homologous DNA loci in different genomes. Large-scale comparative physical mapping has been hindered by the lack of efficient and affordable techniques. We report here the adaptation of fluorescence in situ hybridization (FISH) techniques for comparative physical mapping between Arabidopsis thaliana and Brassica rapa. A set of six bacterial artificial chromosomes (BACs) representing a 431-kb contiguous region of chromosome 2 of A. thaliana was mapped on both chromosomes and DNA fibers of B. rapa. This DNA fragment has a single location in the A. thaliana genome, but hybridized to four to six B. rapa chromosomes, indicating multiple duplications in the B. ra;ba genome. The sizes of the fiber-FISH signals from the same BACs were not longer in B. rapa than those in A. thaliana, suggesting that this genomic region is duplicated but not expanded in the B. mpa genome. The comparative fiber-FISH mapping results support that chromosomal duplications, rather than regional expansion due to accumulation of repetitive sequences in the intergenic regions, played the major role in the evolution of the B. rapa genome. C1 Univ Wisconsin, Dept Hort, Madison, WI 53706 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Jiang, JM (reprint author), Univ Wisconsin, Dept Hort, 1575 Linden Dr, Madison, WI 53706 USA. RI Jiang, Jiming/A-9614-2009 NR 35 TC 65 Z9 82 U1 0 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD OCT PY 2000 VL 156 IS 2 BP 833 EP 838 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 362EZ UT WOS:000089766800031 PM 11014828 ER PT J AU Zhang, LJ Lawrence, R Rosenberg, RD AF Zhang, LJ Lawrence, R Rosenberg, RD TI The biosynthetic pathway for generating the antithrombin binding site on heparan sulfate SO GLYCOBIOLOGY LA English DT Meeting Abstract C1 MIT, Cambridge, MA 02139 USA. BIDMC, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD OCT PY 2000 VL 10 IS 10 MA 32 BP 1086 EP 1086 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 360JN UT WOS:000089664300044 ER PT J AU Chang, L Munakata, J Mayer, EA Schmulson, MJ Johnson, TD Bernstein, CN Saba, L Naliboff, B Anton, PA Matin, K AF Chang, L Munakata, J Mayer, EA Schmulson, MJ Johnson, TD Bernstein, CN Saba, L Naliboff, B Anton, PA Matin, K TI Perceptual responses in patients with inflammatory and functional bowel disease SO GUT LA English DT Article DE ulcerative colitis; irritable bowel syndrome; abdominal pain ID IRRITABLE-BOWEL; ULCERATIVE-COLITIS; RECTAL DISTENSION; VISCERAL PAIN; SENSITIVITY; HYPERALGESIA; DISORDERS; DYSPEPSIA; SYMPTOMS; OPIOIDS AB Background and aims-Enhanced visceral sensitivity following a transient inflammatory process in the got has been postulated as an aetiological mechanism of irritable bowel syndrome (IBS). In this study we compared perceptual responses to rectosigmoid distension in patients with mild chronic inflammation of the rectum (ulcerative colitis (UC)) and patients without mucosal inflammation (IBS) to determine if chronic low grade mucosal inflammation may be a plausible explanation for rectosigmoid hypersensitivity reported in both IBS and UC patients. Methods-UC disease activity was quantified using activity index scores. Perception thresholds for discomfort during rectosigmoid distension were compared between 11 UC patients with quiescent or mild disease activity, 18 IBS patients, and 13 healthy controls. Results-Although UC activity index scores negatively correlated with perceptual thresholds for discomfort (r=-0.76, p=0.016), UC patients had higher discomfort thresholds compared with IBS patients and controls before (p=0.02) and after (p<0.001) a noxious sigmoid conditioning stimulus. Conclusions-Rectal perception was attenuated in UC but enhanced in IBS. in chronic mild inflammation, activation of antinociceptive mechanisms may prevent the development of visceral hyperalgesia. Low grade mucosal inflammation alone is unlikely to be responsible for symptoms in functional gastrointestinal disorders. C1 Univ Calif Los Angeles, Dept Med & Physiol, Neuroenter Dis Program, W Los Angeles VA Med Ctr,Sch Med,CURE, Los Angeles, CA 90073 USA. Harbor UCLA Med Ctr, Ctr Inflammatory Bowel Dis, Torrance, CA 90509 USA. Univ Calif Los Angeles, Sch Med, Dept Biomath, Los Angeles, CA 90024 USA. Univ Manitoba, Dept Med, Winnipeg, MB, Canada. RP Chang, L (reprint author), Univ Calif Los Angeles, Dept Med & Physiol, Neuroenter Dis Program, W Los Angeles VA Med Ctr,Sch Med,CURE, Bldg 115,Room 223, Los Angeles, CA 90073 USA. EM linchang@ucla.edu NR 40 TC 120 Z9 121 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD OCT PY 2000 VL 47 IS 4 BP 497 EP 505 DI 10.1136/gut.47.4.497 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 358AQ UT WOS:000089535400010 PM 10986209 ER PT J AU Dore, MP Sepulveda, AR El-Zimaity, HMT Yamaoka, Y Osato, MS Kato, M Nieddu, AM Graham, DY Realdi, G AF Dore, MP Sepulveda, AR El-Zimaity, HMT Yamaoka, Y Osato, MS Kato, M Nieddu, AM Graham, DY Realdi, G TI Isolation of Helicobacter pylori from sheep: Implications for transmission to humans. SO GUT LA English DT Meeting Abstract C1 Univ Sassari, I-07100 Sassari, Italy. VA Med Ctr, Houston, TX 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 OCT PY 2000 VL 47 SU 1 BP A46 EP A46 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 368RK UT WOS:000090131200175 ER PT J AU El-Zimaity, HMT Yuksul, M Ramchatesingh, J El-Zaatari, FAK Gutierrez, O Dore, MP Graham, DY AF El-Zimaity, HMT Yuksul, M Ramchatesingh, J El-Zaatari, FAK Gutierrez, O Dore, MP Graham, DY TI Natural history of gene rearrangement in patients with malt and malt lymphoma. SO GUT LA English DT Meeting Abstract C1 VA Med Ctr, Houston, TX USA. Univ Nacl Colombia, Bogota, Colombia. NR 0 TC 0 Z9 0 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 OCT PY 2000 VL 47 SU 1 BP A71 EP A71 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 368RK UT WOS:000090131200254 ER PT J AU Fox, JG Taylor, NS Ihrig, M Esteves, MI Chung, RT Kaplan, MM AF Fox, JG Taylor, NS Ihrig, M Esteves, MI Chung, RT Kaplan, MM TI Helicobacter spp. serum antibodies in patients with primary sclerosing cholangitis. SO GUT LA English DT Meeting Abstract C1 MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 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 OCT PY 2000 VL 47 SU 1 BP A67 EP A67 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 368RK UT WOS:000090131200243 ER PT J AU Fox, JG Perkins, SE Dewhirst, FE Taylor, NS Shen, Z Xu, S AF Fox, JG Perkins, SE Dewhirst, FE Taylor, NS Shen, Z Xu, S TI Novel Helicobacter species identified from random source dogs. SO GUT LA English DT Meeting Abstract C1 MIT, Cambridge, MA 02139 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 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 OCT PY 2000 VL 47 SU 1 BP A68 EP A68 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 368RK UT WOS:000090131200247 ER PT J AU Graham, DY AF Graham, DY TI Effect of H-pylori status on the effectiveness of omeprazole for prevention of gastric or duodenal ulcers among chronic NSAID users. SO GUT LA English DT Meeting Abstract C1 VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 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 OCT PY 2000 VL 47 SU 1 BP A77 EP A77 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 368RK UT WOS:000090131200276 ER PT J AU Graham, DY Gutierrez, O Gomez, M Yamaoka, Y El-Zimaity, HMT AF Graham, DY Gutierrez, O Gomez, M Yamaoka, Y El-Zimaity, HMT TI Interleukin-1 (IL-1) is the likely mediator of reduced acid secretion associated with Corpus Gastritis. SO GUT LA English DT Meeting Abstract C1 VA Med Ctr, Houston, TX USA. Univ Nacl Colombia, Bogota, Colombia. 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 OCT PY 2000 VL 47 SU 1 BP A38 EP A38 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 368RK UT WOS:000090131200147 ER PT J AU Malaty, HM Graham, DY ELKasabany, A Reddy, SG Srinivasan, SR Berenson, GS AF Malaty, HM Graham, DY ELKasabany, A Reddy, SG Srinivasan, SR Berenson, GS TI Natural history of Helicobacter pylori infection from infancy to adulthood: A 21-year follow-up cohort study. SO GUT LA English DT Meeting Abstract C1 VA Med Ctr, Houston, TX USA. Tulane Sch Publ Hlth, New Orleans, LA 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 OCT PY 2000 VL 47 SU 1 BP A45 EP A45 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 368RK UT WOS:000090131200171 ER PT J AU Nurgalieva, ZZ Graham, DY Almuchambetova, R Machmudova, A Osato, MS Peacock, J Marchildon, PA Zoltek, RP Zhangabylov, A AF Nurgalieva, ZZ Graham, DY Almuchambetova, R Machmudova, A Osato, MS Peacock, J Marchildon, PA Zoltek, RP Zhangabylov, A TI Storage and transportation of blood samples from developing countries: A dry plasma collection device not affected by freeze-thaw. SO GUT LA English DT Meeting Abstract C1 VA Med Ctr, Houston, TX USA. Almaty State Med Univ, Almaty, Kazakhstan. EPI, Stony Brook, NY USA. Chemat Inc, N Webster, IN USA. NR 0 TC 0 Z9 0 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 OCT PY 2000 VL 47 SU 1 BP A47 EP A47 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 368RK UT WOS:000090131200180 ER PT J AU Patterson, MM Schrenzel, MD Feng, Y Xu, S Thibodeau, SA Versalovic, J Dewhirst, FE Paster, BJ Fox, JG AF Patterson, MM Schrenzel, MD Feng, Y Xu, S Thibodeau, SA Versalovic, J Dewhirst, FE Paster, BJ Fox, JG TI Helicobacter aurati sp nov associated with gastritis and intestinal metaplasia in Syrian hamsters. SO GUT LA English DT Meeting Abstract C1 MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD OCT PY 2000 VL 47 SU 1 BP A67 EP A67 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 368RK UT WOS:000090131200242 ER PT J AU Shiotani, A Saeed, MA Yamaoka, Y El-Zimaity, HMT Osato, MS Klein, PD Graham, DY AF Shiotani, A Saeed, MA Yamaoka, Y El-Zimaity, HMT Osato, MS Klein, PD Graham, DY TI Citric acid enhanced gastric urease activity in man is unrelated to gastric emptying. SO GUT LA English DT Meeting Abstract C1 VA Med Ctr, Houston, TX USA. Meretek, Houston, TX USA. NR 0 TC 0 Z9 0 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 OCT PY 2000 VL 47 SU 1 BP A120 EP A120 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 368RK UT WOS:000090131200434 ER PT J AU Brendel, DH AF Brendel, DH TI Philosophy of mind in the clinic: The relation between causal and meaningful explanation in psychiatry SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article; Proceedings Paper CT Annual Meeting of the Eastern Division of the American-Philosophical-Association CY DEC, 1999 CL BOSTON, MASSACHUSETTS SP Amer Philosoph Assoc ID DISEASE; MODEL AB Conceptual dichotomies between mind and brain, psychology and neuroscience, meaning and causation, and fact and value confound thinking in philosophy of mind, clinical psychiatry, and psychiatric ethics. Paul Churchland's theory of eliminative materialism highlights these dichotomies, stating that advances in neuroscience have restricted, and eventually will eliminate, any need for psychology. The core principles of this theory are questionable, because psychiatrists still need psychology and perhaps always will. The main argument in this essay is that even in cases of well-defined brain pathology (where eliminative materialism seems most plausible), psychological concepts remain critical. Thus, philosophers and psychiatrists should generate conceptual models that lead not to eliminativism but to explanatory pluralism, which is the pragmatic integration of diverse concepts toward the end of better handling clinical challenges. The contributions of Karl Jaspers in opposition to eliminative materialism and in support of pluralism are discussed. Jaspers delineated the role of meaningful psychological explanation in a psychiatry rooted in neuroscientific explanation. However, his notion that meaningful states do not have causal power is disputable and has come under fire in recent philosophy of mind and cognitive neuroscience, which highlight the possibility that meaningful psychological states can be causally significant. This idea has implications for psychiatric ethics and the fact/value debate. C1 McLean Hosp, Dept Psychiat, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Brendel, DH (reprint author), McLean Hosp, Dept Psychiat, 115 Mill St, Belmont, MA 02478 USA. NR 45 TC 10 Z9 11 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD OCT PY 2000 VL 8 IS 4 BP 184 EP 191 DI 10.1093/hrp/8.4.184 PG 8 WC Psychiatry SC Psychiatry GA 367DD UT WOS:000090045700003 PM 11038343 ER PT J AU Coffey, BJ Biederman, J Geller, DA Spencer, T Park, KS Shapiro, SJ Garfield, SB AF Coffey, BJ Biederman, J Geller, DA Spencer, T Park, KS Shapiro, SJ Garfield, SB TI The course of Tourette's disorder: A literature review SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID TIC DISORDERS; CHILDREN; PSYCHOPATHOLOGY; PREVALENCE; ADULTS AB With the goal of evaluating the available literature on the course of Tourette's disorder, we conducted a systematic literature search through electronic databases for pertinent scientific articles in English with a minimum of 20 subjects. We also examined bibliographies of papers identified in this manner for additional sources. We found only 16 articles; most consisted of retrospective reports on treated samples. Overall, the available literature suggests that Tourette's disorder follows a remitting course in a sizeable number of individuals. Little has been published regarding predictors of remission or persistence. More work is needed using longitudinal prospective studies to better define the course and outcome of Tourette's disorder. C1 McLean Hosp, Joint Program Pediat Psychopharmacol, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Clin Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. RP Coffey, BJ (reprint author), McLean Hosp, Joint Program Pediat Psychopharmacol, Recreat Bldg,115 Mill St, Belmont, MA 02478 USA. NR 42 TC 22 Z9 22 U1 2 U2 5 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD OCT PY 2000 VL 8 IS 4 BP 192 EP 198 DI 10.1093/hrp/8.4.192 PG 7 WC Psychiatry SC Psychiatry GA 367DD UT WOS:000090045700004 PM 11038344 ER PT J AU Kornbluh, R Sharfstein, SS Kleinschmidt, TL AF Kornbluh, R Sharfstein, SS Kleinschmidt, TL TI Overscrutinized and undersupported: A resident treats a "capitated" patient SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID MANAGED-CARE; PERSONALITY-DISORDERS; EDUCATION; ERA C1 McLean Hosp, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Univ Maryland, Sheppard Pratt Hlth Syst, Baltimore, MD 21201 USA. Univ Maryland, Dept Psychiat, Baltimore, MD 21201 USA. RP Kornbluh, R (reprint author), McLean Hosp, 115 Mill St, Belmont, MA 02478 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1067-3229 EI 1465-7309 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD OCT PY 2000 VL 8 IS 4 BP 199 EP 205 DI 10.1093/hrp/8.4.199 PG 7 WC Psychiatry SC Psychiatry GA 367DD UT WOS:000090045700005 PM 11038345 ER PT J AU Deschler, DG Hayden, RE AF Deschler, DG Hayden, RE TI The optimum method for reconstruction of complex lateral oromandibular-cutaneous defects SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Article; Proceedings Paper CT 4th International Conference on Head and Neck Surgery CY JUL 28-AUG 01, 1996 CL TORONTO, CANADA DE oromandibular reconstruction; through and through defect; scapula free flap ID MANDIBULAR RECONSTRUCTION; FREE-FLAP AB Background. Ablation of large intraoral cancers can create extensive through-and-through defects of the lateral face. resulting in loss of external facial skin, the lateral and anterior mandible. and the lateral mouth. Repair requires reconstruction of the lips. mandible, and full-thickness cheek defects. Ideal reconstruction with vascularized composite free flaps requires adequate bone and sufficiently large, yet versatile, skin flaps capable of resurfacing extensive intraoral and external defects. Methods. A series of 12 patients with large lateral facial-mandibular detects is reviewed. All patients were treated for squamous cell carcinoma except for 1 patient with osteoblastic sarcoma of the mandible. All patients underwent primary reconstruction with various free flap techniques, including 6 scapular free flaps, 2 iliac crest free flaps, 3 free fibula flaps, and 1 radial forearm flap. Attainment of reconstructive goals, free flap survival. and complication rates were assessed. Results. All defects were successfully reconstructed in the primary setting. No flap failures occurred. One venous occlusion was successfully salvaged. No orocutaneous fistulas or postoperative hematomas were noted. Conclusion. The reconstructive options for extensive defects of the lateral face and jaw are reviewed with attention to the complex three-dimensional soft tissue requirements. The superiority of the scapular composite flap is emphasized because this single free flap provides two independent and versatile skin paddles of optimal thickness in addition to adequate bone stock. (C) 2000 John Wiley & Sons, Inc. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. MCPHU, Dept Otolaryngol Head & Neck Surg, Philadelphia, PA USA. RP Deschler, DG (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. NR 11 TC 32 Z9 36 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD OCT PY 2000 VL 22 IS 7 BP 674 EP 679 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 356RF UT WOS:000089456000006 PM 11002322 ER PT J AU Yoshida, N Liberman, MC AF Yoshida, N Liberman, MC TI Sound conditioning reduces noise-induced permanent threshold shift in mice SO HEARING RESEARCH LA English DT Article DE sound conditioning; acoustic trauma; noise-induced hearing loss; protection ID INDUCED HEARING-LOSS; ACOUSTIC INJURY; ACQUIRED-RESISTANCE; TRAUMATIC EXPOSURE; PROTECTION; STIMULUS AB The phenomenon of conditioning-related protection, whereby prior exposure to moderate-level, non-traumatic, sound protects the ear from subsequent traumatic exposure, has been documented in a number of mammalian species. To probe the molecular mechanisms underlying this effect, the mouse would be a useful model; however, a previous study reported no conditioning effects in this species (Fowler et al., 1995). In our study, mice (CBA/CaJ) were exposed to a traumatic octave-band noise (8-16 kHz at 100 dB SPL for 2 h) with, or without, prior exposure to a sound-conditioning protocol consisting of exposure to the same noise band at lower sound pressure levels. Two conditioning protocols were investigated: one (81 dB SPL for 1 week) was analogous to those used in other conditioning studies in mammals; the second was significantly shorter (89 dB SPL for 15 min). Noise-induced permanent threshold shift (PTS) was assessed in a terminal experiment, after the traumatic exposure, via compound action potentials. Neither conditioning protocol elevated threshold, indeed both protocols increased amplitudes of distortion product otoacoustic emissions when animals were conditioned but not traumatized. Both conditioning exposures significantly reduced PTS from the subsequent traumatic exposure, compared to groups exposed without prior conditioning. Protective effects of 15-min conditioning were maximal when the condition-trauma interval was 24 h; protection disappeared when the traumatic exposure was presented 48 h after conditioning. These data are consistent with the view that protein synthesis is required for expression of the protective effect. The enhancement of distortion products in the condition-only state suggests that conditioning changes outer hair cell function. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Tohoku Univ, Sch Med, Dept Otolaryngol, Sendai, Miyagi 9808574, Japan. RP Liberman, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [P30 DC005209, R01 DC0188] NR 20 TC 55 Z9 61 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 OCT PY 2000 VL 148 IS 1-2 BP 213 EP 219 DI 10.1016/S0378-5955(00)00161-1 PG 7 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 354DX UT WOS:000089315500019 PM 10978838 ER PT J AU Fontana, RJ Perillo, R Hann, HWL Wright, T Rakela, J Bacon, BR Anschuetz, G Gardner, SD Brown, NA AF Fontana, RJ Perillo, R Hann, HWL Wright, T Rakela, J Bacon, BR Anschuetz, G Gardner, SD Brown, NA TI Determinants of survival in 133 patients with decompensated chronic hepatitis B treated with lamivudine. SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. Oschner Clin, New Orleans, LA USA. Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. San Francisco VA Med Ctr, San Francisco, CA USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. St Louis Sch Med, St Louis, MO USA. Glaxo Wellcome Inc, RTP, NC USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2000 VL 32 IS 4 MA 239 BP 221A EP 221A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400235 ER PT J AU Chung, RT He, WP Saquib, A Schmidt, EV AF Chung, RT He, WP Saquib, A Schmidt, EV TI Interferon alfa but not ribavirin directly inhibits RNA and protein synthesis in a novel cell-based replication system. SO HEPATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2000 VL 32 IS 4 MA 261 BP 226A EP 226A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400256 ER PT J AU Chung, RT Contreras, AM Baid, S Consimi, AB Pascual, M Feng, S AF Chung, RT Contreras, AM Baid, S Consimi, AB Pascual, M Feng, S TI Low-dose immunosuppresion is asssociated with narrowing of HCV quasispecies diversity following liver trasplantation. SO HEPATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2000 VL 32 IS 4 MA 396 BP 260A EP 260A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400390 ER PT J AU Lauer, GM Nguyen, TN Chung, RT Walker, BD AF Lauer, GM Nguyen, TN Chung, RT Walker, BD TI Frequent detection of HCV specific CTL recognizing previously undescribed or NON-A2 restricted epitopes in HLA-A2 positive individuals. SO HEPATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2000 VL 32 IS 4 MA 435 BP 270A EP 270A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400431 ER PT J AU Nguyen, TN Lauer, GM Chung, RT Walker, BD AF Nguyen, TN Lauer, GM Chung, RT Walker, BD TI Cellular immune response in HIV/HCV co-infection. SO HEPATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2000 VL 32 IS 4 MA 434 BP 270A EP 270A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400429 ER PT J AU Schiff, ER Heathcote, J Dienstag, JL Hann, HWL Woessner, M Brown, N Dent, JC Gray, F Goldin, RD AF Schiff, ER Heathcote, J Dienstag, JL Hann, HWL Woessner, M Brown, N Dent, JC Gray, F Goldin, RD TI Improvements in liver histology and cirrhosis with extended lamivudine therapy. SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ Miami, Miami, FL 33152 USA. Toronto Hosp, Toronto, ON M5T 2S8, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. Glaxo Wellcome Res & Dev Ltd, Greenford, Middx, England. St Marys Hosp, Sch Med, London, England. NR 0 TC 14 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2000 VL 32 IS 4 MA 546 BP 296A EP 296A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400534 ER PT J AU Beymer, CH Boyko, EJ Dominitz, JA AF Beymer, CH Boyko, EJ Dominitz, JA TI The association of diabetes mellitus with hepatitis C virus infection in a seroprevalence survey of the general US population 1988 to 1994. SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ Washington, Sch Med, Seattle, WA 98195 USA. VA Puget Sound HCS, Seattle, WA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2000 VL 32 IS 4 MA 616 BP 313A EP 313A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400603 ER PT J AU Rudolph, LK DePinho, RA AF Rudolph, LK DePinho, RA TI Telomere shortening inhibits hepatocarcinogenesis in diethylnitrosamine (DEN) treated telomerase deficient mice. SO HEPATOLOGY 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 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 OCT PY 2000 VL 32 IS 4 MA 640 BP 319A EP 319A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400627 ER PT J AU Kweon, YO Hill, C Goodman, ZD Dienstag, JL Schiff, ER Brown, NA Brenner, DA Fried, MW AF Kweon, YO Hill, C Goodman, ZD Dienstag, JL Schiff, ER Brown, NA Brenner, DA Fried, MW TI Lamivudine decreases fibrogenesis in chronic hepatitis B: An immunohistochemical study of paired liver biopsies. SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ N Carolina, Chapel Hill, NC 27515 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Miami, Miami, FL 33152 USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2000 VL 32 IS 4 MA 870 BP 377A EP 377A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400858 ER PT J AU Schiff, ER Cianciara, J Willems, B Karayalcin, S Brown, NA Woessner, M Marr, CL Gray, F Dienstag, JL AF Schiff, ER Cianciara, J Willems, B Karayalcin, S Brown, NA Woessner, M Marr, CL Gray, F Dienstag, JL TI Durability of hBeAg responses to lamivudine and interferon in the early post-treatment period in adults with chronic hepatitis B. SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ Miami, Miami, FL 33152 USA. Med Sch Warsaw, Warsaw, Poland. St Luc Hosp, Montreal, PQ, Canada. Ankara Univ, Sch Med, TR-06100 Ankara, Turkey. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. Glaxo Wellcome PLC, Greenford, Middx, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2000 VL 32 IS 4 MA 872 BP 377A EP 377A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622400859 ER PT J AU Hoppin, AG Premdas, J Davis, PJ Kaplan, LM AF Hoppin, AG Premdas, J Davis, PJ Kaplan, LM TI Identification of genetically determined events underlying non-alcoholic fatty liver disease. SO HEPATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2000 VL 32 IS 4 MA 1050 BP 422A EP 422A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 359PZ UT WOS:000089622401037 ER PT J AU Ganguly, A AF Ganguly, A TI 6B9, anti-alpha 2,6-sialyltransferase SO HYBRIDOMA LA English DT Article C1 Canc Biol Lab, Boston, MA 02215 USA. RP Ganguly, A (reprint author), Canc Biol Lab, 21-27 Burlington Av,BIDMC,POB 15709, Boston, MA 02215 USA. NR 1 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 0272-457X J9 HYBRIDOMA JI Hybridoma PD OCT PY 2000 VL 19 IS 5 BP 421 EP 421 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Immunology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology GA 378CD UT WOS:000165565900011 ER PT J AU Levy, D DeStefano, AL Larson, MG O'Donnell, CJ Lifton, RP Gavras, H Cupples, LA Myers, RH AF Levy, D DeStefano, AL Larson, MG O'Donnell, CJ Lifton, RP Gavras, H Cupples, LA Myers, RH TI Evidence for a gene influencing blood pressure on chromosome 17 - Genome scan linkage results for longitudinal blood pressure phenotypes in subjects from the Framingham Heart Study SO HYPERTENSION LA English DT Article DE genetics; genome scan; linkage; epidemiology; hypertension, essential; blood pressure; Framingham Heart Study ID EPITHELIAL SODIUM-CHANNEL; ESSENTIAL-HYPERTENSION; RAT CHROMOSOME-10; RECEPTOR LOCUS; MUTATIONS; ANGIOTENSINOGEN; ASSOCIATION; DISSECTION; SUBUNIT; CELLS AB Hypertension is a leading cause of morbidity and mortality. Efforts to identify hypertension genes have focused on 3 approaches: mendelian disorders, candidate genes, and genome-wide scans. Thus far, these efforts have not identified genes that contribute substantively to overall blood pressure (BP) variation in the community. A 10-centiMorgan (cM) density genome-wide scan was performed in the largest families from 2 generations of Framingham Heart Study participants. Heritability and linkage for long-term mean systolic and diastolic BP phenotypes were analyzed by use of SOLAR software. Heritability estimates were based on BP measurements in 1593 families. Genotyping was performed on 1702 subjects from 332 large families, and BP data were available for 1585 (93%) genotyped subjects who contributed 12 588 longitudinal BP observations. The mean age was 47 years, and mean BP was 127/80 (systolic/diastolic) mm Hg. Long-term systolic and diastolic BP phenotypes had high heritability estimates, 0.57 and 0.56, respectively. For systolic BP, multipoint log-of-the-odds (LOD) scores >2.0 were located on chromosome 17 at 67 cM (LOD 4.7, P=0.0000016) and 94 cM (LOD 2,2). For diastolic BP, LOD scores >2.0 were identified on chromosome 17 (74 cM, LOD 2.1) and chromosome 18 (7 cM, LOD 2.1). Using a genome-wide scan, we found strong evidence for a BP quantitative trait locus on chromosome 17. Follow-up studies are warranted to identify the gene or genes in this quantitative trait locus that influence BP. Such knowledge could extend our understanding of the genetic basis of essential hypertension and have implications for the evaluation and treatment of patients with high BP. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Div Cardiol, Boston, MA 02118 USA. Boston Univ, Sch Med, Genet Program, Boston, MA 02118 USA. Boston Univ, Sch Med, Hypertens Sect, Dept Med, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Div Cardiol, Boston, MA 02114 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, New Haven, CT 06510 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Med, New Haven, CT 06510 USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. FU NHLBI NIH HHS [N01-HC-38038, P50HL55001, P50HL55007] NR 35 TC 415 Z9 433 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2000 VL 36 IS 4 BP 477 EP 483 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 368GT UT WOS:000090109900003 PM 11040222 ER PT J AU Lloyd-Jones, DM Evans, JC Larson, MG O'Donnell, CJ Roccella, EJ Levy, D AF Lloyd-Jones, DM Evans, JC Larson, MG O'Donnell, CJ Roccella, EJ Levy, D TI Differential control of systolic and diastolic blood pressure - Factors associated with lack of blood pressure control in the community SO HYPERTENSION LA English DT Article DE hypertension detection and control; blood pressure; epidemiology; antihypertensive therapy ID CORONARY HEART-DISEASE; PULSE PRESSURE; CARDIOVASCULAR MORTALITY; HYPERTENSION; FRAMINGHAM; POPULATION; RISK; PREVALENCE AB Data from the Third National Health and Nutrition Examination Survey, phase 2 (1991 to 1994), indicate that among hypertensive individuals in the United States, 53.6% are treated and only 27.4% are controlled to goal levels. We sought to determine whether poor hypertension control is due to lack of systolic or diastolic blood pressure control, or both. We studied Framingham Heart Study participants examined between 1990 and 1995 and determined rates of control to systolic goal (<140 mm Hg), diastolic goal (<90 mm Hg), or both (systolic <140 and diastolic <90 mm Hg). Of 1959 hypertensive subjects (mean age 66 years, 54% women), 32.7% were controlled to systolic goal, 82.9% were controlled to diastolic goal, and only 29.0% were controlled to both. Among the 1189 subjects who were receiving antihypertensive therapy (60.7% of all hypertensive subjects), 49.0% were controlled to systolic goal, 89.7% were controlled to diastolic goal, and only 47.8% were controlled to both. Thus, poor systolic blood pressure control was overwhelmingly responsible for poor rates of overall control to goal. Covariates associated with lack of systolic control in treated subjects included older age (OR for age 61 to 75 years, 2.43, 95% CI 1.79 to 3.29; OR for age >75 years, 4.33, 95% CI 3.10 to 6.09), left ventricular hypertrophy (OR 1.63, 95% CI 1.04 to 2.54), and obesity (OR for body mass index greater than or equal to 30 versus <25 kg/m(2), 1.49, 95% CI 1.08 to 2.06). In this community-based sample of middle-aged and older subjects, overall rates of hypertension control were remarkably similar to those in the Third National Health and Nutrition Examination Survey. Poor blood pressure control was overwhelmingly due to lack of systolic control, even among treated subjects. Therefore, clinicians and policymakers should place greater emphasis on the achievement of goal systolic levels in all hypertensive patients, especially those who are older or obese or have target organ damage. C1 NHLBI, Farmingham Heart Study, Framingham, MA 01702 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA USA. Boston Univ, Sch Med, Dept Epidemiol & Prevent Med, Boston, MA 02118 USA. NHLBI, Natl High Blood Pressure Educ Program, Bethesda, MD 20892 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. RP Levy, D (reprint author), NHLBI, Farmingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. RI Lloyd-Jones, Donald/C-5899-2009 NR 28 TC 231 Z9 242 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2000 VL 36 IS 4 BP 594 EP 599 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 368GT UT WOS:000090109900022 PM 11040241 ER PT J AU O'Regan, AW Nan, GJ Chupp, GL Berman, JS AF O'Regan, AW Nan, GJ Chupp, GL Berman, JS TI Osteopontin (Eta-1) in cell-mediated immunity: teaching an old dog new tricks SO IMMUNOLOGY TODAY LA English DT Article ID MICE LACKING; GRANULOMAS AB Previously regarded as an adhesive bone matrix protein, recent studies suggest that osteopontin (Eta-1) is also a novel RGD-containing cytokine that regulates early cell-mediated immunity. Proteins related to the extracellular matrix may function as important modulators of immune responses. C1 Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Yale Univ, Sch Med, Pulm & Crit Care Med Sect, New Haven, CT 06520 USA. RP O'Regan, AW (reprint author), Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. FU NHLBI NIH HHS [HL04343, HL63339, P50-HL56386] NR 18 TC 133 Z9 136 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0167-5699 J9 IMMUNOL TODAY JI Immunol. Today PD OCT PY 2000 VL 21 IS 10 BP 475 EP 478 DI 10.1016/S0167-5699(00)01715-1 PG 4 WC Immunology SC Immunology GA 366EE UT WOS:000089991200003 PM 11071524 ER PT J AU Cherayil, BJ McCormick, BA Bosley, J AF Cherayil, BJ McCormick, BA Bosley, J TI Salmonella enterica serovar typhimurium-dependent regulation of inducible nitric oxide synthase expression in macrophages by invasins SipB, SipC, and SipD and effector SopE2 SO INFECTION AND IMMUNITY LA English DT Article ID INTESTINAL EPITHELIAL-CELLS; INFLAMMATORY BOWEL-DISEASE; PROTEIN SECRETION SYSTEM; BACTERIAL INTERNALIZATION; NUCLEAR RESPONSES; BINDING; DUBLIN; BACTERIOPHAGE; DETERMINANTS; PHOSPHATASE AB When Salmonella enterica invades mammalian cells, it activates signals leading to increased expression of inflammatory mediators. One such mediator is nitric oxide (NO), which is produced under control of the enzyme inducible NO synthase (iNOS). Induction of iNOS in response to Salmonella infection has been demonstrated, but the bacterial effector molecules that regulate expression of the enzyme have not been identified. In the study reported here, an analysis of Salmonella-dependent iNOS expression in macrophages was carried out. Wild-type Salmonella strains increased the levels of both iNOS protein and mRNA in murine macrophage cell lines in an invasion-independent fashion. Mutant strains lacking a functional pathogenicity island 1-encoded type III secretion system, as well as strains lacking the invasins SipB, SipC, and SipD, were impaired in iNOS induction. Complementation experiments indicated that all three of the invasins were required for induction of iNOS expression. These results suggested that an effector protein, translocated into macrophages via the type III secretion system in a SipB-, SipC-, and SipD-dependent manner, might be the ultimate mediator of iNOS induction. In keeping with this idea, a mutant strain deficient in SopE2, a recently described homolog of SopE, was found to be impaired in the induction of iNOS expression. These observations suggest that iNOS expression is regulated by signals activated by SopE2 land possibly SopE) and that the role of SipB, SipC, and SipD in this process is to facilitate translocation of the relevant effector. C1 Massachusetts Gen Hosp, Mucosal Immunol Lab, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. RP Cherayil, BJ (reprint author), Massachusetts Gen Hosp, Mucosal Immunol Lab, Combined Program Pediat Gastroenterol & Nutr, Rm 3303,MGH E,Bldg 149,13th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [T-32-DK-07477, DK-50989, T32 DK007477] NR 42 TC 30 Z9 30 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 2000 VL 68 IS 10 BP 5567 EP 5574 DI 10.1128/IAI.68.10.5567-5574.2000 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 355QE UT WOS:000089395700014 PM 10992455 ER PT J AU Melby, PC Ogden, GB Flores, HA Zhao, WG Geldmacher, C Biediger, NM Ahuja, SK Uranga, J Melendez, M AF Melby, PC Ogden, GB Flores, HA Zhao, WG Geldmacher, C Biediger, NM Ahuja, SK Uranga, J Melendez, M TI Identification of vaccine candidates for experimental visceral leishmaniasis by immunization with sequential fractions of a cDNA expression library SO INFECTION AND IMMUNITY LA English DT Article ID IMMUNE-RESPONSES; PLASMID DNA; ANTIGENIC DETERMINANTS; MAMMALIAN-CELLS; DONOVANI; INFECTION; MICE; IMMUNOSUPPRESSION; TRANSLATION; PROTECTION AB Visceral leishmaniasis caused by the intracellular parasite Leishmania donovani is a significant public health problem in many regions of the world. Because of its large genome and complex biology, developing a vaccine for this pathogen has proved to be a challenging task and, to date, protective recombinant vaccine candidates have not been identified. To tackle this difficult problem, we adopted a reductionist approach with the intention of identifying cDNA sequences in an L. donovani amastigote cDNA library that collectively or singly conferred protection against parasite challenge in a murine model of visceral leishmaniasis. We immunized BALB/c mice with plasmid DNA isolated and pooled from 15 cDNA sublibraries (similar to 2,000 cDNAs/sublibrary). Following systemic challenge with L. donovani, mice immunized with 6 of these 15 sublibraries showed a significantly reduced (35- to 1,000-fold) hepatic parasite burden. Because of the complexity and magnitude of the sequential fractionation-immunization-challenge approach, we restricted our attention to the two sublibraries that conferred the greatest in vivo protection. From one of these two sublibraries, we identified several groups of cDNAs that afforded protection, including a set of nine novel cDNAs and, surprisingly, a group of five cDNAs that encoded L. donovani histone proteins. At each fractionation step, the cDNA sublibraries or the smaller DNA fractions that afforded in vivo protection against the parasite also induced in vitro parasite-specific T helper 1 immune responses. Our studies demonstrate that immunization with sequential fractions of a cDNA library is a powerful strategy for identifying anti-infective vaccine candidates. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Med Serv, Audie L Murphy Div, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Microbiol, San Antonio, TX 78229 USA. St Marys Univ, Dept Biol Sci, San Antonio, TX USA. RP Melby, PC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, 7703 Floyd Curl Dr,Mailstop 7881, San Antonio, TX 78229 USA. NR 34 TC 71 Z9 74 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 2000 VL 68 IS 10 BP 5595 EP 5602 DI 10.1128/IAI.68.10.5595-5602.2000 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 355QE UT WOS:000089395700018 PM 10992459 ER PT J AU Hou, L Sasakj, H Stashenko, P AF Hou, L Sasakj, H Stashenko, P TI B-cell deficiency predisposes mice to disseminating anaerobic infections: Protection by passive antibody transfer SO INFECTION AND IMMUNITY LA English DT Article ID PORPHYROMONAS-GINGIVALIS VIRULENCE; PERIAPICAL INFLAMMATORY LESIONS; MODEL; LIPOPOLYSACCHARIDE; IMMUNIZATION; DESTRUCTION; RESPONSES; INDUCTION; IMMUNITY; BALB/C AB We have previously demonstrated that a high proportion of RAG-2 SCID knockout mice, which lack T and B cells, develop orofacial abscesses and disseminated infections following pulpal infection, whereas immunocompetent control mice do not. In the present study, we sought to identify the components of the adaptive immune response which contribute to protection against disseminating anaerobic infections and sepsis, For this purpose, various genetically engineered immunodeficient mice were employed, including RAG-2 SCID, Igh-6 (B-cell deficient), Tcrb Tcrd (T-cell deficient) and Hc degrees (C5 deficient), For abscess induction, the mandibular first molars were subjected to pulp exposure on day 0. Teeth were infected with a mixture of four anaerobic pathogens, including Prevotella intermedia, Streptococcus intermedius, Fusobacterium nucleatum, and Peptostreptococcus micros, and teeth were sealed to prevent communication with the oral cavity, The findings demonstrate that both RAG-2 SCID and B-cell-deficient mice, but not T-cell- or CS-deficient mice, have increased susceptibility to the development of disseminating anaerobic infections. Abscess-susceptible RAG-2 SCID and B-cell-deficient mice also showed a significant loss of body weight, splenomegaly, and absent antibacterial antibody production. Furthermore, dissemination was significantly reduced, from 74 to 25%, in susceptible RAG-2 mice by passively transferred antibody, predominantly immunoglobulin G2b (IgG2b) and IOM, against the infecting bacterial innoculum, Fractionated IgG-enriched preparations were more efficient in transferring protection than IgM preparations. We conclude that an antibody-mediated mechanism(s), most likely bacterial opsonization, is of importance in localizing anaerobic root canal infections and in preventing their systemic spread. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. RP Stashenko, P (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-11664, R01 DE011664] NR 38 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 2000 VL 68 IS 10 BP 5645 EP 5651 DI 10.1128/IAI.68.10.5645-5651.2000 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 355QE UT WOS:000089395700024 PM 10992465 ER PT J AU Cheng, YL Shek, CC Tsang, DNC Li, CS Lentino, JR Daugirdas, JT Kjellstrand, CM Ing, TS AF Cheng, YL Shek, CC Tsang, DNC Li, CS Lentino, JR Daugirdas, JT Kjellstrand, CM Ing, TS TI Stability of urea and creatinine in spent hemodialysate SO INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS LA English DT Article DE urea; creatinine; dialysate ID PARTIAL DIALYSATE COLLECTION; SOLUTE REMOVAL INDEX; WATER; QUANTIFICATION; CONTAMINATION; MULTICENTER; ADEQUACY; MONITOR AB Urea and creatinine levels in spent hemodialysates showed only small declines in spite of incubation at 37 degrees C for 36 hours, in the determination of dialysate-side solute removal, it would seem prudent to keep spent dialysate cold during collection to retard bacterial breakdown of these waste products. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Renal & Hypertens Sect, Dept Med, Hines, IL 60141 USA. Queen Elizabeth Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China. Queen Elizabeth Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China. Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. RP Ing, TS (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Renal & Hypertens Sect, Dept Med, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. NR 32 TC 2 Z9 2 U1 0 U2 1 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 0391-3988 J9 INT J ARTIF ORGANS JI Int. J. Artif. Organs PD OCT PY 2000 VL 23 IS 10 BP 670 EP 674 PG 5 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 370ML UT WOS:000165126800003 PM 11075896 ER PT J AU Whitcomb, C Enzmann, G Pershadsingh, HA Johnson, R Ciuryla, V Reisin, E AF Whitcomb, C Enzmann, G Pershadsingh, HA Johnson, R Ciuryla, V Reisin, E TI A comparison of nisoldipine ER and amlodipine for the treatment of mild to moderate hypertension SO INTERNATIONAL JOURNAL OF CLINICAL PRACTICE LA English DT Article ID BLOOD-PRESSURE; COAT-CORE; EFFICACY; HEALTH AB This multicentre, double-blind, double-dummy, randomised trial compared the efficacy and tolerability of nisoldipine extended release (10-40 mg) and amlodipine (2.5-10 mg) in 161 patients. The primary end point was a between-treatment comparison of change from baseline to week 8 in mean office diastolic blood pressure (DBP). The least squares mean reductions in systolic (S)BP/DBP (+/- standard error) for nisoldipine and amlodipine were -11.7/-9.3 +/- 1.4/0.8 and -14.3/-12.0 +/- 1.4/0.8 mmHg, respectively. The DBP treatment difference was 2.7 mmHg (90% confidence interval: 1.1 to 4.3 mmHg; p=0.005). Tolerability profiles were similar between treatments. The drug acquisition cost per mmHg DBP reduction was 40% lower with nisoldipine; an acquisition cost analysis revealed that amlodipine was 80% more expensive than nisoldipine for treating hypertension. In summary, nisoldipine and amlodipine provide clinically equivalent antihypertensive efficacy; however, nisoldipine is more economical than amlodipine. C1 Univ Calif Davis, Primary Care Network, Davis, CA 95616 USA. Calif State Univ Sacramento, Sch Med, Sacramento, CA 95819 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA USA. Joslin Clin, Seattle, WA USA. Kern Med Ctr, Dept Family Practice, Bakersfield, CA USA. AstraZeneca Pharmaceut, Wilmington, DE 19850 USA. Louisiana State Univ, Dept Med, Nephrol Sect, New Orleans, LA USA. RP Reisin, E (reprint author), Louisiana State Univ, Med Ctr, Dept Med, Nephrol Sect, 1542 Tulane Ave, New Orleans, LA 70112 USA. NR 19 TC 4 Z9 4 U1 0 U2 0 PU MEDICOM INTERNATIONAL PI SURREY PA CHURSTON HOUSE, PORTSMOUTH RD, ESHER, SURREY KT10 9AD, ENGLAND SN 1368-5031 J9 INT J CLIN PRACT JI Int. J. Clin. Pract. PD OCT PY 2000 VL 54 IS 8 BP 509 EP 513 PG 5 WC Medicine, General & Internal; Pharmacology & Pharmacy SC General & Internal Medicine; Pharmacology & Pharmacy GA 373VQ UT WOS:000165311100007 PM 11198728 ER PT J AU Young, RH Clement, PB AF Young, RH Clement, PB TI Endocervicosis involving the uterine cervix: A report of four cases of a benign process that may be confused with deeply invasive endocervical adenocarcinoma SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE uterine cervix; endocervicosis; tumorlike lesion; adenocarcinoma ID MINIMAL-DEVIATION ADENOCARCINOMA; ADENOMA-MALIGNUM; GLANDULAR HYPERPLASIA; URINARY-BLADDER; TUNNEL CLUSTERS; LESION AB Four cases of endocervicosis that involved the outer cervical wall and paracervical connective tissue are reported; in one case there was also transmural involvement of the urinary bladder. A diagnosis of cervical adenocarcinoma was an initial concern of the referring pathologist in three cases. The patients were from 29 to 45 years of age; there was a history of cesarean section in two cases. Two patients presented with pelvic pain, one with dysmenorrhea, and one with symptoms related to an ovarian tumor. In three cases, a gross abnormality of the enter aspect of the cervix was noted at the time of hysterectomy and in the fourth at the time of macroscopic pathologic examination. The anterior wall of the cervix in each case was involved by a firm rubbery mass, 1 to 2.5 cm in maximal dimension, with cysts seen on sectioning in two. Microscopic examination disclosed a dominant population of glands of variable size and shape, including cystically dilated glands, lined by mucinous endocervical-type epithelium that ranged from columnar to flattened. All the glands had lining cells with bland cytologic features with absent to rare mitotic figures. A periglandular stromal reaction, present in two cases, was related to mucin extravasation. A cuff of endometriotic stroma was present around rare glands in one case. The appearance of the lesion was similar to that of endocervicosis of the urinary bladder, and as in that site, raised concern for adenocarcinoma, specifically for the minimal deviation (adenoma malignum) type of cervical adenocarcinoma. Awareness of the distinctive features of endocervicosis in this site, including its dominant location in the outer portion of the cervix and paracervical connective tissue and the typical presence of an uninvolved zone of cervical wall between the endocervicosis and the eutopic endocervical glands, facilitate the correct diagnosis. C1 Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Vancouver Gen Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. RP Young, RH (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Dept Pathol, 32 Fruit St, Boston, MA 02114 USA. NR 20 TC 20 Z9 22 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD OCT PY 2000 VL 19 IS 4 BP 322 EP 328 DI 10.1097/00004347-200010000-00005 PG 7 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 374PT UT WOS:000165354100005 PM 11109160 ER PT J AU Bauman, GS Ino, Y Ueki, K Zlatescu, MC Fisher, BJ Macdonald, DR Stitt, L Louis, DN Cairncross, JG AF Bauman, GS Ino, Y Ueki, K Zlatescu, MC Fisher, BJ Macdonald, DR Stitt, L Louis, DN Cairncross, JG TI Allelic loss of chromosome 1p and radiotherapy plus chemotherapy in patients with oligodendrogliomas SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE oligodendroglioma; radiation; chemotherapy; chromosome 1p ID RADIATION; SURVIVAL; GLIOMAS; ADULTS AB Introduction: Allelic loss of the short arm of chromosome 1 predicts radiographic response to chemotherapy and long overall survival times in patients with anaplastic oligodendrogliomas. Using a database of patients with oligodendrogliomas in whom chromosome 1p status was known, we explored whether allelic loss of 1p also predicted longer duration of tumor control when radiotherapy was part of the initial treatment of these patients. Materials and Methods: We measured progression-free survival following radiotherapy in a cohort of patients with World Health Organization (WHO) Grade II and WHO Grade III oligodendrogliomas. The effects on progression-free survival of patient age, Karnofsky performance score (KPS), tumor grade when irradiated and chromosome 1p status were examined by univariate and multivariate statistical analyses. For the subset of patients with newly diagnosed anaplastic oligodendrogliomas, relationships between use of chemotherapy, chromosome 1p status and progression-free survival were also examined. Results: Fifty-five patients (29 male, 26 female; ages 18-75 years; median, 44 years; KPS 50-90, median 80) were irradiated for either a WHO Grade II (n = 19) or Grade III (n = 36) oligodendroglioma. Twenty-eight patients had chemotherapy immediately prior to radiotherapy, and 27 had chemotherapy at progression following radiotherapy, The median radiation dose was 54 Gy in 30 fractions, Loss of heterozygosity (LOH) at chromosome 1p was evident in 36 tumors and absent in 19, Overall median progression-free survival after radiotherapy was 40.4 months. Median progression-free survival was 55.0 months for patients whose tumors harbored 1p loss vs. 6.2 months for those patients whose tumors retained both copies of chromosome 1p (p < 0.001). On both univariate and multivariate analyses, chromosome 1p loss was the principal independent predictor of longer progression-free survival for patients with Grade II and III oligodendrogliomas. For Grade III oligodendrogliomas, chemotherapy as an adjunct to radiotherapy prolonged tumor control for those patients whose tumors harbored allelic loss of chromosome 1p (p = 0.004). Conclusion: These data suggest allelic loss of chromosome 1p in patients with oligodendroglial neoplasms predicts longer progression-free survival among patients receiving radiotherapy +/- chemotherapy as part of their initial treatment. Chromosome 1p loss may be an important stratification variable in future therapeutic trials of oligodendroglioma. (C) 2000 Elsevier Science Inc. C1 London Reg Canc Ctr, Dept Radiat Oncol, London, ON N6A 4L6, Canada. Univ Western Ontario, Dept Oncol, London, ON, Canada. Univ Western Ontario, Dept Epidemiol & Biostat, London, ON, Canada. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Bauman, GS (reprint author), London Reg Canc Ctr, Dept Radiat Oncol, 790 Commissioners Rd E, London, ON N6A 4L6, Canada. RI Bauman, Glenn/D-5986-2011 NR 12 TC 165 Z9 171 U1 0 U2 2 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 OCT 1 PY 2000 VL 48 IS 3 BP 825 EP 830 DI 10.1016/S0360-3016(00)00703-3 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 363ER UT WOS:000089822600025 PM 11020580 ER PT J AU Murray, SK Young, RH Scully, RE AF Murray, SK Young, RH Scully, RE TI Uterine endometrioid carcinoma with small nonvillous papillae: An analysis of 26 cases of a favorable-prognosis tumor to be distinguished from serous carcinoma SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE uterus; endometrioid carcinoma; serous carcinoma; villoglandular carcinoma; endometrial carcinoma; small nonvillous papillae; prognosis; treatment ID GYNECOLOGIC-ONCOLOGY-GROUP; PSAMMOMA BODIES; CLINICOPATHOLOGICAL FEATURES; VILLOGLANDULAR DIFFERENTIATION; ADENOCARCINOMA; SURVIVAL; CRITERIA; UTERUS AB We have encountered a number of endometrioid carcinomas with small papillary buds lacking fibrovascular cores that could be confused with the small cellular papillae of serous papillary carcinoma (SPC). We have designated these tumors "endometrioid carcinoma with small nonvillous papillae" (ECSP). Because they have not been investigated previously we analyzed 26 examples and compared their features with those of 21 SPCs of the uterus. Three hundred and ninety consecutive cases of endometrial carcinoma diagnosed between January, 1989, and January, 1994, were retrieved from our hospital files; 26 (6.7%) of them, (8% of the endometrioid carcinomas) were identified as ECSP, and 21 (5.4%) as SPC. Tumors were classified as ECSP when the small papillae were present within the glands of otherwise typical endometrioid carcinoma or on the villous projections of villoglandular endometrioid carcinoma. Most of the papillae were in the form of buds of cells with ample eosinophilic cytoplasm and a low nuclear-to-cytoplasmic ratio, but some papillae had a more complex pattern. The papillae arose on a background of International Federation of Gynecology and Obstetrics (FIGO) grade 1 or 2 endometrioid carcinomas, which showed squamous differentiation in half the cases. SPCs were identified according to generally accepted criteria. The mean age of the patients with ECSP was 67 years, intermediate between that of the patients with endometrioid carcinoma lacking small nonvillous papillae (62 years) and that of the patients with SPC (71 years). Patients with ECSP more frequently presented at an earlier stage (73% stage I/II) than those with SPC (29% stage I/II). The overall 5-year survival of patients with ECSP was 84% (95% CI: 0.68-1), more than double that of patients with SPC, 73% (95% CI: 0.10-0.56). ECSP may be confused with SPC on microscopic examination but has clinical and pathological features similar to those of endometrioid carcinoma lacking small nonvillous papillae, and unlike SPC, should be treated in the same manner as the former. C1 Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Murray, SK (reprint author), QEII Hlth Sci Ctr, Dept Pathol, 7th Floor,Mackenzie Bldg,5788 Univ Ave, Halifax, NS B3H 1V8, Canada. NR 37 TC 24 Z9 24 U1 0 U2 1 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD OCT PY 2000 VL 8 IS 4 BP 279 EP 289 DI 10.1177/106689690000800407 PG 11 WC Pathology; Surgery SC Pathology; Surgery GA 399RC UT WOS:000166825300005 PM 11494005 ER PT J AU Young, RH Murray, SK AF Young, RH Murray, SK TI Notes on collecting classic pathology textbooks SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA 02115 USA. Dalhousie Univ, Sch Med, QEII Hlth Sci Ctr, Halifax, NS, Canada. RP Young, RH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA 02115 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD OCT PY 2000 VL 8 IS 4 BP 343 EP 345 DI 10.1177/106689690000800417 PG 3 WC Pathology; Surgery SC Pathology; Surgery GA 399RC UT WOS:000166825300015 PM 11494015 ER PT J AU Mulroy, L Kim, J Wu, I Scharper, P Melki, SA Azar, DT Redmond, RW Kochevar, IE AF Mulroy, L Kim, J Wu, I Scharper, P Melki, SA Azar, DT Redmond, RW Kochevar, IE TI Photochemical keratodesmos for repair of lamellar corneal incisions SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID BIOLOGIC TISSUE GLUE; HUMAN ALBUMIN SOLDER; CATARACT INCISIONS; CROSS-LINKING; WOUND CLOSURE; SKIN CLOSURE; YAG LASER; IN-VIVO; COLLAGEN; N-HYDROXY-2-THIOPYRIDONE AB PURPOSE. TO determine the efficacy of photochemical keratodesmos (PKD) for closing surgical incisions in the cornea of enucleated rabbit eyes compared with that achieved using sutures and self-sealing incisions. METHODS. A 3.5-mm incision, at an angle parallel to the iris, was made in the cornea of enucleated New Zealand White rabbit eyes. The intraocular pressure required to cause leakage (IOPL) from the untreated incision was then recorded. Photochemical keratodesmos treatment was then performed by application of a dye, Rose Bengal (RB), in saline solution to the surfaces of the incision wound, followed by laser irradiation at 514 nm from an argon ion laser. Immediately after treatment, the IOPL was measured. Both dose and laser irradiance dependencies were studied in five or more eyes for each condition and appropriate control eyes. The IOP(L)s were compared with those obtained using conventional interrupted 10-0 nylon sutures. Other dyes were tested in a similar fashion. RESULTS. The IOPL of 300 mm Hg was obtained using a fluence of 1270 J/cm(2) with an irradiance of 1.27 W/cm(2) (laser exposure time, 16 minutes 40 seconds). No sealing was observed using dye or light alone where control pressures of approximately 30 mm Hg were found. At higher dose (1524 J/cm(2)) and irradiance (3.82 W/cm(2); 6 minutes 35 seconds), PKD was less effective, which may be attributable to thermal effects. PKD produced IOP(L)s similar to those in closure by sutures. Other dyes such as riboflavin-5-phosphate and N-hydroxy-pyridine thione also produced efficient bonding after PKD. Nonphotochemically active dyes did not produce significant increases in the IOPL at which leakage occurred. CONCLUSIONS. The increase in IOPL after PKD treatment, comparable with that with sutures, in enucleated rabbit eyes demonstrates the feasibility of this technique ex vivo. C1 Harvard Univ, Sch Med, Dept Dermatol, Wellman Labs Photomed,Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cornea & Refract Serv, Boston, MA 02114 USA. RP Kochevar, IE (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Wellman Labs Photomed,Massachusetts Gen Hosp, WEL-224, Boston, MA 02114 USA. NR 42 TC 36 Z9 37 U1 1 U2 5 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 OCT PY 2000 VL 41 IS 11 BP 3335 EP 3340 PG 6 WC Ophthalmology SC Ophthalmology GA 358PZ UT WOS:000089567600014 PM 11006222 ER PT J AU Li-Yu, J Schumacher, HR Gratwick, G AF Li-Yu, J Schumacher, HR Gratwick, G TI Invasive tophaceous pseudogout in the temporomandibular joint: Misdiagnosis as tumor - Case report and review of the literature SO JCR-JOURNAL OF CLINICAL RHEUMATOLOGY LA English DT Review DE tophaceous pseudogout; temporomandibular joint ID DIHYDRATE DEPOSITION DISEASE; CRYSTAL DEPOSITION; PYROPHOSPHATE; CHONDROCALCINOSIS; PSEUDOTUMOR; ARTHROPATHY; CPPD AB We report a case of focal calcium pyrophosphate dihydrate (CPPD) arthropathy in a 72-year-old, white woman that occurred in the temporomandibular joint (TMJ), a relatively unusual location for CPPD crystals. The patient underwent surgical exploration and radiation therapy because of histologic interpretation of an initial biopsy specimen as showing metastatic poorly differentiated carcinoma. Further evaluation of the specimen revealed the presence of positively birefringent crystals under compensated polarizing light microscopic examination. Previously reported cases of CPPD affecting the TMJ have also shown that this may mimic neoplastic or infectious conditions. Tophaceous pseudogout at the TMJ is a surprisingly common complication of CPPD deposition disease. As in our patient, it can occur without, known CPPD at other sites. C1 Univ Penn, Sch Med, Rheumatol Sect, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Arthritis Immunol Ctr, Philadelphia, PA 19104 USA. Block & Gratwick, Bangor, ME USA. NR 23 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-1608 J9 JCR-J CLIN RHEUMATOL JI JCR-J. Clin. Rheumatol. PD OCT PY 2000 VL 6 IS 5 BP 272 EP 277 DI 10.1097/00124743-200010000-00007 PG 6 WC Rheumatology SC Rheumatology GA 363HD UT WOS:000089828800009 PM 19078485 ER PT J AU Tremblay, CL Kollmann, C Giguel, F Chou, TC Hirsch, MS AF Tremblay, CL Kollmann, C Giguel, F Chou, TC Hirsch, MS TI Strong in vitro synergy between the fusion inhibitor T-20 and the CXCR4 blocker AMD-3100 SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 7th Conference on Retroviruses and Opportunistic Infections CY JAN 29-FEB 03, 2000 CL SAN FRANCISCO, CALIFORNIA DE fusion; viral entry; HIV-1 coreceptor inhibitors; CXCR4; drug interactions ID IMMUNODEFICIENCY-VIRUS TYPE-1; HIV-1; THERAPY; COMBINATION; INFECTION; PEPTIDE; ENTRY AB Attachment and entry of HIV-1 into CD4 cells involve a series of events in which different viral envelope proteins interact with specific cell receptors, culminating in fusion of viral and cell membranes. AMD-3100 is a small molecule inhibitor of HIV-1 attachment to the CXCR4 chemokine receptor, and T-20 is a synthetic peptide corresponding to a region of HIV-1 gp41 that blocks fusion to cell membranes. To evaluate the interaction between agents acting at two different steps of the entry process, we conducted in vitro studies of the combination of T-20 and AMD-3100 against an X4 HIV-1 isolate. Single drugs or multiply diluted fixed ratio combinations of drugs were added to peripheral blood mononuclear cells infected with a clinical isolate, 14aPre. Drug interactions were evaluated using the median-effect principle and the combination index technique. The 50% inhibitory concentration (IC50) for T-20 was 0.10 mug/ml and for AMD-3100 was 0.19 mug/ml. Synergy was observed between T-20 and AMD-3100 and this increased with higher inhibitory concentrations, with combination indices ranging from 0.62 at IC50 to 0.02 at IC95. Whether these synergistic interactions translate into clinical benefit will need to be addressed in the context of clinical trials. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Infect Dis Unit, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Hirsch, MS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Infect Dis Unit, Gray 5,Fruit St, Boston, MA 02114 USA. RI Chou, Ting-Chao/B-4111-2009 OI Chou, Ting-Chao/0000-0002-3340-1594 FU NCI NIH HHS [CA12464] NR 15 TC 96 Z9 99 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD OCT 1 PY 2000 VL 25 IS 2 BP 99 EP 102 DI 10.1097/00126334-200010010-00001 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 376AA UT WOS:000165434600001 PM 11103038 ER PT J AU Xie, AL Skatrud, JB Crabtree, DC Puleo, DS Goodman, BM Morgan, BJ AF Xie, AL Skatrud, JB Crabtree, DC Puleo, DS Goodman, BM Morgan, BJ TI Neurocirculatory consequences of intermittent asphyxia in humans SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE sympathetic nervous system; hypoxia; hypercapnia ID SYMPATHETIC ACTIVITY; NERVE RESPONSES; BLOOD-PRESSURE; SLEEP-APNEA; NREM SLEEP; HYPOXIA; VENTILATION; HYPERCAPNIA; ACTIVATION; ELEVATION AB We examined the neurocirculatory and ventilatory responses to intermittent asphyxia (arterial O-2 saturation = 79-85%, end-tidal Pco(2) = 3-5 Torr above eupnea) in seven healthy humans during wakefulness. The intermittent asphyxia intervention consisted of 20-s asphyxic exposures alternating with 40-s periods of room-air breathing for a total of 20 min. Minute ventilation increased during the intermittent asphyxia period (14.2 +/-. 2.0 l/min in the final 5 min of asphyxia vs. 7.5 +/- 0.4 l/min in baseline) but returned to the baseline level within 2 min after completion of the series of asphyxic exposures. Muscle sympathetic nerve activity increased progressively, reaching 175 +/- 12% of baseline in the final 5 min of the intervention. Unlike ventilation, sympathetic activity remained elevated for at least 20 min after removal of the chemical stimuli (150 +/- 10% of baseline in the last 5 min of the recovery period). Intermittent asphyxia caused a small, but statistically significant, increase in heart rate (64 +/- 4 beats/min in the final 5 min of asphyxia vs. 61 +/- 4 beats/min in baseline); however, this increase was not sustained after the return to room-air breathing. These data demonstrate that relatively short-term exposure to intermittent asphyxia causes sympathetic activation that persists after removal of the chemical stimuli. This carryover effect provides a potential mechanism whereby intermittent asphyxia during sleep could lead to chronic sympathetic activation in patients with sleep apnea syndrome. C1 William S Middleton Mem Vet Hosp, Pulm Physiol Lab, Dept Med, Madison, WI 53705 USA. William S Middleton Mem Vet Hosp, Dept Surg, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Madison, WI 53705 USA. Univ Wisconsin, Dept Surg, Madison, WI 53705 USA. RP Xie, AL (reprint author), William S Middleton Mem Vet Hosp, Pulm Physiol Lab, Dept Med, 2500 Overlook Terrace, Madison, WI 53705 USA. NR 25 TC 64 Z9 67 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD OCT PY 2000 VL 89 IS 4 BP 1333 EP 1339 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 362AE UT WOS:000089755800011 PM 11007566 ER PT J AU Reppert, SM Weaver, DR AF Reppert, SM Weaver, DR TI Comparing clockworks: Mouse versus fly SO JOURNAL OF BIOLOGICAL RHYTHMS LA English DT Review DE circadian rhythms; suprachiasmatic nucleus; biological clock; clock genes; molecular biology ID SUPRACHIASMATIC CIRCADIAN CLOCK; DROSOPHILA PERIOD GENE; RPER2 MESSENGER-RNA; MAMMALIAN ORTHOLOG; LIGHT; EXPRESSION; TIMELESS; PROTEIN; MPER1; TRANSCRIPTION C1 Massachusetts Gen Hosp, MassGen Hosp Children, Lab Dev Chronobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Reppert, SM (reprint author), Massachusetts Gen Hosp, MassGen Hosp Children, Lab Dev Chronobiol, Boston, MA 02114 USA. RI huang, hongqi/N-1473-2014 NR 58 TC 60 Z9 61 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0748-7304 J9 J BIOL RHYTHM JI J. Biol. Rhythms PD OCT PY 2000 VL 15 IS 5 BP 357 EP 364 DI 10.1177/074873000129001459 PG 8 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 357XR UT WOS:000089527700002 PM 11039914 ER PT J AU Fowler, AJ Menguc, MP AF Fowler, AJ Menguc, MP TI Propagation of focused and multibeam laser energy in biological tissue SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article ID MONTE-CARLO; LIGHT DISTRIBUTIONS; IRRADIATED TISSUE; BLOOD-VESSELS; MODEL AB The results of a Monte Carlo simulation of laser beam propagation in turbid media are presented The study was performed to determine whether using a focused beam or multiple beams instead of a single collimated beam could improve subsurface laser energy delivery in biological tissue. A parametric study was carried out to determine both the laser fluence at a target depth and the ratio of fluence at the target over surface fluence as a function of tissue properties and the mode of energy delivery. It was found that the reduced scattering coefficient was the primary determinant as to whether multibeam or focused beam delivery could be effective. A focused bean was Sound to be extremely effective in increasing fluence at the target if the dimensionless reduced scattering coefficient was less than 2. The delivered fluence, however, was found to be extremely sensitive to tissue properties. A five-beam laser system was found to be less effective at increasing fluence at the target than a focused beam; but the fluence delivered by a five-beam system was far less sensitive to tissue properties, thereby making accurate dosimetry more feasible. [S0148-0731(00)01205-X]. C1 Univ Massachusetts, Dept Mech Engn, N Dartmouth, MA 02747 USA. Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Univ Kentucky, Dept Mech Engn, Lexington, KY 40506 USA. RP Fowler, AJ (reprint author), Univ Massachusetts, Dept Mech Engn, N Dartmouth, MA 02747 USA. RI Menguc, Pinar/O-3114-2013 NR 17 TC 5 Z9 6 U1 1 U2 2 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD OCT PY 2000 VL 122 IS 5 BP 534 EP 540 DI 10.1115/1.1289993 PG 7 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 404QD UT WOS:000167111200012 PM 11091957 ER PT J AU Zourabian, A Siegel, A Chance, B Rode, M Boas, DA AF Zourabian, A Siegel, A Chance, B Rode, M Boas, DA TI Trans-abdominal monitoring of fetal arterial blood oxygenation using pulse oximetry SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE fetal oxygen saturation; near infra-red spectroscopy; pulse oximetry; hemoglobin; optical properties ID SATURATION; SCATTERING AB Pulse oximetry (oxygen saturation monitoring) has markedly improved medical care in many fields, including anesthesiology, intensive care, and newborn intensive care. In obstetrics, fetal heart rate monitoring remains the standard for intrapartum assessment of fetal well being. Fetal oxygen saturation monitoring is a new technique currently under development. It is potentially superior to electronic fetal heart rate monitoring (cardiotocography) because it allows direct assessment of both the fetal oxygen status and fetal tissue perfusion. Here we present the analysis for determining the most optimal wavelength selection for pulse oximetry. The wavelengths we chose as the most optimal are the first in the range of 670-720 nm and the second in the range of 825-925 nm. Further, we discuss the possible systematic errors during our measurements and their contribution to the obtained saturation results. We present feasibility studies for fetal pulse oximetry, monitored noninvasively through the maternal abdomen. Our preliminary experiments show that the fetal pulse can be discriminated from the maternal pulse and thus, in principle, the fetal arterial oxygen saturation can be obtained. We present the methodology for obtaining these data, and discuss the dependence of our measurements on the fetal position with respect to the optode assembly. (C) 2000 Society of Photo-Optical Instrumentation Engineers. [S1083-3668(00)00604-3]. C1 Massachusetts Gen Hosp, Dept Radiol, NMR Ctr, Charlestown, MA 02129 USA. Tufts Univ, Electroopt & Bioengn Dept, Medford, MA 02155 USA. Univ Penn, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. RP Zourabian, A (reprint author), Massachusetts Gen Hosp, Dept Radiol, NMR Ctr, 13th St,Bldg 149,Room 2301, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [1R43HL61057-01]; NINDS NIH HHS [R29NS37053] NR 26 TC 55 Z9 57 U1 0 U2 0 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD OCT PY 2000 VL 5 IS 4 BP 391 EP 405 DI 10.1117/1.1289359 PG 15 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 365ZR UT WOS:000089980800006 PM 11092427 ER PT J AU Poss, R Mabrey, JD Gillogly, SD Kasser, JR Sweeney, HJ Zarins, B Garrett, WE Cannon, WD AF Poss, R Mabrey, JD Gillogly, SD Kasser, JR Sweeney, HJ Zarins, B Garrett, WE Cannon, WD TI Development of a virtual reality arthroscopic knee simulator SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Orthopaedic-Association CY JUN 07, 1999 CL SUN VALLEY, IDAHO SP Amer Orthopaed Assoc C1 Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. Univ Texas, Hlth Sci Ctr, Dept Orthopaed, San Antonio, TX 78284 USA. Childrens Hosp, Med Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA. Univ Calif San Francisco, Med Ctr, San Francisco, CA 94143 USA. RP Poss, R (reprint author), Brigham & Womens Hosp, Dept Orthopaed Surg, 75 Francis St, Boston, MA 02115 USA. NR 11 TC 11 Z9 12 U1 0 U2 0 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 OCT PY 2000 VL 82A IS 10 BP 1495 EP 1499 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 366BC UT WOS:000089984100017 PM 11057478 ER PT J AU McCarthy, KM Francis, SA McCormack, JM Lai, J Rogers, RA Skare, IB Lynch, RD Schneeberger, EE AF McCarthy, KM Francis, SA McCormack, JM Lai, J Rogers, RA Skare, IB Lynch, RD Schneeberger, EE TI Inducible expression of claudin-1-myc but not occludin-VSV-G results in aberrant tight junction strand formation in MDCK cells SO JOURNAL OF CELL SCIENCE LA English DT Article DE tight junction; claudin-1; occludin ID CANINE KIDNEY-CELLS; TRANSEPITHELIAL ELECTRICAL-RESISTANCE; INTEGRAL MEMBRANE-PROTEINS; PARACELLULAR PERMEABILITY; ZONULA-OCCLUDENS; EPITHELIAL-CELL; MOUSE-LIVER; ZO-1; BARRIER; COMPONENT AB Occludin and 18 distinct members of the claudin family are tetra-span transmembrane proteins that are localized in cell-specific tight junctions (TJs). A previous study showed that expression of chick occludin in Madin-Darby canine kidney (MDCK) cells raised transepithelial electrical resistance (TER) and, paradoxically, increased mannitol flux. In the present study, we employed epitope tagged canine occludin expression, under the control of the tetracycline repressible transactivator, to determine the extent to which the unexpected parallel increase in TER and mannitol flux was related to a structural mismatch between avian and canine occludins, which are only 50% identical. To determine whether the paradoxical changes in permeability was specific to occludin, we assessed the effect of over-expressing epitope tagged murine claudin-1, Our data revealed that over-expression of either of the epitope tagged mammalian tight junction proteins increased TER, mannitol and FITC-dextran flux. We observed a 2- and up to 5.6-fold over-expression of occludin-VSV-G and claudin-1-myc, respectively, with no change in ZO-1, endogenous occludin or clandin-1 expression. Confocal microscopy revealed that occludin-VSV-G, claudin-1-myc and ZO-1 colocalized at the TJ. In addition, claudin-1-myc formed aberrant strands along the lateral cell surface without an underlying ZO-1 scaffold. In fracture labeled replicas these strands consisted of claudin-1-myc with little accompanying occludin. These observations suggest that in epithelial cells claudin-1 can assemble into TJ strands without the participation of either ZO-1 or occludin, The proximity of the myc tag to the COOH-terminal YV sequence of claudin-1 appeared to interfere with its interaction with ZO-1, since over-expression of non-tagged claudin-1 increased TER but had a minimal effect on solute Bur and no aberrant strands formed. From our data we conclude that differences in structure between avian and mammalian occludin do not account for the observed paradoxical increase in mannitol flux, Levels of ZO-1 remained unchanged despite substantial increases in induced TJ integral protein expression, suggesting that an imbalance between levels of ZO-1 and occludin or claudin-1 leads to altered regulation of pores through which noncharged solute flux occurs. We suggest that ion and solute flux are differentially regulated at the TJ. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Physiol Program, Boston, MA 02115 USA. Univ Massachusetts, Dept Biol Sci, Lowell, MA 01854 USA. RP Schneeberger, EE (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL25822] NR 55 TC 135 Z9 138 U1 1 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD OCT PY 2000 VL 113 IS 19 BP 3387 EP 3398 PG 12 WC Cell Biology SC Cell Biology GA 369PW UT WOS:000165077000005 PM 10984430 ER PT J AU Berg, JS Derfler, BH Pennisi, CM Corey, DP Cheney, RE AF Berg, JS Derfler, BH Pennisi, CM Corey, DP Cheney, RE TI Myosin-X, a novel myosin with pleckstrin homology domains, associates with regions of dynamic actin SO JOURNAL OF CELL SCIENCE LA English DT Article DE unconventional myosin; myosin-X; MYO10; pleckstrin homology domain ID UNCONVENTIONAL MYOSINS; PHOSPHOINOSITIDE 3-KINASE; PH DOMAIN; SIGNALING PROTEINS; BINDING-PROTEIN; DEAFNESS DFNB3; IN-VIVO; SPECIFICITY; SEQUENCES; MEMBRANE AB Myosin-X is the founding member of a novel class of unconventional myosins characterized by a tail domain containing multiple pleckstrin homology domains, We report here the full-length cDNA sequences of human and bovine myosin-X as well as the first characterization of this protein's distribution and biochemical properties. The 235 kDa myosin-X contains a head domain with <45% protein sequence identity to other myosins, three IQ motifs, and a predicted stalk of coiled coil. Like several other unconventional myosins and a plant kinesin, myosin-X contains both a myosin tail homology 4 (MyTH4) domain and a FERM (band 4.1/ezrin/radixin/moesin) domain. The unique tail domain also includes three pleckstrin homology domains, which have been implicated in phosphatidylinositol phospholipid signaling, and three PEST sites, which may allow cleavage of the myosin tail. Most intriguingly, myosin-X in cultured cells is present at the edges of lamellipodia, membrane ruffles, and the tips of filopodial actin bundles. The tail domain structure, biochemical features, and localization of myosin-X suggest that this novel unconventional myosin plays a role in regions of dynamic actin. C1 Univ N Carolina, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Cheney, RE (reprint author), Univ N Carolina, Dept Cell & Mol Physiol, Chapel Hill, NC 27599 USA. OI Corey, David/0000-0003-4497-6016 FU NIDCD NIH HHS [DC03299, R29 DC003299] NR 63 TC 141 Z9 144 U1 1 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD OCT PY 2000 VL 113 IS 19 BP 3439 EP 3451 PG 13 WC Cell Biology SC Cell Biology GA 369PW UT WOS:000165077000010 PM 10984435 ER PT J AU Hadigan, C Corcoran, C Piecuch, S Rodriguez, W Grinspoon, S AF Hadigan, C Corcoran, C Piecuch, S Rodriguez, W Grinspoon, S TI Hyperandrogenemia in human immunodeficiency virus-infected women with the lipodystrophy syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID POLYCYSTIC-OVARY-SYNDROME; ANTIRETROVIRAL THERAPY HAART; HIV PROTEASE INHIBITORS; INSULIN-RESISTANCE; BODY-COMPOSITION; FASTING HYPERINSULINEMIA; PERIPHERAL LIPODYSTROPHY; PREMENOPAUSAL WOMEN; FAT; HYPERLIPIDEMIA AB A novel lipodystrophy syndrome characterized by insulin resistance, hypertriglyceridemia, and fat redistribution has recently been described in human immunodeficiency virus (HIV)-infected men and women. Women with the HIV lipodystrophy syndrome exhibit a marked increase in waist-to-hip ratio and truncal adiposity; however, it is unknown whether androgen levels are increased in these patients. In this study, we assessed androgen levels in female patients with clinical lipodystrophy based on evidence of significant fat redistribution in the trunk, extremities, neck and/or face (LIPO: n = 9; age, 35.7 +/- 1.7 yr; BMI, 24.7 +/- 0.8 kg/m(2)) in comparison with age- and BMI-matched nonlipodystrophic HIV-infected females (NONLIPO: n = 14; age, 37.6 +/- 1.1 yr; BMI, 23.4 +/- 0.6 kg/m(2)) and healthy non-HIV-infected control subjects (C: n = 16; age, 35.8 +/- 0.9 yr; BMI, 23.1 +/- 0.4 kg/m(2)). Fasting insulin, lipid levels, virologic parameters, and regional body composition using dual energy x-ray absorptiometry were also assessed. Total testosterone [ LIFO, 33 +/- 6 ng/dL(1.1 +/- 0.2 nmol/L); NONLIPO, 17 +/- 2 ng/dL (0.6 +/- 0.1 nmol/L); C,23 +/- 2 ng/dL(0.8 +/- 0.1 nmol/L); P < 0.05 LIPO us. C and LIPO vs. NONLIPO] and free testosterone determined by equilibrium dialysis [LIPO, 4.5 +/- 0.9 pg/mL (16 +/- 3 pmol/L); NONLIPO, 1.7 +/- 0.2 pg/mL (6 +/- 1 pmol/L); C, 2.4 +/- 0.2 pg/mL (8 +/- 1 pmol/L); P < 0.05 LIPO us. C and LIPO vs. NONLIPO] were increased in the lipodystrophic patients. Sex hormone-binding globulin levels were not significantly different between LIPO and C, but were significantly lower in the LIPO vs. NONLIPO patients (LIPO 84 +/- 7 vs. NONLIPO 149 +/- 17 nmol/L, P < 0.05). The LH/FSH ratio was significantly increased in the LIPO group compared with the NONLIPO and C subjects (LIPO, 2.0 +/- 0.6; NONLIPO, 1.1 +/- 0.1; C, 0.8 +/- 0.1; P < 0.05 LIPO us. NONLIPO and LIPO vs. C). Body fat distribution was significantly different between LIPO and C subjects. Trunk to extremity fat ratio (1.46 +/- 0.17 vs. 0.75 +/- 0.05, LIPO vs. C, P < 0.05) was increased and extremity to total fat ratio decreased (0.40 +/- 0.03 vs. 0.55 +/- 0.01, LIPO vs. C, P < 0.05). In contrast, fat distribution was not different in the NONLIPO group us. control subjects. Among the HIV-infected patients, free testosterone correlated with percent truncal fat (trunk fat/trunk mass) (r = 0.43, P = 0.04). These data suggest that hyperandrogenemia is another potentially important feature of the HIV-lipodystrophy syndrome in women. Additional studies are necessary to determine the clinical significance of increased androgen levels and the relationship of hyperandrogenism to fat redistribution and insulin resistance in this population of patients. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. Brigham & Womens Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. EM sgrinspoon@partners.org FU NCRR NIH HHS [M01-RR01066]; NIDDK NIH HHS [R01-DK-54167, T32-DK07703] NR 29 TC 21 Z9 21 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2000 VL 85 IS 10 BP 3544 EP 3550 DI 10.1210/jc.85.10.3544 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 363DY UT WOS:000089820800013 PM 11061499 ER PT J AU Brenner, BE Van, DC Lazar, EJ Camargo, CA AF Brenner, BE Van, DC Lazar, EJ Camargo, CA TI Determinants of physician reluctance to perform mouth-to-mouth resuscitation SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE cardiac arrest; cardiopulmonary resuscitation; human immunodeficiency virus; acquired immunodeficiency disease; basic life support ID CARDIOPULMONARY-RESUSCITATION; HOUSE STAFF; WILLINGNESS; INTERNISTS; DELAYS; CPR AB Objectives: Mouth-to-mouth resuscitation (MMR) is widely taught and promoted. The purpose of this study was to better characterize the observation that health professionals are reluctant to perform MMR and to identify determinants of this reluctance. Methods: 324 residents and faculty at a New York City teaching hospital were anonymously surveyed regarding their reluctance to perform MMR. One year later, medical staff were resurveyed. Results: Reluctance varied across scenarios: 70-80% of physicians were willing to perform MMR on a newborn or child, 40-50% for an unknown man, and 20-30% for a trauma victim or potentially gay man. Physicians reported very similar percentages for each scenario in the two surveys. Factors associated with MMR reluctance were female gender (OR = 2), resident physician (OR = 2), and higher perceived risk of contracting HIV from MMR (OR = 1.4 per unit on 5-point scale). In the year before the survey, 30% of all respondents witnessed an apneic patient who required MMR for whom ventilation was not provided for at least 2 minutes. Conclusions: Many physicians are reluctant to perform MMR. Marked delays in ventilation of apneic patients are occurring. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Cornell Univ, Weill Coll Med, Brooklyn Hosp Ctr, Dept Emergency Med, Brooklyn, NY 11201 USA. Cornell Univ, Weill Coll Med, Brooklyn Hosp Ctr, Dept Internal Med, Brooklyn, NY 11201 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA USA. RP Brenner, BE (reprint author), Cornell Univ, Weill Coll Med, Brooklyn Hosp Ctr, Dept Emergency Med, 121 DeKalb Ave, Brooklyn, NY 11201 USA. FU NHLBI NIH HHS [HL-03533] NR 23 TC 14 Z9 14 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD OCT PY 2000 VL 53 IS 10 BP 1054 EP 1061 DI 10.1016/S0895-4356(00)00230-4 PG 8 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 363XV UT WOS:000089863700012 PM 11027939 ER PT J AU Zhao, WG Byrne, MH Wang, YM Krane, SM AF Zhao, WG Byrne, MH Wang, YM Krane, SM TI Osteocyte and osteoblast apoptosis and excessive bone deposition accompany failure of collagenase cleavage of collagen SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HUMAN PARATHYROID-HORMONE; OVARIECTOMIZED RATS; I COLLAGEN; OSTEOCLAST DIFFERENTIATION; INTERSTITIAL COLLAGENASE; INTEGRIN ALPHA-V-BETA-3; POTENTIAL MECHANISMS; MOUSE EMBRYOGENESIS; CELLS; MATRIX AB Mice carrying a targeted mutation (r) in Col1a1, encoding a collagenase-resistant form of type I collagen, have altered skeletal remodeling. In hematoxylin and eosin-stained paraffin sections, we detect empty lacunae in osteocytes in calvariae from Col1a1(r/r) mice at age 2 weeks, increasing through age 10-12 months. Empty lacunae appear to result from osteocyte apoptosis, since staining of osteocytes/periosteal osteoblasts with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling is increased in Col1a1(r/r) relative to wild-type bones. Osteocyte perilacunar matrices stained with Ab that recognizes collagenase collagen alpha 1(I) chain cleavage ends in wild-type but not Col1a1(r/r) calvariae. Increased calvarial periosteal and tibial/femoral endosteal bone deposition was found in Col1a1(r/r) mice from ages 3-12 months. Calcein labeling of calvarial surfaces was increased in Col1a1(r/r) relative to wild-type mice. Daily injections of synthetic parathyroid hormone for 30 days increased calcein-surface labeling in wild-type but caused no further increase in the already high calcein staining of Col1a1(r/r) bones. Thus, failure of collagenase cleavage of type I collagen in Col1a1(r/r) mice is associated with osteocyte/osteoblast death but increases bone deposition in a manner that mimics the parathyroid hormone-induced bone surface activation seen in wild-type mice. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Arthrit Unit,Med Serv, Boston, MA 02114 USA. RP Krane, SM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Arthrit Unit,Med Serv, Bulf 165,55 Fruit St, Boston, MA 02114 USA. FU NIAMS NIH HHS [AR-07258, AR-03564, AR-44855, P50 AR044855, R01 AR044815, T32 AR007258] NR 63 TC 77 Z9 82 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2000 VL 106 IS 8 BP 941 EP 949 DI 10.1172/JCI10158 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 364XQ UT WOS:000089919700006 PM 11032854 ER PT J AU Choukroun, GJ Marshansky, V Gustafson, CE McKee, M Hajjar, RJ Rosenzweig, A Brown, D Bonventre, JV AF Choukroun, GJ Marshansky, V Gustafson, CE McKee, M Hajjar, RJ Rosenzweig, A Brown, D Bonventre, JV TI Cytosolic phospholipase A(2) regulates Golgi structure and modulates intracellular trafficking of membrane proteins SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ADP-RIBOSYLATION FACTOR; NA+-K+-ATPASE; SIGNAL-TRANSDUCTION; CULTURED-CELLS; RAT-KIDNEY; ACID; COMPLEX; MICRODOMAINS; ACTIVATION; TRANSPORT AB The Golgi complex and the trans-Golgi network are critical cellular organelles involved in the endocytic and biosynthetic pathways of protein trafficking. Lipids have been implicated in the regulation of membrane-protein trafficking, vesicular fusion, and targeting. We have explored the role of cytosolic group IV phospholipase A(2) (cPLA(2)) in membrane-protein trafficking in kidney epithelial cells. Adenoviral expression of cPLA(2) in LLC-PK1 kidney epithelial cells prevents constitutive trafficking to the plasma membrane of an aquaporin 2-green fluorescent protein chimera, with retention of the protein in the rough endoplasmic reticulum. Plasma membrane Na+-K+-ATPase alpha-subunit localization is markedly reduced in cells expressing cPLA(2), whereas the trafficking of a Cl-/HCO3- anion exchanger to the plasma membrane is not altered in these cells. Expression of cPLA(2) results in dispersion of giantin and beta-COP from their normal, condensed Golgi localization, and in marked disruption of the Golgi cisternae. cPLA(2) is present in Golgi fractions from noninfected LLC-PK1 cells and rat kidney cortex. The distribution of tubulin and actin was not altered by cPLA(2), indicating that the microtubule and actin cytoskeleton remain intact. Total cellular protein synthesis is unaffected by the increase in cPLA(2) activity. Thus cPLA(2) plays an important role in determining Golgi architecture and selective control of constitutive membrane-protein trafficking in renal epithelial cells. C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Med Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Charlestown, MA USA. RP Bonventre, JV (reprint author), Massachusetts Gen Hosp E, Suite 4002,149 13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [R01 HL059521]; NIDDK NIH HHS [DK-38452, DK-39773, P01 DK038452, R01 DK039773, R37 DK039773]; NINDS NIH HHS [F32 NS010828, NS-10828, P01 NS010828, P50 NS010828] NR 45 TC 44 Z9 47 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2000 VL 106 IS 8 BP 983 EP 993 DI 10.1172/JCI8914 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 364XQ UT WOS:000089919700010 PM 11032858 ER PT J AU Cywes, C Stamenkovic, I Wessels, MR AF Cywes, C Stamenkovic, I Wessels, MR TI CD44 as a receptor for colonization of the pharynx by group A Streptococcus SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HYALURONIC-ACID CAPSULE; GROUP-A STREPTOCOCCI; NITRIC-OXIDE SYNTHASE; SHOCK-LIKE SYNDROME; M-PROTEIN; MONOCLONAL-ANTIBODIES; GENE-EXPRESSION; CELLS; PYOGENES; ADHESION AB The pharynx is the primary reservoir for strains of group A Streptococcus (GAS) associated both with pharyngitis (streptococcal sore throat) and with invasive or "flesh-eating" soft tissue infections. We now report that CD44, a hyaluronic acid-binding protein that mediates human cell-cell- and cell-extracellular matrix-binding interactions, functions as a receptor for GAS colonization of the pharynx in vivo. We found that attachment of GAS to murine epithelial keratinocytes was mediated by binding of the GAS hyaluronic acid capsular polysaccharide to CD44. In studies of transgenic mice with a selective defect in epithelial. expression of CD44, GAS adherence to CD44-deficient keratinocytes in vitro was reduced compared with adherence to keratinocytes expressing normal levels of CD44. After intranasal inoculation, GAS colonized the oropharynx of wild-type mice but failed to colonize transgenic mice deficient in CD44 expression. GAS colonization of wild-type mice could be blocked by coadministration of mAb to CD44 or by pretreatment of the animals with exogenous hyaluronic acid. These results provide evidence that CD44 serves as a receptor for GAS colonization of the pharynx and support the potential efficacy of disrupting the interaction between the GAS hyaluronic acid capsule and CD44 as a novel approach to preventing pharyngeal infection. C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Wessels, MR (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [AI75326, R01 AI029952, R15 AI075326, AI29952] NR 39 TC 63 Z9 65 U1 0 U2 5 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT PY 2000 VL 106 IS 8 BP 995 EP 1002 DI 10.1172/JCI10195 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 364XQ UT WOS:000089919700011 PM 11032859 ER PT J AU Patterson, MM Schrenzel, MD Feng, Y Xu, S Dewhirst, FE Paster, BJ Thibodeau, SA Versalovic, J Fox, JG AF Patterson, MM Schrenzel, MD Feng, Y Xu, S Dewhirst, FE Paster, BJ Thibodeau, SA Versalovic, J Fox, JG TI Helicobacter aurati sp nov., a urease-positive Helicobacter species cultured from gastrointestinal tissues of Syrian hamsters SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CAMPYLOBACTER-CINAEDI; BACTERIAL-INFECTION; HEPATICUS INFECTION; B6C3F(1) MICE; CARCINOGENESIS; PHYLOGENY; DISEASE; COLITIS; LIVERS; MUCOSA AB A. novel helicobacter with the proposed name Helicobacter aurati (type strain MIT 97-5075c) has been isolated from the inflamed stomachs and ceca of adult Syrian hamsters, The new species is fusiform with multiple bipolar sheathed flagella and periplasmic fibers; it contains urease and gamma-glutamyl transpeptidase. By 16S rRNA sequencing and repetitive element PCR-based DNA fingerprinting, it was found that H. aurati represents a distinct taxon and clusters with Helicobacter muridarum, Helicobacter hepaticus, and Helicobacter sp. MIT 94-022, H. aurati was recovered from hamsters housed in various research and vendor facilities. Further studies are necessary to define its association with disease and other microbiota in hamsters, as well as its impact on research projects involving hamsters, H. aurati (GenBank accession number AF297868) can be used in animal experiments to define the factors that are important for gastric helicobacter pathogenesis. C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. RP Fox, JG (reprint author), MIT, Div Comparat Med, Bldg 16-825, Cambridge, MA 02139 USA. FU NCRR NIH HHS [RRO7036]; NIAID NIH HHS [R01AI37750, R01 AI037750] NR 29 TC 35 Z9 35 U1 0 U2 1 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 OCT PY 2000 VL 38 IS 10 BP 3722 EP 3728 PG 7 WC Microbiology SC Microbiology GA 361DP UT WOS:000089707600034 PM 11015391 ER PT J AU Scadden, DT AF Scadden, DT TI Epstein-Barr virus, the CNS, and AIDS-related lymphomas: As close as flame to smoke SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dana Farber Partners CancerCare, Boston, MA 02114 USA. RP Scadden, DT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dana Farber Partners CancerCare, Boston, MA 02114 USA. NR 1 TC 12 Z9 12 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 OCT 1 PY 2000 VL 18 IS 19 BP 3323 EP 3324 PG 2 WC Oncology SC Oncology GA 361BA UT WOS:000089700800001 PM 11013270 ER PT J AU Pierce, LJ Strawderman, M Narod, SA Oliviotto, I Eisen, A Dawson, L Gaffney, D Solin, LJ Nixon, A Garber, J Berg, C Isaacs, C Heimann, R Olopade, OI Haffty, B Weber, BL AF Pierce, LJ Strawderman, M Narod, SA Oliviotto, I Eisen, A Dawson, L Gaffney, D Solin, LJ Nixon, A Garber, J Berg, C Isaacs, C Heimann, R Olopade, OI Haffty, B Weber, BL TI Effect of radiotherapy after breast-conserving treatment in women with breast cancer and germline BRCA1/2 mutations SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-18, 1999 CL ATLANTA, GA SP Amer Soc Clin Oncol ID RADIATION-THERAPY; CONSERVATIVE SURGERY; CONTRALATERAL BREAST; FAMILY HISTORY; OVARIAN-CANCER; STAGE-I; RISK; MASTECTOMY; CARCINOMA; IRRADIATION AB Purpose: Recent laboratory data suggest a role for BRCA 1/2 in the cellular response to DNA damage. There is a paucity of clinical data, however, examining the effect of radiotherapy (RT), which causes double-strand breaks, on breast tissue from BRCA 1/2 mutation carriers. Thus the goals of this study were to compare rates of radiation-associated complications, in-breast tumor recurrence, and distant relapse in women with BRCA 1/2 mutations treated with breast-conserving therapy (BCT) using RT with Kites observed in sporadic disease. Patients and Methods: Seventy-one women with a BRCA 1/2 mutation and stage I or II breast cancer treated with BCT were matched 1:3 with 213 women with sporadic breast cancer. Conditional logistic regression models were used ta compare matched cohorts for rates of complications and recurrence. Results: Tumors from women in the genetic cohort were associated with high histologic (P =.0004) and nuclear (P =.009) grade and negative estrogen (P =.0001) and progesterone (9 =.002) receptors compared with tumors from the sporadic cohort. Using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity scaring, there were no significant differences in acute or chronic morbidity in skin, subcutaneous tissue, lung, or bone. The 5-year actuarial overall survival, relapse-free survival, and rates of tumor control in the treated breast for the patients in the genetic cohort were 86%, 78%, and 98%, respectively, compared with 91%, 80%, and 96%, respectively, for the sporadic cohort (P = not significant). Conclusion: There was no evidence of increased radiation sensitivity or sequelae in breast tissue heterozygous for a BRCA 1/2 germline mutation compared with controls, and rates of tumor control in the breast and survival were comparable between BRCA 1/2 carriers and controls at 5 years. Although additional follow-up is needed, these data may help in discussing treatment options in the management of early-stage hereditary breast cancer and should provide reassurance regarding the safety of administering RT to carriers of a germline BRCA 1/2 mutation. J Clin Oncol 18:3360-3369. (C) 2000 by American Society of Clinical Oncology. C1 Univ Michigan, Sch Med, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Canc, Ann Arbor, MI 48109 USA. Univ Toronto, Ctr Res Womens Hlth, Toronto, ON, Canada. British Columbia Canc Agcy, Radiat Therapy Program, Vancouver, BC V5Z 4E6, Canada. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Univ Utah, Dept Radiat Oncol, Salt Lake City, UT USA. Harvard Univ, Joint Ctr Radiotherapy, Boston, MA USA. Harvard Univ, Dana Farber Canc Inst, Boston, MA USA. Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Dept Radiat Oncol, Washington, DC USA. Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Div Hematol Oncol, Washington, DC USA. Univ Chicago, Dept Radiat, Chicago, IL 60637 USA. Univ Chicago, Dept Cellular Oncol, Chicago, IL 60637 USA. Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. Yale Univ, Dept Therapeut Radiol, New Haven, CT USA. RP Pierce, LJ (reprint author), Univ Michigan, Sch Med, Dept Radiat Oncol, UH-B2C490,Box 0010,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM ljpierce@umich.edu NR 50 TC 139 Z9 143 U1 0 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2000 VL 18 IS 19 BP 3360 EP 3369 PG 10 WC Oncology SC Oncology GA 361BA UT WOS:000089700800007 PM 11013276 ER PT J AU Talamonti, MS Catalano, PJ Vaughn, DJ Whittington, R Beauchamp, RD Berlin, J Benson, AB AF Talamonti, MS Catalano, PJ Vaughn, DJ Whittington, R Beauchamp, RD Berlin, J Benson, AB TI Eastern Cooperative Oncology Group phase I trial of protracted venous infusion fluorouracil plus weekly gemcitabine with concurrent radiation therapy in patients with locally advanced pancreas cancer: A regimen with unexpected early toxicity SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ADENOCARCINOMA AB Purpose: We performed a phase I trial of protracted venous infusion (PVI) fluorouracil (5-FU) plus weekly gemcitabine with concurrent radiation therapy in patients with locally advanced pancreas cancer to determine the maximum-tolerated dose of gemcitabine that could be safely administered. We also sought to identify the toxicities associated with this treatment protocol. Patients and Methods: Seven patients with locally advanced pancreas cancer were treated with planned doses of radiation (59.4 Gy) and PVI of 5-FU (200 mg/m(2)/d) with gemcitabine doses of 50 to 100 mg/ m(2)/wk. Results: Two of three patients at the 100-mg/m(2)/wk dose level experienced dose-limiting toxicity (DLT), as did three of four at the 50-mg/m(2)/wk dose level. One patient experienced a mucocutaneous reaction described as a Stevens-Johnson syndrome that was attributed to chemotherapy. Three patients developed gastric or duodenal ulcers with severe bleeding requiring transfusion. One patient developed severe thrombocytopenia lasting longer than 4 weeks. Three of the five episodes of DLT developed at radiation doses less than or equal to 36 Gy, Conclusion: Based on this experience, we cannot recommend further investigation of regimens incorporating gemcitabine into regimens of radiation with PVI 5-FU. The mechanism of this synergistic toxicity remains to be determined. J Clin Oncol 18:3384-3389. (C) 2000 by American Society of Clinical Oncology. C1 Northwestern Univ, Sch Med, Dept Surg, Chicago, IL 60611 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. RP Talamonti, MS (reprint author), Northwestern Univ, Sch Med, Dept Surg, 675 N St Clair,Galter 17-250, Chicago, IL 60611 USA. FU NCI NIH HHS [CA23318, CA15488, CA17145] NR 13 TC 95 Z9 98 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 1 PY 2000 VL 18 IS 19 BP 3384 EP 3389 PG 6 WC Oncology SC Oncology GA 361BA UT WOS:000089700800010 PM 11013279 ER PT J AU Ximenez-Fyvie, LA Haffajee, AD Socransky, SS AF Ximenez-Fyvie, LA Haffajee, AD Socransky, SS TI Microbial composition of supra- and subgingival plaque in subjects with adult periodontitis SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE supragingival plaque; subgingival plaque; microbiology; bacteria periodontal diseases; DNA probes ID BACTEROIDES-FORSYTHUS; SUPRAGINGIVAL PLAQUE; TREPONEMA-DENTICOLA; DISEASE; HUMANS; BACTERIOLOGY; BIOFILMS; DNA; ATTACHMENT; SEVERITY AB Background, aims: The purpose of the present study was to compare and relate the microbial composition of supra and subgingival plaque in 23 adult periodontitis subjects (mean age 51+/-14 years). Methods: A total of 1.170 samples of supra and subgingival plaque were collected from the mesial aspect of every tooth (up to 28 supra and 28 subgingival samples) from each subject and evaluated for the presence and levels of 40 bacterial taxa using whole genomic DNA probes and checkerboard DNA-DNA hybridization. Clinical assessments including dichotomous measures of gingival redness, bleeding on probing, plaque accumulation and suppuration, as well as duplicate measures of pocket depth and attachment level. were made at 6 sites per tooth. The counts (levels), % DNA probe count (proportion) and % of sites colonized (prevalence) of each species in supra and separately in subgingival plaque were computed for each subject. Significance of differences between supra and subgingival plaque for each species was sought using the Wilcoxon signed ranks test and adjusted for multiple comparisons. Results: All 40 taxa were detected in both supra and subgingival plaque, Actinomyces species were the most prevalent taxa in both habitats. 75 to 100% of supra and 62 to 100% of subgingival sites were colonized by at least one of the 5 Actinomyces species. Supragingival samples exhibited significantly higher counts of Actinomyces naeslundii genospecies 1, Actinomyces israelii, Actinomyces odontolyticus, Neisseria mucosa, Streptococcus gordonii, Capnocytophaga ochracea and Capnocytophaga sputigena when compared with mean counts in subgingival samples taken from the same tooth surfaces. Subgingival plaque samples presented significantly higher counts of Prevotella nigrescens, Prevotella intermedia, Bacteroides forsythus and Porphyromonas gingivalis. Subgingival samples exhibited a significantly higher proportion of "red" and "orange complex" species, while supragingival plaque exhibited higher proportions of "green" and "purple" complex species as well as Actinomyces species. Suspected periodontal pathogens could be detected in supragingival plaque From sites where subgingival samples were negative for the same species. Conclusions: The data indicate that supragingival plaque can harbor putative periodontal pathogens, suggesting a possible role of this environment as a reservoir of such species for the spread or reinfection of subgingival sites. C1 Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. RP Haffajee, AD (reprint author), Forsyth Inst, Dept Periodontol, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-04881, DE-10977, DE-12108] NR 31 TC 178 Z9 189 U1 2 U2 18 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD OCT PY 2000 VL 27 IS 10 BP 722 EP 732 DI 10.1034/j.1600-051x.2000.027010722.x PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 358MX UT WOS:000089562800002 PM 11034118 ER PT J AU Ghaemi, SN Boiman, EE Goodwin, FK AF Ghaemi, SN Boiman, EE Goodwin, FK TI Diagnosing bipolar disorder and the effect of antidepressants: A naturalistic study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID MAJOR DEPRESSIVE EPISODE; MANIA; EFFICACY; ILLNESS; SAFETY AB Objectives: To determine if bipolar disorder is accurately diagnosed in clinical practice and to assess the effects of antidepressants on the course of bipolar illness. Method: Charts of outpatients with affective disorder diagnoses seen in an outpatient clinic during 1 year (N = 85 with bipolar or unipolar disorders) were reviewed. Past diagnostic and treatment information was obtained by patient report and systematic psychiatric history. Bipolar diagnosis was based on DSM-IV criteria using a SCID-based interview. Results: Bipolar disorder was found to be misdiagnosed as unipolar depression in 37% of patients who first see a mental health professional after their first manic/hypomanic episode. Antidepressants were used earlier and more frequently than mood stabilizers, and 23% of this unselected sample experienced a new or worsening rapid-cycling course attributable to antidepressant use. Conclusion: These results suggest that bipolar disorder tends be misdiagnosed as unipolar major depressive disorder and that antidepressants seem to be associated with a worsened course of bipolar illness. However, this naturalistic trial was uncontrolled, and more controlled research is required to confirm or refute these findings. C1 Harvard Univ, Sch Med, Psychopharmacol Program, Cambridge Hosp,Consolidated Dept Psychiat, Cambridge, MA 02138 USA. George Washington Univ, Dept Psychiat, Washington, DC USA. RP Ghaemi, SN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Bipolar Res Program, 15 Parkman St,WAC-812, Boston, MA 02114 USA. NR 20 TC 317 Z9 326 U1 3 U2 18 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD OCT PY 2000 VL 61 IS 10 BP 804 EP 808 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 371HM UT WOS:000165173000023 PM 11078046 ER PT J AU Kleespies, PM AF Kleespies, PM TI Special section: An empirical approach to behavioral emergencies part II: Violence to others and interpersonal victimization - Introductory comment SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Editorial Material C1 VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Kleespies, PM (reprint author), VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD OCT PY 2000 VL 56 IS 10 BP 1237 EP 1237 PG 1 WC Psychology, Clinical SC Psychology GA 361YL UT WOS:000089751800001 ER PT J AU Kleespies, PM Dettmer, EL AF Kleespies, PM Dettmer, EL TI The stress of patient emergencies for the clinician: Incidence, impact, and means of coping SO JOURNAL OF CLINICAL PSYCHOLOGY LA English DT Article DE behavioral emergencies; suicidal behavior; patient violence; clinician's stress; therapist coping ID PSYCHIATRY RESIDENCY PROGRAMS; CHILD SEXUAL ABUSE; NATIONAL SURVEY; SUICIDAL-BEHAVIOR; EVENT SCALE; THERAPISTS; PSYCHOLOGY; VIOLENCE; TRAUMA; EDUCATION AB This article presents evidence from the literature on the incidence and impact of behavioral emergencies on clinicians as well as suggestions for improved education and support for work in this area. Behavioral emergencies are conceptualized as including imminent life-threatening behaviors such as patient suicidal behavior, patient violence, and instances in which patients become the victims of interpersonal violence. Suggestions are offered for how clinicians can understand and cope with their own reactions during and after such patient emergencies. Additionally. data on deficits in the education and training of psychologists are presented along with suggestions for how programs and clinical sites can improve their training in emergency and crisis work. (C) 2000 John Wiley & Sons, Inc. C1 VA Boston Healthcare Syst, Psychol Serv 116B, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Kleespies, PM (reprint author), VA Boston Healthcare Syst, Psychol Serv 116B, 150 S Huntington Ave, Boston, MA 02130 USA. NR 55 TC 8 Z9 8 U1 4 U2 6 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9762 J9 J CLIN PSYCHOL JI J. Clin. Psychol. PD OCT PY 2000 VL 56 IS 10 BP 1353 EP 1369 DI 10.1002/1097-4679(200010)56:10<1353::AID-JCLP7>3.0.CO;2-3 PG 17 WC Psychology, Clinical SC Psychology GA 361YL UT WOS:000089751800007 PM 11051063 ER PT J AU Faraone, SV Biederman, J Feighner, JA Monuteaux, MC AF Faraone, SV Biederman, J Feighner, JA Monuteaux, MC TI Assessing symptoms of attention deficit hyperactivity disorder in children and adults: Which is more valid? SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID BEHAVIOR CHECKLIST; COLLEGE-STUDENTS; TWIN; ADHD; CHILDHOOD; COMORBIDITY; SAMPLE; ADOLESCENCE; SCORES; CURVES AB The assessment of attention deficit hyperactivity disorder (ADHD) in adults has been a source of controversy. The authors tested competing ideas by evaluating familial transmission among adult and nonadult relatives of ADHD children. They analyzed ADHD symptom data collected by structured interviews from the members of 280 ADHD and 242 non-ADHD families. For both past and current symptoms. both the boys' and girls' families showed significantly more familial aggregation for adult relatives than for nonadult relatives. The results were similar for inattentive and hyperactive-impulsive symptoms and for relatives with and without psychiatric comorbidity. The results provide further evidence for the validity of adult ADHD and support the intriguing idea that, from a familial perspective, the assessment of ADHD may be more Valid in adults than in children. They do not support the idea that parents of ADHD children are biased to report ADHD symptoms in themselves because of their exposure to an ADHD child. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC 725, Child Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. RP Faraone, SV (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC 725, Child Psychiat Serv, 15 Parkman St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [R01HD37694]; NIMH NIH HHS [R01MH57934, R13MH59126] NR 51 TC 73 Z9 73 U1 1 U2 6 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD OCT PY 2000 VL 68 IS 5 BP 830 EP 842 DI 10.1037/0022-006X.68.5.830 PG 13 WC Psychology, Clinical SC Psychology GA 368GA UT WOS:000090108300009 PM 11068969 ER PT J AU Carson, MA Paulus, LA Lasko, NB Metzger, LJ Wolfe, J Orr, SP Pitman, RK AF Carson, MA Paulus, LA Lasko, NB Metzger, LJ Wolfe, J Orr, SP Pitman, RK TI Psychophysiologic assessment of posttraumatic stress disorder in Vietnam nurse veterans who witnessed injury or death SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID COMBAT VETERANS; IMAGERY; DISASTER; IMPACT; PTSD; PERSONNEL; RESPONSES; VICTIMS; SAMPLE; SCALE AB This study examined whether witnessing death and injury could produce psychophysiologically responsive posttraumatic stress disorder (PTSD). Participants consisted of medication-free female Vietnam nurse veterans with a diagnosis of current PTSD (n = 17) and who never had PTSD (n = 21), related to their military service. Individualized scripts describing personal traumatic military nursing events, a standard military nursing event, and other life events were tape recorded and played back to the participant while heart rate, skin conductance, and facial electromyograms were recorded. Nurses with PTSD showed significantly larger physiologic responses than non-PTSD nurses only during imagery of military-related nursing events. The groups' self-reported emotional responses did not differ during imagery. Psychophysiologic results support the proposition that witnessing death and serious injury to others is sufficiently stressful to cause PTSD. C1 Vet Affairs Med Ctr, Res Serv, Manchester, NH 03103 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Vet Affairs Med Ctr, Natl Ctr PTSD, Boston, MA USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. RP Carson, MA (reprint author), Vet Affairs Med Ctr, Res Serv, 228 Maple St,2nd Floor, Manchester, NH 03103 USA. NR 43 TC 59 Z9 60 U1 3 U2 7 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD OCT PY 2000 VL 68 IS 5 BP 890 EP 897 DI 10.1037/0022-006X.68.5.890 PG 8 WC Psychology, Clinical SC Psychology GA 368GA UT WOS:000090108300015 PM 11068975 ER PT J AU Sagarin, MJ Brown, DFM Nadel, ES Benzer, T Thomas, S Gordon, J Tancredi, D Silvers, S Lewiss, R Nikkanen, H Kobayashi, L AF Sagarin, MJ Brown, DFM Nadel, ES Benzer, T Thomas, S Gordon, J Tancredi, D Silvers, S Lewiss, R Nikkanen, H Kobayashi, L TI Altered mental status in alcoholism SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID LUMBAR PUNCTURE; BACTERIAL-MENINGITIS; COMPUTED-TOMOGRAPHY; WITHDRAWAL; HYPONATREMIA C1 Massachusetts Gen Hosp, Dept Emergency Med CLN115, Boston, MA 02114 USA. Harvard Affiliated Emergency Med Residency, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med CLN115, 15 Fruit St, Boston, MA 02114 USA. NR 15 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 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD OCT PY 2000 VL 19 IS 3 BP 271 EP 274 DI 10.1016/S0736-4679(00)00236-5 PG 4 WC Emergency Medicine SC Emergency Medicine GA 361FK UT WOS:000089712200011 PM 11033274 ER PT J AU Seminara, SB Oliveira, LMB Beranova, M Hayes, FJ Crowley, WF AF Seminara, SB Oliveira, LMB Beranova, M Hayes, FJ Crowley, WF TI Genetics of hypogonadotropic hypogonadism SO JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION LA English DT Article DE hypogonadism; KAL; DAX1; GNRH ID GONADOTROPIN-RELEASING-HORMONE; ADRENAL HYPOPLASIA CONGENITA; LINKED KALLMANN-SYNDROME; GONADAL AXIS; PROP1 GENE; CANDIDATE GENE; DEFICIENCY; MUTATIONS; RECEPTOR; EXPRESSION AB Determining the physiologic influences that modulate GnRH secretion, the prime initiator of reproductive function in the human, is fundamental not only to our understanding of the rare condition of congenital idiopathic hypogonadotropic hypogonadism (IHH), but also common disorders such as constitutional delay of puberty and hypothalamic amenorrhea. IHH is characterized by low levels of sex steroids and gonadotropins, normal findings on radiographic imaging of the hypothalamic-pituitary regions, and normal baseline and reserve testing of the remainder of the hypothalamic-pituitary axes. Failure of the normal pattern of episodic GnRH secretion results in delay of puberty and infertility. IHH is characterized by rich clinical and genetic heterogeneity, variable modes of inheritance, and association with other anomalies. To date, 4 genes have been identified as causes of IHH in the human; KAL [the gene for X-linked Kallmann syndrome (IHH and anosmia)], DAX1 [the gene for X-linked adrenal hypoplasia congenita (IHH and adrenal insufficiency)], GNRHR (the GnRH receptor), and PC1 (the gene for prohormone convertase 1, causing a syndrome of IHH and defects in prohormone processing). As these mutations account for less than 20% of all IHH cases, discovery of additional gene mutations will continue to advance our understanding of this intriguing syndrome. (J. Endocrinol. Invest. 23: 560-565, 2000) (C) 2000, Editrice Kurtis. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Seminara, SB (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Bartlett Hall Extens 505,Fruit St, Boston, MA 02114 USA. FU NICHD NIH HHS [P30 HD028138, R01 HD015788, U54 HD029164, U54 HD028138] NR 51 TC 46 Z9 47 U1 2 U2 6 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 0391-4097 J9 J ENDOCRINOL INVEST JI J. Endocrinol. Invest. PD OCT PY 2000 VL 23 IS 9 BP 560 EP 565 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 366VC UT WOS:000090026100002 PM 11079449 ER PT J AU Kogai, T Curcio, F Hyman, S Cornford, EM Brent, GA Hershman, JM AF Kogai, T Curcio, F Hyman, S Cornford, EM Brent, GA Hershman, JM TI Induction of follicle formation in long-term cultured normal human thyroid cells treated with thyrotropin stimulates iodide uptake but not sodium/iodide symporter messenger RNA and protein expression SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID APICAL PLASMA-MEMBRANE; NA+/I SYMPORTER; FRTL-5 CELLS; CONGENITAL HYPOTHYROIDISM; HORMONE SYNTHESIS; EPITHELIAL-CELLS; GENE-EXPRESSION; COLLAGEN GEL; TRANSPORT; ADENOSINE-3',5'-MONOPHOSPHATE AB Iodide uptake by the sodium/iodide symporter (NIS) in thyrocytes is essential for thyroid hormone production. Reduced NIS activity has been reported in thyroid diseases, including thyroid cancer and congenital hypothyroidism. The study of iodide uptake in thyrocytes has been limited by the availability of appropriate in vitro models, A new culture technique was recently developed that allows normal human thyroid primary culture cells to grow as monolayer cells and express differentiated functions for more than 3 months. We used this technique to study the effect of follicle formation and TSH on iodide uptake in these cells. Iodide uptake by the cells grown in monolayer was very low. Follicle formation was induced from monolayer cells, and electron micrographs demonstrated cell polarity in the follicles. No significant increase in iodide uptake was observed after TSH treatment of cells in monolayer or when follicle formation was induced without TSH. TSH stimulation of follicles, however, significantly increased iodide uptake (similar to4.4-fold; P<0.001). Compared with iodide uptake in monolayers, the combination of follicle formation and TSH treatment stimulated iodide uptake synergistically to 12.0-fold (P<0.001). NIS messenger RNA (mRNA) and protein levels were almost the same in both monolayer cells and follicles. TSH treatment of monolayers and follicles produced significant (P<0.05) stimulation of mRNA (4.8- and 4.3-fold respectively) and protein (similar to6.8- and 4.9-fold respectively). TSH stimulated NIS protein levels in both monolayer and follicles, however, stimulation of functional iodide uptake was only seen with TSH stimulation of follicles. The function of NIS may involve post-transcriptional events, such as intracellular sorting, membrane localization of NIS or another NIS regulatory factor. Polarized functions, such as iodide efflux into follicular lumina, may also contribute to the increased iodide concentration after follicle formation. C1 W Los Angeles VA Med Ctr, Div Endocrinol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90073 USA. Univ Udine, Dipartimento Patol & Med Sperimentale & Clin, I-33100 Udine, Italy. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. W Los Angeles VA Med Ctr, SW Reg VA Epilepsy Ctr, Res Serv, Los Angeles, CA 90073 USA. W Los Angeles VA Med Ctr, SW Reg VA Epilepsy Ctr, Neurol Serv, Los Angeles, CA 90073 USA. RP Hershman, JM (reprint author), W Los Angeles VA Med Ctr, Div Endocrinol & Metab 111D, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Curcio, Francesco/K-4669-2014 FU NIDDK NIH HHS [DK 43714]; NINDS NIH HHS [NS 37360] NR 42 TC 45 Z9 50 U1 0 U2 4 PU SOC ENDOCRINOLOGY PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4NQ, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD OCT PY 2000 VL 167 IS 1 BP 125 EP 135 DI 10.1677/joe.0.1670125 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 406HR UT WOS:000167209300014 PM 11018760 ER PT J AU Sutton, PR Harley, JD Jacobson, AF Lipsky, BA AF Sutton, PR Harley, JD Jacobson, AF Lipsky, BA TI Diagnosing osteomyelitis with percutaneous bone biopsy in patients with diabetes and foot ulcerations. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Dept Radiol, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Dept Nucl Med, Seattle, WA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2000 VL 15 SU 2 BP 6 EP 6 DI 10.1046/j.1525-1497.2000.15200-25.x PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 374CK UT WOS:000165326700026 ER PT J AU Thorndike, AN Biener, L Rigotti, NA AF Thorndike, AN Biener, L Rigotti, NA TI Impact of the switch of nicotine replacement therapy to the over-the-counter status. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2000 VL 15 SU 2 BP 7 EP 7 DI 10.1046/j.1525-1497.2000.15200-28.x PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 374CK UT WOS:000165326700029 ER PT J AU Wee, CC Rigotti, NA Davis, RB Phillips, RS AF Wee, CC Rigotti, NA Davis, RB Phillips, RS TI The relationship between concerns about body weight and smoking behavior. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2000 VL 15 SU 2 BP 9 EP 9 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 374CK UT WOS:000165326700038 ER PT J AU Barry, MJ AF Barry, MJ TI Early detection and aggressive treatment of prostate cancer - Groping in the dark SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material ID MORTALITY; ANTIGEN; MEN C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 20 TC 6 Z9 6 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD OCT PY 2000 VL 15 IS 10 BP 749 EP 751 DI 10.1046/j.1525-1497.2000.00816.x PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 371BZ UT WOS:000165159000009 PM 11089719 ER PT J AU Sonntag, KC Nebhard, N Haller, GW Yasumoto, A Sachs, DH Leguern, C AF Sonntag, KC Nebhard, N Haller, GW Yasumoto, A Sachs, DH Leguern, C TI Assessment of transduction rates of porcine bone marrow SO JOURNAL OF HEMATOTHERAPY & STEM CELL RESEARCH LA English DT Article ID MEDIATED GENE-TRANSFER; HEMATOPOIETIC PROGENITOR CELLS; RETROVIRAL VECTOR; CORD-BLOOD; MINIATURE SWINE; EXPRESSION; TRANSPLANTATION; LEUKEMIA; CULTURE; CDNA AB Although drug resistance is commonly used as an indicator of gene transfer in various cellular contexts, the assessment of drug resistance is often imprecise and over-estimated. To measure accurately transduction efficiencies of the retroviral-mediated transfer of genes encoding the neomycine phosphotransferase (Neo(r)) and porcine major histocompatibility (MHC) class II in pig bone marrow cells (BMC), the fraction of targeted progenitors was evaluated by both colony-forming unit granulocytes/macrophages assays (G418(r) CFU-GM) and by PCR analysis of the transgenes (Tg). Transduced and untransduced BMC were selected at different concentrations of G418 and revealed high individual variability of drug sensitivity. Comparison of the results obtained by estimating the CFU frequency and the PCR assays on drug-resistant colonies demonstrated a marked overestimation of BM transduction rates when determined by G418 resistance alone, because only approximately one-third of individual colonies were positive for both the Neo(r) and the class II Tg. Because this discrepancy is likely to affect the overall assessment of transduction rates using drug resistance markers, our data attest for the need of a combination of molecular assays to determine transduction efficiencies accurately. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Columbia Univ, New York, NY 10027 USA. Chiba Univ, Dept Surg 2, Chiba 260, Japan. RP Leguern, C (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [5RO1 HL46532]; NIAID NIH HHS [2RO1 AI33053, 2RO1 AI31046] NR 28 TC 1 Z9 1 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1525-8165 J9 J HEMATOTH STEM CELL JI J. Hematother. Stem Cell Res. PD OCT PY 2000 VL 9 IS 5 BP 721 EP 726 DI 10.1089/15258160050196768 PG 6 WC Hematology; Medicine, Research & Experimental; Transplantation SC Hematology; Research & Experimental Medicine; Transplantation GA 375ZE UT WOS:000165432700016 PM 11091496 ER PT J AU Gazitt, Y Callander, N Freytes, CO Shaughnessy, P Liu, Q Tsai, TW Devore, P AF Gazitt, Y Callander, N Freytes, CO Shaughnessy, P Liu, Q Tsai, TW Devore, P TI Peripheral blood stem cell mobilization with cyclophosphamide in combination with G-CSF, GM-CSF, or sequential GM-CSF/G-CSF in non-Hodgkin's lymphoma patients: A randomized prospective study SO JOURNAL OF HEMATOTHERAPY & STEM CELL RESEARCH LA English DT Article ID COLONY-STIMULATING FACTOR; HEMATOPOIETIC PROGENITOR CELLS; HIGH-DOSE CHEMOTHERAPY; CLONAL MYELOMA CELLS; MULTIPLE-MYELOMA; ENGRAFTMENT KINETICS; MALIGNANT-LYMPHOMA; SOLID TUMORS; BONE-MARROW; GRANULOCYTE AB We designed a randomized, prospective three-arm mobilization study to determine the kinetics of peripheral blood stem cell (PBSC) mobilization in 60 non-Hodgkin's lymphoma (NHL) patients primed with cyclophosphamide (CTX) in combination with granulocyte colony-stimulating factor (G-CSF) (arm A), granulocyte-macrophage (GM)-CSF (arm B) or GM-CSF/G-CSF (arm C). We also compared mobilization and transplant-related toxicities, pre- and post-transplant support and the probability of survival among the three arms. To date, 35 patients have been enrolled in the study; 13 patients have been enrolled in arm A, 10 patients in arm B, and 13 patients in arm C. Successful collection of the target of greater than or equal to 2x10(6) CD34(+) cells/kg in one to four apheresis collections was 10/13, 6/10, and 7/12 in arms A, B, and C, respectively. The differences between arms were not statistically significant. The median time to achieve the target CD34(+) cells in patients who successfully mobilized the target CD34(+) cells was 3 days, 2 days, and 1 day, in patients in arms A, B, and C, respectively. The time for neutrophil engraftment was 11, 10, and 10 days in arms A, B, and C, respectively. The time for platelet engraftment was 11 days for patients in all arms of the study. Most importantly, no significant differences were observed among the three arms in the duration of neutropenic fever, the extent of mucositis, diarrhea, and nausea/vomiting, or in the number of units of platelets or red cells transfused after transplantation. Risk factors associated with poor mobilization were greater than or equal to3 regimens of chemotherapy prior to mobilization, older age, and disease histology (follicular versus diffuse). Therefore, we conclude that the type of growth factor used for mobilization did not play a major role in the outcome of mobilization and recommend mobilizing NHL patients before they receive multiple regimens of chemotherapy. C1 Univ Texas, Hlth Sci Ctr, Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. Wilford Hall USAF Med Ctr, San Antonio, TX 78284 USA. RP Gazitt, Y (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med Hematol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 36 TC 31 Z9 31 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1525-8165 J9 J HEMATOTH STEM CELL JI J. Hematother. Stem Cell Res. PD OCT PY 2000 VL 9 IS 5 BP 737 EP 748 DI 10.1089/15258160050196786 PG 12 WC Hematology; Medicine, Research & Experimental; Transplantation SC Hematology; Research & Experimental Medicine; Transplantation GA 375ZE UT WOS:000165432700018 PM 11091498 ER PT J AU Sasaki, H Hou, L Belani, A Wang, CY Uchiyama, T Muller, R Stashenko, P AF Sasaki, H Hou, L Belani, A Wang, CY Uchiyama, T Muller, R Stashenko, P TI IL-10, but not IL-4, suppresses infection-stimulated bone resorption in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BLOOD MONONUCLEAR-CELLS; INFLAMMATORY BOWEL-DISEASE; CYTOKINE GENE-EXPRESSION; PERIAPICAL LESIONS; FORMATION INVITRO; HUMAN MONOCYTES; INTERLEUKIN-6 PRODUCTION; RECEPTOR ANTAGONIST; MARROW CULTURE; MESSENGER-RNA AB Periapical bone resorption occurs following infection of the dental pulp and is mediated mainly by IL-1 alpha in the murine model. The production and activity of IL-1 alpha is modulated by a network of regulatory cytokines, including those produced hy Th1 (proinflammatory) and Th2 (anti-inflammatory) subset T cells, This study was designed to assess the functional role of the Th2-type cytokines IL-4 and IL-10 in infection-stimulated bone resorption in vivo. The dental pulps of the first molars were exposed and infected with a mixture of four common endodontic pathogens, and bone destruction was determined by micro-computed tomography at sacrifice on day 21, The results demonstrate that IL-10(-/-) mice had significantly greater infection-stimulated bone resorption in vivo compared with wild-type mice (p < 0.001), whereas IL-4(-/-) exhibited no increased resorption, IL-10(-/-) had markedly elevated IL-1 alpha production within periapical inflammatory tissues (>10-fold) compared with wild type (p < 0.01), whereas IL-4(-/-) exhibited decreased IL-1 alpha production (p < 0.05). IL-10 also suppressed IL-1 alpha production by macrophages in a dose-dependent fashion in vitro, whereas IL-4 had weak and variable effects, We conclude that IL-10, but not IL-4, is an important endogenous suppressor of infection-stimulated bone resorption in vivo, likely acting via inhibition of IL-1 alpha expression. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Univ Michigan, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. Beth Israel Deaconess Med Ctr, Orthopaed Biomech Lab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Stashenko, P (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. RI Muller, Ralph/A-1198-2008 OI Muller, Ralph/0000-0002-5811-7725 FU NIDCR NIH HHS [DE-09018] NR 58 TC 103 Z9 106 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2000 VL 165 IS 7 BP 3626 EP 3630 PG 5 WC Immunology SC Immunology GA 357AZ UT WOS:000089477500014 PM 11034365 ER PT J AU Yang, OO Racke, FK Nguyen, PT Gausling, R Severino, ME Horton, HF Byrne, MC Strominger, JL Wilson, SB AF Yang, OO Racke, FK Nguyen, PT Gausling, R Severino, ME Horton, HF Byrne, MC Strominger, JL Wilson, SB TI CD1d on myeloid dendritic cells stimulates cytokine secretion from and cytolytic activity of V alpha 24J alpha Q T cells: A feedback mechanism for immune regulation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DEPENDENT DIABETES-MELLITUS; IMMUNOGLOBULIN-E PRODUCTION; NATURAL-KILLER-CELLS; V(ALPHA)14 NKT CELLS; ALPHA-GALACTOSYLCERAMIDE; SELECTIVE REDUCTION; DEFICIENT MICE; CUTTING EDGE; HELPER-CELLS; HUMAN BLOOD AB The precise immunologic functions of CD1d-restricted, CD161(+) AV24AJ18 (V alpha 24J alpha Q) T cells are not well defined, although production of IL-4 has been suggested as important for priming Th2 responses, However, activation of human V alpha 224J alpha Q T cell clones by anti-CD3 resulted in the secretion of multiple cytokines notably important for the recruitment and differentiation of myeloid dendritic cells. Specific activation of V alpha 24J alpha Q T cells was CD1d restricted. Expression of CD1d was found on monocyte-derived dendritic cells in vitro, and immunohistochemical staining directly revealed CD1d preferentially expressed on dendritic cells in the paracortical T cell zones of lymph nodes. Moreover, myeloid dendritic cells both activated V alpha 24J alpha Q T cells and were susceptible to lysis by these same regulatory T cells. Because myeloid dendritic cells are a major source of IL-12 and control Th1 cell differentiation, their elimination by lysis is a mechanism for limiting the generation of Th1 cells and thus regulating Th1/Th2 responses. C1 Univ Calif Los Angeles, Div Infect Dis, Med Ctr, Los Angeles, CA 90095 USA. Massachusetts Gen Hosp E, Ctr AIDS Res, Infect Dis Unit, Charlestown, MA 02129 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Genet Inst, Cambridge, MA 02140 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21287 USA. RP Racke, FK (reprint author), Univ Calif Los Angeles, Div Infect Dis, Med Ctr, 37-121 CHS,10833 LeConte Ave, Los Angeles, CA 90095 USA. FU NCI NIH HHS [R35CA47554]; NIAID NIH HHS [R01AI043203, KO8AI0413] NR 57 TC 52 Z9 52 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 OCT 1 PY 2000 VL 165 IS 7 BP 3756 EP 3762 PG 7 WC Immunology SC Immunology GA 357AZ UT WOS:000089477500029 PM 11034380 ER PT J AU Gollob, JA Veenstra, KG Jyonouchi, H Kelly, AM Ferrieri, P Panka, DJ Altare, F Fieschi, C Casanova, JL Frank, DA Mier, JW AF Gollob, JA Veenstra, KG Jyonouchi, H Kelly, AM Ferrieri, P Panka, DJ Altare, F Fieschi, C Casanova, JL Frank, DA Mier, JW TI Impairment of STAT activation by IL-12 in a patient with atypical mycobacterial and staphylococcal infections SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERFERON-GAMMA; TYROSINE PHOSPHORYLATION; INTERLEUKIN-12 RESPONSIVENESS; SERINE PHOSPHORYLATION; CALMETTE-GUERIN; PROTEIN-KINASE; IFN-GAMMA; TH2 CELLS; RECEPTOR; DEFICIENCY AB IL-12 plays a pivotal role in the stimulation of immune responses against intracellular infections. This role is manifested in the increased susceptibility to atypical mycobacterial and salmonella infections among individuals whose lymphocytes lack expression of IL-12R beta 1. Here, we report on a patient with Mycobacterium avium infection, recurrent Staphylococcus aureus sinusitis, and multiple adverse drug reactions whose T cells were unable to produce IFN-gamma or proliferate in response to IL-12 despite the expression of wild-type IL-12R beta 1 and IL-12R beta 2. The defect in these functional responses to IL-12 was selective, as cytolytic activity induced by IL-12 was intact, and lymphocytes were responsive to stimulation by IL-2. An examination of cytokine signaling revealed that STAT4 and extracellular regulated kinase 1 (ERK1) activation by IL-12 was intact, whereas the activation of STAT1, -3, and -5 by IL-12 was lost. This impairment of STAT activation was specific for IL-12, as STAT activation by IL-2, IL-15, and IFN-gamma was unaffected. These findings demonstrate that the activation of STAT4 alone is not sufficient for IL-12-induced IFN-gamma production and proliferation and suggest that other STATs play a role in these responses to IL-12. While the etiology of the impaired IL-12 signaling in this patient has not yet been elucidated, the absence of mutations in IL-12R beta 1 or IL-12R beta 2 and the preservation of STAT4 activation raise the possibility that there may be a mutation in an as yet undiscovered component of the IL-12 signaling complex that is normally required for the recruitment and activation of STAT1, -3, and -5. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Dept Med, Div Hematol Oncol, Boston, MA 02215 USA. Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Lab Med Pathol, Minneapolis, MN 55455 USA. Fac Med Necker, Lab Genet Humaine Malad Infect, Paris, France. Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Gollob, JA (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr,Dept Med, Div Hematol Oncol, 330 Brookline Ave,E Campus,Room KS-158, Boston, MA 02215 USA. FU NCI NIH HHS [CA74401] NR 29 TC 34 Z9 35 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2000 VL 165 IS 7 BP 4120 EP 4126 PG 7 WC Immunology SC Immunology GA 357AZ UT WOS:000089477500073 PM 11034424 ER PT J AU Ferbas, J Giorgi, JV Amini, S Grovit-Ferbas, K Wiley, DJ Detels, R Plaeger, S AF Ferbas, J Giorgi, JV Amini, S Grovit-Ferbas, K Wiley, DJ Detels, R Plaeger, S TI Antigen-specific production of RANTES, macrophage inflammatory protein (MIP)1 alpha, and MIP-1 beta in vitro is a correlate of reduced human immunodeficiency virus burden in vivo SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT International Meeting of the Institute-of-Human-Virology CY AUG 28-SEP 02, 1999 CL BALTIMORE, MARYLAND SP Inst Human Virol ID C-C CHEMOKINES; BETA-CHEMOKINES; HIV-INFECTION; DISEASE PROGRESSION; IN-VITRO; EXPRESSION; INFECTABILITY; INDIVIDUALS; CD4(+); CELLS AB RANTES (regulated on activation, normal T expressed and secreted), macrophage inflammatory protein (MIP)-1 alpha, and MIP-1 beta are human immunodeficiency virus (HIV) suppressor factors by virtue of their ability to compete with HIV for access to cell surface R5. Their ability to block HIV infection in vitro is unequivocal; however, their role as HIV suppressor factors in vivo is not firmly established. We therefore conducted a study to test the hypothesis that production of these factors in vitro was a correlate of decreased virus burden in vivo. Moreover, we asked whether higher beta chemokine production could be demonstrated with cells from people who are R5D32 heterozygotes, compared with people who are R5 wild-type homozygotes. Our data support the thesis that RANTES, MIP-1 alpha, and MIP-1 beta production is associated with decreased in vivo virus load. Moreover, enhanced production of these facto rs may be explained in part by the genetic background of the host. C1 Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Epidemiol, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Ferbas, J (reprint author), Amgen, 1 Amgen Ctr Dr, Thousand Oaks, CA 91320 USA. FU NIAID NIH HHS [AI-37613-04] NR 15 TC 31 Z9 32 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT PY 2000 VL 182 IS 4 BP 1247 EP 1250 DI 10.1086/315849 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 361FJ UT WOS:000089712100034 PM 10979927 ER PT J AU Gillies, R Zonios, G Anderson, RR Kollias, N AF Gillies, R Zonios, G Anderson, RR Kollias, N TI Fluorescence excitation spectroscopy provides information about human skin in vivo SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE collagen; cross-links; elastin; tryptophan ID AUTOFLUORESCENCE; PHOTOGRAPHY AB Fluorescence spectroscopy of human skin has potential to provide useful morphologic and biochemical information. The endogenous fluorescence of human skin has been investigated in vivo on normal human volunteers as well as on patients with psoriasis and it was found that characteristic bands can be identified in the fluorescence spectra that are associated with specific skin fluorophores. One epidermal band (295 nm excitation, attributed to tryptophan) and two dermal bands (335 and 370 nm excitation, attributed to collagen cross-links) were consistently present in all fluorescence spectra. In addition, the fluorescence spectra obtained from lesions and nonlesional sites of psoriatic patients differed from those obtained from healthy volunteers and the hyperproliferative state of the lesions was characterized by a significantly larger signal at 295 nm excitation. These results indicate that fluorescence spectroscopy is a promising technique for the investigation of human skin in vivo. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. RP Kollias, N (reprint author), Johnson & Johnson Consumer Prod Inc, Methods & Models, 199 Grandview Rd, Skillman, NJ 08558 USA. NR 18 TC 81 Z9 81 U1 0 U2 5 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 OCT PY 2000 VL 115 IS 4 BP 704 EP 707 DI 10.1046/j.1523-1747.2000.00091.x PG 4 WC Dermatology SC Dermatology GA 363CK UT WOS:000089816700018 PM 10998147 ER PT J AU Hong, W Morimatsu, S Goto, T Sachs, G Scott, DR Weeks, DL Kohno, T Morita, C Nakano, T Fujioka, Y Sano, K AF Hong, W Morimatsu, S Goto, T Sachs, G Scott, DR Weeks, DL Kohno, T Morita, C Nakano, T Fujioka, Y Sano, K TI Contrast-enhanced immunoelectron microscopy for Helicobacter pylori SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE alcian blue; contrast enhancement; Helicobacter pylori; immunoelectron microscopy ID HEAT-SHOCK PROTEIN; LOCALIZATION; UREASE; VIRUS AB Since a method of contrast enhancement for immunoelectron microscopy has not been available in bacteriology, the morphological localization of proteins of Helicobacter pylori is not well known. In this report, we established a method of contrast enhancement in immunoelectron microscopy in this organism. Immunostained ultrathin sections are stained with a mixture of alcian blue and osmium tetroxide prior to staining with uranyl acetate. This method of staining provided good contrast enhancement of the bacterial cell wall and membrane without any loss of immunolabeled gold particles on the ultrathin section. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Osaka Med Coll, Dept Microbiol, Takatsuki, Osaka 5698686, Japan. Univ Calif Los Angeles, Dept Physiol & Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Sano, K (reprint author), Osaka Med Coll, Dept Microbiol, 2-7 Daigaku Machi, Takatsuki, Osaka 5698686, Japan. NR 17 TC 10 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 J9 J MICROBIOL METH JI J. Microbiol. Methods PD OCT PY 2000 VL 42 IS 2 BP 121 EP 127 DI 10.1016/S0167-7012(00)00165-2 PG 7 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 362UU UT WOS:000089797300002 PM 11018268 ER PT J AU Paster, BJ Dewhirst, FE AF Paster, BJ Dewhirst, FE TI Phylogenetic foundation of spirochetes SO JOURNAL OF MOLECULAR MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article ID BORRELIA-BURGDORFERI; SELECTIVE AGENT; SP-NOV; DIVERSITY; RIFAMPIN; ENUMERATION; POSITION; GUT AB The spirochetes are free-living or host-associated, helical bacteria, some of which are pathogenic to man and animal. Comparisons of 16S rRNA sequences demonstrate that the spirochetes represent a monophyletic phylum within the bacteria. The spirochetes are presently classified in the Class Spirochaetes in the order Spirochetales and are divided into three major phylogenetic groupings, or families. The first family Spirochaetaceae contains species of the genera Borrelia, Brevinema, Cristispira, Spirochaeta, Spironema, and Treponema. The second family Brachyspiraceae contains the genus Brachyspira (Serpulina). The third family Leptospiraceae contains species of the genera Leptonema and Leptospira. Novel spirochetal species, or phylotypes, that can not be presently cultivated in vitro, have been identified from the human oral cavity, the termite gut, and other host-associated or free-living sources. There are now over 200 spirochetal species or phylotypes, of which more than half is presently not cultivable. It is likely that there is still a significant unrecognized spirochetal diversity that should be evaluated. C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. RP Paster, BJ (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-10374] NR 34 TC 64 Z9 65 U1 1 U2 13 PU HORIZON SCIENTIFIC PRESS PI WYMONDHAM PA PO BOX 1, NORFOLK, WYMONDHAM NR18 0JA, ENGLAND SN 1464-1801 J9 J MOL MICROB BIOTECH JI J. Mol. Microbiol. Biotechnol. PD OCT PY 2000 VL 2 IS 4 BP 341 EP 344 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 404JG UT WOS:000167093200002 PM 11075904 ER PT J AU Nagayama, T Lan, J Henshall, DC Chen, DX O'Horo, C Simon, RP Chen, J AF Nagayama, T Lan, J Henshall, DC Chen, DX O'Horo, C Simon, RP Chen, J TI Induction of oxidative DNA damage in the peri-infarct region after permanent focal cerebral ischemia SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE focal cerebral ischemia; DNA fragmentation; apurinic/apyrimidinic abasic sites; 8-hydroxyl-2 '-deoxyguanosine ID PROGRAMMED CELL-DEATH; ABASIC SITES; TIRILAZAD MESYLATE; RADICAL FORMATION; ARTERY OCCLUSION; STRAND BREAKS; NITRIC-OXIDE; BRAIN-DAMAGE; RAT-BRAIN; APOPTOSIS AB To address the role of oxidative DNA damage in focal cerebral ischemia lacking reperfusion, we investigated DNA base and strand damage in a rat model of permanent middle cerebral artery occlusion (MCAO), Contents of 8-hydroxyl-2'-deoxyguanosine (8-OHdG) and apurinic/apyrimidinic abasic sites (AP sites), hallmarks of oxidative DNA damage, were quantitatively measured in nuclear DNA extracts from brains obtained 4-72 h after MCAO, DNA single- and double-strand breaks were detected on coronal brain sections using in situ DNA polymerase I-mediated biotin-dATP nick-translation (PANT) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL), respectively, Levels of 8-OHdG and AP sites were markedly elevated 16-72 h following MCAO in the frontal cortex, representing the peri-infarct region, but levels did not significantly change within the ischemic core regions of the caudate-putamen and parietal cortex. PANT- and TUNEL-positive cells began to be detectable 4-8 h following MCAO in the caudate-putamen and parietal cortex and reached maximal levels at 72 h. PANT- and TUNEL-positive cells were also detected 16-72 h after MCAO in the lateral frontal cortex within the infarct border, where many cells also showed colocalization of DNA single-strand breaks and DNA fragmentation, In contrast, levels of PANT-positive cells alone were transiently increased (16 h after MCAO) in the medial frontal cortex, an area distant from the infarct zone. These data suggest that within periinfarct brain regions, oxidative injury to nuclear DNA in the form of base and strand damage may be a significant and contributory cause of secondary expansion of brain damage following permanent focal ischemia. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Inst Neurodegenerat Disorders, Pittsburgh, PA 15213 USA. Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. Legacy Clin Res & Technol Ctr, Portland, OR USA. RP Chen, J (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, S-507,Biomed Sci Tower, Pittsburgh, PA 15213 USA. RI Henshall, David/C-3364-2012 FU NINDS NIH HHS [NS 25965, NS 36736, NS 38560] NR 59 TC 98 Z9 108 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 2000 VL 75 IS 4 BP 1716 EP 1728 DI 10.1046/j.1471-4159.2000.0751716.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 353EZ UT WOS:000089263000043 PM 10987855 ER PT J AU Proios, H Chialant, D Caplan, D AF Proios, H Chialant, D Caplan, D TI The multidisciplinary assessment of visual hemispatial neglect: a case report of a bilingual patient SO JOURNAL OF NEUROLINGUISTICS LA English DT Article; Proceedings Paper CT Research Conference on the Science of Aphasia: From Therapy to Theory CY SEP 08-13, 2000 CL IRAKLION, GREECE DE hemispatial neglect; bilingual aphasia; assessment; neglect dyslexia C1 Spaulding Rehabil Hosp, Dept Speech & Language Pathol, Boston, MA 02114 USA. Harvard Univ, Dept Psychol, Cognit Neuropsychol Lab, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Cambridge, MA 02138 USA. RP Proios, H (reprint author), Spaulding Rehabil Hosp, Dept Speech & Language Pathol, Boston, MA 02114 USA. NR 7 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0911-6044 J9 J NEUROLINGUIST JI J. Neurolinguist. PD OCT PY 2000 VL 13 IS 4 BP 313 EP 315 PG 3 WC Linguistics; Neurosciences; Psychology, Experimental SC Linguistics; Neurosciences & Neurology; Psychology GA 353QY UT WOS:000089288000025 ER PT J AU Zupan, LH Peterka, RJ Merfeld, DM AF Zupan, LH Peterka, RJ Merfeld, DM TI Neural processing of gravito-inertial cues in humans. I. Influence of the semicircular canals following post-rotatory tilt SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID VESTIBULO-OCULAR REFLEX; VERTICAL OPTOKINETIC NYSTAGMUS; SPATIAL ORIENTATION; VELOCITY STORAGE; SQUIRREL-MONKEY; EYE-MOVEMENTS; POSTROTATORY NYSTAGMUS; LINEAR ACCELERATION; VIEWING DISTANCE; AFTER-NYSTAGMUS AB Sensory systems often provide ambiguous information. Integration of various sensory cues is required for the CNS to resolve sensory ambiguity and elicit appropriate responses. The vestibular system includes two types of sensors: the semicircular canals, which measure head rotation, and the otolith organs, which measure gravito-inertial force (GIF), the sum of gravitational force and inertial force due to linear acceleration. According to Einstein's equivalence principle, gravitational force is indistinguishable from inertial force due to linear acceleration. As a consequence, otolith measurements must be supplemented with other sensory information for the CNS to distinguish tilt from translation. The GIF resolution hypothesis states that the CNS estimates gravity and linear acceleration, so that the difference between estimates of gravity and linear acceleration matches the measured GIF. Both otolith and semicircular canal cues influence this estimation of gravity and linear acceleration. The GIF resolution hypothesis predicts that inaccurate estimates of both gravity and linear acceleration can occur due to central interactions of sensory cues. The existence of specific patterns of vestibuloocular reflexes (VOR) related to these inaccurate estimates can be used to test the GIF resolution hypothesis. To investigate this hypothesis, we measured eye movements during two different protocols. In one experiment, eight subjects were rotated at a constant velocity about an earth-vertical axis and then tilted 90 degrees in darkness to one of eight different evenly spaced final orientations, a so-called "dumping" protocol. Three speeds (200, 100, and 50 degrees/s) and two directions, clockwise (CW) and counterclockwise (CCW), of rotation were tested. In another experiment, four subjects were rotated at a constant velocity (200 degrees/s, CW and CCW) about an earth-horizontal axis and stopped in two different final orientations (nose-up and nose-down), a so-called "barbecue" protocol. The GIF resolution hypothesis predicts that post-rotatory horizontal VOR eye movements for both protocols should include an "induced" VOR component, compensatory to an interaural estimate of linear acceleration, even though no true interaural linear acceleration is present. The GIF resolution hypothesis accurately predicted VOR and induced VOR dependence on rotation direction, rotation speed, and head orientation. Alternative hypotheses stating that frequency segregation may discriminate tilt from translation or that the postrotatory VOR time constant is dependent on head orientation with respect to the GIF direction did not predict the observed VOR for either experimental protocol. C1 Harvard Univ, Massachusetts Eye & Ear Infirmary, Sch Med,Jenks Vestibular Physiol Lab, Dept Otol & Laryngol, Boston, MA 02114 USA. Oregon Hlth Sci Univ, Inst Neurol Sci, Portland, OR 97209 USA. RP Zupan, LH (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirmary, Sch Med,Jenks Vestibular Physiol Lab, Dept Otol & Laryngol, Suite 421,243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01-DC-04158, P60-DC-02072, R29-DC-03066] NR 63 TC 51 Z9 52 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD OCT PY 2000 VL 84 IS 4 BP 2001 EP 2015 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 361VY UT WOS:000089746000032 PM 11024093 ER PT J AU Kegel, KB Kim, M Sapp, E McIntyre, C Castano, JG Aronin, N DiFiglia, M AF Kegel, KB Kim, M Sapp, E McIntyre, C Castano, JG Aronin, N DiFiglia, M TI Huntingtin expression stimulates endosomal-lysosomal activity, endosome tubulation, and autophagy SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Huntington's disease; autophagy; lysosomes; endosome tubulation; cathepsin D; N-terminal huntingtin; huntingtin proteolysis ID NEURONAL INTRANUCLEAR INCLUSIONS; MUTANT HUNTINGTIN; BREFELDIN-A; SUBCELLULAR-LOCALIZATION; SACCHAROMYCES-CEREVISIAE; MOLECULAR CHAPERONES; POLYGLUTAMINE TRACT; PROTEIN; CELLS; DISEASE AB An expansion of polyglutamines in the N terminus of huntingtin causes Huntington's disease (HD) and results in the accrual of mutant protein in the nucleus and cytoplasm of affected neurons. How mutant huntingtin causes neurons to die is unclear, but some recent observations suggest that an autophagic process may occur. We showed previously that huntingtin markedly accumulates in endosomal-lysosomal organelles of affected HD neurons and, when exogenously expressed in clonal striatal neurons, huntingtin appears in cytoplasmic vacuoles causing cells to shrink. Here we show that the huntingtin-enriched cytoplasmic vacuoles formed in vitro internalized the lysosomal enzyme cathepsin D in proportion to the polyglutamine-length in huntingtin. Huntingtin-labeled vacuoles displayed the ultrastructural features of early and late autophagosomes (autolysosomes), had little or no overlap with ubiquitin, proteasome, and heat shock protein 70/heat shock cognate 70 immunoreactivities, and altered the arrangement of Golgi membranes, mitochondria, and nuclear membranes. Neurons with excess cytoplasmic huntingtin also exhibited increased tubulation of endosomal membranes. Exogenously expressed human full-length wild-type and mutant huntingtin codistributed with endogenous mouse huntingtin in soluble and membrane fractions, whereas human N-terminal huntingtin products were found only in membrane fractions that contained lysosomal organelles. We speculate that mutant huntingtin accumulation in HD activates the endosomal-lysosomal system, which contributes to huntingtin proteolysis and to an autophagic process of cell death. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Autonoma Madrid, Fac Med, CSIC, Dept Bioquim, E-28029 Madrid, Spain. Univ Autonoma Madrid, Fac Med, CSIC, Inst Invest Biomed, E-28029 Madrid, Spain. Univ Massachusetts, Med Ctr, Dept Med, Worcester, MA 01655 USA. Univ Massachusetts, Med Ctr, Dept Cell Biol, Worcester, MA 01655 USA. RP DiFiglia, M (reprint author), Massachusetts Gen Hosp E, Dept Neurol, 149 13th St,Room 6604, Charlestown, MA 02129 USA. RI Kim, Manho/J-2738-2012 FU NIA NIH HHS [T32-AG00222] NR 63 TC 308 Z9 317 U1 1 U2 16 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 1 PY 2000 VL 20 IS 19 BP 7268 EP 7278 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 358BY UT WOS:000089538400021 PM 11007884 ER PT J AU Firth, PG Peterfreund, RA AF Firth, PG Peterfreund, RA TI Management of multiple intracranial aneurysms: Neuroanesthetic considerations of sickle cell disease SO JOURNAL OF NEUROSURGICAL ANESTHESIOLOGY LA English DT Article DE subarachnoid hemorrhage; sickle cell disease; craniotomy; intracranial aneurysms; neuroanesthesia ID SUBARACHNOID HEMORRHAGE; CEREBRAL ANEURYSMS; ARTERY ANEURYSM; ANEMIA; PATIENT; PATHOPHYSIOLOGY; TRANSFUSION AB Intracranial aneurysms are a common complication of sickle cell disease. The management of a patient with multiple intracranial aneurysms and sickle cell disease is described. The English language literature is reviewed. Neuroanesthetic management has traditionally been based on the avoidance of factors said to lead to erythrocyte sickling; however neuropathology typically arises from arterial intimal damage, not from venous sickling. Neuroanesthesia should be based on an appreciation of this pathophysiological model. Consideration of precipitants of vaso-occlusive crises, such as hypothermia, dehydration and possibly altered hemodynamics, should influence management. C1 Harvard Univ, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Firth, PG (reprint author), Harvard Univ, Dept Anesthesia & Crit Care, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 29 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0898-4921 J9 J NEUROSURG ANESTH JI J. Neurosurg. Anesthesiol. PD OCT PY 2000 VL 12 IS 4 BP 366 EP 371 DI 10.1097/00008506-200010000-00011 PG 6 WC Anesthesiology; Clinical Neurology; Surgery SC Anesthesiology; Neurosciences & Neurology; Surgery GA 360PL UT WOS:000089676400011 PM 11147387 ER PT J AU Graham, SH Chen, J Clark, RSB AF Graham, SH Chen, J Clark, RSB TI Bcl-2 family gene products in cerebral ischemia and traumatic brain injury SO JOURNAL OF NEUROTRAUMA LA English DT Article DE apoptosis; bax; bcl-2; bcl-w; bcl-x; bid; cerebral ischemia; programmed cell death; traumatic brain injury ID PROGRAMMED CELL-DEATH; PERMEABILITY TRANSITION PORE; CYTOCHROME-C RELEASE; PROTOONCOGENE BCL-2; TRANSGENIC MICE; RAT-BRAIN; ISOLATED-MITOCHONDRIA; SEQUENCE SIMILARITY; GLOBAL-ISCHEMIA; FOCAL ISCHEMIA AB The proto-oncogene bcl-2 plays a key role in regulating programmed cell death in neurons, The present review discusses the mechanisms by which bcl-2 family genes regulate programmed cell death, and their role in controlling cell death in cerebral ischemia and traumatic brain, Expression of several bcl-2 family members is altered in brain tissues after ischemia and trauma, suggesting that bcl-2 family genes could play a role in determining the fate of injured neurons. Furthermore, alteration of expression of bcl-2 family genes using transgenic approaches, viral vectors, or anti-sense oligonucleotides modifies neuronal cell death and neurological outcome after injury, These data suggest that the activity of bcl-2 family gene products participates in determining cellular and neurologic outcomes in ischemia and trauma, Strategies that either mimic the death-suppressor effects or inhibit the death-promoter effects of bcl-2 family gene products may improve outcome after ischemia and trauma. C1 Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Anesthesiol & Crit Care Med, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15213 USA. Vet Affairs Pittsburgh Hlth Ctr, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Graham, SH (reprint author), Univ Pittsburgh, Sch Med, Dept Neurol, 526 S BST, Pittsburgh, PA 15213 USA. FU NINDS NIH HHS [P50 NS3031, K08 NS01946, P01 NS35965] NR 93 TC 67 Z9 99 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD OCT PY 2000 VL 17 IS 10 BP 831 EP 841 DI 10.1089/neu.2000.17.831 PG 11 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 364LR UT WOS:000089894300004 PM 11063051 ER PT J AU Haigh, PI Hansen, NM Giuliano, AE Edwards, GK Ye, W Glass, EC AF Haigh, PI Hansen, NM Giuliano, AE Edwards, GK Ye, W Glass, EC TI Factors affecting sentinel node localization during preoperative breast lymphoscintigraphy SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE breast cancer; lymphoscintigraphy; sentinel node ID GAMMA-PROBE; LYMPH-NODE; CANCER; BIOPSY; LYMPHADENECTOMY; FEASIBILITY; RESECTION; MELANOMA AB Variable success rates for identifying axillary (AX) sentinel nodes in breast cancer patients using preoperative lymphoscintigraphy have been reported. We evaluated the effects of age, weight, breast size, method of biopsy, interval after biopsy, and imaging view on the success of sentinel node identification and on the kinetics of radiopharmaceutical migration. Methods: Preoperative breast lymphoscintigraphy was performed in consecutive breast cancer patients from February 1998 to December 1998. The ipsilateral shoulder was elevated on a foam wedge and the arm was abducted and elevated overhead. Imaging using this modified oblique view of the axilla (MOVA) started immediately after peritumoral injection of Millipore-filtered Tc-99m-sulfur colloid and continued until AX sentinel nodes were identified. Anterior views were obtained after MOVA. AX, internal mammary (IM), and clavicular (CL) basins were monitored in all patients. MOVA was compared with the anterior view for sentinel node identification, Age, weight, breast size, method of biopsy, interval after biopsy, and primary tumor location were evaluated for their effects on sentinel node localization and transit times from injection to arrival at the sentinel nodes. Results: Seventy-six lymphoscintigrams were obtained for 75 patients. AX sentinel nodes were revealed in 75 (99%) cases. IM or CL sentinel nodes were found in 19 (25%) cases and were not related to tumor location; exclusive IM drainage was present in 1 (1%) case. Identification of AX sentinel nodes was equivalent with MOVA and anterior views in 18 (24%) patients, was better with MOVA in 20 (26%) patients, and was accomplished only with MOVA in 38 (50%) patients. Median transit time was 17.5 min (range, 1 min to 18 h) after injection, and larger breast size was associated with increased transit time. No effect of age, weight, biopsy method, interval from biopsy, or tumor location on transit time was found. Conclusion: Use of MOVA can improve identification of AX sentinel nodes. Although AX drainage is the predominant pattern, a tumor in any portion of the breast can drain to IM sentinel nodes. Transit time was influenced by breast size. Overall short arrival times with this technique allow sentinel lymph node dissection to be performed on the same day as lymphoscintigraphy. C1 Joyce Eisenberg Keefer Breast Ctr, Santa Monica, CA USA. St Johns Hlth Ctr, John Wayned Canc Inst, Div Surg Oncol, Santa Monica, CA USA. John Wayne Canc Inst, Stat Coordinating Unit, Santa Monica, CA USA. St Johns Hlth Ctr, Dept Nucl Med, Santa Monica, CA USA. RP Glass, EC (reprint author), W Los Angeles Vet Affairs Med Ctr, Nucl Med Sect 115, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 19 TC 52 Z9 53 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD OCT PY 2000 VL 41 IS 10 BP 1682 EP 1688 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 364JJ UT WOS:000089889000019 PM 11037998 ER PT J AU Padungtod, C Savitz, DA Overstreet, JW Christiani, DC Ryan, LM Xu, XP AF Padungtod, C Savitz, DA Overstreet, JW Christiani, DC Ryan, LM Xu, XP TI Occupational pesticide exposure and semen quality among Chinese workers SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID CIGARETTE-SMOKING; HUMAN-SPERM; METHYL PARATHION; INFERTILE MEN; MORPHOLOGY; FREQUENCY; ALCOHOL; MOUSE AB This study investigated the association between occupational pesticide exposure and semen quality among Chinese workers. Male workers, 32 who were exposed to organophosphate pesticides and 43 who were not exposed were recruited from two nearby factories and interviewed. Following a work shift, semen and urine samples were collected for pesticide metabolite analysis. Semen samples were analyzed for sperm concentration, percentage of motility, and percentage of normal structure. Within the exposed group, the mean end-of-shift urinary p-nitrophenol levels were 0.22 and 0.15 mg/L for the high- and low-exposure subgroups, respectively. Linear regression analysis of individual semen parameters revealed a significant reduction of sperm concentration 35.9 x 10(6) vs 62.8 X 10(6), p < 0.01) and percentage of motility (47% vs 57%, p = 0.03) but not percentage of sperm with normal structure (57% vs 61%, p = 0.13). Multivariate modeling showed a significant overall shift in the mean semen parameter. Occupational exposure to ethylparathion and methamidophos seems to have a moderately adverse effect on semen quality. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. Univ Calif Davis, Inst Toxicol & Environm Hlth, Davis, CA 95616 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. RP Xu, XP (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, 665 Huntington Ave,FXB-101, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 41 TC 54 Z9 63 U1 2 U2 4 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 OCT PY 2000 VL 42 IS 10 BP 982 EP 992 DI 10.1097/00043764-200010000-00004 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 361QA UT WOS:000089732700003 PM 11039162 ER PT J AU Fishman, SM Wilsey, B Yang, J Reisfield, GM Bandman, TB Borsook, D AF Fishman, SM Wilsey, B Yang, J Reisfield, GM Bandman, TB Borsook, D TI Adherence monitoring and drug surveillance in chronic opioid therapy SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Review DE adherence; compliance; noncompliance; drug surveillance; opioids; chronic opioid therapy ID CHRONIC NONMALIGNANT PAIN; POPPY SEED INGESTION; SUBSTANCE-ABUSE; MEDICATION COMPLIANCE; PATIENT COMPLIANCE; HAIR ANALYSIS; MANAGEMENT; CANCER; DISEASE; NONCOMPLIANCE AB Monitoring adherence with chronic opioid therapies is a critical yet often difficult task. Because chronic opioid therapy is often fraught with complex pharmacological, psychological, social and legal issues, its application is often controversial or altogether avoided. Improved drug monitoring and surveillance may help reduce some of the reluctance to use chronic opioid therapy in patients with chronic lain states. We review the literature on patient adherence/compliance with chronic administration of opioids as well as novel methods ly which adherence with opioid therapy can De measured. (C) U.S. Cancer Pain Relief Committee, 2000. C1 Univ Calif Davis, Med Ctr, Dept Anesthesiol & Pain Med, Sacramento, CA 95817 USA. Univ Calif Davis, Med Ctr, Div Pain Med, Sacramento, CA 95817 USA. Massachusetts Gen Hosp, MGH Pain Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Fishman, SM (reprint author), Univ Calif Davis, Med Ctr, Dept Anesthesiol & Pain Med, Ellison Ambulatory Care Bldg,Suite 3730,4860 Y St, Sacramento, CA 95817 USA. NR 78 TC 53 Z9 54 U1 1 U2 4 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 OCT PY 2000 VL 20 IS 4 BP 293 EP 307 DI 10.1016/S0885-3924(00)00195-0 PG 15 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 361ZZ UT WOS:000089755300009 PM 11027912 ER PT J AU Jackson, PG Evans, SRT AF Jackson, PG Evans, SRT TI Intraperitoneal macrophages and tumor immunity: A review SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Review DE macrophage; cytotoxicity; immunity; macrophage physiology; peritoneum; CO2 ID COLONY-STIMULATING FACTOR; ABDOMINAL-WALL METASTASES; LAPAROSCOPIC-ASSISTED SPLENECTOMY; ACTIVATED KILLER-CELLS; NECROSIS-FACTOR-ALPHA; PORT-SITE RECURRENCE; OVARIAN-CANCER; MURINE MODEL; NITRIC-OXIDE; PERITONEAL-MACROPHAGES AB The macrophage (M phi) is considered the first line of defense in immune response to foreign invaders. Increasing evidence suggests that M phis also play an important role against neoplastic cells. M phis exposed to supraphysiologic concentrations of CO2 are suppressed. As surgeons apply newer minimally invasive techniques to oncologic therapies, it is important to evaluate the impact of these techniques on host-tumor interactions. We review the current understanding of M phi biology with specific attention on cytotoxicity in addition to tumor immunity. Although systemic immune function is better preserved after laparoscopy than laparotomy, peritoneal M phis show reduced function after CO2 pneumoperitoneum than exposure to air. M phis have shown cytotoxicity to syngeneic cancer cells and may play an important role in tumor surveillance. The impairment in M phi function after CO2 exposure may have an effect on outcome after oncologic surgery. In our understanding, M phis help destroy neoplastic cells. As CO2 impairs M phi activity, laparoscopy may significantly alter the host-tumor interaction. J. Surg. Oncol. 2000:75:146-155. (C) 2000 Wiley-Liss, Inc. C1 George Washington Univ, Dept Surg, Washington, DC 20037 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Evans, SRT (reprint author), George Washington Univ, Dept Surg, 2150 Penn Ave NW,6B, Washington, DC 20037 USA. NR 129 TC 40 Z9 41 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD OCT PY 2000 VL 75 IS 2 BP 146 EP 154 DI 10.1002/1096-9098(200010)75:2<146::AID-JSO14>3.0.CO;2-1 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA 371JC UT WOS:000165174700014 PM 11064397 ER PT J AU Washizu, J Berthiaume, F Chan, C Tompkins, RG Toner, M Yarmush, ML AF Washizu, J Berthiaume, F Chan, C Tompkins, RG Toner, M Yarmush, ML TI Optimization of rat hepatocyte culture in citrated human plasma SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE bioartificial liver assist system; plasma exposure; anticoagulant; hepatocyte culture; amino acids; hormonal supplementation ID LIVER-ASSIST SYSTEMS; AMINO-ACID-TRANSPORT; BIOARTIFICIAL LIVER; SANDWICH CONFIGURATION; HORMONAL-REGULATION; COLLAGEN SANDWICH; CELL-LINE; SUPPORT; EXPRESSION; SPHEROIDS AB Background. Maintenance of liver-specific functions in hepatocyte cultures during plasma exposure is critical for the clinical application of bioartificial liver assist systems. Sodium citrate is a common anticoagulant but has been shown to be cytotoxic to hepatocytes. We have tested the effect of various supplements on the viability and function of adult primary rat hepatocytes exposed to citrated plasma. Materials and methods. Freshly isolated rat hepatocytes were cultured in the collagen gel sandwich configuration in culture medium for 6 days followed by exposure to citrated human plasma with various supplements for 1 week. Controls were left in culture medium throughout. Viability and synthetic functions were evaluated. Results. Hepatocytes exposed to unsupplemented citrated plasma lost significant viability and function within the first 2 days. Cells cultured in plasma supplemented with a fivefold concentrate of standard hepatocyte culture medium maintained urea (1.2-2.1 mu mol/day/10(6) cells) and albumin (51-62 mug/day/10(6) cells) synthesis rates equal to or higher than those of controls. Among the various components of the concentrated medium supplement, calcium chloride (1.8 mM), magnesium sulfate (0.8 mM), amino acids (fourfold Basal Medium Eagle amino acids including 4 mM glutamine), and glucagon (14 ng/ml) were found to be essential in maintaining urea synthesis. Maintenance of a high albumin synthesis rate also required the addition of hydrocortisone (7.5 mug/ml) and insulin (0.5 U/ml). Conclusions. Appropriate metabolic and hormonal supplementation of citrated human plasma prevents its cytotoxic effects and may be used in conjunction with in vivo use of bioartificial liver assist systems. (C) 2000 Academic Press. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med,Surg Serv, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med,Surg Serv, GRB 1401,55 Fruit St, Boston, MA 02114 USA. EM ireis@sbi.org FU NIDDK NIH HHS [DK41709]; NIGMS NIH HHS [GM07035] NR 44 TC 22 Z9 22 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD OCT PY 2000 VL 93 IS 2 BP 237 EP 246 DI 10.1006/jsre.2000.5986 PG 10 WC Surgery SC Surgery GA 367NT UT WOS:000090068900006 PM 11027466 ER PT J AU Ravicz, ME Melcher, JR Kiang, NYS AF Ravicz, ME Melcher, JR Kiang, NYS TI Acoustic noise during functional magnetic resonance imaging SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID TRANSVERSE GRADIENT COILS; AUDITORY-CORTEX; ECHO-PLANAR; PULSE SEQUENCES; MRI; SOUND; ATTENUATION; FMRI; REDUCTION AB Functional magnetic resonance imaging (fMRI) enables sites of brain activation to be localized in human subjects. For studies of the auditory system, acoustic noise generated during fMRI can interfere with assessments of this activation by introducing uncontrolled extraneous sounds. As a first step toward reducing the noise during fMRI, this paper describes the temporal and spectral characteristics of the noise present under typical fMRI study conditions for two imagers with different static magnetic field strengths. Peak noise levels were 123 and 138 dB re 20 mu Pa in a 1.5-tesla (T) and a 3-T imager, respectively. The noise spectrum (calculated over a 10-ms window coinciding with the highest-amplitude noise) showed a prominent maximum at 1 kHz for the 1.5-T imager (115 dB SPL) and at 1.4 kHz for the 3-T imager (131 dB SPL). The frequency content and timing of the most intense noise components indicated that the noise was primarily attributable to the readout gradients in the imaging pulse sequence. The noise persisted above background levels for 300-500 ms after gradient activity ceased, indicating that resonating structures in the imager or noise reverberating in the imager room were also factors. The gradient noise waveform was highly repeatable. In addition, the coolant pump for the imager's permanent magnet and the room air-handling system were sources of ongoing noise lower in both level and frequency than gradient coil noise. Knowledge of the sources and characteristics of the noise enabled the examination of general approaches to noise control that could be applied to reduce the unwanted noise during fMRI sessions. (C) 2000 Acoustical Society of America. [S0001-4966(00)04610-5]. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Univ, MIT, Joint Div Hlth Sci & Technol, Cambridge, MA 02139 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Serv Neurol, Boston, MA 02114 USA. RP Ravicz, ME (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [P01 DC000119-260023, P01 DC000119, P01 DC00119] NR 68 TC 73 Z9 73 U1 0 U2 5 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD OCT PY 2000 VL 108 IS 4 BP 1683 EP 1696 DI 10.1121/1.1310190 PG 14 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 364LW UT WOS:000089894700033 PM 11051496 ER PT J AU Biederman, J Spencer, TJ AF Biederman, J Spencer, TJ TI Genetics of childhood disorders: XIX. ADHD, part 3: Is ADHD a noradrenergic disorder? SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; MECHANISMS C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Biederman, J (reprint author), Yale Univ, Sch Med, Ctr Child Study, 230 S Frontage Rd, New Haven, CT 06520 USA. NR 8 TC 19 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD OCT PY 2000 VL 39 IS 10 BP 1330 EP 1333 PG 4 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 358KA UT WOS:000089556200023 PM 11026191 ER PT J AU Bonta, MD Tannous, ZS Demierre, MF Gonzalez, E Harris, NL Duncan, LM AF Bonta, MD Tannous, ZS Demierre, MF Gonzalez, E Harris, NL Duncan, LM TI Rapidly progressing mycosis fungoides presenting as follicular mucinosis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID T-CELL LYMPHOMA; ALOPECIA MUCINOSA; REARRANGEMENT; HYPERPLASIA; VARIANT; SCALP; PATCH; GENE; SIGN AB Follicular mucinosis can occur as a primary idiopathic disorder or can arise in association with benign or malignant disease, most notably mycosis fungoides. We describe a patient with an aggressive folliculotropic variant of mycosis fungoides that initially presented as follicular mucinosis with alopecia. One month after the diagnosis of follicular mucinosis, a diagnosis of mycosis fungoides was made, and 3 months later inguinal lymph node involvement with mycosis fungoides developed. A skin biopsy specimen demonstrated prominent follicular mucinosis with folliculotropism of atypical cells and intrafollicular Pautrier's microabscesses. As demonstrated in this case, follicular mucinosis can be a presenting sign of rapidly progressive mycosis fungoides. In our review of follicular mucinosis and its association with mycosis fungoides, we found that the folliculotropic variant of mycosis fungoides appears more commonly to have an aggressive course than classic mycosis fungoides. C1 Massachusetts Gen Hosp, Dermatopathol Unit, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. RP Duncan, LM (reprint author), Massachusetts Gen Hosp, Dermatopathol Unit, Dept Pathol, Warren 827, Boston, MA 02114 USA. RI Duncan, Lyn/E-9878-2013 NR 38 TC 33 Z9 37 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD OCT PY 2000 VL 43 IS 4 BP 635 EP 640 DI 10.1067/mjd.2000.107741 PG 6 WC Dermatology SC Dermatology GA 360MM UT WOS:000089671800011 PM 11004619 ER PT J AU Nghiem, P AF Nghiem, P TI Identifying the missing link between UV and p53: The role of phosphatidyl inositol kinase-related kinases SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID DNA-DAMAGE; RADIATION; PROTEIN C1 Dana Farber Canc Inst, Cutaneous Oncol Unit, Boston, MA 02115 USA. RP Nghiem, P (reprint author), Dana Farber Canc Inst, Cutaneous Oncol Unit, 44 Binney St, Boston, MA 02115 USA. RI Nghiem, Paul/A-9210-2011 OI Nghiem, Paul/0000-0003-2784-963X FU PHS HHS [K08] NR 11 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD OCT PY 2000 VL 43 IS 4 BP 706 EP 707 PG 2 WC Dermatology SC Dermatology GA 360MM UT WOS:000089671800027 PM 11004635 ER PT J AU Canalejo, A Almaden, Y Torregrosa, V Gomez-Villamandos, JC Ramos, B Campistol, JM Felsenfeld, AJ Rodriguez, M AF Canalejo, A Almaden, Y Torregrosa, V Gomez-Villamandos, JC Ramos, B Campistol, JM Felsenfeld, AJ Rodriguez, M TI The in vitro effect of calcitriol on parathyroid cell proliferation and apoptosis SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CHRONIC-RENAL-FAILURE; VITAMIN-D METABOLITES; SECONDARY HYPERPARATHYROIDISM; INTRAVENOUS CALCITRIOL; HEMODIALYSIS-PATIENTS; GLANDS; HYPERPLASIA; HORMONE; CALCIUM; 1,25(OH)2D3 AB Calcitriol treatment is used to reduce parathyroid hormone levels in azotemic patients with secondary hyperparathyroidism (HPT). Whether long-term calcitriol administration reduces parathyroid gland size in patients with severe secondary hyperparathyroidism is not clear. The aim of the study was to evaluate in vitro the effect of calcitriol on parathyroid cell proliferation and apoptosis in normal parathyroid glands and in adenomatous and hyperplastic human parathyroid glands. Freshly harvested parathyroid glands from normal dogs and hyperplastic and adenomatous glands from patients with secondary (2 degrees) and primary (1 degrees) HPT undergoing parathyroidectomy were studied. Flow cytometry was used to quantify the cell cycle and apoptosis of parathyroid cells. Apoptosis was also evaluated by DNA electrophoresis and light and electron microscopy. In normal dog parathyroid glands, culture with calcitriol (10(-10) to 10(-7) M) for 24 h produced a dose-dependent inhibitory effect on the progression of cells into the cell cycle and into apoptosis. When glands from patients with 2 degrees HPT were cultured for 24 h, only high calcitriol concentrations (10-7 M) inhibited the progression through the cell cycle and the induction of apoptosis. In parathyroid adenomas (1 degrees HPT), even a high concentration of calcitriol (10(-7) M) had no significant effect on the cell cycle or apoptosis. The present study shows that in vitro, calcitriol inhibits in a dose-dependent manner in normal parathyroid glands both parathyroid cell proliferation and apoptosis. However, in secondary hyperplasia, only high concentrations of calcitriol inhibited cell proliferation and apoptosis. In 1 degrees HPT, even high concentrations of calcitriol had no effect. Because calcitriol simultaneously inhibits both cell proliferation and apoptosis, a reduction in the parathyroid gland mass may not occur as a direct effect of calcitriol treatment. C1 Univ Cordoba, Reina Sofia Hosp, Res Unit, E-14071 Cordoba, Spain. Univ Cordoba, Reina Sofia Hosp, Serv Nephrol, E-14071 Cordoba, Spain. Hosp Clin Barcelona, Serv Nephrol, Barcelona, Spain. Univ Cordoba, Fac Vet, Dept Pathol, E-14071 Cordoba, Spain. Carlos Haya Hosp, Serv Nephrol, Malaga, Spain. W Los Angeles VA Med Ctr, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Rodriguez, M (reprint author), Hosp Reina Sofia, Unidad Invest, Avda Menendez Pidal S-N, Cordoba 14004, Spain. RI Rodriguez, teresa/H-5452-2011; Canalejo, Antonio/L-8407-2014 OI Canalejo, Antonio/0000-0003-2098-8960 NR 34 TC 37 Z9 39 U1 0 U2 3 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 OCT PY 2000 VL 11 IS 10 BP 1865 EP 1872 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 358DB UT WOS:000089541000010 PM 11004217 ER PT J AU Kaufman, JS Fiore, L Hasbargen, JA O'Connor, TZ Perdriset, G AF Kaufman, JS Fiore, L Hasbargen, JA O'Connor, TZ Perdriset, G TI A pharmacodynamic study of clopidogrel in chronic hemodialysis patients SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE clopidogrel; pharmacodynamics; hemodialysis; platelet aggregation ID VASCULAR ACCESS; TICLOPIDINE; ANTIPLATELET; ASPIRIN; HYPERPLASIA; THROMBOSIS; INHIBITION; THERAPY; GRAFT; ADP AB Combination antiplatelet agents, particularly aspirin and ticlopidine, have found increased use in the prevention of arterial thrombosis. Clopidogrel, a thienopyridine derivative, like ticlopidine was recently approved by the U.S. Food and Drug Administration (FDA) for the reduction of ischemic events in patients with myocardial infarction, stroke, or peripheral arterial disease and appears to have much less hematologic toxicity than ticlopidine has. Thrombosis of hemodialysis access grafts is a major cause of morbidity in this patient population. Combination antiplatelet agents may be particularly useful in the prevention of hemodialysis access graft thrombosis. In preparation for such a study, we have performed a pharmacodynamic study of the platelet inhibitory effects of clopidogrel in patients on maintenance hemodialysis. Nine chronic hemodialysis patients were studied. Baseline platelet aggregation studies were performed, after which the subjects were begun on clopidogrel 75 mg daily. Platelet aggregation studies were repeated after 14 days of therapy. Drug was stopped and a final set of platelet aggregation studies were performed 7 days later. Because clopidogrel acts by inhibiting adenosine diphosphate (ADP)-induced platelet aggregation, we used ADP as the agonist in the platelet aggregation studies. We also measured the time required to achieve hemostasis after removing the dialysis needles at the termination of a dialysis session. Patients were carefully monitored for any adverse reaction to clopidogrel. Fourteen days' treatment with clopidogrel inhibited ADP-induced platelet aggregation from 48 to 23% with ADP 2 mu M (P = 0.0113), from 59 to 38% with ADP 5 mu M (P = 0.0166), and from 66 to 44% with ADP 10 mu M (P = 0.0172). This inhibition of platelet aggregation was reversed 7 days after stopping clopidogrel. Clopidogrel administration did not affect the time required to achieve hemostasis after removal of the dialysis needles. No adverse reactions were noted. No patient had evidence of bleeding, rash or gastro-intestinal (GI) upset. Clopidogrel inhibits ADP-induced platelet aggregation in subjects receiving chronic maintenance hemodialysis. The magnitude of inhibition is similar to that reported in nonuremic subjects with atherosclerosis. This inhibition is reversible within 7 days of discontinuing the drug. No adverse reactions to the drug were noted in this short-term (14-day) trial. C1 VA Boston Healthcare Syst, Renal Sect 111RE, Boston, MA 02130 USA. VA Boston Healthcare Syst, Hematol Sect, Boston, MA 02130 USA. Richard L Roudebush Vet Affairs Med Ctr, Renal Sect, Indianapolis, IN 46202 USA. W Haven Cooperat Studies Program, Coordinating Ctr, W Haven, CT USA. Sanofi Rech, Gentilly, France. RP Kaufman, JS (reprint author), VA Boston Healthcare Syst, Renal Sect 111RE, 150 S Huntington Ave, Boston, MA 02130 USA. NR 25 TC 35 Z9 35 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD OCT PY 2000 VL 10 IS 2 BP 127 EP 131 DI 10.1023/A:1018758308979 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 358HZ UT WOS:000089553700003 PM 11005934 ER PT J AU Kalra, A Jang, IK AF Kalra, A Jang, IK TI Prevalence of early left ventricular thrombus after primary coronary intervention for acute myocardial infarction SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE left ventricular thrombus; acute myocardial infarction; primary percutaneous coronary intervention; stenting ID TWO-DIMENSIONAL ECHOCARDIOGRAPHY; THROMBOLYTIC THERAPY; MURAL THROMBI; INTRACORONARY STREPTOKINASE; INTRAVENOUS STREPTOKINASE; PLASMINOGEN-ACTIVATOR; IMMEDIATE ANGIOPLASTY; NATURAL-HISTORY; ANTICOAGULATION; FREQUENCY AB The prevalence of left ventricular (LV) thrombus after acute myocardial infarction (AMI) has been reported high at 20-60%. Current reperfusion therapies such as thrombolysis have shown a trend toward reducing the incidence of LV thrombosis. However, the prevalence of LV thrombus after primary percutaneous coronary intervention (PCI) for AMI has not been systematically studied. At Massachusetts General Hospital 71 consecutive patients who underwent primary PCI for acute ST elevation MI were reviewed for the prevalence of LV thrombus evaluated by echocardiography. Echocardiography was performed within 5 days of infarction. PCI was successful in all patients. The time delay from symptom onset to intervention was 191 minutes. Thrombolysis in Myocardiol Infarction (TIMI) grade 3 flow was achieved in more than 80% of cases. Only 3 patients (4%) had echocardiographic evidence of LV thrombus. All 3 patients had anterior infarctions. The incidence among patients with anterior MI was 10% (3 of 30 patients). The prevalence of LV thrombus in patients treated with primary PCI for AMI is low (4%). C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, Bulfinch 105,55 Fruit St, Boston, MA 02114 USA. NR 32 TC 28 Z9 30 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD OCT PY 2000 VL 10 IS 2 BP 133 EP 136 DI 10.1023/A:1018710425817 PG 4 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 358HZ UT WOS:000089553700004 PM 11005935 ER PT J AU Sabatine, MS Tu, TM Jang, IK AF Sabatine, MS Tu, TM Jang, IK TI Combination of a direct thrombin inhibitor and a platelet glycoprotein IIb/IIIa blocking peptide facilitates and maintains reperfusion of platelet-rich thrombus with alteplase SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE alteplase; argatroban; GP IIb/IIIa inhibitor; thrombolysis ID ACUTE MYOCARDIAL-INFARCTION; TISSUE-PLASMINOGEN-ACTIVATOR; ANTIPLATELET GPIIB/IIIA ANTIBODY; COMBINED BOLUS INJECTION; FRONT-LOADED ALTEPLASE; CORONARY THROMBOLYSIS; DOUBLE-BLIND; CONCOMITANT HEPARIN; CANINE PREPARATION; TRIAL AB We sought to determine the efficacy of the combination of argatroban, a direct thrombin inhibitor, and G4120, a platelet glycoprotein (GP) IIb/IIIa blocker, to enhance thrombolysis with alteplase. Platelet-rich thrombus in the rabbit arterial thrombosis model is relatively resistant to alteplase despite the addition of aspirin and heparin. The adjunctive use of either direct thrombin inhibitors or GP IIb/IIIa inhibitors in thrombolysis has been investigated with encouraging, but limited, success. The usefulness of combining both agents as adjunctive therapy to thrombolysis has not been fully explored. Following platelet-rich thrombus formation in the rabbit, argatroban (3 mg/kg), G4120 (0.5 mg/kg), G4120 plus heparin (200 U/kg), or G4120 plus argatroban were intravenously infused over 60 minutes. Alteplase was given as intravenous boluses (0.45 mg/kg) at 15-minute intervals up to 4 doses or until reperfusion. Blood flow and bleeding time were monitored for 2 hours. The combination of G4120 plus argatroban resulted in a persistent patency in 5 of 7 animals compared with 0 of 6 for argatroban alone (p = 0.02), 1 of 6 for G4120 alone (p = 0.08), and 2 of 6 for G4120 plus heparin (p = 0.2). Although during the infusion the bleeding times were longer in the groups that received G4120 (26 +/- 7.7 minutes vs. 14 +/- 10 minutes, p < 0.05), by the end of the experiment there were no statistically significant differences. Similarly, during the infusion the activated partial thromboplastin times (aPTT) was higher in groups that received heparin or argatroban (99 +/- 51 seconds vs. 32 +/- 7.6 seconds, p < 0.001), but by the end of the experiment the aPTTs had returned to close to baseline in all groups except the G4120 plus heparin group. These results suggest that lysis of platelet-rich thrombus with alteplase requires the addition of both potent platelet and thrombin inhibitors. Specifically designed agents, G4120 and argatroban, are effective without additional increased risk for bleeding. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, Bulfinch 105,55 Fruit St, Boston, MA 02114 USA. NR 64 TC 8 Z9 8 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD OCT PY 2000 VL 10 IS 2 BP 189 EP 196 DI 10.1023/A:1018722828543 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 358HZ UT WOS:000089553700010 PM 11005941 ER PT J AU McDougal, WS AF McDougal, WS TI Simple cystectomy in patients requiring urinary diversion - Comment SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP McDougal, WS (reprint author), Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD OCT PY 2000 VL 164 IS 4 BP 1172 EP 1172 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 352QR UT WOS:000089229800009 ER PT J AU Wasson, JH Bubolz, TA Lu-Yao, GL Walker-Corkery, E Hammond, CS Barry, MJ AF Wasson, JH Bubolz, TA Lu-Yao, GL Walker-Corkery, E Hammond, CS Barry, MJ CA Patient Outcomes Res Team Prostati TI Transurethral resection of the prostate among medicare beneficiaries: 1984 to 1997 SO JOURNAL OF UROLOGY LA English DT Article DE transurethral resection of prostate; prostatic hyperplasia; prostate ID HYPERPLASIA AB Purpose: We examine the epidemiology and associated risks of transurethral resection of the prostate among Medicare beneficiaries for the period 1984 to 1997. Materials and Methods: We used hospital claims for transurethral resection of the prostate from a 20% national sample of Medicare beneficiaries for the period 1991 to 1997. Risk of mortality and reoperation were evaluated using life table methods and compared to those for the period 1984 to 1990. We also examined the association between surgical volume and adverse outcomes following resection using unique urologist identifier codes from the 1997 part B Medicare claims. Results: Compared to 1984 to 1990, age adjusted rates of transurethral resection for benign prostatic hyperplasia (BPH) during 1991 to 1997 declined by approximately 50% for white (14.6 to 6.72/1,000) and 40% for black (11.8 to 6.58/1,000) men. Of the men who underwent resection for BPH during the recent period 53% were 75 years old or older but 30-day mortality in men 70 years old or older was significantly lower than that in 1984 to 1990. Since 1987 the 5-year risk for reoperation following transurethral resection for BPH has remained 5%. For resection performed in 1997 we observed no statistically significant association between urologist surgical volume and risks of reoperation or 30-day mortality. Conclusions: Compared to the peak period of its use in the 1980s, older men are now undergoing transurethral resection of the prostate. Nevertheless, outcomes for men 65 years old or older continue to be good. C1 Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH 03756 USA. Healthstat, Princeton, NJ USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dartmouth Primary Care Cooperat Res Network, Hanover, NH 03756 USA. Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. RP Wasson, JH (reprint author), Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH 03756 USA. NR 7 TC 46 Z9 49 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD OCT PY 2000 VL 164 IS 4 BP 1212 EP 1215 DI 10.1016/S0022-5347(05)67143-1 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 352QR UT WOS:000089229800021 PM 10992368 ER PT J AU Le Gall, S Buseyne, F Trocha, A Walker, BD Heard, JM Schwartz, O AF Le Gall, S Buseyne, F Trocha, A Walker, BD Heard, JM Schwartz, O TI Distinct tra trafficking pathways mediate Nef-induced and clathrin-dependent major histocompatibility complex class I down-regulation SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CYTOTOXIC T-LYMPHOCYTES; HIV-1 NEF; SORTING SIGNALS; COATED PITS; PROTEIN COMPLEX; INDUCED CD4; MHC-I; EXOGENOUS ANTIGENS; ADAPTER COMPLEXES AB The human immunodeficiency virus type 1 Nef protein alters the post-Golgi stages of major histocompatibility complex class I (MHC-I) biogenesis. Presumed mechanisms involve the disclosure of a cryptic tyrosine based sorting signal (YSQA) located in the cytoplasmic tail of HLA-A and -B heavy chains. We changed this signal for a prototypic sorting motif (YSQI or YSQL). Modified HLA-A2 molecules, termed A2-endo, displayed constitutively low surface levels and accumulated in a region close to or within the Golgi apparatus, a behavior reminiscent of wild-type HLA-A2 in Nef-expressing cells. However, several lines of evidence indicate that the action of prototypic signals on MHC-I trafficking differs from that of Nef. Internalization of surface A2-endo was more rapid and was associated with efficient recycling to the surface. A transdominant-negative mutant of dynamin-1 inhibited A2-endo constitutive internalization and Nef-induced CD4 down-regulation, whereas it did not affect the activity of Nef on MHC-I. Moreover, trafficking of A2 endo was still affected by the viral protein, indicating additive effects of prototypic signals and Nef, Therefore, distinct trafficking pathways regulate clathrin-dependent and Nef-induced MHC-I modulation. C1 Inst Pasteur, CNRS, URA 1930, Unite Retrovirus & Trasfert Genet, F-75724 Paris 15, France. Inst Pasteur, Lab Immunopathol Virale, F-75724 Paris, France. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. RP Schwartz, O (reprint author), Inst Pasteur, CNRS, URA 1930, Unite Retrovirus & Trasfert Genet, 28 Rue Dr Roux, F-75724 Paris 15, France. NR 50 TC 81 Z9 82 U1 1 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 OCT PY 2000 VL 74 IS 19 BP 9256 EP 9266 DI 10.1128/JVI.74.19.9256-9266.2000 PG 11 WC Virology SC Virology GA 352XH UT WOS:000089244300054 PM 10982373 ER PT J AU Rusconi, S Catamancio, SL Citterio, P Bulgheroni, E Croce, F Herrmann, SH Offord, RE Galli, M Hirsch, MS AF Rusconi, S Catamancio, SL Citterio, P Bulgheroni, E Croce, F Herrmann, SH Offord, RE Galli, M Hirsch, MS TI Combination of CCR5 and CXCR4 inhibitors in therapy of human immunodeficiency virus type 1 infection: In vitro studies of mixed virus infections SO JOURNAL OF VIROLOGY LA English DT Article ID CHEMOKINE RECEPTOR CXCR4; SMALL-MOLECULE INHIBITOR; HIV-1 ENTRY; AMINOOXYPENTANE-RANTES; DISEASE PROGRESSION; DOWN-MODULATION; HIGHLY POTENT; V3 DOMAIN; IN-VIVO; SDF-1 AB We studied the combined anti-human immunodeficiency virus type 1 (HIV-1) effects of a derivative of stroma-derived factor 1 beta (SDF-1 beta), Met-SDF-1 beta, and a modified form of RANTES, aminooxypentane (AOP)-RANTES. The antiviral agents were tested singly or in combination at 95 and 99% virus inhibitory concentrations. Clinical R5 and X4 HIV-1 isolates were used. AOP-RANTES inhibited R5 but not X4 viruses, whereas, Met-SDF-1 beta had the opposite effect. Combinations of these compounds inhibited mixed infections with R5 and X4 viruses (95 to 99%), whereas single drugs were less inhibitory (32 to 61%). Combinations of R5 and X4 inhibitors are promising and deserve further evaluation. C1 Univ Milan, Osped Luigi Sacco, Ist Malattie Infett & Trop, I-20157 Milan, Italy. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Genet Inst Inc, Mol Biol Gene Express, Infect Dis, Cambridge, MA USA. Ctr Med Univ Geneva, Dept Biochim Med, Geneva, Switzerland. RP Rusconi, S (reprint author), Univ Milan, Osped Luigi Sacco, Ist Malattie Infett & Trop, Via GB Grassi 74, I-20157 Milan, Italy. RI Rusconi, Stefano/H-9263-2012 FU NCI NIH HHS [CA 12464] NR 35 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 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 2000 VL 74 IS 19 BP 9328 EP 9332 DI 10.1128/JVI.74.19.9328-9332.2000 PG 5 WC Virology SC Virology GA 352XH UT WOS:000089244300063 PM 10982382 ER PT J AU Katz, MS AF Katz, MS TI Geriatrics grand rounds: Eve's rib, or a revisionist view of osteoporosis in men SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID BONE-MINERAL DENSITY; ESTROGEN-RECEPTOR GENE; SEX STEROID-LEVELS; ELDERLY MEN; AROMATASE DEFICIENCY; POSTMENOPAUSAL WOMEN; BINDING GLOBULIN; HIP FRACTURE; HEALTHY-MEN; OLDER MEN AB It is widely accepted that estrogen withdrawal following menopause predisposes women to accelerated bone loss and increased risk of developing osteoporosis. Although osteoporosis is a significant public health problem for aging men as well as women, the cause of osteoporosis in men remains largely unknown. A substantial number of men with osteoporosis present with bone loss secondary to conditions associated with reduced gonadal steroid hormone levels. Although hypogonadism is related to bone loss in men, and androgen levels decline with age in men, it is not at all clear that reduced androgen levels are related to bone loss in older men. What, then, is the role of gonadal steroids in osteoporosis in men? This review focuses on recent research-including clinical investigations of men with genetic disorders of estrogen action, basic biomedical studies of estrogen receptor "knockout" mice, and population-based comparisons of bone density with gonadal steroids in older men-leading to the surprising conclusion that estrogen plays a vital role in maintenance of bone in men as well as in women. Possible mechanisms whereby reduced estrogen levels might result in bone loss in both sexes are also reviewed, as are potential therapeutic implications of a role for estrogen in osteoporosis in men. C1 S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr 182, Audie L Murphy Div, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Geriatr & Gerontol, San Antonio, TX 78284 USA. RP Katz, MS (reprint author), S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr 182, Audie L Murphy Div, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. NR 59 TC 5 Z9 5 U1 1 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD OCT PY 2000 VL 55 IS 10 BP M560 EP M569 PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 373WF UT WOS:000165312500010 PM 11034228 ER PT J AU Saim, AB Cao, YL Weng, YL Chang, CN Vacanti, MA Vacanti, CA Eavey, RD AF Saim, AB Cao, YL Weng, YL Chang, CN Vacanti, MA Vacanti, CA Eavey, RD TI Engineering autogenous cartilage in the shape of a helix using an injectable hydrogel scaffold SO LARYNGOSCOPE LA English DT Article DE microtia; autogenous cartilage; tissue-engineered auricle; hydrogel scaffold ID POLYMER-CELL CONSTRUCT; GROWTH-FACTORS; HUMAN EAR; TISSUE; TRANSPLANTATION; BONE AB Objective: Previous successful efforts to tissue engineer cartilage for an auricle have used an immunocompromised nude mouse xenograft model. Subsequent efforts in an immunocompetent autogenous animal model have been less successful because of an inflammatory response directed against the foreign scaffold polymer used to provide an auricular shape. Ne studied an alternative polymer material and surgical technique to engineer autogenous cartilage in the shape of a human ear helix using injectable hydrogel scaffolding, Pluronic F-127 (polyethylene oxide and polypropylene oxide). Subject: Yorkshire swine. Material and Methods: Fresh autogenous chondrocytes were suspended in a biodegradable, biocompatible co-polymer hydrogel, Pluronic F-127, at a concentration of 3 x 10(7) cells/mL, To support the contour of the implant, a skin fold channel in the shape of the helix of a human ear was created in the skin in three sites on the ventral surface of the animal The cell-hydrogel suspension was injected through the skin fold channel. For controls, injections were made into identical channels using either cells alone or the Pluronic F-127 without cells. After 10 weeks, the specimens mere excised and examined both grossly and histologically, Results: Grossly, all implants retained a helical like shape. Excised specimens possessed flexible characteristics consistent with elastic cartilage. The specimens could be folded and twisted and on release of mechanical pressure would instantly return to the original shape. Histological evaluation of the implants using H&E, Safranin O, trichrome blue, and Verhoeff's stains demonstrated findings consistent with mature elastic cartilage, Control injection of hydrogel alone demonstrated no evidence of cartilage formation and control injection of chondrocytes alone showed evidence only of disassociated elastic cartilage. Conclusion: Injection of autologous porcine auricular chondrocytes suspended in a biodegradable, biocompatible hydrogel of Pluronic F-127 resulted in the formation of cartilage tissue in the approximate size and shape of a human ear helix. This preliminary method extends the concept of auricular tissue engineering from an immunocompromised xenograft animal model to an immunocompetent autologous animal model. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Univ Massachusetts, Med Ctr, Dept Anesthesia, Tissue Engn Lab Ctr, Worcester, MA USA. RP Eavey, RD (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 18 TC 101 Z9 110 U1 0 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD OCT PY 2000 VL 110 IS 10 BP 1694 EP 1697 DI 10.1097/00005537-200010000-00023 PN 1 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 361EH UT WOS:000089709500021 PM 11037827 ER PT J AU Doherty, CP Fitzsimons, M Holohan, T Mohamed, HB Farrell, M Meredith, GE Staunton, H AF Doherty, CP Fitzsimons, M Holohan, T Mohamed, HB Farrell, M Meredith, GE Staunton, H TI Accuracy and validity of stereology as a quantitative method for assessment of human temporal lobe volumes acquired by magnetic resonance imaging SO MAGNETIC RESONANCE IMAGING LA English DT Article DE volumetric analysis; epilepsy; reliability; MEASURE ID HIPPOCAMPAL ATROPHY; BRAIN STRUCTURES; EPILEPSY; MRI; SCANS; RELIABILITY; DIAGNOSIS; SCLEROSIS; SEIZURES; AMYGDALA AB The object of this study was to compare the accuracy and validity of stereology as a method for determining whole temporal lobe volume with the more established technique of semi-automated thresholding acid tracing. Ten, fixed, post-mortem human brains, were imaged using a three dimensional (3D) acquisition protocol. The volume of the left temporal lobe, dissected from each brain, was determined by fluid displacement. Each volume was compared to measurements obtained from magnetic resonance images (MRI) of the post-mortem brain using each of the two segmentation methods. Post-acquisition processing was performed using MEASURE software. Three investigators performed each measurement three times using each method, yielding a total of 180 measurements. Stereology took, on average, half the time of thresholding/tracing. Using a clinically acceptable variation for 95% of repeat measures; both intra-observer and inter-observer variation were acceptable for each technique. However, validity, as demonstrated by graphs of agreement against water displacement showed that the "limits of agreement" using stereology were within the acceptable range, while those using the thresholding/tracing technique were not. Quantitative estimates of variation and a graphical representation of the limits of agreement show that stereology is at least as precise as the thresholding/tracing method but is superior in terms of speed and validity. This has broad implications for published estimates of brain region volumes in human diseases such as epilepsy, dementia and other neurodegenerative disorders. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Royal Coll Surg Ireland, Dept Clin Neurol Sci, Beaumont Hosp, Dublin 9, Ireland. Dr Steevens Hosp, Eastern Hlth Board, Dept Publ Hlth Med, Dublin 8, Ireland. Univ Missouri, Sch Med, Dept Basic Med Sci, Kansas City, MO 64108 USA. RP Doherty, CP (reprint author), Massachusetts Gen Hosp, Dept Neurol, Wang ACC 835,32 Fruit St, Boston, MA 02114 USA. NR 41 TC 27 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD OCT PY 2000 VL 18 IS 8 BP 1017 EP 1025 DI 10.1016/S0730-725X(00)00185-5 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 379CP UT WOS:000165623600014 PM 11121707 ER PT J AU de Nooij, JC Graber, KH Hariharan, IK AF de Nooij, JC Graber, KH Hariharan, IK TI Expression of the cyclin-dependent kinase inhibitor Dacapo is regulated by Cyclin E SO MECHANISMS OF DEVELOPMENT LA English DT Article DE Drosophila; cell cycle; cyclin-dependent kinase inhibitor; dacapo; Cyclin E; embryo; imaginal disc; oogenesis ID CELL-CYCLE; DROSOPHILA EMBRYOGENESIS; S-PHASE; CDK INHIBITOR; MICE LACKING; TRANSCRIPTION FACTOR; PATTERN-FORMATION; PROLIFERATION; P27(KIP1); DIFFERENTIATION AB The Cip/Kip family of cyclin-dependent kinase inhibitors (CKIs) has been implicated in mediating cell cycle arrest prior to terminal differentiation. In many instances, increased expression of CKIs immediately precedes mitotic arrest. However, the mechanism that activates CKI expression in cells that are about to stop dividing has remained elusive. Here we have addressed this issue by investigating the expression pattern of dacapo, a Cip/Kip CKI in Drosophila. We show that the accumulation of dacapo RNA and protein requires Cyclin E and that increased expression of Cyclin E can induce dacapo expression. We also show that the oscillation of the Cyclin E and Dacapo proteins are tightly coupled during ovarian endocycles. Our results argue for a mechanism where Cyclin E/Cdk activity induces Dacapo expression but only within certain windows that are permissive for dacapo expression. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Hariharan, IK (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NEI NIH HHS [EY11632] NR 55 TC 41 Z9 41 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD OCT PY 2000 VL 97 IS 1-2 BP 73 EP 83 DI 10.1016/S0925-4773(00)00435-4 PG 11 WC Developmental Biology SC Developmental Biology GA 367YK UT WOS:000090089900007 PM 11025208 ER PT J AU Kung, JH Chen, GTY Kuchnir, FK AF Kung, JH Chen, GTY Kuchnir, FK TI A monitor unit verification calculation in intensity modulated radiotherapy as a dosimetry quality assurance SO MEDICAL PHYSICS LA English DT Article DE intensity modulated radiotherapy; monitor unit calculation; dosimetry quality assurance; hand calculation ID DOSE-CALCULATION ALGORITHM; MULTILEAF COLLIMATOR; RADIATION-THERAPY; PHOTON BEAMS; ORGAN MOTION; SYSTEM; OPTIMIZATION; MODEL AB In standard teletherapy, a treatment plan is generated with the aid of a treatment planning system, but it is common to perform an independent monitor unit verification calculation (MWC). In exact analogy, we propose and demonstrate that a simple and accurate MUVC in intensity modulated radiotherapy (IMRT) is possible. We introduce the concept of modified Clarkson integration (MCI). In MCI, we exploit the rotational symmetry of scattering to simplify the dose calculation. For dose calculation along a central axis (CAX), we first replace the incident IMRT fluence by an azimuthally averaged fluence. Second, the Clarkson integration is carried over annular sectors instead of over pie sectors. We wrote a computer code, implementing the MCI technique, in order to perform a MWC for IMRT purposes. We applied the code to IMRT plans generated by CORVUS. The input to the code consists of CORVUS plan data (e.g., DMLC files, jaw settings, MU for each IMRT field, depth to isocenter for each IMRT field), and the output is dose contribution by individual IMRTs field to the isocenter. The code uses measured beam data for Sc, Sp, TPR, (D/MU)(ref) and includes effects from multileaf collimator transmission, and radiation field offset. On a 266 MHz desktop computer, the code takes less than 15 to calculate a dose. The doses calculated with the MCI algorithm agreed within +/-3% with the doses calculated by CORVUS, which uses a 1 cmx1 cm pencil beam in dose calculation. In the present version of MCI, skin contour variations and inhomogeneities were neglected. (C) 2000 American Association of Physicists in Medicine. [S0094-2405(00)00308-4]. C1 Massachusetts Gen Hosp, Boston, MA 02144 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Cambridge, England. Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. RP Kung, JH (reprint author), Massachusetts Gen Hosp, Boston, MA 02144 USA. NR 33 TC 59 Z9 60 U1 0 U2 6 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD OCT PY 2000 VL 27 IS 10 BP 2226 EP 2230 DI 10.1118/1.1286553 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 367YG UT WOS:000090089500005 PM 11099189 ER PT J AU Lee, K Berthiaume, F Stephanopoulos, GN Yarmush, DM Yarmush, ML AF Lee, Kyongbum Berthiaume, Francois Stephanopoulos, Gregory N. Yarmush, David M. Yarmush, Martin L. TI Metabolic Flux Analysis of Postburn Hepatic Hypermetabolism SO METABOLIC ENGINEERING LA English DT Article AB The hepatic response to severe injury is characterized by a marked upregulation of glucose, fatty acid, and amino acid turnover, which, if persistent, predisposes the patient to progressive organ dysfunction. To study the effect of injury on liver intermediary metabolism, metabolic flux analysis was applied to isolated perfused livers of burned and sham-burned rats. Intracellular fluxes were calculated using metabolite measurements and a stoichiometric balance model. Significant flux increases were found for multiple pathways, including mitochondrial electron transport, the TCA and urea cycles, gluconeogenesis, and pentose phosphate pathway (PPP). The burn-induced increase in gluconeogenesis did not significantly increase glucose output. Instead, glucose-6-phosphate was diverted into the PPP. These changes were paralleled by increases in glucose-6-phosphate dehydrogenase (G6PDH) and glutathione reductase (GR) activities. Given that G6PDH and GR are the most significant NADPH producers and consumers in the liver, respectively, and that GR is responsible for recycling the free radical scavenger glutathione, these data are consistent with the notion that hepatic metabolic changes are in part due to the induction of liver antioxidant defenses. (C) 2000 Academic press C1 [Lee, Kyongbum; Berthiaume, Francois; Yarmush, David M.; Yarmush, Martin L.] Harvard Univ, Ctr Engn Med, Surg Serv, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. [Lee, Kyongbum; Berthiaume, Francois; Yarmush, David M.; Yarmush, Martin L.] Shriners Burns Hosp, Boston, MA 02114 USA. [Lee, Kyongbum; Stephanopoulos, Gregory N.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Yarmush, ML (reprint author), Harvard Univ, Ctr Engn Med, Surg Serv, Massachusetts Gen Hosp,Med Sch, GRB 1401, Boston, MA 02114 USA. RI Lee, Kyongbum/D-9230-2013 FU NIH [GM58125]; Whitaker Foundation; Shriners Hospitals for Children FX The authors thank Elliot DeHaan for assisting in metabolite assays and S. Patrick Walton for useful discussions. This work was supported by NIH Grant GM58125, the Whitaker Foundation, and the Shriners Hospitals for Children. NR 50 TC 59 Z9 60 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7176 J9 METAB ENG JI Metab. Eng. PD OCT PY 2000 VL 2 IS 4 BP 312 EP 327 DI 10.1006/mben.2000.0160 PG 16 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA V19NU UT WOS:000208079900004 PM 11120643 ER PT J AU Wolfe, J Stern, A Daley, J Zaslavsky, A Roper, SF Wilson, K AF Wolfe, J Stern, A Daley, J Zaslavsky, A Roper, SF Wilson, K TI Changing demographic characteristics of women veterans: Results from a national sample SO MILITARY MEDICINE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; MENTAL-HEALTH-SERVICES; PERSIAN-GULF-WAR; SEXUAL HARASSMENT; FEMALE VETERANS; NONVETERANS USE; CARE; VICTIMIZATION; POPULATION; WORKPLACE AB Women veterans are a small but growing percentage of the U.S. veteran population. There are some indications that, along with this increase, the characteristics and military experiences of younger women veterans differ considerably from those of older colleagues. Many of these characteristics are not well defined, but they could have implications for women's health care needs and health policy initiatives. Using the first sample drawn from the Department of Veterans Affairs' new National Registry of Women Veterans, we designed and administered a telephone survey to a representative sample of women veterans across several major age groups. Groups approximated primary eras of military and wartime service based on the assumption that different eras might be associated with differing military experiences. We found a number of age-related similarities and differences in women veterans' demographic characteristics, military experiences, physical health symptoms, and functional outcomes. Women veterans in general also differed from female civilian counterparts on exposure to sexual trauma. Trends in the population of women veterans are likely to have implications for the variety of health care systems that treat women veterans. C1 VA Boston Healthcare Syst, Natl Ctr Post Traumat Stress Disorder, Womens Hlth Sci Div, Boston, MA USA. RP Wolfe, J (reprint author), 30 Lowell Rd, Wellesley, MA 02481 USA. EM jessicawolfe@mediaone.net NR 45 TC 22 Z9 22 U1 1 U2 2 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 EI 1930-613X J9 MIL MED JI Milit. Med. PD OCT PY 2000 VL 165 IS 10 BP 773 EP 780 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 363MK UT WOS:000089839200017 ER PT J AU Voigt, S Hanspal, M LeRoy, PJ Zhao, PS Oh, SS Chishti, AH Liu, SC AF Voigt, S Hanspal, M LeRoy, PJ Zhao, PS Oh, SS Chishti, AH Liu, SC TI The cytoadherence ligand Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) binds to the P-falciparum Knob-associated Histidine-rich Protein (KAHRP) by electrostatic interactions SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Plasmodium falciparum; Plasmodium falciparum Erythrocyte Membrane Protein 1; PfEMP1; Knob-associated Histidine-rich Protein; KAHRP ID HUMAN CEREBRAL MALARIA; INFECTED ERYTHROCYTES; GENE; LOCALIZATION; ADHERENCE; RECEPTOR; ADHESION; CELL C1 Tufts Univ, Sch Med, St Elizabeths Med Ctr, Dept Med,Sect Incol Hematol Res, Boston, MA 02111 USA. Tufts Univ, Sch Med, St Elizabeths Med Ctr, Dept Anat & Cellular Biol,Sect Incol Hematol Res, Boston, MA 02111 USA. RP Voigt, S (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL37462, HL60961] NR 19 TC 22 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD OCT PY 2000 VL 110 IS 2 BP 423 EP 428 DI 10.1016/S0166-6851(00)00281-4 PG 6 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 360XD UT WOS:000089691900022 PM 11071296 ER PT J AU DiRenzo, J Shang, YF Phelan, M Sif, S Myers, M Kingston, R Brown, M AF DiRenzo, J Shang, YF Phelan, M Sif, S Myers, M Kingston, R Brown, M TI BRG-1 is recruited to estrogen-responsive promoters and cooperates with factors involved in histone acetylation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID STEROID-RECEPTOR COACTIVATOR-1; TRANSCRIPTIONAL ACTIVATION; SACCHAROMYCES-CEREVISIAE; GLUCOCORTICOID RECEPTOR; RETINOBLASTOMA PROTEIN; CHROMATIN STRUCTURE; NUCLEAR RECEPTORS; HUMAN HOMOLOGS; CO-REPRESSOR; COMPLEX AB Several factors that mediate activation by nuclear receptors also modify the chemical and structural composition of chromatin. Prominent in this diverse group is the steroid receptor coactivator 1 (SRC-1) family, which interact with agonist-bound nuclear receptors, thereby coupling them to multifunctional transcriptional coregulators such as CREB-binding protein (CBP), p300, and PCAF, all of which have potent histone acetyltransferase activity. Additionally factors including the Brahma-related gene 1 (BRG-1) that are involved in the structural remodeling of chromatin also mediate hormone-dependent transcriptional activation by nuclear receptors. Here, we provide evidence that these two distinct mechanisms of coactivation may operate in a collaborative manner. We demonstrate that transcriptional activation by the estrogen receptor (ER) requires functional BRG-1 and that the coactivation of estrogen signaling by either SRC-1 or CBP is BRG-1 dependent, We find that in response to estrogen, ER recruits BRG-1, thereby targeting BRG-1 to the promoters of estrogen-responsive genes in a manner that occurs simultaneous to histone acetylation. Finally, we demonstrate that BRG-1-mediated coactivation of ER signaling is regulated by the state of histone acetylation within a cell. Inhibition of histone deacetylation by trichostatin A dramatically increases BRG-1-mediated coactivation of ER signaling, and this increase is reversed by overexpression of histone deacetylase 1. These studies support a critical role for BRG-1 in ER action in which estrogen stimulates an ER-BRG-1 association coupling BRG-1 to regions of chromatin at the sites of estrogen-responsive promoters and promotes the activity of other recruited factors that alter the acetylation state of chromatin. C1 D 730 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. RP Brown, M (reprint author), D 730 Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. OI Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [CA57374] NR 48 TC 161 Z9 164 U1 1 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 OCT PY 2000 VL 20 IS 20 BP 7541 EP 7549 DI 10.1128/MCB.20.20.7541-7549.2000 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 357MB UT WOS:000089504500012 PM 11003650 ER PT J AU Chao, HHA Buchmann, AM DeCaprio, JA AF Chao, HHA Buchmann, AM DeCaprio, JA TI Loss of p19(ARF) eliminates the requirement for the pRB-Binding motif in simian virus 40 large T antigen-mediated transformation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SIMIAN-VIRUS-40 LARGE-T; SV40 LARGE-T; LARGE TUMOR-ANTIGEN; MOUSE EMBRYO FIBROBLASTS; TRANSCRIPTION FACTOR E2F; CELL-CYCLE INHIBITION; RETINOBLASTOMA-PROTEIN; J-DOMAIN; GENE-PRODUCT; FAMILY MEMBERS AB At least three domains of simian virus 40 large T antigen (TAg) participate in cellular transformation. The LXCXE motif of TAg binds to all members of the retinoblastoma protein (pRB) family of tumor suppressors. The N-terminal 70 residues of TAg have significant homology to the J domain of Hsp40/DnaJ and cooperate with the LXCXE motif to inactivate the pRB family. A bipartite C-terminal domain of TAg binds to p53 and thereby disrupts the ability of p53 to act as a sequence-specific transcription factor. The contribution of these three domains of TAg to cellular transformation was evaluated in cells that contained inactivating mutations in the pRB and p53 pathways. Cells that stably expressed wild-type or selected mutant forms of TAg were generated in mouse embryo fibroblasts (MEFs) containing homozygous deletions in the RE, INK4a, and ARF loci. It was determined that the J domain, the LXCXE motif, and the p53-binding domain of TAg were required for full transformation of wild-type and RB-/- MEFs. In contrast, INK4a(-/-) MEFs that lacked expression of p16(INK4a) and p19(ARF) and ARF(-/-) MEFs that lacked p19(ARF) but expressed p16(INK4a) acquired anchorage-independent growth when expressing wild-type TAg or mutant derivatives that disrupted either the pRB-binding or p53-binding domain. The expression and function of the pRB family members were not overly disrupted in ARF(-/-) MEFs expressing LXCXE mutants of TAO. These results suggest that inactivating mutations of p19(ARF) can relieve the requirement for the LXCXE motif in TAg-mediated transformation and that TAg may have additional functions in transformation. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP DeCaprio, JA (reprint author), Dana Farber Canc Inst, Mayer 457,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [T32 CA009361, 2T32CA09361, R01-CA63113, F32 CA081745, F32CA81745, R01 CA063113] NR 81 TC 20 Z9 20 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 2000 VL 20 IS 20 BP 7624 EP 7633 DI 10.1128/MCB.20.20.7624-7633.2000 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 357MB UT WOS:000089504500020 PM 11003658 ER EF