FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Liberthson, RR AF Liberthson, RR TI Arrhythmias in the athlete with congenital heart disease: Guidelines for participation SO ANNUAL REVIEW OF MEDICINE LA English DT Review DE sudden death; sudden cardiac death; cardiac arrhythmia ID SUDDEN UNEXPECTED DEATH; NATURAL DEATH; YOUNG-ADULTS; CHILDREN; ADOLESCENCE; CHILDHOOD AB Advances in the diagnosis and early management of congenital heart disease in recent decades have led to increasing numbers of individuals being sufficiently well to participate in social as well as truly competitive sports. Physicians are increasingly asked whether such participation is safe, advisable, and efficacious, yet few guidelines exist to help them make these decisions. There are three apparent subgroups of patients: (a) those with mild or repaired problems, who function normally or nearly so and may fully participate; (b) those with severe functional deficit or known high risk, for whom strenuous exertion must be strictly proscribed; and (c) those who fall in between, with some limitations and some risk-these patients present a great challenge to the wisdom and clinical skill of the physician. C1 Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Liberthson, RR (reprint author), Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. NR 19 TC 4 Z9 4 U1 0 U2 1 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 J9 ANNU REV MED JI Annu. Rev. Med. PY 1999 VL 50 BP 441 EP 452 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 170XF UT WOS:000078831800029 PM 10073288 ER PT J AU Sheen, J AF Sheen, J TI C-4 gene expression SO ANNUAL REVIEW OF PLANT PHYSIOLOGY AND PLANT MOLECULAR BIOLOGY LA English DT Review DE photosynthesis; bundle sheath; mesophyll; transcription; signal transduction ID LIGHT SIGNAL-TRANSDUCTION; NADP-MALATE DEHYDROGENASE; LEAF CELL-TYPES; PHOSPHOENOLPYRUVATE-CARBOXYLASE KINASE; ORTHOPHOSPHATE DIKINASE GENE; BUNDLE SHEATH-CELLS; SUCROSE-PHOSPHATE SYNTHASE; DEVELOPING MAIZE LEAVES; FLAVERIA-TRINERVIA C-4; DEPENDENT MALIC ENZYME AB C-4 plants, including maize, Flaveria, amaranth, sorghum, and an amphibious sedge Eleocharis vivipara, have been employed to elucidate the molecular mechanisms and signaling pathways that control C-4 photosynthesis gene expression. Current evidence suggests that pre-existing genes were recruited for the Cs pathway after acquiring potent and surprisingly diverse regulatory elements. This review emphasizes recent advances in our understanding of the creation of C-4 genes, the activities of the C-4 gene promoters consisting of synergistic and combinatorial enhancers and silencers, the use of 5' and 3' untranslated regions for transcriptional and posttranscriptional regulations, and the function of novel transcription factors. The research has also revealed new insights into unique or universal mechanisms underlying cell-type specificity, coordinate nuclear-chloroplast actions, hormonal, metabolic, stress and light responses, and the control of enzymatic activities by phosphorylation and reductive processes. C1 Harvard Univ, Sch Med, Dept Genet, Massachusetts Gen Hosp,Dept Mol Biol, Boston, MA 02114 USA. RP Sheen, J (reprint author), Harvard Univ, Sch Med, Dept Genet, Massachusetts Gen Hosp,Dept Mol Biol, Boston, MA 02114 USA. NR 163 TC 134 Z9 145 U1 0 U2 9 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1040-2519 J9 ANNU REV PLANT PHYS JI Annu. Rev. Plant Physiol. Plant Molec. Biol. PY 1999 VL 50 BP 187 EP 217 DI 10.1146/annurev.arplant.50.1.187 PG 31 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA 213TB UT WOS:000081288400008 ER PT J AU McHorney, CA AF McHorney, CA TI Health status assessment methods for adults: Past accomplishments and future challenges SO ANNUAL REVIEW OF PUBLIC HEALTH LA English DT Review DE quality-of-life assessment; health status applications; selection of measures; measurement precision; methodological considerations ID QUALITY-OF-LIFE; SICKNESS IMPACT PROFILE; GENERAL POPULATION SURVEY; PRIMARY-CARE PATIENTS; RHEUMATOID-ARTHRITIS; FUNCTIONAL STATUS; MEDICAL OUTCOMES; CLINICAL-TRIALS; MENTAL-HEALTH; SF-36 AB Over the past 30 years, health status assessment methods for adults have proliferated. Numerous generic, disease-specific, and preference-based measures now exist that tap diverse aspects of functioning, well-being, symptom states, and subjective perceptions of health. The evolution of the state of the art in adult health status assessment is reviewed. Applications of these tools in health services research, health policy, and clinical practice are discussed. Recommendations are offered for selecting among the armamentaria of tools. Conceptual and methodological challenges that confront instrument users and developers alike are identified and discussed. C1 Univ Wisconsin, Sch Med, Dept Prevent Med, Madison, WI 53705 USA. Univ Wisconsin, Sch Med, Dept Med, Madison, WI 53705 USA. William S Middleton Mem Vet Hosp, Hlth Serv Res & Dev Program, Madison, WI 53705 USA. RP McHorney, CA (reprint author), Univ Wisconsin, Sch Med, Dept Prevent Med, Madison, WI 53705 USA. NR 120 TC 145 Z9 147 U1 22 U2 36 PU ANNUAL REVIEWS INC PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0163-7525 J9 ANNU REV PUBL HEALTH JI Annu. Rev. Public Health PY 1999 VL 20 BP 309 EP 335 DI 10.1146/annurev.publhealth.20.1.309 PG 27 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 198RW UT WOS:000080438800018 PM 10352861 ER PT J AU Zhou, XJ Sheiner, LB D'Aquila, RT Hughes, MD Hirsch, MS Fischl, MA Johnson, VA Myers, M Sommadossi, JP AF Zhou, XJ Sheiner, LB D'Aquila, RT Hughes, MD Hirsch, MS Fischl, MA Johnson, VA Myers, M Sommadossi, JP CA Natl Inst Allergy Infectious Dis AIDS Clinical TI Population pharmacokinetics of nevirapine, zidovudine, and didanosine in human immunodeficiency virus-infected patients SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID AIDS-RELATED COMPLEX; PLACEBO-CONTROLLED TRIAL; COMBINATION THERAPY; CLINICAL PHARMACOKINETICS; TOXIC CATABOLITE; DRUG-RESISTANCE; LAMIVUDINE 3TC; DOUBLE-BLIND; IN-VITRO; HIV AB The population pharmacokinetics of nevirapine (NVP), zidovudine (ZDV), and didanosine (ddI) were evaluated in a total of 175 patients infected with human immunodeficiency virus randomized to receive either a double combination of ZDV plus ddI or a triple combination of NVP plus ZDV plus ddI as a substudy of the AIDS Clinical Trials Group Protocol 241. Levels (approximating 3.5 determinations/patient) of the three drugs in plasma were measured during 44 of a total 48 weeks of study treatment, and a set of potential covariates was available far nonlinear mixed-effect modeling analysis. A one-compartment model with zero-order input and first-order elimination was fitted to the NVP data. Individual oral clearance (CL) and volume of distribution (V) averaged 0.0533 liters/h/kg of body weight and 1.17 liters/kg, respectively. Gender was the only covariate which significantly correlated with the CL of NVP. ZDV and ddI data were described by a two-compartment model with zero-order input and first-order elimination. Individual mean oral CL, V-SS, (volume of distribution at steady state), and V of ZDV were 1.84 liters/h/kg and 6.68 and 2.67 liters/kg, respectively, with body weight and age as correlates of CL and body weight as a correlate of V-SS. The average individual oral CL, V-SS, and V of ddI were 1.64 liters/h/kg and 3.56 and 2.74 liters/kg, respectively, with body weight as a significant correlate of both CL and V-SS. The relative bioavailability (F) of ZDV and ddI in the triple combination compared to that in the double combination was also evaluated. No significant effects of the combination regimens on the F of ddI were detected (F-TRIPLE = 1.05 and F-DOUBLE = 1 by definition), but the F of ZDV was markedly reduced by the triple combination, being only 67.7% of that of the double combination. Large (>50%) intraindividual variability was associated with both ZDV and ddI pharmacokinetics. Individual cumulative area under the plasma drug level-time curve of the three drugs was calculated for the entire study period as a measure of drug exposure based on the individual data and the final-model estimates of structural and statistical parameters. C1 Univ Alabama, Vet Affairs Med Ctr, Sch Med, Dept Pharmacol,Div Clin Pharmacol, Birmingham, AL 35294 USA. Univ Alabama, Vet Affairs Med Ctr, Sch Med, Dept Med,Div Infect Dis, Birmingham, AL 35294 USA. Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. London Sch Hyg & Trop Med, London WC1, England. Univ Miami, Sch Med, Miami, FL USA. Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. RP Sommadossi, JP (reprint author), Univ Alabama, Vet Affairs Med Ctr, Sch Med, Dept Pharmacol,Div Clin Pharmacol, Volker Hall G019,1670 Univ Blvd, Birmingham, AL 35294 USA. EM Jean-Pierre.Sommadossi@CCC.UAB.EDU NR 40 TC 63 Z9 67 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 1999 VL 43 IS 1 BP 121 EP 128 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 163UD UT WOS:000078424000021 PM 9869576 ER PT J AU Oh, MD Merrill, DP Hirsch, MS AF Oh, MD Merrill, DP Hirsch, MS TI Induction and maintenance treatment regimens for HIV-1 infection in vitro SO ANTIVIRAL THERAPY LA English DT Article ID RECOMBINANT INTERFERON-ALPHA; ACTIVE ANTIRETROVIRAL THERAPY; IN-VITRO; SYNERGISTIC INHIBITION; REPLICATION INVITRO; ZIDOVUDINE; COMBINATIONS; LAMIVUDINE; RESERVOIR; VIREMIA AB Can aggressive anti-human immunodeficiency virus (HIV) induction regimens be simplified after sufficient virus suppression is achieved? In vitro studies were conducted to evaluate the hypothesis that aggressive induction regimens could be followed by less aggressive maintenance regimens, A clinical HIV-1 isolate and lymphoblastoid cell line (H9) were employed. Virus multiplicities were varied, as were drug inhibitory concentrations (IC90, IC99) and induction periods (1, 2 and 3 weeks) of a three-drug regimen (zidovudine plus lamivudine and indinavir), following which maintenance regimens (no drug, zidovudine alone, indinavir alone, zidovudine plus lamivudine) were employed. After 1 week inductions at IC99 concentrations, viral rebound occurred on none or one-drug maintenance regimens but not on a two-drug regimen. After 2 week inductions, viral rebound occurred with no-drug maintenance, but not with one- and two-drug regimens. After 3 week inductions, viral rebound did not occur in zero-, one-, or two-drug maintenance regimens, although HIV-1 DNA persisted in cultured cells. These studies suggest that although some induction-maintenance regimens will fail, after a sufficient period of HIV-1 suppression with a three-drug antiretroviral regimen, maintenance on fewer drugs may be feasible. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Infect Dis Unit,Dept Med, Boston, MA 02114 USA. RP Hirsch, MS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Infect Dis Unit,Dept Med, Gray 5,Fruit St, Boston, MA 02114 USA. EM hirsch.martin@mgh.harvard.edu FU NCI NIH HHS [CA-12464] NR 23 TC 2 Z9 2 U1 0 U2 0 PU INT MEDICAL PRESS PI LONDON PA 125 HIGH HOLBORN, LONDON WC1V 6QA, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 1999 VL 4 IS 1 BP 29 EP 34 PG 6 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 184YA UT WOS:000079640300005 PM 10682126 ER PT S AU Flanz, JB Bailey, J Bradley, SG Goitein, M Gottshalk, B Jongen, Y Loeffler, J Mandin, J Miyahara, N Newhauser, W Prieels, D Rosenthal, S Rosselot, D Schippers, M Schubert, J Smith, A Wagner, M AF Flanz, JB Bailey, J Bradley, SG Goitein, M Gottshalk, B Jongen, Y Loeffler, J Mandin, J Miyahara, N Newhauser, W Prieels, D Rosenthal, S Rosselot, D Schippers, M Schubert, J Smith, A Wagner, M CA IBA Staff BE Duggan, JL Morgan, IL TI Recent performance of the NPTC equipment compared with the clinical specifications SO APPLICATION OF ACCELERATORS IN RESEARCH AND INDUSTRY, PTS 1 AND 2 SE AIP CONFERENCE PROCEEDINGS LA English DT Proceedings Paper CT 15th International Conference on the Application of Accelerators in Research and Industry CY NOV 04-07, 1998 CL UNIV N TEXAS, DENTON, TX SP US DOE, Natl Sci Fdn, Univ N Texas HO UNIV N TEXAS AB The construction of the Northeast Proton Therapy Center (NPTC) at Massachusetts General Hospital is nearing completion. Preliminary beam tests have begun and clinical acceptance testing is soon to follow. Preliminary measurements have been made to determine the properties of the system as compared to the clinical requirements. These results will be discussed. The procedures and instrumentation to be used for testing will also be described. C1 Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. RP Flanz, JB (reprint author), Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 1-56396-825-8 J9 AIP CONF PROC PY 1999 VL 475 BP 971 EP 974 PG 4 WC Chemistry, Physical; Materials Science, Characterization & Testing; Physics, Atomic, Molecular & Chemical; Physics, Nuclear; Physics, Particles & Fields; Spectroscopy SC Chemistry; Materials Science; Physics; Spectroscopy GA BN31G UT WOS:000081503200231 ER PT J AU Stafford, RS Saglam, D Causino, N Starfield, B Culpepper, L Marder, WD Blumenthal, D AF Stafford, RS Saglam, D Causino, N Starfield, B Culpepper, L Marder, WD Blumenthal, D TI Trends in adult visits to primary care physicians in the United States SO ARCHIVES OF FAMILY MEDICINE LA English DT Article ID HEALTH-CARE; EDUCATION AB Background: Although numerous changes are apparent in the US health care system, little is known about how these changes have altered the work of primary care physicians. Methods: We analyzed a nationally representative sample of 136 233 adult office visits to general internists, general practitioners, and family physicians contained in the 1978 through 1981, 1985, and 1989 through 1994 National Ambulatory Medical Care Surveys. Annual sample sites varied between 5662 and 19 977 visits. Measures included the characteristics of patients presenting to primary care physicians, physician activities during these visits, and the disposition of the visits to primary care physicians. Results: Visits to primary care physicians have diminished as a proportion of all adult visits from 52% in 1978 to 41% in 1994. Dramatic trends in adult primary care included the growing racial or ethnic diversity of patients, the doubling (since 1985) of health maintenance organization coverage, increased provision of prevention services, changes in the most common medications, and an 18% increase in the duration of adult visits to primary care physicians. Conclusions: Trends in primary care practice reflect changes in society and in the US health care system, including demographic changes, an emphasis on prevention, and the growth of managed care. The increasing role of managed care, with its emphasis on increased productivity, appears at odds with primary care physicians' increasing responsibility for prevention and the associated increase in the duration of primary cart visits. C1 Massachusetts Gen Hosp, Div Gen Med, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. Boston Univ, Sch Med, Dept Family Med, Boston, MA 02118 USA. Medstat Grp, Cambridge, MA USA. RP Stafford, RS (reprint author), Massachusetts Gen Hosp, Div Gen Med, Inst Hlth Policy, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM stafford@sol.mgh.harvard.edu FU AHRQ HHS [R01HS07892] NR 35 TC 51 Z9 51 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1063-3987 J9 ARCH FAM MED JI Arch. Fam. Med. PD JAN-FEB PY 1999 VL 8 IS 1 BP 26 EP 32 DI 10.1001/archfami.8.1.26 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 180VD UT WOS:000079405100007 PM 9932068 ER PT J AU Williams, JW Rost, K Dietrich, AJ Ciotti, MC Zyzanski, SJ Cornell, J AF Williams, JW Rost, K Dietrich, AJ Ciotti, MC Zyzanski, SJ Cornell, J TI Primary care physicians' approach to depressive disorders - Effects of physician specialty and practice structure SO ARCHIVES OF FAMILY MEDICINE LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; GENERAL-PRACTITIONERS; TRICYCLIC ANTIDEPRESSANTS; MENTAL-DISORDERS; MEDICAL OUTCOMES; KNOWLEDGE; OUTPATIENTS; DISABILITY; ATTITUDES; PATTERNS AB Background: Because primary care physicians (PCPs) are the initial health care contact for most patients with depression, they are in a unique position to provide early detection and integrated care for persons with depression and coexisting medical illness. Despite this opportunity, care for depression is often suboptimal. Objectives: To better understand how to design interventions to improve care, we examine PCPs' approach to recognition and management and the effects of physician specialty and degree of capitation on barriers to care for 3 common depressive disorders. Methods: A 53-item questionnaire was mailed to 3375 randomly selected subjects, divided equally among family physicians, general internists, and obstetrician-gynecologists. The questionnaire assessed reported diagnosis and treatment practices for each subject's most recent patient recognized to have major or minor depression or dysthymia and barriers to the recognition and treatment of depression. Eligible physicians were PCPs who worked at least half-time seeing outpatients for longitudinal care. Results: Of 2316 physicians with known eligibility, 1350 (58.3%) returned the questionnaire. Respondents were family physicians (n = 621), general internists (n = 474), and obstetrician-gynecologists (n = 255). The PCPs report recognition and evaluation practices related to their most recent case as follows: recognition by routine questioning or screening for depression (9%), diagnosis based on formal criteria (33.7%), direct questioning about suicide (58%), and assessment for substance abuse (68.1%) or medical causes of depression (84.1%). Reported treatment practices were watchful waiting only (6.1%), PCP counseling for more than 5 minutes (39.7%), antidepressant medication prescription (72.5%), and mental health referral (38.4%). Diagnostic evaluation and treatment approaches varied significantly by specialty but not by the type of depression or degree of capitation. Physician barriers differed by specialty more than by degree of capitation. in contrast, organizational barriers, such as time for an adequate history and the affordability of mental health professionals, differed by degree of capitation more than by physician specialty. Patient barriers were com mon but did not vary by physician specialty or degree of capitation. Conclusions: A substantial proportion of PCPs report diagnostic and treatment approaches that are consistent with high-quality care. Differences in approach were associated more with specialty than with type of depressive disorder or degree of capitation. Quality improvement efforts need to (1) be tailored for different physician specialties, (2) emphasize the importance of differentiating major depression from other depressive disorders and tailoring the treatment approach accordingly, and (3) address organizational barriers to best practice and knowledge gaps about depression treatment. C1 S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Div Gen Internal Med, San Antonio, TX USA. Univ Arkansas, Sch Med, Little Rock, AR 72204 USA. Little Rock Hlth Serv Res & Dev Field Program, Little Rock, AR USA. Dartmouth Med Sch, Dept Community & Family Med, Hanover, NH USA. Michigan State Univ, Sch Med, Dept Obstet & Gynecol, Lansing, MI USA. Case Western Reserve Univ, Sch Med, Dept Family Med & Biostat, Cleveland, OH USA. RP Williams, JW (reprint author), S Texas Vet Hlth Care Syst, Audie Murphy Div, Mailstop 11C-6,7400 Merton Minter Blvd, San Antonio, TX 78284 USA. RI Williams, Jr., John/A-3696-2008; Page, Andrew/G-5438-2012 OI Williams, Jr., John/0000-0002-5267-5558; Page, Andrew/0000-0003-3133-2844 NR 50 TC 192 Z9 193 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1063-3987 J9 ARCH FAM MED JI Arch. Fam. Med. PD JAN-FEB PY 1999 VL 8 IS 1 BP 58 EP 67 DI 10.1001/archfami.8.1.58 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 180VD UT WOS:000079405100013 PM 9932074 ER PT J AU Goff, DC Tsai, G Levitt, J Amico, E Manoach, D Schoenfeld, DA Hayden, DL McCarley, R Coyle, JT AF Goff, DC Tsai, G Levitt, J Amico, E Manoach, D Schoenfeld, DA Hayden, DL McCarley, R Coyle, JT TI A placebo-controlled trial of D-cycloserine added to conventional neuroleptics in patients with schizophrenia SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID GLYCINE ADJUVANT THERAPY; NMDA RECEPTOR; NEGATIVE SYMPTOMS; MODULATORY SITE; XENOPUS OOCYTES; GLUTAMATE; CLOZAPINE; DYSFUNCTION; ACTIVATION; AGONIST AB Background: In a preliminary dose-finding study, D-cycloserine, a partial agonist at the glycine modulatory site of the glutamatergic N-methyl-D-aspartate (NMDA) receptor, improved negative symptoms and cognitive function when added to conventional neuroleptics at a dose of 50 mg/d. Methods: Forty-seven patients with schizophrenia meeting criteria for deficit syndrome were randomized to D-cycloserine, 50 mg/d (n = 23) or placebo (n = 24) added to their conventional neuroleptic for an 8-week, double-blind trial. Clinical assessments were performed at baseline and at weeks 1, 2, 4, 6, and 8. Serum concentrations of D-cycloserine. relevant amino acids, and homovanillic acid were assayed at baseline and at weeks 4 and 8. A cognitive battery was performed at baseline and at week 8. Results: Thirty-nine patients completed the 8-week trial. Seven dropouts occurred in the D-cycloserine group and 1 in the placebo group. The mean reduction in negative symptoms with D-cycloserine (23%) was significantly greater than with placebo (7%) as calculated by slopes representing Scale for the Assessment of Negative Symptoms (SANS) total scores. Improvement of negative symptoms was predicted by low neuroleptic dose and low baseline SANS total score. No differences were found in performance on any cognitive test between groups or in changes in any other clinical measure. Clinical response did not correlate significantly with serum amino acid concentrations at baseline or with concentrations of D-cycloserine at weeks 4 and 8. Conclusion: These results support the hypothesis that agents acting at the glycine modulatory site of the NMDA receptor improve primary negative symptoms. C1 Harvard Univ, Consolidated Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Psychot Disorders Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Biostat Program, Boston, MA 02114 USA. Brockton VA Schizophrenia Biol Res Ctr, Brockton, MA USA. RP Goff, DC (reprint author), Harvard Univ, Sch Med, Freedom Trial Clin, 25 Staniford St, Boston, MA 02114 USA. EM goff@psych.mgh.harvard.edu FU NIMH NIH HHS [R01-MH54245] NR 49 TC 274 Z9 279 U1 2 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JAN PY 1999 VL 56 IS 1 BP 21 EP 27 DI 10.1001/archpsyc.56.1.21 PG 7 WC Psychiatry SC Psychiatry GA 156KQ UT WOS:000078000500002 PM 9892252 ER PT J AU van Gorp, WG Wilkins, JN Hinkin, CH Moore, LH Hull, J Horner, MD Plotkin, D AF van Gorp, WG Wilkins, JN Hinkin, CH Moore, LH Hull, J Horner, MD Plotkin, D TI Declarative and procedural memory functioning in abstinent cocaine abusers SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID IN-VIVO MICRODIALYSIS; NEUROPSYCHOLOGICAL DEFICITS; MALE-RATS AB Background: We determined the nature and recovery of procedural and declarative memory functioning in a cocaine-abusing cohort in the 45-day period following use. Methods: Thirty-seven cocaine abusers and 27 control subjects were administered the following memory and mood measures: California Verbal Learning Test, recall of the Rey-Osterrieth Complex Figure Test, Pursuit Rotor Task, and Profile of Mood States at 4 visits (within 72 hours of admission and at 10, 21, and 45 days following abstinence). Results: Analysis of performance on the Rey-Osterrieth Complex Figure Test revealed that both groups improved in their recall over repeated administrations, though the control group recalled significantly more of the information than cocaine subjects during the 45-day interval. Results for the California Verbal Learning Test indicated improved learning for both subject groups over time, but no group x time interaction. On the Pursuit Rotor Task, cocaine abusers improved their performance at a faster rate than controls at visit 1. At day 45 (visit 4), cocaine abusers again showed improvement on the Pursuit Rotor Task, whereas controls demonstrated a relative plateau in rate of learning. Conclusions: This study documented a lasting detrimental effect on a sensitive nonverbal declarative memory task in cocaine-dependent subjects following abstinence of 45 days. In contrast, abstinence from cocaine during this 45-day period was associated with sustained improvement on a motor learning test in the cocaine abusers relative to controls. C1 Cornell Univ, Coll Med, Dept Psychiat, New York, NY 10021 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Psychol, Los Angeles, CA 90024 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP van Gorp, WG (reprint author), Cornell Univ, Coll Med, Dept Psychiat, 525 E 68th St,Box 140, New York, NY 10021 USA. NR 21 TC 70 Z9 70 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JAN PY 1999 VL 56 IS 1 BP 85 EP 89 DI 10.1001/archpsyc.56.1.85 PG 5 WC Psychiatry SC Psychiatry GA 156KQ UT WOS:000078000500010 PM 9892260 ER PT J AU Yasuda, M Maeda, K Hashimoto, M Yamashita, H Ikejiri, Y Bird, TD Tanaka, C Schellenberg, GD AF Yasuda, M Maeda, K Hashimoto, M Yamashita, H Ikejiri, Y Bird, TD Tanaka, C Schellenberg, GD TI A pedigree with a novel presenilin 1 mutation at a residue that is not conserved in presenilin 2 SO ARCHIVES OF NEUROLOGY LA English DT Article ID FAMILIAL ALZHEIMERS-DISEASE; MISSENSE MUTATIONS; CAENORHABDITIS-ELEGANS; GENE; CLONING AB Objective: To disclose a novel mutation of the presenilin 1 (PS1) gene responsible for early-onset Alzheimer disease and to clarify genotype-phenotype correlation that should help to establish the function of this protein. Background: The PS1 and presenilin 2 (PS2) genes carry missense mutations in families with Alzheimer disease. The PS1 and PS2 proteins have similar structures, and all presently known mutations are in nucleotides coding for amino acids that are conserved between the 2 presenilins. Methods: Sequence and restriction fragment length polymorphism analyses of PS1 gene of DNA from a pedigree with early-onset Alzheimer disease Results: Sequence analysis disclosed a novel PS1 mutation in a pedigree of Japanese origin with early-onset Alzheimer disease. This mutation, which is predicted to cause a missense substitution of lysine for glutamic acid, occurred at codon 123 of PS1 that was not a conserved residue in PS2. The 2 patients of this pedigree shared an early clinical phenotype consisting of later-onset, progressive aphasia, but preserved visuospatial ability, which was indistinguishable from those of other PS1-associated Alzheimer disease cases. Conclusion: These results demonstrate that a missense mutation in a region not conserved between PS1 and PS2 can cause Alzheimer disease. C1 Hyogo Inst Aging Brain & Cognit Disorders, Himeji, Hyogo 6700981, Japan. Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. Osaka Univ, Sch Med, Dept Psychiat, Osaka, Japan. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Pharmacol, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. RP Yasuda, M (reprint author), Hyogo Inst Aging Brain & Cognit Disorders, 520 Saisho Ko, Himeji, Hyogo 6700981, Japan. NR 27 TC 15 Z9 16 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JAN PY 1999 VL 56 IS 1 BP 65 EP 69 DI 10.1001/archneur.56.1.65 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 157GQ UT WOS:000078053300009 PM 9923762 ER PT J AU Dryja, TP AF Dryja, TP TI The best excitement in age-related macular degeneration SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material ID TISSUE INHIBITOR; METALLOPROTEINASES-3; DYSTROPHY; MUTATIONS; TIMP3 C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Dryja, TP (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 10 TC 2 Z9 2 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JAN PY 1999 VL 117 IS 1 BP 108 EP 109 PG 2 WC Ophthalmology SC Ophthalmology GA 163VJ UT WOS:000078426800016 PM 9930170 ER PT J AU Dohlman, CH D'Amico, DJ AF Dohlman, CH D'Amico, DJ TI Can an eye in phthisis be rehabilitated? A case of improved vision with 1-year follow up SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Dohlman, CH (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 9 TC 5 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JAN PY 1999 VL 117 IS 1 BP 123 EP 124 PG 2 WC Ophthalmology SC Ophthalmology GA 163VJ UT WOS:000078426800021 PM 9930175 ER PT J AU Pomeranz, HD Lessell, S AF Pomeranz, HD Lessell, S TI A hereditary chiasmal optic neuropathy SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID COMMISSURAL AXONS; CNS MIDLINE; C-ELEGANS; DROSOPHILA; NETRINS; GUIDANCE; PROTEIN; UNC-6 C1 Harvard Univ, Sch Med, Dept Ophthalmol,Neuroophthalmol Unit, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Lessell, S (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol,Neuroophthalmol Unit, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 12 TC 3 Z9 3 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JAN PY 1999 VL 117 IS 1 BP 128 EP 131 PG 4 WC Ophthalmology SC Ophthalmology GA 163VJ UT WOS:000078426800025 PM 9930179 ER PT J AU Kawashima, N Stashenko, P AF Kawashima, N Stashenko, P TI Expression of bone-resorptive and regulatory cytokines in murine periapical inflammation SO ARCHIVES OF ORAL BIOLOGY LA English DT Article DE cytokines; bone-resorption; inflammation; periapical ID TUMOR-NECROSIS-FACTOR; HUMAN INTERFERON-GAMMA; INTERLEUKIN-11 PRODUCTION; OSTEOBLASTIC CELLS; MONONUCLEAR-CELLS; SIGNAL TRANSDUCER; RADICULAR CYSTS; GENE-EXPRESSION; PROSTAGLANDIN-E; GROWTH-FACTORS AB Periapical bone destruction earlier was shown to be mediated primarily by interleukin (IL)-1 alpha in a rat model. The production and action of IL-1 alpha is in turn potentially modulated by a network of cytokines, which are produced by infiltrating T-helper type 1 (Th1) and type 2 (Th2) lymphocytes, and resident connective tissue cells within the lesion. This study was designed to examine the kinetics of expression of 10 cytokines in experimentally induced murine periapical lesions, including bone-resorptive [IL-1 alpha, tumour necrosis factor alpha (TNF alpha), IL-6, IL-11], Th1-type [IL-2, IL-12, interferon-gamma (IFN gamma)] and Th2-type (IL-4, IL-6, IL-10, IL-13) mediators. Cytokine mRNA expression was assessed qualitatively by reverse transcription-polymerase chain reaction, and cytokine proteins quantified by enzyme-linked immunosorbent assay. IL-1 alpha and TNF alpha protein and mRNA were highly expressed, beginning on day 7, and increased to day 28. IL-6 increased to day 14 and then declined, whereas the expression of IL-11 was not modulated by pulp exposure. Most of the Th1-type cytokines, including IL-2, IL-12, and IFN gamma, showed an increase in mRNA and/or protein expression in periapical lesions after pulpal exposure; the expression of Th2-type cytokines was similarly increased, but had declined at the latest time-point (day 28). suggesting possible inhibition by Th1-type mediators. Significant correlations were observed between levels of IL-1 alpha and Th1-derived pro-inflammatory mediators IL-2, IL-12, TNF alpha, and IFN gamma. There was a lack of correlation between IL-1 alpha and Th2-type antiinflammatory mediators, including IL-4, -6, and -10. These results indicate that a cytokine network is activated in the periapex in response to bacterial infection, and that Th1-modulated pro-inflammatory pathways may predominate during periapical bone destruction. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Forsyth Dent Ctr, Dept Cytokine Biol, Boston, MA 02115 USA. Tokyo Med & Dent Univ, Dept Endodont, Tokyo, Japan. RP Stashenko, P (reprint author), Forsyth Dent Ctr, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-09018, DE-11664] NR 65 TC 131 Z9 135 U1 0 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0003-9969 J9 ARCH ORAL BIOL JI Arch. Oral Biol. PD JAN PY 1999 VL 44 IS 1 BP 55 EP 66 DI 10.1016/S0003-9969(98)00094-6 PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 164QQ UT WOS:000078475400009 PM 10075151 ER PT J AU Hammond, EH Compton, CC AF Hammond, EH Compton, CC CA Canc Comm Coll Amer Pathologists TI Protocols for the examination of tumors of diverse sites - Introduction SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID OF-AMERICAN-PATHOLOGISTS; CANCER-COMMITTEE; HISTOLOGIC GRADE; LUNG-CANCER; SPECIMENS; CHECKLISTS; CARCINOMA; SURVIVAL; PUBLICATION; DISEASE AB This issue of the ARCHIVES includes previously unpublished protocols for the examination of specimens removed from patients with cancer of diverse sites. We provide a historical context for the development of these protocols and describe the process of development and approval. General information about the structure and content of the protocols is also provided. Cancer protocol development is an important step in the process of standardized cancer reporting. The value of such standardized reporting is discussed. C1 Univ Utah, Sch Med, Dept Pathol, LDS Hosp, Salt Lake City, UT USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Hammond, EH (reprint author), Care Of Schramm J, Coll Amer Pathologists, 325 Waukegan Rd, Northfield, IL 60093 USA. NR 34 TC 2 Z9 2 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 1999 VL 123 IS 1 BP 11 EP 13 PG 3 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 157QM UT WOS:000078073200002 PM 9923829 ER PT J AU Scully, RE Henson, DE Nielsen, ML Ruby, SG AF Scully, RE Henson, DE Nielsen, ML Ruby, SG CA Canc Comm Coll Amer Pathologists TI Protocol for the examination of specimens from patients with carcinoma of the fallopian tube - A basis for checklists SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NCI, Early Detect Branch, Div Canc Prevent & Control, Bethesda, MD 20892 USA. Pathol Consultants, Wichita, KS USA. Hinsdale Hosp, Dept Pathol & Lab Med, Hinsdale, IL USA. RP Scully, RE (reprint author), Care Of Schramm J, Coll Amer Pathologists, 325 Waukegan Rd, Northfield, IL 60093 USA. NR 11 TC 4 Z9 4 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 1999 VL 123 IS 1 BP 33 EP 38 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 157QM UT WOS:000078073200007 PM 9923834 ER PT J AU Scully, RE AF Scully, RE CA Canc Comm Coll Amer Pathologist TI Protocol for the examination of specimens from patients with carcinoma of the vagina - A basis for checklists SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Scully, RE (reprint author), Care Of Schramm J, Coll Amer Pathologists, 325 Waukegan Rd, Northfield, IL 60093 USA. NR 9 TC 5 Z9 5 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 1999 VL 123 IS 1 BP 62 EP 67 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 157QM UT WOS:000078073200012 PM 9923839 ER PT J AU Compton, CC Harris, NL Ross, DW AF Compton, CC Harris, NL Ross, DW CA Canc Comm Coll Amer Pathologists TI Protocol for the examination of specimens from patients with non-Hodgkin's lymphoma - A basis for checklists SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID LARGE-CELL LYMPHOMA; EUROPEAN-AMERICAN CLASSIFICATION; PROGNOSTIC FACTORS; MALIGNANT-LYMPHOMAS; STAGE-I; LACTIC-DEHYDROGENASE; RADIATION-THERAPY; MACOP-B; SURVIVAL; INTERMEDIATE C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Forsyth Mem Hosp, Dept Pathol, Winston Salem, NC USA. RP Compton, CC (reprint author), Care Of Schramm J, Coll Amer Pathologists, 325 Waukegan Rd, Northfield, IL 60093 USA. NR 36 TC 6 Z9 6 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 1999 VL 123 IS 1 BP 68 EP 74 PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 157QM UT WOS:000078073200013 PM 9923840 ER PT J AU Compton, CC Ferry, JA Ross, DW AF Compton, CC Ferry, JA Ross, DW CA Canc Comm Coll Amer Pathologists TI Protocol for the examination of specimens from patients with Hodgkin's disease - A basis for checklists SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID PROGNOSTIC FACTORS; RADIATION-THERAPY; TUMOR BURDEN; STAGE-III; CHEMOTHERAPY; RADIOTHERAPY; SURVIVAL C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Forsyth Mem Hosp, Dept Pathol, Winston Salem, NC USA. RP Compton, CC (reprint author), Care Of Schramm J, Coll Amer Pathologists, 325 Waukegan Rd, Northfield, IL 60093 USA. NR 27 TC 2 Z9 2 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD JAN PY 1999 VL 123 IS 1 BP 75 EP 80 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 157QM UT WOS:000078073200014 PM 9923841 ER PT J AU Perrin, JM Kuhlthau, K McLaughlin, TJ Ettner, SL Gortmaker, SL AF Perrin, JM Kuhlthau, K McLaughlin, TJ Ettner, SL Gortmaker, SL TI Changing patterns of conditions among children receiving supplemental security income disability benefits SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article AB Objective: To determine the relative growth of types of chronic health conditions among children and adolescents receiving Supplemental Security Income (SSI) benefits before and after major SSI program changes, in: eluding changes in definitions of childhood disability and outreach to identify eligible children. Design: Retrospective analysis of Medicaid claims from California, Georgia, Michigan, and Tennessee. Participants: All children (aged less than or equal to 21 years) newly enrolled in SSI programs in these states from July 1989 (n=21 222) to June 1992 (n=38 789). Methods: Medicaid data indicate eligibility status and diagnoses for services rendered. For children newly enrolled before (time 1, July 1989 to June 1990), during (time 2, July 1990 to June 1991), and after (time 3, July 1991 to June 1992) the program changes, we used claims for the first 6 months of enrollment to determine rates of chronic conditions in general and rates of asthma, attention-deficit/hyperactivity disorder (ADHD), and mental retardation specifically. We also followed up time I enrollees during the study period to determine the likelihood of a chronic condition claim at any time. Main Outcome Measure: Presence of claims for chronic conditions. Results: New SSI enrollees almost doubled during the study period. Increasing numbers of new enrollees had chronic condition claims in their first 6 months (from 29% to 36%); 58% of time 1 enrollees had such claims during any study month. Rates of chronic physical conditions other than asthma increased 14% (time 1 to time 3); asthma rates increased 73%. Rates of mental health conditions other than mental retardation and ADHD increased 63%; rates of mental retardation decreased 29%, while rates of ADHD increased almost 3-fold. Conclusions: The number of children with chronic conditions receiving SSI benefits experienced rapid growth from 1989 to 1992. Growth was particularly marked for children with diagnoses of asthma and ADHD. C1 Massachusetts Gen Hosp, Div Gen Pediat, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Primary Care & Prevent, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. RP Perrin, JM (reprint author), Massachusetts Gen Hosp, Div Gen Pediat, Dept Pediat, Fruit St,WACC 715, Boston, MA 02114 USA. FU PHS HHS [MCJ-250634, 18-C-90455/1-01] NR 11 TC 37 Z9 37 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD JAN PY 1999 VL 153 IS 1 BP 80 EP 84 PG 5 WC Pediatrics SC Pediatrics GA 155ME UT WOS:000077950300013 PM 9895004 ER PT J AU Bridges, L Zhang, ZX AF Bridges, Louis, Jr. Zhang, Zhixin TI Expression of RAG1, RAG2, and TdT in Rheumatoid Arthritis Synovia: Evidence for Receptor Revision of Immunoglobulin Light Chains SO ARTHRITIS RESEARCH & THERAPY LA English DT Meeting Abstract C1 Univ Alabama Birmingham, Birmingham, AL USA. Birmingham VA Med Ctr, Birmingham, AL USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 EI 1478-6362 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 1999 VL 1 SU 1 PG 1 WC Rheumatology SC Rheumatology GA V31MD UT WOS:000208886800010 ER PT J AU Vallhonrat, H Swinford, RD Ingelfinger, JR Williams, WW Ryan, DP Tolkoff-Rubin, N Cosimi, AB Pascual, M AF Vallhonrat, H Swinford, RD Ingelfinger, JR Williams, WW Ryan, DP Tolkoff-Rubin, N Cosimi, AB Pascual, M TI Rapid activation of the alternative pathway of complement by extracorporeal membrane oxygenation SO ASAIO JOURNAL LA English DT Article ID RENAL-FAILURE; GENERATION AB Extracorporeal membrane oxygenation (ECMO) is an effective therapy for patients with severe respiratory distress syndromes. However, an inflammatory response has been observed with the use of this therapy. We measured complement activation in vivo in two adults receiving ECMO for acute respiratory distress syndrome (ARDS). Production of complement activation fragments C4d, Bb, iC3b, and SC5b-9 was determined using commercial ELISA kits. In both patients there was intense activation of complement that peaked 1 hour (mean SC5b-9 increase to 1135% of baseline) after the start of ECMO and occurred predominantly via the alternative pathway (Bb production). Early and acute complement activation may be responsible for the initiation of the inflammatory response that has been observed in patients treated with ECMO. C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Pascual, M (reprint author), Massachusetts Gen Hosp, Renal Unit, Box MZ70,Fruit St, Boston, MA 02114 USA. NR 10 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1058-2916 J9 ASAIO J JI Asaio J. PD JAN-FEB PY 1999 VL 45 IS 1 BP 113 EP 114 DI 10.1097/00002480-199901000-00025 PG 2 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 160KX UT WOS:000078230800026 PM 9952020 ER PT J AU Cooper, RA O'Connor, TJ Robertson, RN Langbein, WE Baldini, FD AF Cooper, RA O'Connor, TJ Robertson, RN Langbein, WE Baldini, FD TI An investigation of the exercise capacity of the Wheelchair Sports USA team SO ASSISTIVE TECHNOLOGY LA English DT Article DE wheelchair athlete; wheelchair sports; exercise physiology; fitness ID MAXIMAL OXYGEN-CONSUMPTION; ARM CRANKING EXERCISE; PHYSIOLOGICAL-RESPONSES; INCREMENTAL WHEELCHAIR; PROPULSION; PARAPLEGICS; ERGOMETRY; RACERS; POWER AB This investigation collected descriptive data on selected metabolic and cardiorespiratory parameters for Wheelchair Sports-USA (WS-USA) Elite and Developmental Team members to determine if differences in these parameters occurred between arm-crank ergometry (ACE) and wheelchair ergometry (WCE). Fifteen men with paraplegia, seven women with paraplegia, four men with tetraplegia, and three women with tetraplegia were tested. Multiple t-tests were used to determine if there were significant differences between responses to the two modes of exercise and also to compare athletes by disability etiology (tetraplegia versus paraplegia), gender, and training base (aerobic versus anaerobic). Both modes of exercise (ACE, WCE) elicited similar peak metabolic responses. Although some individuals responded differently to the two tests, none of the groupings showed significant differences (p > 0.05). Metabolic values show some dependence on gender and disability etiology. The results indicate that WS-USA team members in general are quite aerobically fit. Some athletes in anaerobic sports could benefit from aerobic exercise. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151R1, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA USA. UPMC Hlth Syst, Div Phys Med & Rehabil, Pittsburgh, PA USA. Calif State Univ Sacramento, Dept Hlth & Phys Educ, Sacramento, CA 95819 USA. Edward Hines Vet Affairs Hosp, Res Serv, Hines, IL USA. RP VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151R1, 7180 Highland Dr, Pittsburgh, PA 15206 USA. NR 27 TC 3 Z9 3 U1 0 U2 1 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 EI 1949-3614 J9 ASSIST TECHNOL JI Assist. Technol. PY 1999 VL 11 IS 1 BP 34 EP 42 PG 9 WC Rehabilitation SC Rehabilitation GA 312CZ UT WOS:000086926800004 ER PT S AU Boas, DA Gaudette, T Wang, L Ay, H Koroshetz, W Sorensen, G AF Boas, DA Gaudette, T Wang, L Ay, H Koroshetz, W Sorensen, G BE Pien, HH TI Preliminary investigation into the use of diffuse optical tomography for monitoring and imaging stroke SO BATTLEFIELD BIOMEDICAL TECHNOLOGIES SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Battlefield Biomedical Technologies CY APR 06, 1999 CL ORLANDO, FL SP Soc Photo Opt Instrumentat Engineers DE diffuse optical tomography; cerebral hemorrhage; ischemic stroke; indocyanine green ID NEAR-INFRARED SPECTROSCOPY; CEREBRAL BLOOD-FLOW; NEWBORN-INFANTS; INDOCYANINE GREEN; XE-133 CLEARANCE; HEMODYNAMICS; SCATTERING; MEDIA AB For patients with ischemic stroke there is benefit to early treatment (within 3 hours) with recombinant tissue plasminogen activator, rt-PA, an FDA approved thrombolytic drug. The use of rt-PA within the first 3 hours of an ischemic stroke is based upon a clinical trial showing an increased probability of good functional recovery in the treated group. The challenge is now to individualize therapy in order to decrease the degree of permanent brain injury due to ischemia in as many patients as possible. This requires new tools to assay brain blood flow and tissue injury. However, there is currently no means to non-invasively monitor brain perfusion. There is no non-invasive method to determine whether administration of thrombolytic drug in an individual patient is actually effective in causing reperfusion. We have developed such a method based on using light in conjunction with periodic bolus injections of an optical vascular contrast agent to continuously monitor brain perfusion noninvasively. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, Charlestown, MA 02139 USA. RP Boas, DA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, Charlestown, MA 02139 USA. NR 18 TC 1 Z9 1 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X J9 P SOC PHOTO-OPT INS PY 1999 VL 3712 BP 56 EP 61 DI 10.1117/12.353023 PG 6 WC Emergency Medicine; Engineering, Biomedical; Medical Laboratory Technology; Optics SC Emergency Medicine; Engineering; Medical Laboratory Technology; Optics GA BN53J UT WOS:000082158300007 ER PT J AU Medoff, D AF Medoff, D TI MMPI-2 validity scales in child custody evaluations: Clinical versus statistical significance SO BEHAVIORAL SCIENCES & THE LAW LA English DT Article AB The MMPI-2 is commonly used in the psychological assessment of parents within child custody evaluations. Due to the interface of mental health practitioners with non-mental-health professionals in the context of child custody cases, careful attention must be paid to the potential misunderstanding or misuse of data from psychological testing. While traditional clinical lore has maintained an expectation of clinically significant defensiveness on the MMPI-2 with this population, the research data does not support this view. Despite empirical findings that identify patterns of elevations on the MMPI-2 validity scales with parents involved in child custody disputes, these patterns have been demonstrated to reach statistical but not clinical significance. That is, MMPI-2 profiles that contain elevations on scales L or K that either invalidate or notably suppress clinical scales are not to be expected in the child custody population. False causal attributions contributing to the potential mischaracterization or loss of important data related to personality functioning within this population are identified and discussed. Potential dangers associated with such false causal attributions are reviewed. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 Massachusetts Gen Hosp, Children & Law Program, Boston, MA 02114 USA. RP Medoff, D (reprint author), Massachusetts Gen Hosp, Children & Law Program, 60 Staniford St, Boston, MA 02114 USA. NR 8 TC 7 Z9 7 U1 0 U2 5 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0735-3936 J9 BEHAV SCI LAW JI Behav. Sci. Law PY 1999 VL 17 IS 4 BP 409 EP 411 DI 10.1002/(SICI)1099-0798(199910/12)17:4<409::AID-BSL357>3.0.CO;2-N PG 3 WC Psychology, Applied; Law SC Psychology; Government & Law GA 276TT UT WOS:000084894000002 PM 10653990 ER PT J AU Wilhelm, S Otto, MW Lohr, B Deckersbach, T AF Wilhelm, S Otto, MW Lohr, B Deckersbach, T TI Cognitive behavior group therapy for body dysmorphic disorder: a case series SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article ID EXPOSURE AB The treatment of Body Dysmorphic Disorder (BDD) has received little empirical attention despite evidence that BDD is a debilitating mental health problem. This open case series provides data on a new cognitive-behavioral treatment for BDD. Participants diagnosed with BDD were treated in small groups that met for 12 weekly 90-minute sessions. Patients improved significantly over the course of treatment, with reductions in both BDD and depression symptoms. This finding adds to a nascent literature documenting the potential efficacy of short-term cognitive-behavior therapy for patients suffering from BDD. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Wilhelm, S (reprint author), Massachusetts Gen Hosp, Charlestown, MA 02129 USA. NR 12 TC 74 Z9 75 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD JAN PY 1999 VL 37 IS 1 BP 71 EP 75 DI 10.1016/S0005-7967(98)00109-0 PG 5 WC Psychology, Clinical SC Psychology GA 126AK UT WOS:000076270300007 PM 9922559 ER PT J AU Lewandrowski, KU Bondre, SP Gresser, JD Wise, DL Tomford, WW Trantolo, DJ AF Lewandrowski, KU Bondre, SP Gresser, JD Wise, DL Tomford, WW Trantolo, DJ TI Improved osteoconduction of cortical bone grafts by biodegradable foam coating SO BIO-MEDICAL MATERIALS AND ENGINEERING LA English DT Article DE bioresorbable coating; bone allograft; osteoconductivity ID DEMINERALIZED BONE; ALLOGRAFTS; OSTEOINDUCTION AB Alteration of the geometrical surface configuration of cortical bone allografts may improve incorporation into host bone. A porous biodegradable coating that would maintain immediate structural recovery and subsequently allow normal graft healing and remodeling by promoting bony ingrowth could provide an osteoconductive surface scaffold. We investigated the feasibility of augmenting cortical bone grafts with osteoconductive biodegradable polymeric scaffold coatings. Three types of bone grafts were prepared: Type I - cortical bone without coating (control), Type II - cortical bone coated with PLGA-foam, Type III - cortical bone coated with PPF-foam. The grafts were implanted into the rat tibial metaphysis (16 animals for each type of bone graft). Post-operatively the animals were sacrificed at 2 weeks and 4 weeks (8 animals for each type of bone graft at each time point). Histologic and histomorphometric analysis of grafts showed that the amount of new bone forming around the foam-coated grafts was significantly higher than in the control group (uncoated; p<0.02). Although both foam formulations were initially equally osteoconductive, PLGA-based foam coatings appeared to have degraded at two weeks postoperatively, whereas PPF-based foam coatings were still present at 4 weeks postoperatively. While significant resorption was present in control allografts with little accompanying reactive new bone formation, PLGA-coated bone grafts showed evidence of bone resorption and subsequent bony ingrowth earlier than those coated with PPF-based foams suggesting that PPF-coated cortical bone grafts were longer protected against host reactions resulting in bone resorption. C1 Cambridge Sci Inc, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. Northeastern Univ, Dept Chem Engn, Boston, MA 02115 USA. RP Trantolo, DJ (reprint author), Cambridge Sci Inc, 180 Fawcett St, Cambridge, MA 02138 USA. FU NIAMS NIH HHS [AR 45062, 2 R44 AR 44317] NR 29 TC 7 Z9 8 U1 2 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0959-2989 J9 BIO-MED MATER ENG JI Bio-Med. Mater. Eng. PY 1999 VL 9 IS 5-6 BP 265 EP 275 PG 11 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 305UT UT WOS:000086559500001 PM 10822482 ER PT J AU Lewandrowski, KU Bondre, S Gresser, JD Silva, AE Wise, DL Trantolo, DJ AF Lewandrowski, KU Bondre, S Gresser, JD Silva, AE Wise, DL Trantolo, DJ TI Augmentation of osteoinduction with a biodegradable poly(propylene glycol-co-fumaric acid) bone graft extender - A histologic and histomorphometric study in rats SO BIO-MEDICAL MATERIALS AND ENGINEERING LA English DT Article DE bioresorbable; bone graft extender; osteoconduction; osteoinduction ID IN-VITRO DEGRADATION; TISSUE; CEMENT; TRANSPLANTATION; REGENERATION; SCAFFOLD AB We investigated the feasibility of enhancing the regeneration of skeletal tissues by augmenting bone grafts with a composite biodegradable bone graft extender material based on the polymer poly(propylene fumarate), PPF. The material was mixed with autograft and allograft and placed directly into a cylindrical metaphyseal defect made in the rat tibia. These formulations were compared to defects without any graft material, autografts, allografts and PPF alone. Nine animals were included in each group. Animals were sacrificed at 1 and 4 weeks postoperatively. Implantation sites were then evaluated using histologic and histomorphometric methods. Results of this study showed that defects did not heal in sham operated animals. In the experimental groups, there was early new woven bone formation in the autograft group with near complete healing of the defect at four weeks. When PPF was used alone, gradual ingrowth of new bone was seen. Mixing of the PPF bone graft extender with either allograft or autograft material resulted in enhancement of new bone formation with both allo- and autograft. However, significantly more new bone formation than in the autograft group was only seen when the PPF bone graft extender was mixed with fresh autograft. Histomorphometry corroborated these findings. Results of this study suggest that a PPF-based material may be used to increase the volume of smaller amounts of bone grafts supporting the concept of "bone graft extenders" by application of engineered biodegradable porous scaffolds. C1 Cambridge Sci Inc, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. Northeastern Univ, Dept Chem Engn, Boston, MA 02115 USA. RP Trantolo, DJ (reprint author), Cambridge Sci Inc, 180 Fawcett St, Cambridge, MA 02138 USA. FU NIAMS NIH HHS [5 R44 AR44317-03, AR 45062] NR 24 TC 4 Z9 5 U1 0 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0959-2989 J9 BIO-MED MATER ENG JI Bio-Med. Mater. Eng. PY 1999 VL 9 IS 5-6 BP 325 EP 334 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 305UT UT WOS:000086559500007 PM 10822488 ER PT S AU Wu, H Avgoustiniatos, ES Swette, L Bonner-Weir, S Weir, GC Colton, CK AF Wu, H Avgoustiniatos, ES Swette, L Bonner-Weir, S Weir, GC Colton, CK BE Hunkeler, D Prokop, A Cherrington, AD Rajotte, RV Sefton, M TI In situ electrochemical oxygen generation with an immunoisolation device SO BIOARTIFICIAL ORGANS II: TECHNOLOGY, MEDICINE, AND MATERIALS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Bioartificial Organs II - Technology, Medicine and Materials CY JUL 18-22, 1998 CL BANFF, CANADA SP Engn Fdn, Baxter Hlthcare Corp, Juvenile Diabetes Fdn, Natl Inst Hlth, Natl Sci Fdn, NY Acad Sci, Roche/Boehringer Mannheim, Whitaker Fdn ID MEMBRANE MICROARCHITECTURE; DIABETIC MICE; ISLETS; XENOGRAFTS; CELLS; IMMUNOSUPPRESSION; TRANSPLANTATION; NEOVASCULARIZATION; DESTRUCTION; VIABILITY AB The viability and function of transplanted tissue encapsulated in immunobarrier devices is subject to oxygen transport limitation, In this study, we have designed and used an in situ electrochemical oxygen generator which decomposes water electrolyticaly to provide oxygen to the adjacent planer immunobarrier diffusion chamber, The rate of oxygen generation, which increases linearly with electrical current, was accurately controlled, A theoretical model of oxygen diffusion was also developed and was used to calculate the oxygen profiles in some of the experimental systems, bt vitro culture experiments were carried out with beta TC3 cells encapsulated in titanium ring devices, The growth and viability of cells with or without in situ oxygen generation was studied, We found that under otherwise similar culturing conditions, the thickness of the cell layer and the viability of cells was the highest in devices cultured in stirred media with oxygen generation, even though the thickness had not reached the theoretically predicted value, and lowest in those unstirred and without oxygen generation. C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Giner Inc, Waltham, MA 02451 USA. Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. RP Colton, CK (reprint author), MIT, Dept Chem Engn, Room 66-452,77 Massachusets Ave, Cambridge, MA 02139 USA. FU NIDDK NIH HHS [1R43DK51909-01, DK-50657, DK-35449] NR 42 TC 28 Z9 29 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-194-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 875 BP 105 EP 125 DI 10.1111/j.1749-6632.1999.tb08497.x PG 21 WC Engineering, Biomedical; Materials Science, Biomaterials; Multidisciplinary Sciences; Transplantation SC Engineering; Materials Science; Science & Technology - Other Topics; Transplantation GA BN31W UT WOS:000081586000009 PM 10415561 ER PT S AU Hayashi, T Dufresne, SD Aronson, D Sherwood, DJ Hirshman, MF Boppart, MD Fielding, RA Goodyear, LJ AF Hayashi, T Dufresne, SD Aronson, D Sherwood, DJ Hirshman, MF Boppart, MD Fielding, RA Goodyear, LJ BE Hargreaves, M Thompson, M TI Intracellular signaling pathways in contracting skeletal muscle SO BIOCHEMISTRY OF EXERCISE X SE INTERNATIONAL SERIES ON SPORT SCIENCES LA English DT Proceedings Paper CT 10th International Conference on the Biochemistry of Exercise - Membranes, Muscle and Exercise CY JUL 15-19, 1997 CL SYDNEY, AUSTRALIA ID ACTIVATED PROTEIN-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; MICROTUBULE-ASSOCIATED PROTEIN-2; MAP KINASE; C-JUN; TRANSDUCTION PATHWAYS; S6 KINASE; PHOSPHORYLATION SITES; INSULIN STIMULATION; CARDIAC MYOCYTES C1 Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. RP Hayashi, T (reprint author), Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Div Res, 75 Francis St, Boston, MA 02115 USA. NR 74 TC 0 Z9 0 U1 0 U2 0 PU HUMAN KINETICS PUBL PI CHAMPAIGN PA BOX 5076, CHAMPAIGN, IL 61825-5076 USA SN 0160-0559 BN 0-88011-758-3 J9 INT S SPORT PY 1999 BP 19 EP 34 PG 16 WC Biochemistry & Molecular Biology; Sport Sciences SC Biochemistry & Molecular Biology; Sport Sciences GA BM56Y UT WOS:000079120200003 ER PT J AU Torchilin, VP AF Torchilin, VP TI Biotin-conjugated polychelating agent SO BIOCONJUGATE CHEMISTRY LA English DT Article ID CHELATING POLYMERS; POLYCLONAL IMMUNOGLOBULIN; FOCAL INFLAMMATION; AVIDIN; ANTIBODY; STREPTAVIDIN; LOCALIZATION; INFARCTION; SYSTEM AB A procedure is described for preparing a polychelating agent-biotin conjugate through the interaction of biotin-maleimide with poly-L-lysine modified with multiple residues of diethylenetriaminepentaacetic acid and containing amino-terminal pyridylthio-propionate group. The conjugate can be easily loaded with multiple metal atoms, such as In-111, and preserves its ability to specifically interact with avidin (as avidin-agarose). Polychelate-biotin conjugate may be used for signal amplification in visualization and analytical protocols involving the application of the avidin-biotin system. C1 Massachusetts Gen Hosp, Ctr Imaging & Pharmaceut Res, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Torchilin, VP (reprint author), Northeastern Univ, Dept Pharmaceut Sci, Mugar Bldg 312,360 Huntington Ave, Boston, MA 02115 USA. NR 18 TC 13 Z9 13 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JAN-FEB PY 1999 VL 10 IS 1 BP 146 EP 149 DI 10.1021/bc9800567 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 171QK UT WOS:000078874800021 PM 9893977 ER PT J AU Ubel, PA Baron, J Asch, DA AF Ubel, PA Baron, J Asch, DA TI Social responsibility, personal responsibility, and prognosis in public judgments about transplant allocation SO BIOETHICS LA English DT Article ID RETRANSPLANTATION; ACCESS; LIVERS AB Background Some members of the general public feel that patients who cause their own organ failure through smoking; alcohol use, or drug use should not receive equal priority for scarce transplantable organs. This may reflect a belief that these patients (1) cause their own illness, (2) have poor transplant prognoses or, (3) are simply unworthy. We explore the role that social acceptability, personal responsibility, and prognosis play in people's judgments about transplant allocation. Methods By random allocation, we presented 283 prospective jurors in Philadelphia county with one of five questionnaire versions. In all questionnaires, subjects were asked to distribute transplantable hearts between patients with and without a history of three controversial behaviors (eating high fat diets against doctors' advice, cigarette smoking; or intravenous drug use). Across the Jive questionnaire versions, we varied the relative prognosis of the transplant candidates and whether their behavior caused their primary organ failure. Results Subjects were significantly less willing to distribute organs to intravenous drug users than to cigarette smokers or people eating high fat diets (p < 0.0005), even when intravenous drug users had better transplant outcomes than other patients. Subjects' allocation decisions were influenced by transplant prognosis, but not by whether the behavior in question was causally responsible for the patients' organ failure. Conclusion People's unwillingness to give scarce transplantable organs to patients with controversial behaviors cannot be explained totally on the basis of those behaviors either causing their primary organ failure or making them have worse transplant prognoses. Instead many people believe that such patients are simply less worthy of scarce transplantable organs. C1 Vet Affairs Med Ctr, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Ubel, PA (reprint author), Vet Affairs Med Ctr, Dept Med, Philadelphia, PA 19104 USA. NR 11 TC 28 Z9 28 U1 0 U2 5 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0269-9702 J9 BIOETHICS JI Bioethics PD JAN PY 1999 VL 13 IS 1 BP 57 EP 68 DI 10.1111/1467-8519.00131 PG 12 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 164ZU UT WOS:000078494100004 PM 11657059 ER PT J AU Beal, MF AF Beal, MF TI Coenzyme Q(10) administration and its potential for treatment of neurodegenerative diseases SO BIOFACTORS LA English DT Article ID SUPEROXIDE-DISMUTASE MUTATION; AMYOTROPHIC-LATERAL-SCLEROSIS; HUNTINGTONS-DISEASE; MITOCHONDRIAL ENCEPHALOMYOPATHY; H-1-NMR SPECTROSCOPY; INDUCED DEGENERATION; LIPID-PEROXIDATION; IN-VIVO; RAT; UBIQUINONE AB Coenzyme Q(10) (CoQ(10)) is an essential cofactor of the electron transport chain as well as an important antioxidant. Previous studies have suggested that it may exert therapeutic effects in patients with known mitochondrial disorders. We investigated whether it can exert neuroprotective effects in a variety of animal models. We have demonstrated that CoQ(10) can protect against striatal lesions produced by both malonate and 3-nitropropionic acid. It also protects against MPTP toxicity in mice. It extended survival in a transgenic mouse model of amyotrophic lateral sclerosis. We demonstrated that oral administration can increase plasma levels in patients with Parkinson's disease. Oral administration of CoQ(10) significantly decreased elevated lactate levels in patients with Huntington's disease. These studies therefore raise the prospect that administration of CoQ(10) may be useful for the treatment of neurodegenerative diseases. C1 Massachusetts Gen Hosp, Serv Neurol, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Beal, MF (reprint author), Massachusetts Gen Hosp, Serv Neurol, Neurochem Lab, Warren 408,32 Fruit St, Boston, MA 02114 USA. FU NIA NIH HHS [P01 AG12992]; NINDS NIH HHS [NS16367, NS31579] NR 39 TC 72 Z9 74 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA VAN DIEMENSTRAAT 94, 1013 CN AMSTERDAM, NETHERLANDS SN 0951-6433 J9 BIOFACTORS JI Biofactors PY 1999 VL 9 IS 2-4 BP 261 EP 266 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 284KW UT WOS:000085332400022 PM 10416039 ER PT J AU Shults, CW Haas, RH Beal, MF AF Shults, CW Haas, RH Beal, MF TI A possible role of coenzyme Q(10) in the etiology and treatment of Parkinson's disease SO BIOFACTORS LA English DT Article ID PLATELET MITOCHONDRIAL-FUNCTION; COMPLEX-I; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; UBIQUINOL-10; LEVODOPA; II/III; CHAIN AB Parkinson's disease (PD) is a degenerative neurological disorder. Recent studies have demonstrated reduced activity of complex I of the electron transport chain in brain and platelets from patients with PD. Platelet mitochondria from parkinsonian patients were found to have lower levels of coenzyme Q(10) (CoQ(10)) than mitochondria from age/sex-matched controls. There was a strong correlation between the levels of CoQ(10) and the activities of complexes I and II/III. Oral CoQ(10) was found to protect the nigrostriatal dopaminergic system in one-year-old mice treated with MPTP, a toxin injurious to the nigrostriatal dopaminergic system. We further found that oral CoQ(10) was well absorbed in parkinsonian patients and caused a trend toward increased complex I activity. These data suggest that CoQ(10) may play a role in cellular dysfunction found in PD and may be a potential protective agent for parkinsonian patients. C1 VA Med Ctr, Neurol Serv 9127, VA Hlth Care Syst, San Diego, CA 92161 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Cornell New York Hosp, New York, NY USA. RP Shults, CW (reprint author), VA Med Ctr, Neurol Serv 9127, VA Hlth Care Syst, 3350 La Jolla Village Dr, San Diego, CA 92161 USA. FU NIA NIH HHS [P01 AG12992]; NINDS NIH HHS [NS32365, NS31579] NR 26 TC 51 Z9 53 U1 0 U2 2 PU IOS PRESS PI AMSTERDAM PA VAN DIEMENSTRAAT 94, 1013 CN AMSTERDAM, NETHERLANDS SN 0951-6433 J9 BIOFACTORS JI Biofactors PY 1999 VL 9 IS 2-4 BP 267 EP 272 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 284KW UT WOS:000085332400023 PM 10416040 ER PT J AU Loberg, EM Hugdahl, K Green, MF AF Loberg, EM Hugdahl, K Green, MF TI Hemispheric asymmetry in schizophrenia: A "dual deficits" model SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; laterality; dichotic listening; attention; dual deficit processing ID ACUTE PSYCHOTIC ILLNESS; AUDITORY HALLUCINATIONS; CEREBRAL LATERALITY; ATTENTION AB Background: The aim was 1) to investigate left hemisphere functional integrity for auditory language processing in schizophrenic patients; and 2) to investigate the interaction between brain laterality and attentional processing by having subjects shift attention to the left or right ear. Methods: The subjects were 33 schizophrenic inpatients, and 33 healthy comparison subjects with the same age, handedness, and gender distribution as the patient subjects. All subjects were rested with dichotic listening (DL) to consonant-vowel syllables, which is a measure of lateralized temporal lobe language processing. The subjects were rested under three different attentional conditions: a non-forced attention condition, attention focused to the right ear stimulus, and attention focused to the left ear stimulus. Results: The main findings were 1) an absence of the expected right ear advantage in the schizophrenic group during the non-forced attention condition; and 2) a failure to modify DL performance through shifting of attention to either the right or left ear. The comparison group showed a right ear advantage during the non-forced and forced-right attention conditions (increased right ear advantage during the forced-right condition), and a left ear advantage during the forced-left attention condition. There were no significant effects of handedness. Conclusions: This pattern of results may indicate a "dual deficit" involving both automatic and controlled processing deficits in schizophrenia. Biol Psychiatry 1999;45: 76-81 (C) 1999 Society of Biological Psychiatry. C1 Univ Bergen, Dept Biol & Med Psychol, N-5009 Bergen, Norway. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Hugdahl, K (reprint author), Univ Bergen, Dept Biol & Med Psychol, Arstadveien 21, N-5009 Bergen, Norway. NR 26 TC 70 Z9 74 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 1 PY 1999 VL 45 IS 1 BP 76 EP 81 DI 10.1016/S0006-3223(98)00219-4 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 155VW UT WOS:000077967900009 PM 9894578 ER PT J AU Wang, EY Draper, LB Lee, E Polak, A Sluss, P Weiss, J Woodruff, TK AF Wang, EY Draper, LB Lee, E Polak, A Sluss, P Weiss, J Woodruff, TK TI Identification of naturally occurring follistatin complexes in human biological fluids SO BIOLOGY OF REPRODUCTION LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; RAT ESTROUS-CYCLE; ACTIVIN-A; INHIBIN-A; GENE-EXPRESSION; TISSUES; LOCALIZATION; PREGNANCY; FEMALE; CELLS AB Follistatin (FS) binds activin and inhibin proteins. Many organs are sensitive to activin and inhibin; thus the formation of FS-activin/inhibin complexes is important to our understanding of ligand activity Other investigators studying FS have detected large molecular weight immunoreactive FS bands (greater than the expected molecular weight of FS alone) that have not been well characterized. The goal of this study was to identify naturally occurring FS monomers and FS-activin/inhibin complexes in several organ systems. The pituitary, ovary, kidney, and urine were chosen for this investigation. Molecular masses were assigned to in vitro assemblies of complexes containing recombinant inhibin or activin with FS for comparison with naturally occurring FS forms. The recombinant complex of FS-activin was primarily 97-kDa size, while FS-inhibin complexes were detected in a range of molecular sizes from 66 kDa to 97 kDa, 133 kDa, and > 220 kDa. FS-containing complexes of 66-kDa, 97-kDa, and 133-kDa were identified in the tissues examined and in pregnant urine. Our study points to the assembly of a series of FS-activin/inhibin complexes in a variety of organ systems that may impact upon the available amount of free versus bound (or "complexed") ligand, which must be considered when investigating the biology of activin- or inhibin-responsive cells. In addition, urine may be an important biological fluid that can be used to measure significant changes in circulating FS complexes. C1 Northwestern Univ, Dept Neurobiol & Physiol, Evanston, IL 60208 USA. Northwestern Univ, Sch Med, Dept Obstet & Gynecol, Chicago, IL 60611 USA. Northwestern Univ, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Woodruff, TK (reprint author), Northwestern Univ, Dept Neurobiol & Physiol, OT Hogan 4-150,2153 Sheridan Rd, Evanston, IL 60208 USA. FU NICHD NIH HHS [P30-HD-28048, U54-HD-29164] NR 26 TC 9 Z9 10 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 JAN PY 1999 VL 60 IS 1 BP 8 EP 13 DI 10.1095/biolreprod60.1.8 PG 6 WC Reproductive Biology SC Reproductive Biology GA 153AH UT WOS:000077810200002 PM 9858480 ER PT J AU Sidis, Y Schneyer, L Johnson, LN Wang, QF Sluss, PM Keutmann, HT AF Sidis, Y Schneyer, L Johnson, LN Wang, QF Sluss, PM Keutmann, HT TI Structure-function analysis of follistatin: Role of methionine residues. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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. PY 1999 VL 60 SU 1 MA 72 BP 116 EP 116 PG 1 WC Reproductive Biology SC Reproductive Biology GA 211CA UT WOS:000081141300141 ER PT J AU Sadatsuki, M Sidis, Y Schneyer, AL AF Sadatsuki, M Sidis, Y Schneyer, AL TI Activin promotes nuclear maturation in denuded mouse oocytes. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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. PY 1999 VL 60 SU 1 MA 298 BP 186 EP 186 PG 1 WC Reproductive Biology SC Reproductive Biology GA 211CA UT WOS:000081141300364 ER PT S AU Garrido, L AF Garrido, L BE Neenan, T Marcolongo, M Valentini, RF TI Non-destructive evaluation of synthetic tissue scaffolds with NMR SO BIOMEDICAL MATERIALS-DRUG DELIVERY, IMPLANTS AND TISSUE ENGINEERING SE MATERIALS RESEARCH SOCIETY SYMPOSIUM PROCEEDINGS LA English DT Proceedings Paper CT Symposium on Biomedical Materials-Drug Delivery, Implants and Tissue Engineering CY NOV 30-DEC 01, 1998 CL BOSTON, MA SP Mat Res Soc AB Proton magnetic resonance imaging (MRI) is applied to determine non-destructively the open porosity of biodegradable scaffolds of poly(3-hydroxybutyrate-3-hydroxyvalerate) in vitro and tissue infiltration in vivo. Porous matrices with copolymers having 12% and 24% 3-hydroxyvalerate (HV) are prepared using a solvent casting technique. The results of open porosity P (%) measured by MRI (P-MRI) show good agreement with those obtained by gravimetry analysis (P-GA) Thus, for scaffolds with 12% HV, P-MRI = 91.0 +/-1.0 (mean +/- s.d.) and P-GA = 88.0 +/- 0.75; and for those with 24% HV, P-MRI = 89.4 +/- 1.3 and PGA = 88.8 +/- 1.0. Also, the extent of tissue infiltration in these scaffolds determined by MRI in vivo was similar to that observed by histology. These results illustrate the potential of MRI methods for investigating the behavior of biodegradable scaffolds non-invasively in applications for tissue engineering. C1 Massachusetts Gen Hosp, Dept Radiol, NMR Ctr, Biomat Lab, Charlestown, MA 02129 USA. RP Garrido, L (reprint author), Massachusetts Gen Hosp, Dept Radiol, NMR Ctr, Biomat Lab, 149 13th St, Charlestown, MA 02129 USA. RI Garrido, Leoncio/K-3092-2014 OI Garrido, Leoncio/0000-0002-7587-1260 NR 9 TC 2 Z9 2 U1 0 U2 2 PU MATERIALS RESEARCH SOCIETY PI WARRENDALE PA 506 KEYSTONE DRIVE, WARRENDALE, PA 15088-7563 USA SN 0272-9172 BN 1-55899-456-4 J9 MATER RES SOC SYMP P PY 1999 VL 550 BP 171 EP 176 PG 6 WC Biotechnology & Applied Microbiology; Materials Science, Multidisciplinary; Materials Science, Biomaterials; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Materials Science; Pharmacology & Pharmacy GA BN11N UT WOS:000080751700026 ER PT J AU O'Quigley, J Xu, RH Blin, P Charpak, Y AF O'Quigley, J Xu, RH Blin, P Charpak, Y TI Interphase clinical trials: Phase III/Phase IV SO BIOMETRICAL JOURNAL LA English DT Article DE clinical trial; extrapolation; Phase III studies; Phase IV studies; prediction; proportional hazard regression; regression errors; survival analysis ID LIVER-TRANSPLANT PATIENTS; EXPECTED SURVIVAL AB In this paper we investigate ways in which the results of a controlled Phase III clinical trial can be used in subsequent Phase IV, and possibly further Phase III studies. Specifically we are interested in; 1) developing particular hypothesis relating to a modified study population, 2) studying how changes in the particularities of the Phase III study group can influence certain outcome variables of interest and 3) using the results of the Phase III study applied to specific target groups, having particular characteristics, to updating observations from the Phase III study with information obtained at a later stage. These issues are all concerned with the way in which we can exploit information from a Phase III trial, information that is of high quality but not necessarily directly related to the way in which many post Phase III studies, focussing on different patient population groups, are carried out. Since it is often these post Phase III studies that have the strongest influence on clinical practice we aim to develop a framework around which the post Phase III studies might be structured. C1 Univ Calif San Diego, Dept Math, La Jolla, CA 92093 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA USA. EVAL, Paris, France. RI O'Quigley, John/E-2073-2017 NR 17 TC 0 Z9 0 U1 0 U2 1 PU AKADEMIE VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 1999 VL 41 IS 7 BP 773 EP 782 PG 10 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 258VP UT WOS:000083860200001 ER PT J AU Addona, GH Husain, SS Miller, KW AF Addona, GH Husain, SS Miller, KW TI Identification of the contact residue between adenylate kinase and the general anesthetic 3,3-azioctan-1-ol by mass spectrometry SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Biol Chem, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Pharmacol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 1999 VL 76 IS 1 BP A103 EP A103 PN 2 PG 1 WC Biophysics SC Biophysics GA 210BU UT WOS:000081085900599 ER PT J AU Arystarkhova, E Sweadner, KJ AF Arystarkhova, E Sweadner, KJ TI Modulation or Na,K-ATPase Na+ affinity by expression of the Gamma subunit SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA USA. Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 1999 VL 76 IS 1 BP A452 EP A452 PN 2 PG 1 WC Biophysics SC Biophysics GA 210BU UT WOS:000081085902644 ER PT J AU Bersohn, MM Carmack, CR Shalaby, AE Philipson, KD AF Bersohn, MM Carmack, CR Shalaby, AE Philipson, KD TI Ischemic tolerance of hearts from transgenic mice over-expressing the sodium-calcium exchanger SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 1999 VL 76 IS 1 BP A253 EP A253 PN 2 PG 1 WC Biophysics SC Biophysics GA 210BU UT WOS:000081085901480 ER PT J AU Cogwell, LP Mok, WM Parekh, S Maggio, JE Raines, DE Strichartz, GR AF Cogwell, LP Mok, WM Parekh, S Maggio, JE Raines, DE Strichartz, GR TI Development of a novel probe of drug-protein interactions SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Anesthesia Res Labs, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Cincinnati, Coll Med, Dept Pharmacol & Cell Biophys, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 1999 VL 76 IS 1 BP A111 EP A111 PN 2 PG 1 WC Biophysics SC Biophysics GA 210BU UT WOS:000081085900649 ER PT J AU Donnet, C Cantiello, HF AF Donnet, C Cantiello, HF TI Changes in actin filament organization control Na+ pump ion currents. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp East, Charlestown, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 1999 VL 76 IS 1 BP A452 EP A452 PN 2 PG 1 WC Biophysics SC Biophysics GA 210BU UT WOS:000081085902646 ER PT J AU Feschenko, MS Sweadner, KJ AF Feschenko, MS Sweadner, KJ TI Evidence for a cAMP activated phosphatase in modulation of Na,K-ATPase phosphorylation by PKC. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Neurosci, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 1999 VL 76 IS 1 BP A452 EP A452 PN 2 PG 1 WC Biophysics SC Biophysics GA 210BU UT WOS:000081085902643 ER PT J AU Luo, Y Li, B Gergely, L Tao, T AF Luo, Y Li, B Gergely, L Tao, T TI Interactions of troponin-I met121 with the N-terminal hydrophobic pocket of troponin-C. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Boston Biomed Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 1999 VL 76 IS 1 BP A158 EP A158 PN 2 PG 1 WC Biophysics SC Biophysics GA 210BU UT WOS:000081085900922 ER PT J AU Raines, DE Zachariah, VT AF Raines, DE Zachariah, VT TI The fluorescent agonist Dns-C6-Cho binds with micromolar affinity to the alpha-delta binding site of the nicotinic acetylcholine receptor resting state SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 1999 VL 76 IS 1 BP A373 EP A373 PN 2 PG 1 WC Biophysics SC Biophysics GA 210BU UT WOS:000081085902178 ER PT J AU Takahashi, MP Cannon, SC AF Takahashi, MP Cannon, SC TI Slow inactivation is enhanced by V445M: A sodium channel mutation associated with myotonia SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 1999 VL 76 IS 1 BP A195 EP A195 PN 2 PG 1 WC Biophysics SC Biophysics GA 210BU UT WOS:000081085901143 ER PT J AU Liska, V Ruprecht, RM AF Liska, V Ruprecht, RM TI Isolation of high-molecular-weight genomic DNA from intact biohazardous mammalian tissues SO BIOTECHNIQUES LA English DT Article C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Smith Bldg,Room 836,44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [R01-AI35533, R01-AI32330] NR 6 TC 5 Z9 5 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JAN PY 1999 VL 26 IS 1 BP 62 EP + PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 156JH UT WOS:000077997500009 PM 9894593 ER PT J AU Andreadis, ST Roth, CM Le Doux, JM Morgan, JR Yarmush, ML AF Andreadis, ST Roth, CM Le Doux, JM Morgan, JR Yarmush, ML TI Large-scale processing of recombinant retroviruses for gene therapy SO BIOTECHNOLOGY PROGRESS LA English DT Review ID MURINE LEUKEMIA-VIRUS; PACKAGING CELL-LINE; HIGH-TITER; LENTIVIRAL VECTOR; EXPRESSION SYSTEM; NONDIVIDING CELLS; MAMMALIAN-CELLS; HALF-LIFE; TRANSDUCTION; PROTEIN AB Gene therapy is a new therapeutic modality with the potential of treating inherited and acquired diseases. Several viral and physicochemical vehicles have been used for the transfer of genes to mammalian cells, but recombinant retroviruses are used in the majority of gene therapy clinical trials today. In this communication, we review the major concerns associated with the large-scale production and processing of retroviral particles. While some of the current processes for manufacturing recombinant proteins will be applicable to recombinant retroviruses, the instability, sensitivity to inhibitors, complexity, and size of retroviral particles require that new technologies be designed and evaluated. Here, we examine those issues critical to the design of strategies for production, concentration, and purification as well as formulation and storage of recombinant retroviruses. Processes for large-scale manufacturing of recombinant retroviruses that can produce high gene transfer efficiencies will have significant impact on the clinical implementation of gene therapy. C1 Harvard Univ, Ctr Engn Med, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Surg Serv, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Shriners Burns Hosp, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Harvard Univ, Ctr Engn Med, Sch Med, Massachusetts Gen Hosp, 55 Fruit St,GRB 1401, Boston, MA 02114 USA. OI Morgan, Jeffrey/0000-0002-7546-3443; Roth, Charles/0000-0002-4924-0721 NR 80 TC 59 Z9 61 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD JAN-FEB PY 1999 VL 15 IS 1 BP 1 EP 11 DI 10.1021/bp980106m PG 11 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 166DJ UT WOS:000078560700001 PM 9933508 ER PT J AU Koenig, F McGovern, FJ Larne, R Enquist, H Schomacker, KT Deutsch, TF AF Koenig, F McGovern, FJ Larne, R Enquist, H Schomacker, KT Deutsch, TF TI Diagnosis of bladder carcinoma using protoporphyrin IX fluorescence induced by 5-aminolaevulinic acid SO BJU INTERNATIONAL LA English DT Article DE 5-aminolaevulinic acid; protoporphyrin IX; fluorescence; diagnosis; bladder neoplasm ID TRANSITIONAL-CELL-CARCINOMA; 5-AMINOLEVULINIC ACID; PHOTODYNAMIC THERAPY; URINARY-BLADDER; CANCER; PERMEABILITY; EXPRESSION AB Objective To report the results of a clinical study investigating the diagnosis of malignant and dysplastic bladder lesions by protoporphyrin IX (PPIX) fluorescence and to compare them with those from earlier studies. Patients and methods The study included 55 patients with suspected bladder carcinoma (at initial diagnosis or at tumour follow-up visits); 130 bladder biopsies from 49 patients were classified by pathological analysis. All patients received an intravesical instillation of 50 mL, of a 3% 5-aminolaevulinic acid (ALA) solution a mean of 135 min before cystoscopy, which was then performed under white and blue light. Malignant/ dysplastic lesions showing red fluorescence under blue-light excitation were noted and the increase in detection rate calculated. Results There were 63 benign and 67 malignant/dysplastic areas biopsied; 10 malignant/dysplastic lesions (four transitional cell carcinoma, two carcinoma in situ, four dysplastia) were not detected during routine white-light cystoscopy but were identified under blue light. Fluorescence cystoscopy improved the overall diagnosis of malignant/dysplastic bladder lesions by 18% over standard white-light cystoscopy. The improvement was greater for dysplastic lesions and carcinoma in situ (50%). However, the improvement over standard cystoscopy was less than that found by other groups, Conclusion The ALA-based fluorescence detection system significantly enhanced the diagnosis of malignant/dysplastic bladder lesions. However, determining the optimum drug exposure time requires further investigation using well-characterized instrumentation and study protocols, which would then allow comparison of the results from different groups. C1 Humboldt Univ, Dept Urol, Clin Charite, Berlin, Germany. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Wellman Labs Photomed, Boston, MA USA. RP Koenig, F (reprint author), Humboldt Univ, Dept Urol, Charite Med Sch, Schumannstr 20-21, D-10117 Berlin, Germany. NR 24 TC 83 Z9 87 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD JAN PY 1999 VL 83 IS 1 BP 129 EP 135 DI 10.1046/j.1464-410X.1999.00917.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 187EY UT WOS:000079775000022 PM 10233465 ER PT J AU Dalmau, J Gultekin, SH Voltz, R Hoard, R DesChamps, T Balmaceda, C Batchelor, T Gerstner, E Eichen, J Frennier, J Posner, JB Rosenfeld, MR AF Dalmau, J Gultekin, SH Voltz, R Hoard, R DesChamps, T Balmaceda, C Batchelor, T Gerstner, E Eichen, J Frennier, J Posner, JB Rosenfeld, MR TI Ma1, a novel neuron- and testis-specific protein, is recognized by the serum of patients with paraneoplastic neurological disorders SO BRAIN LA English DT Article DE Ma1; paraneoplastic; brain/testis proteins; antineuronal antibody; cerebellar degeneration ID NEOPLASTIC CEREBELLAR DEGENERATION; CYTOLYTIC T-LYMPHOCYTES; NERVOUS-SYSTEM; SENSORY NEURONOPATHY; HUMAN-MELANOMA; LUNG-CANCER; ANTIGEN; ANTIBODY; EXPRESSION; AUTOANTIBODIES AB The identification of antineuronal antibodies has facilitated the diagnosis of paraneoplastic neurological disorders and the early detection of the associated tumours, It has also led to the cloning of possibly important neuron-specific proteins, In this study we wanted to identify novel antineuronal antibodies in the sera of patients with paraneoplastic neurological disorders and to clone the corresponding antigens, Serological studies of 1705 sera from patients with suspected paraneoplastic neurological disorders resulted in the identification of four patients with antibodies that reacted with 37 and 40 kDa neuronal proteins (anti-Ma antibodies), Three patients had brainstem and cerebellar dysfunction, and one had dysphagia and motor weakness, Autopsy of two patients showed loss of Purkinje cells, Bergmann gliosis and deep cerebellar white matter inflammatory infiltrates, Extensive neuronal degeneration, gliosis and infiltrates mainly composed of CD8(+) T cells were also found in the brainstem 'of one patient, In normal human and rat tissues, the anti-Ma antibodies reacted exclusively with neurons and with testicular germ cells; the reaction was mainly with subnuclear elements (including the nucleoli) and to a lesser degree the cytoplasm, Anti-Ma antibodies also reacted with the cancers (breast, colon and parotid) available from three anti-Ma patients, but not with 66 other tumours of varying histological types, Preincubation of tissues with any of the anti-Ma sera abrogated the reactivity of the other anti-Ma immunoglobulins. Probing of a human complementary DNA library with anti-Ma serum resulted in the cloning of a gene that encodes a novel 37 kDa protein (Mal), Recombinant Mal was specifically recognized by the four anti-Ma sera but not by 337 control sera, including those from 52 normal individuals, 179 cancer patients without paraneoplastic neurological symptoms, 96 patients with paraneoplastic syndromes and 10 patients with non-cancer-related neurological disorders, The expression of Mal mRNA is highly restricted to the brain and testis, Subsequent analysis suggested that Mal is likely to be a phosphoprotein, Our study demonstrates that some patients with paraneoplastic neurological disorders develop antibodies against Ma1, a new member of an expanding family of 'brain/testis' proteins. C1 Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Cotzias Lab Neurooncol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Cornell Univ, Coll Med, Dept Neurol & Neurosci, Ithaca, NY 14853 USA. Columbia Univ Coll Phys & Surg, Columbia Presbyterian Med Ctr, Neurol Inst, Dept Neurol, New York, NY 10032 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Rosenfeld, MR (reprint author), Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10021 USA. OI Dalmau, Josep/0000-0001-5856-2813 FU NINDS NIH HHS [NS-26064, NS01625-04] NR 47 TC 127 Z9 133 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JAN PY 1999 VL 122 BP 27 EP 39 DI 10.1093/brain/122.1.27 PN 1 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 164TB UT WOS:000078478700004 PM 10050892 ER PT J AU Arciniegas, D Adler, L Topkoff, J Cawthra, E Filley, CM Reite, M AF Arciniegas, D Adler, L Topkoff, J Cawthra, E Filley, CM Reite, M TI Attention and memory dysfunction after traumatic brain injury: cholinergic mechanisms, sensory gating, and a hypothesis for further investigation SO BRAIN INJURY LA English DT Review ID MINOR HEAD-INJURY; ALZHEIMERS-DISEASE; EVOKED RELEASE; RAT-BRAIN; ACETYLCHOLINE; CONCUSSION; AMNESIA; BINDING; DAMAGE; SCHIZOPHRENICS AB Traumatic brain injury (TBI) is a common occurrence, with a rate of nearly 400000 new injuries per year. Cognitive and emotional disturbances may become persistent and disabling for many injured persons, and frequently involve symptomatic impairment in attention and memory. Impairments in attention and memory have been well characterized in TBI, and are likely related to disruption of cholinergic functioning in the hippocampus. Additionally, disturbances in this neurotransmitter system may also account for disturbances in sensory gating and discriminative attention in this population. The electroencephalographic P50 waveform of the evoked response to paired auditory stimuli may provide a physiologic market of impaired sensory gating among TBI survivors. The first application of this recording assessment to the TBI population is reported. Preliminary findings in three cases are presented, and the interpretation of impaired sensory gating in this population is discussed. Given the impact of TBI on cholinergic systems, the effects of cholinergic augmentation on attention and memory impairment, and the availability of an electrophysiologic marker of cholinergic dysfunction responsive to cholinergic agents, a testable cholinergic hypothesis for investigation and treatment of these patients is proposed. C1 Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Serv Neurol, Denver, CO USA. Denver Vet Affairs Med Ctr, Psychiat Serv, Denver, CO USA. Univ Colorado, Dept Biol, Denver, CO 80202 USA. RP Arciniegas, D (reprint author), Campus Box C268-68,4200 E 9th Ave, Denver, CO 80262 USA. RI Arciniegas, David/A-3792-2009 NR 89 TC 86 Z9 89 U1 2 U2 7 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0269-9052 J9 BRAIN INJURY JI Brain Inj. PD JAN PY 1999 VL 13 IS 1 BP 1 EP 13 DI 10.1080/026990599121827 PG 13 WC Neurosciences; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 158TA UT WOS:000078131200001 PM 9972437 ER PT J AU Browne, SE Ferrante, RJ Beal, MF AF Browne, SE Ferrante, RJ Beal, MF TI Oxidative stress in Huntington's disease SO BRAIN PATHOLOGY LA English DT Review ID 3-NITROPROPIONIC ACID NEUROTOXICITY; NEURONAL INTRANUCLEAR INCLUSIONS; METHYL-D-ASPARTATE; NEURODEGENERATIVE DISEASES; BASAL GANGLIA; SUPEROXIDE-DISMUTASE; EXCITOTOXIC LESIONS; FUNCTIONAL-ANATOMY; STRIATAL NEURONS; TRANSGENIC MICE AB It has been five years since the elucidation of the genetic mutation underlying the pathogenesis of Huntington's disease (HD) (97), however the precise mechanism of the selective neuronal death it propagates still remains an enigma, Several different etiological processes may play roles, and strong evidence from studies in both humans and animal models suggests the involvement of energy metabolism dysfunction, excitotoxic processes, and oxidative stress. Importantly, the recent development of transgenic mouse models of HD led to the identification of neuronal intranuclear inclusion bodies in affected brain regions in both mouse models and in HD brain, consisting of protein aggregates containing fragments of mutant huntingtin protein. These observations opened new avenues of investigation into possible huntingtin protein interactions and their putative pathogenetic sequelae, Amongst these studies, findings of elevated levels of oxdative damage products such as malondialdehyde, 8-hydroxy-deoxyguanosine, 3-nitrotyrosine and heme oxygenase in areas of degeneration in HD brain, and of increased free radical production in animal models, indicate the involvement of oxidative stress either as a causative event, or as a secondary constituent of the cell death cascade in the disease, Here we review the evidence for oxidative damage and potential mechanisms of neuronal death in HD. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Bedford VA Med Ctr, Bedford, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. New York Hosp, Dept Neurol, New York, NY 10021 USA. Cornell Univ, Coll Med, New York, NY USA. RP Browne, SE (reprint author), Massachusetts Gen Hosp, Dept Neurol, Warren 408,Fruit St, Boston, MA 02114 USA. EM browne@helix.mgh.harvard.edu FU NINDS NIH HHS [NS16367, NS35255] NR 105 TC 304 Z9 315 U1 2 U2 13 PU INT SOC NEUROPATHOLOGY PI PITTSBURGH PA 200 LOTHROP ST A506, PITTSBURGH, PA 15213 USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD JAN PY 1999 VL 9 IS 1 BP 147 EP 163 PG 17 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 164TG UT WOS:000078479200012 PM 9989457 ER PT J AU Kristensen, CA Askenasy, N Jain, RK Koretsky, AP AF Kristensen, CA Askenasy, N Jain, RK Koretsky, AP TI Creatine and cyclocreatine treatment of human colon adenocarcinoma xenografts: P-31 and H-1 magnetic resonance spectroscopic studies SO BRITISH JOURNAL OF CANCER LA English DT Article DE creatine; cyclocreatine; tumour xenograft; magnetic resonance spectroscopy; tumour growth ID ENERGY-METABOLISM; KINASE ISOZYMES; BROAD-SPECTRUM; SOLID TUMORS; NUDE-MICE; GROWTH; CANCER; CELLS; TRANSPORTER; EXPRESSION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA. Carnegie Mellon Univ, NMR Ctr, Pittsburgh, PA 15213 USA. RP Kristensen, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab, Boston, MA 02114 USA. RI Koretsky, Alan/C-7940-2015 OI Koretsky, Alan/0000-0002-8085-4756 FU NCI NIH HHS [R35-CA-56591] NR 31 TC 27 Z9 28 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JAN PY 1999 VL 79 IS 2 BP 278 EP 285 DI 10.1038/sj.bjc.6690045 PG 8 WC Oncology SC Oncology GA 152CP UT WOS:000077758300014 PM 9888469 ER PT J AU Kroning, R Katz, D Lichtenstein, AK Nagami, GT AF Kroning, R Katz, D Lichtenstein, AK Nagami, GT TI Differential effects of cisplatin in proximal and distal renal tubule epithelial cell lines SO BRITISH JOURNAL OF CANCER LA English DT Article DE renal tubule epithelial cell lines; cisplatin; carboplatin; nephrotoxicity; transport; apoptosis ID ACQUIRED-RESISTANCE; CYTO-TOXICITY; PLATINUM; RAT; DEATH; CIS-DIAMMINEDICHLOROPLATINUM(II); DRUGS; DNA; METABOLITES; MECHANISM C1 W Los Angeles Vet Affairs Med Ctr, Nephrol Sect 111L, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Hematol Oncol Sect, Med & Res Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. RP Nagami, GT (reprint author), W Los Angeles Vet Affairs Med Ctr, Nephrol Sect 111L, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 30 TC 23 Z9 24 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JAN PY 1999 VL 79 IS 2 BP 293 EP 299 PG 7 WC Oncology SC Oncology GA 152CP UT WOS:000077758300016 PM 9888471 ER PT J AU Tse, WT Lux, SE AF Tse, WT Lux, SE TI Red blood cell membrane disorders SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review ID DOMINANT HEREDITARY SPHEROCYTOSIS; DELETIONAL FRAMESHIFT MUTATION; SOUTHEAST-ASIAN OVALOCYTOSIS; LOW-EXPRESSION ALLELE; ALPHA-SPECTRIN GENE; TRUNCATED BETA-SPECTRIN; RENAL TUBULAR-ACIDOSIS; BAND-3 AE1 GENE; HEMOLYTIC-ANEMIA; PROTEIN-4.2 GENE C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Tse, WT (reprint author), Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. NR 117 TC 167 Z9 172 U1 1 U2 11 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 JAN PY 1999 VL 104 IS 1 BP 2 EP 13 DI 10.1111/j.1365-2141.1999.01130.x PG 12 WC Hematology SC Hematology GA 164TD UT WOS:000078478900002 PM 10027705 ER PT J AU Fishman, JA AF Fishman, JA TI The process of discovery SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Infect Dis, Transplantat Infect Dis Program, Boston, MA 02114 USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Transplantat Infect Dis Program, Fruit St, Boston, MA 02114 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA DISTRIBUTION AND SALES, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PY 1999 VL 77 IS 1 BP 73 EP 75 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 164RX UT WOS:000078478300018 PM 10206764 ER PT J AU Fung, CY Grossbard, ML Linggood, RM Younger, J Flieder, A Harris, NL Graeme-Cook, F AF Fung, CY Grossbard, ML Linggood, RM Younger, J Flieder, A Harris, NL Graeme-Cook, F TI Mucosa-associated lymphoid tissue lymphoma of the stomach - Long term outcome after local treatment SO CANCER LA English DT Article; Proceedings Paper CT 32nd Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 18-21, 1996 CL PHILADELPHIA, PENNSYLVANIA SP Amer Soc Clin Oncol DE mucosa-associated lymphoid tissue lymphoma; stomach; non-Hodgkin's lymphoma; radiation therapy; gastrectomy ID HELICOBACTER-PYLORI INFECTION; PRIMARY GASTRIC LYMPHOMA; NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMA; MALT LYMPHOMA; ANTIBIOTIC-TREATMENT; MALIGNANT-LYMPHOMA; REGRESSION; FEATURES; CLASSIFICATION AB BACKGROUND. Although antibiotic therapy is emerging as effective initial treatment for patients with gastric lymphoma of mucosa-associated lymphoid tissue (MALT), there is a subset of patients for whom antibiotics are ineffective or inappropriate. Surgical resection can be curative, but total gastrectomy may be required for the eradication of all disease. To identify the optimal nonantibiotic therapy for early stage gastric MALT lymphoma, the authors retrospectively evaluated the Massachusetts General Hospital experience with gastric MALT lymphoma. METHODS. Disease patterns and treatment outcomes were retrospectively analyzed in data from 21 consecutive patients with gastric MALT lymphoma who were treated between 1978 and 1995 at the Massachusetts General Hospital. RESULTS. Sixteen patients were Stage IE, and 5 were in higher stages. Treatment consisted of resection with or without radiation or chemotherapy (14 patients), radiation alone (4 patients), or radiation plus chemotherapy (2 patients). Thirteen Stage IE patients received local therapy only. The 10-year actuarial relapse free survival rate for Stage IE patients was 93%, with I relapse among 15 treated patients. Because the patient who relapsed was treated successfully with chemotherapy, the 10-year cancer free survival was 100%. Overall survival for Stage IE patients was 93% at 5 years and 58% at 10 years, with no deaths from lymphoma. CONCLUSIONS. These data indicate that a high probability of long term. remission can be achieved with only local treatment of patients with Stage I gastric MALT lymphoma. Preliminary results suggest that radiation therapy is well tolerated and effective and may well be the optimal nonantibiotic treatment for patients with localized gastric MALT lymphoma. Cancer 1999;85:9-17. (C) 1999 American Cancer Society. C1 Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Dept Internal Med, Massachusetts Gen Hosp,Sch Med, Div Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Fung, CY (reprint author), Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, Fruit St, Boston, MA 02114 USA. NR 48 TC 40 Z9 47 U1 1 U2 1 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 JAN 1 PY 1999 VL 85 IS 1 BP 9 EP 17 DI 10.1002/(SICI)1097-0142(19990101)85:1<9::AID-CNCR2>3.0.CO;2-S PG 9 WC Oncology SC Oncology GA 157LV UT WOS:000078064100002 PM 9921968 ER PT J AU Arun, B Slack, R Gehan, E Spitzer, T Meehan, KR AF Arun, B Slack, R Gehan, E Spitzer, T Meehan, KR TI Survival after autologous hematopoietic stem cell transplantation for patients with inflammatory breast carcinoma SO CANCER LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Hematology CY DEC 06-10, 1996 CL ORLANDO, FLORIDA SP Amer Soc Hematol, US Dept Vet Affairs Merit Res Funds, NIH DE inflammatory breast carcinoma; dose intensity; transplantation; survival ID HIGH-DOSE CYCLOPHOSPHAMIDE; ADJUVANT THERAPY; BONE-MARROW; CANCER; CHEMOTHERAPY; CARBOPLATIN; INTENSITY; ETOPOSIDE; TOXICITY; SUPPORT AB BACKGROUND. The authors retrospectively determined the clinical outcome of patients with inflammatory breast carcinoma (IBC) treated with high dose chemotherapy (HDC) and autologous bone marrow (ABM) or peripheral blood stem cell (PBSC) support. METHODS. Twenty-four consecutive patients with IBC received HDC, including escalating doses of carboplatin (range, 1.2-1.8 g/m(2)) and cyclophosphamide (range, 4.8-6.0 g/m(2)) over 3 days followed by ABM (n = 5) or PBSC infusion (n = 19). Restaging evaluation was performed 100 days after transplant, every 6 months for 2 years, and then yearly thereafter. After transplantation, fifteen patients received immunotherapy with interleukin-2 (IL-2) or IL-2 and interferon-alpha. RESULTS. The 2-year estimated disease free survival (DFS) and overall survival (OS) for these patients were 71% (90% confidence interval [CI], 55-87%) and 73% (90% CI, 53-93%), respectively. The median follow-up of surviving patients was 19 months (range, 8-68 months). Six patients developed disease recurrence at a median of 10 months (range, 4-16 months) after transplantation. Four of these 6 patients died from metastatic disease at a median of 18 months (range, 14-21 months). Using the generalized Wilcoxon test and the Cox proportional hazards regression model, patients with tumors that demonstrated estrogen receptors had an improved DFS (P = 0.03). CONCLUSIONS. Combining HDC and ABM or PBSC for patients with IBC may yield an improved OS and DFS. Cancer 1999;85:93-9. (C) 1999 American Cancer Society. C1 Georgetown Univ, Med Ctr, Div Hematol & Oncol, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Div Biostat, Washington, DC 20007 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Bone Marrow Transplant Program, Boston, MA 02114 USA. RP Meehan, KR (reprint author), Georgetown Univ, Med Ctr, Div Hematol & Oncol, 3800 Reservoir Rd NW, Washington, DC 20007 USA. NR 28 TC 15 Z9 16 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD JAN 1 PY 1999 VL 85 IS 1 BP 93 EP 99 DI 10.1002/(SICI)1097-0142(19990101)85:1<93::AID-CNCR13>3.0.CO;2-C PG 7 WC Oncology SC Oncology GA 157LV UT WOS:000078064100013 PM 9921979 ER PT J AU Havlin, KA Ramirez, MJ Legler, CM Harris, LN Matulonis, UA Hohneker, JA Hayes, DF Winer, EP AF Havlin, KA Ramirez, MJ Legler, CM Harris, LN Matulonis, UA Hohneker, JA Hayes, DF Winer, EP TI Inability to escalate vinorelbine dose intensity using a daily x3 schedule with and without filgrastim in patients with metastatic breast cancer SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE vinorelbine; breast cancer; phase I; dose intensity; growth factor ID FIRST-LINE; PHASE-II; CHEMOTHERAPY AB Purpose: Vinorelbine (Navelbine) is a semisynthetic vinca alkaloid with documented activity in breast cancer. The major dose-limiting toxicity (DLT) when given weekly is myelosuppression with minimal neurologic toxicity. This phase I study attempted to define the maximally tolerated dose (MTD) and the DLT of vinorelbine on a daily x3 schedule with and without filgrastim support, Methods: A total of 19 patients with stage IV breast cancer were enrolled in separate studies at Duke University Medical Center (DUMC) and the Dana-Farber Cancer Institute (DFCI). Eligible patients could have received up to two prior chemotherapy regimens in the metastatic setting and had to have an ANC > 1500/mm(2), PLT > 100000 m(3), creatinine < 2.0 mg/dl, bilirubin < 2.0 mg/dL, SGOT not more than three times normal, and performance status 0-1. Vinorelbine was administered using a daily x3 schedule every 3 weeks. The protocols were designed to study dose escalation with and without growth factor support. At DUMC, in the initial phase of the study, the starting dose was 15 mg/m(2) per day and dose escalations of 5 mg/m(2) were planned until DLT developed and the MTD was defined. DLT was defined as granulocytopenia < 500/mm(3) for > 7 days, grade IV thrombocytopenia, febrile neutropenia, or grade III or greater nonhematologic toxicity. In the second phase of the study, growth factor support was given with vinorelbine at the MTD. Filgrastim at a dose of 5 mu g/kg was started on day 4 of the 21-day cycle and was continued until the neutrophil count exceeded 10000 cells/mm(3). At DFCI, all patients received growth factor starring on day 4 and the starting dose of vinorelbine was 25 mg/m(2). Results: At DUMC, DLT was seen at 20 mg/m(2) in three of three patients and included febrile neutropenia, grade IV neutropenia > 7 days, grade III neurotoxicity, and grade III vomiting. Despite the addition of filgrastim, DLT was again seen at 20 mg/m(2) and included grade III neurotoxicity (law pain, abdominal pain, constipation. ileus) and grade IV mucositis. Three patients at DFCI were treated with vinorelbine at a dose of 25 mg/m(2) with growth factor support, and two developed DLT including febrile neutropenia, neutropenia > 7 days, and grade III stomatitis. Conclusions: Our effort to escalate the dose intensity of vinorelbine on this schedule was not successful and was complicated by hematologic and nonhematologic toxicity. A daily x3 schedule of vinorelbine should not be pursued as an alternative treatment regimen in patients with previously treated metastatic breast cancer. C1 Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA. Duke Univ, Med Ctr, Div Hematol Oncol, Durham, NC 27110 USA. Montreal Gen Hosp, Montreal, PQ H3G 1A4, Canada. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Washington, DC 20007 USA. RP Winer, EP (reprint author), Dana Farber Canc Inst, Breast Oncol Ctr, 44 Binney St,D1210, Boston, MA 02115 USA. NR 13 TC 3 Z9 3 U1 0 U2 0 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 JAN PY 1999 VL 43 IS 1 BP 68 EP 72 DI 10.1007/s002800050864 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 144ZU UT WOS:000077347000010 PM 9923543 ER PT J AU Barnett, FH Rainov, NG Ikeda, K Schuback, DE Elliott, P Kramm, CM Chase, M Qureshi, NH Harsh, G Chiocca, EA Breakefield, XO AF Barnett, FH Rainov, NG Ikeda, K Schuback, DE Elliott, P Kramm, CM Chase, M Qureshi, NH Harsh, G Chiocca, EA Breakefield, XO TI Selective delivery of herpes virus vectors to experimental brain tumors using RMP-7 SO CANCER GENE THERAPY LA English DT Article DE blood-brain barrier; blood-tumor barrier; carotid artery; gene therapy; herpes simplex virus type I; intra-arterial application ID LONG-TERM SURVIVAL; GENE-THERAPY; DRUG-DELIVERY; INTRACAROTID INFUSION; BARRIER DISRUPTION; BRADYKININ ANALOG; SOLID TUMORS; BLOOD; GANCICLOVIR; NEOPLASMS AB RMP-7, a bradykinin analog, has been shown to selectively open the blood-tumor barrier for the delivery of chemotherapeutic drugs to brain tumors. In contrast to bradykinin, RMP-7 has no hypotensive effects and has been approved for human use. This study was initiated to determine whether RMP-7 would open the blood-tumor barrier to virus vectors encoding tumor-killing genes in an experimental model. The herpes virus vector used, hrR3, which encodes virus thymidine kinase gene and the lacZ reporter gene, is defective in a gene encoding ribonucleotide reductase, replicates selectively in dividing tumor cells and not in postmitotic neural cells. It was determined that an optimum dose of RMP-7 (1.5-3.0 mu g/kg over 10-15 minutes) enhanced viral delivery to brain tumors in rats bearing intracranial 9 L gliosarcomas when infused through the carotid artery immediately prior to virus vector application. Maximum expression of the lacZ reporter gene occurred at 3 days after intracarotid infusion. By 8 days, transgene expression was largely confined to tumor foci away from the main tumor mass. Viral delivery was essentially specific to tumor cells, with little transgene expression elsewhere in the brain. Minimal uptake and pathology was noted in the kidney, spleen, and liver. These findings indicate that intracarotid delivery of RMP-7 can augment the selective delivery of virus vectors to brain tumors in an experimental rat model, with the potential for application to human brain tumors. C1 Childrens Hosp, Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurosurg, Charlestown, MA 02129 USA. Scripps Clin, Div Neurosurg, La Jolla, CA 92037 USA. Univ Halle Wittenberg, Fac Med, Dept Neurosurg, Halle Saale, Germany. Alkermes Inc, Cambridge, MA 02138 USA. Univ Dusseldorf, Fac Med, Dept Pediat, Dusseldorf, Germany. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp E, 13th St,Bldg 149, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA69246]; NINDS NIH HHS [NS352580] NR 37 TC 25 Z9 26 U1 1 U2 2 PU STOCKTON PRESS PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD JAN-FEB PY 1999 VL 6 IS 1 BP 14 EP 20 DI 10.1038/sj.cgt.7700003 PG 7 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 197WY UT WOS:000080390400002 PM 10078959 ER PT J AU Shapiro, CL Keating, J Angell, JE Janicek, M Gelman, R Hayes, D LeBoff, MS AF Shapiro, CL Keating, J Angell, JE Janicek, M Gelman, R Hayes, D LeBoff, MS TI Monitoring therapeutic response in skeletal metastases using dual-energy X-ray absorptiometry: A prospective feasibility study in breast cancer patients SO CANCER INVESTIGATION LA English DT Article ID BONE METASTASES; PHOTON-ABSORPTIOMETRY; COMPUTED-TOMOGRAPHY; CLINICAL COURSE; LUMBAR SPINE; PREMENOPAUSAL; RADIOGRAPHY; WOMEN; SCAN; BODY AB Response to systemic therapy in breast cancer patients with lytic skeletal metastases manifests as a shift from increased bone resorption to new bone formation. We hypothesized that dual-energy x-ray absorptiometry (DXA) could be used to prospectively quantitate changes in bone mineral density (BMD) in metastatic skeletal lesions in breast cancer patients receiving systemic therapy. Nine metastatic breast cancer patients with one or more assessable lytic skeletal metastases receiving systemic therapy were prospectively evaluated with DXA, skeletal radiographs, computed tomography (CT), and radionuclide bone scans at baseline (t = 0 months, 2 months, and 6 months). The median (range) percentage change in BMD in skeletal lesions among patients responding to systemic therapy was 10.7% (0.1-21.85), 5.0% (-1.3-23.8), and 16.7% (-2.0-50.8) at 0-2, 2-6 and 0-6 months, respectively. Changes in BMD between 0-2, and 0-6 months were significant (Wilcoxin signed rank test; p = 0.013 and p = 0.017, respectively). The percentage change in BMD skeletal lesions between 0-2 and 2-6 months correlated with the changes imaged on skeletal x-rays (Spearman rank order correlation coefficient [R-s] = 0.511, p = 0.011) and CTs (R-s = 0.416 p = 0.046) but less so with bone scans (R-s = 0.293, p = 0.189). It is technically feasible to use DXA To prospectively monitor changes in lytic skeletal metastases in breast cancer patients receiving systemic therapy. The BMD of skeletal metastases increases in patients responding to treatment and was significantly correlated with the changes imaged on skeletal xrays and CTs. Additional studies of DXA to evaluate response in skeletal metastasis are warranted. C1 Dana Farber Canc Inst, Breast Evaluat Ctr, Dept Oncoradiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Internal Med, Skeletal Hlth & Osteoporosis Program, Boston, MA USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Shapiro, CL (reprint author), B 421 Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA. NR 28 TC 15 Z9 15 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 1999 VL 17 IS 8 BP 566 EP 574 DI 10.3109/07357909909032841 PG 9 WC Oncology SC Oncology GA 261AM UT WOS:000083985700002 PM 10592763 ER PT J AU Tsao, H Zhang, X Majewski, P Haluska, FG AF Tsao, H Zhang, X Majewski, P Haluska, FG TI Mutational and expression analysis of the p73 gene in melanoma cell lines SO CANCER RESEARCH LA English DT Article ID HUMAN-MALIGNANT MELANOMA; P53 GENE; DYSPLASTIC NEVUS; CHROMOSOME 1P; DELETION; REGION; ABNORMALITIES; NEUROBLASTOMA; IP AB A novel p53-related gene, p73, was recently isolated and cytogenetically mapped to chromosome region 1p36, Functionally, p73 expression induces p21(waf) and suppresses tumor cell grow th. We mapped p73 using radiation hybrids and localized the gene to an interval that putatively harbors a melanoma tumor suppressor locus. We then analyzed p73 transcripts from 24 melanoma cell lines using reverse transcription-PCR/single strand conformation polymorphism and identified nine polymorphic sequence changes (three novel and six previously published polymorphisms); furthermore, we found evidence of biallelic transcription in our cell lines. However, we did not detect any deleterious mutations. These data suggest that the p73 gene is unlikely to be essential in melanoma tumorigenesis. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Dana Farber Partners Canc Care, Boston, MA 02114 USA. China Med Univ, Dept Med Genet, Shenyang, Peoples R China. RP Haluska, FG (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Jackson 1021,Fruit St, Boston, MA 02114 USA. EM haluska.frank@mgh.harvard.edu FU NIAMS NIH HHS [5T32ARO7098-23] NR 26 TC 51 Z9 51 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 1999 VL 59 IS 1 BP 172 EP 174 PG 3 WC Oncology SC Oncology GA 156AM UT WOS:000077979300030 PM 9892203 ER PT J AU Brothers, TE Rios, GA Robison, JG Elliott, BM AF Brothers, TE Rios, GA Robison, JG Elliott, BM TI Justification of intervention for limb-threatening ischemia: a surgical decision analysis SO CARDIOVASCULAR SURGERY LA English DT Article DE decision support techniques; peripheral vascular diseases; vascular surgery ID COST-EFFECTIVENESS; CAROTID ENDARTERECTOMY; BYPASS; SALVAGE AB Intervention for vascular occlusive disease of the distal lower extremity in elderly patients will inevitably be scrutinized as medical resources decline, The authors applied surgical decision analysis to three treatment options: revascularization, amputation and expectant management. The appropriate outcome probabilities were derived from our experience with revascularization to the tibial and pedal vessels, and utility scores were obtained by formalized patient assessment. Revascularization was predicted to improve patient outcome by 1.10 quality-adjusted life-years compared with primary amputation and by 1.16 quality-adjusted life-years compared with expectant management, To gain one additional quality-adjusted life-years, revascularization would cost $5280 more than expectant management, but $33,900 less than primary amputation. Sensitivity analysis predicted revascularization to be the least costly treatment per quality-adjusted life-years as long as 1-month patency exceeds 11%. Revascularization for limb-threatening ischemia of the distal lower extremity is justified and can be performed at a reasonable cost. (C) 1998 The International Society for Cardiovascular Surgery. Published by Elsevier Science Ltd. All rights reserved. C1 Med Univ S Carolina, Dept Surg, Vasc Surg Sect, Charleston, SC 29425 USA. Ralph Henry Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Brothers, TE (reprint author), 171 Ashley Ave, Charleston, SC 29425 USA. NR 24 TC 12 Z9 13 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-2109 J9 CARDIOVASC SURG JI Cardiovasc. Surg. PD JAN PY 1999 VL 7 IS 1 BP 62 EP 69 DI 10.1016/S0967-2109(98)00037-4 PG 8 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 160UR UT WOS:000078250000013 PM 10073763 ER PT J AU Martin, KJ Pardee, AB AF Martin, KJ Pardee, AB TI Principles of differential display SO CDNA PREPARATION AND CHARACTERIZATION SE METHODS IN ENZYMOLOGY LA English DT Review ID ALTERED GENE-EXPRESSION; MESSENGER-RNA; REGULATED GENES; CHAIN-REACTION; CANCER-CELLS; PCR; IDENTIFICATION; PRIMERS; CDNAS; DNA C1 Dana Farber Canc Inst, Boston, MA 02113 USA. RP Martin, KJ (reprint author), Dana Farber Canc Inst, Boston, MA 02113 USA. NR 43 TC 44 Z9 51 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1999 VL 303 BP 234 EP 258 PG 25 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BN43D UT WOS:000081913000014 PM 10349648 ER PT J AU Green, N Rosebrook, J Cochran, N Tan, KM Wang, JH Springer, TA Briskin, MJ AF Green, N Rosebrook, J Cochran, N Tan, KM Wang, JH Springer, TA Briskin, MJ TI Mutational analysis of MAdCAM-1/alpha 4 beta 7 interactions reveals significant binding determinants in both the first and second immunoglobulin domains SO CELL ADHESION AND COMMUNICATION LA English DT Article DE MAdCAM-1; VCAM-1; ICAM-1; IgCAM; mAb; MEM; FCS ID CELL-ADHESION MOLECULE-1; AMINO-ACID-RESIDUES; FUNCTION-ASSOCIATED ANTIGEN-1; INTEGRIN ALPHA-4-BETA-7; CRYSTAL-STRUCTURE; T-CELLS; MADCAM-1; VCAM-1; FIBRONECTIN; RECOGNITION AB The selective emigration of blood born leukocytes into tissues is mediated, in part by interactions of Ig-like cell adhesion molecules (IgCAMs) expressed on vascular endothelium and their cognate ligands, the leukocyte integrins. Within mucosal lymphoid tissues and gastrointestinal sites the mucosal vascular addressin, MAdCAM-1 is the predominant IgCAM, mediating specific lymphocyte homing via interactions with its ligand on lymphocytes, the integrin alpha 4 beta 7. Previous studies have shown that an essential binding motif resides in the first Ig domain of all IgCAMs, containing an acidic residue (D or E) preceded by an aliphatic residue (L or I) that resides in strand C or the CD loop. However, domain swap experiments with MAdCAM-1 and VCAM-1 have shown a requirement for both Ig domains 1 and 2 for efficient integrin binding. We describe the use of chimeric MAdCAM-1/VCAM-1 receptors and point mutations in MAdCAM-1 to define other sites that are required for binding to the integrin alpha 4 beta 7. We find that, in addition to critical CD loop residues, other regions in both domain one and two contribute to MAdCAM-1/alpha 4 beta 7 interactions, including a buried arginine residue in the F strand of domain one and several acidic residues in a highly extended DE ribbon in domain 2. These mutations, when placed in the recently solved crystal structure of human MAdCAM-I give insight into the integrin binding preference of this unique receptor. C1 LeukoSite Inc, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Briskin, MJ (reprint author), LeukoSite Inc, 215 1st St, Cambridge, MA 02142 USA. NR 47 TC 10 Z9 10 U1 2 U2 3 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1061-5385 J9 CELL ADHES COMMUN JI Cell Adhes. Commun. PY 1999 VL 7 IS 3 BP 167 EP + DI 10.3109/15419069909010800 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 260EF UT WOS:000083936000002 PM 10626902 ER PT J AU Walss, C Kreisberg, JI Luduena, RF AF Walss, C Kreisberg, JI Luduena, RF TI Presence of the beta(II) isotype of tubulin in the nuclei of cultured mesangial cells from rat kidney SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Article DE tubulin isotypes; microtubules; nucleolus; nuclear matrix ID BOVINE BRAIN; PROTEIN-TAU; LOCALIZATION; MICROTUBULES; ESTRAMUSTINE; ORGANIZATION; CHROMATIN; CARCINOMA; DISTINCT; DYNAMICS AB Tubulin has generally been considered to be a cytosolic protein whose only function is to form microtubules. This assumption is supported by a great dear of evidence derived from immunohistochemical studies using antibodies directed against whole tubulin or its component polypeptides alpha- and beta-tubulin. We have re-examined the intracellular distribution of tubulin using monoclonal antibodies specific for the beta(I), beta(II), beta(III), and beta(IV) isotypes of beta-tubulin. Our test system is the cultured rat kidney mesangial cell. We have found that Pur is absent from these cells and that beta(I) and beta(IV) are present in microtubules throughout the cytosol. In contrast, Err is present largely in the nuclei. Immunoblotting of purified nuclear extracts shows that the beta(II)-reactive antigen co-migrates with beta-tubulin. Extraction of the cytosol and chromatin suggests that beta(II) is concentrated in the nucleoli and also in a reticulated network in the rest of the nucleoplasm. An antibody to tyrosinated alpha-tubulin shows that or is also present in the nucleoli. Treatment of the cells with fluorescent colchicine shows an accumulation of colchicine in the nucleoli. Finally, fluorescently labeled alpha beta(II)-tubulin dimers, when microinjected into the cells, enter the nuclei and are concentrated in the nucleoli. These results suggest that the beta(II) isotype of tubulin is present as an alpha beta(II) dimer in the nuclei of cultured mesangial cells and suggest the possibility that different tubulin isotypes may have specific functions within the cell. Cell Motil. Cytoskeleton 42:274-284, 1999. (C) 1999 Wiley-Liss.Inc. C1 Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Dept Vet Affairs, Res & Dev Serv, San Antonio, TX 78284 USA. RP Luduena, RF (reprint author), Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA. FU NCI NIH HHS [CA26376]; NIGMS NIH HHS [GM23476] NR 46 TC 36 Z9 38 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0886-1544 J9 CELL MOTIL CYTOSKEL JI Cell Motil. Cytoskeleton PY 1999 VL 42 IS 4 BP 274 EP 284 DI 10.1002/(SICI)1097-0169(1999)42:4<274::AID-CM2>3.0.CO;2-5 PG 11 WC Cell Biology SC Cell Biology GA 185DR UT WOS:000079653300002 PM 10223634 ER PT S AU Kyriakis, JM AF Kyriakis, JM BE Downes, CP Wolf, CR Lane, DP TI Making the connection: coupling of stress-activated ERK/MAPK (extracellular-signal-regulated kinase mitogen-activated protein kinase) core signalling modules to extracellular stimuli and biological responses SO CELLULAR RESPONSES TO STRESS SE BIOCHEMICAL SOCIETY SYMPOSIUM LA English DT Article; Proceedings Paper CT Biochemical-Society Meeting CY JUL, 1997 CL UNIV LIVERPOOL, LIVERPOOL, ENGLAND HO UNIV LIVERPOOL ID NF-KAPPA-B; CELL-CYCLE PROGRESSION; C-JUN; TNF RECEPTOR-1; TRANSDUCTION PATHWAYS; ACTIN POLYMERIZATION; MOLECULAR-CLONING; INDUCED APOPTOSIS; GENE-EXPRESSION; BINDING PROTEIN AB Signal-transduction pathways that employ members of the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) family of protein Ser/Thr kinases are widely conserved among eukaryotes. The multiplicity of these pathways allows the cell to respond to divergent extracellular stimuli by initiating a broad array of responses ranging from cell growth to apoptosis. ERK/MAPK pathways are comprised of a three-tiered core-signalling module wherein ERK/MAPKs are regulated by MAPK/ERK kinases (MEKs) and MEKs, in turn, are regulated by MAPK kinase kinases (MAPKKKs). The regulation of MAPKKK-->MEK-->ERK/MAPK core-signalling modules by upstream components is poorly understood. Mammalian stress-activated ERK/MAPK pathways have been implicated in numerous important physiological functions, including inflammatory responses and apoptosis. In this review, I will discuss how mammalian stress-regulated ERK/MAPK core-signalling modules couple with members of the SPS1 family of protein kinases and to other upstream elements, and how these stress-regulated pathways influence cell function. C1 Massachusetts Gen Hosp, Diabet Res Lab, Charlestown, MA 02129 USA. Harvard Med Sch, Dept Med, Charlestown, MA 02129 USA. RP Kyriakis, JM (reprint author), Massachusetts Gen Hosp, Diabet Res Lab, MGH E,149 13th St, Charlestown, MA 02129 USA. NR 86 TC 5 Z9 5 U1 0 U2 1 PU PORTLAND PRESS LTD PI LONDON PA 59 PORTLAND PL, LONDON W1N 3AJ, ENGLAND SN 0067-8694 BN 1-85578-123-9 J9 BIOCHEM SOC SYMP PY 1999 IS 64 BP 29 EP 48 PG 20 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BM57Q UT WOS:000079152800003 ER PT J AU Larson, JL Covey, MK Berry, J Wirtz, S Alex, CG Matsuo, M AF Larson, JL Covey, MK Berry, J Wirtz, S Alex, CG Matsuo, M TI Discontinuous incremental threshold loading test - Measure of respiratory muscle endurance in patients with COPD SO CHEST LA English DT Article DE COPD; pulmonary rehabilitation; respiratory muscles ID OBSTRUCTIVE PULMONARY-DISEASE; INSPIRATORY PRESSURE; PERFORMANCE; TREADMILL AB Study objective: To assess the discontinuous incremental threshold lending (DC-ITL) test as a measure of respiratory muscle endurance for patients with COPD in terms of perceived breathing difficulty, reliability, and validity. Design: The DC-ITL test was repeated three times at weekly intervals under identical test conditions. Setting: Clinical research laboratory. Patients: Forty-eight patients with moderate to severe COPD, Measurements and results: Rating of perceived breathing difficulty (RPBD) was measured at the end of each stage of the DC-ITL test with a Borg category-ratio scale, The maximal inspiratory pressure (Pimax) was measured before and after the DC-ITL test. Breathing patterns were measured during the DC-ITL test. The mean (+/- SD) for RPBD at the maximal load was 6.3 (3.1), 6.6 (2.8), and 6.7 (2.7) for visits one, two, and three, respectively (not significant). The mean relative maximal load for the DC-ITL test (peak mouth pressure as a percent of Pimax) at the last completed stage was 59 +/- 23%, 62 +/- 20%, and 63 +/- 19% for visits one, two, and three, respectively (not significant). Test-retest reliability was r(1,2) = 0.82 and r(2,3) = 0.69 for relative maximal load and r(1,2) = 0.90 and r(2,3) = 0.90 for absolute maximal load (peak mouth pressure). Tidal volume decreased (p < 0.01) and respiratory rate increased (p < 0.01) from the next-to-the-last to the last completed stage. Pimax decreased after the DC-ITL test (p < 0.01). Conclusions: Moderate breathing difficulty was experienced during the DC-ITL test. The test was reliable and the results of this study support its validity as a measure of respiratory muscle endurance. C1 Univ Illinois, Coll Nursing MC802, Dept Med Surg Nursing, Chicago, IL 60612 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Dept Pulm & Crit Care Med, Hines, IL 60141 USA. RP Larson, JL (reprint author), Univ Illinois, Coll Nursing MC802, Dept Med Surg Nursing, 845 S Damen Ave, Chicago, IL 60612 USA. FU NINR NIH HHS [NRO1428] NR 22 TC 14 Z9 14 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 1999 VL 115 IS 1 BP 60 EP 67 DI 10.1378/chest.115.1.60 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 157QY UT WOS:000078074200013 PM 9925063 ER PT J AU Hess, DR Acosta, FL Ritz, RH Kacmarek, RM Camargo, CA AF Hess, DR Acosta, FL Ritz, RH Kacmarek, RM Camargo, CA TI The effect of heliox on nebulizer function using a beta-agonist bronchodilator SO CHEST LA English DT Article DE asthma; bronchodilator administration; equipment design; helium/oxygen gas mixture; inhalation aerosols; nebulizers; particle size ID ACUTE SEVERE ASTHMA; JET NEBULIZERS; INTERMITTENT; DEPOSITION; OXYGEN; FLOW; ALBUTEROL; AIR; DELIVERY AB Objective: To evaluate nebulizer performance when heliox was used to power the nebuliser, Methods: Conventional and continuous nebulizer designs were evaluated. The conventional nebulizer was used with 5 mg albuterol and flows of 8 L/min air; 8 L/min heliox and 11 L/min heliox; it was also used with In mg albuterol and a heliox flow of 8 L/min. The continuous nebulizer was set to deliver 10 mg of albuterol over 40 min at flows of 2 L/min air, 2 L/min heliox and 3 L/min heliox; it was also used with 20 lug albuterol and a heliox flow of 2 L/min, A cotton plug at die nebulizer mouthpiece was used to trap aerosol during simulated spontaneous breathing. The amount of albuterol deposited on the cotton plug was determined spectrophotometrically. Particle size was determined using an 11-stage cascade impactor. Results: For both nebulizer was, particle size and inhaled mass of albuterol decreased significantly (p < 0.001) when the nebulizer nas powered with heliox rather than air. When powered with heliox, the reduction in inhaled mass of albuterol was less for the conventional nebulizer (16%) than the continuous nebulizer (67%). The nebulization time, however, was more than twofold greater with heliox (p < 0,001), Increasing the flow of heliox increased the particle size (p < 0.05), inhaled mass of albuterol (p < 0.05), and inhaled mass of particles 1 to 5 mu m (p < 0.05) to levels similar to powering the nebulizer with air at the lower flow. Increasing the albuterol concentration in the nebulizer and using the lower heliox flow increased the inhaled mass of albuterol (p < 0.05) while maintaining the smaller particle size pl produced with that flow. Conclusions: The use of hellos to power a nebulizer affects both the inhaled mass of medication and the size of the aerosol particles, The flow to power the nebulizer should be increased when heliox is used. C1 Massachusetts Gen Hosp, Dept Resp Care, Channing Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Channing Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA USA. RP Hess, DR (reprint author), Massachusetts Gen Hosp, Dept Resp Care, Channing Lab, Ellison 401,55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-03533] NR 24 TC 70 Z9 71 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JAN PY 1999 VL 115 IS 1 BP 184 EP 189 DI 10.1378/chest.115.1.184 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 157QY UT WOS:000078074200032 PM 9925082 ER PT J AU Strauss, EC Orkin, SH AF Strauss, EC Orkin, SH TI Guanine-adenine ligation-mediated polymerase chain reaction in vivo footprinting SO CHROMATIN SE METHODS IN ENZYMOLOGY LA English DT Review ID DOMINANT CONTROL REGION; LOCUS-CONTROL REGION; PROTEIN DNA INTERACTIONS; GLOBIN GENE-EXPRESSION; ERYTHROID-CELLS; HYPERSENSITIVE SITES; REGULATORY ELEMENT; TRANSGENIC MICE; INVIVO; TRANSCRIPTION C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Childrens Hosp, Howard Hughes Med Inst, Div Hematol Oncol, Boston, MA 02115 USA. RP Strauss, EC (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. NR 31 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1999 VL 304 BP 572 EP 584 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BQ12X UT WOS:000087254800031 PM 10372382 ER PT J AU Lessin, SR Benoit, BM Li, GQ Moskovitz, A Zweiman, B AF Lessin, SR Benoit, BM Li, GQ Moskovitz, A Zweiman, B TI Quantitative analysis of T-cell receptor beta variable-gene usage in cutaneous late-phase reactions: Implications for T-lymphocyte recruitment in cutaneous inflammation SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; PSORIASIS-VULGARIS; ATOPIC SUBJECTS; SKIN; RESPONSES; LESIONS; AMPLIFICATION; EXPRESSION; HECA-452; RELEASE AB To determine if functionally distinct T-lymphocyte (T cell) subsets accumulate in late-phase immunoglobulin E-mediated reactions (LPR), we quantitatively analyzed the immunophenotype and the T-cell receptor beta variable-gene (V beta) repertoire of T cells in cutaneous LPR. Peripheral blood and skin biopsies were obtained 6 or 24 h after sensitive subjects were challenged with intradermal injections of grass pollen allergen (Ag) and control (C) solution. The frequency of cells expressing CD3, CD4, CD8, CD45RO, and CD25/mm(2) was determined by immunohistochemistry in nine subjects. V beta usage was assessed by reverse transcription-PCR in five of nine subjects. A significantly greater frequency of CD3(+) and CD45RO(+) (memory) T cells was detected in Ag sites than in C sites at 24 h after challenge hut not at 6 h. The frequency of activated (CD25(+)) and helper (CD4(+)) T cells appeared to be increased in Ag sites as well, though not significantly. V beta 6 was the most commonly expressed V beta detected in Ag sites, but it was also detected in accompanying C sites. V beta 2 was the most commonly expressed V beta detected in C sites. Sequence analysis in one case revealed V beta expression in a 6-h Ag site to be essentially polyclonal. Our findings suggest that memory T cells with V beta expression similar to that in normal skin accumulate in developing cutaneous LPR. The limited usage of V beta suggests a preferential recruitment or retention of reactive T cells from an endogenous subset of skin-homing T cells with its own skewed V beta repertoire. C1 Univ Penn, Med Ctr, Dept Dermatol, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, Dept Internal Med, Div Allergy & Immunol, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Lessin, SR (reprint author), Univ Penn, Med Ctr, Dept Dermatol, 217 Clin Res Bldg,415 Curie Blvd, Philadelphia, PA 19104 USA. FU NCI NIH HHS [CA-55017]; NIAID NIH HHS [R01 AI-14332]; NIAMS NIH HHS [T32 AR-07565] NR 26 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD JAN PY 1999 VL 6 IS 1 BP 85 EP 88 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 156BE UT WOS:000077980900015 PM 9874669 ER PT J AU Lara-Marquez, ML Yunis, JJ Layrisse, Z Ortega, F Carvallo-Gil, E Montagnani, S Makhatadze, NJ Pocino, M Granja, C Yunis, E AF Lara-Marquez, ML Yunis, JJ Layrisse, Z Ortega, F Carvallo-Gil, E Montagnani, S Makhatadze, NJ Pocino, M Granja, C Yunis, E TI Immunogenetics of atopic asthma: association of DRB1*1101 DQA1*0501 DQB1*0301 haplotype with Dermatophagoides spp.-sensitive asthma in a sample of the Venezuelan population SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Article DE atopy; asthma; HLA-class I alleles; HLA-class II alleles; Dermatophagoides pteronyssinus; Dermatophagoides farinae; IgE; house dust mite allergy; genetics; HLA-DRB1*11; eosinophils ID CLASS-II ALLELES; T-CELL EPITOPES; HLA-DR; INTERNATIONAL TRENDS; HUMAN INTERLEUKIN-5; BRONCHIAL-ASTHMA; ALLERGIC-ASTHMA; IMMUNE-RESPONSE; EOSINOPHIL; MORTALITY AB Background Genes linked to the major histocompatibility complex (MHC), have been implicated in atopic asthma. Asthma is highly prevalent in the Venezuelan population (estimated at 20%) and genetic markers are needed to identify populations at risk and plan intervention strategies. Objective To study the influence of the MHC class I and class Il genes in the susceptibility to atopic asthma. Methods MHC-class I HLA-A, -C, -B and MHC-class II HLA-DR, -DQ, -DP gene haplotype frequencies were determined in 135 Venezuelan mestizos, 71 belong to 20 atopic asthmatic families and 64 unrelated controls. The index cases were 20 atopic asthmatics with positive skin-prick tests and specific serum immunoglobulin E (IgE) for Dermatophagoides pteronyssinus (Der p) and Dermatophagoides farinae (Der f). To ascertain the genes associated with susceptibility to atopy and/or asthma, two control groups were studied, 41 non-atopic subjects with skin-prick negative test, and undetectable levels of specific IgE and 23 non-asthmatic atopic subjects with detectable specific IgE to Der p and Der f. A linkage analysis was performed in those families with two or more atopic siblings (with or without asthma). Results MHC-class I genes analysis showed that HLA-Cw7 was absent in the asthmatic patients studied, whereas the frequency of this allele was 14.3% in non-atopic controls (P = 0.017, PC = 0.19) and 20.8% in the atopic controls (P = 0.0066, PC = 0.07). MHC-class II gene analysis showed a significant increase of the HLA-DRB1*11 in the asthmatic patients compared with non-atopic controls (allele frequencies of 25.6 vs 4.4% P = 0.0017, PC= 0.02). There were no significant differences among asthmatic and atopic controls in the frequency of HLA-DRB1*11 (25.6 vs 17.4%). In contrast, the HLA-DRB1*1101+ haplotypes were significantly higher in asthmatics compared with atopic and non-atopic controls (19.6% vs 2.2% vs 2.3%, PC < 0.05). The HLA-DRB1*1101, DQA1*0501, DQB1*0301 haplotype was found significantly increased in the patients vs non-atopic controls (15.4 vs 1.1%, PC < 0.01). The serum levels of specific IgE were detectable in both atopic asthmatics and atopic controls; however, it was higher in atopic asthmatics vs atopic controls Der p (median, 58.7 vs 2.7 kU/L, P < 0.001) and Der f (median, 46.9 vs 2.7 kU/L, P < 0.001). No linkage between MHC genes and mite-atopy could be documented on informative families with two or more atopic siblings. Conclusions We have identified an association between the haplotype HLA-DRB1*1101, DQA1*0501, DQB1*0301 and atopic asthma that confers susceptibility to develop mite-sensitive asthma to atopics (relative risk, RR 8.2), and to non-atopic controls (RR = 15.8) that carry this haplotype. Conversely, the allele HLA-Cw7 was absent in the asthmatics studied and had higher frequencies in the atopic (RR = 0.05) and non-atopic (RR = 0.08) controls. Thus, it may have a protective role for developing atopic asthma in the population studied. C1 Hosp Mil Carlos Arvelo, Dept Alergia & Immunol, Sta Fe De Bogota, Colombia. Hosp Mil Carlos Arvelo, Dept Enfermedades Resp, Sta Fe De Bogota, Colombia. Univ Nacl Colombia, Inst Venezolano Invest Cient, Sta Fe De Bogota, Colombia. Univ Nacl Colombia, Inst Genet, Sta Fe De Bogota, Colombia. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Lara-Marquez, ML (reprint author), Childrens Hosp Res Fdn, 240 Wexner,700 Childrens Dr, Columbus, OH 43205 USA. NR 54 TC 45 Z9 48 U1 0 U2 3 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD JAN PY 1999 VL 29 IS 1 BP 60 EP 71 PG 12 WC Allergy; Immunology SC Allergy; Immunology GA 169PG UT WOS:000078757300010 PM 10051703 ER PT J AU Robertson, MJ Cameron, C Atkins, MB Gordon, MS Lotze, MT Sherman, ML Ritz, J AF Robertson, MJ Cameron, C Atkins, MB Gordon, MS Lotze, MT Sherman, ML Ritz, J TI Immunological effects of interleukin 12 administered by bolus intravenous injection to patients with cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL STIMULATORY FACTOR; NATURAL-KILLER-CELL; INTERFERON-GAMMA PRODUCTION; VIRUS-INFECTED CELLS; VERSUS-HOST DISEASE; T-CELLS; NK-CELLS; ADHESION MOLECULES; CYTOLYTIC ACTIVITY; RECOMBINANT IL-12 AB The immunological effects of recombinant human interleukin 12 (rhIL-12) administration were examined during the conduct of a Phase I clinical trial, Forty patients with advanced cancer received bolus i.v. injections of rhIL-12 in doses ranging between 3 and 1000 ng/kg, Dose-dependent increases in serum IFN-gamma levels were seen during rhIL-12 therapy. Significant lymphopenia was observed 24 h after single i.v. injections of rhIL-12 at each dose level, The degree of lymphopenia was dose dependent, and a plateau effect was seen with rhIL-12 doses of 100 ng/kg and higher. Lymphocyte counts reached nadir levels at approximately 10 h after rhIL-12 injection and returned to baseline within 14 days postinjection, Rebound lymphocytosis as seen after interleukin 2 therapy, was not observed after recovery from rhIL-12-induced lymphopenia. rhIL-12-induced lymphopenia involved all, major lymphocyte subsets, although natural killer (NK) cell numbers were the most profoundly affected, and CD4 T-cell numbers mere the least affected. CD2, LFA-1, and CD56 were transiently up-regulated on the surface of NK cells exposed to rhIL-12 in vivo. Peripheral blood mononuclear cells obtained from cancer patients before rhIL-12 therapy exhibited defective NK cell cytotoxicity and T-cell-proliferative responses. Peripheral blood mononuclear cells obtained after lymphocyte recovery following the administration of a single 500 ng/kg dose of rhIL-12 displayed augmented NK cell cytolytic activity in four of four patients tested and enhanced T-cell proliferation in three of four patients tested. These studies confirm that doses of rhIL-12 resulting in significant immunological activity can be administered with acceptable toxicity to cancer patients. Furthermore, rhIL-12 therapy can reverse defects in NK cell and T-cell function that are associated with advanced cancer in humans. C1 Indiana Univ, Med Ctr, Div Hematol Oncol, Indianapolis, IN 46202 USA. Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. Tufts Univ, New England Med Ctr, Tupper Res Inst, Boston, MA 02111 USA. Tufts Univ, New England Med Ctr, Div Hematol Oncol, Boston, MA 02111 USA. Univ Pittsburgh, Sch Med, Pittsburgh Canc Inst, Div Surg Oncol, Pittsburgh, PA 15261 USA. Genet Inst, Cambridge, MA 02140 USA. RP Robertson, MJ (reprint author), Indiana Univ, Sch Med, Dept Med, Bone Marrow Transplant Program, 1044 W Walnut St,Room R4-202, Indianapolis, IN 46202 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA01730, CA41619]; NIAID NIH HHS [AI27314] NR 55 TC 127 Z9 131 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 JAN PY 1999 VL 5 IS 1 BP 9 EP 16 PG 8 WC Oncology SC Oncology GA 157AX UT WOS:000078037600004 PM 9918197 ER PT J AU Genest, DR Di Salvo, D Rosenblatt, MJ Holmes, LB AF Genest, DR Di Salvo, D Rosenblatt, MJ Holmes, LB TI Terminal transverse limb defects with tethering and omphalocele in a 17 week fetus following first trimester misoprostol exposure SO CLINICAL DYSMORPHOLOGY LA English DT Article DE misoprostol; amniotic band syndrome; terminal transverse limb defect; omphalocele ID VARICELLA-ZOSTER VIRUS; MATERNAL VARICELLA; MOBIUS-SYNDROME; EARLY-PREGNANCY; 1ST TRIMESTER; FETAL; INFECTION; ABORTION AB We report a fetus from an elective termination at 17 weeks gestation following maternal ingestion of 1200 mu g of misoprostol at 7 weeks of gestation. The fetus had abscence of the middle and distal phalanges of fingers 1, 3, 4 and 5 with tethering by thin strands of tissue on one hand, a below-knee amputation of one leg and omphalocele. There was absence of amnion on the chorionic surface of the placenta, a pathologic feature of early amnion rupture. The association in this case of the phenotypic features of the amniotic band syndrome suggests that the teratogenicity of misoprostol at 9 to 12 weeks gestation can overlap that of other acute insults at that time, such as chorionic villus sampling, dilatation and curettage and abdominal trauma in the first trimester. Clin Dysmorphol 8: 53-58 (C) 1999 Lippincott Williams & Wilkins. C1 Brigham & Womens Hosp, Dept Pathol, Div Womens Perinatal Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Childrens Serv, Genet & Teratol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Genest, DR (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Womens Perinatal Pathol, 75 Francis St, Boston, MA 02115 USA. NR 24 TC 18 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0962-8827 J9 CLIN DYSMORPHOL JI Clin. Dysmorphol. PD JAN PY 1999 VL 8 IS 1 BP 53 EP 58 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 267EC UT WOS:000084343100010 PM 10327252 ER PT J AU Robbins, GK AF Robbins, GK TI Time for a new paradigm - Optimal management of patients with human immunodeficiency virus infection and AIDS - Editorial response SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID CD4 CELL COUNTS; PRIMARY CARE; HOSPITAL EXPERIENCE; CUBIC MILLIMETER; CONTROLLED TRIAL; HIV; ZIDOVUDINE; MORTALITY; DISEASE C1 Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Partners AIDS Res Ctr, Boston, MA USA. RP Robbins, GK (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, 55 Fruit St, Boston, MA 02114 USA. NR 37 TC 5 Z9 5 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN PY 1999 VL 28 IS 1 BP 23 EP 25 DI 10.1086/515082 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 162RE UT WOS:000078359900004 PM 10028064 ER PT J AU Krings, T Chiappa, KH Cuffin, BN Cochius, JI Connolly, S Cosgrove, GR AF Krings, T Chiappa, KH Cuffin, BN Cochius, JI Connolly, S Cosgrove, GR TI Accuracy of EEG dipole source localization using implanted sources in the human brain SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE artificial; dipole; human; source; localization ID REALISTICALLY SHAPED HEAD; INVERSE SOLUTIONS; PARTIAL EPILEPSY; SPHERICAL MODEL; MEG; PROPAGATION; PATTERNS; LOCATION; SPIKES AB Objectives: The location of electrical sources in the brain can be estimated by calculating inverse solutions in which the location, amplitude and orientation of the electrical sources are fitted to the scalp EEG. To assess localization accuracy of the moving dipole inverse solution algorithm (ISA), we studied two patients who had depth electrodes implanted for presurgical planning of epilepsy surgery. Methods: Artificial dipoles were created by connecting a single sine wave pulse generator to different pairs of electrodes in multiple orientations and depths. Surface EEG recordings of the resulting pulses were evaluated with the ISA using a 4 shell spherical head model and plotted on the subjects' MRI. Dipole localization errors were evaluated with respect to the number of averaged pulses, different electrode montages and different dipole locations and orientations. Results: Dipoles located at 40-57 mm from the scalp surface had localization errors that were greater than those located at 62-85 mm. Localization accuracy improved with increasing numbers of pulses and recording electrodes. Results with a standard 10-20 array of 21 electrodes showed an average localization error of 17 mm, whereas 41 electrodes improved this to 13 mm. Mean angular errors were 31 and 30 degrees, respectively. Conclusions: The ISA was able to differentiate between tangential and radial dipoles. We conclude that our implementation of the ISA is a useful and sound method for localizing electrical activity in the brain. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Serv Neurol, Clin Neurophysiol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Epilepsy Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, MIT, Francis Bitter Natl Magnet Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Chiappa, KH (reprint author), Massachusetts Gen Hosp, Serv Neurol, Clin Neurophysiol Lab, Boston, MA 02114 USA. NR 34 TC 55 Z9 57 U1 0 U2 1 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 JAN PY 1999 VL 110 IS 1 BP 106 EP 114 DI 10.1016/S0013-4694(98)00106-0 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 193CK UT WOS:000080118100015 PM 10348329 ER PT J AU Lipsky, BA Dorr, MB Magner, DJ Talbot, GH AF Lipsky, BA Dorr, MB Magner, DJ Talbot, GH TI Safety profile of sparfloxacin, a new fluoroquinolone antibiotic SO CLINICAL THERAPEUTICS LA English DT Article DE sparfloxacin; fluoroquinolones; antibiotics; safety; phototoxicity ID HUMAN LIVER-MICROSOMES; QUINOLONE ANTIBACTERIALS; RESPIRATORY-TRACT; PHARMACOKINETICS; THEOPHYLLINE; METABOLISM; CLEARANCE AB The safety profile of sparfloxacin, a newer fluoroquinolone antibiotic, was examined through an integrated analysis of safety data from 6 multicenter phase III trials. These consisted of 5 double-masked, randomized, comparative trials of sparfloxacin (a 400-mg oral loading dose followed by 200 mg/d for 10 days) versus standard therapies (erythromycin, cefaclor, ofloxacin, clarithromycin, and ciprofloxacin) and 1 open-label trial (noncomparative) in patients with: community-acquired pneumonia (2 trials); acute bacterial exacerbations of chronic bronchitis (1 trial); acute maxillary sinusitis (2 trials, one of which was the noncomparative trial); and complicated skin and skin-structure infections (1 trial). Overall, 401 (25.3%) of 1585 patients treated with sparfloxacin and 374 (28.1%) of 1331 receiving a comparator regimen experienced at least 1 adverse event considered to be related to the study medication. Photosensitivity reactions, usually of mild-to-moderate severity, were seen more frequently with sparfloxacin (7.4%) than with comparator agents (0.5%), whereas gastrointestinal reactions (diarrhea, nausea, dyspepsia, abdominal gain, vomiting, and flatulence), insomnia, and taste perversion were more common in patients taking comparator drugs (22.3% vs 12.1%, 4.3% vs 1.5%, and 2.9% vs 1.2%, respectively). Analysis of electrocardiographic findings showed that the mean change from baseline in QT interval corrected for heart rate (QT,) was significantly greater in sparfloxacin-treated patients (10 msec) than in patients given comparator drugs (3 msec), but no associated ventricular arrhythmias were detected. Adverse events led to discontinuation of study medication in 104 (6.6%) patients receiving sparfloxacin and Ils (8.9%) given comparator drugs. Sparfloxacin may be considered an appropriate choice for the treatment of certain community-acquired infections for patients who are not at risk for photosensitivity reactions or adverse events associated with prolongation of the QT(c) interval. C1 Univ Washington, Seattle, WA 98195 USA. RP Lipsky, BA (reprint author), VA Puget Sound Hlth Care Syst, Gen Internal Med Clin 111M, 1660 S Columbian Way, Seattle, WA 98108 USA. OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 31 TC 20 Z9 20 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD JAN PY 1999 VL 21 IS 1 BP 148 EP 159 DI 10.1016/S0149-2918(00)88275-2 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 169CQ UT WOS:000078730300011 PM 10090432 ER PT J AU Koipally, J Kim, J Jones, B Jackson, A Avitahl, N Winandy, S Trevisan, M Nichogiannopoulou, A Kelley, C Georgopoulos, K AF Koipally, J Kim, J Jones, B Jackson, A Avitahl, N Winandy, S Trevisan, M Nichogiannopoulou, A Kelley, C Georgopoulos, K TI Ikaros chromatin remodeling complexes in the control of differentiation of the hemo-lymphoid system SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT 64th Symposia: Signaling and Gene Expression in the Immune System CY JUN 02-07, 1999 CL NEW YORK, NEW YORK SP Alafi Capital Co, Amgen Inc, BASF Biores Corp, Bayer Corp, Bristol Myers Squibb Co, Chiron Corp, Chugai Res Inst Molec Med, Diagnost Prod Corp, Du Pont Pharmaceut Co, Forest Labs, Genentech Inc, Genet Inst, Glaxo Wellcome Inc, Hoechst Marion Roussel, Hoffmann La Roche Inc, Johnson & Johnson, Eli Lilly & Co, Merck Res Labs, New England BioLabs Inc, Novartis Pharma Res, OSI Pharmaceut Inc, Pall Corp, Parke Davis Pharmaceut Res, PE Biosyst, Pfizer Inc, Pharmacia & Upjohn Inc, Res Genet Inc, Schering Plough Corp, SmithKline Beecham Pharmaceut, Wyeth Ayerst Res, Zeneca Grp PLC ID TRANSCRIPTION FACTOR; HEMATOPOIETIC PROGENITORS; GENE LEADS; MUTATION; PROTEIN; DEFECTS; HELIOS; MICE C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Koipally, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RI Kelley, Clair/O-2688-2015 FU NIAID NIH HHS [R01 AI-33062, R01-AI-38342] NR 19 TC 13 Z9 13 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 1999 VL 64 BP 79 EP 86 DI 10.1101/sqb.1999.64.79 PG 8 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 317KW UT WOS:000087225400012 PM 11232340 ER PT J AU Sekiguchi, JM Gao, Y Gu, Y Frank, K Sun, Y Chaudhuri, J Zhu, C Cheng, HL Manis, J Ferguson, D Davidson, L Greenberg, ME Alt, FW AF Sekiguchi, JM Gao, Y Gu, Y Frank, K Sun, Y Chaudhuri, J Zhu, C Cheng, HL Manis, J Ferguson, D Davidson, L Greenberg, ME Alt, FW TI Nonhomologous end-joining proteins are required for V(D)J recombination, normal growth, and neurogenesis SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT 64th Symposia: Signaling and Gene Expression in the Immune System CY JUN 02-07, 1999 CL NEW YORK, NEW YORK SP Alafi Capital Co, Amgen Inc, BASF Biores Corp, Bayer Corp, Bristol Myers Squibb Co, Chiron Corp, Chugai Res Inst Molec Med, Diagnost Prod Corp, Du Pont Pharmaceut Co, Forest Labs, Genentech Inc, Genet Inst, Glaxo Wellcome Inc, Hoechst Marion Roussel, Hoffmann La Roche Inc, Johnson & Johnson, Eli Lilly & Co, Merck Res Labs, New England BioLabs Inc, Novartis Pharma Res, OSI Pharmaceut Inc, Pall Corp, Parke Davis Pharmaceut Res, PE Biosyst, Pfizer Inc, Pharmacia & Upjohn Inc, Res Genet Inc, Schering Plough Corp, SmithKline Beecham Pharmaceut, Wyeth Ayerst Res, Zeneca Grp PLC ID DNA-LIGASE-IV; STRAND-BREAK-REPAIR; SEVERE COMBINED IMMUNODEFICIENCY; CENTRAL-NERVOUS-SYSTEM; PROGRAMMED CELL-DEATH; PRE-B CELLS; CATALYTIC SUBUNIT; MAMMALIAN-CELLS; TARGETED DISRUPTION; ODORANT RECEPTORS C1 Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst,Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Dept Genet, Sch Med, Boston, MA 02115 USA. RP Sekiguchi, JM (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst,Ctr Blood Res, Boston, MA 02115 USA. OI Sekiguchi, JoAnn/0000-0002-7178-4258 FU NIAID NIH HHS [AI-35714, AI-01285, AI-01428] NR 69 TC 30 Z9 30 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 1999 VL 64 BP 169 EP 181 DI 10.1101/sqb.1999.64.169 PG 13 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 317KW UT WOS:000087225400021 PM 11232282 ER PT J AU Korsmeyer, SJ Gross, A Harada, H Zha, J Wang, K Yin, XM Wei, M Zinkel, S AF Korsmeyer, SJ Gross, A Harada, H Zha, J Wang, K Yin, XM Wei, M Zinkel, S TI Death and survival signals determine active/inactive conformations of pro-apoptotic BAX, BAD, and BID molecules SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT 64th Symposia: Signaling and Gene Expression in the Immune System CY JUN 02-07, 1999 CL NEW YORK, NEW YORK SP Alafi Capital Co, Amgen Inc, BASF Biores Corp, Bayer Corp, Bristol Myers Squibb Co, Chiron Corp, Chugai Res Inst Molec Med, Diagnost Prod Corp, Du Pont Pharmaceut Co, Forest Labs, Genentech Inc, Genet Inst, Glaxo Wellcome Inc, Hoechst Marion Roussel, Hoffmann La Roche Inc, Johnson & Johnson, Eli Lilly & Co, Merck Res Labs, New England BioLabs Inc, Novartis Pharma Res, OSI Pharmaceut Inc, Pall Corp, Parke Davis Pharmaceut Res, PE Biosyst, Pfizer Inc, Pharmacia & Upjohn Inc, Res Genet Inc, Schering Plough Corp, SmithKline Beecham Pharmaceut, Wyeth Ayerst Res, Zeneca Grp PLC ID PROGRAMMED CELL-DEATH; CYTOCHROME-C RELEASE; PROTEIN-KINASE-A; BCL-X-L; BH3 DOMAIN; ANCHORING PROTEIN; ION-CHANNEL; IN-VIVO; MITOCHONDRIA; PHOSPHORYLATION C1 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. RP Korsmeyer, SJ (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NR 70 TC 46 Z9 50 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 1999 VL 64 BP 343 EP 350 DI 10.1101/sqb.1999.64.343 PG 8 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 317KW UT WOS:000087225400042 PM 11232306 ER PT J AU Lopez-Rodriguez, C Aramburu, J Rakeman, AS Copeland, NG Gilbert, DJ Thomas, S Disteche, C Jenkins, NA Rao, A AF Lopez-Rodriguez, C Aramburu, J Rakeman, AS Copeland, NG Gilbert, DJ Thomas, S Disteche, C Jenkins, NA Rao, A TI NF-AT5: The NF-AT family of transcription factors expands in a new direction SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT 64th Symposia: Signaling and Gene Expression in the Immune System CY JUN 02-07, 1999 CL NEW YORK, NEW YORK SP Alafi Capital Co, Amgen Inc, BASF Biores Corp, Bayer Corp, Bristol Myers Squibb Co, Chiron Corp, Chugai Res Inst Molec Med, Diagnost Prod Corp, Du Pont Pharmaceut Co, Forest Labs, Genentech Inc, Genet Inst, Glaxo Wellcome Inc, Hoechst Marion Roussel, Hoffmann La Roche Inc, Johnson & Johnson, Eli Lilly & Co, Merck Res Labs, New England BioLabs Inc, Novartis Pharma Res, OSI Pharmaceut Inc, Pall Corp, Parke Davis Pharmaceut Res, PE Biosyst, Pfizer Inc, Pharmacia & Upjohn Inc, Res Genet Inc, Schering Plough Corp, SmithKline Beecham Pharmaceut, Wyeth Ayerst Res, Zeneca Grp PLC ID ACTIVATED T-CELLS; KAPPA-B SITE; NUCLEAR FACTOR; FACTOR NFAT1; FUNCTIONAL-CHARACTERIZATION; GENE-EXPRESSION; BINDING PROTEIN; CYCLOSPORINE-A; MICE LACKING; CALCINEURIN C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mammalian Genet Lab, Frederick, MD 21702 USA. Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. RP Lopez-Rodriguez, C (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RI Lopez-Rodriguez, C/G-4482-2014; Aramburu, J/G-8991-2014 OI Lopez-Rodriguez, C/0000-0002-2311-2406; Aramburu, J/0000-0001-9279-9523 FU NCI NIH HHS [CA-42471]; NIAID NIH HHS [AI-40127] NR 53 TC 24 Z9 26 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 1999 VL 64 BP 517 EP 526 DI 10.1101/sqb.1999.64.517 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 317KW UT WOS:000087225400062 PM 11233530 ER PT J AU Chen, L Rao, A Harrison, SC AF Chen, L Rao, A Harrison, SC TI Signal integration by transcription-factor assemblies: Interactions of NF-AT1 and AP-1 on the IL-2 promoter SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Article; Proceedings Paper CT 64th Symposia: Signaling and Gene Expression in the Immune System CY JUN 02-07, 1999 CL NEW YORK, NEW YORK SP Alafi Capital Co, Amgen Inc, BASF Biores Corp, Bayer Corp, Bristol Myers Squibb Co, Chiron Corp, Chugai Res Inst Molec Med, Diagnost Prod Corp, Du Pont Pharmaceut Co, Forest Labs, Genentech Inc, Genet Inst, Glaxo Wellcome Inc, Hoechst Marion Roussel, Hoffmann La Roche Inc, Johnson & Johnson, Eli Lilly & Co, Merck Res Labs, New England BioLabs Inc, Novartis Pharma Res, OSI Pharmaceut Inc, Pall Corp, Parke Davis Pharmaceut Res, PE Biosyst, Pfizer Inc, Pharmacia & Upjohn Inc, Res Genet Inc, Schering Plough Corp, SmithKline Beecham Pharmaceut, Wyeth Ayerst Res, Zeneca Grp PLC ID NF-KAPPA-B; CRYSTAL-STRUCTURE; NUCLEAR FACTOR; FACTOR NFAT1; DNA; CALCINEURIN; COMPLEX; GENE; FOS; JUN C1 Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Chen, L (reprint author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RI Chen, Lin/A-3392-2008 NR 25 TC 9 Z9 10 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 1999 VL 64 BP 527 EP 531 DI 10.1101/sqb.1999.64.527 PG 5 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 317KW UT WOS:000087225400063 PM 11232329 ER PT S AU Kahn, CR AF Kahn, CR BE Imura, H Kasuga, M Nakao, K TI Insulin signaling and the molecular mechanisms of insulin resistance SO COMMON DISEASE: GENETIC AND PATHOGENETIC ASPECTS OF MULTIFACTORIAL DISEASES SE INTERNATIONAL CONGRESS SERIES LA English DT Review CT 6th Uehara-Memorial-Foundation International Symposium on Common Disease CY JUN 30-JUL 02, 1999 CL TOKYO, JAPAN SP Uehara Mem Fdn ID DEPENDENT DIABETES-MELLITUS; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; NECROSIS-FACTOR-ALPHA; RECEPTOR SUBSTRATE-1 PHOSPHORYLATION; PROTEIN-TYROSINE-PHOSPHATASE; MEMBRANE GLYCOPROTEIN PC-1; AMINO-ACID POLYMORPHISM; SKELETAL-MUSCLE; GLUCOSE-TRANSPORT; KINASE-ACTIVITY C1 Joslin Diabet Ctr, Harvard Med Sch, Div Res, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Harvard Med Sch, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. NR 112 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50200-9 J9 INT CONGR SER PY 1999 VL 1181 BP 61 EP 77 PG 17 WC Genetics & Heredity; Medicine, General & Internal SC Genetics & Heredity; General & Internal Medicine GA BP49E UT WOS:000085307700008 ER PT J AU Michiels, B Molenberghs, G Lipsitz, SR AF Michiels, B Molenberghs, G Lipsitz, SR TI A pattern-mixture odds ratio model for incomplete categorical data. SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE categorical data; longitudinal data; missing data; multiple imputation; maximum likelihood estimation; odds ratio model ID NONIGNORABLE NONRESPONSE; MULTIPLE IMPUTATION; MISSING DATA; ORDINAL DATA; DROP-OUT; RESPONSES; JOINT AB Most models for incomplete data are formulated within the selection model framework. Pattern-mixture models are increasingly seen as a viable alternative, both from an interpretational as well as from a computational point of view (Little 1993, Hogan:and Laird 1997, Ekholm and Skinner 1998). Whereas most applications are either for continuous normally distributed data or for simplified categorical settings such as contingency tables, we show how a multivariate odds ratio model (Molenberghs and Lesaffre 1994, 1998) can be used to fit pattern-mixture models to repeated binary outcomes with continuous covariates. Apart from point estimation, useful methods-for interval estimation are presented and data from a clinical study are analyzed to illustrate the methods. C1 Limburgs Univ Ctr, Ctr Stat, B-3590 Diepenbeek, Belgium. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. NR 36 TC 9 Z9 9 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0361-0926 J9 COMMUN STAT-THEOR M JI Commun. Stat.-Theory Methods PY 1999 VL 28 IS 12 BP 2843 EP 2869 DI 10.1080/03610929908832453 PG 27 WC Statistics & Probability SC Mathematics GA 263JU UT WOS:000084122200004 ER PT J AU Abraham, HD Fava, M AF Abraham, HD Fava, M TI Order of onset of substance abuse and depression in a sample of depressed outpatients SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID DSM-III-R; STRUCTURED CLINICAL INTERVIEW; TEST-RETEST RELIABILITY; PSYCHIATRIC-DIAGNOSIS; SECONDARY DEPRESSION; MAJOR DEPRESSION; DRUG-DEPENDENCE; RISK-FACTORS; SYMPTOMS; COMORBIDITY AB Drug abuse has been thought to cause depression, or to serve as a form of self-medication for depression. Our objective was to examine whether specific types of drug abuse preceded or followed the onset of depression. A retrospective, blinded case-controlled assessment of the drug and depressive history of depressed outpatients was conducted. Three hundred seventy-five patients with major depressive disorder were evaluated for comorbid drug dependence using the Structured Clinical Interview for DSM-III-R (SCID). They were selected from the psychiatric outpatient department of a metropolitan teaching hospital and grouped into homogeneous classes of drug dependence including alcohol, cannabis, cocaine, amphetamine, LSD, hypnosedative, opiate, and polysubstance use. We determined the percent of depressed patients with each specific type of drug abuse, their age of onset of depression and onset of specific drug abuse, and the mean number of lifetime depressive episodes for each patient. We found that alcohol dependence followed the onset of first life depression by 4.7 years (P=.02, two-tailed). Among polydrug-dependent patients, each drug abused followed the onset of depression, except for LSD, which coincided with the onset of depression. Among polydrug users, cocaine dependence occurred 6.8 years after the first major depressive episode (P =.007) and alcohol dependence 4.5 years after the onset of depression (P =.007). Opiate and sedative users had the least number of lifetime depressive episodes (3.7), and LSD and cocaine users had the greatest number (12.2). We conclude that alcohol and cocaine use in this sample of depressed outpatients conformed to a pattern of self-medication. Copyright (C) 1999 by W,B. Saunders Company. C1 Brown Univ, Dept Psychiat & Human Behav, Providence, RI 02912 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Consolidated Dept Psychiat, Boston, MA USA. RP Abraham, HD (reprint author), 175 Bedford St,Suite 11, Lexington, MA 02420 USA. FU NIDA NIH HHS [R01 DA07120-01]; NIMH NIH HHS [R01 MH48483-01A1, R01 MH48483-01A2] NR 45 TC 73 Z9 73 U1 2 U2 11 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JAN-FEB PY 1999 VL 40 IS 1 BP 44 EP 50 DI 10.1016/S0010-440X(99)90076-7 PG 7 WC Psychiatry SC Psychiatry GA 158LD UT WOS:000078116200007 PM 9924877 ER PT J AU Webb, RH AF Webb, RH TI Theoretical basis of confocal microscopy SO CONFOCAL MICROSCOPY SE METHODS IN ENZYMOLOGY LA English DT Review ID OPTICAL MICROSCOPY C1 Massachusetts Gen Hosp, Schepens Eye Res Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Webb, RH (reprint author), Massachusetts Gen Hosp, Schepens Eye Res Inst, Boston, MA 02114 USA. NR 12 TC 34 Z9 42 U1 2 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1999 VL 307 BP 3 EP 20 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BP32T UT WOS:000084720900001 PM 10506964 ER PT J AU Melo, J Peters, JI AF Melo, J Peters, JI TI Low systemic vascular resistance: differential diagnosis and outcome SO CRITICAL CARE LA English DT Article DE systemic vascular resistance; hypotension; sepsis; cirrhosis; pancreatitis; adrenal insufficiency; anaphylaxis ID UNCOMPLICATED SEPTIC SHOCK; BERIBERI HEART-DISEASE; HEMODYNAMIC-CHANGES; ORGAN FAILURE; HYPERDYNAMIC SHOCK; LIVER-CIRRHOSIS; CARDIAC-OUTPUT; NITRIC-OXIDE; INJURY; INSUFFICIENCY AB Objective: To determine the frequency and prognosis of the various causes of low systemic vascular resistance (SVR). Design: Analysis of consecutive patients over a 5-year period; retrospective review. Setting: Medical intensive care unit of a large university hospital. Patients: Fifty-five patients with unexplained hypotension and a SVR less than 800 dynes x s/cm(5). Background: There are minimal data in the medical literature determining the frequency or outcome of patients with a low SVR that is unrelated to sepsis or the sepsis syndrome. We retrospectively reviewed and analyzed all hemodynamic data in a large university hospital over a 5-year period to determine the frequency and prognosis of the various causes of low SVR. Fifty-five patients with unexplained hypotension and a SVR less than 800 dynes x s/cm(5) were identified. Main results: Twenty-two patients (Groups 1 and 2) met the criteria for sepsis syndrome. The mean SVR for this group was 445 +/- 168 dynes x s/cm(5) with an associated mortality of 50%. Group 3 contained 20 patients with possible sepsis. Thirteen patients (Group 4) were nonseptic. The mean SVR of this group was 435 +/- 180 dynes x s/cm(5) with an associated mortality of 46%. Extremely low SVR (below 450 dynes x s/cm(5)) was associated with a significantly higher mortality regardless of the etiology. Conclusions: At least a quarter of patients with hypotension and a low SVR have nonseptic etiologies. The patients with nonseptic etiologies have a similar mortality to septic patients. Clinicians should be aware of the wide spectrum of conditions that induce a low SVR. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Pulm Dis Crit Care Med, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Mem Vet Hosp Div, San Antonio, TX USA. RP Peters, JI (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Pulm Dis Crit Care Med, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 49 TC 8 Z9 8 U1 0 U2 2 PU CURRENT SCIENCE LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LE, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PY 1999 VL 3 IS 3 BP 71 EP 77 DI 10.1186/cc343 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 271JD UT WOS:000084589700004 ER PT J AU Souba, WW AF Souba, WW TI Hepatic arginine metabolism: Major questions remain unanswered SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE amino acid transport; arginine; system y(+); liver; membrane vesicles; critical illness ID AMINO-ACID-TRANSPORT; HUMAN LIVER; STIMULATION; RAT C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Souba, WW (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 15 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 1999 VL 27 IS 1 BP 25 EP 26 DI 10.1097/00003246-199901000-00016 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 159ET UT WOS:000078159400016 PM 9934884 ER PT J AU Schnitzer, JJ Thompson, JE Hedrick, HL AF Schnitzer, JJ Thompson, JE Hedrick, HL TI A new ventilator improves CO2 removal in newborn lambs with congenital diaphragmatic hernia SO CRITICAL CARE MEDICINE LA English DT Article DE intratracheal pulmonary ventilation; congenital diaphragmatic hernia; barotrauma; reverse thrust catheter; microprocessor controlled ventilator; anatomic dead space; peak inspiratory pressure; CO2 removal; sheep model; mechanical ventilation; high frequency ventilation ID INTRATRACHEAL PULMONARY VENTILATION; MECHANICAL VENTILATION; AIRWAY PRESSURES; MODEL; SHEEP AB Objectives: To demonstrate improved ventilation with intratracheal pulmonary ventilation (ITPV) in newborn lambs with congenital diaphragmatic hernia, using a new microprocessor controlled ITPV specific ventilator. Design: Prospective study, with each animal serving as its own control (paired data). Setting: Large animal research laboratory. Subjects: Diaphragmatic hernias were created surgically in seven fetal sheep on gestational day 100 (term = 145 days). Interventions: Lambs (2.7 to 5.0 kg) were delivered by cesarean section anywhere between gestational days 136 and 140, Arterial and venous catheterizations, bilateral chest tube thoracostomies, and tracheostomies were performed while the lambs received placental bypass. Initially, congenital diaphragmatic hernia lambs were supported on conventional pressure control mechanical ventilation to achieve steady state with measurements of baseline vital signs, arterial blood gases, and ventilatory settings. ITPV was instituted while maintaining constant peak carinal pressures and oxygen saturations. Statistical comparisons were made using the paired t-test, Measurements and Main Results: Postductal PaCO2 decreased from 110 +/- 21 (SD) torr (14.7 +/- 2.8 kPa) to 52 +/- 24 torr (6.93 +/- 3.2 kPa; p=.0014) on ITPV, Simultaneously, pH improved from 7.04 +/- 0.07 to 7.31 +/- 0.15 (p =.0012) and minute ventilation increased from 0.66 +/- 0.40 to 4.00 +/- 1.35 L/min (p =.0016), Peak carinal pressures and postductal PaCO2 were unchanged. Conclusions: ITPV significantly improved CO2 removal in newborn lambs with diaphragmatic hernias without increasing airway pressures or changing oxygenation. Based on these results, we are conducting human clinical trials. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Surg Res Labs,Pediat Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Childrens Hosp, Dept Resp Therapy, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Schnitzer, JJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Surg Res Labs,Pediat Surg Serv, 55 Fruit St,Warren 11, Boston, MA 02114 USA. FU NCI NIH HHS [CA09535]; NHLBI NIH HHS [HL03132] NR 28 TC 6 Z9 6 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 JAN PY 1999 VL 27 IS 1 BP 109 EP 112 DI 10.1097/00003246-199901000-00037 PG 4 WC Critical Care Medicine SC General & Internal Medicine GA 159ET UT WOS:000078159400035 PM 9934903 ER PT J AU Tabbutt, S Miura, T Schermerhorn, M Newburger, JW Hickey, PR Mayer, JE Neufeld, EJ AF Tabbutt, S Miura, T Schermerhorn, M Newburger, JW Hickey, PR Mayer, JE Neufeld, EJ TI Time course of early ICAM-1 mRNA induction in lung and ventricle following cardiopulmonary bypass in lambs. SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 Childrens Hosp, Dana Farber Canc Inst, Dept Cardiol, Boston, MA 02115 USA. Childrens Hosp, Dana Farber Canc Inst, Dept Cardiac Surg, Boston, MA 02115 USA. Childrens Hosp, Dana Farber Canc Inst, Dept Anesthesia, Boston, MA 02115 USA. Childrens Hosp, Dana Farber Canc Inst, Div Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RI Neufeld, Ellis/F-9331-2011 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 1999 VL 27 IS 1 SU S MA 60 BP A55 EP A55 DI 10.1097/00003246-199901001-00100 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 160NN UT WOS:000078236900104 ER PT J AU Cooper, RA AF Cooper, RA TI Engineering manual and electric powered wheelchairs SO CRITICAL REVIEWS IN BIOMEDICAL ENGINEERING LA English DT Review DE wheelchair; design; engineering; standards; controls; human factors ID SPINAL-CORD INJURY; LOCAL COORDINATE SYSTEM; STATIC REAR STABILITY; OCCUPIED WHEELCHAIRS; PROPULSION TECHNIQUE; RACING WHEELCHAIR; PUSHRIM FORCES; 2 SPEEDS; 3-DIMENSIONAL KINEMATICS; ASSISTIVE TECHNOLOGY AB The sophistication required to develop and properly configure a wheelchair is illustrated by the amount and complexity of the research being conducted. At this time there appears to be between 1.5 and 2.0 million full-time wheelchair users within the United States. The reliance of the user on the wheelchair and the amount of time in the wheelchair provide significant challenges for the wheelchair design engineer. Currently there are a wide variety of wheelchair designs that are commercially available. These wheelchairs accommodate a variety of people's needs, and represent significant progress. The current trend among manufacturers of manual wheelchairs seems to be cost-reduction engineering. The ergonomics of long-term wheelchair use are critical to the advancement of wheelchair design and to the clinical selection of wheelchairs. Electric powered wheelchairs appear to be progressing faster than nearly all other types of wheelchairs. This is due to the availability of computing power with low cost microcontrollers and associated peripherals. The greater range and availability of sensors are also making changes into the design of electric powered wheelchairs. The interaction between an electric powered wheelchair and the user can be extremely complex. In many cases, individual solutions are necessary. One of the more challenging questions is determining the abilities of the user required to drive an electric powered wheelchair effectively. There have been substantial improvements in the engineering of all wheelchairs. However, there remain significant issues to be addressed. C1 Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15261 USA. VA Pittsburgh Hlth Care Syst, Human Engn Res Labs, Pittsburgh, PA USA. UPMC Hlth Syst, Div Phys Med & Rehabil, Pittsburgh, PA USA. RP Cooper, RA (reprint author), Univ Pittsburgh, Dept Rehabil Sci & Technol, 5044 Forbes Tower, Pittsburgh, PA 15261 USA. NR 147 TC 26 Z9 26 U1 3 U2 5 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 USA SN 0278-940X J9 CRIT REV BIOMED ENG JI Crit. Rev. Biomed. Eng. PY 1999 VL 27 IS 1-2 BP 27 EP 73 PG 47 WC Engineering, Biomedical SC Engineering GA 235KA UT WOS:000082539800002 PM 10638849 ER PT J AU Ecker, JL Parer, JT AF Ecker, JL Parer, JT TI Obstetric evaluation of fetal acid-base balance SO CRITICAL REVIEWS IN CLINICAL LABORATORY SCIENCES LA English DT Review DE obstetric evaluation; fetal acid-base; antepartum; intrapartum; cordocentesis ID UMBILICAL-CORD BLOOD; INTRAPARTUM ASSESSMENT; GAS DETERMINATIONS; SCALP STIMULATION; GESTATIONAL-AGE; BIRTH ASPHYXIA; APGAR SCORE; PH; COMPLICATIONS; OXYGENATION AB Several techniques may be used to evaluate fetal acid-base status during the ante- and intrapartum periods. Percutaneous blood sampling (cordocentesis) may be used to measure standard blood-gas parameters while the fetus is still in utero, but because of the risks associated with such procedures and the limited clinical utility of the results, this procedure is recommended for blood gas analysis only as part of a research protocol. Intrapartum blood specimens may be safely obtained via fetal scalp sampling, but the need for such sampling has been dramatically reduced by the use of other noninvasive tests such as fetal scalp stimulation or vibroacoustic stimulation. Finally, assay of blood obtained from a segment of umbilical cord collected at delivery indicates acid-base status at birth, but the range of normal values is wide, and only the most abnormal results have any prognostic significance. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. RP Parer, JT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Mem Obstet & Gynecol Serv, Boston, MA 02114 USA. NR 67 TC 2 Z9 2 U1 0 U2 0 PU CRC PRESS INC PI BOCA RATON PA 2000 CORPORATE BLVD NW, JOURNALS CUSTOMER SERVICE, BOCA RATON, FL 33431 USA SN 1040-8363 J9 CRIT REV CL LAB SCI JI Crit. Rev. Clin. Lab. Sci. PY 1999 VL 36 IS 5 BP 407 EP 451 DI 10.1080/10408369991239268 PG 45 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 251AX UT WOS:000083423400001 PM 10560887 ER PT J AU Huang, LL Guan, RJ Pardee, AB AF Huang, LL Guan, RJ Pardee, AB TI Evolution of transcriptional control from prokaryotic beginnings to eukaryotic complexities SO CRITICAL REVIEWS IN EUKARYOTIC GENE EXPRESSION LA English DT Article DE protein complexes; chromatin structure; histone acetylation; DNA methylation; superrepression ID HISTONE DEACETYLASE COMPLEX; DNA METHYLATION; REPRESS TRANSCRIPTION; BINDING; PROTEINS; ACETYLTRANSFERASES; ACETYLATION; ACTIVATION; PATTERNS; PROMOTER AB Mechanisms for regulating gene transcription became increasingly complex as organisms evolved. In prokaryotes the relatively simple mechanism of repression is based on a few proteins that bind to specific DNA sequences in a ligand-dependent fashion. In eukaryotes large complexes that include ligand binding proteins regulate transcription. Lower eukaryotes developed an additional level of control based on protein complexes that include modifying enzymes. The DNA/histone complex, in combination with gene-specific transcriptional factors, is the basis of gene regulation in eukaryotes. Higher eukaryotes took regulation a level further by methylating CpGs in promoter sequences of DNA, thereby allowing binding of histone deacetylases and inhibiting transcription. Finally, long-lasting "superrepression" provides another mechanism for coordinate transcriptional regulation of large blocks of genes. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. FU NCI NIH HHS [CA 61253] NR 35 TC 19 Z9 21 U1 0 U2 3 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 USA SN 1045-4403 J9 CRIT REV EUKAR GENE JI Crit. Rev. Eukaryot. Gene Expr. PY 1999 VL 9 IS 3-4 BP 175 EP 182 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 275HT UT WOS:000084815300002 PM 10651234 ER PT J AU Qureshi, NH Chiocca, EA AF Qureshi, NH Chiocca, EA TI A review of gene therapy for the treatment of central nervous system tumors SO CRITICAL REVIEWS IN ONCOGENESIS LA English DT Review DE gene therapy; vectors; viruses; brain tumors; central nervous system ID HERPES-SIMPLEX VIRUS; EXPERIMENTAL BRAIN-TUMORS; THYMIDINE KINASE GENE; PSEUDOTYPED RETROVIRAL VECTORS; HUMAN GLIOMA-CELLS; IN-VIVO; ADENOASSOCIATED VIRUS; HIGH-TITER; RAT-BRAIN; HSV-TK AB The transfer of genes into tumors of the central nervous system has been touted as a novel treatment. However, several scientific and technological hurdles will have to be resolved before such strategies become useful clinical tools. This review summarizes the current knowledge in the field. Some of the gene delivery vectors employed both preclinically and clinically are those based on retroviruses, herpes simplex viruses, adenoviruses, adeno-associated viruses, and reoviruses, Cells such as fibroblasts and neural progenitor cells may also provide therapeutic value. These vectors are used to deliver into the tumor cell a variety of anticancer genes, such as those that activate chemotherapy agents, increase tumor immunogenicity, modulate tumor apoptosis and/or angiogenesis. One of the issues confronting such therapeutic strategies revolves around the blood-brain-barrier that may limit the penetration of vectors and genes form the circulation into the tumor. Results from a variety of clinical trials are becoming available. While the safety of this treatment strategy appears to have been established, therapeutic efficacy has been lacking. Additional refinements in the basic technology of vector construction and further understanding of the basic biology of gene transfer and expression will help in establishing gene therapy as clinically useful against brain tumors. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv,Mol Neurooncol Labs, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Brain Tumor Ctr, Boston, MA 02129 USA. RP Chiocca, EA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv,Mol Neurooncol Labs, 13th St,Bldg 149, Boston, MA 02129 USA. NR 134 TC 9 Z9 10 U1 0 U2 0 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 USA SN 0893-9675 J9 CRIT REV ONCOGENESIS JI Crit. Rev. Oncog. PY 1999 VL 10 IS 4 BP 261 EP 274 PG 14 WC Biochemistry & Molecular Biology; Oncology; Cell Biology SC Biochemistry & Molecular Biology; Oncology; Cell Biology GA 280PJ UT WOS:000085110900001 PM 10654926 ER PT J AU Levine, B AF Levine, B TI Effect of eprosartan and enalapril in the treatment of black hypertensive patients: Subgroup analysis of a 26-week double-blind, multicentre study SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article DE eprosartan; angiotensin II antagonists; enalapril; angiotensin-converting enzyme (ACE) inhibitors; black hypertensive patients ID CONVERTING ENZYME-INHIBITION; ANTIHYPERTENSIVE AGENTS; RENAL HEMODYNAMICS; AFRICAN-AMERICANS; PATHOPHYSIOLOGY; THERAPY; COUGH AB A double-blind comparator study was performed in 528 hypertensive patients [baseline sitting diastolic blood pressure (SitDBP) 95-114 mmHg]. The primary objective was to compare the incidence of drug-related cough in patients treated with enalapril and eprosartan. The secondary objective was to compare antihypertensive efficacy between treatments. This paper reports the results of a prespecified subgroup analysis performed in the 40 black patients recruited into the study. Eprosartan was titrated from 200 mg b.i.d. to 300 mg b.i.d. and enalapril from 5 mg o.d. to 20 mg o.d. over 12 weeks. Hydrochlorothiazide (HCTZ) 12.5-25 mg o.d. could be added where required to the treatment for the final six weeks of the titration phase if SitDBP greater than or equal to 90 mmHg. Patients received the maximum titrated dosage during the maintenance phase. In the study overall, the incidence of cough at monotherapy endpoint was significantly higher in the enalapril-treated group than in the eprosartan-treated group (p = 0.018). This trend was reflected in the black subgroup but the numbers were 200 small to confirm significance. At study endpoint the mean change in SitDBP was -10.5 +/- 1.9 mmHg and -9.6 +/- 2.4 mmHg for eprosartan-treated and enalapril-treated patients, respectively The mean change in SitSBP for eprosartan-treated black patients was -18.8 +/- 3.5 mmHg and for enalapril-treated patients was -10.5 +/- 3.7 mmHg. The black subpopulation mirrored the response of the study as a whole. Both treatments lowered BP with a further reduction evident following the addition of HCTZ at week 18. In conclusion, eprosartan is effective and appears to be safe in black hypertensive patients. The combination of eprosartan and HCTZ was also well tolerated and provided additional efficacy in those patients not responding to eprosartan alone. The incidence of treatment-associated cough in the black subgroup was low, but there were no apparent differences between treatment groups. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Levine, B (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd,W111L, Los Angeles, CA 90073 USA. NR 20 TC 21 Z9 23 U1 0 U2 0 PU LIBRAPHARM PI NEWBURY PA C/O DR. PETER L CLARKE, GEMINI HOUSE, 162 CRAVEN RD, NEWBURY, BERKSHIRE, ENGLAND RG14 5NR SN 0300-7995 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PY 1999 VL 15 IS 1 BP 25 EP 32 DI 10.1185/03007999909115170 PG 8 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 176GC UT WOS:000079142200004 PM 10216808 ER PT J AU Schmulson, MJ Mayer, EA AF Schmulson, MJ Mayer, EA TI Evolving concepts in irritable bowel syndrome SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article ID SLEEP; CARE; MOTILITY; DISTRESS; SEEKING; MOTOR AB Converging evidence from investigations of the peripheral and central aspects of bidirectional brain-gut interactions is beginning to shape a pathophysiological model of irritable bowel syndrome (IBS) and related functional gastrointestinal (GI) disorders. This neurobiological model includes alterations in autonomic, neuroendocrine, and pain modulatory mechanisms. The frequent association of IBS and other functional GI disorders with co-morbid affective disorders and temporal association of symptom exacerbation with psychosocial or physical stressors are consistent with alterations in the neurobiological mechanisms underlying the central stress response. Renewed interest in drug development for IBS has resulted in development of instruments for the better assessment of the impact of global symptoms on quality of life and in the development of candidate compounds undergoing clinical evaluation. C1 W Los Angeles Vet Affairs Med Ctr, CURE UCLA Neuroenter Dis Program, Dept Med, Div Infect Dis, Los Angeles, CA 90073 USA. RP Schmulson, MJ (reprint author), W Los Angeles Vet Affairs Med Ctr, CURE UCLA Neuroenter Dis Program, Dept Med, Div Infect Dis, Bldg 115,Room 223,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 52 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD JAN PY 1999 VL 15 IS 1 BP 16 EP 21 DI 10.1097/00001574-199901000-00004 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 173JK UT WOS:000078977300004 PM 17023912 ER PT J AU Miller, JB Schaefer, L Dominov, JA AF Miller, JB Schaefer, L Dominov, JA TI Seeking muscle stem cells SO CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY, VOL 43 SE CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY LA English DT Review ID REGULATORY FACTOR PROTEINS; MYOTOME PRECURSOR CELLS; QUAIL-CHICK CHIMERAS; MOUSE SOLEUS MUSCLE; C-MET RECEPTOR; SKELETAL-MUSCLE; SATELLITE CELLS; NEURAL-TUBE; SONIC HEDGEHOG; FIBER TYPES C1 Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02215 USA. Massachusetts Gen Hosp, Neuromuscular Lab, Charlestown, MA 02129 USA. RP Miller, JB (reprint author), Massachusetts Gen Hosp, Neuromuscular Lab, Charlestown, MA 02129 USA. NR 155 TC 74 Z9 77 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2153 J9 CURR TOP DEV BIOL PY 1999 VL 43 BP 191 EP 219 PG 29 WC Developmental Biology SC Developmental Biology GA BQ13D UT WOS:000087256300006 PM 9891887 ER PT B AU Flanz, JB Bradley, SG Goitein, M Smith, S Jongen, Y Bailey, J Ladeuze, M Schmidt, S Schubert, J VanMeerbeeck, A Hurn, T Junge, R AF Flanz, JB Bradley, SG Goitein, M Smith, S Jongen, Y Bailey, J Ladeuze, M Schmidt, S Schubert, J VanMeerbeeck, A Hurn, T Junge, R BE Baron, E Lieuvin, M TI Initial equipment commissioning of the Northeast Proton Therapy Center SO CYCLOTRONS AND THEIR APPLICATIONS 1998 LA English DT Proceedings Paper CT 15th International Conference on Cyclotrons and Their Applications CY JUN 14-19, 1998 CL CAEN, FRANCE SP Int Union Pure & Appl Phys, Commissariat Energie Atom, CNRS, Consril Gen & Conseil Reg Lower Normandy, GANIL AB The equipment for the Northeast Proton Therapy Center (NPTC) is currently being installed and commissioned in Boston. Aspects of the facility goals, design, and status will be presented. C1 Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. RP Flanz, JB (reprint author), Massachusetts Gen Hosp, NE Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND BN 0-7503-0663-7 PY 1999 BP 319 EP 322 PG 4 WC Nuclear Science & Technology; Physics, Applied; Physics, Atomic, Molecular & Chemical; Physics, Nuclear SC Nuclear Science & Technology; Physics GA BN49J UT WOS:000082032800081 ER PT J AU Okano, M Takebayashi, S Okumura, K Li, E AF Okano, M Takebayashi, S Okumura, K Li, E TI Assignment of cytosine-5 DNA methyltransferases Dnmt3a and Dnmt3b to mouse chromosome bands 12A2-A3 and 2H1 by in situ hybridization SO CYTOGENETICS AND CELL GENETICS LA English DT Article ID CLONING; CELLS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiovasc Res Ctr, Charlestown, MA USA. Mie Univ, Fac Bioresources, Biol Chem Lab, Tsu, Mie, Japan. RP Okano, M (reprint author), Massachusetts Gen Hosp E, Cardiovasc Res Ctr, 149 13th St, Charlestown, MA 02129 USA. FU NIGMS NIH HHS [GM52106] NR 9 TC 24 Z9 26 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0171 J9 CYTOGENET CELL GENET JI Cytogenet. Cell Genet. PY 1999 VL 86 IS 3-4 BP 333 EP 334 DI 10.1159/000015331 PG 2 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 260LC UT WOS:000083951300035 PM 10575238 ER PT J AU Schmid, I Ferbas, J Uittenbogaart, CH Giorgi, JV AF Schmid, I Ferbas, J Uittenbogaart, CH Giorgi, JV TI Flow cytometric analysis of live cell proliferation and phenotype in populations with low viability SO CYTOMETRY LA English DT Article; Proceedings Paper CT 19th Congress of the International-Society-for-Analytical-Cytology CY MAR, 1998 CL COLORADO SPRINGS, COLORADO SP Int Soc Analyt Cytol DE flow cytometry; dead cell exclusion; fixation; permeabilization; cell surface immunofluorescence; DNA content analysis; 7-amino-actinomycin D; pyronin Y ID DUAL-COLOR IMMUNOFLUORESCENCE; NUCLEIC-ACIDS; MEASURING APOPTOSIS; SURFACE PHENOTYPE; NONVIABLE CELLS; CYCLE ANALYSIS; PYRONIN-Y; DNA; FIXATION; 7-AMINO-ACTINOMYCIN-D AB Background: Combined analysis of DNA content and immunofluorescence on single cells by flow cytometry provides information on the proliferative response of subpopulations to stimuli in mixed cell preparations; however, in low-viability cell preparations, dead cells interfere with accurate flow cytometric data analysis because of nonspecific binding of antibodies and altered DNA-staining profiles. Light scatter differences between nonviable and viable cells are unreliable, particularly after the cell permeabilization step that is necessary for DNA staining. We developed a method for identification of nonviable cells by fluorescence in cell preparations that are stained simultaneously for cell surface or intracellular immunofluorescence and DNA content. Materials and Methods: Nonviable cells that have lost membrane integrity are identified by uptake of 7-amino-actinomycin D (7-AAD). Transfer of 7-AAD from stained nonviable cells to unstained viable cells after permeabilization is prevented by blocking DNA binding with nonfluorescent actinomycin D (AD). Pyronin Y(G) (PY) is used for DNA staining because the orange spectral emission of PY call be separated from the green fluorescein isothiocyanate (FITC) emission and the fed emission of I-AAD, respectively. Results: Application of the method to the analysis of the T-cell leukemia cell line Molt-4f and of cultured human peripheral blood mononuclear cells is presented. In both cell preparations, 7-AAD staining permitted reliable dead cell exclusion. Live, 7-AAD-negative Molt-4f cells showed higher expression levels of cell surface CD4 and of intracellular CD3, showed a higher proportion of cells in the GI phase of the cell cycle, and showed a lower coefficient of variation of the G(1) peak compared with data obtained from all the cells in the preparation. Live, CD8(+) lymphocytes from OKT3-stimulated cultures of human peripheral blood mononuclear cells showed a specific proliferative response as measured by DNA content analysis. Conclusions: The results show that cells stained with FITC-labeled antibodies can be analyzed by single-laser flow cytometry for DNA content combined with dead cell discrimination. Furthermore, they emphasize the need for exclusion of dead cells from the analysis of cell preparations with low viability to obtain reliable data on immunofluorescence and cell-cycle distributions. Cytometry 35: 64-74, 1999. (C) 1999 Wiley-Liss, Inc. C1 Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Microbiol & Immunol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90095 USA. RP Schmid, I (reprint author), Univ Calif Los Angeles, Sch Med, Dept Med, 12-236 Factor Bldg, Los Angeles, CA 90095 USA. EM schmid@mednet.ucla.edu FU NCI NIH HHS [CA-16042]; NIAID NIH HHS [AI-28697]; NICHD NIH HHS [HD-29341] NR 39 TC 25 Z9 25 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOMETRY JI Cytometry PD JAN 1 PY 1999 VL 35 IS 1 BP 64 EP 74 DI 10.1002/(SICI)1097-0320(19990101)35:1<64::AID-CYTO9>3.0.CO;2-Y PG 11 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 154LM UT WOS:000077890700008 PM 10554182 ER PT J AU Webb, IJ Schlossman, RL Jiroutek, M Doss, D Cohen, CA Freeman, A Schott, DM Anderson, KC AF Webb, IJ Schlossman, RL Jiroutek, M Doss, D Cohen, CA Freeman, A Schott, DM Anderson, KC TI Predictors of high yield and purity of CD34(+) cell-selected PBPC, collected from patients with multiple myeloma SO CYTOTHERAPY LA English DT Article DE CD34(+) cell selection; peripheral blood stem cell transplantation; stem cell purification; multiple myeloma ID BONE-MARROW TRANSPLANTATION; HIGH-DOSE CHEMOTHERAPY; NON-HODGKINS-LYMPHOMA; BLOOD STEM-CELLS; PERIPHERAL-BLOOD; AUTOLOGOUS TRANSPLANTATION; HEMATOPOIETIC RECOVERY; BREAST-CANCER; MOBILIZATION; THERAPY AB Background Wide ranges in cell recovery and purity may be observed following CD34(+) cell selection of mobilized HPC components. Characteristics of the mobilized HPC, associated with isolation of a high CD34(+) cell yield and purity following cell selection, have yet to be defined. Methods Cell numbers and purities were determined before and after 56 CD34(+) cell-selection procedures, performed using the CellPro Ceprate SC system from April 1997 to February 1998. HPC were collected from 28 patients with multiple myeloma, following cyclophosphamide (60 mg/kg) and G-CSF (10 mu g/kg) mobilization. Results. A median of 47.9% (range 1.5-109.6%) CD34(+) cells were recovered ill the enriched (ENR) fraction. A linear correlation existed between total CD34(+) cells in the ENR fraction and total CD34(+) cells in the START fraction (R2 = 0.93); there was a log-arithmic correlation between CD34 ENR fraction purity and START fraction purity (R2 = 0.73). A START CD34(+) cell purity > 0.42% improved purity in the ENR fraction. A median of one (range one to nine) procedure was required to isolate 2 x 10(6) CD34(+) cells/kg. Three patients pretreated with alkylating agents failed to mobilize adequate numbers of HPC. Discussion Isolation of highly purified CD34(+) cell-selected components using the Ceprate SC system is dependent on the CD34(+) purity of the leukapheresis component collected. Mobilization regimens should be used to maximize CD34(+) cell purity in stem cell autografts if CD34(+) cell selection is to be performed. Similar strategies should be used to evaluate other cell-selection devices as they become available. C1 Dana Farber Canc Inst, Cell Manipulat Gene Transfer & Cryopreservat Labs, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Webb, IJ (reprint author), Dana Farber Canc Inst, Cell Manipulat Gene Transfer & Cryopreservat Labs, 44 Binney St,Dana 530, Boston, MA 02115 USA. FU NCI NIH HHS [P01 CA78378] NR 36 TC 0 Z9 0 U1 0 U2 0 PU ISIS MEDICAL MEDIA LTD PI OXFORD PA 59 ST ALDATES, OXFORD OX1 1ST, ENGLAND SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 1999 VL 1 IS 3 BP 175 EP 182 PG 8 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 277ZU UT WOS:000084964100003 PM 12881173 ER PT S AU Sutton, JP Sha, DD Perry, S Guan, L AF Sutton, JP Sha, DD Perry, S Guan, L BE Dubey, AC Harvey, JF Broach, JT Dugan, RE TI Enhancing mine signatures in sonar images using nested neural networks SO DETECTION AND REMEDIATION TECHNOLOGIES FOR MINES AND MINELIKE TARGETS IV, PTS 1 AND 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Detection and Remediation Technologies for Mines and Minelike Targets IV Conference CY APR 05-09, 1999 CL ORLANDO, FL SP SPIE DE neural networks; mine hunting; image enhancement; hierarchical networks; dynamic clustering; pattern recognition AB An adaptive image regularization algorithm', based on the Network of Networks (NoN) neural computing theory(2), is applied to enhance mine signatures. The algorithm, developed by Guan and Sutton (GS), uses vector connections among model neurons (pixels) to delineate dynamic boundaries corresponding to critical features of images. The boundaries subdivide large networks into many smaller networks, where each smaller network has, in many instances, attractor properties. In this report, the GS algorithm is applied to deblur and segment three sets of underwater mine data. The results suggest that the CS algorithm requires minimal training, performs well under inhomogeneous conditions and generates contours, which can be fed into other NoN architectures for further processing, including classification. C1 Massachusetts Gen Hosp, Neurol Syst Grp, Boston, MA 02129 USA. RP Sutton, JP (reprint author), Massachusetts Gen Hosp, Neurol Syst Grp, Bldg 149,9th Fl,13th St, Boston, MA 02129 USA. NR 11 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3184-2 J9 P SOC PHOTO-OPT INS PY 1999 VL 3710 BP 570 EP 577 DI 10.1117/12.357079 PN 1&2 PG 8 WC Engineering, Electrical & Electronic; Instruments & Instrumentation; Optics SC Engineering; Instruments & Instrumentation; Optics GA BN59G UT WOS:000082322300058 ER PT J AU Ghiglione, C Perrimon, N Perkins, LA AF Ghiglione, C Perrimon, N Perkins, LA TI Quantitative variations in the level of MAPK activity control patterning of the embryonic termini in Drosophila SO DEVELOPMENTAL BIOLOGY LA English DT Article ID RECEPTOR TYROSINE KINASE; EPIDERMAL GROWTH-FACTOR; EGF RECEPTOR; BODY PATTERN; PHOSPHATASE CORKSCREW; SIGNAL-TRANSDUCTION; INSULIN-RECEPTOR; GENE-EXPRESSION; PC12 CELLS; TORSO AB We have examined the role in patterning of quantitative variations of MAPK activity in signaling from the Drosophila Torso (Tor) receptor tyrosine kinase (RTK). Activation of Tor at the embryonic termini leads to differential expression of the genes tailless and huckebein. We demonstrate, using a series of mutations in the signal transducers Corkscrew/SHP-2 and D-Raf, that quantitative variations in the magnitude of MAPK activity trigger both qualitatively and quantitatively distinct transcriptional responses. We also demonstrate that two chimeric receptors, Tor(extracellular)-Egfr(cytoplasmic) and Tor(extracellular)-Sev(cytoplasmic) cannot fully functionally replace the wild-type Tor receptor, revealing that the precise activation of MAPK involves not only the number of activated RTK molecules but also the magnitude of the signal generated by the RTK cytoplasmic domain. Altogether, our results illustrate how a gradient of MAPK activity controls differential gene expression and, thus, the establishment of various cell fates. We discuss the roles of quantitative mechanisms in defining RTK specificity. (C) 1999 Academic Press. 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, Massachusetts Gen Hosp, Sch Med, Pediat Surg Res Labs, Boston, MA 02114 USA. RP Ghiglione, C (reprint author), Harvard Univ, Sch Med, Dept Genet, 200 Longwood Ave, Boston, MA 02115 USA. NR 63 TC 34 Z9 34 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JAN 1 PY 1999 VL 205 IS 1 BP 181 EP 193 DI 10.1006/dbio.1998.9102 PG 13 WC Developmental Biology SC Developmental Biology GA 162VN UT WOS:000078367800014 PM 9882506 ER PT J AU Majumdar, A Drummond, IA AF Majumdar, A Drummond, IA TI Podocyte differentiation in the absence of endothelial cells as revealed in the zebrafish avascular mutant, cloche SO DEVELOPMENTAL GENETICS LA English DT Article DE podocyte; differentiation; endothelium; zebrafish; cloche; pronephros ID GLOMERULAR-BASEMENT-MEMBRANE; NEWBORN RAT KIDNEYS; WILMS-TUMOR GENE; CARDIOVASCULAR-SYSTEM; METANEPHRIC CULTURE; GROWTH-FACTOR; EXPRESSION; EMBRYO; LAMININ; ORIGIN AB The physiological functions of the zebrafish pronephros are blood plasma filtration and osmoregulation. The pronephric glomerulus is vascularized through a capillary network sprouting from the dorsal aorta. Vascularization of the glomerulus, visualized by flk-1 expression and alkaline phosphatase reactivity, involves the intimate association between podocytes and endothelial cells and the formation of an intervening glomerular basement membrane (GBM). Cell-cell interactions between podocytes and endothelial cells are thought to play an important role in glomerular angiogenesis. in order to determine whether endothelial cell-derived signals were required for podocyte differentiation, we employed in situ hybridization and electron microscopy to investigate glomerulogenesis in the zebrafish mutant cloche (clo), where endothelial cell development is blocked at on early stage. In cio mutants, glomerular epithelial cells expressing the podocyte specific marker wt1 display well-formed foot processes and are able to form a GEM, suggesting podocytes are able to morphologically differentiate in the absence of endothelia or endothelial-derived signals. The presence of irregular aggregates in the cio GEM as well as the apparent effacement of podocyte fool processes implies a role for endothelial cells in the maintenance of the mature glomerular filtration barrier. (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. RP Drummond, IA (reprint author), Massachusetts Gen Hosp, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK09763, R01 DK53093] NR 49 TC 66 Z9 68 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0192-253X J9 DEV GENET JI Dev. Genet. PY 1999 VL 24 IS 3-4 BP 220 EP 229 DI 10.1002/(SICI)1520-6408(1999)24:3/4<220::AID-DVG5>3.0.CO;2-1 PG 10 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 194JL UT WOS:000080189000005 PM 10322630 ER PT J AU Tarazi, FI Tomasini, EC Baldessarini, RJ AF Tarazi, FI Tomasini, EC Baldessarini, RJ TI Postnatal development of dopamine D-1-like receptors in rat cortical and striatolimbic brain regions: An autoradiographic study SO DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE autoradiography; caudate-putamen; cerebral cortex; dopamine D-1-like receptor; entorhinal cortex; frontal cortex; hippocampus; nucleus accumbens septi; postnatal development ID PREFRONTAL CORTEX; DIFFERENTIAL REGULATION; D1-DOPAMINE RECEPTORS; NUCLEUS-ACCUMBENS; MESSENGER-RNA; STRIATUM; D1; SUBTYPES; EXPRESSION; ONTOGENY AB Postnatal development of dopamine D-1-like (D-1/D-5) receptors in rat caudate-putamen (CPu), nucleus accumbens (NAc), hippocampus, frontal and entorhinal cerebral cortex was assessed between postnatal days (PD) 7-60 by in vitro receptor autoradiography. Density of [H-3]SCH-23390 binding to D-1-like receptors increased from PD-7 to a peak at PD-28 in CPu (11-fold) and NAc (23-fold), then declined by 20-40% in both regions over PD-35-60, to adult levels. In hippocampus, frontal and entorhinal cortex, D-1-like receptors increased by lesser amounts (3- to 4-fold) from PD-7 to stable, maximal adult levels at PD-60. Evidently, excess D-1-like receptors were eliminated during maturation of CPu and NAc, but not in the other forebrain regions. Postnatal D-1-like receptor development in rat forebrain paralleled that of D2- and D-4-like receptors in the same regions. C1 Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Colsolidated Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA USA. RP Tarazi, FI (reprint author), Harvard Univ, Sch Med, McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02178 USA. EM ftarazi@warren.med.harvard.edu FU NIMH NIH HHS [MH-47370, MH-19905, MH-34006] NR 46 TC 100 Z9 104 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-5866 J9 DEV NEUROSCI-BASEL JI Dev. Neurosci. PD JAN-FEB PY 1999 VL 21 IS 1 BP 43 EP 49 DI 10.1159/000017365 PG 7 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 177PL UT WOS:000079219300006 PM 10077701 ER PT J AU McNeely, MJ Boyko, EJ Weigle, DS Shofer, JB Chessler, SD Leonnetti, DL Fujimoto, WY AF McNeely, MJ Boyko, EJ Weigle, DS Shofer, JB Chessler, SD Leonnetti, DL Fujimoto, WY TI Association between baseline plasma leptin levels and subsequent development of diabetes in Japanese Americans SO DIABETES CARE LA English DT Article; Proceedings Paper CT 58th Annual Meeting and Scientific Session of the American-Diabetes-Association CY JUN 13-16, 1998 CL CHICAGO, ILLINOIS SP Amer Diabet Assoc ID PANCREATIC BETA-CELLS; INSULIN-RESISTANCE; FAT DISTRIBUTION; SERUM LEPTIN; OBESE GENE; BODY-FAT; HUMANS; ADIPOSITY; MELLITUS; WEIGHT AB OBJECTIVE - Plasma leptin levels correlate strongly with increased total adipose tissue, a known risk factor for type 2 diabetes, yet the role of leptin in the etiology of diabetes remains unclear. We sought to determine whether leptin is a risk factor for development of diabetes in Japanese Americans. RESEARCH DESIGN AND METHODS - We compared baseline leptin levels in 370 nondiabetic Japanese Americans who remained nondiabetic for 5-6 years of follow-up with those of 40 nondiabetic Japanese Americans who developed diabetes during follow-up. All participants had computed tomography measurements of baseline subcutaneous chest, abdomen, thigh, and intra-abdominal fat, with total fat defined as the sum of all these measurements. RESULTS - The mean age was 51.7 +/- 11.7 years for men and 51.9 +/- 12.0 years for women. The 23 men who developed diabetes had significantly higher leptin levels than the 212 men who remained nondiabetic (P < 0.01). Among men, baseline leptin levels predicted diabetes risk independent of baseline total fat, insulin, insulin resistance, glucose, or age in separate multiple logistic regression models (relative risk adjusted for baseline total fat = 18.0 per SD increase [2.7 ng/m1], 95% CI 1.02-3.17). This association was particularly strong among men in the top decile for intra-abdominal fat. In contrast, the 17 women who developed diabetes had leptin levels similar to those of the 158 women who remained nondiabetic (P = 0.31). CONCLUSIONS - Among Japanese Americans, increased baseline leptin levels are associated with increased risk of developing diabetes in men but not in women. C1 Univ Washington, Sch Med, Div Gen Internal Med, Dept Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA. Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. RP McNeely, MJ (reprint author), Univ Washington, Sch Med, Div Gen Internal Med, Dept Med, Box 356429, Seattle, WA 98195 USA. EM mcneely@u.washington.edu FU NHLBI NIH HHS [HL-49293]; NIDDK NIH HHS [DK-31170] NR 41 TC 71 Z9 81 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JAN PY 1999 VL 22 IS 1 BP 65 EP 70 DI 10.2337/diacare.22.1.65 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 150WT UT WOS:000077689400011 PM 10333905 ER PT J AU Genuth, S Nathan, D Shamoon, H Duffy, H Dahms, B Mayer, L Brillion, D Lackaye, M Whitehouse, F Kruger, D Bergenstal, R Johnson, M Jacobson, A Doyle, J Waters, M Nathan, D Crowell, S Godine, J McKitrick, C Service, J Ziegler, G Colwell, J Wood, D Maytield, R Molitch, M Schaefer, B Kolterman, O Lorenzi, G Sivitz, M Bayless, M Counts, D Kowarski, A Ostrowski, D Greene, D Martin, C Bantle, J Rogness, B Goldstein, D Smith, A Schade, D Johannes, C Schwartz, S Maschak-Carey, BJ Orchard, T Silvers, N Malone, J Mangione, A Kitabchi, A Murphy, MB Raskin, P Strowig, S Zinman, B Barnie, A Palmer, J Ginsberg, J Dupre, J Harth, J Lorenz, R Lipps, J White, N Santiago, J Levandoski, L Tamborlane, W Gatcomb, P Dahms, B Corcoran, P Quin, J Lachin, J Cleary, P Kenny, D Diminick, L Lamas, D Cowie, C Eastman, R Davis, M Hubbard, L Geithman, P Brickbauer, J Kastorff, L Neider, M Steffes, M Bucksa, J Chavers, B O'Leary, D Crow, R O'Donnell, C Weir, G Clark, C D'Agostino, R Espeland, M Klein, B Jacobson, H Manolio, T Rand, L Singer, D Stern, M Cleary, P Barnie, A Genuth, S Maffin, C Tamborlane, W Wesche, J Nathan, D AF Genuth, S Nathan, D Shamoon, H Duffy, H Dahms, B Mayer, L Brillion, D Lackaye, M Whitehouse, F Kruger, D Bergenstal, R Johnson, M Jacobson, A Doyle, J Waters, M Nathan, D Crowell, S Godine, J McKitrick, C Service, J Ziegler, G Colwell, J Wood, D Maytield, R Molitch, M Schaefer, B Kolterman, O Lorenzi, G Sivitz, M Bayless, M Counts, D Kowarski, A Ostrowski, D Greene, D Martin, C Bantle, J Rogness, B Goldstein, D Smith, A Schade, D Johannes, C Schwartz, S Maschak-Carey, BJ Orchard, T Silvers, N Malone, J Mangione, A Kitabchi, A Murphy, MB Raskin, P Strowig, S Zinman, B Barnie, A Palmer, J Ginsberg, J Dupre, J Harth, J Lorenz, R Lipps, J White, N Santiago, J Levandoski, L Tamborlane, W Gatcomb, P Dahms, B Corcoran, P Quin, J Lachin, J Cleary, P Kenny, D Diminick, L Lamas, D Cowie, C Eastman, R Davis, M Hubbard, L Geithman, P Brickbauer, J Kastorff, L Neider, M Steffes, M Bucksa, J Chavers, B O'Leary, D Crow, R O'Donnell, C Weir, G Clark, C D'Agostino, R Espeland, M Klein, B Jacobson, H Manolio, T Rand, L Singer, D Stern, M Cleary, P Barnie, A Genuth, S Maffin, C Tamborlane, W Wesche, J Nathan, D CA Epidemiology Diabetes Intervention Complication TI Epidemiology of Diabetes Interventions and Complications (EDIC): Design, implementation, and preliminary results of a long-term follow-up of the Diabetes Control and Complications Trial cohort SO DIABETES CARE LA English DT Article ID CORONARY-ARTERY DISEASE; LONGITUDINAL DATA; JUVENILE-ONSET; RISK-FACTORS; RETINOPATHY; IDDM; NEPHROPATHY; PROGRESSION; NEUROPATHY; PREDICTION AB OBJECTIVE - The Diabetes Control and Complications Trial (DCCT) demonstrated the powerful impact of glycemic control on the early manifestations of microvascular complications. Contemporary prospective data on the evolution of macrovascular and late microvascular complications of type 1 diabetes are limited. The Epidemiology of Diabetes Interventions and Complications (EDIC) study is a multicenter, longitudinal, observational study designed to use the well-characterized DCCT cohort of >1,400 patients to determine the long-term effects of prior separation of glycemic levels on micro- and macrovascular outcomes. RESEARCH DESIGN AND METHODS - Using a standardized annual history and physical examination, 28 EDIC clinical centers that were DCCT clinics will follow the EDIC cohort for 10 years. Annual evaluation also includes resting electrocardiogram, Doppler ultrasound measurements of ankle/arm blood pressure, and screening for nephropathy At regular intervals, a timed 4-h urine is collected, lipid profiles are obtained, and stereoscopic fundus photographs are taken. In addition, dual B-mode Doppler ultrasound scans of the common and internal carotid arteries will be performed at years 1 and 6 and at study end. RESULTS - Written informed consent was obtained from 96% of the DCCT subjects. The participants, compared with nonparticipants, tended to have better glycemic control at the completion of the DCCT and were more likely to have their diabetes care provided by DCCT personnel. The EDIC baseline measurement stratified by sex delineates multiple cardiovascular disease risk factor differences such as age (older in men), waist-to-hip ratio (higher in men), HDL cholesterol (lower in men), hypertension (more prevalent in men), and maximum intimal-medial thickness of common and internal carotid arteries (thicker in men). Of the original conventional treatment group, 69% have changed to continuous subcutaneous insulin infusion or multiple daily injections. Although the mean HbA(1c) difference between the intensive and conventional treatment groups narrowed at EDIC years 1 and 2, HbA(1c) remained significantly lower in the intensive group. Of all expected clinic visits, 95% were completed, and the quality of EDIC data is very similar to that observed in the DCCT. CONCLUSIONS - Although obvious problems exist in extended follow-up studies of completed clinical trials, these are balanced by the value of continued systematic observation of the DCCT cohort. In contrast to other epidemiologic studies, EDIC will provide 1) definitive data on type 1 as distinct from type 2 diabetes; 2) reliance on prospective rather than on cross-sectional analysis; 3) long-term followup in a large population; 4) consistent use of objective, reliable measures of outcomes and glycemia; and 5) observation of patients from before the onset of complications. C1 Albert Einstein Coll Med, Bronx, NY 10461 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Cornell Univ, Med Ctr, Ithaca, NY 14853 USA. Henry Ford Hlth Syst, Detroit, MI USA. Int Diabet Ctr, Minneapolis, MN USA. Joslin Diabet Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin & Mayo Fdn, Rochester, MN USA. Med Univ S Carolina, Charleston, SC USA. Northwestern Univ, Evanston, IL 60208 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Iowa, Iowa City, IA 52242 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Univ Missouri, Columbia, MO 65211 USA. Univ New Mexico, Albuquerque, NM 87131 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ S Florida, Tampa, FL 33620 USA. Univ Tennessee, Knoxville, TN 37996 USA. Univ Texas, SW Univ Med Ctr, Houston, TX USA. Univ Toronto, Toronto, ON, Canada. Univ Washington, Seattle, WA 98195 USA. Univ Western Ontario, London, ON N6A 3K7, Canada. Vanderbilt Univ, Nashville, TN USA. Washington Univ, St Louis, MO 63130 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. George Washington Univ, Ctr Biostat, Washington, DC 20052 USA. NIDDKD, Program Off, Bethesda, MD USA. Univ Wisconsin, Madison, WI 53706 USA. Tufts Univ New England Med Ctr, Boston, MA USA. RP Genuth, S (reprint author), EDIC Res Grp, Box NDIC-DCCT, Bethesda, MD 20892 USA. RI Zinman, Bernard/E-7266-2013; OI Shamoon, Harry/0000-0002-5014-5211 NR 50 TC 252 Z9 254 U1 1 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD JAN PY 1999 VL 22 IS 1 BP 99 EP 111 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 150WT UT WOS:000077689400016 ER PT J AU Moczulski, DK Burak, W Doria, A Zychma, M Zukowska-Szczechowska, E Warram, JH Grzeszczak, W AF Moczulski, DK Burak, W Doria, A Zychma, M Zukowska-Szczechowska, E Warram, JH Grzeszczak, W TI The role of aldose reductase gene in the susceptibility to diabetic nephropathy in Type II (non-insulin-dependent) diabetes mellitus SO DIABETOLOGIA LA English DT Article DE diabetic nephropathy; genetic susceptibility; aldose reductase; Type II diabetes mellitus ID NIDDM PATIENTS; 5'-END AB The dinucleotide repeat polymorphism (5'-ALR2) in the promoter region of the aldose reductase gene on chromosome 7q35 has been implicated in the development of diabetic nephropathy in Type I (insulin-dependent) diabetes mellitus, and markers flanking the aldose reductase locus have given evidence suggestive of a linkage between diabetic nephropathy and Type II (non-insulin-dependent) diabetes mellitus in Pima Indians. To examine whether the 5'-ALR2 polymorphism in the aldose reductase gene is involved in the development of diabetic nephropathy in Caucasians with Type II diabetes, we carried out a large association study. Patients with Type II diabetes from one outpatient clinic were screened for diabetic nephropathy and divided into three groups according to the degree of this disease: 179 patients with normoalbuminuria, 225 patients with microalbuminuria and 70 patients with proteinuria. Patients with normoalbuminuria were included in the study only if they had had Type II diabetes for 10 or more years. DNA from all patients was genotyped for the 5'-AL-R2 polymorphism using a previously established polymerase chain reaction protocol. The frequency of the putative risk allele Z-2 was 34.6%, 34.2% and 33.6% in the normoalbuminuria, microalbuminuria and proteinuria groups, respectively. Similarly no difference among groups was found for the frequency of the putative protective allele Z + 2. In conclusion, the results of our association study in Caucasian patients with Type II diabetes do not support the hypothesis that the 5'-ALR2 polymorphism in the aldose reductase gene contributes to susceptibility to diabetic nephropathy. C1 Silesian Sch Med, Dept Internal Med & Diabetol, PL-41800 Zabrze, Poland. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Grzeszczak, W (reprint author), Silesian Sch Med, Dept Internal Med & Diabetol, Ul 3 Maja 13-15, PL-41800 Zabrze, Poland. NR 10 TC 39 Z9 39 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 JAN PY 1999 VL 42 IS 1 BP 94 EP 97 DI 10.1007/s001250051119 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 160YQ UT WOS:000078261300016 PM 10027585 ER PT J AU Compton, CC AF Compton, CC TI Pathology report in colon cancer: What is prognostically important? SO DIGESTIVE DISEASES LA English DT Review DE TNM; prognostic factors; stage; grade; pathology ID MALIGNANT COLORECTAL POLYPS; LARGE BOWEL-CANCER; RECTAL-CANCER; INVASIVE-CARCINOMA; MULTIVARIATE-ANALYSIS; ENDOSCOPIC POLYPECTOMY; MUCINOUS CARCINOMA; LYMPH-NODES; REGRESSION-ANALYSIS; LOCAL RECURRENCE AB Surgical resection is the primary treatment modality for colorectal cancer, and the most powerful tool for assessing prognosis following surgery is pathologic analysis of the resection specimen. Although the parameters that determine the pathologic stage are the strongest predictors of postoperative outcome, a number of additional pathologic features have prognostic significance that is independent of stage. These include: histologic grade; small vessel (lymphatic or venular) invasion; extramural venous invasion; perineural invasion; tumor border configuration; host lymphoid response to tumor, and the status of surgical margins. For specimens in which the radial (circumferential) margin is applicable, surgical clearance around the tumor is also of import. It is self-evident that, compared to data derived from additional assays, prognostic information that can be derived directly from standard histologic sections of a tumor is of the greatest cost-benefit to the patient. In the current era of cost containment, it is essential that surgical pathologists evaluate and report the pathologic features that are of prognostic and/or predictive significance in every case of colorectal cancer and, in turn, that the import of these be understood by the treating physicians. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Compton, CC (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 256,55 Fruit St, Boston, MA 02114 USA. NR 94 TC 46 Z9 49 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0257-2753 J9 DIGEST DIS JI Dig. Dis. PY 1999 VL 17 IS 2 BP 67 EP 79 DI 10.1159/000016908 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 243HN UT WOS:000082991500002 PM 10545712 ER PT J AU Jenkins, TD Friedman, LS AF Jenkins, TD Friedman, LS TI Adenocarcinoma of the esophagogastric junction SO DIGESTIVE DISEASES LA English DT Review DE esophageal adenocarcinoma; Barrett's esophagus; esophagogastric junction; intestinal metaplasia ID HELICOBACTER-PYLORI INFECTION; GASTROESOPHAGEAL REFLUX DISEASE; GASTRIC CARDIA ADENOCARCINOMA; COLUMNAR-LINED ESOPHAGUS; BARRETTS-ESOPHAGUS; CHANGING PATTERN; CANCER; RISK; CARCINOMA; PREVALENCE AB Adenocarcinoma of the esophagogastric junction (EGJ) has increased rapidly in incidence in the latter half of the twentieth century. The increase in incidence has affected white men between the ages of 40 and 60 disproportionately. Understanding the etiology and improving treatment requires careful classification of EGJ tumors. A recent consensus conference recognized three types of EGJ adenocarcinomas: distal esophageal, cardia, and subcardia gastric. Distal esophageal adenocarcinomas are associated with Barrett's esophagus, Heilcobacter pylori infection may play a role in some adenocarcinomas of the subcardia, but the association is unproven. Therapy for all types of EGJ tumors is surgical, but multimodal forms of treatment are commonly used because of the advanced stage at which these tumors often present. Several endoscopic options exist for primary therapy of early-stage tumors and for palliation. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. Hosp Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Friedman, LS (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Blake 456D, Boston, MA 02114 USA. FU NIDDK NIH HHS [K08 DK02588-01] NR 80 TC 9 Z9 12 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0257-2753 J9 DIGEST DIS JI Dig. Dis. PY 1999 VL 17 IS 3 BP 153 EP 162 DI 10.1159/000016920 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 267PB UT WOS:000084367500004 PM 10697664 ER PT J AU Goldberg, RT Pachas, WN Keith, D AF Goldberg, RT Pachas, WN Keith, D TI Relationship between traumatic events in childhood and chronic pain SO DISABILITY AND REHABILITATION LA English DT Article ID CHRONIC PELVIC PAIN; SEXUAL ABUSE; PARENTAL ALCOHOLISM; SUBSTANCE-ABUSE; PHYSICAL ABUSE; WOMEN; HISTORY; FIBROMYALGIA; DEPRESSION; PREVALENCE AB Purpose: The purpose was to examine the relationships between traumatic events in childhood, such as sexual and physical abuse, alcoholism, and drug addiction, and three types of chronic pain: facial pain, myofascial paint and fibromyalgia. A fourth group, a heterogeneous group of other pain, was used as a comparison group. Method: Ninety one patients with chronic pain, age range 20-60, were consecutively recruited from the outpatient clinics of a rehabilitation hospital and a general hospital. Patients were given four measures for completion at evaluation: Childhood History Questionnaire; Childhood Traumatic Events Scale; McGill Melzack Pain Questionnaire; Pain Disability Index. Chi-square was used to test significant differences among four pain groups on sexual, physical. and verbal abuse; alcoholism; drug dependence; medications; major upheaval, childhood illness, death of a family member or friend, and separation or divorce of parents. Logistic regression was used to predict membership in the four pain groups. Results: All pain groups had a history of abuse exceeding 48 % : fibromyalgia, 64.7 %; myofascial, 61.9 %; facial, 50 %; other pain, 48.3 %. All groups had a history of family alcohol dependence exceeding 38 %, and a history of drug dependence ranging from 5.8 to 19.1 %. A combined history of pain, child physical abuse, and alcoholism was prevalent in 12.9 to 35.3 %. Logistic regression showed patients who were female, with an alcoholic parent, using non-narcotic drugs were more likely to be members of the facial, myofascial, and fibromyalgia groups. Conclusions: Child traumatic events are significantly related to chronic pain. Since the problem of child abuse is broader than physical and sexual abuse, health and rehabilitation agencies must shift from individualized treatment to interdisciplinary treatment of the family and patient. C1 Harvard Univ, Spaulding Rehabil Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Spaulding Rehabil Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Cambridge, MA 02138 USA. RP Goldberg, RT (reprint author), Harvard Univ, Spaulding Rehabil Hosp, Sch Med, Dept Psychiat, 125 Nashua St, Boston, MA 02114 USA. NR 30 TC 77 Z9 78 U1 0 U2 8 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0963-8288 J9 DISABIL REHABIL JI Disabil. Rehabil. PD JAN PY 1999 VL 21 IS 1 BP 23 EP 30 DI 10.1080/096382899298061 PG 8 WC Rehabilitation SC Rehabilitation GA 159HQ UT WOS:000078166900003 PM 10070600 ER PT J AU Rojas, B Zafirakis, P Christen, W Markomichelakis, NN Foster, CS AF Rojas, B Zafirakis, P Christen, W Markomichelakis, NN Foster, CS TI Medical treatment of macular edema in patients with uveitis SO DOCUMENTA OPHTHALMOLOGICA LA English DT Article; Proceedings Paper CT 2nd International Symposium on Macular Edema CY APR 23, 1998-APR 25, 1999 CL LAUSANNE, SWITZERLAND DE macular edema; uveitis ID INTRAOCULAR INFLAMMATORY DISEASE; INJECTIONS; CORTICOSTEROIDS AB Purpose: To determine the efficacy of medical treatment of cystoid macular edema (CME) in patients with uveitis. Methods: Retrospective study of 40 patients (57 eyes) with uveitis and CME. Inclusion criteria were presence of CME with minimal and no macular pathology, or vascular disease which could account for CME. Patients who had undergone intraocular surgery or had visual aucity (VA) of greater than or equal to 20/40 were excluded. The diagnosis of CME was based on clinical and/or angiographic findings. Three treatment groups were defined: (1) transseptal injection of steroids (n=13 eyes); (2) systemic non steroidal anti-inflammatory drugs (NSAIDs) (n=11 eyes); both 1 and 2 (n=33 eyes). Results: Overall, 79% of eyes improved 3 or more lines of Snellen VA after treatment: 51% improved 4 or more lines. The average number of lines improved was 3.8 for eyes treated with transseptal injections of steroids, 2.9 for eyes treated with NSAIDs, and 4 for eyes treated with both. For all 3 treatment groups between 60-70% of eyes improving 2 or more lines reached best VA only after a minimum of 6 months of follow up. Conclusions: CME, a vision threatening complication of uveitis, respond fairly well to medical treatment; however, the best VA is achieved after several months. The improvement in VA did not differ markedly among the three treatment groups. C1 Massachusetts Eye & Ear Infirm, Hilles Immunol Lab, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02114 USA. RP Foster, CS (reprint author), Massachusetts Eye & Ear Infirm, Hilles Immunol Lab, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. OI ROJAS LOPEZ, MARIA BLANCA/0000-0002-8980-4659 NR 15 TC 16 Z9 16 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0012-4486 J9 DOC OPHTHALMOL JI Doc. Ophthalmol. PY 1999 VL 97 IS 3-4 BP 399 EP 407 DI 10.1023/A:1002525619764 PG 9 WC Ophthalmology SC Ophthalmology GA 314LF UT WOS:000087056700024 PM 10896356 ER PT J AU Hooper, DC AF Hooper, DC TI Mechanisms of fluoroquinolone resistance SO DRUG RESISTANCE UPDATES LA English DT Review ID MULTIPLE-ANTIBIOTIC-RESISTANCE; DNA TOPOISOMERASE-IV; COMPLETE GENOME SEQUENCE; MULTIDRUG EFFLUX TRANSPORTER; KLEBSIELLA-PNEUMONIAE STRAINS; STAPHYLOCOCCUS-AUREUS STRAINS; PSEUDOMONAS-AERUGINOSA PAO; GYRASE GYRA GENE; MEXA-MEXB-OPRM; ESCHERICHIA-COLI AB Mechanisms of bacterial resistance to fluoroquinolones fall into two principal categories, alterations in drug target enzymes and alterations that limit permeation of drug to the target, both resulting from chromosomal mutations. No specific resistance mechanisms of quinolone degradation or modification have been found. The target enzymes, DNA gyrase and topoisomerase IV are most commonly altered in domains near the enzyme active sites and in some cases reduced drug binding affinity has been demonstrated. Drug permeation is altered by mutations that increase expression of endogenous multidrug efflux pumps, alter outer membrane diffusion channels, or both. Recently a new plasmid-mediated resistance of an as yet undefined mechanism was found in clinical isolates of Klebsiella pneumoniae. C1 Harvard Univ, Div Infect Dis, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Hooper, DC (reprint author), Harvard Univ, Div Infect Dis, Massachusetts Gen Hosp, Sch Med, 55 Fruit St, Boston, MA 02114 USA. NR 174 TC 238 Z9 259 U1 1 U2 19 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1368-7646 J9 DRUG RESIST UPDATE JI Drug Resist. Update PY 1999 VL 2 IS 1 BP 38 EP 55 DI 10.1054/drup.1998.0068 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 189TM UT WOS:000079922300007 ER PT J AU Hooper, DC AF Hooper, DC TI Mode of action of fluoroquinolones SO DRUGS LA English DT Article; Proceedings Paper CT 6th International Symposium on New Quinolones CY NOV 15-17, 1998 CL DENVER, COLORADO ID COMPLETE GENOME SEQUENCE; QUINOLONE RESISTANCE LOCUS; II DNA TOPOISOMERASES; ESCHERICHIA-COLI; STAPHYLOCOCCUS-AUREUS; STREPTOCOCCUS-PNEUMONIAE; CHROMOSOME SEGREGATION; STRAND CLEAVAGE; PRIMARY TARGET; GYRASE AB The mode of action of quinolones involves interactions with both DNA gyrase, the originally recognised drug target, and topoisomerase IV, a related type II topoisomerase. In a given bacterium these 2 enzymes often differ in their relative sensitivities to many quinolones, and commonly DNA gyrase is more sensitive in Gram-negative bacteria and topoisomerase IV more sensitive in Gram-positive bacteria. Usually the more sensitive enzyme represents the primary drug target determined by genetic tests, but poorly understood exceptions have been documented. The formation of the ternary complex of quinolone, DNA, and either DNA gyrase or topoisomerase IV occurs through interactions in which quinolone binding appears to induce changes in both DNA and the topoisomerase that occur separately from the DNA cleavage that is the hallmark of quinolone action. X-ray crystallographic studies of a fragment of the gyrase A subunit. as well as of yeast topoisomerase IV, which has homology to the subunits of both DNA gyrase and topoisomerase IV, have revealed domains that are likely to constitute quinolone binding sites, but no topoisomerase crystal structures that include DNA and quinolone have been reported to date. Inhibition of DNA synthesis by quinolones requires the targeted topoisomerase to have DNA cleavage capability, and collisions of the replication fork with reversible quinolone-DNA-topoisomerase complexes convert them to an irreversible form. However, the molecular factors that subsequently generate DNA double-strand breaks from the irreversible complexes and that probably initiate cell death have yet to be defined. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. RP Hooper, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. NR 38 TC 131 Z9 135 U1 3 U2 24 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 1999 VL 58 SU 2 BP 6 EP 10 DI 10.2165/00003495-199958002-00002 PG 5 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 248VY UT WOS:000083298500004 PM 10553698 ER PT J AU Ince, D Aras, R Hooper, DC AF Ince, D Aras, R Hooper, DC TI Mechanisms and frequency of resistance to moxifloxacin in comparison with ciprofloxacin in Staphylococcus aureus SO DRUGS LA English DT Meeting Abstract ID TOPOISOMERASE-IV; PRIMARY TARGET; DNA GYRASE; FLUOROQUINOLONES; QUINOLONE; MUTATIONS; LOCUS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv, Boston, MA 02114 USA. NR 6 TC 4 Z9 4 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 1999 VL 58 SU 2 BP 132 EP 133 DI 10.2165/00003495-199958002-00032 PG 2 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 248VY UT WOS:000083298500034 ER PT J AU Ince, D Aras, R Hooper, DC AF Ince, D Aras, R Hooper, DC TI Mechanisms and frequency of resistance to gatifloxacin in comparison with ciprofloxacin in Staphylococcus aureus SO DRUGS LA English DT Meeting Abstract ID TOPOISOMERASE-IV; 6-FLUORO-8-METHOXY QUINOLONE; PRIMARY TARGET; DNA GYRASE; FLUOROQUINOLONES; MUTATIONS; AM-1155; LOCUS C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv, Boston, MA 02114 USA. NR 7 TC 6 Z9 6 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0012-6667 J9 DRUGS JI Drugs PY 1999 VL 58 SU 2 BP 134 EP 135 DI 10.2165/00003495-199958002-00033 PG 2 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 248VY UT WOS:000083298500035 ER PT J AU Das, DK Sato, M Ray, PS Maulik, G Engelman, RM Bertelli, AAE Bertelli, A AF Das, DK Sato, M Ray, PS Maulik, G Engelman, RM Bertelli, AAE Bertelli, A TI Cardioprotection of red wine: Role of polyphenolic antioxidants SO DRUGS UNDER EXPERIMENTAL AND CLINICAL RESEARCH LA English DT Article; Proceedings Paper CT Meeting on Drugs Under Experimental and Clinical Research - Recent Advances in the Healthy Effects of Nonalcoholic Wine Compounds CY NOV 26-28, 1998 CL FLORENCE, ITALY ID ISCHEMIA-REPERFUSION; DENSITY-LIPOPROTEIN; LIPID-PEROXIDATION; FREE-RADICALS; HEART; CONSUMPTION; INJURY; PLASMA; RISK AB Epidemiological studies suggest that the consumption of wine, particularly of red wine, reduces the incidence of mortality and morbidity from coronary hear? disease. This has given rise to what is now popularly termed the "French paradox". The cardioprotective effect has been attributed to antioxidants present in the polyphenol fraction of red wine. Grapes contain a variety of antioxidants, including resveratrol, catechin, epicatechin and proanthocyanidins. Of these resveratrol is present mainly in grape skin while proanthocyanidin is present in the seeds. In this report, we provide evidence that red wine extract as well as resveratrol and proanthocyanidins are equally effective in reducing myocardial ischemic reperfusion injury which suggests that these red wine polyphenolic antioxidants play a crucial role in cardioprotection. C1 Univ Connecticut, Sch Med, Farmington, CT 06030 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Baystate Med Ctr, Springfield, MA USA. Univ Milan, Inst Anat, Milan, Italy. Univ Milan, Dept Pharmacol, Milan, Italy. RP Das, DK (reprint author), Univ Connecticut, Sch Med, Farmington, CT 06030 USA. NR 24 TC 208 Z9 214 U1 2 U2 15 PU BIOSCIENCE EDIPRINT INC PI CAROUGE PA RUE ALEXANDRE-GAVARD 16, 1227 CAROUGE, SWITZERLAND SN 0378-6501 J9 DRUG EXP CLIN RES JI Drug Exp. Clin. Res PY 1999 VL 25 IS 2-3 BP 115 EP 120 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 202KU UT WOS:000080652100010 PM 10370873 ER PT S AU Robinson, D Huang, RY Lian, JP Toker, A Badwey, JA AF Robinson, D Huang, RY Lian, JP Toker, A Badwey, JA BE Honn, KV Marnett, LJ Nigam, S Dennis, EA TI Functions of the p21-activated protein kinases (Paks) in neutrophils and their regulation by complex lipids SO EICOSANOIDS AND OTHER BIOACTIVE LIPIDS IN CANCER, IMFLAMMATION AND RADIATION INJURY, 4 SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 5th International Conference on Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Related Diseases CY SEP 17-20, 1997 CL LA JOLLA, CALIFORNIA ID HEAVY-CHAIN KINASE; MYOSIN-I; COUPLED RECEPTORS; ACTIVATION; PHOSPHORYLATION; AUTOPHOSPHORYLATION; SPHINGOLIPIDS; STIMULATION; SPHINGOSINE; SUBSTRATE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Arthrit Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston Biomed Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02114 USA. RP Robinson, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Arthrit Unit, Boston, MA 02114 USA. FU NIAID NIH HHS [AI23323]; NIAMS NIH HHS [AR43518]; NIDDK NIH HHS [DK50015] NR 41 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC / PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46138-2 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1999 VL 469 BP 385 EP 390 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA BP58H UT WOS:000085570100056 PM 10667357 ER PT S AU Tapp, A Douglas, A Tandon, R Wood, AE AF Tapp, A Douglas, A Tandon, R Wood, AE BE DeClercq, M Andreoli, A Lamarre, S Forster, P TI Prevalence, characteristics, and methods to address assaultive patients in a large neuropsychiatric hospital SO EMERGENCY PSYCHIATRY IN A CHANGING WORLD SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 5th World Congress of the International-Association-for-Emergency-Psychiatry CY OCT 15-17, 1998 CL BRUSSELS, BELGIUM SP World Psychiatr Assoc, Assoc European Psychiatrists, European Region Council World Federat Ment Hlth, Belgian Royal Soc Ment Hlth Med, Belgian Soc Emergency & Disaster Med DE assaultive behavior; hospitals; psychiatric; schizophrenia ID VIOLENT BEHAVIOR; SCHIZOPHRENIC INPATIENTS; PSYCHIATRIC-INPATIENTS; STAFF; PATTERNS AB Background Violence in psychiatric facilities is prevalent and is frequently associated with costs both to property and persons. Methods. The prevalence of assaultive behavior was measured over 3 years in a large 991-bed psychiatric VA medical center. Data was collected on sex, age, diagnosis, medications prescribed, and injuries sustained. A specialized unit designed to treat schizophrenic patients in a less restricted environment was developed and level of assaultive behavior was of measured before implementation and 3 years following. Results. The prevalence of assaultive patients, calculated over 31/2 years, was 9.65%. The time of year, and the day of the occurrence of 281 incidents, revealed an increased incidence during 2 winter months and at rimes when the patient's space was restricted to medication distribution and meals. A random sample of 81 assaultive patients more often carried a diagnosis of schizophrenia and received higher doses of neuroleptics, but were no different in age than other nonassaultive patients. Assaultive behavior in schizophrenic patients on the specialized schizophrenia unit decreased over 3 years. Conclusions. These data suggest a need to address the special therapeutic and environmental needs of a population of chronic, treatment resistant schizophrenics. C1 VA Puget Sound Hlth Care Syst, Amer Lake Div 116, Tacoma, WA 98493 USA. RP Tapp, A (reprint author), VA Puget Sound Hlth Care Syst, Amer Lake Div 116, Tacoma, WA 98493 USA. NR 26 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50017-0 J9 INT CONGR SER PY 1999 VL 1179 BP 265 EP 270 PG 6 WC Psychiatry SC Psychiatry GA BQ28U UT WOS:000087816100033 ER PT J AU Hayes, FJ Welt, CK Martin, KA Crowley, WF AF Hayes, FJ Welt, CK Martin, KA Crowley, WF TI Gonadotropin-releasing hormone deficiency: Differential diagnosis and treatment SO ENDOCRINOLOGIST LA English DT Review ID FOLLICLE-STIMULATING-HORMONE; IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; HUMAN CHORIONIC-GONADOTROPIN; MENSTRUAL-CYCLE; ABNORMAL PATTERNS; MEN; AMENORRHEA; SECRETION; WOMEN; LH AB A normal frequency and amplitude of gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus is critical for both the initiation and maintenance of reproductive function in the human. Hypogonadotropic hypogonadism (HH) is the clinical syndrome that results from absence, decreased frequency or decreased amplitude of pulsatile GnRH release. Typically, the diagnosis of GnRN deficiency is made in adolescence when secondary sexual characteristics fail to develop. In a subset of patients, HH may present postpubertally with decreased libido, impotence, and oligo- or azoospermia in men and secondary amenorrhea and infertility in women. HH can be congenital or can arise from a variety of structural or functional lesions of the hypothalamic-pituitary axis. Congenital GnRH deficiency can be an isolated finding, as in idiopathic hypogonadotropic hypogonadism, or it may occur in association with anosmia +/- a variety of midline defects, in which case the term Kallmann's syndrome is applied. One-third of cases of congenital HH are familial. Autosomal inheritance is the commonest mode of inheritance, although X-linked transmission due to a mutation in the KAL gene is the best generically characterized form of GnRH deficiency. In prepubertal patients, sex steroid replacement is necessary to allow normal development of secondary sexual characteristics. In adult women, estrogen replacement with an oral contraceptive or with conjugated estrogens and a progestogen is important to protect bone mass. Androgen replacement in adult men with HH may take the farm. of either an intramuscular or transdermal preparation. The fertility potential of patients with HH is generally excellent. Ovulation may be induced in more than 90% of HH women with either gonadotropin therapy or with intravenous pulsatile GnRH. GnRH therapy has the advantage of not causing higher order multiple births. In GnRH-deficient men, spermatogenesis can be stimulated using the combination of hCG and FSH or with pulsatile subcutaneous GnRH therapy. Although both are very effective therapeutic modalities, testicular growth is greater and the time taken to achieve spermatogenesis is shorter in patients treated with GnRH. C1 Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Boston, MA 02114 USA. RP Hayes, FJ (reprint author), Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, BHX 5,Bartlett Hall Ext 511,Fruit St, Boston, MA 02114 USA. OI Welt, Corrine/0000-0002-8219-5504 NR 40 TC 1 Z9 2 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-2144 EI 1539-9192 J9 ENDOCRINOLOGIST JI Endocrinologist PD JAN-FEB PY 1999 VL 9 IS 1 BP 36 EP 44 DI 10.1097/00019616-199901000-00008 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 171VE UT WOS:000078884100009 ER PT J AU Yang, H Yuan, PQ Wu, V Tache, Y AF Yang, H Yuan, PQ Wu, V Tache, Y TI Feedback regulation of thyrotropin-releasing hormone gene expression by thyroid hormone in the caudal raphe nuclei in rats SO ENDOCRINOLOGY LA English DT Article ID HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; MESSENGER-RIBONUCLEIC-ACID; GASTRIC-SECRETION; HDC ACTIVITY; SUBSTANCE-P; NEURONS; TRH; RNA; HYPOTHYROIDISM; TRIIODOTHYRONINE AB Medullary TRH regulates autonomic activity, and altered thyroid status is associated with autonomic disorders. We investigated whether thyroid hormone exerts a negative feedback regulation on TRH gene expression in the medullary caudal raphe nuclei. Medullary pro-TRH messenger RNAs (mRNAs) were mainly located in the raphe pallidus and raphe obscurus neurons as shown by in situ hybridization and were significantly increased by 70% and 160-230% by Northern blot analyses in 24 h fasted rats at 1 and 3-5 weeks after thyroidectomy, respectively, when serum T-4 levels were reduced by 75-87%. The increased pro-TRH mRNA on the 30th day after thyroidectomy was reversed to euthyroid levels by T-4 replacement (2 or 4 mu g/100 g.day). T-4 injections (10 or 100 mu g/100 g day for 30 days) did not significantly influence medullary pro-TRH mRNA levels in sham-operated rats. Thyroidectomized rats fed normally showed a 500% increase in pro-TRH mRNA levels 30 days after the surgery, while those fasted for 24 h showed only a 180% increase. These data indicate that medullary TRH gene expression is enhanced during hypothyroidism due to the lack of negative feedback regulation by thyroid hormone, and this response is modulated by feeding state. These findings may have important relevance to understanding autonomic-related visceral alterations induced by hypothyroidism. C1 Univ Calif Los Angeles, W Los Angeles VA Med Ctr, CURE DDRC, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, W Los Angeles VA Med Ctr, CURE DDRC, Inst Brain Res, Los Angeles, CA 90073 USA. RP Yang, H (reprint author), Univ Calif Los Angeles, W Los Angeles VA Med Ctr, CURE DDRC, Dept Med, Bldg 115,Room 203,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM hoyang@ucla.edu NR 44 TC 19 Z9 20 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 1999 VL 140 IS 1 BP 43 EP 49 DI 10.1210/en.140.1.43 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 149VH UT WOS:000077626500007 PM 9886805 ER PT J AU Markuns, JF Napoli, R Hirshman, MF Davalli, AM Cheatham, B Goodyear, LJ AF Markuns, JF Napoli, R Hirshman, MF Davalli, AM Cheatham, B Goodyear, LJ TI Effects of streptozocin-induced diabetes and islet cell transplantation on insulin signaling in rat skeletal muscle SO ENDOCRINOLOGY LA English DT Article ID PROTEIN-KINASE-B; STIMULATED GLUCOSE-UPTAKE; PHOSPHATIDYLINOSITOL 3-KINASE; S6 KINASE; ANIMAL-MODELS; TRANSPORT; ACTIVATION; AKT; PHOSPHORYLATION; TRANSLOCATION AB Streptozocin-induced diabetes is associated with alterations in insulin signaling in rat skeletal muscle, including increased insulin receptor substrate-1 phosphorylation and phosphotidylinositol 3-kinase activity. In the current study, we determined the effects of streptozocin-induced diabetes and treatment of diabetes by islet cell transplantation on several proximal insulin-activated signaling proteins. Three groups of male Lewis rats (untreated streptozocin-diabetic animals, islet cell-transplanted diabetic rats, and nondiabetic control rats) were studied in the basal state or 30 min after ip insulin injection (20 U/rat). Mixed hindlimb skeletal muscle lysates were used to determine the expression and enzymatic activities of the extracellular regulated kinase 2 (ERK2), p90 ribosomal S6 kinase (RSK2), Akt, and p70 S6 kinase (p70S6k). In all three groups of rats, insulin significantly increased ERK2, RSK2, Akt, and p70S6k activities. There was no effect of diabetes on insulin-stimulated ERK2 activity or ERK2 protein levels. RSK2 expression and insulin-stimulated RSK2 activity were significantly elevated in diabetic rats compared with those in the control animals. Insulin-stimulated Akt activity was also significantly greater in the diabetic animals, but there was no change in protein expression. In contrast, there was a decrease in insulin-stimulated p70S6k activity With no change in protein expression in the diabetic rats. Islet transplantation partially (RSK2) or fully (Akt, p70S6k) normalized these diabetes-induced changes in insulin signaling proteins. We conclude that streptozocin diabetes results in the dysregulation of several critical insulin-activated proteins in rat skeletal muscle, but islet cell transplantation is an effective therapy to partially correct these alterations in insulin signaling. C1 Brigham & Womens Hosp, Div Res, Joslin Diabet Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM goodyeal@joslab.harvard.edu OI Markuns, Jeffrey/0000-0002-8044-2575; NAPOLI, Raffaele/0000-0002-3366-2321 NR 45 TC 12 Z9 13 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 1999 VL 140 IS 1 BP 106 EP 111 DI 10.1210/en.140.1.106 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 149VH UT WOS:000077626500015 PM 9886813 ER PT J AU Ecker, JL AF Ecker, JL TI Just do it SO EPIDEMIOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Obstet, Boston, MA 02114 USA. RP Ecker, JL (reprint author), Massachusetts Gen Hosp, Dept Obstet, Founders 431,32 Fruit St, Boston, MA 02114 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 1999 VL 10 IS 1 BP 6 EP 7 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 151HR UT WOS:000077715100003 PM 9888273 ER PT J AU Chiappa, KH Hill, RA Huang-Hellinger, F Jenkins, BG AF Chiappa, KH Hill, RA Huang-Hellinger, F Jenkins, BG TI Photosensitive epilepsy studied by functional magnetic resonance imaging and magnetic resonance spectroscopy SO EPILEPSIA LA English DT Article DE functional MRI; MR spectroscopy; generalized epilepsy; photosensitive; EEG ID HUMAN VISUAL-CORTEX; PHOTIC-STIMULATION; SEIZURES; EEG; MRI AB Purpose: To study metabolic and hemodynamic correlates of photic stimulation-triggered discharges. Methods: Simultaneous EEG, functional MRI (fMRI) and magnetic resonance spectroscopy (MRS) were performed in nine patients with photosensitive epilepsy and in 12 normal subjects. Results: Prominent visual cortex activation was seen in all normal subjects and patients, and no fMRI-registered hemodynamic abnormalities were correlated with the brief photoparoxysmal spike-wave activity evoked in the photosensitive patients. However, irrespective of the presence of a spike-wave response to the photic stimulation, the photosensitive patients showed four findings not seen in the normal subjects: (a) slightly, but significantly, elevated lactate levels in the occipital cortex in the resting state; (b) an increased area of visual cortical activation with photic stimulation; (c) simultaneous with the occipital cortex stimulus-induced increased fMRI signal, there were noncontiguous areas of signal attenuation most prominent in perirolandic regions; and (d) a marked decrement (undershoot) of fMRI signal intensity immediately after the photic stimulation in the occipital cortex and in the region of the posterior cingulate gyrus, Conclusions: These findings suggest abnormal interictal metabolism and increased vascular reactivity in the photosensitive patients. C1 Massachusetts Gen Hosp, Dept Neurol, Dept Clin Neurophysiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, NMR Ctr, Boston, MA 02114 USA. RP Chiappa, KH (reprint author), Massachusetts Gen Hosp, EEG Lab, Boston, MA 02214 USA. NR 12 TC 30 Z9 30 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 1999 VL 40 SU 4 BP 3 EP 7 DI 10.1111/j.1528-1157.1999.tb00899.x PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 233DX UT WOS:000082411200002 PM 10487166 ER PT J AU Fujikawa, DG Shinmei, SS Nguyen, PQ AF Fujikawa, DG Shinmei, SS Nguyen, PQ TI Caspase inhibition does not protect against seizure-induced neuronal necrosis with internucleosomal DNA cleavage SO EPILEPSIA LA English DT Meeting Abstract C1 VA Greater LA Healthcare Syst, Sepulveda, 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 1999 VL 40 SU 7 BP 19 EP 20 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 242NR UT WOS:000082947600076 ER PT J AU Murray, B Beer, T Alessandrini, A Cole, AJ AF Murray, B Beer, T Alessandrini, A Cole, AJ TI Pre- and post-synaptic activation of p44/42 MAP kinase in hippocampus after kainate-induced seizures SO EPILEPSIA LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Epilepsy Res Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 1999 VL 40 SU 7 BP 21 EP 21 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 242NR UT WOS:000082947600081 ER PT J AU Brisman, JL Cole, AJ AF Brisman, JL Cole, AJ TI Phosphorylation of p44/42 MAP kinase is both spatially and temporally regulated in the perforant pathway stimulation model of limbic epilepsy in the rat SO EPILEPSIA 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 1999 VL 40 SU 7 BP 22 EP 22 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 242NR UT WOS:000082947600086 ER PT J AU Licht, EA Jacobsen, RH Curran, J Fujikawa, DG AF Licht, EA Jacobsen, RH Curran, J Fujikawa, DG TI Electrographic seizures and cognitive function: Raising concerns for low frequency events SO EPILEPSIA LA English DT Meeting Abstract C1 Sepulveda ACC, VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 1999 VL 40 SU 7 BP 59 EP 59 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 242NR UT WOS:000082947600233 ER PT J AU Folek, J Norris, DM Prady, S Lester, JE Hoch, DB AF Folek, J Norris, DM Prady, S Lester, JE Hoch, DB TI Internet use of an epilepsy clinic population SO EPILEPSIA LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 1999 VL 40 SU 7 BP 74 EP 74 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 242NR UT WOS:000082947600293 ER PT J AU Fujikawa, DG Shinmei, SS Cai, B AF Fujikawa, DG Shinmei, SS Cai, B TI Seizure-induced-neuronal death is morphologically necrotic, with internucleosomal DNA cleavage: Implications for programmed cell death mechanisms. SO EPILEPSIA LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, Expt Neurol Lab, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 1999 VL 40 SU 2 BP 111 EP 112 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 225BU UT WOS:000081936800454 ER PT J AU Tanabe, SM Grant, E Cosgrove, GR Hoch, DB Cole, AJ AF Tanabe, SM Grant, E Cosgrove, GR Hoch, DB Cole, AJ TI Delayed diagnosis of lesional epilepsy: Utility of modern imaging SO EPILEPSIA LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Epilepsy Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 1999 VL 40 SU 7 BP 189 EP 190 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 242NR UT WOS:000082947600762 ER PT J AU Delgado-Escueta, AV Fong, GCY Alonso, ME Shah, PU Fois, A Castroviejo, IP Serratosa, JM Medina, MT Gee, MN Huang, Y Cordova, S Donnadieu, FR AF Delgado-Escueta, AV Fong, GCY Alonso, ME Shah, PU Fois, A Castroviejo, IP Serratosa, JM Medina, MT Gee, MN Huang, Y Cordova, S Donnadieu, FR TI Childhood absence epilepsy genotypes in chromosomes 8q24 and 1p: Clinical and EEG phenotypes. SO EPILEPSIA LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Comp Epilepsy Prog, Los Angeles, CA 90024 USA. VA GLAHS Med Ctr, Los Angeles, CA USA. Natl Inst Neurol & Neurosurg, Mexico City, DF, Mexico. KEM Hosp & GS Seth Med Coll, Bombay, Maharashtra, India. Univ Siena, I-53100 Siena, Italy. Univ Hosp La Paz, Madrid, Spain. Fdn Jimenez Diaz, E-28040 Madrid, Spain. Natl Univ, Tegucigalpa, Honduras. 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 1999 VL 40 SU 2 BP 215 EP 215 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 225BU UT WOS:000081936800894 ER PT J AU Rogers, SJ Szabo, CA Hartig, JL Mayes, BN AF Rogers, SJ Szabo, CA Hartig, JL Mayes, BN TI Topiramate in the treatment of primary generalized epilepsy SO EPILEPSIA LA English DT Meeting Abstract C1 Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 1999 VL 40 SU 7 BP 219 EP 219 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 242NR UT WOS:000082947600880 ER PT J AU Walton, NY AF Walton, NY TI Harkoseride, a novel anticonvulsant: Efficacy in treatment of experimental status epilepticus, plasma protein binding, plasma and brain pharmacokinetics. SO EPILEPSIA LA English DT Meeting Abstract C1 VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 1999 VL 40 SU 7 BP 242 EP 242 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 242NR UT WOS:000082947600974 ER PT J AU Folli, F Saad, MJA Velloso, L Hansen, H Carandente, O Feener, EP Kahn, CR AF Folli, F Saad, MJA Velloso, L Hansen, H Carandente, O Feener, EP Kahn, CR TI Crosstalk between insulin and angiotensin II signalling systems SO EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES LA English DT Article DE insulin; angiontensin II; IRS-1; IRS-2; PI 3-kinase; serine phosphorylation ID TYROSINE KINASE-ACTIVITY; SMOOTH-MUSCLE CELLS; RECEPTOR SUBSTRATE-1; PHOSPHATIDYLINOSITOL 3-KINASE; SERINE PHOSPHORYLATION; RISK-FACTORS; DISEASE; HYPERTENSION; TRANSDUCTION; STIMULATION AB Insulin resistance and hypertension commonly occur together. Pharmacological inhibition of the renin-angiotensin system has been found to reduce not only hypertension, but also insulin resistance. This raises the possibility that the renin-angiotensin system may interact with insulin signalling. We have investigated the relationship between insulin and angiotensin II (AII) intracellular signalling in vivo using an intact rat heart model, and hz vitro using rat aorta smooth muscle cells (RASMC). Results generated in the in vivo studies indicate that, like insulin, AII stimulates tyrosine phosphorylation of the insulin receptor substrates IRS-1 and IRS-3. This leads to binding of IRS-I and IRS-2 to PI3-kinase. However, in contrast to the effect of insulin, IRS-1- and IRS-2-associated PI3-kinase activity is inhibited by AII in a dose-dependent manner. Moreover, AII inhibits insulin-stimulated IRS-1/IRS-2-associated PI3-kinase activity. The in vivo effects of AII are mediated via the AT(1) receptor. The results of the in vitro studies indicate that AII inhibits insulin-stimulated, IRS-l-associated PI3-kinase activity by interfering with the docking of IRS-I with the p85 regulatory subunit of PI3-kinase. It appears that AII achieves this effect by stimulating serine phosphorylation of the insulin receptor beta-subunit IRS-I, and the p85 regulatory subunit of PI3-kinase. These actions result in the inhibition of normal interactions between the insulin signalling pathway components. Thus, we believe that AII negatively modulates insulin signalling by stimulating multiple serine phosphorylation events in the early components of the insulin signalling cascade. Overactivity of the renin-angiotensin system is likely to impair insulin signalling and contribute to insulin resistance observed in essential hypertension. C1 Dept Med 1, Milan, Italy. Unit Metab Dis, Milan, Italy. UNICAMP, FMC, Dept Med, Campinas, SP, Brazil. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Univ Milan, Ist Malattie Cardiovasc & Resp, Milan, Italy. RP Folli, F (reprint author), IRCCSH San Raffaele, Dept Med 1, Milan, Italy. OI folli, franco/0000-0001-9824-5222 FU NIDDK NIH HHS [P30 DK036836] NR 21 TC 107 Z9 113 U1 0 U2 5 PU JOHANN AMBROSIUS BARTH VERLAG PI HEIDELBERG PA IM WEIHER 10, D-69121 HEIDELBERG, GERMANY SN 0947-7349 J9 EXP CLIN ENDOCR DIAB JI Exp. Clin. Endocrinol. Diabet. PY 1999 VL 107 IS 2 BP 133 EP 139 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 187HM UT WOS:000079781300008 PM 10320054 ER PT J AU Zulewski, H Siggelkov, H Walden, C Becker, W Hufner, M AF Zulewski, H Siggelkov, H Walden, C Becker, W Hufner, M TI Evaluation of procollagen III peptide as a marker of tissue hyperthyroidism in long-term treated women with TSH suppressive doses of thyroxine SO EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES LA English DT Article DE procollagen III peptide; TSH suppression; thyroxine treatment; hyperthyroidism ID HORMONE-BINDING GLOBULIN; HYPOTHYROIDISM; THERAPY; LEVOTHYROXINE; DISEASE; LEVEL AB Increased serum concentrations of the aminoterminal propeptide of collagen III (PIIINP) are found in overt hyperthyroidism. Thus. measurement of serum PIIINP might be useful as an early marker of tissue hyperthyroidism in patients with TSH suppressive thyroxine treatment. In a prospective study we evaluated female patients followed in the thyroid outpatient clinic. Serum PIIINP concentrations were analysed in three groups: patients with TSH suppressive thyroxine treatment for more than 6 months (n = 33, TSH < 0.1 mU/l), patients with thyroxine substitution for hypothyroidism for more than 6 months (n = 20. TSH 0.2-4.0 mU/l) and spontaneous hyperthyroid patients (n = 8. TSH < 0.03 mU/l, increased freeT4 and/or T3). Beside TSH. thyroid hormones and serum PIIINP we measured serum SHBG and a clinical score. Hyperthyroid patients had clearly elevated serum PIIINP and SHBG values and a higher clinical score when compared with other study groups (p < 0.001). Patients with TSH suppressive thyroxine treatment had higher fT4 and T3 concentrations than the thyroxine substitution group (fT4 22 +/- 4.8 pmol/l vs. 17 +/- 2.6 pmol/l, T3 2.2 +/- 0.4 nmol/l vs. 1.8 +/- 0.3 nmol/l. p < 0.001) and also elevated serum SHBG values (77.6 +/- 27.5 nmol/l vs 58.4 +/- 18 nmol/l, p < 0.01). However, serum PIIINP concentrations and the clinical score were very similar in both thyroxine treated groups (PIIINP in TSH suppression group 3.0 +/- 0.67 mu g/l vs. 2.8 +/- 0.65 mu g/l in the substitution group. clinical score 2 +/- 1.8 pts. vs. 1.7 +/- 1.5 pts, p = n.s). In conclusion, serum PIIINP is not a reliable early market for detection of tissue hyperthyroidism in long-term thyroxine treated women with suppressed TSH. C1 Univ Hosp Gottingen, Dept Internal Med, Div Gastroenterol & Endocrinol, Endocrine Unit, Gottingen, Germany. Univ Hosp Gottingen, Dept Nucl Med, Gottingen, Germany. RP Zulewski, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Endocrinol Lab, Wellman 320,50 Blossom St, Boston, MA 02114 USA. RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 17 TC 0 Z9 0 U1 0 U2 0 PU JOHANN AMBROSIUS BARTH VERLAG PI HEIDELBERG PA IM WEIHER 10, D-69121 HEIDELBERG, GERMANY SN 0947-7349 J9 EXP CLIN ENDOCR DIAB JI Exp. Clin. Endocrinol. Diabet. PY 1999 VL 107 IS 3 BP 190 EP 194 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 199GH UT WOS:000080472200006 PM 10376444 ER PT J AU Marino, M Latrofa, F Barbesino, G Chiovato, L AF Marino, M Latrofa, F Barbesino, G Chiovato, L TI Pathogenetic and clinical aspects of autoimmune thyroiditis SO EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES LA English DT Article; Proceedings Paper CT International Symposium on Autoimmunity and Endocrinology CY SEP 10, 1999 CL FRANKFURT, GERMANY SP German Soc Endocrinol DE autoimmune thyroiditis; thyroid autoantibodies; silent thyroiditis; post-partum thyroiditis ID SODIUM-IODIDE SYMPORTER; HASHIMOTOS-THYROIDITIS; GRAVES-DISEASE; ANTIGEN; SERA; FAS; AUTOANTIBODY; THYROTROPIN; TRANSPORTER; MODULATION C1 Univ Pisa, Dept Endocrinol, I-56124 Pisa, Italy. Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA USA. RP Chiovato, L (reprint author), Univ Pisa, Dept Endocrinol, Via Paradisa 2, I-56124 Pisa, Italy. NR 39 TC 0 Z9 0 U1 0 U2 0 PU JOHANN AMBROSIUS BARTH VERLAG PI HEIDELBERG PA IM WEIHER 10, D-69121 HEIDELBERG, GERMANY SN 0947-7349 J9 EXP CLIN ENDOCR DIAB JI Exp. Clin. Endocrinol. Diabet. PY 1999 VL 107 SU 3 BP S79 EP S83 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 242PL UT WOS:000082949400006 PM 10522811 ER PT J AU Laroux, S Lefer, D Huang, P Scalia, R Grisham, MB AF Laroux, S Lefer, D Huang, P Scalia, R Grisham, MB TI Role of the different nitric oxide synthase (NOS) isoforms in modulating leukocyte-endothelial cell interactions in vivo. SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 LSU, Ctr Med, Shreveport, LA USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1999 VL 27 SU 1 MA 135 BP S52 EP S52 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 254EL UT WOS:000083598900159 ER PT J AU Li, SJ Yan, T Yang, JQ Oberley, TD Oberley, LW AF Li, SJ Yan, T Yang, JQ Oberley, TD Oberley, LW TI Hydrogen peroxide or other hydroperoxide are critical players in the suppression of tumor cell growth by MnSOD SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 Univ Iowa, Radiat Res Lab, Med Labs B180, Iowa City, IA 52242 USA. Univ Wisconsin, William S Middleton Mem Vet Hosp, Pathol Serv, Madison, WI 53705 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1999 VL 27 SU 1 MA 446 BP S146 EP S146 DI 10.1016/S0891-5849(99)90982-6 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 254EL UT WOS:000083598900471 ER PT J AU Retsky, KL Chen, K Zeind, J Frei, B AF Retsky, KL Chen, K Zeind, J Frei, B TI Inhibition of copper-induced LDL oxidation by vitamin C is associated with decreased copper-binding to LDL and 2-oxo-histidine formation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE ascorbic acid; vitamin C; atherosclerosis; free radicals; lipid peroxidation; metal ions ID LOW-DENSITY-LIPOPROTEIN; METAL-CATALYZED OXIDATION; HUMAN-BLOOD PLASMA; LIPID-PEROXIDATION; ASCORBIC-ACID; HISTIDINE-RESIDUES; ATHEROGENIC MODIFICATION; SUPEROXIDE-DISMUTASE; AMINO-ACIDS; ANTIOXIDANT AB Oxidatively modified low-density lipoprotein (LDL) has numerous atherogenic properties, and antioxidants that can prevent LDL oxidation may act as antiatherogens. We have previously shown that vitamin C (L-ascorbic acid, AA) and its two-electron oxidation product dehydro-l-ascorbic acid (DHA) strongly inhibit copper (Cu)-induced LDL oxidation. These findings are unusual, as AA is known to act not only as an antioxidant, but also a pro-oxidant in the presence of transition metal ions in vitro, and DHA has no known reducing capacity. Here we report that human LDL (0.4 mg protein/ml) incubated with 40 mu M Cu2+ binds 28.0 @ 3.3 Cu ions per LDL particle (mean @ SD, n = 10). Go-incubation of LDL with AA or DHA led to the time- and concentration-dependent release of up to 70% of bound Cu, which was associated with the inhibition of LDL oxidation. Incubation of LDL with Cu and AA or DHA also led to the time-dependent formation of 2-oxo-histidine, an oxidized derivative of histidine with a low affinity for Cu. Addition of free histidine prevented the formation of the LDL-Cu complexes and inhibited LDL oxidation, despite the fact that Cu remained redox-active. Interestingly, histidine was more effective than AA or DHA at limiting Cu binding to LDL, but at low concentrations AA and DHA were more effective than histidine at inhibiting LDL oxidation. These data suggest that there are at least two types of Cu binding sites on LDL: those that bind Cu in a redox-active form critical for initiation of LDL oxidation, and those that bind Cu ina redox-inactive form not contributing to LDL oxidation. The former sites may be primarily histidine residues of apolipoprotein B-100 that are oxidized to 2-oxo-histidine in the presence of Cu and AA or DHA, thus explaining, at least in part, the unusual inhibitory effect of vitamin C on Cu-induced LDL oxidation. (C) 1998 Elsevier Science Inc. C1 Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Evans Mem Dept Med, Boston, MA 02118 USA. Oregon State Univ, Linus Pauling Inst, Corvallis, OR 97331 USA. Beth Israel Hosp, Core Lab, Boston, MA 02215 USA. Deaconess Med Ctr, Boston, MA USA. RP Frei, B (reprint author), Oregon State Univ, Linus Pauling Inst, 571 Weniger Hall, Corvallis, OR 97331 USA. EM balz.frei@orst.edu FU NHLBI NIH HHS [HL-49954, HL-56170] NR 46 TC 58 Z9 59 U1 0 U2 0 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 JAN PY 1999 VL 26 IS 1-2 BP 90 EP 98 DI 10.1016/S0891-5849(98)00151-8 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 147PB UT WOS:000077574700011 PM 9890644 ER PT J AU Laposata, M AF Laposata, M TI The prothrombin G20210A mutation: A new high-prevalence congenital risk factor for thrombosis SO GASTROENTEROLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Div Lab Med, Boston, MA 02114 USA. RP Laposata, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Div Lab Med, Boston, MA 02114 USA. NR 7 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JAN PY 1999 VL 116 IS 1 BP 213 EP 215 DI 10.1016/S0016-5085(99)70247-7 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 152PG UT WOS:000077785500033 PM 9869621 ER PT J AU Force, T Hajjar, R Del Monte, F Rosenzweig, A Choukroun, G AF Force, T Hajjar, R Del Monte, F Rosenzweig, A Choukroun, G TI Signaling pathways mediating the response to hypertrophic stress in the heart SO GENE EXPRESSION LA English DT Article DE cardiac hypertrophy; stress-activated protein kinases; c-Jun N-terminal kinases; heart failure ID ACTIVATED PROTEIN-KINASES; CARDIAC MYOCYTE HYPERTROPHY; RAT VENTRICULAR MYOCYTES; ADENOVIRAL GENE-TRANSFER; MUSCLE CELL HYPERTROPHY; N-TERMINAL KINASES; C-JUN; PRESSURE-OVERLOAD; TRANSCRIPTION FACTOR; MAP KINASE AB Cardiac hypertrophy is an increase in the mass of the heart. It is a major risk: factor for the development of myocardial infarction and congestive heart failure, diseases that afflict millions of patients worldwide. Hypertrophy can be caused by intrinsic defects of the proteins of the contractile apparatus of the heart, or by extrinsic stimuli such as hypertension. In this review, we will focus on the cytosolic signal transduction pathways that mediate the hypertrophic response to extrinsic stimuli. Although a large number of signaling molecules have been implicated in the hypertrophic response, we will review data that, we believe, suggest there may be only a few molecules that serve as signaling funnels through which many hypertrophic signals must pass on their way to the nucleus. These include the stress response protein kinases (the stress-activated protein kinases or SAPKs, and, possibly, the p38 kinases) and calcineurin. These molecules have as their primary targets transcription factors, many of which have been implicated in the complex yet stereotypic genetic response to hypertrophic stress. In most cases, it is not possible at present to complete the link from hypertrophic stimulus through a specific signaling molecule and a specific transcription factor to the induction of a specific gene that initiates a particular biologic response. We will attempt to identify some of the most important areas where major questions remain in the hopes of stimulating further research into this major cause of death and disability. C1 Massachusetts Gen Hosp, Med Serv, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Choukroun, G (reprint author), Massachusetts Gen Hosp E, Suite 4002,149 13th St, Charlestown, MA 02129 USA. OI Force, Thomas/0000-0002-0450-8659 FU NHLBI NIH HHS [HL54202, HL50361, HL57623] NR 74 TC 25 Z9 25 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 1052-2166 J9 GENE EXPRESSION JI Gene Expr. PY 1999 VL 7 IS 4-6 BP 337 EP 348 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 219XY UT WOS:000081634900013 PM 10440234 ER PT J AU Yu, Q Stamenkovic, I AF Yu, Q Stamenkovic, I TI Localization of matrix metalloproteinase 9 to the cell surface provides a mechanism for CD44-mediated tumor invasion SO GENES & DEVELOPMENT LA English DT Article DE CD44; tumor; invasion; MMP-9; cell surface ID EXTRACELLULAR-MATRIX; CARCINOMA-CELLS; HOMING RECEPTOR; SPLICED EXONS; CD44 ISOFORMS; HYALURONATE; BINDING; IDENTIFICATION; EXPRESSION; INHIBITORS AB The cell surface hyaluronan receptor CD44 promotes tumor growth and metastasis by mechanisms that remain poorly understood. We show here that CD44 associates with a proteolytic form of the matrix metalloproteinase-9 (MMP-9) on the surface of mouse mammary carcinoma and human melanoma cells. CD44-associated cell surface MMP-9 promotes cell-mediated collagen IV degradation in vitro and mediates tumor cell invasion of G8 myoblast monolayers. Several distinct CD44 isoforms coprecipitate with MMP-9 and CD44/MMP-9 coclustering is observed to be dependent on the ability of CD44 to form hyaluronan-induced aggregates. Disruption of CD44/MMP-9 cluster formation, by overexpression of soluble or truncated cell surface CD44, is shown to inhibit tumor invasiveness in vivo. Our observations indicate that CD44 serves to anchor MMP-9 on the cell surface and define a mechanism for CD44-mediated tumor invasion. C1 Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02129 USA. RP Stamenkovic, I (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02129 USA. EM stamenko@helix.mhg.harvard.edu FU NCI NIH HHS [CA55735, T32 CA009216]; NIGMS NIH HHS [GM48614, GM54176] NR 51 TC 467 Z9 491 U1 4 U2 16 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 JAN 1 PY 1999 VL 13 IS 1 BP 35 EP 48 DI 10.1101/gad.13.1.35 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 158NJ UT WOS:000078121400005 PM 9887098 ER PT J AU Bhattacharya, S Michels, CL Leung, MK Arany, ZP Kung, AL Livingston, DM AF Bhattacharya, S Michels, CL Leung, MK Arany, ZP Kung, AL Livingston, DM TI Functional role of p35srj, a novel p300/CBP binding protein, during transactivation by HIF-1 SO GENES & DEVELOPMENT LA English DT Article DE hypoxia; HIF-1; transcription; p35srj; p300; CBP; regulation ID MEDIATES TRANSCRIPTIONAL ACTIVATION; HYPOXIA-INDUCIBLE FACTOR-1; FACTOR 1-ALPHA; GENE; CBP; FAMILY; RECRUITMENT; ADAPTER; COMPLEX; DOMAINS AB Recruitment of p300/CBP by the hypoxia-inducible factor, HIF-1, is essential for the transcriptional response to hypoxia and requires an interaction between the p300/CBP CH1 region and HIF-1 alpha. A new p300-CH1 interacting protein, p35srj, has been identified and cloned. p35srj is an alternatively spliced isoform of MRG1, a human protein of unknown function. Virtually all endogenous p35srj is bound to p300/CBP in vivo, and it inhibits HIF-1 transactivation by blocking the HIF-1 alpha/p300 CH1 interaction. p35srj did not affect transactivation by transcription factors that bind p300/CBP outside the CHI region. Endogenous p35srj is up-regulated markedly by the HIF-1 activators hypoxia or deferoxamine, suggesting that it could operate in a negative-feedback loop. In keeping with this notion, a p300 CH1 mutant domain, defective in HIF-1 but not p35srj binding, enhanced endogenous HIF-1 function. In hypoxic cells, p35srj may regulate HIF-1 transactivation by controlling access of HIF-1 alpha to p300/CBP, and may keep a significant portion of p300/CBP available for interaction with other transcription factors by partially sequestering and functionally compartmentalizing cellular p300/CBP. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Livingston, DM (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. RI Bhattacharya, Shoumo/F-4127-2010; OI Kung, Andrew/0000-0002-9091-488X NR 40 TC 249 Z9 258 U1 0 U2 16 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 JAN 1 PY 1999 VL 13 IS 1 BP 64 EP 75 DI 10.1101/gad.13.1.64 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 158NJ UT WOS:000078121400007 PM 9887100 ER PT J AU Brummel, T Abdollah, S Haerry, TE Shimell, MJ Merriam, J Raftery, L Wrana, JL O'Connor, MB AF Brummel, T Abdollah, S Haerry, TE Shimell, MJ Merriam, J Raftery, L Wrana, JL O'Connor, MB TI The Drosophila Activin receptor Baboon signals through dSmad2 and controls cell proliferation but not patterning during larval development SO GENES & DEVELOPMENT LA English DT Article DE Activin; Baboon; dSmad2; optic proliferation centers; imaginal disc; TGF-beta ID TGF-BETA RECEPTOR; MAD-RELATED PROTEIN; TUMOR-SUPPRESSOR; DPP RECEPTORS; SMAD PROTEINS; GROWTH; GENE; MELANOGASTER; COMPLEX; PHOSPHORYLATION AB The TGP-beta superfamily of growth and differentiation factors, including TGF-beta, Activins and bone morphogenetic proteins (BMPs) play critical roles in regulating the development of many organisms. These factors signal through a heteromeric complex of type I and II serine/threonine kinase receptors that phosphorylate members of the Smad family of transcription factors, thereby promoting their nuclear localization. Although components of TGF-beta/Activin signaling pathways are well defined in vertebrates, no such pathway has been clearly defined in invertebrates. In this study we describe the role of Baboon (Babo), a type I Activin receptor previously called Atr-I, in Drosophila development and characterize aspects of the Babe intracellular signal-transduction pathway. Genetic analysis of babe loss-of-function mutants and ectopic activation studies indicate that Babe signaling plays a role in regulating cell proliferation In mammalian cells, activated Babe specifically stimulates Smad2-dependent pathways to induce TGF-beta/Activin-responsive promoters but not BMP-responsive elements. Furthermore, we identify a new Drosophila Smad, termed dSmad2, that is most closely related to vertebrate Smads 2 and 3. Activated Babe associates with dSmad2 but nor Mad, phosphorylates the carboxy-terminal SSXS motif and induces heteromeric complex formation with Medea, the Drosophila Smad4 homolog. Our results define a novel Drosophila Activin/TGF-beta pathway that is analogous to its vertebrate counterpart and show that this pathway functions to promote cellular growth with minimal effects on patterning. C1 Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA. Hosp Sick Children, Program Dev Biol, Toronto, ON M5G 1X8, Canada. Univ Toronto, Dept Med Genet & Microbiol, Toronto, ON M5G 1X8, Canada. Univ Calif Los Angeles, Dept Biol, Los Angeles, CA 90024 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. Univ Minnesota, Howard Hughes Med Inst, St Paul, MN 55108 USA. Univ Minnesota, Dept Genet & Cell Biol, St Paul, MN 55108 USA. RP O'Connor, MB (reprint author), Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA. RI Raftery, Laurel/H-1406-2012; Wrana, Jeffrey/F-8857-2013; OI Raftery, Laurel/0000-0003-4797-4163; O'Connor, Michael/0000-0002-3067-5506 FU NIGMS NIH HHS [GM47462] NR 66 TC 124 Z9 125 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JAN 1 PY 1999 VL 13 IS 1 BP 98 EP 111 DI 10.1101/gad.13.1.98 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 158NJ UT WOS:000078121400010 PM 9887103 ER PT J AU Lunetta, KL Wilcox, M Smoller, J Neuberg, D AF Lunetta, KL Wilcox, M Smoller, J Neuberg, D TI Exploring linkage for alcoholism using affection status and quantitative event related potential phenotypes SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 11th Genetic Analysis Workshop on Analysis of Genetic and Environmental Factors in Common Diseases CY SEP 08-10, 1998 CL ARCACHON, FRANCE SP INSERM, Commiss Europeenne, Assoc Francaise Myopathiers, Inst Rhone Poulence Rorer France, Conseil Reg Aquitaine DE affected family members; affected sib pairs; quantitative traits ID TRAITS AB Using genome-scan data from the Collaborative Study on the Genetics of Alcoholism (COGA), we compared results of linkage analyses using a qualitative alcoholism phenotype to results of linkage analyses using event related potential (ERP) quantitative phenotypes, and compared our results to the results of Reich et al. [1998] and Begleiter et al. [1998]. We describe a general and simple strategy for identifying regions of the genome which may harbor genes involved in alcohol dependence which takes into consideration the results of both the affection status and ERP linkage analyses. (C) 1999 Wiley-Liss, Inc. C1 Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Psychiat Genet Program Mood & Anxiety Disorders, Boston, MA 02114 USA. RP Lunetta, KL (reprint author), Dana Farber Canc Inst, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. NR 8 TC 0 Z9 0 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 1999 VL 17 SU 1 BP S241 EP S246 PG 6 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 260JM UT WOS:000083945800039 PM 10597443 ER PT J AU Wilcox, MA Smoller, JW Lunetta, KL Neuberg, D AF Wilcox, MA Smoller, JW Lunetta, KL Neuberg, D TI Using recursive partitioning for exploration and follow-up of linkage and association analyses SO GENETIC EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 11th Genetic Analysis Workshop on Analysis of Genetic and Environmental Factors in Common Diseases CY SEP 08-10, 1998 CL ARCACHON, FRANCE SP INSERM, Commiss Europeenne, Assoc Francaise Myopathiers, Inst Rhone Poulence Rorer France, Conseil Reg Aquitaine DE alcoholism; association analyses; COGA; recursive partitioning; SDT AB We first conducted a genome-wide screen for association with discordant sibships using the multi allelic and diallelic SDT. Markers at D4S1628, D8S1109, D9S66 and D7S1797 showed multi-allelic association. Deleterious diallelic association was found for markers at D1S1613, D1S534, D3S2459, D7S1817, and D9S131. Protective association was found at markers D8S1109, D8S1136, and D9S66. We then incorporated these findings with previous linkage findings in the exploration of oligogenes and epistasis using recursive partitioning. We conclude that recursive partitioning can be a useful adjunct to traditional linkage and association analyses in the exploration of these effects. (C) 1999 Wiley-Liss, Inc. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Psychiat Genet Program Mood & Anxiety Disorders, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Neuberg, D (reprint author), Dana Farber Canc Inst, M232,44 Binney St, Boston, MA 02115 USA. NR 6 TC 6 Z9 6 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PY 1999 VL 17 SU 1 BP S391 EP S396 PG 6 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 260JM UT WOS:000083945800064 PM 10597468 ER PT J AU Klein, C Friedman, J Bressman, S Vieregge, P Brin, MF Pramstaller, PP De Leon, D Hagenah, J Sieberer, M Fleet, C Kiely, R Xin, WN Breakefield, XO Ozelius, LJ Sims, KB AF Klein, C Friedman, J Bressman, S Vieregge, P Brin, MF Pramstaller, PP De Leon, D Hagenah, J Sieberer, M Fleet, C Kiely, R Xin, WN Breakefield, XO Ozelius, LJ Sims, KB TI Genetic testing for early-onset torsion dystonia (DYT1): Introduction of a simple screening method, experiences from testing of a large patient cohort, and ethical aspects SO GENETIC TESTING LA English DT Article ID AUTOSOMAL DOMINANT INHERITANCE; ASHKENAZI JEWS; NEED AB Early-onset, generalized primary torsion dystonia (PTB) is an autosomal dominantly inherited disorder, characterized by involuntary movements and abnormal postures. The majority of cases are caused by a 3-bp deletion in the DYT1 gene on chromosome 9q34 that allows for specific genetic testing. We developed a simple, reliable, and cost-effective, PCR-based screening method for this mutation. Testing results from a cohort of 550 cases, including patients with different forms of dystonia:and unclassified movement disorders, revealed that 72.2% of the patients with typical early-onset generalized PTD carried the GAG deletion in the DYT1 gene. Among 300 cases with late-onset focal/segmental dystonia, only 3 patients tested positive for the GAG deletion whereas 12.8% of the patients with an unclassified movement disorder were GAG positive. Our results confirm a genotype/phenotype correlation in early-onset PTD and show that application of strict clinical criteria leads to accurate prediction of carrier status in more than two-thirds of patients with this type of dystonia, Currently, we suggest that testing be recommended in individuals with age of onset of dystonia below 30 years and/or a positive family history of early-onset PTD. Testing is not recommended in patients with onset of symptoms after 30 years or in asymptomatic individuals under the age of 18. C1 Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02114 USA. Beth Israel Med Ctr, Dept Neurol, New York, NY 10003 USA. Univ Lubeck, Dept Neurol, D-2400 Lubeck, Germany. CUNY Mt Sinai Sch Med, Dept Neurol, Movement Disorders Program, New York, NY 10029 USA. Reg Gen Hosp, Dept Neurol, Bolzano Bozen, Italy. Massachusetts Gen Hosp E, Ctr Neurosci, Neurogenet DNA Diagnost Lab, Charlestown, MA 02129 USA. RP Ozelius, LJ (reprint author), AECOM, Mol Genet, 1300 Morris Pk Ave, Bronx, NY 10461 USA. RI Pramstaller, Peter/C-2357-2008 FU FIC NIH HHS [R03-TW00071-91]; NINDS NIH HHS [R01NS26656] NR 29 TC 39 Z9 41 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1090-6576 J9 GENET TEST JI Genet. Test. PY 1999 VL 3 IS 4 BP 323 EP 328 DI 10.1089/gte.1999.3.323 PG 6 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 267UT UT WOS:000084378200001 PM 10627938 ER PT J AU Levy, ML Cummings, JL Kahn-Rose, R AF Levy, ML Cummings, JL Kahn-Rose, R TI Neuropsychiatric symptoms and cholinergic therapy for Alzheimer's disease SO GERONTOLOGY LA English DT Article; Proceedings Paper CT 13th International Conference of Alzheimers Disease International CY SEP 29, 1997 CL HELSINKI, FINLAND DE Alzheimer's disease; neuropsychiatric symptoms; acetylcholinesterase inhibitors ID NURSING-HOME PLACEMENT; PSYCHIATRIC-SYMPTOMS; BEHAVIORAL SYMPTOMS; MAJOR DEPRESSION; CONTROLLED TRIAL; DOUBLE-BLIND; TACRINE; DELUSIONS; DEMENTIA; PHYSOSTIGMINE AB Neuropsychiatric abnormalities, as well as the commonly associated neuropsychological symptoms, are clinical characteristics of Alzheimer's disease (AD), the most common form of dementia. Thus, in addition to a general cognitive and functional decline, neuropsychiatric manifestations, such as agitation, apathy, anxiety, psychoses and disinhibition, are frequently evident in AD patients. Such neuropsychiatric symptoms of AD are the source of considerable patient and caregiver distress, resulting in the prescription of neuroleptics, benzodiazepines or other psychotropic agents, and are a major factor in the decision to transfer the care of patients into nursing homes. Recent evidence suggests that some neuropsychiatric changes associated with AD are related to the cholinergic deficits in the brains of AD patients and that such abnormalities may be responsive to cholinergic therapy. Cholinergic drug therapies indicated for the symptomatic treatment of AD, for example tacrine and the newer cholinesterase (ChE) inhibitors such as donepezil, have been demonstrated to improve memory, language and praxis. Furthermore, although less is known about the effect of ChE inhibitors on the neuropsychiatric symptoms of AD, preliminary evidence suggests that they reduce apathy, anxiety, hallucinations, disinhibition and aberrant motor behaviour. Thus, the newer-generation ChE inhibitors that are! well tolerated, easy to administer and show promise in reducing the cognitive, as well as neuropsychiatric disturbances of AD, may emerge as important treatments for some neuropsychiatric symptoms in patients with central cholinergic deficits, including AD. C1 Univ Calif Los Angeles, Sch Med, Reed Neurol Res Ctr, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Psychiat Serv, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. RP Cummings, JL (reprint author), Univ Calif Los Angeles, Sch Med, Reed Neurol Res Ctr, Dept Psychiat & Biobehav Sci, 710 Westwood Plaza, Los Angeles, CA 90095 USA. FU NIA NIH HHS [AG10123] NR 63 TC 74 Z9 76 U1 2 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0304-324X J9 GERONTOLOGY JI Gerontology PY 1999 VL 45 SU 1 BP 15 EP 22 DI 10.1159/000052760 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 160NQ UT WOS:000078237100003 PM 9876214 ER PT J AU Mischoulon, D Rosenbaum, JF AF Mischoulon, D Rosenbaum, JF TI The use of natural remedies in psychiatry: A commentary SO HARVARD REVIEW OF PSYCHIATRY LA English DT Editorial Material ID SCHIZOPHRENIC-PATIENTS; UNITED-STATES; KAVA; MEDICINE; DEPRESSION; FOLATE C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Mischoulon, D (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WAC-812,15 Parkman St, Boston, MA 02114 USA. NR 42 TC 11 Z9 11 U1 2 U2 3 PU MOSBY-YEAR BOOK 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 JAN-FEB PY 1999 VL 6 IS 5 BP 279 EP 283 DI 10.3109/10673229909000340 PG 5 WC Psychiatry SC Psychiatry GA 160BV UT WOS:000078211200006 PM 10372293 ER PT S AU Okuda, K Foster, R Griffin, JD AF Okuda, K Foster, R Griffin, JD BE Orlic, D Bock, TA Kanz, L TI Signaling domains of the beta c chain of the GM-CSF/IL-3/IL-5 receptor SO HEMATOPOIETIC STEM CELLS: BIOLOGY AND TRANSPLANTATION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 2nd International Symposium and Workshop on Hematopoietic Stem Cells CY JUL 01-04, 1998 CL UNIV TUBINGEN, MEERSBURG, GERMANY SP AMGEN, Germany, AMGEN, Europe, KIRIN, Japan HO UNIV TUBINGEN ID COLONY-STIMULATING FACTOR; TYROSINE PHOSPHORYLATION; MYELOID CELLS; STEEL FACTOR; DEFICIENT MICE; GM-CSF; INTERLEUKIN-3; PROLIFERATION; P210(BCR/ABL); SUBUNIT AB The granulocyte/macrophage colony-stimulating factor (GM-CSF)/interleukin-3 (IL-3)/IL-5 receptors are a family of heterodimeric transmembrane proteins expressed by myeloid lineage cells. Each receptor has a unique ligand-binding alpha chain and they share a common beta chain (beta c chain). Binding of GM-CSF activates at least one receptor-associated tyrosine kinase, JAK2, and rapidly induces tyrosine phosphorylation of the GMR beta c chain (GMR beta), but not the GMR or chain (GMR alpha). Mutation of each of the 8 tyrosine residues in the cytoplasmic domain of the human GMR beta to phenylalanine (GMR beta-F-8) reduced tyrosine phosphorylation of GMR beta, SHP2 and SHC, but not JAK2 or STAT5. Interestingly, GMR beta-F-8 was still capable of inducing at least short-term proliferation and enhancing viability. The role of each individual tyrosine residue was explored by replacing each mutated phenylalanine with the wild-type tyrosine residue. Tyrosine 577 was found to be sufficient to regenerate GM-CSF dependent phosphorylation of SHC, and any of Y577, Y612, or Y695 were sufficient to regenerate GM-CSF-inducible phosphorylation of SHP2. Next, a series of four internal deletion mutants were generated, which deleted small sections from aa 518 to 626. One of these, deleting residues 566-589 was profoundly defective in signaling and supporting viability, and may identify an important viability signaling domain for this receptor family. Overall, these results indicate that GMR beta tyrosine residues are not necessary for activation of the JAK/STAT pathway, or for proliferation, viability, or adhesion signaling in Ba/F3 cells, although tyrosine residues significantly affect the magnitude of the response. However, internal deletion mutant studies identify critical domains for viability and proliferation. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Griffin, JD (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 20 TC 25 Z9 26 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-188-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 872 BP 305 EP 313 DI 10.1111/j.1749-6632.1999.tb08474.x PG 9 WC Cell Biology; Hematology; Multidisciplinary Sciences; Transplantation SC Cell Biology; Hematology; Science & Technology - Other Topics; Transplantation GA BN24X UT WOS:000081273400028 PM 10372132 ER PT J AU Gralnek, IM Jensen, DM Kovacs, TOG Jutabha, R Machicado, GA Gornbein, J King, J Cheng, S Jensen, ME AF Gralnek, IM Jensen, DM Kovacs, TOG Jutabha, R Machicado, GA Gornbein, J King, J Cheng, S Jensen, ME TI The economic impact of esophageal variceal hemorrhage: Cost-effectiveness implications of endoscopic therapy SO HEPATOLOGY LA English DT Article; Proceedings Paper CT American-Association-for-the-Study-of-Liver-Diseases Presidential Plenary Section of Digestive Disease Week CY MAY, 1996 CL SAN FRANCISCO, CALIFORNIA SP Amer Assoc Study Liver Dis ID PROSPECTIVE RANDOMIZED TRIAL; INJECTION SCLEROTHERAPY; PORTAL-HYPERTENSION; BANDING LIGATION; MANAGEMENT; SHUNT AB Esophageal variceal hemorrhage (EVH) is a serious and expensive sequela of chronic liver disease, leading to increased utilization of resources. Today, endoscopic sclerotherapy (ES) and endoscopic ligation (EL) are the accepted, community standards of endoscopic treatment of patients with EVH. However, there are no published studies comparing the economic costs of treating EVH using these interventions. As part of a prospective, randomized trial comparing ES and EL for the treatment of EVH, we estimated the direct costs of health care utilization and cost-effectiveness for the prevention of variceal rebleeding and patient survival at 1-year follow-up. Treatment groups were similar in incidence of variceal rebleeding (41.9% vs. 42.9%), variceal obliteration (41.9% vs. 40.0%), hospital days, blood transfusions, shunt requirements, and survival (71.0% vs. 60.0%). There were significantly more treatment failures for active bleeding using EL (42% vs. 0%; P =.027) and esophageal stricture formation in the ES-treated patients (19.4% vs. 2.9%; P = 0.03). Median total direct cost outcomes were similar between groups (EL = $9,696 and ES = $13,197; P =.46). EL and ES had similar cost/variceal rebleeding prevented ($28,678 vs. $29,093) and cost/survival ($27,313 vs. $23,804). In the subgroup of active bleeders, ES had a substantially lower cost/survival ($28,523 vs. $51,696). We conclude that resource utilization was similar between treatment groups and that the choice of endoscopic therapy for EVH must still rely on clinical grounds. Further studies comparing costs and resource utilization in this patient population are needed. C1 Univ Calif Los Angeles, Sch Med, Div Digest Dis & CURE,Digest Dis Res Ctr, W Los Angeles VA Med Ctr,Ctr Hlth Sci,Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Biomath, Los Angeles, CA USA. RP Gralnek, IM (reprint author), Univ Calif Los Angeles, Sch Med, Div Digest Dis, CHS 44-138,10833 LeConte Ave, Los Angeles, CA 90095 USA. FU NCRR NIH HHS [M01-RR00865-23]; NIDDK NIH HHS [R01 DK 33273, NIDDK 41301] NR 36 TC 41 Z9 43 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 1999 VL 29 IS 1 BP 44 EP 50 DI 10.1002/hep.510290141 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 152CU UT WOS:000077758700008 PM 9862848 ER PT J AU Mohr, L Schauer, JI Boutin, RH Moradpour, D Wands, JR AF Mohr, L Schauer, JI Boutin, RH Moradpour, D Wands, JR TI Targeted gene transfer to hepatocellular carcinoma cells in vitro using a novel monoclonal antibody-based gene delivery system SO HEPATOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; THYMIDINE KINASE GENE; IN-VIVO; HEPATOMA-CELLS; DNA COMPLEXES; ALPHA-FETOPROTEIN; THERAPY; EXPRESSION; IMMUNOLIPOSOMES; CANCER AB Gene therapy approaches for the treatment of malignant tumors will require high-level expression of therapeutic genes in tumors compared with normal tissues. This may be achieved either by targeted gene delivery to tumor cells or by the use of tumor-specific promoters. Here, we describe the use of a novel conjugate consisting of a tumor-reactive monoclonal antibody (mAb), designated AF-20, coupled to a DNA-binding cationic amphiphile, cholesteryl-sp ermine, for gene delivery to hepatocellular carcinoma (HCC) cells. The high-affinity mAb, AF-20, recognizes a rapidly internalized 180-kd cell-surface glycoprotein that is abundantly expressed on HCC and other human tumors. The AF-20 mAb and an isotype-matched control antibody (C7-57) were covalently coupled to cholesteryl-spermine. Binding and internalization of AF-20-cholesteryl-spermine was confirmed by fluorescence microscopy using fluorescein isothiocyanate (FITC)-labeled anti-mouse IgG antibody. Following transfection of FITC-labeled oligonucleotides and ethidium monoazide-labeled plasmid DNA, cellular uptake and intracellular localization of nucleic acids were examined by laser scanning confocal microscopy. Transfection of luciferase or P-galactosidase reporter genes complexed to AF-20-cholesteryl-spermine resulted in high levels of gene expression in AF-20 antigen-positive tumor cells. Very low levels of gene expression were observed using the control compound (C7-57-cholesteryl-spermine), which does not recognize the AF-20 tumor antigen or when AF-20 antigen-negative NIH 3T3 cells were transfected with AF-20-cholesteryl-spermine. Thus, covalent coupling of the AF-20 mAb to cholesteryl-spermine generated a highly specific and efficient nonviral vector system for targeted gene delivery to AF-20 antigen-positive HCC cells. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Mol Hepatol Lab, Charlestown, MA 02129 USA. Apollon Inc, Malvern, PA 19355 USA. RP Wands, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Canc Ctr,Mol Hepatol Lab, 149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-02666] NR 44 TC 37 Z9 37 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 1999 VL 29 IS 1 BP 82 EP 89 DI 10.1002/hep.510290148 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 152CU UT WOS:000077758700014 PM 9862854 ER PT J AU Schacter, DL Wagner, AD AF Schacter, DL Wagner, AD TI Medial temporal lobe activations in fMRI and PET studies of episodic encoding and retrieval SO HIPPOCAMPUS LA English DT Article DE functional neuroimaging; PET; fMRI; encoding; retrieval; medial temporal lobes ID POSITRON EMISSION TOMOGRAPHY; HUMAN HIPPOCAMPAL-FORMATION; MEMORY RETRIEVAL; BRAIN ACTIVITY; REGIONS; RECOGNITION; TASK; KNOWLEDGE; ASSOCIATIONS; TRIALS AB Early neuroimaging studies often failed to obtain evidence of medial temporal lobe (MTL) activation during episodic encoding or retrieval, but a growing number of studies using functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) have provided such evidence. We review data from fMRI studies that converge on the conclusion that posterior MTL is associated with episodic encoding; too few fMRI studies of retrieval have reported MTL activations to allow firm conclusions about their exact locations. We then turn to a recent meta-analysis of PET studies (Lepage et al., Hippocampus 1998;8:313-322) that appears to contradict the fMRI encoding data. Based on their analysis of the rostrocaudal distribution of activations reported during episodic encoding or retrieval, Lepage et al. (1998) concluded that anterior MTL is strongly associated with episodic encoding, whereas posterior MTL is strongly associated with episodic retrieval. After considering the evidence reviewed by Lepage et al. (1998) along with additional studies, we conclude that PET studies of encoding reveal both anterior and posterior MTL activations. These observations indicate that the contradiction between fMRI and PET studies of encoding was more apparent than real. However, PET studies have reported anterior MTL encoding activations more frequently than have fMRI studies. We consider possible sources of these differences. Hippocampus 1999;9:7-24. (C) 1999 Wiley-Liss, Inc. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, Boston, MA USA. RP Schacter, DL (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA. EM dls@wjh.harvard.edu OI Schacter, Daniel/0000-0002-2460-6061 FU NIA NIH HHS [AG05778, AG08441]; NIMH NIH HHS [MH57915] NR 86 TC 480 Z9 485 U1 2 U2 22 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 1999 VL 9 IS 1 BP 7 EP 24 DI 10.1002/(SICI)1098-1063(1999)9:1<7::AID-HIPO2>3.0.CO;2-K PG 18 WC Neurosciences SC Neurosciences & Neurology GA 173WD UT WOS:000079002000002 PM 10088896 ER PT J AU Stern, CE Hasselmo, ME AF Stern, CE Hasselmo, ME TI Bridging the gap: Integrating cellular and functional magnetic resonance imaging studies of the hippocampus SO HIPPOCAMPUS LA English DT Review DE medial temporal lobe; neuroimaging studies; neurophysiological studies; cellular level; system level ID MEDIAL TEMPORAL-LOBE; POSITRON EMISSION TOMOGRAPHY; LONG-TERM POTENTIATION; THETA-RHYTHM; PYRAMIDAL CELLS; NEURONAL-ACTIVITY; PHASE PRECESSION; EPISODIC MEMORY; UNIT-ACTIVITY; SYNAPTIC ENHANCEMENT AB The importance of the medial temporal lobe in memory has been studied extensively at the neuronal, neural ensemble, and systems level. In this report, we discuss recent systems level neuroimaging results in relation to neurophysiological studies of the hippocampus and related structures within the medial temporal lobe. By combining our knowledge across the cellular and systems levels we sought to gain theoretical insight and a better understanding of the function of the hippocampus and related medial temporal robe structures. The integration of information from studies carried out at the cellular and neural ensemble revel with studies at the systems level is difficult because of the vast differences in spatial and temporal resolution of the different research methodologies, differences in neuroanatomy across species, and differences in the types of behavioral and cognitive paradigms used in rat, nonhuman primate, and human studies. Despite these methodological and species-related differences, the neurophysiological studies offer insight into many of the questions raised by recent neuroimaging studies. For instance, there is physiological evidence that suggests that the hippocampal memory system is functionally heterogeneous, which may explain some of the discrepancies in the location and extent of activation reported by different imaging studies of the medial temporal lobe. In addition, we describe recent computational models of the hippocampus which may be useful for bridging the gap between neurophysiological and neuroimaging data. Hippocampus 1999; 9:45-53. (C) 1999 Wiley-Liss, Inc. C1 Boston Univ, Dept Psychol, Cognit Neuroimaging Lab, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, Boston, MA USA. Boston Univ, Dept Psychol, Computat Neurophysiol Lab, Boston, MA 02215 USA. RP Stern, CE (reprint author), Boston Univ, Dept Psychol, Cognit Neuroimaging Lab, 64 Cummington St, Boston, MA 02215 USA. OI Hasselmo, Michael/0000-0002-9925-6377 NR 103 TC 16 Z9 16 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 1999 VL 9 IS 1 BP 45 EP 53 DI 10.1002/(SICI)1098-1063(1999)9:1<45::AID-HIPO5>3.0.CO;2-T PG 9 WC Neurosciences SC Neurosciences & Neurology GA 173WD UT WOS:000079002000005 PM 10088899 ER PT J AU Dupuy-Davies, S Houser, CR AF Dupuy-Davies, S Houser, CR TI Evidence for changing positions of GABA neurons in the developing rat dentate gyrus SO HIPPOCAMPUS LA English DT Article DE glutamate decarboxylase; GAD; hippocampus; in situ hybridization; bromodeoxyuridine ID GLUTAMIC-ACID DECARBOXYLASE; GAMMA-AMINOBUTYRIC-ACID; SOMATOSTATIN-LIKE IMMUNOREACTIVITY; CENTRAL NERVOUS-SYSTEM; EARLY POSTNATAL LIFE; ENCODING 2 FORMS; HIPPOCAMPAL-FORMATION; GABAERGIC NEURONS; GRANULE CELLS; IMMUNOCYTOCHEMICAL LOCALIZATION AB In recent studies, we demonstrated a distinct change in the distribution of glutamate decarboxylase 67 (GAD67) mRNA-containing neurons within the rat dentate gyrus from embryonic day 20 (E20) to postnatal day 15 (PN15) (Dupuy and Houser, J Comp Neurol 1997;389:402-418). We also observed a similar changing pattern for cells with birthdates of many of the mature GAD-containing neurons in the dentate gyrus (Dupuy and Houser, J Comp Neurol 1997;389:402-418), These observations suggested that some early-appearing GABA neurons within the developing molecular layer of the dentate gyrus may gradually alter their positions to become the mature GABAergic cells along the inner border of the granule cell layer. The goal of the present study was to provide additional evidence for our hypothesis by demonstrating the spatial relationships between GAD-containing neurons and granule cells at progressively older ages during development. In this study, immunohistochemical or in situ hybridization methods for the localization of GAD67 or its mRNA were combined with bromodeoxyuridine birthdating techniques that labeled early-generated granule cells with birthdates on E17. At E20, GAD67-containing neurons were located above the granule cell layer that contained E17 birthdated granule cells. During the first two postnatal weeks, both GAD67 mRNA-containing neurons and early-born granule cells were primarily concentrated within the granule cell layer. Double-labeled neurons were rarely observed, and this suggests that these two groups are separate populations. By PN15-PN30, most GAD67 mRNA-containing neurons were distributed along the base of the granule cell layer, significantly below the E17 birthdated granule cells. These findings support our new hypothesis that mature GABA neurons along the inner border of the granule cell layer reach their positions by migrating or translocating through the developing granule cell layer. Hippocampus 1999;9:186-199. (C) 1999 Wiley-Liss, Inc. C1 Univ Calif Los Angeles, Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Wadsworth Div, Serv Neurol, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Wadsworth Div, Res Serv, Los Angeles, CA 90073 USA. RP Houser, CR (reprint author), Univ Calif Los Angeles, Sch Med, Dept Neurobiol, 73-235 CHS, Los Angeles, CA 90095 USA. FU NINDS NIH HHS [NS33360] NR 70 TC 18 Z9 18 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 1050-9631 J9 HIPPOCAMPUS JI Hippocampus PY 1999 VL 9 IS 2 BP 186 EP 199 DI 10.1002/(SICI)1098-1063(1999)9:2<186::AID-HIPO9>3.0.CO;2-B PG 14 WC Neurosciences SC Neurosciences & Neurology GA 190JQ UT WOS:000079959700009 PM 10226778 ER PT J AU Dale, AM AF Dale, AM TI Optimal experimental design for event-related fMRI SO HUMAN BRAIN MAPPING LA English DT Article DE EEG; MEG; ERP; overlap correction; deconvolution; linear model; systems identification ID FUNCTIONAL MRI; TRIALS; RATES AB An important challenge in the design and analysis of event-related or single-trial functional magnetic resonance imaging (fMRI) experiments is to optimize statistical efficiency, i.e., the accuracy with which the event-related hemodynamic response to different stimuli can be estimated for a given amount of imaging time. Several studies have suggested that using a fixed inter-stimulus-interval (ISI) of at least 15 sec results in optimal statistical efficiency or power and that using shorter ISIs results in a severe loss of power. In contrast, recent studies have demonstrated the feasibility of using ISIs as short as 500 ms while still maintaining considerable efficiency or power. Here, we attempt to resolve this apparent contradiction by a quantitative analysis of the relative efficiency afforded by different event-related experimental designs. This analysis shows that statistical efficiency falls off dramatically as the ISI gets sufficiently short, if the ISI is kept fixed for all trials. However, if the ISI is properly jittered or randomized from trial to trial, the efficiency improves monotonically with decreasing mean ISI. importantly, the efficiency afforded by such variable ISI designs can be more than 10 times greater than that which can be achieved by fixed ISI designs. These results further demonstrate the feasibility of using identical experimental designs with fMRI and electro-/magnetoencephalography (EEG/MEG) without sacrificing statistical power or efficiency of either technique, thereby facilitating comparison and integration across imaging modalities. (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. RP Dale, AM (reprint author), Massachusetts Gen Hosp, NMR Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Dale, Anders/A-5180-2010; Li, Chong/F-4265-2015 FU NCRR NIH HHS [R01-RR13609] NR 19 TC 967 Z9 971 U1 5 U2 65 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1999 VL 8 IS 2-3 BP 109 EP 114 DI 10.1002/(SICI)1097-0193(1999)8:2/3<109::AID-HBM7>3.0.CO;2-W PG 6 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 242TM UT WOS:000082957800007 PM 10524601 ER PT J AU Fischl, B Sereno, MI Tootell, RBH Dale, AM AF Fischl, B Sereno, MI Tootell, RBH Dale, AM TI High-resolution intersubject averaging and a coordinate system for the cortical surface SO HUMAN BRAIN MAPPING LA English DT Article DE intersubject averaging; coordinate systems; atlas ID CEREBRAL-CORTEX; VISUAL AREAS; HUMAN BRAIN; MEMORY; LOCALIZATION AB The neurons of the human cerebral cortex are arranged in a highly folded sheet, with the majority of the cortical surface area buried in folds. Cortical maps are typically arranged with a topography oriented parallel to the cortical surface. Despite this unambiguous sheetlike geometry, the most commonly used coordinate systems for localizing cortical features are based on 3-D stereotaxic coordinates rather than on position relative to the 2-D cortical sheet. In order to address the need for a more natural surface-based coordinate system for the cortex, we have developed a means for generating an average folding pattern across a large number of individual subjects as a function on the unit sphere and of nonrigidly aligning each individual with the average. This establishes a spherical surface-based coordinate system that is adapted to the folding pattern of each individual subject, allowing for much higher localization accuracy of structural and functional features of the human brain. (C) 1999 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92093 USA. RP Dale, AM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Dale, Anders/A-5180-2010; Sereno, Martin/F-7657-2012 OI Sereno, Martin/0000-0002-7598-7829 FU NEI NIH HHS [EY07980] NR 40 TC 1347 Z9 1351 U1 5 U2 26 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1999 VL 8 IS 4 BP 272 EP 284 DI 10.1002/(SICI)1097-0193(1999)8:4<272::AID-HBM10>3.0.CO;2-4 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 263LY UT WOS:000084127200010 PM 10619420 ER PT J AU Chee, MWL O'Craven, KM Bergida, R Rosen, BR Savoy, RL AF Chee, MWL O'Craven, KM Bergida, R Rosen, BR Savoy, RL TI Auditory and visual word processing studied with fMRI SO HUMAN BRAIN MAPPING LA English DT Article DE functional magnetic resonance imaging; semantic processing; lexical processing; frontal cortex; supplementary motor area ID POSITRON EMISSION TOMOGRAPHY; FUNCTIONAL-ANATOMY; PREFRONTAL CORTEX; MEMORY RETRIEVAL; CORTICAL AREAS; TASK; LATERALIZATION; COMPREHENSION; LOCALIZATION; ACTIVATION AB Brain activations associated with semantic processing of visual and auditory words were investigated using functional magnetic resonance imaging (fMRI). For each form of word presentation, subjects performed two tasks: one semantic, and one nonsemantic. The semantic task was identical for both auditory and visual presentation: single words were presented and subjects determined whether the word was concrete or abstract. In the nonsemantic task for auditory words, subjects determined whether the word had one syllable or multiple syllables. In the nonsemantic task for visual words, subjects determined whether the word was presented in lower case or upper case. There was considerable overlap in where auditory and visual word semantic processing occurred. Visual and auditory semantic tasks both activated the left inferior frontal (BA 45), bilateral anterior prefrontal (BA 10, 46), and left premotor regions (BA 6) and anterior SMA (BA 6, 8). Left posterior temporal (middle temporal and fusiform gyrus) and predominantly right-sided cerebellar activations were observed during the auditory semantic task but were not above threshold during visual word presentation. The data, when averaged across subjects, did not show obligatory activation of left inferior frontal and temporal language areas during nonsemantic word tasks. Individual subjects showed differences in the activation of the inferior frontal region while performing the same task, even though they showed similar response latency and accuracy. (C) 1999 Wiley-Liss, Inc. C1 Singapore Gen Hosp, Dept Neurol, Singapore 0316, Singapore. Massachusetts Gen Hosp, MGH NMR Ctr, Charlestown, MA USA. Singapore Gen Hosp, Dept Neurol, Singapore 0316, Singapore. Rowland Inst Sci Inc, Cambridge, MA 02142 USA. RP Chee, MWL (reprint author), Singapore Gen Hosp, Dept Neurol, Singapore 0316, Singapore. EM mchee@pacific.net.sg OI Chee, Michael/0000-0002-6087-0548 NR 45 TC 160 Z9 165 U1 1 U2 12 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1999 VL 7 IS 1 BP 15 EP 28 DI 10.1002/(SICI)1097-0193(1999)7:1<15::AID-HBM2>3.0.CO;2-6 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 142VM UT WOS:000077221100002 PM 9882087 ER PT J AU Vaina, LM Cowey, A Kennedy, D AF Vaina, LM Cowey, A Kennedy, D TI Perception of first- and second-order motion: Separable neurological mechanisms? SO HUMAN BRAIN MAPPING LA English DT Article DE visual motion deficits; neurological patients; first and second order motion; cortical parcellation ID HUMAN VISUAL-CORTEX; HUMAN CEREBRAL-CORTEX; HUMAN BRAIN; 2ND-ORDER MOTION; AREAS; ORGANIZATION; CONNECTIONS; IMPAIRMENT; LESIONS; IMAGES AB An unresolved issue in visual motion perception is how distinct are the processes underlying "first-order" and "second-order" motion. The former is defined by spatiotemporal variations of luminance and the latter by spatiotemporal variations in other image attributes, such as contrast or depth. Here we describe two neurological patients with focal unilateral lesions whose contrasting perceptual deficits on psychophysical tasks of "first-order" and "second-order" motion are related to the maps of the human brain established by functional neuroimaging and gross anatomical features. We used a relatively fine-grained neocortical parcellation method applied to high-resolution MRI scans of the patients' brains to illustrate a subtle, yet highly specific dissociation in the visual motion system in humans. Our results suggest that the two motion systems are mediated by regionally separate mechanisms from an early stage of cortical processing. (C) 1999 Wiley-Liss, Inc. C1 Boston Univ, Dept Biomed Engn & Neurol, Brain & Vis Res Lab, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England. Massachusetts Gen Hosp, Ctr Morphometr Anal, Charlestown, MA USA. RP Vaina, LM (reprint author), Boston Univ, Dept Biomed Engn, Brain & Vis Res Lab, 44 Cummington St, Boston, MA 02215 USA. EM vaina@enga.bu.edu RI Kennedy, David/H-3627-2012 FU NEI NIH HHS [2EY07861-3, R01 EY007861] NR 40 TC 57 Z9 57 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1999 VL 7 IS 1 BP 67 EP 77 DI 10.1002/(SICI)1097-0193(1999)7:1<67::AID-HBM6>3.0.CO;2-K PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 142VM UT WOS:000077221100006 PM 9882091 ER PT J AU Talavage, TM Edmister, WB Ledden, PJ Weisskoff, RM AF Talavage, TM Edmister, WB Ledden, PJ Weisskoff, RM TI Quantitative assessment of auditory cortex responses induced by imager acoustic noise SO HUMAN BRAIN MAPPING LA English DT Article DE fMRI; pulse sequence; brain mapping; stimulus masking; response suppression ID HUMAN BRAIN; MRI AB A clustered volume acquisition functional MRT pulse sequence was modified to assess the response to the acoustic noise of echo-planar imaging in the auditory cortex and to determine whether it is possible to obtain data which is relatively free of acoustic contamination. The spatial location and strength (percent signal change) of cortical responses to the imager noise were examined by introducing extra gradient readouts, without slice excitation, to provide acoustic stimulation immediately prior to acquisition of a cerebral volume. The duration of acoustic stimulation was controlled by varying the number of extra gradient readouts. Slice acquisitions were clustered at the end of the repetition time (TR) period to prevent a response from being induced by the volume acquisition itself ("Intra-Acquisition Response"). The cerebral volumes were acquired using a long TR in order to limit the integration of the cortical response across volume acquisitions ("Inter-Acquisition Response"). Cortical responses were observed to be largest and most significant on the medial two-thirds of Heschl's gyrus, the location of primary auditory cortex. Mean signal changes induced by the imager noise were observed to be as high as 0.95%. A 2 sec delay prior to onset of the BOLD response was empirically determined. These results demonstrate that clustered volume acquisitions may be utilized for up to 2 sec of volume acquisition without inducing an appreciable Intra-Acquisition Response and can be used, with a sufficiently long TR, to provide data which are similarly free of any Inter-Acquisition Response. (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Radiol, NMR Ctr, MGH, Boston, MA 02114 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Speech & Hearing Sci Program, Cambridge, MA 02139 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Med Engn Med Phys Program, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, MD PhD Program, Boston, MA USA. RP Talavage, TM (reprint author), Purdue Univ, Sch Elect & Comp Engn, 1285 Elect Engn Bldg,Room 336, W Lafayette, IN 47907 USA. FU NIDA NIH HHS [P01DA09467-03]; NIDCD NIH HHS [T32DC00038-04, P01DC00119] NR 13 TC 85 Z9 86 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 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1999 VL 7 IS 2 BP 79 EP 88 DI 10.1002/(SICI)1097-0193(1999)7:2<79::AID-HBM1>3.0.CO;2-R PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 160HU UT WOS:000078225200001 PM 9950065 ER PT J AU Edmister, WB Talavage, TM Ledden, PJ Weisskoff, RM AF Edmister, WB Talavage, TM Ledden, PJ Weisskoff, RM TI Improved auditory cortex imaging using clustered volume acquisitions SO HUMAN BRAIN MAPPING LA English DT Article DE fMRI; pulse sequence; brain mapping; EPI ID HUMAN BRAIN; MRI AB The effects of the noise of echo-planar functional magnetic resonance imaging on auditory cortex responses were compared for two methods of acquiring functional MR data. Responses observed with a distributed volume acquisition sequence were compared to those obtained with clustered volume acquisition sequence. In the former case, slices from the volume were acquired at equal intervals within the repetition time, whereas the latter acquired all slices in rapid succession at the end of the imaging period. The clustered volume acquisition provides a period of quiet during which a stimulus may be presented uninterrupted and uncontaminated by the noise of echo-planar imaging. Both sequences were implemented on a General Electric Signa imager retrofitted for echo-planar imaging by Advanced NMR Systems, Inc. The sequences were used to acquire 60 images per slice of a fixed volume of cerebral cortex while subjects were presented an instrumental music stimulus in an On vs. OK paradigm. Data were acquired for both sequences using TR values of 2, 3, 4, 6 and 8 sec. The clustered volume acquisition sequence was found to yield greater measures of dynamic range (percent signal change, mean statistical power per unit imaging time) across the tested range of TR values. Observations of more consistent spatial extent of responses, greater mean signal changes, and higher and more consistent values of mean t-statistic per unit imaging time demonstrate the efficacy of using a clustered volume acquisition for fMRI of auditory cortex. (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Med Engn Med Phys Program, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, MD PhD Program, Boston, MA USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Speech & Hearing Sci Program, Cambridge, MA 02139 USA. RP Edmister, WB (reprint author), Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, 2nd Floor,Bldg 149,13th St, Charlestown, MA 02129 USA. FU NIDA NIH HHS [P01DA09467-03]; NIDCD NIH HHS [P01DC00119, T32DC00038-04] NR 10 TC 242 Z9 245 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PY 1999 VL 7 IS 2 BP 89 EP 97 DI 10.1002/(SICI)1097-0193(1999)7:2<89::AID-HBM2>3.0.CO;2-N PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 160HU UT WOS:000078225200002 PM 9950066 ER PT J AU Wheeler, VC Auerbach, W White, JK Srinidhi, J Auerbach, A Ryan, A Duyao, MP Vrbanac, V Weaver, M Gusella, JF Joyner, AL MacDonald, ME AF Wheeler, VC Auerbach, W White, JK Srinidhi, J Auerbach, A Ryan, A Duyao, MP Vrbanac, V Weaver, M Gusella, JF Joyner, AL MacDonald, ME TI Length-dependent gametic CAG repeat instability in the Huntington's disease knock-in mouse SO HUMAN MOLECULAR GENETICS LA English DT Article ID AGE-OF-ONSET; TRINUCLEOTIDE REPEAT; (CAG)(N) REPEAT; MOLECULAR ANALYSIS; TRANSGENIC MICE; HD GENE; SOMATIC INSTABILITY; MEIOTIC VARIABILITY; PATERNAL REPEAT; EXPANSION AB The CAG repeats in the human Huntington's disease (HD) gene exhibit striking length-dependent intergenerational instability, typically small size increases or decreases of one to a few CAGs, but little variation in somatic tissues. In a subset of male transmissions, larger size increases occur to produce extreme HD alleles that display somatic instability and cause juvenile onset of the disorder. Initial efforts to reproduce these features in a mouse model transgenic for HD exon 1 with 48 CAG repeats revealed only mild intergenerational instability (similar to 2% of meioses), A similar pattern was obtained when this repeat was inserted into exon 1 of the mouse Hdh gene. However, lengthening the repeats in Hdh to 90 and 109 units produced a graded increase in the mutation frequency to >70%, with instability being more evident in female transmissions. No large jumps in CAG length were detected in either male or female transmissions. Instead, size changes were modest increases and decreases, with expansions typically emanating from males and contractions from females. Limited CAG variation in the somatic tissues gave way to marked mosaicism in liver and striatum for the longest repeats in older mice. These results indicate that gametogenesis is the primary source of inherited instability in the Hdh knock-in mouse, as it is in man, but that the underlying repeat length-dependent mechanism, which may or may not be related in the two species, operates at higher CAG numbers. Moreover, the large CAG repeat increases seen in a subset of male HD transmissions are not reproduced in the mouse, suggesting that these arise by a different fundamental mechanism than the small size fluctuations that are frequent during gametogenesis in both species. C1 Massachusetts Gen Hosp East, Mol Neurogenet Unit, Boston, MA 02129 USA. NYU Med Ctr, Dev Genet Program, Skirball Inst Biomol Med, New York, NY 10016 USA. NYU Med Ctr, Dept Cell Biol, New York, NY 10016 USA. RP MacDonald, ME (reprint author), Massachusetts Gen Hosp East, Mol Neurogenet Unit, Bldg 149,13th St, Boston, MA 02129 USA. EM macdonam@helix.mgh.harvard.edu FU NINDS NIH HHS [NS16367, NS32765] NR 55 TC 214 Z9 217 U1 0 U2 6 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 JAN PY 1999 VL 8 IS 1 BP 115 EP 122 DI 10.1093/hmg/8.1.115 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 162ZF UT WOS:000078377200014 PM 9887339 ER PT J AU Niida, Y Lawrence-Smith, N Banwell, A Hammer, E Lewis, J Beauchamp, RL Sims, K Ramesh, VL Ozelius, L AF Niida, Y Lawrence-Smith, N Banwell, A Hammer, E Lewis, J Beauchamp, RL Sims, K Ramesh, VL Ozelius, L TI Analysis of both TCS1 and TSC2 for germline mutations in 126 unrelated patients with tuberous sclerosis SO HUMAN MUTATION LA English DT Article DE tuberous sclerosis complex; TSC1; TSC2; SSCP; hamartin; tuberin ID EKER RAT MODEL; GENE-2 PRODUCT; DIAGNOSTIC-CRITERIA; HETEROZYGOSITY; IDENTIFICATION; HAMARTOMAS; 9Q34; COMPLEX; DISEASE; HOMOLOG AB Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the development of multiple hamartomas involving many organs. About two thirds of the cases are sporadic and appear to represent. new mutations, With the cloning of two causative genes, TSC1 and TSC2 it is now possible to analyze both genes in TSC patients and identify germline mutations, Here we report the mutational analysis of the entire coding region of both TSC1 and TSC2 genes in 126 unrelated TSC patients, including 40 familial and 86 sporadic cases, by single-stranded conformational polymorphism (SSCP) analysis followed by direct sequencing. Mutations were identified in a total of 74 (59%) cases, including 16 TSC1 mutations (5 sporadic and 11 familial cases) and 58 TSC2 mutations (42 sporadic and 16 familial cases). Overall, significantly more TSC2 mutations were found in our population, with a relatively equal distribution of mutations between TSC1 and TSC2 among the familial cases, but a marked underrepresentation of TSC1 mutations among the sporadic cases (P = 0.0035, Fisher's exact test), All TSC1 mutations were predicted to be protein truncating. However, in TSC2 13 missense mutations were found, five clustering in the GAP-related domain and three others occurring in exon 16. Upon comparison of clinical manifestations, including the incidence of intellectual disability, we could not find any observable differences between TSC1 and TSC2 patients. Our data help define the distribution and spectrum of mutations associated with the TSC loci and will be useful for both understanding the function of these genes as well as generic counseling in patients with the disease. Hum Mutat 14:412-422, 1999, (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. RP Ramesh, VL (reprint author), Massachusetts Gen Hosp E, Mol Neurogenet Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. EM ramesh@helix.mgh.harvard.edu FU NINDS NIH HHS [NS24279] NR 44 TC 94 Z9 98 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1059-7794 EI 1098-1004 J9 HUM MUTAT JI Hum. Mutat. PY 1999 VL 14 IS 5 BP 412 EP 422 DI 10.1002/(SICI)1098-1004(199911)14:5<412::AID-HUMU7>3.0.CO;2-K PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 253LK UT WOS:000083557900007 PM 10533067 ER PT J AU Kraus, JP Janosik, M Kozich, V Mandell, R Shih, V Sperandeo, MP Sebastio, G de Franchis, R Andria, G Kluijtmans, LAJ Blom, H Boers, GHJ Gordon, RB Kamoun, P Tsai, MY Kruger, WD Koch, HG Ohura, T Gaustadnes, M AF Kraus, JP Janosik, M Kozich, V Mandell, R Shih, V Sperandeo, MP Sebastio, G de Franchis, R Andria, G Kluijtmans, LAJ Blom, H Boers, GHJ Gordon, RB Kamoun, P Tsai, MY Kruger, WD Koch, HG Ohura, T Gaustadnes, M TI Cystathionine beta-synthase mutations in homocystinuria SO HUMAN MUTATION LA English DT Article DE cystathionine beta synthase; CBS; homocystinuria; homocysteine; inborn error ID PYRIDOXINE-RESPONSIVE HOMOCYSTINURIA; MOLECULAR-BASIS; MESSENGER-RNA; NONRESPONSIVE HOMOCYSTINURIA; MISSENSE MUTATIONS; 3 MUTATIONS; CBS GENE; PATIENT; DEFICIENCY; IDENTIFICATION AB The major cause of homocystinuria is mutation of the gene encoding the enzyme cystathionine beta-synthase (CBS), Deficiency of CBS activity results in elevated levels of homocysteine as well as methionine in plasma and urine and decreased levels of cystathionine and cysteine, Ninety-two different disease associated mutations have been identified in the CBS gene in 310 examined homocystinuric alleles in more than a dozen laboratories around the world. Most of these mutations are missense, and the vast majority of these are private mutations. The two most frequently encountered of these mutations are the pyridoxine responsive I278T and the pyridoxine nonresponsive G307S, Mutations due to deaminations of methylcytosines represent 53% of all point substitutions in the coding region of the CBS gene. Hum Mutat 13:362-375, 1999, (C) 1999 Wiley-Liss, Inc. C1 Univ Colorado, Sch Med, Dept Pediat C233, Denver, CO 80262 USA. Charles Univ, Fac Med 1, Inst Inherited Metab Disorders, Prague, Czech Republic. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Naples Federico II, Dept Pediat, Naples, Italy. Univ Nijmegen Hosp, Dept Pediat, Nijmegen, Netherlands. Univ Nijmegen Hosp, Dept Internal Med, Nijmegen, Netherlands. Univ Queensland, Princess Alexandra Hosp, Dept Med, Brisbane, Qld, Australia. Hop Necker Enfants Malad, Biochim Genet Lab, F-75743 Paris, France. Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. Univ Munster, Klin Kinderheilkunde, Muenster, Germany. Tohoku Univ, Dept Pediat, Sendai, Miyagi 980, Japan. Skejby Univ Hosp, Dept Clin Chem, Aarhus, Denmark. RP Kraus, JP (reprint author), Univ Colorado, Sch Med, Dept Pediat C233, 4200 E 9th Ave, Denver, CO 80262 USA. RI kruger, warren/A-6407-2008; Kozich, Viktor/A-7672-2008; Kluijtmans, L.A.J./L-4437-2015 OI kruger, warren/0000-0002-4990-3695; Kozich, Viktor/0000-0001-5820-5277; FU NICHD NIH HHS [P01HD0805] NR 48 TC 193 Z9 205 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PY 1999 VL 13 IS 5 BP 362 EP 375 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 192LD UT WOS:000080079400003 PM 10338090 ER PT J AU Osei, SY Price, DA Fisher, NDL Porter, L Laffel, LMB Hollenberg, NK AF Osei, SY Price, DA Fisher, NDL Porter, L Laffel, LMB Hollenberg, NK TI Hyperglycemia and angiotensin-mediated control of the renal circulation in healthy humans SO HYPERTENSION LA English DT Article; Proceedings Paper CT 52nd Annual Fall Conference and Scientific Session of the American-Heart-Association, Council-for-High-Blood-Pressure-Research CY SEP 15-18, 1998 CL PHILADELPHIA, PENNSYLVANIA SP Amer Heart Assoc, Council High Blood Pressure Res DE renal blood flow; glomerular filtration rate; hyperglycemia; sodium; renin ID CONVERTING ENZYME-INHIBITION; PLASMA-RENIN ACTIVITY; INSULIN-DEPENDENT DIABETICS; ACE-INHIBITION; MELLITUS; SYSTEM; NEPHROPATHY; SODIUM; HYPERTENSION; RESPONSES AB Type 1 and type 2 diabetics have an enhanced renal vasodilator response to angiotensin-converting enzyme (ACE) inhibition despite suppressed plasma renin activity (PRA), indicating possible activation of the intrarenal renin angiotensin system. To investigate the role of hyperglycemia, we evaluated the renal hemodynamic response to ACE inhibition in 9 healthy subjects in high-salt balance after steady-state hyperglycemia (8.4+/-1 mmol/L) was achieved via intravenous glucose administration. Renal plasma flow (RPF) and glomerular filtration rate (GFR) responses to captopril and to angiotensin II (Ang II) were measured as paraminohippuric acid and inulin clearances. Hyperglycemia produced a significant increase in RPF of 117 mL.min(-1).1.73 m(-2) after 90 minutes but not GFR, Administration of captopril at a dose of 25 mg during glucose infusion led to an increase in RPF of 173+/-24 mL.min(-1).1.73 m(-2) (P<0.01) but did not significantly change RPF in the absence of hyperglycemia (7+/-21 mL.min(-1).1.73 m(-2)). Captopril did not alter GFR in the presence or absence of hyperglycemia. Ang II infusion during hyperglycemia decreased RPF by 45+/-16 mL.min(-1).1.73 m(-2), and this was significantly enhanced by captopril (-98+/-26 mL.min(-1).1.73 m(-2), P<0.05). In contrast, there was no enhancement of the vasoconstrictor response to Ang II in the absence of hyperglycemia. PRA did not change with hyperglycemia. Enhancement of renal vasodilation during hyperglycemia by captopril without alteration of PRA suggests activation of the intrarenal renin angiotensin system. C1 Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Endocrine Hypertens, Dept Med, Boston, MA 02115 USA. RP Osei, SY (reprint author), Brigham & Womens Hosp, Div Endocrine Hypertens, Dept Med, 221 Longwood Ave, Boston, MA 02115 USA. EM syosei@bics.bwh.harvard.edu FU NIDDK NIH HHS [1 RO1 DK544668-01] NR 38 TC 24 Z9 25 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JAN PY 1999 VL 33 IS 1 SU S BP 559 EP 564 PN 2 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 163AC UT WOS:000078379200067 PM 9931165 ER PT S AU del Rio, MS Moskowitz, MA AF del Rio, MS Moskowitz, MA BE Roach, RC Wagner, PD Hackett, PH TI High altitude headache - Lessons from headaches at sea level SO HYPOXI: INTO THE NEXT MILLENNIUM SE Advances in Experimental Medicine and Biology LA English DT Article; Proceedings Paper CT 11th International Hypoxia Symposium CY FEB 28-MAR 03, 1999 CL EDMONTON, CANADA DE pain; headache; hypoxia; high altitude ID ACUTE MOUNTAIN-SICKNESS; RAT DURA-MATER; SUBSTANCE-P; CEREBRAL EDEMA; HYPOXIA; BRAIN; STIMULATION AB There is little known about high altitude headache, except that it is an important and serious problem that often heralds the onset of acute mountain sickness. We do know that the brain itself is an insensate organ except for its meninges which contain sensory axons projecting from the trigeminal nerve. These nerve fibers travel in proximity to meningeal blood vessels and constitute an important component of the trigeminovascular system. Signals generated at high altitude which may activate the trigeminovascular system can arise from brain, blood or the blood vessel wall, include protons, neurotransmitters and other potential noxious agents which can discharge or sensitize small unmyelinated fibers. Brain edema and raised intracranial pressure may cause headache by compressing brain structures leading to displacement and stretching of the pain-sensitive intracranial structures. Small hemorrhage may irritate and discharge these fibers chemically. Furthermore, high altitude seems capable of decreasing the threshold of response to sensory stimulation. Therefore, headache can be attributed to activation of a common pathway, the trigeminovascular system by both chemical or mechanical stimulation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab, Boston, MA 02129 USA. RP del Rio, MS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab, Boston, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 NR 34 TC 27 Z9 28 U1 0 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46289-3 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1999 VL 474 BP 145 EP 153 PG 9 WC Medicine, General & Internal; Medicine, Research & Experimental; Physiology SC General & Internal Medicine; Research & Experimental Medicine; Physiology GA BP33G UT WOS:000084730500013 PM 10634999 ER PT J AU Fischl, B Schwartz, EL AF Fischl, B Schwartz, EL TI Adaptive nonlocal filtering: A fast alternative to anisotropic diffusion for image enhancement SO IEEE TRANSACTIONS ON PATTERN ANALYSIS AND MACHINE INTELLIGENCE LA English DT Article DE segmentation; diffusion; scale-space; anisotropic diffusion; nonlinear diffusion; filtering; permutation filter; nonlocal filter ID EDGE-DETECTION; NEURAL DYNAMICS; PERCEPTION; FEATURES; SHAPE AB Nonlinear anisotropic diffusion algorithms provide significant improvement in image enhancement as compared to linear filters. However, the excessive computational cost of solving nonlinear PDEs precludes their use in real-time vision applications. In the present paper, we show that two orders of magnitude speed improvement is provided by a new image filtering paradigm in which an adaptively determined vector field specifies nonlocal application points for an image filter. C1 Boston Univ, Dept Cognit & Neural Syst, Boston, MA 02215 USA. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. RP Fischl, B (reprint author), Boston Univ, Dept Cognit & Neural Syst, 677 Beacon St, Boston, MA 02215 USA. EM eric@thing4.bu.edu; fischl@cns.bu.edu NR 35 TC 38 Z9 41 U1 0 U2 2 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA SN 0162-8828 J9 IEEE T PATTERN ANAL JI IEEE Trans. Pattern Anal. Mach. Intell. PD JAN PY 1999 VL 21 IS 1 BP 42 EP 48 DI 10.1109/34.745732 PG 7 WC Computer Science, Artificial Intelligence; Engineering, Electrical & Electronic SC Computer Science; Engineering GA 163DZ UT WOS:000078388900005 ER PT J AU Gerwin, N Gonzalo, JA Lloyd, C Coyle, AJ Reiss, Y Banu, N Wang, BP Xu, H Avraham, H Engelhardt, B Springer, TA Gutierrez-Ramos, JC AF Gerwin, N Gonzalo, JA Lloyd, C Coyle, AJ Reiss, Y Banu, N Wang, BP Xu, H Avraham, H Engelhardt, B Springer, TA Gutierrez-Ramos, JC TI Prolonged eosinophil accumulation in allergic lung interstitium of ICAM-2-deficient mice results in extended hyperresponsiveness SO IMMUNITY LA English DT Article ID ADHESION MOLECULE-1-DEFICIENT MICE; T-CELLS; BRONCHIAL HYPERREACTIVITY; RESPIRATORY EPITHELIUM; COUNTER-RECEPTOR; MURINE MODEL; GUINEA-PIGS; IN-VITRO; INFLAMMATION; LYMPHOCYTE AB ICAM-2-deficient mice exhibit prolonged accumulation of eosinophils in lung interstitium concomitant with a delayed increase in eosinophil numbers in the airway lumen during the development of allergic lung inflammation. The ICAM-2-dependent increased and prolonged accumulation of eosinophils in lung interstitium results in prolonged, heightened airway hyperresponsiveness. These findings reveal an essential role for ICAM-2 in the development of the inflammatory and respiratory components of allergic lung disease. This phenotype is caused by the lack of ICAM-2 expression on non-hematopoietic cells. ICAM-2 deficiency on endothelial cells causes reduced eosinophil transmigration in vitro. ICAM-2 is not essential for lymphocyte homing or the development of leukocytes, with the exception of megakaryocyte progenitors, which are significantly reduced. C1 Millennium Biotherapeut, Cambridge, MA 02139 USA. Millennium Pharmaceut, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Max Planck Inst Physiol & Klin Forsch, D-61231 Bad Nauheim, Germany. Harvard Univ, Sch Med, New England Deaconess Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Beth Israel Hosp, Div Immunol, Boston, MA 02215 USA. RP Gerwin, N (reprint author), Millennium Biotherapeut, Cambridge, MA 02139 USA. FU Wellcome Trust [087618] NR 42 TC 82 Z9 83 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JAN PY 1999 VL 10 IS 1 BP 9 EP 19 DI 10.1016/S1074-7613(00)80002-3 PG 11 WC Immunology SC Immunology GA 163WE UT WOS:000078428700002 PM 10023766 ER PT J AU Slavik, JM Hutchcroft, JE Bierer, BE AF Slavik, JM Hutchcroft, JE Bierer, BE TI CD28/CTLA-4 and CD80/CD86 families - Signaling and function SO IMMUNOLOGIC RESEARCH LA English DT Review DE T lymphocytes; signal transduction; cell-surface molecules; costimulatory molecules ID T-CELL RECEPTOR; PROTEIN-KINASE-C; PHOSPHATIDYLINOSITOL 3-KINASE ASSOCIATION; MULTIORGAN TISSUE DESTRUCTION; LYMPHOCYTE ANTIGEN RECEPTORS; CD28 COSTIMULATORY PATHWAY; CTLA-4 COUNTER-RECEPTOR; P70 S6 KINASE; TYROSINE KINASE; CTLA-4-DEFICIENT MICE AB T cell stimulation in the absence of a second, costimulatory signal can lead to anergy or the induction of cell death. CD28 is a major T cell costimulatory receptor, the coengagement of which can prevent anergy and cell death. The CD28 receptor is a member of a complex family of polypeptides that includes at least two receptors and two ligands. Cytotoxic lymphocyte-associated molecule-4 (CTLA-4, CD152) is the second member of the CD28 receptor family. The ligands or counterreceptors for these two proteins are the B7 family members, CD80 (B7-1) and CD86 (B7-2). This article reviews the CD28/CTLA4 and CD80/CD86 families, and outlines the functional outcomes an biochemical signaling pathways recruited after CD28 ligation. C1 NHLBI, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Purdue Univ, Dept Biochem, W Lafayette, IN 47907 USA. RP Bierer, BE (reprint author), NHLBI, NIH, Bldg 10,Room 5D49,10 Ctr Dr, Bethesda, MD 20892 USA. NR 199 TC 112 Z9 126 U1 0 U2 8 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0257-277X J9 IMMUNOL RES JI Immunol. Res. PY 1999 VL 19 IS 1 BP 1 EP 24 DI 10.1007/BF02786473 PG 24 WC Immunology SC Immunology GA 193CN UT WOS:000080118400001 PM 10374692 ER PT J AU Chang, MP Norman, DC AF Chang, MP Norman, DC TI Ethanol impairs major histocompatibility complex (MHC) class II molecule-mediated but not MHC class I molecule-mediated T cell response in alcohol-consuming mice SO IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; TOXIC LYMPHOCYTES-T; MURINE SPLEEN-CELLS; STIMULATORY FACTOR; CYTO-TOXICITY; INVITRO; GENERATION; PROLIFERATION; IMMUNOSUPPRESSION; DIFFERENTIATION AB The goal of this study was to determine whether alcohol affects alloantigen-induced proliferative and cytolytic activity of T cells in mice, and whether the altered immune response was in part due to a defect of IL-2 activity. The ability of spleen cells from individual alcohol-consuming C57BL/6 mice to generate allo-specific mixed lymphocyte response (MLR) and cytotoxic T lymphocyte (CTL) was compared to that of mice fed on an isocaloric maltose diet and regular diet. Allospecific MLR and CTL were generated by sensitizing spleen cells of C57BL/6 mice against spleen cells from BALB/c mice, and the allo-specific CTL activity was determined by the ability of the CTL to kill Cr-51-labeled P815 mastocytoma target cells. Our results showed that the allo-specific MLR of the responder cells from alcohol-consuming mice was significantly reduced (40% reduction, p<0.01), and the addition of exogenous interleukin 2 (IL-2) could not reverse the suppression of MLR induced by ethanol. However, our results clearly showed that ethanol has little suppressive effect on allo-reactive CTL of alcohol-consuming mice as compared to the alloreactivity of the control mice (P>0.05). Finally, we also demonstrated that ethanol did not impair the alloantigen-induced IL-2 production in the mixed lymphocyte cultures (P>0.1). C1 W Los Angeles Vet Affairs Med Ctr, GRECC, W Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. RP Chang, MP (reprint author), W Los Angeles Vet Affairs Med Ctr, GRECC, W Los Angeles, CA 90073 USA. NR 68 TC 7 Z9 7 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0892-3973 J9 IMMUNOPHARM IMMUNOT JI Immunopharmacol. Immunotoxicol. PY 1999 VL 21 IS 1 BP 65 EP 87 DI 10.3109/08923979909016395 PG 23 WC Immunology; Pharmacology & Pharmacy; Toxicology SC Immunology; Pharmacology & Pharmacy; Toxicology GA 173GN UT WOS:000078972900005 PM 10084331 ER PT J AU Ring, D Jupiter, JB AF Ring, D Jupiter, JB TI Mangling upper limb injuries in industry SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article DE upper limb; vascular injury; open fracture; soft tissue injury; internal fixation; industrial injuries ID LOWER-EXTREMITY; VASCULAR INJURIES; ARTERIAL INJURIES; TRAUMA; AMPUTATION; FRACTURES; SALVAGE; MANAGEMENT; WOUNDS; FOREARM AB The salvage of upper limbs mangled by industrial machinery became possible with the development of predictable techniques of vascular and microvascular anastamosis. Unfortunately, many of these salvaged limbs are associated with fair and poor functional outcomes. The quality of the skeletal fixation can have a substantial effect on the functional outcome and should be a major focus of the limb repair process, internal plate fixation facilitates wound care and limb mobilization without tethering muscle-tendon units and is safe in the majority of severe upper limb injuries provided that all devitalized tissue is debrided and, if necessary, reconstructed using microvascular tissue transfers. Injury patterns, especially those which involve associated injury of the elbow or forearm ligaments, must be identified and treated appropriately. Internal fixation should restore anatomical alignment and provide sufficient stability to allow immediate active mobilization of the limb without contributing to devascularization of the soft tissues or skeleton. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ring, D (reprint author), 11 Hancock St,Unit 4, Boston, MA 02114 USA. NR 75 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 J9 INJURY JI Injury-Int. J. Care Inj. PY 1999 VL 30 SU 2 BP S5 EP S13 PG 9 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA 233EL UT WOS:000082412500003 ER PT S AU King, GL Wakasaki, H AF King, GL Wakasaki, H BE Crepaldi, G Tiengo, A DelPrato, S TI Protein kinase C activation and the formation of diabetic vascular complications SO INSULIN RESISTANCE, METABOLIC DISEASES AND DIABETIC COMPLICATIONS SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 7th European Symposium on Metabolism - Insulin Resistance, Metabolic Diseases and Diabetic Complications CY SEP 30-OCT 03, 1998 CL PADUA, ITALY ID SMOOTH-MUSCLE CELLS; GROWTH-FACTOR-BETA; GENE-EXPRESSION; HEART-DISEASE; MELLITUS; INSULIN; RATS; PATHOGENESIS; PERMEABILITY; ENDOTHELIUM C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. RP King, GL (reprint author), 1 Joslin Pl, Boston, MA 02215 USA. NR 41 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50022-7 J9 INT CONGR SER PY 1999 VL 1177 BP 61 EP 73 PG 7 WC Endocrinology & Metabolism; Medicine, General & Internal SC Endocrinology & Metabolism; General & Internal Medicine GA BN57S UT WOS:000082290000010 ER PT J AU Jia, GQ Gonzalo, JA Hidalgo, A Wagner, D Cybulsky, M Gutierrez-Ramos, JC AF Jia, GQ Gonzalo, JA Hidalgo, A Wagner, D Cybulsky, M Gutierrez-Ramos, JC TI Selective eosinophil transendothelial migration triggered by eotaxin via modulation of Mac-1/ICAM-1 and VLA-4/VCAM-1 interactions SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE chemokine; eotaxin; eosinophil; integrin; transendothelial migration ID IN-VIVO; ALLERGIC INFLAMMATION; COMPLEMENT RECEPTOR; TARGETED DISRUPTION; ENDOTHELIAL-CELLS; EXPRESSION; MICE; LUNG; CHEMOATTRACTANT; HEMATOPOIESIS AB We have recently cloned eotaxin, a highly efficacious eosinophilic chemokine involved in the development of lung eosinophilia during allergic inflammatory reactions. To understand more precisely how eotaxin facilitates the specific migration of eosinophils, we have studied which adhesion receptors are essential for eotaxin action both in vivo and in vitro. Experiments using mice genetically deficient in adhesion receptors demonstrated that molecules previously reported to be involved in both leukocyte tethering/rolling (P-selectin and E-selectin) and in sticking/transmigration (ICAM-1 and VCAM-1) are required for eotaxin action in vivo, To further elucidate the mechanism(s) involved in this process, we have used an in vitro transendothelial chemotaxis model. mAb neutralization studies performed in this system suggest that the integrins Mac-1 (CD11b/18), VLA-4 (alpha(4)beta(1)) and LFA-1 (CD11a/18) are involved in the transendothelial chemotaxis of eosinophils to eotaxin, Accordingly, the expression of these integrins on eosinophils is elevated by direct action of this chemokine in a concentration-dependent manner. Taken together, our results suggest that eotaxin-induced eosinophil transendothelial migration in vivo and in vitro relies on Mac-1/ICAM-1 and VLA-4/VCAM-1 interactions, the latter ones becoming more relevant at later time points of the eotaxin-induced recruitment process. C1 Millennium Pharmaceut Inc, Cambridge, MA 02139 USA. Ctr Blood Res Inc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet & Pathol, Boston, MA 02115 USA. Ctr Invest Biol, E-28006 Madrid, Spain. Toronto Hosp, Toronto, ON M5G 2C4, Canada. RP Jia, GQ (reprint author), Millennium Pharmaceut Inc, 640 Mem Dr, Cambridge, MA 02139 USA. RI Hidalgo, Andres/L-5643-2014 OI Hidalgo, Andres/0000-0001-5513-555X FU NHLBI NIH HHS [HL 148675-02]; NIDDK NIH HHS [DK1543, DK33506] NR 37 TC 65 Z9 66 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JAN PY 1999 VL 11 IS 1 BP 1 EP 10 DI 10.1093/intimm/11.1.1 PG 10 WC Immunology SC Immunology GA 161LB UT WOS:000078289300001 PM 10050668 ER PT J AU Parsons, SK Barlow, SE Levy, SL Supran, SE Kaplan, SH AF Parsons, SK Barlow, SE Levy, SL Supran, SE Kaplan, SH TI Health-related quality of life in pediatric bone marrow transplant survivors: According to whom? SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article; Proceedings Paper CT International Workshop on Assessing Health-Related Quality of Life in Children with Cancer CY JUN 21-24, 1998 CL NIAGARA ON THE LAKE, CANADA ID OF-LIFE; EMOTIONAL-PROBLEMS; CHRONIC ILLNESS; SELF-REPORT; CHILDREN; ADOLESCENCE; ADJUSTMENT; MOTHERS; PERCEPTIONS; DEPRESSION AB Historically, health-related quality of life (HRQL) assessment in pediatrics, including the few validated instruments in pediatric oncology, has been based on proxy reporting, relying primarily on parental assessment. Children have been deemed incapable of providing consistent and reliable information about their level of functioning or state of well-being. Previous studies have been hampered by either limited or poor correlation among the proxy reporters, i.e., teachers, parents and physicians, and in comparisons to disease severity. Simply stated, proxy reporters have greater agreement about what the child can do vs. what the child thinks or feels. Comparisons among proxy reporters have been hindered also by a lack of parallel content in the instruments used, which may result in poorly congruent assessments simply because the instruments measure different constructs. In addition to the measurement issues, the emotional milieu of the parent, particularly the mother, has been shown to influence assessments of the child's functioning. Maternal distress, marital adjustment and health locus of control all co-vary with reports of the child's behavior. What, then, is the proxy reporter telling us about the child? We conducted a cross-sectional study of school-aged pediatric bone marrow transplant (BMT) patients at our institution to evaluate children's self-reported HRQL and functional status, We formally tested the Child Health Rating Inventories (CHRIs), a recently developed generic hearth-status measure, with its companion measure, the Disease Impairment Inventories-Bone Marrow Transplant (DSII-BMT). Separate questionnaires were administered to patients, parents and physicians at a scheduled outpatient visit after BMT. The questionnaires were designed to have parallel content. All responses were confidential, The psychometric properties of the CHRIs and DSII-BMT are reported elsewhere. In brief, the responses of all raters were reliable, based on measurements of internal consistency. The children's self-reported health status was correlated significantly with the physicians' disease severity rating (DSR) across all generic and disease-specific domains. In contrast, parental reports of child health status were not correlated significantly with the DSR for disease-specific problems or the child's pain. Parental ratings deviated most from the children's ratings within the dimensions of mental health and quality of life (p < 0.001), For the entire sample, parental ratings were significantly lower than the children's ratings. Within the subgroup "early after transplant (<6 months)", parental ratings were significantly lower than the children's self-reports in all categories. in the subgroup "> 12 months after transplant", with the exception of mental health and quality of life, parental scores were the same as or higher than the children's ratings. Our results confirm previous studies that the parental reporting of children's health status is a complex construct and that valuable information can be elicited directly from the children. Further research is needed to substantiate these findings, particularly in longitudinal applications with adequate sample sizes. Int. J. Cancer Suppl. 12:46-51, 1999, (C) 1999 Wiley-Liss, Inc. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. New England Med Ctr, Boston, MA 02111 USA. Harvard Med Sch, Boston, MA USA. RP Parsons, SK (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. NR 39 TC 5 Z9 6 U1 2 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PY 1999 SU 12 BP 46 EP 51 PG 6 WC Oncology SC Oncology GA 271VV UT WOS:000084615500009 ER PT J AU Albert, MR Mackool, BT AF Albert, MR Mackool, BT TI Pityriasis rubra pilaris SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; FOCAL ACANTHOLYTIC DYSKERATOSIS; INFLAMMATORY PUSTULAR DERMATOSES; GENERALIZED LICHEN SPINULOSUS; RETINOL-BINDING PROTEIN; ERYTHEMA-GYRATUM-REPENS; HIV-INFECTION; 13-CIS-RETINOIC ACID; LAMELLAR ICHTHYOSIS; INITIAL MANIFESTATION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA 02114 USA. RP Albert, MR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, ACC-489,32 Fruit St, Boston, MA 02114 USA. NR 158 TC 51 Z9 55 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD JAN PY 1999 VL 38 IS 1 BP 1 EP 11 DI 10.1046/j.1365-4362.1999.00513.x PG 11 WC Dermatology SC Dermatology GA 167CH UT WOS:000078614700001 PM 10065602 ER PT J AU Daniels, GH AF Daniels, GH TI Hyperthyroidism: Multiple possibilities in the female patient SO INTERNATIONAL JOURNAL OF FERTILITY AND WOMENS MEDICINE LA English DT Article DE diagnosis; Graves' disease; reproduction (female); postpartum thyroiditis ID GRAVES OPHTHALMOPATHY; THYROTROPIN ASSAY; THYROID-FUNCTION AB Hyperthyroidism is a clinical syndrome characterized by an excess of thyroid hormone, and its clinical consequences. A suppressed serum TSH concentration is the earliest biochemical manifestation of hyperthyroidism. Subclinical hyperthyroidism, characterized by suppressed serum TSH concentration alone, has important clinical consequences. These include bone loss in postmenopausal women and atrial fibrillation. A twenty-four hour radioiodine uptake and radionuclide scan are indispensable in the differential diagnosis of hyperthyroidism. Graves' Disease, an autoimmune disorder, demonstrates a strong female prevalence; the twenty-four hour radioiodine uptake is normal or elevated. Therapeutic options, including anti-thyroid drugs, radioactive iodine (I-131) and surgery are utilized in all age groups. These include use in women during the reproductive years. Toxic nodular goiter and "hot" nodules are less common forms of hyperthyroidism; these too have normal or elevated radioiodine uptake, with characteristic radionuclide scans. Hyperthyroidism with a near-zero radioiodine uptake also has important clinical implications. Factitious (exogenous) hyperthyroidism is characterized by a low serum thyroglobulin concentration. Treatment consists of decreasing the dosage of, or withdrawing, thyroid hormone. Painful subacute thyroiditis, a post-vital syndrome, causes spontaneously resolving hyperthyroidism, which is often followed by hypothyroidism. The most common cause of hyperthyroidism with a low radioiodine uptake is painless, lymphocytic subacute thyroiditis. Here too, hyperthyroidism spontaneously resolves and often passes through a hypothyroid phase. This phase often requires therapy, and permanent mild or severe hypothyroidism may result. C1 Massachusetts Gen Hosp, Thyroid Unit ACC730, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Daniels, GH (reprint author), Massachusetts Gen Hosp, Thyroid Unit ACC730, Boston, MA 02114 USA. NR 22 TC 1 Z9 1 U1 0 U2 0 PU MEDICAL SCIENCE PUBLISHING INT INC PI PORT WASHINGTON PA 405 MAIN ST, PORT WASHINGTON, NY 11050 USA SN 1069-3130 J9 INT J FERTIL WOMEN M JI Int. J. Fertil. Womens Med. PD JAN-FEB PY 1999 VL 44 IS 1 BP 6 EP 11 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 175EY UT WOS:000079081400001 PM 10206194 ER PT J AU Counselman, EF Gans, JS AF Counselman, EF Gans, JS TI The missed session in psychodynamic group psychotherapy SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Article AB Missed sessions in group psychotherapy are often overlooked or not talked about, thus forfeiting an important therapeutic opportunity. Group members miss meetings for many different reasons, be they the result of real-life events or clinically driven occurrences. Missed sessions can have important emotional and metaphorical meanings for the missing member, the other group members, and the leader. Countertransference difficulties may interfere with optimal exploration of the many meanings of missed sessions. Five clinical examples illustrate meanings that may reside in the missed session. A cancellation policy that provides a framework for such exploration is recommended. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Counselman, EF (reprint author), 67 Leonard St,Suite 2, Belmont, MA 02178 USA. NR 16 TC 4 Z9 4 U1 1 U2 1 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0020-7284 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD JAN PY 1999 VL 49 IS 1 BP 3 EP 17 PG 15 WC Psychology, Clinical SC Psychology GA 150LM UT WOS:000077666400001 PM 10388234 ER PT J AU Fenn, AJ Wolf, GL Fogle, RM AF Fenn, AJ Wolf, GL Fogle, RM TI An adaptive microwave phased array for targeted heating of deep tumours in intact breast: animal study results SO INTERNATIONAL JOURNAL OF HYPERTHERMIA LA English DT Article DE hyperthermia; adaptive phased array; breast cancer; animal trials; temperature distribution ID REGIONAL HYPERTHERMIA; RADIATION-THERAPY; TEMPERATURE DISTRIBUTION; OPTIMAL EXCITATION; RANDOMIZED TRIAL; CANCER-THERAPY; ANTENNA-ARRAY; SYSTEM; OPTIMIZATION; RADIOTHERAPY AB It has previously been reported in phantoms, that an adaptive radiofrequency phased array can generate deep focused heating distributions without overheating the skin and superficial healthy tissues. The present study involves adaptive microwave phased array hyperthermia tests in animals (rabbits) with and without tumours. The design of the adaptive phased array as applied to the treatment of tumours in intact breast, is described. The adaptive phased array concept uses breast compression and dual-opposing 915 MHz air-cooled waveguide applicators with electronic phase shifters and electric-field feedback, to focus automatically by computer control the microwave radiation in deep tissue. Temperature measurements for a clinical adaptive phased array hyperthermia system demonstrate tissue heating at depth with reduced skin heating. C1 MIT, Lincoln Lab, Lexington, MA 02420 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Imaging & Pharmaceut Res, Charlestown, MA 02129 USA. RP Fenn, AJ (reprint author), MIT, Lincoln Lab, Lexington, MA 02420 USA. NR 68 TC 42 Z9 43 U1 2 U2 5 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0265-6736 J9 INT J HYPERTHER JI Int. J. Hyperthermia PD JAN-FEB PY 1999 VL 15 IS 1 BP 45 EP 61 DI 10.1080/026567399285846 PG 17 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 171KU UT WOS:000078863500005 PM 10193756 ER PT J AU Gazda, H AF Gazda, H TI Congenital bone marrow failure SO INTERNATIONAL JOURNAL OF PEDIATRIC HEMATOLOGY/ONCOLOGY LA English DT Review DE Diamond-Blackfan anemia; severe congenital neutropenia; Fanconi anemia; bone marrow transplantation; point mutation; G-CSF treatment ID DIAMOND-BLACKFAN-ANEMIA; COLONY-STIMULATING-FACTOR; UMBILICAL-CORD BLOOD; RED-CELL APLASIA; SEVERE CHRONIC NEUTROPENIA; RECOMBINANT HUMAN INTERLEUKIN-3; GROUP-C GENE; FANCONI-ANEMIA; HYPOPLASTIC-ANEMIA; FACTOR-RECEPTOR AB Congenital bone marrow failure (CBMF) presents as single cytopenias or aplastic anemia; and is frequently associated with congenital malformations. Although these disorders are very rare, the understanding of their pathophysiology may lead to new insights into the regulations of hematopoiesis. In this review two syndromes, representing selective failure erythropoiesis and myelopoiesis as well as congenital aplastic anemia, are presented. All three syndromes show an increased rate of malignancy. Diamond-Blackfan anemia (DBA) is a congenital red cell disorder characterized by normochromic macrocytic or normocytic anemia, reticulocytopenia, and selective erythroblastopenia in an otherwise normocellular bone marrow. Recently, the gene involved in DBA was mapped to chromosome 19, and further genetic heterogeneity of the disease was demonstrated. Steroid therapy is the primary treatment for DBA; however bone marrow transplantation (BMT) from an HLA-identical sibling donor may be indicated when conventional therapy fails. Severe congenital neutropenia (SCN) is a rare disorder of myelopoiesis characterized by an arrest of myeloid differentiation at the promyelocytic/ myelocytic stage, with normal erythroid and megakaryocytic lineages. Granulocyte colony-stimulating factor (G-CSF) is highly effective treatment and recommended in patients with SCN. Fanconi anemia (FA) is an autosomal recessive disorder characterized by multiple congenital malformations, and a high rate of bone marrow failure. FA cells show elevated levels of chromosomal breakage and increased sensitivity to DNA cross-linking agents such as mitomycin C (MMC) or diepoxybutane (DEB). BMT from HLA-identical sibling donors is the treatment of choice for FA patients. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gazda, H (reprint author), Dana Farber Canc Inst, Rm M615,44 Binney St, Boston, MA 02115 USA. NR 148 TC 0 Z9 0 U1 0 U2 0 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1070-2903 J9 INT J PEDIAT HEM ONC JI Int. J. Pediatr. Hematol-Oncol. PY 1999 VL 6 IS 2 BP 131 EP 145 PG 15 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 195MW UT WOS:000080255800007 ER PT J AU Sonawalla, S Parikh, R Parikh, F AF Sonawalla, S Parikh, R Parikh, F TI Coping mechanisms in patients presenting for in-vitro-fertilization SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN MEDICINE LA English DT Article DE coping; in-vitro-fertilization; stress; depression; anxiety ID INVITRO FERTILIZATION; COGNITIVE APPRAISAL; INFERTILITY; EMBRYO AB Objectives: The purpose of this study was to assess the coping mechanisms in patients presenting for in-vitro fertilization (IVF). Methods: We evaluated thirty consecutive couples presenting for in-vitro-fertilization. All couples were interviewed individually at first, and then together, using a semistructured interview technique. Psychiatric diagnoses were made using the Diagnostic and Statistical Manual-IV (DSM-IV) criteria. Coping mechanisms used by the individuals were assessed using the Mechanisms of Coping Scale (MOCS). Other instruments used were Hamilton Depression Rating Scale (HAM-D-17), Hamilton Anxiety Rating Scale (HAM-A), Brief Psychiatric Rating Scale (BPRS), Self-Rating Symptom Scale (SRSS), and Eysenck Personality Inventory (EPI). Results: The mean age of the sixty patients was 32.3 +/- 5.2 years. Fatalism was the commonest factor on the mechanisms of coping scale. Analysis of variance (ANOVA) across all factors of the MOCS for demographic factors showed that men used problem-solving mechanisms significantly more often than women (F = 3.0, df = 1, 58, p < 0.05). ANOVA across coping factors on stressors with post-hoc tests of significance revealed that individuals facing social stress used fatalism significantly more often than other coping mechanisms, while those facing career stress used problem-solving significantly more often than other coping mechanisms (F = 5.6, df = 1, 58, p < 0.05 and F = 3.04, df = 1, 58, p < 0.01 respectively). ANOVA across coping factors on HAM-D-17 scores revealed that individuals who used fatalism had significantly higher HAM-D-17 scores compared to those who did not (F = 4.4, df = 1, 58, p < 0.05). ANOVA across coping factors on HAM-A scores revealed that individuals who used escape-avoidance had significantly lower HAM-A scores than those who did not (F = 4.3, df = 1, 58, p < 0.05). ANOVA across coping factors on SRSS scores revealed that individuals who used passivity or fatalistic coping mechanisms had significantly higher scores on SRSS than who did not (F = 4.6, df = 1, 58, p < 0.05 and F = 3.5, df = 1, 58, p < 0.05). Conclusions: Differential patterns of coping were found among the sixty individuals presenting for TVF and were associated with a variety of factors including gender, education, stressors, and levels of depression, anxiety, and overall psychopathology. Efforts to recognize and recruit the coping mechanisms of infertile individuals are likely to enhance their ability to participate effectively in treatment. C1 Massachusetts Gen Hosp, Dept Psychiat, Harvard Med Sch, Boston, MA 02114 USA. Jaslok Hosp & Res Ctr, Bombay, Maharashtra, India. RP Sonawalla, S (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Harvard Med Sch, WACC 812,15 Parkman St, Boston, MA 02114 USA. NR 34 TC 1 Z9 1 U1 0 U2 2 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, AMITYVILLE, NY 11701 USA SN 0091-2174 J9 INT J PSYCHIAT MED JI Int. J. Psychiatr. Med. PY 1999 VL 29 IS 2 BP 251 EP 260 PG 10 WC Psychiatry SC Psychiatry GA 257XQ UT WOS:000083808400009 PM 10587818 ER PT J AU Mendez, MF AF Mendez, MF TI Multiple sclerosis presenting as catatonia SO INTERNATIONAL JOURNAL OF PSYCHIATRY IN MEDICINE LA English DT Article DE catatonia; multiple sclerosis; depression; cataplexy ID PSYCHIATRIC-DISORDERS; DEPRESSION; MOOD; INVOLVEMENT; SYMPTOMS; ECT AB Objective: Catatonic disorder due to general medical condition must be excluded in psychiatric patients presenting with this movement disorder. This report emphasizes the association of catatonia with multiple sclerosis. Method: A patient with catatonia, psychotic depression, and the subsequent diagnosis of multiple sclerosis is described and the literature reviewed. Results: Mutism, immobility, cataplexy, waxy flexibility, and other aspects of catatonia occur in multiple sclerosis, usually as a consequence of a severe mood disorder and extensive cerebral demyelination. These symptoms may be the presenting manifestations of multiple sclerosis. Conclusions: A high index of suspicion for neurological disease is indicated in patients with new-onset catatonia. Neuroimaging and other studies may reveal underlying demyelination requiring specific therapy. C1 VA Greater Los Angeles Healthcare Syst, Neurobehav Unit, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Syst, Neurobehav Unit, 116AF,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 34 TC 15 Z9 16 U1 0 U2 0 PU BAYWOOD PUBL CO INC PI AMITYVILLE PA 26 AUSTIN AVE, AMITYVILLE, NY 11701 USA SN 0091-2174 J9 INT J PSYCHIAT MED JI Int. J. Psychiatr. Med. PY 1999 VL 29 IS 4 BP 435 EP 441 PG 7 WC Psychiatry SC Psychiatry GA 300DC UT WOS:000086236700042 PM 10782426 ER PT J AU Gelman, R Harris, JR AF Gelman, R Harris, JR TI Editorial comment on "The link between local recurrence and distant metastasis in human breast cancer" by Serge Koscielny and Maurice Tubiana SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Editorial Material ID PREMENOPAUSAL WOMEN; RADIOTHERAPY; CHEMOTHERAPY; TRIALS C1 Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. RP Harris, JR (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney, Boston, MA 02215 USA. NR 8 TC 13 Z9 13 U1 0 U2 0 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 JAN 1 PY 1999 VL 43 IS 1 BP 7 EP 9 PG 3 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 160BT UT WOS:000078211000002 PM 9989509 ER PT J AU Hilditch-Maguire, PA Lieppe, DM West, D Lambert, PF Frazer, IH AF Hilditch-Maguire, PA Lieppe, DM West, D Lambert, PF Frazer, IH TI T cell-mediated and non-specific inflammatory mechanisms contribute to the skin pathology of HPV 16 E6E7 transgenic mice SO INTERVIROLOGY LA English DT Article DE HPV16; E7; transgenic mice; alpha ACE6E7#19 ID HUMAN PAPILLOMAVIRUS TYPE-16; TUMOR-NECROSIS-FACTOR; CYCLOSPORINE-A; HUMAN KERATINOCYTES; PROTEIN; E7; TRANSFORMATION; E7-ONCOPROTEIN; CYTOKINES; EPITOPES AB One of three lines of mice transgenic for the E6 and E7 genes of human papillomavirus type 16 (HPV16) expressed from an alpha A-crystallin promoter also expresses the transgene ectopically in the skin. This line, designated alpha ACE6E7#19, develops skin disease from 3 months of age, characterised by epidermal hyperplasia and eventual skin loss. Administration of complete Freund's adjuvant (CFA) to alpha ACE6E7#19 mice, but not to nontransgenic littermate controls, induced local epidermal hyperplasia which was histologically similar to the spontaneously arising skin pathology. Local application of 2,4-dinitrochlorobenzene (DNCB) to DNCB-sensitised aACE6E7#19 mice, but not DNCB-sensitised controls, also induced hyperplasia. Treatment with cyclosporin A (CsA) or systemic depletion of CD4+ cells significantly reduced the incidence of skin disease. These data suggest that local inflammation, and cytokines produced by T helper cells, contribute to the induction of hyperplastic skin disease in alpha ACE6E7#19 mice. Spontaneous skin disease with similar histological appearance, frequency, age of onset and severity in alpha ACE6E7#19 mice was observed in scid-/- aACE6E7#19 mice, despite immune paresis. Antigen-specific immune responses and T-cell cytokines a re therefore not necessary for the induction of skin disease. We propose that epidermal hyperplasia associated with HPV16 E6 and E7 expression in skin is accelerated by local secretion of pro-inflammatory cytokines, whose production can be enhanced by activated CD4+ T cells. C1 Univ Queensland, Ctr Immunol & Canc Res, Dept Med, Princess Alexandra Hosp, Woolloongabba, Qld 4102, Australia. Massachusetts Gen Hosp, Charlestown, MA USA. Univ Wisconsin, Sch Med, Mcardle Lab Canc Res, Madison, WI 53706 USA. RP Frazer, IH (reprint author), Univ Queensland, Ctr Immunol & Canc Res, Dept Med, Princess Alexandra Hosp, Woolloongabba, Qld 4102, Australia. FU NCI NIH HHS [R0-1 CA67366] NR 26 TC 5 Z9 7 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0300-5526 J9 INTERVIROLOGY JI Intervirology PD JAN-FEB PY 1999 VL 42 IS 1 BP 43 EP 50 DI 10.1159/000024959 PG 8 WC Virology SC Virology GA 209LP UT WOS:000081049800007 PM 10393503 ER PT B AU Podolsky, DK AF Podolsky, DK BE Domschke, W Stoll, R Brasitus, TA Kagnoff, MF TI Healing gastrointestinal mucosal injury: two sides SO INTESTINAL MUCOSA AND ITS DISEASES: PATHOPHYSIOLOGY AND CLINICS SE FALK SYMPOSIUM LA English DT Proceedings Paper CT International Symposium on Intestinal Mucosa and Its Diseases - Pathophysiology and Clinics CY OCT 16-17, 1998 CL TITISEE, GERMANY SP Falk Fdn ID INTESTINAL EPITHELIAL-CELLS; EPIDERMAL GROWTH-FACTOR; TRANSFORMED MODEL EPITHELIUM; TREFOIL FACTOR; FACTOR-BETA; SPASMOLYTIC POLYPEPTIDE; PRIMARY CULTURE; WOUND REPAIR; FACTOR-ALPHA; PEPTIDE PS2 C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 32 Fruit St, Boston, MA 02114 USA. NR 58 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 0-7923-8754-6 J9 FALK SYMP PY 1999 VL 110 BP 375 EP 382 PG 8 WC Gastroenterology & Hepatology; Medicine, General & Internal SC Gastroenterology & Hepatology; General & Internal Medicine GA BP01D UT WOS:000083828400033 ER PT J AU Witte, RS Ryan, LM Schutt, AJ Carbone, PP Engstrom, PF AF Witte, RS Ryan, LM Schutt, AJ Carbone, PP Engstrom, PF TI PALA versus streptozotocin, doxorubicin, and MeCCNU in the treatment of patients with advanced pancreatic carcinoma SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE pancreatic carcinoma; PALA; streptozotocin; doxorubicin; MeCCNU ID PHASE-II TRIAL; ASPARTATE-TRANSCARBAMYLASE; MITOMYCIN-C; ADRIAMYCIN; 5-FLUOROURACIL; GEMCITABINE; FAM; ADENOCARCINOMA; CHEMOTHERAPY; CANCER AB Seventy-three eligible, chemotherapy-naive, ambulatory patients with advanced pancreatic carcinoma were allocated to one of two treatment regimens: 35 received PALA (1250 mg/m(2) daily x 5 every 4 weeks) and 38 were given SAM (streptozotocin 400 mg/m(2) IV daily x 5, doxorubicin 45 mg/m(2) IV on day 1 and 22, and methyl CCNU 60 mg/m(2) orally on days 1 and 22 every 6 weeks). Doses were modified for myelo-, gi-, or cardiotoxicity. Adequate organ, bone marrow and cardiac function; a measurable lesion; adequate caloric intake; and a life expectancy of 2 months were required for treatment on this trial. One patient on each regimen had a partial response for response rates of 3% (95% confidence intervals, 0.08 to 17%). Median survival on the PALA arm was 5 months and median time to treatment failure was 2.6 months. SAM patients experienced median overall and progression free survivals of 3.4 and 1.9 months, respectively. The severe toxicity observed was almost exclusively myelosuppression on both regimens. One patient receiving SAM had lethal leukopenic sepsis during the first cycle as the only treatment-related death. Neither PALA nor SAM offer any therapeutic utility to patients with advanced pancreatic cancer. C1 Gundersen Lutheran, La Crosse, WI USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Witte, RS (reprint author), Gundersen Clin Ltd, Med Oncol Sect, 1836 South Ave, La Crosse, WI 54601 USA. NR 20 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PY 1999 VL 16 IS 4 BP 315 EP 318 PG 4 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 206FJ UT WOS:000080866400004 ER PT J AU Lu, PCS Ye, HQ Maeda, M Azar, DT AF Lu, PCS Ye, HQ Maeda, M Azar, DT TI Immunolocalization and gene expression of matrilysin during corneal wound healing SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MATRIX METALLOPROTEINASE FAMILY; PHOTOREFRACTIVE KERATECTOMY; COLLAGENASE; CELLS; STROMELYSIN; LOCALIZATION; FIBROBLASTS; INHIBITORS; CARCINOMA; MEMBERS AB PURPOSE. TO investigate the protein level of matrilysin and stromelysin-1 and the gene expression of matrilysin in rat corneas after excimer keratectomy using immunofluorescence staining, reverse transcriptase-polymerase Chain Reaction (RT-PCR), and in situ hybridization. METHODS. Rat corneas were treated with 3-mm excimer laser keratectomy (193-nm ArF). Unwounded corneas served as controls. Confocal microscopy was used to immunolocalize matrilysin protein at 6 hours, 1 day, 3 days, 1 week, 4 weeks, and 8 weeks after surgery. RT-PCR was performed to analyze matrilysin mRNA in unwounded controls and in 3-day wounded corneas. In situ hybridization was performed to localize matrilysin mRNA. RESULTS. Matrilysin was immunolocalized to the epithelial layers of unwounded and wounded corneas, predominantly to the leading edge at 6 hours and 1 day after wounding and to the epithelial layer at 3 to 7 daps after surgery. Stromelysin-1 was expressed in the deep stromal layer in the first 3 days after wounding and in the area of newly synthesized stromal matrix 1 week after surgery. Upregulation of matrilysin expression 3 days after wounding was confirmed by RT-PCR. In situ hybridization revealed that the gene expression of matrilysin in rat corneas was upregulated during the migration phase (6 hours, 1 day) and that matrilysin mRNA was predominantly localized to the basal cell layers during the subsequent cell proliferation phase (7 and 14 days). CONCLUSIONS. Basal epithelial cells express matrilysin during the migration proliferation phase of corneal wound healing after excimer keratectomy. C1 Massachusetts Eye & Ear Infirm, Corneal External Dis & Refract Surg Serv, Schepens Eye Res Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Azar, DT (reprint author), Massachusetts Eye & Ear Infirm, Corneal External Dis & Refract Surg Serv, Schepens Eye Res Inst, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY10101] NR 41 TC 57 Z9 57 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JAN PY 1999 VL 40 IS 1 BP 20 EP 27 PG 8 WC Ophthalmology SC Ophthalmology GA 154TR UT WOS:000077905600005 PM 9888422 ER PT J AU Yagnik, P Dhopesh, V AF Yagnik, P Dhopesh, V TI Spinal epidural abscess (SEA) in substance abuse patients SO JOURNAL OF ADDICTIVE DISEASES LA English DT Meeting Abstract C1 Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 1999 VL 18 IS 2 MA 34A BP 138 EP 138 PG 1 WC Substance Abuse SC Substance Abuse GA 189VR UT WOS:000079927300044 ER PT J AU Obeidallah, DA Hauser, ST Jacobson, AM AF Obeidallah, DA Hauser, ST Jacobson, AM TI The long branch of phase-environment fit: Concurrent and longitudinal implications of match and mismatch among diabetic and nondiabetic youth SO JOURNAL OF ADOLESCENT RESEARCH LA English DT Article ID 10-YEAR FOLLOW-UP; EGO DEVELOPMENT; ONSET COHORT; CHILDREN; MELLITUS; ADOLESCENTS AB Based on the stage-environment fit perspective (Eccles Br Midgley), we hypothesized that diabetic adolescents who experience a developmental match would be more likely to experience optimal psychosocial outcomes. Three questions were addressed: Are there links between developmental match and adolescents' psychosocial outcomes, and if so do such links differ by diabetic status' what are the long-term implications for later psychosocial outcomes of developmental match, and do such links differ by diabetic status ? Do adolescents differentially perceive community support as a function of their developmental match and diabetic status? we assessed diabetic and nondiabetic adolescent boys and girls from a larger longitudinal study of chronic illness. Family characteristics were observed in a revealed difference task. Results suggested that even after controlling for psychosocial factors during adolescence, the benefits of developmental march (and the costs of developmental mismatch) could be observed during young adulthood. In addition, preadolescents with diabetes perceived their community as more supportive than any other group of adolescents. Results are discussed within a developmental contextual perspective, with particular attention to the experiences of diabetic adolescents. C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Obeidallah, DA (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 43 TC 2 Z9 2 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0743-5584 J9 J ADOLESCENT RES JI J. Adolesc. Res. PD JAN PY 1999 VL 14 IS 1 BP 95 EP 121 DI 10.1177/0743558499141006 PG 27 WC Psychology, Developmental SC Psychology GA 157DH UT WOS:000078044100005 ER PT J AU Ghaemi, SN Sachs, GS Chiou, AM Pandurangi, AK Goodwin, FK AF Ghaemi, SN Sachs, GS Chiou, AM Pandurangi, AK Goodwin, FK TI Is bipolar disorder still underdiagnosed? Are antidepressants overutilized? SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE bipolar disorder; drug therapy; diagnosis; nosology; antidepressants; treatment; depression; manic-depressive illness ID LITHIUM-CARBONATE; AFFECTIVE-ILLNESS; I DISORDER; MANIA; SCHIZOPHRENIA; DEPRESSION; RISPERIDONE; DIAGNOSIS; SYMPTOMS AB Background: Previous studies have suggested that bipolar disorder may be underdiagnosed, and that antidepressants may be over-utilized in its treatment, Methods: Consecutively admitted patients (n = 48) diagnosed with DSM-IV bipolar disorder, type I, (n = 44) or schizoaffective disorder, bipolar type, (n = 4) were interviewed systematically and their charts were reviewed to confirm diagnosis before admission. They were then treated according to systematic structured interview diagnoses. These data reflect the changes in diagnoses and treatment. Results: 40% (19/48) were identified with previously undiagnosed bipolar disorder, all previously diagnosed with unipolar major depressive disorder. A period of 7.5+/-9.8 years elapsed in this group before bipolar diagnosis was made. Antidepressant use was high on admission (38%) and was reduced with acceptable treatment response rates. The adjunctive use of risperidone appeared to be a good treatment alternative. Limitations: While diagnoses were made prospectively, treatment response was assessed retrospectively, and was based on non-randomized, naturalistic therapy. Conclusions: Systematic application of DSM-IV criteria identified previously undiagnosed bipolar disorder in 40% of a referred population of patients with mood disorders, all previously misdiagnosed as unipolar major depressive disorder. Antidepressants appeared overutilized and risperidone was an effective alternative adjunctive therapy agent, (C) 1999 Elsevier Science B.V. All rights reserved. C1 George Washington Univ, Dept Psychiat, Psychopharmacol Res Ctr, Bipolar Disorder Res Program, Washington, DC 20037 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Bipolar Res Program, Boston, MA USA. Virginia Commonwealth Univ, Med Coll Virginia, Inpatient Psychiat Program, Richmond, VA 23298 USA. RP Ghaemi, SN (reprint author), George Washington Univ, Dept Psychiat, Psychopharmacol Res Ctr, Bipolar Disorder Res Program, 2150 Penn Ave NW,8th Floor, Washington, DC 20037 USA. RI Ghaemi, Nassir/J-4934-2013 NR 25 TC 222 Z9 237 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JAN-MAR PY 1999 VL 52 IS 1-3 BP 135 EP 144 DI 10.1016/S0165-0327(98)00076-7 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 196JT UT WOS:000080305800015 PM 10357026 ER PT J AU Tedlow, J Leslie, V Keefe, BR Alpert, J Nierenberg, AA Rosenbaum, JF Fava, M AF Tedlow, J Leslie, V Keefe, BR Alpert, J Nierenberg, AA Rosenbaum, JF Fava, M TI Axis I and Axis II disorder comorbidity in unipolar depression with anger attacks SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE anger attacks; unipolar depression; comorbidity ID PERSONALITY-DISORDERS; FLUOXETINE TREATMENT AB Objective: We evaluated whether anger attacks in patients with major depressive disorder (MDD) are associated with higher rates of panic or other Axis I or II comorbid disorders. Methods: 306 out-patients (163 women, mean age 39.5 +/- 10.5) with MDD were administered the Structured Clinical Interviews for Axis I and II Disorders, and the Anger Attacks Questionnaire. Results: Patients with anger attacks showed only a trend toward a significantly higher rate of current panic disorder (P = 0.06) but no other difference in Axis I comorbidity. In addition patients with anger attacks had a slightly but significantly greater degree of depression severity. Consistent with previous studies, we have also found that depressed patients with anger attacks had significantly higher rates of dependent, avoidant, narcissistic, borderline, and antisocial personality disorders than those without anger attacks. Conclusion: Anger attacks do not appear to be associated with any specific pattern of Axis I comorbidity, but they are certainly linked with certain personality disorders. It is possible that the acute depressive state may have confounded the assessment of personality disorder rates, as well as the presence of anger attacks. On the other hand, both depressed patient groups (with or without anger attacks) were subject to the same confounding effect as their depression severity was rather comparable, thereby limiting the impact of this potential bias. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. RP Tedlow, J (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, WAC-812,15 Parkman St, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X NR 18 TC 25 Z9 25 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD JAN-MAR PY 1999 VL 52 IS 1-3 BP 217 EP 223 DI 10.1016/S0165-0327(98)00074-3 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 196JT UT WOS:000080305800025 PM 10357036 ER PT J AU Abi-Younes, SA Luster, AD AF Abi-Younes, SA Luster, AD TI Role of chemokines in platelet activation in atopic asthmatics. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1999 VL 103 IS 1 SU S MA 797 BP S207 EP S207 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 165FC UT WOS:000078509000799 ER PT J AU Bingham, CO Tobia, CS Boyce, JA Sheffer, AL AF Bingham, CO Tobia, CS Boyce, JA Sheffer, AL TI Hydroxychloroquine in the treatment of autoimmune chronic urticaria. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1999 VL 103 IS 1 SU S MA 592 BP S155 EP S155 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 165FC UT WOS:000078509000596 ER PT J AU Chen, HJL Bloch, KJ AF Chen, HJL Bloch, KJ TI Syndrome of syndromes: An unusual presentation of chronic urticaria. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1999 VL 103 IS 1 SU S MA 584 BP S153 EP S153 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 165FC UT WOS:000078509000588 ER PT J AU Eapen, S Sanchez, H Cook, E Stahl, J Bush, RK AF Eapen, S Sanchez, H Cook, E Stahl, J Bush, RK TI Quantitation of the Alternaria allergen, Alt a 2, by an IgY-based immunoassay SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 William S Middleton Mem Vet Adm Hosp, Madison, WI USA. Univ Wisconsin, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1999 VL 103 IS 1 SU S MA 605 BP S158 EP S158 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 165FC UT WOS:000078509000609 ER PT J AU Geisler, D Schneider, B Schroth, M Sanchez, H Bush, RK Middleton, WS AF Geisler, D Schneider, B Schroth, M Sanchez, H Bush, RK Middleton, WS TI Effect of Alternaria extract on airway epithelial cell RANTES and IL-8 production in vitro. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 William S Middleton Mem Vet Adm Hosp, Madison, WI 53705 USA. Univ Madison, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1999 VL 103 IS 1 SU S MA 711 BP S186 EP S186 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 165FC UT WOS:000078509000714 ER PT J AU Gjerset, BG Walker, JE Yusin, JS Klaustermeyer, WB AF Gjerset, BG Walker, JE Yusin, JS Klaustermeyer, WB TI Value of two controls when screening for tuberculosis in ambulatory and hospitalized veterans. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1999 VL 103 IS 1 SU S MA 21 BP S6 EP S6 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 165FC UT WOS:000078509000022 ER PT J AU MacLean, JA De Sanctis, GT Sarafi, M Sauty, A Charo, IF Luster, AD AF MacLean, JA De Sanctis, GT Sarafi, M Sauty, A Charo, IF Luster, AD TI Antigen-induced pulmonary eosinophilia in C-C chemokine receptor 2 (CCR2) knockout (KO) mice. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Calif San Francisco, Gladstone Inst, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1999 VL 103 IS 1 SU S MA 741 BP S193 EP S193 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 165FC UT WOS:000078509000743 ER PT J AU Sanchez, H Geisler, D Bush, RK AF Sanchez, H Geisler, D Bush, RK TI Detection of enolase DNA in various fungal species. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Univ Wisconsin, Madison, WI USA. William S Middleton Mem Vet Adm Hosp, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1999 VL 103 IS 1 SU S MA 602 BP S157 EP S157 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 165FC UT WOS:000078509000606 ER PT J AU Strauss, EC Larson, KA Foster, CS Larsen, GR Lee, NA Lee, JJ AF Strauss, EC Larson, KA Foster, CS Larsen, GR Lee, NA Lee, JJ TI Soluble P-selectin glycoprotein ligand-1 inhibits ocular inflammation. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Mayo Clin Scottsdale, Scottsdale, AZ USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Genet Inst, Cambridge, MA 02140 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1999 VL 103 IS 1 SU S MA 478 BP S125 EP S125 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 165FC UT WOS:000078509000483 ER PT J AU Tobia, CN Krinzman, SJ Penrose, JF Bloch, KJ MacLean, JA Wong, JT AF Tobia, CN Krinzman, SJ Penrose, JF Bloch, KJ MacLean, JA Wong, JT TI Rapid oral challenge/desensitization for patients with aspirin(ASA)-induced urticaria/angioedema. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 1999 VL 103 IS 1 SU S MA 145 BP S37 EP S37 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 165FC UT WOS:000078509000147 ER PT J AU Noviski, N Brewer, JP Skornik, WA Galli, SJ Drazen, JM Martin, TR AF Noviski, N Brewer, JP Skornik, WA Galli, SJ Drazen, JM Martin, TR TI Mast cell activation is not required for induction of airway hyperresponsiveness by ozone in mice SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE pulmonary inflammation; asthma ID TYROSINE KINASE RECEPTOR; GUINEA-PIGS; BRONCHIAL HYPERREACTIVITY; RESPIRATORY RESPONSES; INDUCED INFLAMMATION; BRONCHOALVEOLAR LAVAGE; CHILDHOOD ASTHMA; PROTO-ONCOGENE; MEXICO-CITY; TIME COURSE AB Exposure to ambient ozone (O-3) is associated with increased exacerbations of asthma. We sought to determine whether mast-cell degranulation is induced by in vivo exposure to O-3 in mice and whether mast cells play an essential role in the development of pulmonary pathophysiological alterations induced by O-3 For this we exposed mast cell-deficient WBB6F(1)-kis(W)/kit(W-v) (kit(W)/kit(W-v)) mice and the congenic normal WBB6F(1) (+/+) mice to air or to 1 or 3 parts/million O-3 for 4 h and studied them at different intervals from 4 to 72 h later. We found evidence of O-3-induced cutaneous, as well as bronchial, mast cell degranulation. Polymorphonuclear cell influx into the pulmonary parenchyma was observed after exposure to 1 part/million O-3 only in mice that possessed mast cells. Airway hyperresponsiveness to intravenous methacholine measured in vivo under pentobarbital anesthesia was observed in both kif(W)/kit(W-v) and +/+ mice after exposure to O-3. Thus, although mast cells are activated in vivo by O-3 and participate in O-3-induced polymorphonuclear cell infiltration into the pulmonary parenchyma, they do not participate detectably in the development of O-3-induced airway hyperresponsiveness in mice. C1 Childrens Hosp, Div Pulm, Dept Pediat, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Environm Hlth, Boston, MA 02115 USA. Beth Israel Hosp, Combined Program Pulm & Crit Care Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Childrens Serv, Neonatol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Childrens Serv, Pediat Intens Care Unit, Boston, MA 02114 USA. RP Martin, TR (reprint author), Childrens Hosp, Div Pulm, Dept Pediat, 300 Longwood Ave, Boston, MA 02115 USA. RI Drazen, Jeffrey/E-5841-2012 NR 66 TC 17 Z9 17 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JAN PY 1999 VL 86 IS 1 BP 202 EP 210 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 191EN UT WOS:000080009600028 PM 9887132 ER PT J AU McGibbon, CA Krebs, DE Trahan, CA Trippel, SB Mann, RW AF McGibbon, CA Krebs, DE Trahan, CA Trippel, SB Mann, RW TI Cartilage degeneration in relation to repetitive pressure - Case study of a unilateral hip hemiarthroplasty patient SO JOURNAL OF ARTHROPLASTY LA English DT Article DE acetabular cartilage; cartilage degeneration; hemiarthroplasty; repetitive pressure ID HUMAN ARTICULAR-CARTILAGE; CONTACT PRESSURES; BIOCHEMICAL-CHANGES; OSTEOARTHRITIS; INVIVO; JOINT; GAIT AB In vivo acetabular contact pressures were measured over 32 months in an elderly man with a pressure instrumented hemiarthroplasty. After death, left (hemiarthroplasty) and right (control) acetabula were explanted. Cartilage thickness and degeneration were quantified from magnetic resonance imaging and histological analysis. Highest repetitive in viva contact pressures during gait (4.5 to 6.5 MPa) were measured in the superior dome of the acetabulum and decreased at a rate of approximately I MPa per year after implant (R-2 = 0.48, P <.001). Contact pressure magnitudes measured during gait correlated positively with regional histology score (R-2 = 0.34 P <.0001) and negatively with cartilage thickness (R-2 = 0.35, P <.0001). Although histology scores were typical of early osteoarthritis (histological grade of 4-6), there were no significant: differences in overall histology score for the left and right acetabula (P =.23). We conclude that acetabular cartilage degeneration was explained, in part, by repetitive stress, but the degeneration did not appear to be mediated solely by articulation with the metallic endoprosthesis. C1 Massachusetts Gen Hosp, Dept Orthopaed, Biomot Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, MGH Inst Hlth Profess, Boston, MA 02114 USA. Massachusetts Gen Hosp, Orthopaed Res Lab, Boston, MA 02114 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP McGibbon, CA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, Biomot Lab, 40 Parkman St,RSH 010, Boston, MA 02114 USA. FU NIAMS NIH HHS [R01-AR31068, R01-AR40036]; NICHD NIH HHS [R01-HD30063] NR 39 TC 20 Z9 21 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD JAN PY 1999 VL 14 IS 1 BP 52 EP 58 DI 10.1016/S0883-5403(99)90202-4 PG 7 WC Orthopedics SC Orthopedics GA 157UG UT WOS:000078079600009 PM 9926953 ER PT J AU Xu, JH Mironova, R Ivanov, IG Abouhaidar, MG AF Xu, JH Mironova, R Ivanov, IG Abouhaidar, MG TI A polylinker-derived sequence, PL, highly increased translation efficiency in Escherichia coli SO JOURNAL OF BASIC MICROBIOLOGY LA English DT Article ID TOBACCO MOSAIC-VIRUS; MESSENGER-RNA; RIBOSOMAL-RNA; CHEMICAL SYNTHESIS; INITIATION SIGNAL; GENE-EXPRESSION; DOWNSTREAM BOX; BINDING-SITE; REGION; CHAIN AB Pokeweed (Phytolacca americana) antiviral protein (PAP) is a highly specific ribosome-inactivating glycosidase. The PAP gene was isolated and cloned in an expression vector containing a polylinker-derived sequence (PL) but devoid of a Shine-Dalgarno (SD) sequence. Surprisingly, E. coli cells transformed with this vector produced over twice the amount of PAP than that with the consensus SD sequence. Computer analysis of the 5' terminal region of PAP mRNA revealed a nucleotide sequence (ACCUACUCGAGUUAG) which was complementary to two domains in 16S rRNA. The heptanucleotide ACCUACU (box I) is complementary to nucleotides 1434-1440 and the GAGUUAG (box II) to nucleotides 507-513 in 16S rRNA of E. coli. To examine the role of this sequence in the trans translation of PAP mRNA, single or both boxes were mutated and the protein yield was measured. Mutation of box I and of box II resulted in a 2.7 and 5.3 fold decrease in protein yield respectively, indicating that the PAP gene expression was dependent on the presence of both boxes. To investigate whether PL also increases expression of other genes, human calcitonin monomeric and tetrameric genes were used as reporters. It was found that the expression level was doubled compared to that by SD. These results demonstrate that the PL is an efficient translational initiator and may be used for high level expression of certain genes in E. coli. The possible mechanisms for the high level expression are discussed. C1 Univ Toronto, Dept Bot, Toronto, ON M5S 3B2, Canada. Bulgarian Acad Sci, Inst Mol Biol, Dept Gene Regulat, BU-1113 Sofia, Bulgaria. RP Xu, JH (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Mironova, Roumyana /D-7413-2013 NR 24 TC 3 Z9 3 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0233-111X J9 J BASIC MICROB JI J. Basic Microbiol. PY 1999 VL 39 IS 1 BP 51 EP 60 DI 10.1002/(SICI)1521-4028(199903)39:1<51::AID-JOBM51>3.0.CO;2-0 PG 10 WC Microbiology SC Microbiology GA 166LL UT WOS:000078578000008 PM 10071866 ER PT J AU Zhang, XA Hemler, ME AF Zhang, XA Hemler, ME TI Interaction of the integrin beta(1) cytoplasmic domain with ICAP-1 protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-CYCLE PROGRESSION; MONOCLONAL-ANTIBODIES; FIBRONECTIN RECEPTOR; SIGNAL-TRANSDUCTION; ADHESION; EXPRESSION; KINASE; SUBUNIT; ACTIVATION; PEPTIDES AB In a yeast two-hybrid screen, a protein named ICAP-1 (beta(1) integrin cytoplasmic domain associated protein) associated with the integrin beta(1) cytoplasmic tail but not with tails from three other integrin beta subunits (beta(2), beta(3), and beta(5)) or from seven different a subunits, Likewise in human cells, ICAP-1 associated specifically with the beta(1) but not beta(2), beta(3), Or beta(5) tails. The carboxyl-terminal 14 amino acids of beta(1) were critical for ICAP-1 interaction. ICAP-1 is a ubiquitously expressed protein of 27 and 31 kDa, with the smaller form being preferentially solubilized by Triton X-100. Phosphorylation of both 27- and 31-kDa forms was constitutive but was increased by 1.5-2-fold upon cell spreading on fibronectin, compared with poly-L-lysine. Also, ICAP-1 contributes to beta(1) integrin-dependent migration because (i) ICAP-1 transfection markedly increased chemotactic migration of COS7 cells through fibronectin-coated but not vitronectin-coated porous filters, and (ii) support of beta(1)-dependent cell migration (in Chinese hamster ovary cells transfected with various wild type and mutant beta(1) forms) correlated with ICAP-1 association. In summary, ICAP-1 (i) associates specifically with beta(1) integrins, (ii) is phosphorylated upon beta(1) integrin-mediated adhesion, and (iii) may regulate beta(1) dependent cell migration. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, Rm D-1410,44 Binney St, Boston, MA 02115 USA. EM Hemler@dfci.harvard.edu FU NIGMS NIH HHS [GM46526] NR 66 TC 69 Z9 72 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 JAN 1 PY 1999 VL 274 IS 1 BP 11 EP 19 DI 10.1074/jbc.274.1.11 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 154QP UT WOS:000077900200004 PM 9867804 ER PT J AU Hsueh, YP Sheng, M AF Hsueh, YP Sheng, M TI Requirement of N-terminal cysteines of PSD-95 for PSD-95 multimerization and ternary complex formation, but not for binding to potassium channel Kv1.4 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DENSITY PROTEIN PSD-95; NMDA RECEPTOR SUBUNITS; GUANYLATE KINASES; PDZ DOMAINS; CLUSTERING ACTIVITY; FASCICLIN-II; K+ CHANNELS; SHAKER; FAMILY; RECOGNITION AB The PSD-95 family of PSD-95/Discs large/ZO-1 (PDZ) domain-containing proteins plays a role in the clustering and localization of specific ion channels and receptors at synapses. Previous studies have shown that PSD-95 forms multimers through an N-terminal region (termed the N-segment) and that the multimerization of PSD-95 is critical for its ability to cluster Shaker-type potassium channel Kv1.4 in heterologous cells. We show here that the PSD-95 N-segment functions as a multimerization domain only when located at the N-terminal end of a heterologous protein. A pair of N-terminal cysteines, Cys(3) and Cys(5), is essential for the ability of PSD-95 to self-associate and to form cell surface clusters with Kv1.4. However, PSD-95 mutants lacking these cysteine residues retain their ability to associate with membranes and to bind to Kv1.4, Unlike wild type PSD-95, the cysteine mutant of PSD-95 cannot form a ternary complex with Kv1.4 and the cell adhesion molecule Fas-ciclin II. These results suggest that the N-terminal cysteines are essential for PSD-95 multimerization and that multimerization is required for simultaneous binding of multiple membrane protein ligands by PSD-95. C1 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 Sheng, M (reprint author), Howard Hughes Med Inst, Boston, MA 02114 USA. OI Hsueh, Yi-Ping/0000-0002-0866-6275 NR 25 TC 68 Z9 70 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 JAN 1 PY 1999 VL 274 IS 1 BP 532 EP 536 DI 10.1074/jbc.274.1.532 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 154QP UT WOS:000077900200076 PM 9867876 ER PT J AU Napadow, VJ Chen, Q Wedeen, VJ Gilbert, RJ AF Napadow, VJ Chen, Q Wedeen, VJ Gilbert, RJ TI Intramural mechanics of the human tongue in association with physiological deformations SO JOURNAL OF BIOMECHANICS LA English DT Article DE muscle magnetic resonance imaging; muscle biomechanics ID GENIOGLOSSUS MUSCLE; SPATIAL MODULATION; HYOID APPARATUS; MAGNETIZATION; MOTION; MODEL; STRAINS; HEART; 3-D AB Contraction of the tongue musculature during speech and swallowing is associated with characteristic patterns of tissue deformation. In order to quantify local deformation (strain) in the human tongue, we used a non-invasive NMR lagging technique that represents tissue as discrete deforming elements. Subjects were studied with a fast gradient echo pulse sequence (TR/TE 2.3/0.8 ms, slice thickness 10 mm, and effective spatial resolution 1.3 x 1.3 mm). Individual elements were defined by selectively supersaturating bands of magnetic spins in resting tongue tissue along the antero-posterior and superior-inferior directions of the mid-sagittal plane, resulting in a rectilinear square grid. Axial and shear strains relative to the rest condition were determined for each element and represented by two-dimensional surface strain maps. During forward protrusion, the anterior tongue underwent positive antero-posterior strain (elongation) (maximum 200%) and symmetrical negative medial-lateral and superior-inferior strain (contraction). During sagittal curl directed to the hard palate, the tongue exhibited positive asymmetrical antero-posterior strain (maximum 160%) that increased radially as a function of distance from the center of curvature (r = 0.9216, p < 0.0005), and commensurate negative strain in the medial-lateral direction. Similarly, the magnitude of anterior-posterior strain during left-directed tongue curl was proportional to the distance from the curved inner surface (r = 0.8978, p < 0.0005). We conclude that the regulation of tongue position for the motions studied was related to regional activation of the intrinsic lingual musculature. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 MIT, Dept Mech Engn, Cambridge, MA 02138 USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. St Elizabeths Med Ctr, Dept Med & Biomed Res, Boston, MA USA. RP Gilbert, RJ (reprint author), MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02138 USA. EM rgilb1228@aol.com NR 31 TC 70 Z9 70 U1 0 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD JAN PY 1999 VL 32 IS 1 BP 1 EP 12 DI 10.1016/S0021-9290(98)00109-2 PG 12 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 163PB UT WOS:000078413000001 PM 10050946 ER PT J AU Bierbaum, BE Callaghan, JJ Galante, JO Rubash, HE Tooms, RE Welch, RB AF Bierbaum, BE Callaghan, JJ Galante, JO Rubash, HE Tooms, RE Welch, RB TI An analysis of blood management in patients having a total hip or knee arthroplasty SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID AUTOLOGOUS BLOOD; ELECTIVE SURGERY; TRANSFUSION; COLLECTION; DONATION AB Three hundred and thirty orthopaedic surgeons in the United States participated in a study of transfusion requirements associated with total joint arthroplasty, A total of 9482 patients (3920 patients who had a total hip replacement and 5562 patients who had a total knee replacement) were evaluated prospectively from September 1996 through June 1997. Of those patients, 4409 (46 percent [57 percent of the patients who had a hip replacement and 39 percent of the patients who had a knee replacement]) had a blood transfusion. Two thousand eight hundred and ninety patients (66 percent) received autologous blood, and 1519 patients (34 percent) received allogenic blood. Ordered logistic regression analysis showed the most important predictors of the transfusion of allogenic blood to be a low baseline hemoglobin level and a lack of predonated autologous blood. Preoperative donation of autologous blood decreases the risk of transfusion of allogenic blood; however, inefficiencies in the procedures for obtaining autologous blood were identified. Sixty-one percent (5741) of the patients had predonated blood for autologous transfusion, but 4464 (45 percent) of the 9920 units of the predonated autologous blood were not used. Primary procedures and revision total knee arthroplasty were associated with the greatest number of masted autologous units. Of the 5741 patients who had predonated blood, 503 (9 percent) needed a transfusion of allogenic blood. The frequency of allogenic blood transfusion varied,vith respect to the type of operative procedure (revision total hip arthroplasty and bilateral total knee arthro plasty mere associated with the highest prevalence of such transfusions) and with a baseline hemoglobin lever of 130 grams per liter or less. Transfusion of allogenic blood was also associated,vith infection (p less than or equal to 0.001), fluid overload (p less than or equal to 0.001), and increased duration of hospitalization (p less than or equal to 0.01). These letter findings warrant further evaluation in controlled studies. C1 Univ Iowa, Iowa City, IA 52242 USA. New England Baptist Hosp, Chestnut Hill, MA 02167 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Campbell Clin Orthopaed, Memphis, TN 38103 USA. St Marys Hosp & Med Ctr, San Francisco, CA 94117 USA. RP Callaghan, JJ (reprint author), Univ Iowa, 200 Hawkins Dr, Iowa City, IA 52242 USA. NR 29 TC 482 Z9 504 U1 2 U2 13 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 JAN PY 1999 VL 81A IS 1 BP 2 EP 10 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 161JN UT WOS:000078285600002 PM 9973048 ER PT J AU Clohisy, JC Harris, WH AF Clohisy, JC Harris, WH TI The Harris-Galante porous-coated acetabular component with screw fixation - An average ten-year follow-up study SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID TOTAL HIP-REPLACEMENT; IMPROVED CEMENTING TECHNIQUES; ARTHROPLASTY AB Two hundred and thirty-seven consecutive primary acetabular reconstructions were performed, in 213 patients, with use of a Harris-Galante porous-coated acetabular component with screw fixation between January 1984 and December 1987. Twenty-four patients (twenty-seven hips) died before a minimum duration of follow-up of eighty-four months, five patients (five hips) were too ill to return for a detailed follow-up examination at the time of the study, four patients (four hips) refused clinical and radiographic follow-up (but one of these patients had more than eighty-four months of follow-up for one side of a bilateral total hip replacement), two patients (two hips) were lost to follow-np, and two patients (two hips) refused radiographic follow-up but had adequate clinical follow-up. In addition, one patient who had had a bilateral total hip replacement had a resection arthroplasty on one side because of a late infection 115 months after the index procedure. Thus, 196 hips (83 per cent) in 177 patients were available for radiographic and clinical review after an average duration of follow-up of 122 months (range, eighty-four to 155 months). The average age of these 177 patients at the time of the operation was fifty-nine years (range, twenty-three to eighty-seven years). Eight well fixed acetabular shells (4 percent) were revised: three were revised because of dissociation of the liner in association with fractures of the tines, three were revised during revision of the femoral component, and two were revised because of retroacetabular osteolysis. In eight other hips, the acetabular liner,vas exchanged during revision of a loose femoral component. No acetabular component migrated, was classified as radiographically loose, or was revised because of aseptic loosening. There was no evidence of fragmentation or disruption of the titanium porous mesh of any cup. One of 528 screws broke. There were no complications associated with the insertion of the acetabular fixation screws. Osteolytic lesions were identified adjacent to nine (5 percent) of the 188 acetabular components that were in place at the time of the most recent examination. One hip, which had discontinuous osteolytic lesions in all three acetabular zones, was treated with bone-grafting around the well fixed acetabular component. Eight hips had a discontinuous radiolucent line that was 1.0 millimeter wide or less in all three zones and another two had a continuous radiolucent line that was 0.5 millimeter wide in all three zones. The average Harris hip score for the 188 hips (169 patients) that did not have revision of the acetabular shell improved from 47 points (range, 22 to 71 points) preoperatively to 89 points (range, 35 to 100 points) at the time of the latest examination. One hundred and thirty-four hips had an excellent result; twenty-six, a good result; nineteen, a fair result; and nine, a poor result. All nine hips that had a poor result were in patients who had of her factors, unrelated to the acetabular component, that contributed to the low Harris hip score. In the present study the Harris-Galante porous-coated acetabular component continued to provide excellent fixation and clinical results for most patients at an average of approximately ten years after the operation. C1 Massachusetts Gen Hosp, Orthopaed Biomech Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Hip & Implant Unit, Boston, MA 02114 USA. RP Clohisy, JC (reprint author), Johnson Cty Orthopaed, 20375 W 151st St,Suite 106, Olathe, KS 66061 USA. NR 28 TC 110 Z9 111 U1 0 U2 1 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 JAN PY 1999 VL 81A IS 1 BP 66 EP 73 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 161JN UT WOS:000078285600010 PM 9973056 ER PT J AU Takasu, H Guo, J Bringhurst, FR AF Takasu, H Guo, J Bringhurst, FR TI Dual signaling and ligand selectivity of the human PTH/PTHrP receptor SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID PARATHYROID-HORMONE RECEPTOR; PROTEIN-KINASE-C; (PTH)/PTH-RELATED PEPTIDE RECEPTOR; OSTEOBLAST-LIKE CELLS; FUNCTIONAL EXPRESSION; PHOSPHOLIPASE-C; DOWN-REGULATION; INTRACELLULAR STORES; OVARIECTOMIZED RATS; OSTEOSARCOMA CELLS AB Parathyroid hormone (PTH) activates PTH/PTH-related peptide-related receptors (PTHRs) to stimulate both adenylyl cyclase (AC) and phospholipase C (PLC). How these parallel signals mediate specific cellular and tissue responses to PTH, such as the complex anabolic versus catabolic actions of PTH on bone, remains unsettled. Previous studies of PTHR signaling and function employed mainly rodent or other cell lines that express endogenous PTHRs and, possibly, alternate species of PTH receptors, To preclude confounding effects of such receptors, we stably expressed recombinant human PTHRs (hPTHRs) at different levels of surface density in LLC-PK1 porcine renal epithelial cells that lack endogenous PTH responsiveness. hPTH(1-34) induced concentration-dependent activation of both AC and PLC via transfected hPTHRs, Maximal intensity of each signal increased with receptor density, but more hPTHRs: were required for PLC than for AC activation. Coupling to AC was saturated at receptor densities too low to detect sustained PLC activation. hPTH(3-34), found by others to be a PLC/protein kinase C (PKC)-selective peptide in rat cells, did not activate PLC via human (or rat) PTHRs: under conditions (1 mu M peptide, 10(6) hPTHRs/cell) where hPTH(1-34) stimulated PLC several fold. Other cellular responses that require PKC activation in these cells, such as sodium-dependent phosphate transport and cAMP-independent secretion of plasminogen activator, were induced by PTH(1-34) but not by hPTH(3-34) or hPTH(7-34). We conclude that amino-truncated PTH analogs reported to activate PKC cannot directly activate phosphatidylinositol-specific PLC via the human or rat PTHR and therefore that PTH receptors may access alternate, PLC-independent pathways of PKC activation in some target cells. The relative intensity of AC and PLC signaling via the hPTHR may be strongly regulated by changes in its surface expression. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Bringhurst, FR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Wellman 5, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK11794] NR 50 TC 80 Z9 81 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JAN PY 1999 VL 14 IS 1 BP 11 EP 20 DI 10.1359/jbmr.1999.14.1.11 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 151HZ UT WOS:000077715800004 PM 9893061 ER PT J AU Holmvang, G AF Holmvang, G TI A magnetic resonance imaging method for evaluating atrial septal defects SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Article C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Unit, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Cambridge, MA 02138 USA. Boston Heart Fdn, Cambridge, MA USA. RP Holmvang, G (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Unit, Cambridge, MA 02138 USA. NR 3 TC 8 Z9 8 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1097-6647 J9 J CARDIOV MAGN RESON JI J. Cardiov. Magn. Reson. PY 1999 VL 1 IS 1 BP 59 EP 64 DI 10.3109/10976649909080835 PG 6 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 278CQ UT WOS:000084970700010 PM 11550342 ER PT J AU Pedrozo, HA Schwartz, Z Mokeyev, T Ornoy, A Xin-Sheng, W Bonewald, LF Dean, DD Boyan, BD AF Pedrozo, HA Schwartz, Z Mokeyev, T Ornoy, A Xin-Sheng, W Bonewald, LF Dean, DD Boyan, BD TI Vitamin D-3 metabolites regulate LTBP1 and latent TGF-beta 1 expression and latent TGF-beta 1 incorporation in the extracellular matrix of chondrocytes SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE vitamin D-3, LTBP1,TGF-beta, chondrocytes; latent TGF-beta, 1,25-(OH)(2)D-3, 24,25-(OH)(2)D-3 ID GROWTH-FACTOR-BETA; CARTILAGE CELLS-INVITRO; TGF-BETA; BINDING-PROTEIN; RESTING ZONE; PROTEOGLYCAN SYNTHESIS; COMPLEX; OSTEOBLAST; CULTURES; 1,25-DIHYDROXYVITAMIN-D3 AB Growth plate chondrocytes make TCF-beta 1 in latent form (LTGF-beta 1) and store it in the extracellular matrix via LTGF-beta 1 binding protein (LTBP1). 1,25-(OH)(2)D-3 (1,25) regulates matrix protein production in growth zone (CC) chondrocyte cultures, whereas 24,25-(OH)(2)D-3 (24,25) does so in resting zone (RC) cell cultures. The aim of this study was to determine if 24,25 and 1,25 regulate LTBP1 expression as well as the LTBP1-mediated storage of TGF-beta 1 in the extracellular matrix of RC and CC cells. Expression of LTBP1 and TGF-beta 1 in the growth plate and in cultured RC and CC cells was determined by in situ hybridization using sense and antisense oligonucleotide probes based on the published rat LTBP1 and TGF-beta 1 cDNA sequences. Fourth passage male rat costochondral RC and CC chondrocytes were treated for 24 h with 10(-7)-10(-9) M 24,25 and 10(-8)-10(-10) M 1,25, respectively. LTBP1 and TGF-beta 1 mRNA levels were measured by in situ hybridization; production of LTGF-beta 1, LTGF-beta 2, and LTBP1 protein in the conditioned media was verified by immunoassays of FPLC-purified fractions. In addition, ELISA assays were used to measure the effect of 1,25 and 24,25 on the level of TGF-beta 1 in the media and matrix of the cultures. Matrix-bound LTGF-beta 1 was released by digesting isolated matrices with 1 U/ml plasmin for 3 h at 37 degrees C. LTBP1 and TGF-beta 1 mRNAs are co-expressed throughout the growth plate, except in the lower hypertrophic area. Cultured GC cells express more LTBP1 and TGF-beta 1 mRNAs than RC cells. FPLC purification of the conditioned media confirmed that RC cells produce LTGF-beta 1, LTGF-beta 2, and LTBP1. GC cells also produce LTGF-beta 2, but at lower concentrations. 1,25 dose-dependently increased the number of GC cells with high LTBP1 expression, as seen by in situ hybridization. 24,25 had a similar, but less pronounced, effect on RC cells. 1,25 also caused a dose-dependent increase in the amount of TGF-beta 1 protein found in the matrix, significant at 10(-8) and 10(-9) M, and a corresponding decrease in TGF-beta 1 in the media. 24,25 had no effect on the level of TGF-beta 1 in the matrix or media produced by RC cells. This indicates that 1,25 induces the production of LTBP1 by GC cells and suggests that the TGF-beta 1 content of the media is reduced through the formation of latent TGF-beta 1-LTBP1 complexes which mediates storage in the matrix. Although 24,25 induced the expression of LTBP1 by RCs, TGF-beta 1 incorporation into the matrix is not regulated by this vitamin D-3 metabolite. Thus, vitamin D-3 metabolites may play a role in regulating the availability of TGF-beta 1 by modulating LTBP1 production. J. Cell. Biochem. 72:151-165, 1999. (C) 1999 Wiley-Liss, Inc. C1 Univ Texas, Hlth Sci Ctr, Dept Orthopaed, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Periodont, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med Endocrinol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. Hebrew Univ Hadassah, Dept Periodont, IL-91010 Jerusalem, Israel. Hebrew Univ Hadassah, Dept Anat, IL-91010 Jerusalem, Israel. RP Boyan, BD (reprint author), Univ Texas, Hlth Sci Ctr, Dept Orthopaed, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM boyanb@uthscsa.edu FU NIDCR NIH HHS [DE-07160, DE-08603, DE-05937] NR 45 TC 40 Z9 40 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JAN 1 PY 1999 VL 72 IS 1 BP 151 EP 165 DI 10.1002/(SICI)1097-4644(19990101)72:1<151::AID-JCB16>3.0.CO;2-E PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 141NX UT WOS:000077151000016 PM 10025676 ER PT J AU Ford, HL Pardee, AB AF Ford, HL Pardee, AB TI Cancer and the cell cycle SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE cell cycle; cancer; literature ID DNA-REPLICATION; S-PHASE; CHECKPOINTS; P53; PHOSPHORYLATION; PROLIFERATION; PROTEOLYSIS; SEQUENCES; PROTEIN; MITOSIS AB The purpose of this short review is to provide an overview of mammalian somatic cell cycle events and their controls. Cell cycle-related studies have been under way for only 5% of this millennium, yet since then nearly 20,000 references have appeared. This vast literature cannot be detailed here, nor can fundamental information obtained with Other organisms such as yeast and Xenopus, or topics such as the abbreviated cell cycle in early embryonic cells. (C) 1999 Wiley-Liss, Inc. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ford, HL (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 56 TC 13 Z9 14 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PY 1999 SU 32-33 BP 166 EP 172 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 273BG UT WOS:000084686400020 ER PT J AU Kashket, S AF Kashket, S TI Historical review of remineralization research SO JOURNAL OF CLINICAL DENTISTRY LA English DT Article ID ENAMEL LESION REMINERALIZATION; CARIES-LIKE LESIONS; CHEWING-GUM USE; IN-SITU; DENTAL-CARIES; PLAQUE PH; DEMINERALIZATION; MODEL; INVIVO; MICRORADIOGRAPHY AB Although not always the case, remineralization has become an accepted area of study within oral care research, and many new study possibilities have arisen. In addition, many in the clinical dentistry community have recognized remineralization as an important factor in maintaining the health of the tooth. This paper, through an extensive review of the dental literature, explores the history of investigations on de- and remineralization. C1 Forsyth Dent Ctr, Boston, MA 02115 USA. RP Kashket, S (reprint author), Forsyth Dent Ctr, 140 Fenway, Boston, MA 02115 USA. NR 82 TC 5 Z9 5 U1 1 U2 1 PU PROFESSIONAL AUDIENCE COMMUNICATIONS, INC PI YARDLEY PA PO BOX 243, YARDLEY, PA 19067 USA SN 0895-8831 J9 J CLIN DENT JI J. Clin. Dent. PY 1999 VL 10 IS 2 BP 56 EP 64 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 246TF UT WOS:000083180100002 ER PT J AU Welt, CK McNicholl, DJ Taylor, AE Hall, JE AF Welt, CK McNicholl, DJ Taylor, AE Hall, JE TI Female reproductive aging is marked by decreased secretion of dimeric inhibin SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; GONADOTROPIN-RELEASING-HORMONE; HUMAN MENSTRUAL-CYCLE; AGE-RELATED-CHANGES; LUTEINIZING-HORMONE; ALPHA-SUBUNIT; OLDER WOMEN; IMMUNOREACTIVE INHIBIN; MENOPAUSAL TRANSITION; OVARIAN-FOLLICLES AB The increase in serum FSH that accompanies female reproductive aging occurs before changes in estradiol (E2). A decrease in negative feedback from inhibin A (a product of the dominant follicle and corpus luteum) and/or inhibin B (secreted by developing follicles) may explain the rise in FSH with age. To test the hypothesis that decreases in inhibin A or inhibin B occur at an age at which the first increase in follicular phase FSH is evident, daily blood samples were obtained across the menstrual cycle from younger (<35 yr; n = 23) and older (35-46 yr; n = 21) cycling women. These cross-sectional studies were complemented by longitudinal data in 3 women studied at a 10-yr interval. In the early follicular phase, mean inhibin B was lower in older cycling women (88 +/- 7 vs. 112 +/- 10 pg/mL; P < 0.05) and FSH was higher (13.0 +/- 0.5 vs. 11.2 +/- 0.7 IU/L in older vs. younger, respectively; P < 0.04). In the mid- and late follicular phases, inhibin B was also lower in the older women (117 +/- 9 vs. 146 +/- 10 and 85 +/- 8 vs. 117 +/- II pg/mL; P < 0.04), whereas E2 was higher(105 +/- 14 us. 68 +/- 5 and 240 +/- 27 vs. 163 +/- 9 pg/mL; P < 0.02), and no differences in FSH were observed in the two groups at these times. In women studied longitudinally, FSH and inhibin B varied inversely in the follicular phase. In the early luteal phase, mean inhibin B was lower in the older group (64 +/- 6 vs. 94 +/- 12 pg/mL; P < 0.03), and FSH was higher (12.5 +/- 1.0 vs. 9.7 +/- 0.6 IU/L; P < 0.03). In the mid- and late luteal phases, inhibin B was also lower in older subjects (21 +/- 2 vs. 33 +/- 5 and 22 +/- 2 us. 36 +/- 6 pg/mL; P < 0.02). No difference in inhibin A, E2, or progesterone was observed across the luteal phase, between the two groups. However, in all subjects studied longitudinally, increased age was associated with a decrease in inhibin A, inhibin B, and progesterone in the absence of changes in E2. Our conclusions were: 1) reproductive aging is accompanied by decreases in both inhibin B and inhibin A; 2) the decrease in inhibin B precedes the decrease in inhibin A and occurs in concert with an increase in E2, suggesting that inhibin B negative feedback is the most important factor controlling the earliest increase in FSH with aging; 3) these studies suggest that the decrease in inhibin B is the earliest marker of the decline in follicle number across reproductive aging. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Reprod Endocrine Sci Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Natl Ctr Infertil Res, Dept Med, Boston, MA 02114 USA. RP Welt, CK (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Reprod Endocrine Sci Ctr, 55 Fruit St, Boston, MA 02114 USA. OI Welt, Corrine/0000-0002-8219-5504 FU NCRR NIH HHS [M-01-RR-01066]; NICHD NIH HHS [U-54-HD-29164, P-30-HD-28138] NR 40 TC 240 Z9 252 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 EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JAN PY 1999 VL 84 IS 1 BP 105 EP 111 DI 10.1210/jc.84.1.105 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 155VN UT WOS:000077967200018 PM 9920069 ER PT J AU Grinspoon, S Corcoran, C Rosenthal, D Stanley, T Parlman, K Costello, M Treat, M Davis, S Burrows, B Basgoz, N Klibanski, A AF Grinspoon, S Corcoran, C Rosenthal, D Stanley, T Parlman, K Costello, M Treat, M Davis, S Burrows, B Basgoz, N Klibanski, A TI Quantitative assessment of cross-sectional muscle area, functional status, and muscle strength in men with the acquired immunodeficiency syndrome wasting syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PLACEBO-CONTROLLED TRIAL; SKELETAL-MUSCLE; VIRUS INFECTION; BODY; MASS; HEART; AIDS AB The acquired immunodeficiency syndrome wasting syndrome (AWS) in men is characterized by the loss of lean body mass out of proportion to weight. Although the wasting syndrome has been thought to contribute to reduced functional capacity, the relationships among lean body mass, muscle size, functional status, and regional muscle strength have not previously been investigated in this population. In this study, 24 eugonadal men with the AWS (weight <90% of the ideal body weight or weight loss >10% from preillness maximum) underwent determination of body composition by dual energy x-ray absorptiometry (DXA), K-40 isotope analysis, urinary creatinine excretion, and quantitative computed tomographic analysis of cross-sectional muscle areas of the midarm and thigh. Overall exercise functional capacity was evaluated using the 6-min walk test, and performance of upper and lower extremities was determined with the quantitative muscle function test. Subjects were 37 +/- 1 yr of age and weighed 95.5 +/- 3.0% of ideal body weight, with a body mass index of 21.9 +/- 0.7 kg/m(2) and an average weight loss of 15 +/- 1%. The mean CD4 count among the subjects was 354 +/- 70 cells/mm(3), and viral load was 58,561 +/- 32,205 copies. Sixty-two percent of subjects were receiving protease inhibitor therapy. The subjects demonstrated 90% of the expected muscle mass by the creatinine height index method. Overall performance status on the Karnofsky scale was highly correlated to weight (r = 0.51; P = 0.018; by body mass index), lean body mass (r = 0.46; P = 0.036; by DXA), and body cell mass (r = 0.47; P = 0.037; by K-40 isotope analysis). Cross-sectional muscle area of the upper extremity was the best predictor (P < 0.001) of Karnofsky score, accounting for 52% of the variability in a stepwise regression analysis. Upper body muscle strength was most significantly predicted by lean body mass (by DXA; r(2) = 0.78; P < 0.0001), whereas lower body strength and performance on the 6-min walk test were best predicted by lower extremity cross-sectional muscle area (r(2) = 0.70; P < 0.0001 and r(2) = 0.26; P = 0.030, respectively). These data demonstrate that cross-sectional muscle area is highly predictive of functional status and muscle strength in men with the AWS. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Phys Therapy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Boston Vet Affairs, Med Ctr, Dept Radiol, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02130 USA. RP Grinspoon, S (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457B, Boston, MA 02114 USA. FU NCRR NIH HHS [MO1-RR-01066]; NIDDK NIH HHS [F32-DK-09218, R01-DK-49302] NR 27 TC 46 Z9 46 U1 0 U2 2 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 JAN PY 1999 VL 84 IS 1 BP 201 EP 206 DI 10.1210/jc.84.1.201 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 155VN UT WOS:000077967200033 PM 9920084 ER PT J AU Yueh, B Feinstein, AR AF Yueh, B Feinstein, AR TI Abstruse comparisons: The problems of numerical contrasts of two groups SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE Abstrusity; contrasts; indexes; qualitative; quantitative ID ACUTE MYELOGENOUS LEUKEMIA; IMMUNODEFICIENCY-VIRUS INFECTION; BONE-MARROW TRANSPLANTATION; RANDOMIZED CONTROLLED TRIAL; ACUTE MYOCARDIAL-INFARCTION; COLONY-STIMULATING FACTOR; CLINICAL-TRIAL; BREAST-CANCER; ELDERLY PATIENTS; FOLLOW-UP AB The most common quantitative comparison in medical Literature is a contrast of two numbers, such as two means or two rates. The two numbers, A and B, can be compared as a direct increment (A-B), ratio (A/B), relative change ([A-B]/B), or other index of contrast. To appreciate the quantitative distinction, a reader must know the "setting" reflected by the basic Values of A and B. For example, a ratio of 2.0 does not distinguish comparisons between rates of 60% versus 30% and 0.006% versus 0.003%. Despite the frequency of published comparisons, they can be expressed with two types of abstrusity: quantitatives, if the basic values for A and B are not readily evident; and qualitative, if the component underlying variables are unfamiliar and not suitably explained. Among the published articles during the first six months of 1995 for JAMA and New England Journal of Medicine, 57 that satisfied inclusion criteria were reviewed for compliance with standards for avoiding the two types of abstrusity. The standards for quantitative abstrusity were applied to the published abstract-summary, because it is often the only "sound bite" that is read and remembered by most readers. The standards for qualitative abstrusity, however, could be fulfilled in the text, not just in the abstract-summaries of each article. Among the 57 abstract-summaries, 30% were abstruse quantitatively, and 11 (48%) of 23 pertinent papers were qualitatively abstruse. Abstrusity can be eliminated if authors and editors insist that quantitative contrasts cite the basic numbers being compared and the meaning of the associated variables and their rating scales. J CLIN EPIDEMIOL 52;1:13-18, 1999. (C) 1999 Elsevier Science Inc. C1 VA Puget Sound Hlth Care Syst, Surg Serv 112OTO, Seattle, WA 98108 USA. Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Epidemiol, New Haven, CT 06510 USA. RP Yueh, B (reprint author), VA Puget Sound Hlth Care Syst, Surg Serv 112OTO, 1660 S Columbian Way, Seattle, WA 98108 USA. OI Yueh, Bevan/0000-0003-1380-1053 NR 65 TC 6 Z9 6 U1 2 U2 4 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 JAN PY 1999 VL 52 IS 1 BP 13 EP 18 DI 10.1016/S0895-4356(98)00133-4 PG 6 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 159TC UT WOS:000078189600003 PM 9973069 ER PT J AU Tesch, GH Schwarting, A Kinoshita, K Lan, HY Rollins, BJ Kelley, VR AF Tesch, GH Schwarting, A Kinoshita, K Lan, HY Rollins, BJ Kelley, VR TI Monocyte chemoattractant protein-1 promotes macrophage-mediated tubular injury, but not glomerular injury, in nephrotoxic serum nephritis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID STIMULATING FACTOR-I; CRESCENTIC GLOMERULONEPHRITIS; CHEMOTACTIC PEPTIDE-1; CHEMOKINE RECEPTOR-2; EPITHELIAL-CELLS; LUPUS NEPHRITIS; MICE DEFICIENT; CC-CHEMOKINE; P-SELECTIN; EXPRESSION AB Monocyte chemoattractant protein-1 (MCP-1) is upregulated in renal parenchymal cells during kidney disease. To investigate whether MCP-1 promotes tubular and:or glomerular injury, we induced nephrotoxic serum nephritis (NSN) in MCP-1 genetically deficient mice. Mice were analyzed when tubules and glomeruli were severely damaged in the MCP-1-intact strain (day 7). MCP-1 transcripts increased fivefold in MCP-1-intact mice. MCP-1 was predominantly localized within cortical tubules (90%), and most cortical tubules were damaged, whereas few glomerular cells expressed MCP-1 (10%). By comparison, there was a marked reduction (>40%) in tubular injury in MCP-1-deficient mice (histopathology, apoptosis). MCP-1-deficient mice were not protected from glomerular injury (histopathology, proteinuria, macrophage influx). Macrophage accumulation increased adjacent to tubules in MCP-1-intact mice compared with MCP-1-deficient mice (70%, P < 0.005), indicating that macrophages recruited by MCP-1 induce tubular epithelial cell (TEC) damage. Lipopolysaccharide-activated bone marrow macrophages released molecules that induced TEC death that was not dependent on MCP-1 expression by macrophages or TEC. In conclusion, MCP-1 is predominantly expressed by TEC and not glomeruli, promotes TEC and not glomerular damage, and increases activated macrophages adjacent to TEC that damage TEC during NSN. Therefore, we suggest that blockage of TEC MCP-1 expression is a therapeutic strategy for some forms of kidney disease. C1 Harvard Univ, Brigham & Womens Hosp, Inst Med, Renal Div,Lab Mol Autoimmune Dis, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Monash Med Ctr, Dept Nephrol, Clayton, Vic 3168, Australia. RP Kelley, VR (reprint author), Harvard Univ, Brigham & Womens Hosp, Inst Med, Renal Div,Lab Mol Autoimmune Dis, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM VKelley@rics.bwh.harvard.edu RI Tesch, Greg/I-1444-2013; Lan, hui/C-9734-2015 OI Tesch, Greg/0000-0002-6137-3092; Lan, hui/0000-0003-4283-9755 FU NIDDK NIH HHS [R01 DK036149, DK 36149, Z01 DK036149] NR 43 TC 207 Z9 220 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 JAN PY 1999 VL 103 IS 1 BP 73 EP 80 DI 10.1172/JCI4876 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 155LJ UT WOS:000077948100011 PM 9884336 ER PT J AU Igarashi, M Wakasaki, H Takahara, N Ishii, H Jiang, ZY Yamauchi, T Kuboki, K Meier, M Rhodes, CJ King, GL AF Igarashi, M Wakasaki, H Takahara, N Ishii, H Jiang, ZY Yamauchi, T Kuboki, K Meier, M Rhodes, CJ King, GL TI Glucose or diabetes activates p38 mitogen-activated protein kinase via different pathways SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SMOOTH-MUSCLE CELLS; CYTOSOLIC PHOSPHOLIPASE A(2); GLOMERULAR MESANGIAL CELLS; TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR; MAP KINASE; C-JUN; RECOMBINANT ADENOVIRUS; DIACYLGLYCEROL MASS; CELLULAR STRESSES AB Hyperglycemia can cause vascular dysfunctions by multiple factors including hyperosmolarity, oxidant formation, and protein kinase C (PKC) activation. We have characterized the effect of hyperglycemia on p38 mitogen-activated protein (p38) kinase activation, which can be induced by oxidants, hyperosmolarity, and proinflammatory cytokines, leading to apoptosis, cell growth, and gene regulation. Glucose at 16.5 mM increased p38 kinase activity in a time-dependent manner compared with 5.5 mM in rat aortic smooth muscle cells (SMC). Mannitol activated p38 kinase only at or greater than 22 mM. High glucose levels and a PKC agonist activated p38 kinase, and a PKC inhibitor, GF109203X, prevented its activation. However, p38 kinase activation by mannitol or tumor necrosis factor-alpha was not inhibited by GF109203X. Changes in PKC isoform distribution after exposure to 16.5 mM glucose in SMC suggested that both PKC-beta 2 and PKC-delta isoforms were increased. Activities of p38 kinase in PKC-delta- but not PKC-beta 1-overexpressed SMC were increased compared with control cells. Activation of p38 kinase was also observed and characterized in various vascular cells in culture and aorta from diabetic rats. Thus, moderate hyperglycemia can activate p38 kinase by a PKC-delta isoform-dependent pathway, but glucose at extremely elevated levels can also activate p38 kinase by hyperosmolarity via a PKC-independent pathway. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res,Sect Vasc Cell Biol, Boston, MA 02215 USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res,Sect Vasc Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. FU NEI NIH HHS [EY05110]; NIDDK NIH HHS [DK36836, P30 DK036836] NR 68 TC 287 Z9 306 U1 2 U2 4 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 JAN PY 1999 VL 103 IS 2 BP 185 EP 195 DI 10.1172/JCI3326 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 160TP UT WOS:000078247400005 PM 9916130 ER PT J AU Nguyen, TD Moody, MW Steinhoff, M Okolo, C Koh, DS Bunnett, NW AF Nguyen, TD Moody, MW Steinhoff, M Okolo, C Koh, DS Bunnett, NW TI Trypsin activates pancreatic duct epithelial cell ion channels through proteinase-activated receptor-2 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID MOLECULAR-CLONING; THROMBIN RECEPTOR; TRYPTASE; PEPTIDES; PAR-2; GENE AB Proteinase-activated receptor-2 (PAR-2) is a G protein-coupled receptor that is cleaved by trypsin within the NH2-terminus, exposing a tethered ligand that binds and activates the receptor. We examined the secretory effects of trypsin, mediated through PAR-2, on well-differentiated nontransformed dog pancreatic duct epithelial cells (PDEC). Trypsin and activating peptide (AP or SLIGRL-NH2, corresponding to the PAR-2 tethered ligand) stimulated both an I-125(-) efflux inhibited by Ca2+-activated Cl- channel inhibitors and a Rb-86(+) efflux inhibited by a Ca2+-activated Kt channel inhibitor. The reverse peptide (LRGILS-NH2) and inhibited trypsin were inactive. Thrombin had no effect, suggesting absence of PAR-1, PAR-3, or PAR-4. In Ussing chambers, trypsin and AP stimulated a short-circuit current from the basolateral, but not apical, surface of PDEC monolayers. In monolayers permeabilized basolaterally or apically with nystatin, AP activated apical Cl- and basolateral K+ conductances. PAR-2 agonists increased [Ca2+](i) in PDEC, and the calcium chelator BAPTA inhibited the secretory effects of AP. PAR-2 expression on dog pancreatic ducts and PDEC was verified by immunofluorescence. Thus, trypsin interacts with basolateral PAR-2 to increase [Ca2+](i) and activate ion channels in PDEC. In pancreatitis, when trypsinogen is prematurely activated, PAR-2-mediated ductal secretion may promote clearance of toxins and debris. C1 Univ Washington, Dept Med, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA. RP Nguyen, TD (reprint author), Vet Adm Med Ctr, GI Sect 111GI, 1660 S Columbian Way, Seattle, WA 98108 USA. RI Steinhoff, Martin/F-6312-2013; OI Steinhoff, Martin/0000-0002-7090-2187 FU NIDDK NIH HHS [T32 DK007742, DK-07742]; NINDS NIH HHS [NS08174, R01 NS008174, R37 NS008174] NR 31 TC 138 Z9 147 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 JAN PY 1999 VL 103 IS 2 BP 261 EP 269 DI 10.1172/JCI2539 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 160TP UT WOS:000078247400013 PM 9916138 ER PT J AU Fagan, KA Fouty, BW Tyler, RC Morris, KG Hepler, LK Sato, K LeCras, TD Abman, SH Weinberger, HD Huang, PL McMurtry, IF Rodman, DM AF Fagan, KA Fouty, BW Tyler, RC Morris, KG Hepler, LK Sato, K LeCras, TD Abman, SH Weinberger, HD Huang, PL McMurtry, IF Rodman, DM TI The pulmonary circulation of homozygous of heterozygous eNOS-null mice is hyperresponsive to mild hypoxia SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NITRIC-OXIDE SYNTHASE; VASCULAR-RESISTANCE; RAT LUNG; HYPERTENSION; VASOCONSTRICTION; GENE; EXPRESSION; LACKING; HUMANS; ARTERY AB Acute hypoxic vasoconstriction and development of hypoxic pulmonary hypertension (PHTN) are unique properties of the pulmonary circulation. The pulmonary endothelium produces vasoactive factors, including nitric oxide (NO), that modify these phenomena. We tested the hypothesis that NO produced by endothelial nitric oxide synthase (eNOS) modulates pulmonary vascular responses to hypoxia using mice with targeted disruption of the eNOS gene (eNOS(-/-)). Marked PHTN was found in eNOS(-/-) mice raised in mild hypoxia when compared with either controls or eNOS(-/-) mice raised in conditions simulating sea level. We found an approximate twofold increase in partially and fully muscularized distal pulmonary arteries in eNOS(-/-) mice compared with controls. Consistent with vasoconstriction being the primary mechanism of PHTN, however, acute inhalation of 25 ppm NO resulted in normalization of RV pressure in eNOS(-/-) mice. In addition to studies of eNOS(-/-) mice, the dose-effect of eNOS was tested using heterozygous eNOS(+/-) mice. Although the lungs of eNOS(+/-) mice had 50% of normal eNOS protein, the response to hypoxia was indistinguishable from that of eNOS(-/-) mice. We conclude that eNOS-derived NO is an important modulator of the pulmonary vascular response to chronic hypoxia and that more than 50% of eNOS expression is required to maintain normal pulmonary vascular tone. C1 Univ Colorado, Hlth Sci Ctr, Cardiovasc Pulm Res Lab, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Div Pulm Sci & Crit Care Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Div Cardiol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Physiol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Fagan, KA (reprint author), Univ Colorado, Hlth Sci Ctr, Cardiovasc Pulm Res Lab, 4200 E 9th Ave,C-272, Denver, CO 80262 USA. EM karen.fagan@uchsc.edu FU NHLBI NIH HHS [HL-48038, HL-07085, HL-14985, P01 HL014985, T32 HL007085] NR 39 TC 213 Z9 220 U1 0 U2 3 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 JAN PY 1999 VL 103 IS 2 BP 291 EP 299 DI 10.1172/JCI3862 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 160TP UT WOS:000078247400016 PM 9916141 ER PT J AU Saunders, KE Shen, ZL Dewhirst, FE Paster, BJ Dangler, CA Fox, JG AF Saunders, KE Shen, ZL Dewhirst, FE Paster, BJ Dangler, CA Fox, JG TI Novel intestinal Helicobacter species isolated from cotton-top tamarins (Saguinus oedipus) with chronic colitis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID INFLAMMATORY BOWEL-DISEASE; SP-NOV; CAMPYLOBACTER-FENNELLIAE; ULCERATIVE-COLITIS; MICE; HEPATICUS; INFECTION; PYLORI; FERRETS; MODEL AB A disease similar to ulcerative colitis in humans has been identified in cotton-top tamarins (CTTs) in captivity. The clinical signs include weight loss, diarrhea, and rectal bleeding with the pathological features and biochemical abnormalities of ulcerative colitis. Approximately 25 to 40% of these animals develop colon cancer after 2 to 5 years of captivity. An infectious etiology has been proposed; however, no microbial agent to date has been identified. Helicobacter spp. have been associated with enterocolitis and inflammatory bowel disease (IBD) in humans and animals. Infection with Helicobacter pylori or Helicobacter mustelae is associated with an increased risk of gastric adenocarcinoma and lymphoma of the mucosa-associated lymphoid tissue. Helicobacter hepaticus causes hepatitis, hepatic adenomas, and hepatocellular carcinomas in susceptible strains of mice. The aim of this study was to assess a colony of CTTs with a high incidence of IBD and colon cancer for the presence of colonic Helicobacter spp, A fusiform, gram-negative bacterium,vith bipolar flagella and periplasmic fibers was isolated from the feces of CTTs, The bacterium grew under microaerobic conditions at 37 and 42 degrees C but not at 25 degrees C, did not hydrolyze urea, was positive for catalase and oxidase, did not reduce nitrate to nitrite, did not hydrolyze indoxyl acetate or alkaline phosphatase, and was resistant to nalidixic acid, cephalothin, and trimethoprim-sulfamethoxazole. On the basis of 16S rRNA gene sequence analysis, the organism was classified as a novel Helicobacter species. This is the first Helicobacter isolated from CTTs. Further studies are needed to elucidate the role of this novel Helicobacter sp, in the pathogenesis of ulcerative colitis and colonic adenocarcinoma in CTTs. C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. Forsyth Dent Ctr, Div Mol Genet, Boston, MA 02115 USA. RP Fox, JG (reprint author), MIT, Div Comparat Med, 16-825,77 Massachusetts Ave, Cambridge, MA 02139 USA. FU NCI NIH HHS [P01 CA026731, R01 CA067529, R01CA67529, P01CA26731]; NCRR NIH HHS [RR010146]; NIDCR NIH HHS [R01 DE010374, R01 DE011443] NR 43 TC 68 Z9 69 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 1999 VL 37 IS 1 BP 146 EP 151 PG 6 WC Microbiology SC Microbiology GA 149CQ UT WOS:000077587900027 PM 9854080 ER PT J AU Goss, PE Winer, EP Tannock, IF Schwartz, LH AF Goss, PE Winer, EP Tannock, IF Schwartz, LH CA North Amer Vorozole Study Grp TI Randomized phase III trial comparing the new potent and selective third-generation aromatase inhibitor vorozole with megestrol acetate in postmenopausal advanced breast cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TAMOXIFEN; WOMEN; ESTROGEN; THERAPY; ANDROSTENEDIONE; CHEMOTHERAPY; CONVERSION; STANDARD; LIFE AB Purpose: to compare the efficacy and safety of vorozole (VOR) 2.5 mg once daily with that of megestrol acetate (MA) 40 mg four times per day as second-line therapy in postmenopausal women with advanced breast cancer whose disease progressed after tamoxifen treatment, Patients and Methods: A total of 452 patients were enrolled onto an open, multicenter, randomized phase III trial comparing VOR to MA for tumor response, safety, and quality of life (as indicated by the Functional Living Index-Cancer score). Results: Vorozole produced a response rate of 9.7%, compared with 6.8% for MA (P = .24). Clinical benefit (complete response + partial response + no change in > 6 months) was demonstrated in 23.5% and 27.2% of patients treated with VOR and MA, respectively (P = .42). Median duration of response was 18.2 months for VOR versus 12.5 months for MA (P = .074). There was no significant difference in time to progression or survival between the treatment groups. Discontinuation of treatment because of adverse events occurred less frequently in the VOR-treated group (3.1% v 6.2%; P = .18). patients on the VOR arm reported significantly more nausea, hot flushes, arthralgia, upper respiratory tract infection, anorexia, and paresthesia, whereas those treated with MA had significantly more dyspnea, increased appetite, and weight increase. There was no difference between the two treatment groups in Functional Living Index-cancer scores (total or subscales). However, when analyzed by objective response, patients with complete or partial responses (P = .032) or no change (P = .033) who were receiving VOR had significant improvement in the psychologic well-being subscale, compared with patients given MA. Conclusion:Vorozole is well tolerated and as effective as MA in the treatment of postmenopausal advanced breast cancer patients with disease progression after tamoxifen treatment. J Clin Oncol 17:52-63. (C) 1999 by American Society of Clinical Oncology. C1 Toronto Hosp, Gen Div, Div Hematol Oncol, Toronto, ON M5G 2C4, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Princess Margaret Hosp, Dept Med Oncol Hematol, Toronto, ON M4X 1K9, Canada. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Goss, PE (reprint author), Toronto Hosp, Gen Div, Div Hematol Oncol, 200 Elizabeth St,MLW 2-022, Toronto, ON M5G 2C4, Canada. NR 45 TC 84 Z9 84 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 1999 VL 17 IS 1 BP 52 EP 63 PG 12 WC Oncology SC Oncology GA 155CB UT WOS:000077927400009 PM 10458218 ER PT J AU Abrams, J Aisner, J Cirrincione, C Berry, DA Muss, HB Cooper, MR Henderson, IC Panasci, L Kirshner, J Ellerton, J Norton, L AF Abrams, J Aisner, J Cirrincione, C Berry, DA Muss, HB Cooper, MR Henderson, IC Panasci, L Kirshner, J Ellerton, J Norton, L TI Dose-response trial of megestrol acetate in advanced breast cancer: Cancer and leukemia group B phase III study 8741 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID QUALITY-OF-LIFE; MEDROXYPROGESTERONE ACETATE; PROGESTATIONAL AGENTS; POSTMENOPAUSAL WOMEN; RANDOMIZED TRIAL; RECEPTOR LEVELS; ANOREXIA; PROGESTINS; INDUCTION; APPETITE AB Purpose: To investigate whether dose escalation of megestrol acetate (MA) improves response rate and survival in comparison with standard doses of MA. Patients and Methods: Three hundred sixty-eight patients with metastatic breast cancer, positive and/or unknown estrogen and progesterone receptors, zero or one prior trial of hormonal therapy and no prior chemotherapy for metastatic disease were prospectively randomized into three groups. The groups of patients received either MA 160 mg/d (one tablet per day), MA 800 mg/d (five tablets per day), or MA 1,600 mg/d (10 tablets per day). Results: patient characteristics were well balanced in the three treatment groups. Three hundred sixty-six patients received treatment and were included in the analyses. The response rates were 23%, 27%, and 27% For the 160-mg, 800-mg, and 1,600-mg arms, respectively. Response duration correlated inversely with dose, Median durations of response were 17 months, 14 months, and 8 months for the 160-mg, 800-mg, and 1,600-mg arms, respectively No significant differences in the treatment arms were noted for time to disease progression or for survival; survival medians were 28 months (low dose), 24 months (mid dose) and 29 months (high dose). The mast frequent and troublesome toxicity, weight gain, was dose-related, with approximately 20% of patients on the two higher-dose arms reporting weight gain of more than 20% of their prestudy weight, compared with only 2% in the 160-mg dose arm. Conclusion: With a median follow-up of 8 years, these results demonstrate no advantage for dose escalation of MA in the treatment of metastatic breast cancer. J Clin Oncol 17:64-73, (C) 1999 by American Society of Clinical Oncology. C1 Univ Maryland, Ctr Canc, Baltimore, MD 21201 USA. Stat Off, Leukemia Grp B, Durham, NC USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. McGill Canc Ctr, Montreal, PQ, Canada. SUNY Syracuse, Syracuse, NY USA. Univ Calif San Diego, San Diego, CA 92103 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Abrams, J (reprint author), NCI, 6130 Execut Blvd,EPN 741, Bethesda, MD 20892 USA. NR 30 TC 24 Z9 24 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 1999 VL 17 IS 1 BP 64 EP 73 PG 10 WC Oncology SC Oncology GA 155CB UT WOS:000077927400010 PM 10458219 ER PT J AU Ng, AK Weeks, JC Mauch, PM Kuntz, KM AF Ng, AK Weeks, JC Mauch, PM Kuntz, KM TI Laparotomy versus no laparotomy in the management of early-stage, favorable-prognosis Hodgkin's disease: A decision analysis SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; EXTENDED-FIELD RADIOTHERAPY; RADIATION-THERAPY SALVAGE; SOUTHWEST-ONCOLOGY-GROUP; HIGH-DOSE CHEMOTHERAPY; CLINICAL-TRIALS; COMBINED-MODALITY; FOLLOW-UP; COMBINATION CHEMOTHERAPY; EUROPEAN ORGANIZATION AB Purpose: To perform a decision analysis that compared the life expectancy and quality-adjusted life expectancy of early-stage, favorable-prognosis Hodgkin's disease (HD) managed with and without staging laparotomy, incorporating data on treatment outcomes of HD in the modern era. Methods: We constructed a decision-analytic model to compare laparotomy versus no laparotomy staging for a hypothetical cohort of 25-year-old patients with clinical stages I and II, favorable-prognosis HD. Markov models were used to simulate the lifetime clinical course of patients, whose prognosis depended on the true pathologic stage and initial treatment. The baseline probability estimates used in the model were derived from results of published studies. Quality-of-life adjustments for procedures and treatments, as well as the various long-term health states, were incorporated. Results: The life expectancy was 36.67 years for the laparotomy strategy and 35.92 years for no laparotomy, yielding a net expected benefit of 0.75 years for laparotomy staging, The corresponding quality-adjusted life expectancies for the two strategies were 35.97 and 35.38 quality-adjusted life years (QALYs), respectively, resulting in a net expected benefit of laparotomy staging of 0.59 QALYs. Sensitivity analysis showed that the decision of laparotomy versus no laparotomy was most heavily influenced by the quality-of-life weight assigned to the postlaparotomy state. Conclusion: Our model predicted that on average, for a 25-year-old patient, proceeding with staging laparotomy resulted in a gain in life expectancy of 9 months, or 7 quality-adjusted months, These results suggest that a role remains for surgical staging in the management of early-stage HD. J Clin Oncol 17:241-252, (C) 1999 by American Society of Clinical Oncology. C1 Harvard Univ, Sch Publ Hlth, Ctr Risk Anal, Dept Hlth Policy & Management, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kuntz, KM (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Risk Anal, Dept Hlth Policy & Management, 718 Huntington Ave, Boston, MA 02115 USA. NR 81 TC 15 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 1999 VL 17 IS 1 BP 241 EP 252 PG 12 WC Oncology SC Oncology GA 155CB UT WOS:000077927400030 PM 10458239 ER PT J AU Eng, C AF Eng, C TI RET proto-oncogene in the development of human cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID MULTIPLE-ENDOCRINE-NEOPLASIA; MEDULLARY-THYROID CARCINOMA; RECEPTOR TYROSINE KINASE; PROTOONCOGENE POINT MUTATIONS; SPORADIC NEUROENDOCRINE TUMORS; GENOTYPE-PHENOTYPE CORRELATION; MEN 2A; HIRSCHSPRUNG DISEASE; NEUROTROPHIC FACTOR; GERMLINE MUTATIONS AB The RET proto-oncogene, located on chromosome subband 10q11.2, encodes a receptor tyrosine kinase expressed in tissues and tumors derived from neural crest. Germline (present in every cell of the body) mutations in RET cause multiple endocrine neoplasia type 2 (MEN 2), an inherited cancer syndrome characterized by medullary thyroid carcinoma (MIC), pheochromocytoma (PC), and hyperparathyroidism (HPT). This knowledge has allowed molecular diagnosis and presymptomatic DNA-based testing to become possible. RET testing is considered the standard of care in MEN 2 families because clinical decisions are made based on the results of such gene testing, There appears to be a correlation between specific RET mutation type and organ-specific tumor development, Such knowledge might be useful in tailoring targeted surveillance in the near future. Somatic (in the tumor only) RET mutations have been found in a proportion of sporadic MTCs and PCs, Whether the presence of somatic RET mutation is associated with a poor prognosis is currently being investigated as another tool for molecular medicine. J Clin Oncol 17:380-393, (C) 1999 by American Society of Clinical Oncology. C1 Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Columbus, OH 43210 USA. Dana Farber Canc Inst, Dept Adult Oncol, Translat Res Lab, Charles A Dana Human Canc Genet Unit, Boston, MA 02115 USA. Univ Cambridge, Canc Res Campaign, Human Canc Genet Res Grp, Cambridge, England. RP Eng, C (reprint author), Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, 420 W 12th Ave,690C MRF, Columbus, OH 43210 USA. EM eng-1@medctr.osu.edu OI Eng, Charis/0000-0002-3693-5145 FU NIA NIH HHS [1P30AG13314-02] NR 126 TC 223 Z9 234 U1 1 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 1999 VL 17 IS 1 BP 380 EP 393 PG 14 WC Oncology SC Oncology GA 155CB UT WOS:000077927400048 PM 10458257 ER PT J AU Shipp, MA Abeloff, MD Antman, KH Carroll, G Hagenbeek, A Loeffler, M Montserrat, E Radford, JA Salles, G Schmitz, N Symann, M Armitage, JO Philip, T Coiffier, B AF Shipp, MA Abeloff, MD Antman, KH Carroll, G Hagenbeek, A Loeffler, M Montserrat, E Radford, JA Salles, G Schmitz, N Symann, M Armitage, JO Philip, T Coiffier, B TI International consensus conference on high-dose therapy with hematopoietic stem cell transplantation in aggressive non-hodgkin's lymphomas: Report of the jury SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; SEQUENTIAL CHEMOTHERAPY; INTERMEDIATE-GRADE; RANDOMIZED TRIAL; BLOOD; CHOP C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Oncol Ctr, Baltimore, MD USA. Columbia Presbyterian Med Ctr, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA. N Essex Hlth Author, Witham, Essex, England. Christie Hosp & Holt Radium Inst, Manchester M20 9BX, Lancs, England. Univ Utrecht Hosp, Utrecht, Netherlands. Inst Med Informat, Leipzig, Germany. Med Klin & Poliklin, Kiel, Germany. Hosp Clin Barcelona, Barcelona, Spain. Ctr Hosp Lyon Sud, Lyon, France. Oncol Clin, Brussels, Belgium. Univ Nebraska, Med Ctr, Omaha, NE USA. RP Shipp, MA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Radford, John/N-1331-2015 OI Radford, John/0000-0001-7898-2786 NR 32 TC 192 Z9 198 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN PY 1999 VL 17 IS 1 BP 423 EP 429 PG 7 WC Oncology SC Oncology GA 155CB UT WOS:000077927400052 PM 10458261 ER PT J AU Pollack, MH AF Pollack, MH TI New frontiers in the management of social anxiety disorder: Diagnosis, treatment, and clinical course - Introduction SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID NATIONAL-COMORBIDITY-SURVEY; PHOBIA C1 Massachusetts Gen Hosp, Anxiety Disorders Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Pollack, MH (reprint author), Massachusetts Gen Hosp, Anxiety Disorders Program, WACC 815,15 Parkman St, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 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 PY 1999 VL 60 SU 9 BP 3 EP 3 PG 1 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 195YP UT WOS:000080280800001 ER PT J AU Nierenberg, AA Wright, EC AF Nierenberg, AA Wright, EC TI Evolution of remission as the new standard in the treatment of depression SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Depression/Anxiety Working Group Conference CY JAN 30-31, 1999 CL DALLAS, TX ID COGNITIVE-BEHAVIORAL TREATMENT; NATIONAL-COMORBIDITY-SURVEY; MAJOR DEPRESSION; RESIDUAL SYMPTOMS; DOUBLE-BLIND; DISORDER; RELAPSE; VENLAFAXINE; THERAPY; PHARMACOTHERAPY AB Epidemiologic and clinical data support the goal of treating depressed patients to wellness or full remission. Many patients improve but fail to achieve full remission with antidepressant treatment and continue to have residual symptoms, which cause distress and dysfunction. These residual symptoms may meet criteria for subsyndromal and minor depression. Patients who have these milder syndromes after treatment have a greater risk of relapse and recurrence than do those who remain symptom-free. Clinical trials of antidepressants have shown lower rates of remission than of responses that fall short of remission, although some dual-acting antidepressants (e.g., serotonin-norepinephrine reuptake inhibitors) may have higher remission rates than other agents. Treatment with such robust dual-acting antidepressants may result in higher rates of remission and fewer residual symptoms than treatment with selective serotonin reuptake inhibitors. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Depress Clin & Res Program, Boston, MA 02114 USA. RP Nierenberg, AA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Depress Clin & Res Program, WACC 812,15 Parkman St, Boston, MA 02114 USA. NR 37 TC 133 Z9 142 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 752870, MEMPHIS, TN 38175-2870 USA SN 0160-6689 EI 1555-2101 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1999 VL 60 SU 22 BP 7 EP 11 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 273BC UT WOS:000084685900002 PM 10634349 ER PT J AU Otto, MW AF Otto, MW TI Cognitive-behavioral therapy for social anxiety disorder: Model, methods, and outcome SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on New Frontiers in the Management of Social Anxiety Disorder, in Conjunction with the 151st Annual Meeting of American-Psychiatric-Association CY MAY 31, 1998 CL TORONTO, CANADA SP Amer Psychiat Assoc ID 2-YEAR FOLLOW-UP; PANIC DISORDER; LONGITUDINAL COURSE; PHOBIA; METAANALYSIS; BELIEFS AB Cognitive-behavioral therapy for social anxiety disorder has typically emphasized cognitive-restructuring and exposure interventions, delivered alone or in combination, in either individual or group formats. Treatment programs emphasizing these interventions are associated with both acute improvements and longer term maintenance of treatment gains. In this article, the nature and application of these interventions are reviewed in relation to a cognitive-behavioral model of the development and maintenance of social anxiety disorder. Strategies for change and outcome findings are discussed, with attention to both individual studies and meta-analytic reviews of the literature. Strategies for improving outcomes and future directions for research are also discussed. C1 Massachusetts Gen Hosp, Anxiety Disorders Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Otto, MW (reprint author), Massachusetts Gen Hosp, Anxiety Disorders Program, WACC 815,15 Parkman St, Boston, MA 02114 USA. NR 28 TC 19 Z9 22 U1 2 U2 6 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 PY 1999 VL 60 SU 9 BP 14 EP 19 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 195YP UT WOS:000080280800004 PM 10335675 ER PT J AU Sachs, GS Guille, C AF Sachs, GS Guille, C TI Weight gain associated with use of psychotropic medications SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on Weight Gain Associated With the Use of Psychotropic Medications CY AUG 26, 1998 CL BOSTON, MASSACHUSETTS ID LITHIUM; VALPROATE; EPILEPSY; MECHANISMS; MANAGEMENT; VIGABATRIN; CLOZAPINE AB Weight gain is associated with the use of many psychotropic medications, including lithium, valproic acid, and several conventional and newer antipsychotics. Patients asked to select from among several comparable drugs often choose the one least likely to cause weight gain, even if the drug is less effective or has other troublesome adverse effects. For many patients, weight gain is so intolerable that they discontinue treatment. Patients who continue treatment are at risk for clinically significant weight gain that can progress to obesity, Even after patients stop taking the drug, weight gained during therapy may be difficult to lose. Thus, the best approach is to attempt to prevent weight gain when feasible, possibly through pretreatment dietary counseling and judicious drug selection, and to intervene as soon as weight gain becomes evident. C1 Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Boston, MA 02114 USA. RP Sachs, GS (reprint author), Massachusetts Gen Hosp, Clin Psychopharmacol Unit, WACC-815,15 Parkman St, Boston, MA 02114 USA. NR 27 TC 102 Z9 104 U1 0 U2 3 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PY 1999 VL 60 SU 21 BP 16 EP 19 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 251GB UT WOS:000083435300004 PM 10548137 ER PT J AU Pollack, MH AF Pollack, MH TI Social anxiety disorder: Designing a pharmacologic treatment strategy SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on New Frontiers in the Management of Social Anxiety Disorder, in Conjunction with the 151st Annual Meeting of American-Psychiatric-Association CY MAY 31, 1998 CL TORONTO, CANADA SP Amer Psychiat Assoc ID NATIONAL-COMORBIDITY-SURVEY; LONG-TERM TREATMENT; DOUBLE-BLIND; PHOBIA; FLUOXETINE; PLACEBO; MOCLOBEMIDE; CLONAZEPAM; PAROXETINE; BUSPIRONE AB Growing appreciation of the prevalence of and morbid sequelae associated with social anxiety disorder has focused increasing interest on the development of effective treatment strategies. A number of pharmacologic interventions, including the monoamine oxidase inhibitors, reversible inhibitors of monoamine oxidase A, P-blockers, benzodiazepines, and selective serotonin reuptake inhibitors, have demonstrated efficacy for the treatment of social anxiety disorder. The choice of initial treatment depends on a variety of factors including comorbidity, prior treatment history, patient preference, and adverse effect profile. This article will examine the effectiveness of various pharmacologic agents for the treatment of social anxiety disorder, discuss considerations for long-term management, and review strategies for optimizing treatment in patients who are partially responsive or unresponsive to initial therapy. C1 Massachusetts Gen Hosp, Anxiety Disorders Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Pollack, MH (reprint author), Massachusetts Gen Hosp, Anxiety Disorders Program, WACC 815,15 Parkman St, Boston, MA 02114 USA. NR 51 TC 36 Z9 36 U1 0 U2 1 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 PY 1999 VL 60 SU 9 BP 20 EP 26 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 195YP UT WOS:000080280800005 PM 10335676 ER PT J AU Fava, M Rosenbaum, JF AF Fava, M Rosenbaum, JF TI Anger attacks in patients with depression SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Closed Symposium on the Phenomenology and Treatment of Agression Across Psychiatric Illnesses CY AUG 31, 1998 CL CHICAGO, ILLINOIS SP Abbott Labs ID FLUOXETINE TREATMENT; UNIPOLAR DEPRESSION; DISORDERS AB Anger attacks are sudden intense spells of anger that resemble panic attacks but lack the predominant affects of fear and anxiety associated with panic attacks. They typically occur in situations in which an individual feels emotionally trapped and experiences outbursts of anger that are later described by the patient as being uncharacteristic and inappropriate to the situation at hand. Anger attacks consist of both behavioral and autonomic features, and various criteria and an Anger Attacks Questionnaire have been designed to identify the presence of these attacks. The prevalence of anger attacks in depressed patients is approximately 30% to 40%, and the attacks have disappeared in 53% to 71% of depressed patients treated with fluoxetine, sertraline, or imipramine. This article discusses the development of the concept of anger attacks, the presence of anger attacks in depression and other psychiatric disorders, and the current treatment of anger attacks. C1 Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Depress Clin & Res Program, Outpatient Psychiat Div, Boston, MA 02114 USA. RP Rosenbaum, JF (reprint author), Massachusetts Gen Hosp, Clin Psychopharmacol Unit, Depress Clin & Res Program, Outpatient Psychiat Div, WACC 815,15 Parkman St, Boston, MA 02114 USA. NR 16 TC 66 Z9 67 U1 1 U2 5 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 PY 1999 VL 60 SU 15 BP 21 EP 24 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 218FX UT WOS:000081543500005 PM 10418810 ER PT J AU Glazer, WM AF Glazer, WM TI Does loxapine have "atypical" properties? Clinical evidence SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Closed Symposium on What Makes an Antipsychotic Atypical CY MAY 06-07, 1998 CL DALLAS, TEXAS SP Watson Labs Inc ID LONG-TERM; BLIND; SCHIZOPHRENIA; HALOPERIDOL; CHLORPROMAZINE; OLANZAPINE; 5-HT2; D-2 AB Given findings at a pharmacologic level that loxapine has a ratio of serotonin (5-HT2) and dopamine (D-2) binding affinity similar to that of the atypical antipsychotics, I review data at a clinical level to see if this agent has correlating effects an symptoms and behaviors. I conclude that there is reason to infer that: loxapine may be more beneficial for negative symptoms and refractory states than other typical antipsychotic agents. However, because of the limitations within these older studies, controlled fixed-dose designs employing current outcome methodologies are needed before concluding chat loxapine is an atypical antipsychotic agent. C1 Harvard Univ, Sch Med, Dept Psychiat, Menemsha, MA USA. Massachusetts Gen Hosp, Menemsha, MA USA. RP Glazer, WM (reprint author), Glazer Med Solut, 260 W Broadway,Suite 7D, New York, NY 10013 USA. NR 38 TC 30 Z9 31 U1 0 U2 0 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 PY 1999 VL 60 SU 10 BP 42 EP 46 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 198CG UT WOS:000080403900006 PM 10340686 ER PT J AU Raskind, MA AF Raskind, MA TI Evaluation and management of aggressive behavior in the elderly demented patient SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Closed Symposium on the Phenomenology and Treatment of Agression Across Psychiatric Illnesses CY AUG 31, 1998 CL CHICAGO, ILLINOIS SP Abbott Labs ID ALZHEIMERS-DISEASE; EFFICACY; NOREPINEPHRINE; TOLERABILITY; DISTURBANCES; DIVALPROEX; DISORDERS; AGITATION; SYMPTOMS AB Aggression is common in elderly patients with dementia and often leads to placement of these patients in long-term care facilities. Unfortunately, identification and evaluation of aggression is sometimes hindered by disagreement as to how aggression is distinguished from agitation. Aggression in elderly patients with dementia is best understood as a product of the interaction of neurobiological, cognitive, and environmental factors. Such a complex etiology calls for an approach to treatment that considers pharmacologic therapy as well as environmental manipulation; however, further research is needed to clarify the causes of aggression in elderly patients with dementia and thus allow the refinement of approaches to treatment. C1 VA Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Raskind, MA (reprint author), VA Puget Sound Hlth Care Syst, Mental Hlth Serv, 116,1660 S Columbian Way, Seattle, WA 98108 USA. NR 26 TC 27 Z9 27 U1 0 U2 1 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 PY 1999 VL 60 SU 15 BP 45 EP 49 PG 5 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 218FX UT WOS:000081543500010 PM 10418815 ER PT J AU Nahas, Z Bohning, DE Molloy, MA Oustz, JA Risch, SC George, MS AF Nahas, Z Bohning, DE Molloy, MA Oustz, JA Risch, SC George, MS TI Safety and feasibility of repetitive transcranial magnetic stimulation in the treatment of anxious depression in pregnancy: A case report SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID SYMPTOMS AB Background: The proper treatment of mood disorders occurring during pregnancy is a major therapeutic problem since no antidepressant medications have been established as safe for the developing fetus. Several double-blind placebo-controlled studies have explored the efficacy of repetitive transcranial magnetic stimulation (rTMS) in depression. Case: We report the case of a 36-year-old woman in her second trimester of pregnancy, whose depression (DSM-IV) and anxiety were successfully treated with rTMS. Further studies of rTMS in depressed pregnant women appear warranted. C1 Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Healthsource Access Ctr, Charleston, SC USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Nahas, Z (reprint author), Med Univ S Carolina, Dept Psychiat, 171 Ashley Ave, Charleston, SC 29425 USA. EM nahasz@musc.edu NR 18 TC 44 Z9 46 U1 0 U2 4 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 JAN PY 1999 VL 60 IS 1 BP 50 EP 52 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 165GJ UT WOS:000078512300010 PM 10074879 ER PT J AU Tondo, L Baldessarini, RJ Hennen, J Minnai, GP Salis, P Scamonatti, L Masia, M Ghiani, C Mannu, P AF Tondo, L Baldessarini, RJ Hennen, J Minnai, GP Salis, P Scamonatti, L Masia, M Ghiani, C Mannu, P TI Suicide attempts in major affective disorder patients with comorbid substance use disorders SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on the Effects of Medical Interventions on Suicidal Behavior CY FEB 26-28, 1998 CL MIAMI, FLORIDA SP Amer Fdn Suicide Prevent, Johns Hopkins Univ Sch Med, Long Island Jewish Med Ctr, Suicide Prevent Advocacy Network, Solvay Pharmaceut Inc ID HIGH-SCHOOL-STUDENTS; RISK-FACTORS; ADOLESCENT SUICIDE; YOUNG-PEOPLE; DEPRESSION; BEHAVIOR; ABUSE; ALCOHOLISM; VETERANS; PERIOD AB Background: The widely accepted impression that substance abuse and dependence are associated with increased suicidal risk was evaluated by literature review and with new data. Method: Previous research on this association was reviewed, and clinical data on suicide attempts and substance use in 504 mood disorder patients hospitalized in 4 psychiatric units in Sardinia affiliated with the Italian mental health system were analyzed. Results: The literature supports associations of alcohol and drug use comorbidity with major affective disorders, and of some substances (polyabuse, alcohol, heroin, cocaine, and even tobacco, but perhaps not marijuana or hallucinogens) with suicidal behavior. Our new findings generally supported these Zway associations. Suicidal risks were similar in hospitalized men and women but were associated with bipolar II, bipolar I (mainly mixed), and unipolar depressive disorders as well as substance abuse, with little effect of type of agent. Substance abuse was more common in nonmixed bipolar disorders, men, and age below 30. Conclusion: The tendency for bipolar I, mainly nonmixed patients, to have a relatively high risk of substance abuse and low risk of suicide attempts indicates that mainly depressive or dysphoric (bipolar II, nonbipolar, and bipolar I, mainly mixed) mood disorders may be especially lethal. Differences in risks of substance abuse and suicidal behavior in men and in bipolar I patients further suggest that substance abuse and mood disorders may contribute to suicidal risk with at least partial independence or additivity. C1 Int Consortium Res Bipolar Disorders, Boston, MA USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, McLean Div, Bipolar & Psychot Disorders Program, Belmont, MA 02178 USA. Massachusetts Gen Hosp, McLean Div, Psychopharmacol Program, Belmont, MA 02178 USA. Univ Cagliari, Dept Psychiat, Sardinia, Italy. Univ Cagliari, Dept Psychol, Sardinia, Italy. S Martino Hosp, Dept Psychiat, Oristano, Sardinia, Italy. SS Trinita Hosp, Dept Psychiat, Cagliari, Sardinia, Italy. Clin Lay Hosp, Cagliari, Sardinia, Italy. Lucio Bini Psychiat Ctr, Cagliari, Sardinia, Italy. RP Tondo, L (reprint author), McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02178 USA. EM ltondo@aol.com FU NIMH NIH HHS [MH-47370] NR 60 TC 115 Z9 117 U1 5 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 PY 1999 VL 60 SU 2 BP 63 EP 69 PG 7 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 171JZ UT WOS:000078861300013 PM 10073390 ER PT J AU Baldessarini, RJ Tondo, L Hennen, J AF Baldessarini, RJ Tondo, L Hennen, J TI Effects of lithium treatment and its discontinuation on suicidal behavior in bipolar manic-depressive disorders SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on the Effects of Medical Interventions on Suicidal Behavior CY FEB 26-28, 1998 CL MIAMI, FLORIDA SP Amer Fdn Suicide Prevent, Johns Hopkins Univ Sch Med, Long Island Jewish Med Ctr, Suicide Prevent Advocacy Network, Solvay Pharmaceut Inc ID RECURRENT MOOD DISORDERS; MAINTENANCE TREATMENT; MORTALITY; RISK; ANTIDEPRESSANTS; PROPHYLAXIS; PREVENTION; CARBAMAZEPINE; POPULATION; BENEFIT AB Background: Whether mood-altering treatments reduce risk of suicidal behavior remains largely unproved. Method: We compared suicidal rates in published studies of patients treated with lithium with those who were not, and in a mood disorders clinic before, during, and after discontinuing lithium. Results: Published reports indicate a 7.0-fold lower rate of suicidal acts with lithium treatment of manic-depressive patients. In new findings in over 300 bipolar patients, latency from illness onset to lithium maintenance averaged 8.3 years (from 11.0 years in women with bipolar II disorder to 6.9 years in men with bipolar I disorder), but half of all suicidal acts occurred in the first 7.5 of 18.3 years at risk. Most acts (89%) occurred during depressive (73%) or dysphoric-mixed (16%) mood states and were associated with previous severe depression, prior attempts, and lower age at onset. Morbidity was reduced 2.7-fold and suicidal acts per year 6.5-fold during lithium treatment, with 8.3-fold cumulative sparing of risk by 15 years on lithium. In the first year off lithium, affective illness recurred in 67% of patients, and suicidal rates rose 20-fold but were much lower thereafter; fatalities were 14 times more frequent after discontinuation of lithium. Early morbidity was 2.5-fold lower, and suicidal risk was 2.0-fold lower after slow versus rapid discontinuation. Conclusion: Lithium maintenance is associated with sustained reduction of suicidal acts in manic-depressive disorders. Treatment discontinuation, particularly abruptly, led to early affective morbidity and suicidal behavior. Improved diagnosis and treatment as well as earlier intervention for potentially lethal bipolar depression are urgently needed, as are studies of all mood-altering agents for effects on suicidal behavior. C1 Int Consortium Res Bipolar Disorders, Boston, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Massachusetts Gen Hosp, McLean Div, Biopolar & Psychot Disorders Program, Belmont, MA USA. Massachusetts Gen Hosp, McLean Div, Psychopharmacol Program, Belmont, MA USA. Univ Cagliari, Dept Psychiat, Cagliari, Sardinia, Italy. Univ Cagliari, Dept Psychol, Cagliari, Sardinia, Italy. Stanley Fdn European Res Ctr, Lucio Bini Psychiat Ctr, Cagliari, Sardinia, Italy. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. FU NIMH NIH HHS [MH-47370] NR 58 TC 141 Z9 144 U1 1 U2 5 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 PY 1999 VL 60 SU 2 BP 77 EP 84 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 171JZ UT WOS:000078861300016 PM 10073392 ER PT J AU Baldessarini, RJ Jamison, KR AF Baldessarini, RJ Jamison, KR TI Effects of medical interventions on suicidal behavior - Summary and conclusions SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material AB Background: An international symposium evaluated current knowledge of the epidemiology, psychobiology, and effects of medical treatment on suicidal behavior. Method: Moderators summarized the main findings and conclusions of the participants on the basis of presentations and consensus statements at the meeting. Results: Despite striking advances in the medical treatment of mood disorders in the past half-century, rates of suicidal acts have changed little in the general population. Evidence of reduction of long-term rates of suicidal acts in specific at-risk populations remains very limited, particularly persons with major affective illnesses and other common, primary or comorbid psychiatric and substance use disorders. It is plausible that reduction of psychiatric morbidity should limit suicidal risk, but very little is known about specific effects of most psychiatric treatments or other interventions aimed at suicide prevention. An exception is substantial evidence of lower suicidal risk during long-term lithium treatment that was not equaled with carbamazepine. However, diagnosis and timely therapeutic interventions reach only a minority of psychiatrically ill persons at risk for suicide. Conclusion: Renewed efforts are strongly urged to: (1) improve public and professional awareness of risk factors for suicide, (2) enhance earlier access to appropriate clinical assessment and increasingly safe and effective treatments for affective and psychotic disorders, and (3) encourage and support research to clarify specific benefits and risks of medical treatments and social interventions aimed at preventing suicide. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Massachusetts Gen Hosp, McLean Div, Belmont, MA USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. FU NIMH NIH HHS [MH-47370] NR 0 TC 37 Z9 37 U1 0 U2 0 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 PY 1999 VL 60 SU 2 BP 117 EP 122 PG 6 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 171JZ UT WOS:000078861300024 PM 10073398 ER PT J AU Caplan, D Alpert, N Waters, G AF Caplan, D Alpert, N Waters, G TI Brain organization for syntactic processing studied with positron emission tomography. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. Boston Univ, Dept Commun Disorders, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 1999 SU S BP 9 EP 9 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 238FJ UT WOS:000082700000012 ER PT J AU Lindenberger, U Baltes, PB AF Lindenberger, U Baltes, PB TI Decrements in performance level, increments in variance and covariance: A behavioral perspective on brain aging. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02114 USA. Boston Univ, Dept Commun Disorders, Boston, MA 02215 USA. RI Lindenberger, Ulman/A-5846-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 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. PY 1999 SU S BP 9 EP 10 PG 2 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 238FJ UT WOS:000082700000014 ER PT J AU Badgaiyan, RD Schacter, DL Alpert, NM AF Badgaiyan, RD Schacter, DL Alpert, NM TI Deactivation of extrastriate cortex in unimodal auditory priming but not in cross modal priming. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, PET Imaging Lab, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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. PY 1999 SU S BP 39 EP 39 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 238FJ UT WOS:000082700000153 ER PT J AU Bergida, R Kegl, J AF Bergida, R Kegl, J TI Categorization of American sign language question faces by hearing non-signers. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Boston Univ, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ So Maine, Portland, ME 04103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 1999 SU S BP 81 EP 82 PG 2 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 238FJ UT WOS:000082700000373 ER PT J AU Pena, CS Kaufman, JA Geller, SC Waltman, AC AF Pena, CS Kaufman, JA Geller, SC Waltman, AC TI Gadopentetate dimeglumine: A possible alternative contrast agent for CT angiography of the aorta SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE computed tomography; angiography; contrast media; computed tomographic angiography (CTA); gadolinium dimeglumine ID GD-DTPA AB We report the use of a gadolinium chelate for limited CT angiography of the aorta in a patient in whom iodinated contrast agent was contraindicated and who had undergone nondiagnostic MRI. C1 Massachusetts Gen Hosp, Div Vasc Radiol, Boston, MA 02114 USA. RP Kaufman, JA (reprint author), Massachusetts Gen Hosp, Div Vasc Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 8 TC 19 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JAN-FEB PY 1999 VL 23 IS 1 BP 23 EP 24 DI 10.1097/00004728-199901000-00006 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 169QJ UT WOS:000078759800006 PM 10050802 ER PT J AU Rao, PM AF Rao, PM TI Cecal apical changes with appendicitis: Diagnosing appendicitis when the appendix is borderline abnormal or not seen SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE gastrointestinal tract, infection; appendix, infection; gastrointestinal tract, anatomy; computed tomogaphy ID CT AB In most cases, CT of appendicitis shows a distended appendix with peri-appendiceal inflammation. A distended appendix, however, is not always visualized. In these patients, identifying: changes at the anatomic cecal apex can secure a diagnosis of appendicitis. Cecal apical changes with appendicitis include focal cecal apical thickening, the arrowhead sign, and the cecal bar. This pictorial essay describes and illustrates the spectrum of CT appearances of cecal apical changes that can be seen with appendicitis. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Rao, PM (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 9 TC 14 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD JAN-FEB PY 1999 VL 23 IS 1 BP 55 EP 59 DI 10.1097/00004728-199901000-00012 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 169QJ UT WOS:000078759800012 PM 10050808 ER PT J AU Brown, DFM Nadel, ES Greenberg, M Richards, C Nagurney, JT Cranmer, H Wolfe, R Walls, R Wuerz, R AF Brown, DFM Nadel, ES Greenberg, M Richards, C Nagurney, JT Cranmer, H Wolfe, R Walls, R Wuerz, R TI The differential diagnosis of shock SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID COMPLICATIONS C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Clin 115,55 Fruit St, Boston, MA 02114 USA. NR 7 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 JAN-FEB PY 1999 VL 17 IS 1 BP 105 EP 109 PG 5 WC Emergency Medicine SC Emergency Medicine GA 229DY UT WOS:000082179300019 PM 9950396 ER PT J AU Kirikae, T Kirikae, F Iwai, H Qureshi, N Fukase, K Kusumoto, S Nakano, M AF Kirikae, T Kirikae, F Iwai, H Qureshi, N Fukase, K Kusumoto, S Nakano, M TI LPS-dependent changes in the expression of 57 kDa and 53 kDa cell membrane proteins without participation of CD14 SO JOURNAL OF ENDOTOXIN RESEARCH LA English DT Article ID DIPHOSPHORYL-LIPID-A; RHODOPSEUDOMONAS-SPHAEROIDES; MURINE MACROPHAGES; BACTERIAL LIPOPOLYSACCHARIDE; NITRIC-OXIDE; FATTY-ACIDS; TAXOL; INDUCTION; ENDOTOXIN AB It is widely presumed that in addition to CD14, other molecules are necessary for lipopolysaccharide (LPS)-induced cell activation. In order to shed light on some of the biological and biochemical properties of these molecules, we examined the LPS responsiveness of CD14-negative, ST2 cells. Although ST2 cells do not express CD14 mRNA, they, nonetheless, expressed IL-6 mRNA and synthesized IL-6 protein when incubated with LPS in serum-free medium (i.e. without soluble CD14). Paxlitacel (Taxol(TM)) also induced IL-6 mRNA expression in ST2 cells, while Rhodobacter sphaeroides diphoshoryl lipid A (RsDPLA) inhibited both LPS- and Taxol-induced expression of Br 6 mRNA. Collectively, these data suggest that LPS, RsDPLA, and Taxol all recognize the same receptor complex on ST2 cells and do not require the participation of CD14. In addition, using antibody raised against the STZ cell membrane fraction, we detected a set of LPS-specific membrane antigens in murine peritoneal macrophages, including two designated p57 (57 kDa) and p53 (53 kDa). There was no qualitative difference in the expression of p57 and p53 in LPS-responsive, C3H/HeN and LPS-hyporesponsive, C3H/HeJ macrophages. However, after stimulating the macrophages with LPS or Taxol, expression of p57 and p53 was diminished in C3H/HeN macrophages, but not in C3H/HeJ macrophages. Phorbol ester (PMA) and A23187 calcium ionophore did not suppress p57 or p53 expression, and the lipid A precursor, PE406, did not bind to either protein. Thus, p57 and p53 may play important roles in LPS-evoked responses, but they do not appear to serve as LPS receptors. C1 Int Med Ctr Japan, Res Inst, Dept Trop Med & Infect Dis, Shinjuku Ku, Tokyo 1628655, Japan. Jichi Med Sch, Dept Microbiol, Mibu, Tochigi, Japan. William S Middleton Mem Vet Hosp, Mycobacteriol Res Lab, Madison, WI USA. Osaka Univ, Fac Sci, Toyonaka, Osaka 560, Japan. RP Kirikae, T (reprint author), Int Med Ctr Japan, Res Inst, Dept Trop Med & Infect Dis, Shinjuku Ku, 1-21-1 Toyama, Tokyo 1628655, Japan. NR 14 TC 2 Z9 2 U1 0 U2 0 PU MANEY PUBLISHING LTD PI LEEDS PA HUNDSON RD, LEEDS LS9 7DL, ENGLAND SN 0968-0519 J9 J ENDOTOXIN RES JI J. Endoxtin Res. PY 1999 VL 5 IS 1-2 BP 62 EP 65 DI 10.1177/09680519990050010301 PG 4 WC Biochemistry & Molecular Biology; Immunology; Medicine, Research & Experimental; Microbiology SC Biochemistry & Molecular Biology; Immunology; Research & Experimental Medicine; Microbiology GA 230PF UT WOS:000082259000011 ER PT J AU Hellman, J Warren, HS AF Hellman, J Warren, HS TI Antibodies against bacterial membrane proteins SO JOURNAL OF ENDOTOXIN RESEARCH LA English DT Article ID GRAM-NEGATIVE BACTERIA; ESCHERICHIA-COLI J5; LIPOPOLYSACCHARIDES; BINDING; ANTISERUM; INVIVO; SERUM AB Prior studies have shown that antiserum raised to the Escherichia coli J5 vaccine binds to three bacterial outer membrane proteins (OMPs) that are present on serum-exposed smooth Enterobacteriaceae and in LPS-containing fragments that are released by bacteria incubated in human serum. The present studies were performed to further analyze release of the three OMPs into human serum. Normal human serum was incubated with E. coli O18K(+) bacteria and then filtered to remove intact bacteria. Lipopolysaccharide (LPS) was affinity-purified from sterile filtrates using murine monoclonal IgG directed against the O-polysaccharide chain of E. coli O18 LPS (monoclonal anti-O IgG). Components of sterile filtrates were also separated by ultracentrifugation on sequential potassium bromide and cesium chloride gradients. Samples were analyzed by immunoblotting, using anti-J5 IgG and polyclonal anti-O IgG as primary antibodies. Three OMPs, of MWs 5-9, 18, and 35 kDa were detected in samples that were affinity-purified using monoclonal anti-O IgG, indicating that complexes containing at least these three OMPs and LPS (OMP/LPS complexes) are released into human serum. The 18 kDa OMP was detected in low density fractions of the density gradients, indicating that this OMP is also released separately from the OMP/LPS complexes in a form that floats at the same density as serum lipoproteins. C1 Massachusetts Gen Hosp CNY, Infect Dis Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. RP Hellman, J (reprint author), Massachusetts Gen Hosp CNY, Infect Dis Unit, 5th Floor,149 13th St, Charlestown, MA 02129 USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU MANEY PUBLISHING LTD PI LEEDS PA HUNDSON RD, LEEDS LS9 7DL, ENGLAND SN 0968-0519 J9 J ENDOTOXIN RES JI J. Endoxtin Res. PY 1999 VL 5 IS 4 BP 213 EP 215 PG 3 WC Biochemistry & Molecular Biology; Immunology; Medicine, Research & Experimental; Microbiology SC Biochemistry & Molecular Biology; Immunology; Research & Experimental Medicine; Microbiology GA 269PP UT WOS:000084487000006 ER PT J AU Warshaw, AL AF Warshaw, AL TI The challenge of success SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, 55 Fruit St,WHT506, Boston, MA 02114 USA. NR 13 TC 1 Z9 1 U1 0 U2 0 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 JAN-FEB PY 1999 VL 3 IS 1 BP 1 EP 6 DI 10.1016/S1091-255X(99)80001-8 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 247LT UT WOS:000083222800001 ER PT J AU Yoon, SS Carroll, NM Chiocca, EA Tanabe, KK AF Yoon, SS Carroll, NM Chiocca, EA Tanabe, KK TI Influence of p53 on herpes simplex virus type 1 vectors for cancer gene therapy SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE HSV 1; p53; colorectal cancer; gene therapy ID WILD-TYPE P53; COLORECTAL-CANCER; CELLS; METASTASES; GROWTH; COLON; REPLICATION; INHIBITION; APOPTOSIS; MUTANT AB Herpes simplex virus type 1 (HSV 1) vectors are under investigation for use in gene therapy for colorectal cancer liver metastases. Approximately 60% of colorectal cancers possess p53 mutations, and p53 mutations can cause tumor cell resistance to radiation therapy and chemotherapy. p53 is also known to colocalize with at least one HSV 1 protein and influence HSV 1 gene expression. The purpose of this study was to determine if the loss or mutation of p53 in tumor cells alters the cytotoxicity of HSV 1 vectors. HSV 1 vector-mediated in vitro cytotoxicity assays were performed using stable transfectants of SAOS-2-LM2 cells and WiDr cells that express no p53, wild-type p53, mutant p53, or both wild-type p53 and mutant p53. AU stable transfectants were equally susceptible to HSV 1 vector cytotoxicity, and cell lines with mutant p53 were not resistant to HSV 1 vectors. These results provide additional rationale for the application of HSV 1 vector gene therapy for colorectal cancer. C1 Massachusetts Gen Hosp, Div Surg Oncol, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Tanabe, KK (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Dept Surg, Cox 626,100 Blossom St, Boston, MA 02114 USA. FU NCI NIH HHS [CA60011, CA64454]; NIDDK NIH HHS [DK43351] NR 25 TC 8 Z9 8 U1 0 U2 0 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 JAN-FEB PY 1999 VL 3 IS 1 BP 34 EP 38 DI 10.1016/S1091-255X(99)80005-5 PG 5 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 247LT UT WOS:000083222800007 PM 10457321 ER PT J AU Vedantham, V Cannon, SC AF Vedantham, V Cannon, SC TI The position of the fast-inactivation gate during lidocaine block of voltage-gated Na+ channels SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article DE local anesthetic; SkM1; antiarrhythmic; patch clamp; methanethiosulfonate ID CARDIAC SODIUM-CHANNELS; SQUID GIANT-AXONS; LOCAL-ANESTHETICS; DEPENDENT BLOCK; INHIBITION; ACTIVATION; RECEPTOR; CURRENTS AB Lidocaine produces voltage- and use-dependent inhibition of voltage-gated Na+ channels through preferential binding to channel conformations that are normally populated at depolarized potentials and by slowing the rate of Na+ channel repriming after depolarizations. It has been proposed that the fast-inactivation mechanism plays a crucial role in these processes. However, the precise role of fast inactivation in lidocaine action has been difficult to probe because gating of drug-bound channels does not involve changes in ionic current. For that reason, we employed a conformational marker for the fast-inactivation gate, the reactivity of a cysteine substituted at phenylalanine 1304 in the rat adult skeletal muscle sodium channel ct subunit (rSkM1) with [2-(trimethylammonium) ethyl] methanethiosulfonate (MTS-ET), to determine the position of the fast-inactivation gate during lidocaine block. We found that lidocaine does not compete with fast-inactivation. Rather, it favors closure of the fast-inactivation gate in a voltage-dependent manner, causing a hyperpolarizing shift in the voltage dependence of site 1304 accessibility that parallels a shift in the steady state availability curve measured for ionic currents. More significantly, we found that the lidocaine-induced slowing of sodium channel repriming does not result from a slowing of recovery of the fast-inactivation gate, and thus that use-dependent block does not involve an accumulation of fast-inactivated channels. Based on these data, we propose a model in which transitions along the activation pathway, rather than transitions to inactivated states, play a crucial role in the mechanism of lidocaine action. C1 Massachusetts Gen Hosp, Dept Neurol, EDR413A, Boston, MA 02214 USA. Harvard Univ, Sch Med, Program Neurosci, Div Med Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Cannon, SC (reprint author), Massachusetts Gen Hosp, Dept Neurol, EDR413A, Boston, MA 02214 USA. FU NIAMS NIH HHS [R37 AR042703, R01 AR042703, AR-42703] NR 25 TC 77 Z9 78 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JAN PY 1999 VL 113 IS 1 BP 7 EP 16 DI 10.1085/jgp.113.1.7 PG 10 WC Physiology SC Physiology GA 156RX UT WOS:000078016800003 PM 9874684 ER PT J AU Chin, KR Lonner, JH Jupiter, BS Jupiter, JB AF Chin, KR Lonner, JH Jupiter, BS Jupiter, JB TI The surgeon as a hand patient: The clinical and psychological impact of hand and wrist fractures SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE surgeons; hand injuries; psychological; motivated ID PHYSICIAN AB To gain insight into the management of patients with hand and wrist injuries, a series of clinical and psychological analyses was performed on 9 surgeons, each of whom underwent operative fixation of a hand or wrist fracture. The results of these analyses suggest that the functional outcome after hand surgery was affected by the surgeons' personality, motivation, and ability to accept and adapt to the injury; the nature of the injury; and the importance of the hand to the surgeons' careers. Surgeons are highly motivated and compulsive individuals who consider their career involvement a major source of identity and self-worth. Most returned to their operative duties ahead of the schedule set by their hand surgeons (average, 25 days after surgery), regarded their injuries as a positive challenge, and changed their lifestyles after injury to protect their hands. (J Hand Surg 1999;24A:59-63. Copyright (C) 1999 by the American Society for Surgery of the Hand.). C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Hand Surg Serv, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Jupiter, JB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Hand Surg Serv, Dept Orthopaed Surg, WACC 527, Boston, MA 02114 USA. NR 17 TC 10 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD JAN PY 1999 VL 24A IS 1 BP 59 EP 63 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 163VK UT WOS:000078426900009 PM 10048517 ER PT J AU Cahill, CM Rogers, JT AF Cahill, CM Rogers, JT TI Anti-idiotypic sera against monoclonal antiporcine growth hormone antibodies: Production in rabbits and characterization of specificity SO JOURNAL OF IMMUNOASSAY LA English DT Article DE anti-idiotypic antibodies; growth hormone ID ANTIIDIOTYPIC ANTIBODY; SUPPRESSION AB Antisera were raised in rabbits against two mouse monoclonal anti-porcine growth hormone (pGH) antibodies. Anti-idiotypic antibodies were isolated from rabbit sera by successive passage over immunoadsorbent columns of normal mouse Ig (mIg), followed by the specific immunizing monoclonal and elution from the latter. Enzyme linked immunoadsorbent assay (ELISA) for anti-idiotype and free idiotype were established. While showing specificity for their respective inducing monoclonals, anti-idiotypes also cross reacted in varying degrees with other anti-pGH monoclonals regardless of specificity differences between the antibodies, demonstrating the presence of a cross-reactive idiotype. C1 Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Hematol, Boston, MA 02115 USA. RP Cahill, CM (reprint author), Massachusetts Gen Hosp, Dept Med, Diabet Unit, Wellman 340,50 Blossom St, Boston, MA 02114 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0197-1522 J9 J IMMUNOASSAY JI J. Immunoass. PY 1999 VL 20 IS 1-2 BP 45 EP 55 DI 10.1080/01971529909349313 PG 11 WC Biochemistry & Molecular Biology; Immunology; Medical Laboratory Technology SC Biochemistry & Molecular Biology; Immunology; Medical Laboratory Technology GA 185CR UT WOS:000079651000004 PM 10225514 ER PT J AU Wang, KS Ritz, J Frank, DA AF Wang, KS Ritz, J Frank, DA TI IL-2 induces STAT4 activation in primary NK cells and NK cell lines, but not in T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; CILIARY NEUROTROPHIC FACTOR; JAK-3 JANUS KINASE; TYROSINE PHOSPHORYLATION; RECEPTOR EXPRESSION; SIGNAL TRANSDUCER; HUMAN-LYMPHOCYTES; IFN-ALPHA; INTERLEUKIN-2; RESPONSES AB IL-2 exerts potent but distinct functional effects on two critical cell populations of the immune system, T cells and NK cells. Whereas IL-2 leads to proliferation in both cell types, it enhances cytotoxicity primarily in NR cells. In both T cells and NK cells, IL-2 induces the activation of STAT1, STAT3, and STAT5. Given this similarity in intracellular signaling, the mechanism underlying the distinct response to IL-2 in T cells and NK cells is not clear. In this study, we show that in primary NK cells and NK cell lines, in addition to the activation of STAT1 and STAT5, IL-2 induces tyrosine phosphorylation of STAT4, a STAT previously reported to be activated only in response to IL-12 and IFN-alpha. This activation of STAT4 in response to IL-2 is not due to the autocrine production of IL-12 or IFN-alpha. STAT4 activated in response to IL-2 is able to bind to a STAT-binding DNA sequence, suggesting that in NK cells IL-2 is capable of activating target genes through phosphorylation of STAT4. IL-2 induces the activation of Jak2 uniquely in NK cells, which may underlie the ability of IL-2 to activate STAT4 only in these cells. Although the activation of STAT4 in response to IL-2 occurs in primary resting and activated NK cells, it does not occur in primary resting T cells or mitogen-activated T cells. The unique activation of the STAT4-signaling pathway in NK cells may underlie the distinct functional effect of IL-2 on this cell population. C1 Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Dept Adult Oncol, Boston, MA 02115 USA. RP Frank, DA (reprint author), Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA41619] NR 31 TC 56 Z9 58 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 JAN 1 PY 1999 VL 162 IS 1 BP 299 EP 304 PG 6 WC Immunology SC Immunology GA 151YK UT WOS:000077748100038 PM 9886399 ER PT J AU Wang, W Wykrzykowska, J Johnson, T Sen, R Sen, J AF Wang, W Wykrzykowska, J Johnson, T Sen, R Sen, J TI A NF-kappa B/c-myc dependent survival pathway is targeted by corticosteroids in immature thymocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; MURINE B-CELLS; C-MYC; TRANSGENIC MICE; INDUCED APOPTOSIS; INTRATHYMIC SIGNALS; POSITIVE SELECTION; RECEPTOR; ALPHA; INHIBITION AB Glucocorticoid hormones modulate T cell maturation in vivo, While low levels of hormones are required for appropriate T cell development, high levels of glucocorticoid hormones target immature developing thymocytes for cell death during systemic stress. In this report, we propose a molecular mechanism for the induction of apoptosis in CD4(+)CD8(+) double-positive thymocytes by dexamethasone in vivo, Dexamethasone injection induced the expression of I kappa B alpha: and I kappa B beta in thymocytes and down-regulated NF-kappa B DNA binding activated by intrathymic signals, Down-regulation of NF-kappa B DNA binding preceded cell death, suggesting that NF-kappa B may be important for the survival of immature thymocytes. In addition, ex vivo treatment of thymocyte single-cell suspension with dexamethasone, accelerated p65/RelA down-regulation and cell death. Conversely, NF-kappa B induction diminished dexamethasone-induced death. Expression of the c-myc proto-oncogene, a NF-kappa B target, was also reduced in thymocytes of dexamethasone-treated animals, and ectopic transgenic expression of c-myc in mice provided partial rescue of double-positive thymocytes from dexamethasone mediated cell death, These observations suggest that viability of CD4(+)CD8(+) thymocytes may be maintained by an NF-kappa B/c-myc-dependent pathway in vivo. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02254 USA. Brandeis Univ, Dept Biol, Waltham, MA 02254 USA. RP Sen, J (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA74404]; NIGMS NIH HHS [GM43874] NR 41 TC 44 Z9 45 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 JAN 1 PY 1999 VL 162 IS 1 BP 314 EP 322 PG 9 WC Immunology SC Immunology GA 151YK UT WOS:000077748100040 PM 9886401 ER PT J AU Hausmann, S Martin, M Gauthier, L Wucherpfennig, KW AF Hausmann, S Martin, M Gauthier, L Wucherpfennig, KW TI Structural features of autoreactive TCR that determine the degree of degeneracy in peptide recognition SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; T-CELL RECOGNITION; MULTIPLE-SCLEROSIS; ALPHA-BETA; AUTOIMMUNITY; LIGANDS; ENCEPHALOMYELITIS; BINDING; COMPLEX; REGION AB Structural aspects of human TCRs that allow the activation of autoreactive T cells by diverse microbial peptides were examined using two human myelin basic protein (MBP)-specific T cell clones. The TCR sequences of these clones differed only in the N region of TCR-alpha and -beta since the clones had the same V alpha-J alpha and V beta-J beta rearrangements. The two clones had a similar fine specificity for the MBP peptide, except for the P5 position of the peptide (lysine), In the crystal structure of the HLA-DR2/MBP peptide complex, P5 lysine is a prominent, solvent-exposed residue in the center of the DR2/MBP peptide surface. Five microbial peptides with conservative or nonconservative changes at the P5 position (lysine to arginine, serine, or proline) activated one of these clones. In contrast, the other clone was activated only by three of these peptides which had a conservative lysine to arginine change at P5, The degree of specificity/degeneracy in recognition of the P5 side chain was the key difference between these TCRs since the Escherichia coli/Haemophilus influenzae peptide stimulated both clones when the P5 position was substituted from serine to arginine, These results demonstrate that the complementarity-determining region 3 loops contribute to the degree of degeneracy in peptide recognition by human MBP-specific TCRs. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM wucherpf@mbcrr.harvard.edu RI Martin, Margarita/H-2025-2015 OI Martin, Margarita/0000-0002-9245-4899 FU NIAID NIH HHS [AI 42316] NR 27 TC 56 Z9 58 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 JAN 1 PY 1999 VL 162 IS 1 BP 338 EP 344 PG 7 WC Immunology SC Immunology GA 151YK UT WOS:000077748100043 PM 9886404 ER PT J AU Ierino, FL Yamada, K Hatch, T Rembert, J Sachs, DH AF Ierino, FL Yamada, K Hatch, T Rembert, J Sachs, DH TI Peripheral tolerance to class I mismatched renal allografts in miniature swine: Donor antigen-activated peripheral blood lymphocytes from tolerant swine inhibit antidonor CTL reactivity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HELPER T-CELLS; PRIMARILY VASCULARIZED ALLOGRAFTS; SUPPRESSOR CELLS; TRANSPLANTATION TOLERANCE; INDUCTION; INTERLEUKIN-2; ALLOANTIGEN; UNRESPONSIVENESS; CYCLOSPORINE; RESPONSES AB Studies utilizing partially inbred miniature swine have demonstrated that a short course of cyclosporin A leads to indefinite survival of two haplotype class I mismatched renal allografts. Tn the present study, we have examined peripheral regulatory mechanisms that may be involved in maintenance of tolerance by coculturing PBT, from long-term tolerant animals with naive recipient-matched PBL in cell-mediated lympholysis assays. We show that PBT, from tolerant animals, primed in vitro with donor Ag, suppress antidonor CTL reactivity by naive recipient-matched PBL. Suppression was not observed when PBT, from naive animals, primed with donor-matched PBL, were cocultured with PBL from a second naive animal, nor did PBL from either tolerant or naive recipient-matched control animals, primed with third-party Ag, suppress the generation of anti-third-party CTL, by a second naive animal. The suppression was cell dose-dependent, radiation-sensitive, required cell-to-cell contact not reversed by the provision of exogenous IL-2, and associated with lower levels of IL-2R expression on the suppressive effector group (particularly the CD8 single positive cells) when compared with the control effector group. These data indicate an association between the presence of peripheral regulatory cells demonstrable in vitro and the maintenance of tolerance to renal allografts. C1 Massachusetts Gen Hosp East, Renal Unit, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Sachs, DH (reprint author), Massachusetts Gen Hosp East, Renal Unit, MGH-E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NHLBI NIH HHS [HL18646]; PHS HHS [A131046] NR 54 TC 43 Z9 43 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 JAN 1 PY 1999 VL 162 IS 1 BP 550 EP 559 PG 10 WC Immunology SC Immunology GA 151YK UT WOS:000077748100071 PM 9886432 ER PT J AU Rappaport, JM Bhatt, SM Burkard, RF Merchant, SN Nadol, JB AF Rappaport, JM Bhatt, SM Burkard, RF Merchant, SN Nadol, JB TI Prevention of hearing loss in experimental pneumococcal meningitis by administration of dexamethasone and ketorolac SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 20th Midwinter Research Meeting of the Association-for-Research-in-Otolaryngology CY FEB 01-06, 1997 CL ST PETERSBURG, FLORIDA SP Assoc Res Otolaryngol ID ANTI-INFLAMMATORY AGENTS; BACTERIAL-MENINGITIS; THERAPY; CORTICOSTEROIDS; AMPICILLIN; CHILDREN; TRIALS AB Pneumococcal meningitis remains a significant cause of morbidity, particularly sensorineural hearing loss. Recent literature has suggested that a vigorous host immune response to Staphylococcus pneumoniae is responsible for much of the neurologic sequelae, including deafness, after bacterial meningitis. This study used a rabbit model of hearing loss in experimental pneumococcal meningitis to evaluate the therapeutic effect of two anti-inflammatory agents, dexamethasone and ketorolac, coadministered with ampicillin, Both adjunctive drugs minimized or prevented sensorineural hearing loss compared with placebo. Dexamethasone, administered 10 min before ampicillin, was particularly effective in minimizing mean hearing threshold change compared with placebo for both clicks (dexamethasone: 6.7-dB sound pressure level [SPL] vs, placebo: 33.4-dB SPL, P = .0078) and 10-kHz tone bursts (dexamethasone: 8.4-dB SPL vs. placebo: 53.4-dB SPL, P = .0003), These findings support the beneficial role of anti-inflammatory agents in reducing the incidence of hearing loss from pneumococcal meningitis, especially if therapy is instituted early in the course of infection. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA USA. SUNY Buffalo, Ctr Hearing & Deafness, Buffalo, NY 14260 USA. RP Rappaport, JM (reprint author), Sir Mortimer B Davis Jewish Hosp, Dept Otolaryngol, Room E-209,3755 Cote Ste Catherine Rd, Montreal, PQ H3T 1E2, Canada. NR 18 TC 35 Z9 35 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 JAN PY 1999 VL 179 IS 1 BP 264 EP 268 DI 10.1086/314531 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 151MW UT WOS:000077725000038 PM 9841852 ER PT J AU Paris, JJ Cassem, EH Dec, GW Reardon, FE AF Paris, JJ Cassem, EH Dec, GW Reardon, FE TI Use of a DNR order over family objections: The case of Gilgunn v. MGH SO JOURNAL OF INTENSIVE CARE MEDICINE LA English DT Article ID PHYSICIANS REFUSAL; CARE; ETHICS AB After the U.S. Supreme Court's 1990 Cruzan [1] decision there is a clear consensus in our society that patients are free to decline any and all medical treatments. Still unresolved is the pressing question of physician refusal of requested life-sustaining treatment. What is involved in this issue is not only the limits, if any, on the exercise of self-determination, but the role of professional integrity and the physician's commitment "to do no harm" [2]. Despite a plethora of articles on the topic of physician refusal of ineffective or so-called futile treatment, there is still no definitive court ruling on the subject nor a consensus in the bioethics or medical communities on the issue [3]. The early legal disputes between physicians and families on refusal to provide requested treatment such as Baby L [4], Wanglie [5], or Baby K [6] did not directly confront the issue. During the trial court hearing Baby L was transferred to a physician willing to treat her as the parents requested. In Wanglie, the probate court addressed only the question of replacement of the husband as guardian. The court was not asked nor did it discuss the question of termination of treatment. Baby K, in which a federal appeals court upheld a mother's right to have ventilatory support for her anencephalic infant daughter, was decided on a narrow statutory interpretation of the Emergency Medical Treatment and Active Labor Act's requirement that a patient presenting in an emergency room with a life-threatening medical condition must be stabilized before consideration of a transfer. That court never directly addressed the dilemma faced by intensivists who are asked to provide treatment thought to be ineffective or "futile" [7]. Decision making in such cases is neither an issue of physician domination nor solely that of patient self-determination. Choices about treatment options are not exclusively scientific judgments. They are, rather, value assumptions about the nature and worth of life, and as such they belong to a broader community than medicine alone. The question is not whether but which value judgments physicians may use in determining whether to follow patient demands. It is not the personal predilections of the provider or the idiosyncratic views of the patient but the common social sense of what practices are to prevail. Those questions, as Tomlinson and Brody [8] note, signal a turn away from individual toward social conceptions of the reasonableness and worthwhileness of the proposed procedure. Giligunn v. Massachusetts General Hospital is the first case in which a jury was asked to assess the legitimacy of the values involved in a physician's refusal to attempt CPR in an elderly comatose patient with multiple medical problems for whom the physician believed the procedure would be ineffective. C1 Boston Coll, Dept Theol, Chestnut Hill, MA 02467 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Optimal Care Comm, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Hassan & Reardon, Boston, MA USA. RP Paris, JJ (reprint author), Boston Coll, Dept Theol, Chestnut Hill, MA 02467 USA. NR 17 TC 13 Z9 13 U1 1 U2 6 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0885-0666 J9 J INTENSIVE CARE MED JI J. Intensive Care Med. PD JAN-FEB PY 1999 VL 14 IS 1 BP 41 EP 45 DI 10.1046/j.1525-1489.1999.00041.x PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 150XC UT WOS:000077690500005 PM 11657848 ER PT J AU Hibino, T Matsuda, Y Takahashi, T Goetinck, PF AF Hibino, T Matsuda, Y Takahashi, T Goetinck, PF TI Suppression of keratinocyte proliferation by plasminogen activator inhibitor-2 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE cell synchrony; growth inhibition; serpin; uPA ID AMINO-TERMINAL FRAGMENT; UROKINASE-TYPE; PSORIATIC EPIDERMIS; HUMAN-PLACENTA; BREAST-CANCER; CELL-LINE; TISSUE; RECEPTOR; PURIFICATION; INVASION AB We have previously shown that urokinase plasminogen activator (uPA) stimulates the growth of human keratinocytes in culture. For this effect, uPA activity is essential to generate the active amino terminal fragment, by an autolytic process. Our findings indicated further that inhibition of uPA may result in the suppression of growth of keratinoytes, Here, we provide evidence that plasminogen activator inhibitor (PAI)-2 has an anti-proliferative effect on keratinocytes. The uPA activity in cultured keratinocytes increased in parallel with cell proliferation, reaching a maximum level at confluency and decreasing gradually thereafter. The analysis of synchronized cells showed that the peak uPA activity in the medium occured just prior to S-phase, suggesting that the production and secretion of uPA is related to cell proliferation. In contrast, PAI-2 levels showed a steady increase, even after confluency, When PAI-2, purified from human cornified cells, was added to synchronized keratinocytes, S-phase was no longer evident and the peak uPA activity was eliminated. In experiments with a bacterially expressed PAI-2 fusion protein, [H-3] thymidine incorporation by keratinocytes was significantly suppressed, confirming an anti-proliferative effect of PAI-2, These results strongly suggest that PAI-2 is involved in the regulation of keratinocyte proliferation and differentiation. C1 Shiseido Res Ctr, Life Sci Res Labs, Yokohama, Kanagawa 236, Japan. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Dept Dermatol, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Hibino, T (reprint author), Shiseido Res Ctr, Life Sci Res Labs, 2 2-12-1 Fukuura, Yokohama, Kanagawa 236, Japan. NR 38 TC 30 Z9 30 U1 0 U2 0 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 JAN PY 1999 VL 112 IS 1 BP 85 EP 90 DI 10.1046/j.1523-1747.1999.00466.x PG 6 WC Dermatology SC Dermatology GA 153BR UT WOS:000077813300014 PM 9886269 ER PT J AU Issekutz, AC Rowter, D Springer, TA AF Issekutz, AC Rowter, D Springer, TA TI Role of ICAM-1 and ICAM-2 and alternate CD11/CD18 ligands in neutrophil transendothelial migration SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE adhesion molecule; leukocyte; endothelium; Mac-1; CD102; LFA-1 ID INTERCELLULAR-ADHESION MOLECULE-1; INTEGRIN MAC-1 CD11B/CD18; LEUKOCYTE-ENDOTHELIAL ADHESION; POLYMORPHONUCLEAR LEUKOCYTE; MONOCLONAL-ANTIBODIES; COMPLEMENT RECEPTOR-TYPE-3; GLYCOPROTEIN COMPLEX; I-DOMAIN; LFA-1; CD18 AB We evaluated the relative contribution of ICAM-1 and ICAM-2, known ligands on endothelium for LFA-1 and Mac-1, in spontaneous neutrophil (PMN) transendothelial migration (TEM) across LL-l-activated HUVEC monolayers or TEM induced by C5a or IL-8 across unstimulated HUVEC grown on polycarbonate filters. Adhesion blocking mAb to ICAM-1 [R6.5 F(ab)(2)] or ICAM-2 [CBR IC2/2 F(ab)(2)] tended to inhibit TEM under each condition but, in general, inhibition was significant only with both ICAM-1 and ICAM-2 blockade. mAb to LFA-1 partially inhibited migration to C5a or IL-8 across unstimulated HUVEC and inhibition was not altered by additional treatment of HUVEC with mAbs to ICAM-1 and -2, In contrast, with IL-1 HUVEC, mAb to ICAM-1 significantly inhibited this LFA-1-independent TEM, mAb to Mac-1 alone partially inhibited TEM and, when combined with mAb to LFA-1, migration was almost completely blocked with all TEM conditions tested. The contribution of alternate Ligands for Mac-1 in mediating Mac-1-dependent but ICAM-1/-2-independent C5a-induced TEM was examined using anti-LFA-1-treated PMN and anti-ICAM-treated resting HUVEC. Addition of RGD peptides, fibronectin, fibrinogen, heparins, collagens alone or in combination, even to heparinase-treated HUVEC, did not inhibit this Mac-1-mediated PMN TEM, The results indicate that: (1) LFA-1 mediates PMN TEM primarily by interaction with ICAM-1 and ICAM-2; (2) ICAM-2 may function in concert with ICAM-1 in this role, especially on unstimulated endothelium, and (3) Mac-1 on PMN also plays a major role in TEM and can utilize yet to be identified ligands distinct from ICAM-1 or -2, especially on unstimulated endothelium. C1 Dalhousie Univ, Dept Pediat, Infect Immunol Res Labs, IWK Grace Hlth Ctr, Halifax, NS B3J 3G9, Canada. Dalhousie Univ, Dept Pathol, Halifax, NS B3J 3G9, Canada. Dalhousie Univ, Dept Immunol Microbiol, Halifax, NS B3J 3G9, Canada. Harvard Med Sch, Ctr Blood Res, Boston, MA USA. Harvard Med Sch, Dept Pathol, Boston, MA USA. RP Issekutz, AC (reprint author), Dalhousie Univ, Dept Pediat, Infect Immunol Res Labs, IWK Grace Hlth Ctr, 5850 Univ Ave, Halifax, NS B3J 3G9, Canada. FU NCI NIH HHS [CA31799] NR 53 TC 122 Z9 126 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 JAN PY 1999 VL 65 IS 1 BP 117 EP 126 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 155MF UT WOS:000077950400016 PM 9886254 ER PT J AU Park, KD Kang, YH Park, JB AF Park, KD Kang, YH Park, JB TI Interfacial strength between molded UHMWPE and PMMA-MMA monomer treated UHMWPE SO JOURNAL OF LONG-TERM EFFECTS OF MEDICAL IMPLANTS LA English DT Article DE UHMWPE powder; PMMA; interfacial tensile strength; compression-molding ID MOLECULAR-WEIGHT POLYETHYLENE; TOTAL HIP-REPLACEMENT; FIXATION; COMPONENT AB To solve aseptic loosening of cemented acetabular cup and tibial plateaus of hips and knee joint prostheses in total joint replacement, adhesion between the polymeric prostheses made of ultra-high molecular weight polyethylene (UHMWPE) and bone cement made of polymethyl-methacrylate (PMMA) has been investigated. Previous studies using xylene, PMMA, and MMA monomer solution to treat bulk surfaces of UHMWPE resulted in 11.5 +/- 0.65 MPa as the maximum interfacial strength between the treated UHMWPE and bone cement. The present study eliminates the use of xylene; instead, UHMWPE powders were treated with MMA monomer and PMMA-MMA solution, dried, and then compression-molded with untreated UHMWPE powders. The interfacial tensile strengths were measured and the best molding conditions investigated by varying temperature, pressure, and time. Temperature was the predominant factor when compared to that of pressure or time. The maximum interfacial strength between the treated UHMWPE and untreated UHMWPE was 16.3 +/- 0.94 MPa with the molding conditions of 166.5 degrees C, 38.7 MPa, and 1 h. Scanning electron microscopic (SEM) pictures show the coating of the nodules and fibrils of UHMWPE powder with PMMA. Pulled out aggregated nodular space and coated PMMA after fracture could be seen easily from PMMA-MMA treated UHMWPE powder. C1 Univ Iowa, Dept Biomed Engn, Iowa City, IA 52242 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Univ Iowa, Dept Biomed Engn, Iowa City, IA 52242 USA. EM joon_park@uiowa.edu NR 34 TC 9 Z9 9 U1 0 U2 1 PU BEGELL HOUSE INC PI DANBURY PA 50 NORTH ST, DANBURY, CT 06810 USA SN 1050-6934 EI 1940-4379 J9 J LONG-TERM EFF MED JI J. Long-Term Eff. Med. Implants PY 1999 VL 9 IS 4 BP 303 EP 318 PG 16 WC Engineering, Biomedical; Medicine, Research & Experimental; Orthopedics; Pathology SC Engineering; Research & Experimental Medicine; Orthopedics; Pathology GA 281MF UT WOS:000085163800004 PM 10847970 ER PT J AU Morgalla, MH Mettenleiter, H Katzenberger, T AF Morgalla, MH Mettenleiter, H Katzenberger, T TI ICP measurement accuracy: the effect of temperature drift. Design of a laboratory test for assessment of ICP transducers SO JOURNAL OF MEDICAL ENGINEERING & TECHNOLOGY LA English DT Article ID RAISED INTRACRANIAL-PRESSURE; MANAGEMENT; GAELTEC; DEVICE AB Intracranial pressure (ICP) monitoring has become the mainstay of multimodal neuromonitoring of comatous patients after head injury. In the presence of rising ICP and faced with pressures, difficult to control, aggressive measures, such as hypothermia may be used. The ICP reading should not be influenced by temperature changes. A laboratory test was designed to simulate temperature variations between 20 degrees C and 45 degrees C at different pressure levels under physiological conditions. Five types of transducers were examined: Epidyn(R) Braun Melsungen, ICT/B-Titan Gaeltec(R), Camino(R) -OLM-110-4B, Codman(R) MicroSensor ICP-Transducer, Neurovent(R) ICP transducer Rehau Ag+Co. Tests were performed at 6 different pressure levels between 0 mmHg and 50mmHg. The results show very low drifts of less than 0.15 mmHg degrees C-1 for Codman, Epidyn and Neurovent. Gaeltec and Camino exhibited higher drifts of 0.18 mmHg and 0.2 mmHg degrees C-1 respectively. Within the temperature range from 35 degrees C to 42 degrees C all probes tested show insignificant temperature drift. Whether these results also apply to other types of transducers needs further evaluation. Problems and requirements related to the design of a laboratory test for the in vitro assessment of ICP transducers are discussed in detail. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, Boston, MA 02114 USA. Univ Tubingen, Div Neurosurg, D-72074 Tubingen, Germany. RP Morgalla, MH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, Boston, MA 02114 USA. NR 14 TC 10 Z9 11 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0309-1902 J9 J MED ENG TECHNOL JI J. Med. Eng. Technol. PD JAN-FEB PY 1999 VL 23 IS 1 BP 10 EP 14 DI 10.1080/030919099294375 PG 5 WC Engineering, Biomedical; Medical Informatics; Medical Laboratory Technology SC Engineering; Medical Informatics; Medical Laboratory Technology GA 173CG UT WOS:000078963200003 PM 10202697 ER PT J AU Haddow, JE Bradley, LA Palomaki, GE Doherty, RA AF Haddow, JE Bradley, LA Palomaki, GE Doherty, RA TI Issues in implementing prenatal screening for cystic fibrosis: results of a working conference SO JOURNAL OF MEDICAL SCREENING LA English DT Article DE cystic fibrosis; prenatal screening; generic screening ID CONTINUING MEDICAL-EDUCATION; COST-EFFECTIVENESS; PREGNANT-WOMEN; POPULATION; CARRIERS; INFORMATION; ACCEPTABILITY; TRIAL; GENE AB Objective-To summarise a conference convened to examine how cystic fibrosis screening might appropriately be introduced into routine prenatal practice. Methods-Participant included experts from various relevant disciplines. Systematic reviews and data from individual trials were presented; issues were identified and discussed. Results-Judged by published criteria, prenatal cystic fibrosis screening is suitable for introduction. Screening can be performed cost effectively by identifying racial/ethnic groups at sufficient risk and then using either of two models for delivering laboratory services. Validated educational materials exist. Ethical issues are not unique. Conclusions-Once adequate facilities for patient and provider education, testing, counselling, quality control, and monitoring are in place, individual programmes can begin prenatal screening for cystic fibrosis. C1 Fdn Blood Res, Scarborough, ME 04070 USA. Johns Hopkins Sch Med, Baltimore, MD USA. Univ Edinburgh, Edinburgh, Midlothian, Scotland. Univ N Carolina, Chapel Hill, NC USA. Calif State Dept Hlth, Berkeley, CA USA. Penn Hosp, Philadelphia, PA 19107 USA. Roche Mol Syst, Alameda, CA USA. Zeneca Diagnost, Northwich, Cheshire, England. Cyst Fibrosis Fdn, Bethesda, MD USA. Vincent Mem Obstet Assoc, Boston, MA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Cent Manchester Hlth Care Trust, Manchester, Lancs, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Miami, Sch Med, Miami, FL USA. March Dimes Birth Defects Fdn, White Plains, NY USA. Genzyme, Framingham, MA USA. Univ Missouri, Columbia, MO USA. Univ Penn, Philadelphia, PA 19104 USA. Mt Sinai Sch Med, New York, NY USA. Allegheny Univ Hlth Sci, Pittsburgh, PA USA. Univ Rochester, Sch Med, Rochester, NY USA. Univ Chicago, Chicago, IL 60637 USA. Rapigene Inc, Bothell, WA USA. Wolfson Inst Prevent Med, London, England. Alliance Genet Support Grp, Washington, DC USA. Kaiser Permanente No Calif, San Jose, CA USA. RP Haddow, JE (reprint author), Fdn Blood Res, POB 190, Scarborough, ME 04070 USA. NR 46 TC 11 Z9 11 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0969-1413 J9 J MED SCREEN JI J. Med. Screen. PY 1999 VL 6 IS 2 BP 60 EP 66 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 215GF UT WOS:000081373000002 PM 10444721 ER PT J AU O'Brien, TX Schuyler, GT Rackley, MS Thompson, JT AF O'Brien, TX Schuyler, GT Rackley, MS Thompson, JT TI F1-ATP synthase beta-subunit and cytochrome c transcriptional regulation in right ventricular hemodynamic overload and hypertrophically stimulated cardiocytes SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Endothelial Dysfunction - A Novel Therapeutic Target CY MAY 27, 1998 CL RHODES, GREECE DE cardiac hypertrophy; pulmonary artery banding; transient transfection; oxidative phosphorylation; F-1-ATP synthase beta-subunit; cytochrome c; neonatal cardiocytes ID MITOCHONDRIAL GENE-EXPRESSION; ATP SYNTHASE; PRESSURE-OVERLOAD; NUCLEAR GENES; ELECTRICAL-STIMULATION; CARDIAC-HYPERTROPHY; CONTRACTILE ACTIVITY; SEQUENCE-ANALYSIS; SKELETAL-MUSCLE; DNA AB Cardiac hypertrophic growth secondary to hemodynamic pressure overload causes changes in energy requirements that map involve the transcriptional upregulation of oxidative phosphorylation genes. Therefore, two representative nuclear-encoded genes, the mitochondrial F-1-ATP synthase beta-subunit (beta-subunit) and cytochrome c (cyt c), were examined in a feline chronic pulmonary artery banded right ventricular pressure-overload model. In the hypertrophying right ventricle, beta-subunit and cyt c mRNA levels increased after two and seven days, during the peak growth response. To examine cardiac transcriptional regulation, neonatal rat cardiac myocytes (cardiocytes) were transiently transfected with beta-subunit promoter constructs ranging from -1519 nucleotides (nt) upstream of transcription initiation as well as cyt c promoter constructs ranging from - 726 nt. A full-length p1519 beta-subunit/Luc construct was alpha-adrenergically inducible by 275% (+/-30%) with this activation being mapped to an enhancer region between -1519 to -1480 nt, Smaller constructs containing more proximal promoter elements were not inducible. Additionally, the full-length and enhancer deleted beta-subunit constructs were also inducible in electrically stimulated cardiocytes, suggesting a different mechanism of activation. Cyt c constructs containing known constitutive elements from -191 to -167 nt and -139 to -84 nt were responsible for the majority of the reporter activity of the full-length promoter but were not inducible in the presence of phenylephrine. Hence, we show that promoter regions containing elements common in other metabolism-related gene families are active in neonatal rat cardiocytes, Once more, we have identified a beta-subunit genomic region responsive to alpha-adrenergic and electrical stimulation. (C) 1999 Academic Press. C1 Med Univ S Carolina, Div Cardiol, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA. Med Univ S Carolina, Gazes Cardiac Res Inst, Charleston, SC 29425 USA. RP O'Brien, TX (reprint author), Med Univ S Carolina, Div Cardiol, Dept Med, 816 CSB,171 Ashley Ave, Charleston, SC 29425 USA. FU NHLBI NIH HHS [T32-HL-07260-19, HL-55284] NR 42 TC 4 Z9 5 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JAN PY 1999 VL 31 IS 1 BP 167 EP 178 DI 10.1006/jmcc.1998.0852 PG 12 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 163VU UT WOS:000078427700016 PM 10072725 ER PT J AU Ristow, M Vorgerd, M Mohlig, M Schatz, H Pfeiffer, A AF Ristow, M Vorgerd, M Mohlig, M Schatz, H Pfeiffer, A TI Insulin resistance and impaired insulin secretion due to phosphofructo-1-kinase-deficiency in humans SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Article; Proceedings Paper CT International Symposium on Endocrine Cell Transplantation and Genetic Engineering CY JUN 16-19, 1996 CL GIESSEN, GERMANY DE diabetes; genetics; phosphofructokinase; glycogenosis; NIDDM; PFK ID DEPENDENT DIABETES-MELLITUS; MUSCLE PHOSPHOFRUCTOKINASE DEFICIENCY; GLYCOGEN-SYNTHASE GENE; PANCREATIC-ISLETS; INTRAVENOUS GLUCOSE; PHOSPHATE-DEPLETION; GLUCOKINASE GENE; SUPPRESSION TEST; NIDDM; PATHOGENESIS AB The etiology of non-insulin-dependent diabetes mellitus (NIDDM) is usually explained as a combination of peripheral insulin resistance and impaired beta-cell Function. Phosphofructo-1-kinase (PFK1) is a rate limiting enzyme in glycolysis, and its muscle subtype (PFK1-M) deficiency leads to an autosomal recessively inherited disorder known as glycogenosis type VII or Tarui's disease. It was evaluated whether PFK1-M deficiency leads to NIDDM in humans. A core family of four was evaluated for PFK1-M deficiency by DNA- and enzyme-activity-analyses. All members underwent oral and intravenous glucose tolerance test (oGTT/ivgtt), as well as an insulin sensitivity test (IST) using octreotide. Results: Father (46 years, BMI 22.4 kg/m(2)) and older son (19 years, BMI 17.8 kg/m5) showed homozygous PFK1-M deficiency, while mother (47 years, BMI 28.4 kg/m5) and younger son (13 years, BMT 16.5 kg/m5) were shown to be heterozygously PFK1-M-deficient on enzyme activity levels. DNA analysis revealed an exon 5-missense-mutation at one allele of all four members, and an exon 22-frameshift-mutation at the other allele of the two homozygously affected individuals. By oGTT the father showed impaired glucose tolerance, and the mother clinical diabetes. By ivGTT both parents and the older son had a decreased first phase insulin secretion, and a diminished glucose disappearance rate. The IST showed marked insulin resistance in both parents and the older son, and moderate resistance in the younger son, previously not described. Conclusion: PFK1-M-deficiency leads to a metabolic state typical for early NIDDM in homozygously affected humans, especially concerning insulin resistance and loss of first phase beta-cell insulin secretion, and may contribute to the manifestation of NIDDM in a subgroup of patients. C1 Ruhr Univ Bochum, Hosp Bergmannsheil, Clin Internal Med, Bochum, Germany. Ruhr Univ Bochum, Hosp Bergmannsheil, Neurol Clin, Bochum, Germany. RP Ristow, M (reprint author), Joslin Diabet Ctr, Div Res, Room 610,1 Joslin Pl, Boston, MA 02215 USA. RI Ristow, Michael/O-9858-2014 OI Ristow, Michael/0000-0003-2109-2453 NR 55 TC 7 Z9 8 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD JAN PY 1999 VL 77 IS 1 BP 96 EP 103 DI 10.1007/s001090050311 PG 8 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 144EG UT WOS:000077300500021 PM 9930938 ER PT J AU de la Monte, SM AF de la Monte, SM TI Molecular abnormalities of the brain in Down Syndrome: relevance to Alzheimer's neurodegeneration SO JOURNAL OF NEURAL TRANSMISSION-SUPPLEMENT LA English DT Article ID NEURONAL THREAD PROTEIN; AMYOTROPHIC-LATERAL-SCLEROSIS; CU/ZN-SUPEROXIDE-DISMUTASE; AMYLOID PRECURSOR PROTEIN; CENTRAL-NERVOUS-SYSTEM; NITRIC-OXIDE; GENE-EXPRESSION; TRANSGENIC MICE; NEUROFILAMENT SUBUNIT; MITOCHONDRIAL-DNA AB Down syndrome is caused by over-expression of genes located within a segment of chromosome 21, termed the Down locus. Down syndrome is associated with developmental abnormalities of the central nervous system that result in mental retardation and age-dependent Alzheimer-type neurodegeneration. Some of the neurodegenerative lesions, including A beta amyloid deposition, apoptotic cell death, and aberrant dendritic arborization, are in part due to constitutively increased expression of genes that encode the amyloid precursor protein, superoxide dismutase I, and S100-beta, and located within the Down locus. However, neurodegeneration in Down syndrome is also associated with aberrant expression of genes that are not linked to the Down locus, including the growth associated protein, GAP-43, nitric oxide synthase 3, neuronal thread protein, and pro-apoptosis genes such as p53, Bar, and interleukin-1 beta-converting enzyme. Increased expression of these non-Down locus genes correlates with proliferation of dystrophic neurites and apoptotic cell death, two important correlates of cognitive impairment in Alzheimer's disease. This article reviews the functional importance of abnormal gene expression in relation to Alzheimer-type neurodegeneration in brains of individuals with Down syndrome. C1 Brown Univ, Mem Hosp Rhode Isl, Sch Med, Dept Med, Providence, RI USA. Brown Univ, Mem Hosp Rhode Isl, Sch Med, Dept Pathol, Providence, RI USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP de la Monte, SM (reprint author), Brown Univ, Mem Hosp Rhode Isl, Sch Med, Dept Med, 55 Claverick St,Room 419, Providence, RI USA. NR 76 TC 43 Z9 44 U1 1 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0303-6995 J9 J NEURAL TRANSM-SUPP JI J. Neural Transm.-Suppl. PY 1999 IS 57 BP 1 EP 19 PG 19 WC Neurosciences SC Neurosciences & Neurology GA 263BU UT WOS:000084103400002 ER PT J AU Das, A Hochberg, FH McNelis, S AF Das, A Hochberg, FH McNelis, S TI A review of the therapy of paraneoplastic neurologic syndromes SO JOURNAL OF NEURO-ONCOLOGY LA English DT Review DE cancer-associated neurologic disease; immunosuppressive treatment ID NEOPLASTIC CEREBELLAR DEGENERATION; CELL LUNG-CANCER; EATON MYASTHENIC SYNDROME; ANTI-HU ANTIBODY; STIFF-MAN SYNDROME; ENCEPHALOMYELITIS SENSORY NEURONOPATHY; CENTRAL-NERVOUS-SYSTEM; HODGKINS-DISEASE; LAMBERT SYNDROME; BREAST-CANCER AB The therapy of paraneoplastic neurologic syndromes remains unclear and warrants a systematic review of the literature. Reports in English and foreign language literature were abstracted. Data were sorted by the primary paraneoplastic neurologic syndrome, the primary malignancy, and the methods of treatment. Neurologic improvement follows surgical, chemotherapeutic, and radiation treatments. Adjuvant immunosuppressive therapy with steroids, plasmapheresis, or immunoglobulin may help stabilize the progression of neurologic symptoms. Syndromes characterized by inflammation or neurotransmitter production without neuronal loss are most responsive to therapy. While treatment of the underlying cancer with appropriate surgery, chemotherapy, and radiation is recommended, the paraneoplastic syndrome should probably be managed with immunosuppressive therapy. C1 Natl Univ Singapore, Singapore 117548, Singapore. Singapore Gen Hosp, Singapore 0316, Singapore. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hochberg, FH (reprint author), 1 Hawthorne Pl,Suite 105, Boston, MA 02114 USA. NR 210 TC 11 Z9 13 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JAN PY 1999 VL 41 IS 2 BP 181 EP 194 DI 10.1023/A:1006133102928 PG 14 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 186HU UT WOS:000079723500011 PM 10222439 ER PT J AU Andreassen, OA Hughes, DB Klivenyi, P Ferrante, RJ Ona, VO Schleicher, JR Friedlander, RM Beal, MF AF Andreassen, OA Hughes, DB Klivenyi, P Ferrante, RJ Ona, VO Schleicher, JR Friedlander, RM Beal, MF TI Transgenic mice expressing a dominant negative mutant interleukin-1 beta converting enzyme show resistance to neurotoxins. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RI Friedlander, Robert/A-2845-2016 OI Friedlander, Robert/0000-0003-4423-9219 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 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 73 SU S BP S15 EP S15 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 218CW UT WOS:000081536500059 ER PT J AU Gibson, GE Haroutunian, V Park, LCH Zhang, H Mohs, R Sheu, RKF Blass, JP AF Gibson, GE Haroutunian, V Park, LCH Zhang, H Mohs, R Sheu, RKF Blass, JP TI Reductions in a key mitochondrial enzyme in brains from Alzheimer's disease patients correlate with a clinical dementia rating. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 Cornell Univ, Coll Med, Burke Med Res Inst, White Plains, NY 10605 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, Bronx, NY 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 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 73 SU S BP S23 EP S23 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 218CW UT WOS:000081536500091 ER PT J AU Lenz, G Tasca, C Luo, Z Avruch, J Rodnight, R Neary, JT AF Lenz, G Tasca, C Luo, Z Avruch, J Rodnight, R Neary, JT TI Signaling from P2Y nucleotide receptors to c-Raf, MEK and ERK in astrocyte cultures. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 UFRGS, Dept Biofis, Porto Alegre, RS, Brazil. UFRGS, Dept Bioquim, Porto Alegre, RS, Brazil. UFSC, Dept Bioquim, Florianopolis, SC, Brazil. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. VA Med Ctr, Res Serv, Miami, FL 33215 USA. Univ Miami, Sch Med, Dept Pathol, Miami, FL 33215 USA. Univ Miami, Sch Med, Dept Biochem & Mol Biol, Miami, FL 33215 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 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 73 SU S BP S150 EP S150 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 218CW UT WOS:000081536500591 ER PT J AU Yao, JK Reddy, RD van Kammen, DP AF Yao, JK Reddy, RD van Kammen, DP TI Abnormal antioxidant defense system in patients with schizophrenia SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15213 USA. RW Johnson Pharmaceut Res Inst, Raritan, NJ 08869 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 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S20 EP S20 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100078 ER PT J AU Yao, JK Leonard, S Reddy, RD AF Yao, JK Leonard, S Reddy, RD TI Phospholipid defects in schizophrenic brain SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, WPIC, Pittsburgh, PA 15213 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 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 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1999 VL 72 SU S BP S19 EP S19 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 167YQ UT WOS:000078663100077 ER PT J AU Adler, H Beland, JL Del-Pan, NC Kobzik, L Sobel, RA Rimm, IJ AF Adler, H Beland, JL Del-Pan, NC Kobzik, L Sobel, RA Rimm, IJ TI In the absence of T cells, natural killer cells protect from mortality due to HSV-1 encephalitis SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE HSV-1; NK cells; encephalitis ID HERPES-SIMPLEX-VIRUS; MURINE CYTOMEGALOVIRUS-INFECTION; VIRAL-INFECTIONS; IMMUNE-RESPONSE; NK CELLS; MICE; TYPE-1; RESISTANCE; INVIVO; GAMMA AB The importance of natural killer (NK) cells in the resistance to herpes simplex virus type 1 (HSV-I), a common infection of immunocompromised patients, is unclear. Previous data on the role of NK cells in murine HSV-I infection has been contradictory. Adoptive transfer studies suggested that NK cells mediated resistance to HSV-1, but in vivo depletion approaches demonstrated that NK cells were not important. We studied the course of HSV-I infection after intranasal (i.n.) inoculation of E26 mice (lacking NK and T cells), T cell knockout (T cell ko) mice (lacking T cells only), or normal control mice. The E26 mice showed greater mortality and an impaired ability to clear virus from lung and brain compared to T cell ko mice and control mice, and had severe necrotizing HSV-1 encephalitis. Therefore, the data support the hypothesis that NK cells play an important role in the natural defense of murine HSV-1 infection. (C) 1999 Elsevier Science B.V. AU rights reserved. C1 Harvard Univ, Sch Med,Childrens Hosp, Dept Pediat Hematol Oncol, Dana Farber Canc Inst,Dept Pediat, Boston, MA 02115 USA. Brigham & Womens Hosp, Physiol Program, Harvard Sch Publ Hlth, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Stanford Univ, Sch Med, Lab Serv, Palo Alto Vet Affairs Hlth Care Syst, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. RP Rimm, IJ (reprint author), Genet Inst, 87 Cambridge Pk Dr, Cambridge, MA 02140 USA. EM irimm@genetics.com NR 38 TC 41 Z9 44 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JAN 1 PY 1999 VL 93 IS 1-2 BP 208 EP 213 DI 10.1016/S0165-5728(98)00236-7 PG 6 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 160TM UT WOS:000078247200023 PM 10378885 ER PT J AU Cramer, SC Finklestein, SP Schaechter, JD Bush, G Rosen, BR AF Cramer, SC Finklestein, SP Schaechter, JD Bush, G Rosen, BR TI Activation of distinct motor cortex regions during ipsilateral and contralateral finger movements SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID CORTICOSPINAL PROJECTIONS; HAND MOVEMENTS; MONKEY; AREAS; ORGANIZATION; STIMULATION; STROKE; BRAIN; ZONE AB Previous studies have shown that unilateral finger movements are normally accompanied by a small activation in ipsilateral motor cortex. The magnitude of this activation has been shown to be altered in a number of conditions, particularly in association with stroke recovery. The site of this activation, however, has received limited attention. To address this question, functional magnetic resonance imaging (MRI) was used to study precentral gyrus activation in six control and three stroke patients during right index finger tapping, then during left index finger tapping. In each hemisphere, the most significantly activated site (P < 0.001 required) was identified during ipsilateral and during contralateral finger tapping. In the motor cortex of each hemisphere, the site activated during use of the ipsilateral hand differed from that found during use of the contralateral hand. Among the 11 control hemispheres showing significant activation during both motor tasks, the site for ipsilateral hand representation (relative to contralateral hand site in the same hemisphere) was significantly shifted ventrally in all 11 hemispheres (mean, 11 mm), laterally in 10/11 hemispheres (mean, 12 mm), and anteriorly in 8/11 hemispheres (mean, 10 mm). In 6 of 11 hemispheres, tapping of the contralateral finger simultaneously activated both the ipsilateral and the contralateral finger sites, suggesting bilateral motor control by the ipsilateral finger site. The sites activated during ipsilateral and contralateral hand movement showed similar differences in the unaffected hemisphere of stroke patients. The region of motor cortex activated during ipsilateral hand movements is spatially distinct from that identified during contralateral hand movements. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,MGHNMR Ctr, Charlestown, MA 02129 USA. Beth Israel Deaconess Med Ctr, Pfizer Inc, Boston, MA 02114 USA. Harvard Mit Div Hlth Sci & Technol, Clin Investigator Training Program, Boston, MA 02114 USA. Northeastern Univ, Bouve Coll Pharm & Hlth Sci, Dept Phys Therapy, Boston, MA 02115 USA. RP Cramer, SC (reprint author), Univ Washington, Dept Neurol, 1959 NE Pacific,Rm RR650,Box 356465, Seattle, WA 98195 USA. NR 35 TC 188 Z9 188 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JAN PY 1999 VL 81 IS 1 BP 383 EP 387 PG 5 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 162NT UT WOS:000078353800036 PM 9914297 ER PT J AU Lee, RYN Sawin, ER Chalfie, M Horvitz, HR Avery, L AF Lee, RYN Sawin, ER Chalfie, M Horvitz, HR Avery, L TI EAT-4, a homolog of a mammalian sodium-dependent inorganic phosphate cotransporter, is necessary for glutamatergic neurotransmission in Caenorhabditis elegans SO JOURNAL OF NEUROSCIENCE LA English DT Article DE C- elegans; behavior; genetics; glutamate; synaptic neurotransmission; sodium-dependent inorganic phosphate cotransporter ID NERVOUS-SYSTEM; C-ELEGANS; GENE-EXPRESSION; CNS TRANSMITTER; NEURONS; GLUTAMINE; CLONING; CDNA; PROTEIN; ENCODES AB The Caenorhabditis elegans gene eat-4 affects multiple glutamatergic neurotransmission pathways. We find that eat-4 encodes a protein similar in sequence to a mammalian brain-specific sodium-dependent inorganic phosphate cotransporter I (BNPI). Like BNPI in the rat CNS, eat-4 is expressed predominantly in a specific subset of neurons, including several proposed to be glutamatergic. Loss-of-function mutations in eat-4 cause defective glutamatergic chemical transmission but appear to have little effect on other functions of neurons. Our data suggest that phosphate ions imported into glutamatergic neurons through transporters such as EAT-4 and BNPI are required specifically for glutamatergic neurotransmission. C1 Univ Texas, SW Med Ctr, Dept Mol Biol & Oncol, Dallas, TX 75235 USA. MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. Columbia Univ, Dept Biol Sci, New York, NY 10027 USA. RP Lee, RYN (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Wellman 8,Blossom St, Boston, MA 02114 USA. FU NHLBI NIH HHS [R37 HL046154, HL46154, R01 HL046154]; NIGMS NIH HHS [GM24663, R01 GM024663, R37 GM024663] NR 66 TC 194 Z9 200 U1 2 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 1 PY 1999 VL 19 IS 1 BP 159 EP 167 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 153NP UT WOS:000077839400020 PM 9870947 ER PT J AU Shrieve, DC Alexander, E Black, PM Wen, PY Fine, HA Kooy, HM Loeffler, JS AF Shrieve, DC Alexander, E Black, PM Wen, PY Fine, HA Kooy, HM Loeffler, JS TI Treatment of patients with primary glioblastoma multiforme with standard postoperative radiotherapy and radiosurgical boost: prognostic factors and long-term outcome SO JOURNAL OF NEUROSURGERY LA English DT Article DE glioblastoma multiforme; radiation therapy; radiosurgery; prognosis ID RECURSIVE PARTITIONING ANALYSIS; RADIATION-THERAPY; STEREOTAXIC RADIOSURGERY; MALIGNANT GLIOMAS; INITIAL MANAGEMENT; BRAIN-TUMORS; SURVIVAL; TRIALS AB Object. To assess the value of stereotactic radiosurgery (SRS) as adjunct therapy in patients suffering from glioblastoma multiforme (GBM), the authors analyzed their experience with 78 patients. Methods. Between June 1988 and January 1995, 78 patients underwent SRS as part of their initial treatment for GEM. All patients had undergone initial surgery or biopsy confirming the diagnosis of GEM and received conventional external beam radiotherapy. Stereotactic radiosurgery was performed using a dedicated 6-MV stereotactic linear accelerator. Thirteen patients were alive at the time of analysis with a median follow-up period of 40.8 months. The median length of actuarial survival for all patients was 19.9 months. Twelve- and 24-month survival rates were 88.5% and 35.9%, respectively. Patient age and Radiation Therapy Oncology Group (RTOG) class were significant prognostic indicators according to univariate analysis (p < 0.05). Twenty-three patients aged younger than 40 years had a median survival time of 48.6 months compared with 55 older patients who had 18.2 months (p < 0.001). Patients in this series fell into RTOG Classes III (27 patients), IV (29 patients), or V (22 patients). Class III patients had a median survival time of 29.5 months following diagnosis; this was significantly longer than median survival times for Classes TV and V, which were 19.2 and 18.2 months, respectively (p = 0.001). Only patient age (< 40 years) was a significant prognostic factor according to multivariate analysis. Acute complications were unusual and limited to exacerbation of existing symptoms. There were no new neuropathies secondary to SRS. Thirty-nine patients (50%) underwent reoperation for symptomatic necrosis or recurrent tumor. The rate of reoperation at 24 months following SRS was 54.8%. Conclusions. The addition of a radiosurgery boost appears to confer a survival advantage to selected patients. C1 Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg Neurosurg, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Brain Tumor Ctr, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Joint Ctr Radiat Therapy, Boston, MA 02115 USA. RP Shrieve, DC (reprint author), Univ Arkansas Med Sci, 4301 W Markham St,Slot 771, Little Rock, AR 72205 USA. NR 20 TC 150 Z9 154 U1 0 U2 2 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JAN PY 1999 VL 90 IS 1 BP 72 EP 77 DI 10.3171/jns.1999.90.1.0072 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 168TH UT WOS:000078708400010 PM 10413158 ER PT J AU Maxwell, M Borges, LF Zervas, NT AF Maxwell, M Borges, LF Zervas, NT TI Renal cell carcinoma: a rare source of cauda equina metastasis - Case report SO JOURNAL OF NEUROSURGERY LA English DT Article DE cauda equina metastasis; renal cell carcinoma; protooncogene; tumor suppressor gene; metastasis ID CANCER METASTASIS; GENE; EXPRESSION; TUMOR; MODULATION; SURVIVAL AB The authors present the case of a patient in whom intradural metastasis from renal cell carcinoma spread to the cauda equina. To the authors' knowledge, this is only the second report of its kind. This male patient had undergone nephrectomy for the treatment of renal cell carcinoma for 5 years and was diagnosed as having metastatic lung disease I year prior to admission. The patient presented with lower back pain that radiated to both legs, but he exhibited no sensorimotor deficits. The majority of cauda equina tumors are primary tumors, and metastases are very rare. The literature is reviewed with reference to current molecular genetic paradigms of metastatic renal cell carcinoma. C1 Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Zervas, NT (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, White 502,14 Fruit St, Boston, MA 02114 USA. NR 34 TC 20 Z9 22 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD JAN PY 1999 VL 90 IS 1 SU S BP 129 EP 132 DI 10.3171/spi.1999.90.1.0129 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 169XH UT WOS:000078774400021 PM 10413138 ER PT J AU Xu, RH O'Quigley, J AF Xu, RH O'Quigley, J TI A R-2 type measure of dependence for proportional hazards models SO JOURNAL OF NONPARAMETRIC STATISTICS LA English DT Article DE correlation; dependence; explained randomness; information gain; Kaplan-Meier estimate; proportional hazards ID EXPLAINED VARIATION; SURVIVAL-DATA; REGRESSION AB A measure of dependence for survival data was presented by Kent and O'Quigley (1988). The purpose of this present work is to show that an alternative, although less immediate specification of the problem, leads to great simplification and generality. This alternative specification is in fact more natural in the context of the semi-parametric proportional hazards regression. One consequence of this is that the alternative specification can immediately accommodate time dependent covariates, a natural feature of the proportional hazards model and one that the Kent and O'Quigley specification was unable to deal with. This measure is invariant to monotonically increasing transformations on the time scale, such invariance being considered fundamental in the case of the regression coefficient beta. Computational aspects involve only those quantities routinely calculated in a proportional hazards analysis. In practice our impressions are that the two measures will generally be close. A disadvantage of the alternative specification over the original Kent and O'Quigley one occurs with discrete covariates having few levels where the upper bound of the measure can be less than one. Nonetheless, for the ranges of values considered in the Kent and O'Quigley work, the two measures show good agreement. The new measure can be adapted to general forms of relative risk for survival models. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif San Diego, Dept Math, La Jolla, CA 92093 USA. RP Xu, RH (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RI O'Quigley, John/E-2073-2017 NR 20 TC 30 Z9 30 U1 0 U2 2 PU GORDON BREACH SCI PUBL LTD PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1048-5252 J9 J NONPARAMETR STAT JI J. Nonparametr. Stat. PY 1999 VL 12 IS 1 BP 83 EP 107 DI 10.1080/10485259908832799 PG 25 WC Statistics & Probability SC Mathematics GA 287GD UT WOS:000085497400005 ER PT J AU Testa, MA Lenderking, WR AF Testa, MA Lenderking, WR TI The impact of AIDS-associated wasting on quality of life: Qualitative issues of measurement and evaluation SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Workshop on Clinical Trials for the Treatment of Secondary Wasting and Cachexia - Selection of Appropriate Endpoints CY MAY 22-23, 1997 CL BETHESDA, MARYLAND SP US FDA, Off AIDS Res, Natl Canc Inst, NIMH, Bristol Myers Squibb, Abbott Labs, Serono Labs Inc, Amer Inst Canc Res, Roxane Labs, NIDA, SmithKline Beecham, NIA, Eli Lilly & Co ID HEALTH C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Phase V Technol Inc, Wellesley, MA 02418 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. RP Testa, MA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 677 Huntington Ave, Boston, MA 02115 USA. FU AHRQ HHS [R01 HS07767-03] NR 17 TC 6 Z9 6 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JAN PY 1999 VL 129 IS 1 SU S BP 282S EP 289S PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 160PA UT WOS:000078238000015 PM 9915916 ER PT J AU Emmons, KM Macario, E Sorensen, G Hunt, MK Rudd, RE AF Emmons, KM Macario, E Sorensen, G Hunt, MK Rudd, RE TI Nutrition education for cancer prevention among low-income populations: An extension of the EFNEP model SO JOURNAL OF NUTRITION EDUCATION LA English DT Article ID SOCIAL NETWORKS; ALAMEDA COUNTY; FRUIT; FOOD; PROGRAM; FAT AB This paper reports a pilot test of the feasibility of implementing an extension of the Expanded Food and Nutrition Education Program (EFNEP) home-based nutrition education intervention in order to maximize involvement of participants' naturally occurring social networks and to target cancer prevention eating patterns. Community residents served as hostesses of a two-session "Nutrition Home Party" and invited at least six family members/friends to attend the sessions, which were held in their homes. Paraprofessionals indigenous to the community facilitated the sessions. Nutrition education sessions were based on the Food Guide Pyramid and the Nutrition Facts label, with emphasis placed on encouraging participants to consume at least five servings of fruits and vegetables a day to reduce their risk of cancer. Preliminary experience with a home-based intervention model indicates that there is considerable potential for working through existing social networks to reach low-income populations. C1 Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Emmons, KM (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, L-2,44 Binney St, Boston, MA 02115 USA. EM Karen_Emmons@DFCI.harvard.edu NR 43 TC 5 Z9 5 U1 2 U2 4 PU DECKER PERIODICALS INC PI HAMILTON PA 4 HUGHSON STREET SOUTH PO BOX 620, LCD 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0022-3182 J9 J NUTR EDUC JI J. Nutr. Educ. PD JAN-FEB PY 1999 VL 31 IS 1 BP 47 EP 53 DI 10.1016/S0022-3182(99)70384-5 PG 7 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA 165ZB UT WOS:000078550800009 ER PT J AU Chatzis, C Danaka, G Linos, A Kales, SN Christiani, DC AF Chatzis, C Danaka, G Linos, A Kales, SN Christiani, DC TI Lung cancer and occupational risk factors in Greece SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID ENDOMETRIAL CANCER; EXPOSURE; PROPORTION; SMOKING; ASBESTOS; DEATH; AREAS; DIET AB This study estimated the proportion of lung cancer in Greece that was attributable to occupational exposure. Two hundred eighty-two patients with lung cancer and 494 controls were interviewed about their socioeconomic characteristics, sex, age, and occupational, smoking, and residential histories. Each subject was classified as exposed or unexposed to known occupational lung carcinogens, Because of the small number of females exposed, only males were included in the multivariate analyses. When the occupationally exposed subjects were compared with the unexposed subjects and an adjustment for smoking was made, the relative risk fm lung cancer was 2.9 (95% confidence interval, 1.95-4.31). If 5% to 10% of the Greek population were occupationally exposed, the attributable risk would be 9.9% to 16.6%, respectively. Occupational exposures conferred an additional risk that was approximately threefold that of smoking alone, Risks increased in a dose-response fashion with increasing cigarette consumption. C1 Athens Med Sch, Dept Hyg & Epidemiol, Athens 11527, Greece. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Cambridge Hosp, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm Crit Care Unit, Boston, MA USA. Massachusetts Resp Hosp, Ctr Occupat & Environm Med, Braintree, MA USA. RP Chatzis, C (reprint author), Athens Med Sch, Dept Hyg & Epidemiol, M Asias 75 Goudi, Athens 11527, Greece. FU NIEHS NIH HHS [ES00002, 1K07ES00266-01]; NIOSH CDC HHS [1 K01 OH00156-01] NR 30 TC 6 Z9 6 U1 0 U2 0 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 JAN PY 1999 VL 41 IS 1 BP 29 EP 35 DI 10.1097/00043764-199901000-00006 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 157WX UT WOS:000078085600006 PM 9924718 ER PT J AU Wong, DTW Todd, R AF Wong, DTW Todd, R TI Carcinoma of the tongue in two siblings - Discussion SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Editorial Material C1 Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Div Oral Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wong, DTW (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost Sci, Div Oral Biol, 188 Longwood Ave, Boston, MA 02115 USA. NR 2 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD JAN PY 1999 VL 57 IS 1 BP 69 EP 69 DI 10.1016/S0278-2391(99)90637-7 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 153NV UT WOS:000077839900020 ER PT J AU Bhattacharyya, N Varvares, MA AF Bhattacharyya, N Varvares, MA TI Anomalous relationship of the facial nerve and the retromandibular vein: A case report SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID ANATOMY C1 Joint Ctr Otolaryngol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Bhattacharyya, N (reprint author), Joint Ctr Otolaryngol, 333 Longwood Ave, Boston, MA 02115 USA. NR 3 TC 6 Z9 6 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 JAN PY 1999 VL 57 IS 1 BP 75 EP 76 DI 10.1016/S0278-2391(99)90639-0 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 153NV UT WOS:000077839900022 PM 9915401 ER PT J AU Asselin, BL Kreissman, S Coppola, DJ Bernal, SD Leavitt, PR Gelber, RD Sallan, SE Cohen, HJ AF Asselin, BL Kreissman, S Coppola, DJ Bernal, SD Leavitt, PR Gelber, RD Sallan, SE Cohen, HJ TI Prognostic significance of early response to a single dose of asparaginase in childhood acute lymphoblastic leukemia SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE efficacy; toxicity; asparaginase; acute lymphoblastic leukemia; prognosis ID ACUTE LYMPHOCYTIC-LEUKEMIA; GLYCOL-L-ASPARAGINASE; INTENSIVE ASPARAGINASE; ESCHERICHIA-COLI; INDUCTION; CHILDREN; REMISSION; VINCRISTINE; PREDNISONE; INVITRO AB Purpose: The in vitro and in vivo efficacy of a single dose of asparaginase in children with newly diagnosed acute lymphoblastic leukemia and the correlation between in vitro and in vivo antileukemic response and long-term outcome were prospectively evaluated. Patients and Methods: Two hundred fifty-one patients were randomized to receive 1 of 3 asparaginase preparations (Escherichia coli, Erwinia chrysanthemi [Erwinia], or pegaspargase). In vitro assessment of efficacy was expressed as the percent total cell kill (TCK), based on the number of viable cells found after 5 days of culture in the presence of asparaginase. In vivo leukemia cell kill (LCK) was calculated by comparing bone marrow cellularity and percent leukemic blasts in marrow obtained before and 5 days after treatment with a single dose of asparaginase. Acute toxicity was determined by clinical and laboratory assessment. Results: There was equivalent cell kill with all three types of asparaginase. The mean in vitro TCKs for E. coli, Erwinia, and pegaspargase were 31%, 39%, and 36%, respectively (P = 0.63). The mean LCKs in marrow of patients exposed to E. coli, Erwinia. and pegaspargase were 69%, 74%, and 65%, respectively (P = 0.88). The lack of response to asparaginase in vitro predicted a higher risk for clinical relapse regardless of risk assignment (12 leukemic events among 21 in vitro nonresponders; 57% P < 0.001). There was no difference in acute toxicity among the three asparaginase preparations. Conclusions: All three asparaginase preparations produced equivalent LCKs in in vitro and in vivo analyses. In vitro response to asparaginase provided a risk group-independent prognostic factor. C1 Univ Rochester, Med Ctr, Strong Childrens Res Ctr, Rochester, NY 14642 USA. Univ Rochester, Med Ctr, Ctr Canc, Rochester, NY 14642 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA USA. RP Asselin, BL (reprint author), Univ Rochester, Med Ctr, Dept Pediat, Box 777, Rochester, NY 14642 USA. FU NCI NIH HHS [5P01CA68484, P30CA11199]; PHS HHS [00199-03] NR 30 TC 46 Z9 48 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD JAN-FEB PY 1999 VL 21 IS 1 BP 6 EP 12 DI 10.1097/00043426-199901000-00003 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 163VP UT WOS:000078427300003 PM 10029805 ER PT J AU Islam, S Narra, V Cote, GM Manganaro, TF Donahoe, PK Schnitzer, JJ AF Islam, S Narra, V Cote, GM Manganaro, TF Donahoe, PK Schnitzer, JJ TI Prenatal vitamin E treatment improves lung growth in fetal rats with congenital diaphragmatic hernia SO JOURNAL OF PEDIATRIC SURGERY LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the American-Pediatric-Surgical-Association CY MAY 10-13, 1998 CL HILTON HEAD ISL, SOUTH CAROLINA SP Amer Pediat Surg Assoc DE prenatal vitamin E; congenital diaphragmatic hernia; pulmonary hypoplasia; fetal lung organ culture ID PULMONARY IMMATURITY; ANTIOXIDANT; SHEEP; HYPOPLASIA AB Purpose: Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypoplasia. To discover factors that would accelerate fetal lung growth, the authors developed models of hypoplasia, found that antioxidants im proved lung growth in vitro, and then proceeded to in vivo studies. Methods: Timed-pregnant rats were fed nitrofen (100 mg) on gestational day 9.5 (term, 22), and fetal lungs were harvested at day 13.5 and placed in organ culture in serum-free media with (n = 10) or without (n = 9) additional vitamin E (0.134 IU/mL). Camera lucida tracings were made daily on live, unstained lungs for 4 days, scanned, digitized, and analyzed for multiple growth parameters. Similar nitrofen-exposed rats were fed an optimized total dose of 150 IU vitamin E (n = 19) or olive oil (n = 13) from days 16.5 to 20.5, and fetal lungs were harvested at day 21.5, weighed and fixed for histology, or homogenized and biochemically analyzed. Results: Vitamin E accelerated hypoplastic fetal lung growth in vitro as measured by area, perimeter, lung bud count, perimeter over square root area, and fractal dimension. In vivo Vitamin E significantly increased lung weights, total DNA, and protein contents. Conclusions: Vitamin E accelerates hypoplastic fetal rat lung growth and complexity in vitro, and prenatal vitamin E treatment in vivo improves pulmonary hypoplasia in fetal rats with CDH. J Pediatr Surg 34:172-177. Copyright (C) 1999 by W.B. Saunders Company. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Surg Serv,Pediat Surg Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Schnitzer, JJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Surg Serv,Pediat Surg Res Labs, 55 Fruit St,Warren 11, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL03132] NR 27 TC 38 Z9 39 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0022-3468 J9 J PEDIATR SURG JI J. Pediatr. Surg. PD JAN PY 1999 VL 34 IS 1 BP 172 EP 176 DI 10.1016/S0022-3468(99)90251-8 PG 5 WC Pediatrics; Surgery SC Pediatrics; Surgery GA 158VE UT WOS:000078137400063 PM 10022166 ER PT J AU Malament, KA Socransky, SS AF Malament, KA Socransky, SS TI Survival of Dicor glass-ceramic dental restorations over 14 years: Part I. Survival of Dicor complete coverage restorations and effect of internal surface acid etching, tooth position, gender, and age SO JOURNAL OF PROSTHETIC DENTISTRY LA English DT Article; Proceedings Paper CT 78th Annual Meeting of the Academy-of-Prosthodontics CY MAY, 1996 CL NEWPORT BEACH, CALIFORNIA SP Acad Prosthodont ID STRENGTH; PORCELAIN; ENAMEL; CROWNS; SYSTEMS; WEAR AB Statement of problem. There are no long-term data on Dicor glass-ceramic restoration survival in the human oral cavity and the effect that different technical and clinical variables have on survival. Purpose. This prospective study examined the relationship of different clinical parameters on the survival of Dicor glass-ceramic restorations in the human oral cavity Material and methods. A total of 417 subjects (from 17 to 91 years of age) participated. ALL subjects required single unit fixed prosthodontics in any area of the mouth and/or 3-unit fixed partial dentures or cantilevered anterior restorations. They were offered the option of a gold or conventional metal-ceramic restoration, or a Dicor restoration with potentially improved esthetic results, better wear characteristics, and diminished oral prague accumulation. Overall survival of the restorations was determined and the effect of various clinical parameters evaluated with Kaplan-Meier survival curves. Log rank tests were used to determine statistically significant differences among parameters. Results. For the 1444 units placed, 188 failures were recorded. Total time at risk for the units was 7319 years providing an estimated risk of 2.45% per year. Probabilities of survival of "typical" acid-etched Dicor and nonacid-etched Dicor restorations were 76% and 50%, respectively, at 14.1 years (P<.001). Probabilities of survival of typical acid-etched and nonacid-etched Dicor complete coverage restorations were virtually identical to those observed in the full data set. There was a 2.2 times greater risk of failure associated with the use of nonacid-etched Dicor complete coverage than acid-etched restorations (P<.01). Complete coverage restoration survival was highest in the incisor region and decreased to the molars in both arches. Second molars showed the highest failure rate. No complete coverage restorations failed on lateral incisors during the entire study.. Probability of survival of a typical acid-etched Dicor complete coverage restoration in male subjects was 71%, and 75% for female subjects at 14.1 years (P<.01). The major difference appeared to be due to a greater failure rate in the maxillary arch of the male. Survivor functions of acid-etched Dicor complete coverage restorations for subjects in <33 years, 33 to 52 years, and 52 years age groups were 88% at 9 years, 62% at 14 years, and 82% at 14 years, respectively. Conclusions. Dicor restorations can survive successfully over time with certain reservations. Long-term survival improved significantly when restorations were acid-etched before luting. Complete coverage restoration failures per year decreased from molars to incisors in both arches, suggesting that complete coverage restorations on molars represented a serious risk. No Dicor complete coverage restoration on lateral incisors failed during the study. Restorations failed less often in female than male subjects. C1 Tufts Univ, Sch Dent Med, Dept Grad Prosthodont, Boston, MA 02111 USA. Forsyth Dent Ctr, Dept Periodontol, Boston, MA 02115 USA. RP Malament, KA (reprint author), 50 Staniford St, Boston, MA 02114 USA. NR 37 TC 128 Z9 130 U1 0 U2 9 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-3913 J9 J PROSTHET DENT JI J. Prosthet. Dent. PD JAN PY 1999 VL 81 IS 1 BP 23 EP 32 DI 10.1016/S0022-3913(99)70231-3 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 153LT UT WOS:000077835100004 PM 9878971 ER PT J AU Sachdev, D Chirgwin, JM AF Sachdev, D Chirgwin, JM TI Properties of soluble fusions between mammalian aspartic proteinases and bacterial maltose-binding protein SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article DE aspartic proteinases; protein folding; protein fusions ID INCLUSION-BODY FORMATION; HUMAN PROCATHEPSIN-D; ESCHERICHIA-COLI; CATHEPSIN-D; LYSOSOMAL-ENZYMES; EXPORTED PROTEIN; IN-VITRO; AGGREGATION; EXPRESSION; DOMAINS AB The mammalian aspartic proteinases procathepsin D and pepsinogen form insoluble inclusion bodies when expressed in bacteria. They become soluble but nonnative when synthesized as fusions to the carboxy terminus of E. coli maltose-binding protein (MBP). Since these nonnative states of the mio aspartic proteinases showed no tendency to form insoluble aggregates, their biophysical properties were analyzed. The MBP portions were properly folded as shown by binding to amylose, but the aspartic proteinase moieties failed to bind pepstatin and lacked enzymatic activity, indicating that they were not correctly folded. When treated with proteinase K, only the MBP portion of the fusions was resistant to proteolysis. The fusion between MBP and cathepsin D had increased hydrophobic surface exposure compared to the two unfused partners, as determined by bis-ANS binding. Ultracentrifugal sedimentation analysis of MBP-procathepsin D and MBP-pepsinogen revealed species with very large and heterogeneous sedimentation values. Refolding of the fusions from 8 M urea generated proteins no larger than dimers. Refolded MBP-pepsinogen was proteolytically active, while only a few percent of renatured MBP-procathepsin D was obtained. The results suggest that MBP-aspartic proteinase fusions can provide a source of soluble but nonnative folding states of the mammalian polypeptides in the absence of aggregation. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Endocrinol & Metab, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Chirgwin, JM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Endocrinol & Metab, San Antonio, TX 78284 USA. NR 39 TC 22 Z9 26 U1 1 U2 4 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0277-8033 J9 J PROTEIN CHEM JI J. Protein Chem. PD JAN PY 1999 VL 18 IS 1 BP 127 EP 136 DI 10.1023/A:1020663903669 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 169GZ UT WOS:000078740400015 PM 10071937 ER PT J AU Cooper, RA O'Connor, TJ Gonzalez, JP Boninger, ML Rentschler, A AF Cooper, RA O'Connor, TJ Gonzalez, JP Boninger, ML Rentschler, A TI Augmentation of the 100 kg ISO wheelchair test dummy to accommodate higher mass: A technical note SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE anthropometry; quality; standards; test dummies; wheelchairs ID ADIPOSE-TISSUE DISTRIBUTION; BODY-COMPOSITION; WOMEN AB Most of the 22 approved or developing ISO standards rely on a wheelchair test dummy, a specialized device described in ISO 7176-11. The purpose of this study was to develop a means for modifying the design of the ISO 7176-11 test dummy to be suitable for testing with higher masses. The changes are based upon published data for obese individuals. With these data, we derived equations for determining the distribution of the additional mass among the test dummy components, and the locations of the centers of mass. The results of this study provide guidelines for adding mass to the 100 kg wheelchair test dummy to accommodate resting of wheelchairs designed for obese individuals. C1 VA Pittsburgh Hlth Care Syst, Human Engn Res Labs 151RI, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, Dept Orthopaed Surg, Div Phys Med & Rehabil, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Mech Engn & Bioengn, Pittsburgh, PA 15261 USA. RP Cooper, RA (reprint author), VA Pittsburgh Hlth Care Syst, Human Engn Res Labs 151RI, 7180 Highland Dr, Pittsburgh, PA 15206 USA. OI Boninger, Michael/0000-0001-6966-919X NR 20 TC 4 Z9 4 U1 1 U2 3 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD JAN PY 1999 VL 36 IS 1 BP 48 EP 54 PG 7 WC Rehabilitation SC Rehabilitation GA 288VE UT WOS:000085584500010 PM 10659894 ER PT J AU Fotieo, GG Reiber, GE Carter, JS Smith, DG AF Fotieo, GG Reiber, GE Carter, JS Smith, DG TI Diabetic amputations in the VA: Are there opportunities for interventions? SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE amputation; diabetes mellitus; foot ulcer; pivotal event ID PREVENTION; FOOT AB Lower limb amputation (LLA) is a devastating complication experienced by some veterans with diabetes. The Veterans Affairs (VA) Healthcare system has identified the prevention of LLA as a priority goal. This study was designed to describe the sources of outpatient care received by veterans with diabetes who have undergone I,LA, to determine whether these persons would have been impacted by a VA amputation prevention program. This study was also designed to describe prior amputation history, footwear history, and the pivotal events that led to these amputations. We found that the vast majority of these subjects identified the VA as their primary source of care, and thus would have been available for enrollment in a prevention program. Since over one-half of them had had a prior amputation, diabetics with a prior amputation should be particularly targeted for foot care interventions. Lastly, prescription of protective footwear has the potential to reduce the incidence of shoe-related ulcers and amputations. C1 Albuquerque VA Med Ctr, Albuquerque, NM 87109 USA. Univ New Mexico, Dept Med, Albuquerque, NM 87113 USA. VA Puget Sound Healthcare Syst, Seattle, WA 98108 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98014 USA. Univ Washington, Dept Epidemiol & Orthoped Surg, Seattle, WA 98014 USA. RP Fotieo, GG (reprint author), Albuquerque VA Med Ctr, 111 GIM,1501 San Pedro SE, Albuquerque, NM 87109 USA. NR 11 TC 6 Z9 6 U1 0 U2 0 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD JAN PY 1999 VL 36 IS 1 BP 55 EP 59 PG 5 WC Rehabilitation SC Rehabilitation GA 288VE UT WOS:000085584500011 PM 10659895 ER PT J AU Warner, JJP Bowen, MK Deng, XH Torzilli, PA Warren, RF AF Warner, JJP Bowen, MK Deng, XH Torzilli, PA Warren, RF TI Effect of joint compression on inferior stability of the glenohumeral joint SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID SHOULDER INSTABILITY; ANTERIOR; CADAVER AB To determine the relative importance of negative intraarticular pressure, capsular tension, and joint compression on inferior stability of the glenohumeral joint we studied 17 Fresh, normal adult cadaver shoulders using a "3 degrees of freedom" shoulder test apparatus. Translations were measured in intact and vented shoulders while a 50-N superior and inferior directed force was applied to the shoulder Three different joint compressive loads (22 N, 1 1 1 N, 222 N) were applied externally. Tests were performed in 3 positions of humeral abduction in the scapular plane (0 degrees, 45 degrees, 90 degrees) and in 3 positions of rotation (neutral, maximal internal, and maximal external). After tests of the intact and vented shoulder the glenohumeral ligaments were sectioned and tests were repeated. With minimal joint compression of 22 N, negative intraarticular pressure and capsular tension limited translation of the humeral head on the glenoid. Increasing the joint compressive load to 1 1 1 N resulted in a reduction of mean inferior translation from 11.0 mm to 2.0 mm at 0 degrees abduction, From 21.5 mm to 1.4 mm at 45 degrees abduction, and from 4.5 mm to 1.2 mm at 90 degrees abduction. With a compressive load of 1 1 1 N, venting the capsule or sectioning of glenohumeral ligaments had no effect on inferior stability Clinical relevance: Glenohumeral joint compression through muscle contraction provides stability against inferior translation of the humeral head, and this effect is more important than negative intraarticular pressure or ligament tension. C1 Hosp Special Surg, Lab Soft Tissue Res, New York, NY 10021 USA. Hosp Special Surg, Sports Med & Shoulder Serv, New York, NY 10021 USA. RP Warner, JJP (reprint author), Massachusetts Gen Hosp, Harvard Shoulder Serv, POB 403,275 Cambridge St, Boston, MA 02114 USA. NR 37 TC 36 Z9 36 U1 0 U2 4 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD JAN-FEB PY 1999 VL 8 IS 1 BP 31 EP 36 DI 10.1016/S1058-2746(99)90051-4 PG 6 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 171LW UT WOS:000078866100007 PM 10077793 ER PT J AU Ring, D Jupiter, JB AF Ring, D Jupiter, JB TI Complex fractures of the distal humerus and their complications SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Review ID INTERCONDYLAR FRACTURES; OPERATIVE TREATMENT; INTERNAL-FIXATION; ELBOW JOINT; INTRAARTICULAR FRACTURES; SUPRACONDYLAR FRACTURES; POSTTRAUMATIC STIFFNESS; SURGICAL-TREATMENT; STABILITY; MOTION C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Orthopaed Hand Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Ring, D (reprint author), 11 Hancock St,Unit 4, Boston, MA 02114 USA. NR 122 TC 43 Z9 47 U1 0 U2 4 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD JAN-FEB PY 1999 VL 8 IS 1 BP 85 EP 97 DI 10.1016/S1058-2746(99)90063-0 PG 13 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 171LW UT WOS:000078866100019 PM 10077805 ER PT J AU Samuel, VJ George, P Thornell, A Curtis, S Taylor, A Brome, D Mick, E Faraone, SV Biederman, J AF Samuel, VJ George, P Thornell, A Curtis, S Taylor, A Brome, D Mick, E Faraone, SV Biederman, J TI A pilot controlled family study of DSM-III-R and DSM-IV ADHD in African-American children SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE African-Americans; attention-deficit hyperactivity disorder; comorbidity ID ATTENTION-DEFICIT HYPERACTIVITY; RISK-FACTORS; DISORDER; RELIABILITY; COMORBIDITY; ADOLESCENTS; INTERVIEW AB Background: Very little is known about attention-deficit hyperactivity disorder (ADHD) in African-American children, and although the familial transmission of ADHD has been well established in white samples, prior work has not evaluated this feature of ADHD in African-American families. Method: Subjects were 37 first-degree relatives of children with DSM-III-R-defined ADHD and 52 first-degree relatives of non-ADHD comparison children matched for ethnicity, age, and gender. DSM-lll-R-based structured interviews (modified to include DSM-IV diagnoses) provided the basis for psychiatric diagnoses in relatives. Results: The risks for both DSM-III-R and DSM-IV ADHD were significantly greater in first-degree relatives of ADHD probands than in relatives of controls. In addition, the relatives of ADHD probands also were at higher risk for oppositional defiant disorder, antisocial personality disorder, major depression, generalized anxiety, and substance use disorders. Conclusions: These results suggest that ADHD and related disorders are familial in African-Americans. Further work is needed to confirm the familial transmission of ADHD in African-American children and to explore the role of genetics as well as environmental factors in the transmission of the disorder. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, ACC 725, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, ACC 725, Boston, MA 02114 USA. EM biederman@helix.mgh.harvard.edu OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH50657-05] NR 28 TC 14 Z9 16 U1 1 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 JAN PY 1999 VL 38 IS 1 BP 34 EP 39 DI 10.1097/00004583-199901000-00017 PG 6 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 154CN UT WOS:000077871100017 PM 9893414 ER PT J AU Wozniak, J Crawford, MH Biederman, J Faraone, SV Spencer, TJ Taylor, A Blier, HK AF Wozniak, J Crawford, MH Biederman, J Faraone, SV Spencer, TJ Taylor, A Blier, HK TI Antecedents and complications of trauma in boys with ADHD: Findings from a longitudinal study SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE trauma; mania; attention-deficit hyperactivity disorder; comorbidity ID POSTTRAUMATIC-STRESS-DISORDER; ATTENTION-DEFICIT HYPERACTIVITY; PAST 10 YEARS; FOLLOW-UP; COMORBIDITY; POPULATION; CHILDREN; FAMILY; ADOLESCENTS; MANIA AB Objective: To examine the relationship between trauma and attention-deficit hyperactivity disorder (ADHD), evaluating whether ADHD increases the risk for trauma, the risk for posttraumatic stress disorder (PTSD), or the risk for trauma-associated psychopathology. Method: Data from a longitudinal sample of 260 children and adolescents with and without ADHD were examined. All were evaluated comprehensively with assessments in multiple domains of functioning including systematic assessments of trauma and PTSD. Comparisons were made between traumatized and nontraumatized youths with and without ADHD. Results: No meaningful differences were detected in comparisons between ADHD and control children, either in the rate of trauma exposure or in the development of PTSD. Although trauma was associated with the development of major depression, this effect was independent of ADHD status. In contrast, bipolar disorder at baseline assessment was a significant risk factor for subsequent trauma exposure. Conclusions: ADHD was not found to be a risk factor for either trauma exposure or PTSD, but childhood mania was. If confirmed, this finding stresses the potential severe clinical sequelae of childhood mania in children. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Pediat Psychopharmol Unit, Child Psychiat Serv,ACC, Boston, MA 02114 USA. RP Wozniak, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Pediat Psychopharmol Unit, Child Psychiat Serv,ACC, 15 Parkman St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH41314-07] NR 25 TC 36 Z9 38 U1 5 U2 6 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 JAN PY 1999 VL 38 IS 1 BP 48 EP 55 DI 10.1097/00004583-199901000-00019 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 154CN UT WOS:000077871100019 PM 9893416 ER PT J AU Cohen, LG Biederman, J Wilens, TE Spencer, TJ Mick, E Faraone, SV Prince, J Flood, JG AF Cohen, LG Biederman, J Wilens, TE Spencer, TJ Mick, E Faraone, SV Prince, J Flood, JG TI Desipramine clearance in children and adolescents: Absence of effect of development and gender SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE desipramine; pharmacokinetics; gender ID DEFICIT HYPERACTIVITY DISORDER; SPARTEINE OXIDATION PHENOTYPE; TRICYCLIC ANTI-DEPRESSANT; DOUBLE-BLIND; CLINICAL PHARMACOKINETICS; IMIPRAMINE DEMETHYLATION; TOURETTES-SYNDROME; DRUG DEVELOPMENT; INDUCED MANIA; IN-VIVO AB Objective: To examine the influence of development and gender on the pharmacokinetics of desipramine (DMI) in the pediatric population. Method: DMI pharmacokinetic parameters were calculated from 407 routinely drawn, dose- and weight-normalized serum concentrations in 173 youths receiving DMI (90 children, 83 adolescents; 29 were female, 144 were male). Results: Mean pharmacokinetic parameters for the entire population included dose (3.78 +/- 1.51 mg/kg), weight- and dose-normalized serum concentration (45.41 +/- 47.39 [mu g/L]/[mg/kg]) and DMI clearance (0.68 +/-1.51 [L/kg]/hr). No between-group differences for children and adolescents were detected in dose (child, adolescent) (3.73 +/- 1.40 mg/kg, 3.83 +/- 1.68 mg/kg), weight- and dose-normalized serum concentrations (44.52 +/- 39.6 [mu g/L]/[mg/kg], 46.34 +/- 34.89 [mu g/L]/[mg/kg]; p = .62), and clearance (0.680 +/- 0.890 [L/kg]/hr, 0.695 +/- 1.05 [L/kg]/hr; p = .103). No between-group gender differences were detected in dose (male, female) (3.83 +/- 1.55 mg, 3.39 +/- 1.84 mg), weight- and dose-normalized serum concentrations (45.15 +/-37.76 [mu g/L]/[mg/kg], 47.14 +/- 34.96 [mu g/L]/[mg/kg]; p = .720), and clearance (0.699 +/- 0.89 [L/kg]/hr, 0.606 +/- 0.535 [L/kg]/hr; p = .390). Conclusions: These results suggest that age and gender do not significantly influence DMI clearance or dose-normalized serum concentrations in the pediatric population. C1 Massachusetts Gen Hosp, Dept Pharm, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Psychiat Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Chem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Cohen, LG (reprint author), Massachusetts Gen Hosp, Dept Pharm, VBK BA 020,55 Fruit St, Boston, MA 02114 USA. OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 NR 67 TC 5 Z9 5 U1 0 U2 2 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 JAN PY 1999 VL 38 IS 1 BP 79 EP 85 DI 10.1097/00004583-199901000-00023 PG 7 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 154CN UT WOS:000077871100023 PM 9893420 ER PT J AU Kirkish, P Sreenivasan, S AF Kirkish, P Sreenivasan, S TI Neuropsychological assessment of competency to stand trial evaluations: A practical conceptual model SO JOURNAL OF THE AMERICAN ACADEMY OF PSYCHIATRY AND THE LAW LA English DT Article ID MINI-MENTAL STATE; CAPACITY AB Competency for adjudication is a complex concept that, despite judicial efforts to articulate functional criteria, has presented conscientious clinicians with the need to filter through multiple levels of psychological data to adequately evaluate and describe the germane functional capacities and deficits of a given defendant. Practitioners are confronted with preparing evaluations that are either psychologically inclusive and too broad to be judicially useful or too brief (opinions with inadequate descriptions of how a specific defendant's abilities and impediments affect the legal criteria). The trend toward harsh sentencing guidelines has further increased defendants' incentives either to postpone adjudication or to attempt to establish a foundation for an insanity plea. Therefore, accurate identification of malingered deficits has become a more significant problem in evaluating competency to stand trial than it previously was. When neuropsychological factors are introduced, competency assessment becomes complex. This article presents a methodology for managing these complexities. Strategies for preparing concise competency evaluations for defendants presenting neuropsychological symptoms are provided along with examples that help illustrate the evaluation process. C1 Patton State Hosp, Patton, CA 92369 USA. Loma Linda Univ, Dept Psychiat, Loma Linda, CA 92350 USA. W Los Angeles Vet Affairs Hosp, Los Angeles, CA USA. Univ So Calif, Sch Med, Dept Psychiat & Law, Los Angeles, CA USA. RP Kirkish, P (reprint author), Patton State Hosp, 3102 E Highland Ave, Patton, CA 92369 USA. NR 28 TC 11 Z9 12 U1 0 U2 1 PU AMER ACAD PSYCHIATRY LAW PI BLOOMFIELD PA ONE REGENCY DR, PO BOX 30, BLOOMFIELD, CT 06002 USA SN 0091-634X J9 J AM ACAD PSYCHIATRY JI J. Am. Acad. Psychiatry Law PY 1999 VL 27 IS 1 BP 101 EP 113 PG 13 WC Law; Psychiatry SC Government & Law; Psychiatry GA 181BQ UT WOS:000079421100008 PM 10212030 ER PT J AU Pires, LA Lehmann, MH Steinman, RT Baga, JJ Schuger, CD AF Pires, LA Lehmann, MH Steinman, RT Baga, JJ Schuger, CD TI Sudden death in implantable cardioverter-defibrillator recipients: Clinical context, arrhythmic events and device responses SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID VENTRICULAR-FIBRILLATION; LEAD SYSTEMS; CARDIAC DEATH; THRESHOLD; REDETECTION; MECHANISM; EFFICACY; THERAPY; TRIALS AB Objectives. We sought to investigate the nature of terminal events and potential contributory clinical and nonclinical (e.g., device-related) factors associated with sudden death (SD) in recipients of an implantable cardioverter-defibrillator (ICD). Background. The ICD is very effective in terminating ventricular tachycardia (VT) or ventricular fibrillation (VF), but protection against SD is not absolute. Little is known about the nature and potential causes of SD in patients with ICDs. Methods. We analyzed 25 cases of out-of-hospital SD among patients enrolled in the clinical investigation of the Cadence Tiered-Therapy Defibrillator System. Results. All patients (24 men and 1 woman, mean age 62 +/- 10 years) received epicardial lead systems. The majority (92%) had coronary artery disease and a previous myocardial infarction (MI), with a mean left ventricular ejection fraction 0.25 +/- 0.07. At device implantation, the mean defibrillation threshold was 13 +/- 5 J. Sudden death occurred 13 +/- 11 months later. Twenty patients (80%) had received appropriate ICD therapies before death, and 18 (72%) were receiving greater than or equal to 1 antiarrhythmic drugs at the time of death. Sudden death was tachyarrhythmia-associated in 16 patients (64%), non tachyarrhythmia-associated in 7 (28%) and indeterminate in 2 (8%). In the 16 patients with tachyarrhythmia-associated SD, the overall first therapy success rate in tachycardia and fibrillation zones was 60% and 67%, respectively. However, despite protracted therapies (greater than or equal to 2 shocks) in 7 (66%) of 12 patients who received fibrillation therapies, the final tachyarrhythmic episode was ultimately terminated by the ICD in 15 (94%) of the 16 patients, whereas 1 patient died after multiple (initially successful) internal and external shocks for intractable VT/VF during exercise. In 10 patients (40%) one or more, primarily clinical, factors potentially contributory to SD mere identified: heart failure (n = 8), angina (n = 2), hypokalemia (n = 1), adverse antiarrhythmic drug treatment (n = 1) and acute MI (n = 1). An additional 10 patients (40%) had experienced an increase in frequency of ICD shocks within 3 months of SD. Appropriate battery voltages and normal circuitry function were found in all devices interrogated and analyzed after death. Conclusions. In this select group of patients receiving a third-generation ICD, SD was associated with VT or VF events in nearly two thirds of patients, and death occurred despite ultimately successful, although often protracted, device therapies. These observations, along with evidence of recent worsening clinical status, suggest acute cardiac mechanical dysfunction as a frequent terminal factor. In recipients with ICDs, SD directly attributable to device failure seems to be rare. (C) 1998 by the American College of Cardiology. C1 Sinai Hosp, Arrhythmia Ctr, Detroit, MI 48235 USA. Wayne State Univ, Sch Med, Detroit, MI USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Cottage Hosp, Santa Barbara, CA USA. Good Samaritan Hosp, Los Angeles, CA USA. Holy Cross Hosp, Ft Lauderdale, FL USA. Hosp Univ Penn, Philadelphia, PA 19104 USA. Humana Hosp, Las Vegas, NV USA. Illinois Masonic Med Ctr, Chicago, IL 60657 USA. Iowa Heart Ctr, Des Moines, IA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Methodist Hosp, Memphis, TN USA. Sequoia Hosp, Redwood City, CA USA. St Josephs Hosp, Milwaukee, WI USA. St Vincents Hosp, Indianapolis, IN USA. Univ Colorado, Denver, CO 80202 USA. Univ Hosp Hannover, Hannover, Germany. Virginia Mason Clin, Seattle, WA 98101 USA. Western Penn Hosp, Pittsburgh, PA 15224 USA. RP Pires, LA (reprint author), St Johns Hosp, Ctr Med, 22101 Moross, Detroit, MI 48236 USA. NR 34 TC 53 Z9 55 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN PY 1999 VL 33 IS 1 BP 24 EP 32 DI 10.1016/S0735-1097(98)00519-1 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 157YB UT WOS:000078088300005 PM 9935004 ER PT J AU Rubenstein, LZ AF Rubenstein, LZ TI The importance of including the home environment in assessment of frail older persons SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material C1 Univ Calif Los Angeles, Sch Med, GRECC, VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. RP Rubenstein, LZ (reprint author), Univ Calif Los Angeles, Sch Med, GRECC, VA Greater Los Angeles Healthcare Syst, Sepulveda, CA USA. NR 9 TC 11 Z9 12 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JAN PY 1999 VL 47 IS 1 BP 111 EP 112 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 156RY UT WOS:000078016900018 PM 9920239 ER PT J AU Blewett, DR Barnett, GO Chueh, HC AF Blewett, DR Barnett, GO Chueh, HC TI Experience with an electronic health record for a homeless population SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Medical-Informatics-Association CY NOV 06-10, 1999 CL WASHINGTON, D.C. SP Amer Med Informat Assoc ID URBAN HOMELESS; ADULTS; BOSTON; DEATH AB A computerized electronic medical record (EMR) system using client-server architecture was designed and implemented by the Laboratory of Computer Science for use by the Boston Health Care for the Homeless Program (BHCHP) to meet the unique medical record needs of the homeless. For the past three years, this EMR has been used to assist providers in the delivery of health care to the homeless population of Boston. As the BHCHP has grown and technology improved, it is important to review what features of the EMR work, and to investigate what improvements can be made for the better delivery of care to the homeless, especially as we approach the next century. C1 Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. RP Blewett, DR (reprint author), Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. NR 16 TC 0 Z9 0 U1 1 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 1999 SU S BP 481 EP 485 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RA UT WOS:000170207300099 ER PT J AU Payne, TH AF Payne, TH TI The transition to automated practitioner order entry in a teaching hospital: The VA Puget Sound experience SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Medical-Informatics-Association CY NOV 06-10, 1999 CL WASHINGTON, D.C. SP Amer Med Informat Assoc ID PHYSICIAN; MANAGEMENT; IMPACT AB Me recently installed an automated practitioner order entry system on our busiest inpatient wards and critical care units. The installation followed 20 months preparation in which we created the workstation, network, and host infrastructure, developed requisite policies, recruited personnel to support the system, and installed the software in areas where the pace of order entry was less intense. Since implementing automated order entry, we have experienced problems such as an increase in time required for practitioners to enter orders, workflow changes on inpatient units, difficulties with patient transfers, and others. Our user support system has been heavily used during the transition period. Software tailoring and enhancements designed to address these problems are planned, as is installation of the order entry system in remaining clinical units in our medical centers. C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Payne, TH (reprint author), VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 7 TC 8 Z9 8 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 1999 SU S BP 589 EP 593 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RA UT WOS:000170207300121 ER PT J AU Murphy, SN Morgan, MM Barnett, GO Chueh, HC AF Murphy, SN Morgan, MM Barnett, GO Chueh, HC TI Optimizing healthcare research data warehouse design through past COSTAR query analysis SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Medical-Informatics-Association CY NOV 06-10, 1999 CL WASHINGTON, D.C. SP Amer Med Informat Assoc AB Over the past two years we have reviewed and implemented the specifications for a large relational database (a data warehouse) to find research cohorts from data similar to that contained within the clinical COSTAR database at the Massachusetts General Hospital. A review of 16 years of COSTAR research queries was conducted to determine the most common search strategies. These search strategies are relevant to the general research community, because they use the Medical Query Language (MQL) developed for the COSTAR M database which is extremely flexible (much more so than SQL) and allows searches by coded fields, text reports, and laboratory values in a completely ad hoc fashion. By reviewing these search strategies, we were able to obtain user specifications for a research oriented healthcare data warehouse that could support 90% of the queries. The data warehouse was implemented in a relational database using the star schema, allowing for highly optimized analytical processing. This allowed queries that performed slowly in the M database to be performed very rapidly in the relational database. Tt also allowed the data warehouse to scale effectively. C1 Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. NR 7 TC 15 Z9 15 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 1999 SU S BP 892 EP 896 PG 5 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RA UT WOS:000170207300183 ER PT J AU Behal, R Murphy, SN Barnett, GO Chueh, HC AF Behal, R Murphy, SN Barnett, GO Chueh, HC TI Deriving patient profiles from clinical repositories SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 1999 SU S BP 1023 EP 1023 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RA UT WOS:000170207300221 ER PT J AU Berkowiez, DA Barnett, GO Chueh, HC AF Berkowiez, DA Barnett, GO Chueh, HC TI eWhiteBoard: A real time clinical scheduler SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Lab Comp Sci, Boston, MA USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 1999 SU S BP 1026 EP 1026 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RA UT WOS:000170207300224 ER PT J AU Dubey, AK Chueh, HC AF Dubey, AK Chueh, HC TI Utilizing a use case approach to develop an object information model for online guideline system output SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract AB With the advent of new web standards such as XML (the extensible markup language), there lies the promise of increased connectivity among informatics applications; such promise can only be realized however if the data models of the information sources are compatible. While work has been done in modeling the logical specification of automated guideline/reminder systems and the clinical data that form their input, little has been done on modeling the output of such systems. A data model for automated guideline output can help foster such compatibility by providing a common frame of reference. We have begun to utilize the "use case" approach by Jacobson et al to develop an object oriented information model of guideline output. We derived use cases from previously published implementations of guideline systems. We present our preliminary results. C1 Massachusetts Gen Hosp, Lab Comp Sci, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 1999 SU S BP 1050 EP 1050 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RA UT WOS:000170207300248 ER PT J AU Payne, TH Andrews, RD Breeling, J Ben Davoren, J Smith, RM Volpp, B AF Payne, TH Andrews, RD Breeling, J Ben Davoren, J Smith, RM Volpp, B TI Graphing clinical events in the VA Computerized Patient Record System SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract C1 US Dept Vet Affairs, Seattle, WA USA. US Dept Vet Affairs, Salt Lake City, UT USA. US Dept Vet Affairs, Brockton, CT USA. US Dept Vet Affairs, San Francisco, CA USA. US Dept Vet Affairs, San Diego, CA USA. US Dept Vet Affairs, W Palm Beach, FL USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 1999 SU S BP 1137 EP 1137 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RA UT WOS:000170207300335 ER PT J AU Shkovskiy-Kordi, N Zingerman, B Kobeliackiy, V Gudilina, J Freidn, J Goldberg, S Davis, S AF Shkovskiy-Kordi, N Zingerman, B Kobeliackiy, V Gudilina, J Freidn, J Goldberg, S Davis, S TI A time axis presentation of clinical and diagnostic information from multiple sources SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Natl Ctr Hematol, Moscow, Russia. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 1999 SU S BP 1161 EP 1161 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RA UT WOS:000170207300359 ER PT J AU Meldrum, KC Volpp, BD Vertigan, R AF Meldrum, KC Volpp, BD Vertigan, R TI Department of veterans affairs' Computerized Patient Record System SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Meeting Abstract C1 US Dept Vet Affairs, Vet Hlth Adm, Salt Lake City, UT USA. US Dept Vet Affairs, Vet Hlth Adm, W Palm Beach, FL USA. US Dept Vet Affairs, Vet Hlth Adm, Albany, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PY 1999 SU S BP 1214 EP 1214 PG 1 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 458RA UT WOS:000170207300410 ER PT J AU Baid, S Pascual, M Williams, WW Tolkoff-Rubin, N Johnson, SM Collins, B Chung, RT Delmonico, FL Cosimi, AB Colvin, RB AF Baid, S Pascual, M Williams, WW Tolkoff-Rubin, N Johnson, SM Collins, B Chung, RT Delmonico, FL Cosimi, AB Colvin, RB TI Renal thrombotic microangiopathy associated with anticardiolipin antibodies in hepatitis C-positive renal allograft recipients SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; SYSTEMIC LUPUS-ERYTHEMATOSUS; ANTIPHOSPHOLIPID SYNDROME; VIRUS-INFECTION; PLASMA-EXCHANGE; GLOMERULONEPHRITIS; TRANSPLANTATION; KIDNEY; IMMUNOSUPPRESSION; CRYOGLOBULINEMIA AB Hepatitis C virus (HCV) infection has been associated with de novo or recurrent membranoproliferative glomerulonephritis and acute transplant glomerulopathy in transplanted kidneys. Recently, anticardiolipin antibodies (ACA) have been linked with chronic HCV infection. A few reports have suggested an association between ACA and renal allograft thrombosis. This study examines the clinical and pathologic features of HCV-positive renal allograft recipients at our institution. From 1990 to 1996, 379 kidney transplants were performed. We identified 18 recipients (4.8%) with HCV-positive serology pretransplant. Determination of IgG and IgM ACA was performed by enzyme-linked immunosorbent assay, using pretransplant sera. Among the 18 patients, five patients presented with biopsy-proven de novo renal thrombotic microangiopathy (RTMA), occurring 5 to 120 d (median, 14 d) after transplant. No differences in pretransplant characteristics were observed between patients with (n = 5) or without (n = 13) RTMA. All five patients had a positive ACA test (either IgG or IgM titer > 2 SD above normal), compared with only one of 13 patients without RTMA. The mean value for IgG ACA was significantly higher in the RTMA patients than in patients without RTMA (22.9 +/- 14.1 versus 6.9 +/- 4.9 IgG phospholipid units, P = 0.02); however, there were no significant differences in IgM ACA titers. Rheumatoid factor and complement C4 levels were normal in pretransplant sera of patients with RTMA. Patients with RTMA had their cyclosporine withdrawn (four of five or the dose was decreased tone of five), and one of five underwent plasmapheresis. Four of five patients died within 5 yr after transplant, compared with no deaths in the other 13 patients. Finally, as a control group, seven HCV-negative renal allograft recipients who presented with RTMA/hemolytic uremic syndrome during the same time period were found to have normal ACA values (IgG or IgM). RTMA associated with ACA in HCV-positive renal allograft recipients may represent a new clinical entity. The occurrence of this syndrome may have deleterious consequences for patient and graft survival. C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Baid, S (reprint author), Massachusetts Gen Hosp, Renal Unit, 100 Charles River Plaza,5th Floor, Boston, MA 02114 USA. FU NIDDK NIH HHS [K08DK02209] NR 37 TC 100 Z9 104 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JAN PY 1999 VL 10 IS 1 BP 146 EP 153 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 154FN UT WOS:000077878300018 PM 9890320 ER PT J AU Koff, E Zaitchik, D Montepare, J Albert, MS AF Koff, E Zaitchik, D Montepare, J Albert, MS TI Emotion processing in the visual and auditory domains by patients with Alzheimer's disease SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE emotion processing; Alzheimer's disease ID AFFECT RECOGNITION; RIGHT-HEMISPHERE; ELDERLY PERSONS; PERCEPTION; SENILE; LATERALIZATION; COMMUNICATION; PROSODY AB The ability to process emotional information was assessed in 42 individuals: 23 patients with Alzheimer's disease (AD) and 19 healthy elderly controls. Four tasks assessed the ability to recognize emotion in audiotaped voices, in drawings of emotional situations, and in videotaped vignettes displaying emotions in facial expression, gestures, and body movements. Hemispheric dominance for processing facial expressions of emotions was also examined. There were no consistent group differences in the ability to process emotion presented via the auditory domain (i.e., nonverbal sounds, such as crying or shrieking, and speech prosody). Controls were, however, significantly better than the AD patients in identifying emotions depicted in drawings of emotional situations and in videotaped scenes displaying faces, gestures, and body movements. These differences were maintained after statistically adjusting for the visuospatial abilities of the participants. After a statistical adjustment for abstraction ability, some of the tasks continued to differentiate the groups (e.g., the emotional drawings task, the videotaped displays of faces), but others did not. These results confirm and extend previous results indicating that AD patients do not have a primary deficit in the processing of emotion. They suggest that the difficulties of the AD patients in perceiving emotion are secondary to the cognitive impairments associated with AD. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. Wellesley Coll, Dept Psychol, Wellesley, MA 02181 USA. Emerson Coll, Dept Psychol, Boston, MA 02116 USA. RP Albert, MS (reprint author), Massachusetts Gen Hosp, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [P01-AG04390] NR 33 TC 54 Z9 54 U1 2 U2 8 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD JAN PY 1999 VL 5 IS 1 BP 32 EP 40 PG 9 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 162BR UT WOS:000078325800005 PM 9989022 ER PT J AU Hadlock, TA Koka, R Vacanti, JP Cheney, ML AF Hadlock, TA Koka, R Vacanti, JP Cheney, ML TI A comparison of assessments of functional recovery in the rat SO JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM LA English DT Article DE behavioral testing; Sciatic Function Index; walking track analysis ID SCIATIC-NERVE BLOCKADE; NEUROPATHIC PAIN BEHAVIORS; NEUROLOGIC EVALUATION; IN-VIVO; REGENERATION; INJURY; MODEL; MICROSPHERES; HYPERALGESIA; INDEX AB Assessment of functional recovery following any peripheral nerve manipulation is critical. While quantitative neurobehavioral testing has been developed in the anesthesia literature for the assessment of neural function, the surgical literature relies mainly on walking track analysis for evaluation of motor recovery. The latter method is both cumbersome to perform and difficult to quantify. We compared standard walking track analysis with the quantitative neurobehavioral tests recently developed for anesthetic testing. We found a close correlation between the recovery predicted by walking track analysis and that suggested by neurobehavioral testing. In addition, the neurobehavioral test battery offered information regarding the rate of return of pure motor function, complex integrated function, proprioceptive function. and sensation. The tests are easier to perform and less susceptible to interpretative error. Neurobehavioral testing may be an effective substitute for walking track analysis in the assessment of functional recovery following manipulation of the rat sciatic nerve. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Facial Plast & Reconstruct Surg, Boston, MA 02114 USA. Childrens Hosp, Dept Surg, Lab Transplantat & Tissue Engn, Boston, MA USA. RP Hadlock, TA (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Facial Plast & Reconstruct Surg, 243 Charles St, Boston, MA 02114 USA. NR 29 TC 21 Z9 22 U1 0 U2 1 PU WOODLAND PUBLICATIONS, INC PI NEW YORK PA 69 MURRAY ST, NEW YORK, NY 10007 USA SN 1085-9489 J9 J PERIPHER NERV SYST JI J. Peripher. Nerv. Syst. PY 1999 VL 4 IS 3-4 BP 258 EP 264 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 270XP UT WOS:000084562700005 PM 10642093 ER PT J AU Ibrahim, JG Lipsitz, SR AF Ibrahim, JG Lipsitz, SR TI Missing covariates in generalized linear models when the missing data mechanism is non-ignorable SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY LA English DT Article DE EM algorithm; Gibbs sampling; logistic regression; maximum likelihood estimation; missing data mechanism; Monte Carlo EM algorithm ID MAXIMUM-LIKELIHOOD ESTIMATION; NONIGNORABLE NONRESPONSE; MULTIPLE IMPUTATION; REGRESSION-MODELS; EM ALGORITHM; VALUES AB We propose a method for estimating parameters in generalized linear models with missing covariates and a non-ignorable missing data mechanism. We use a multinomial model for the missing data indicators and propose a joint distribution for them which can be written as a sequence of one-dimensional conditional distributions, with each one-dimensional conditional distribution consisting of a logistic regression. We allow the covariates to be either categorical or continuous. The joint covariate distribution is also modelled via a sequence of one-dimensional conditional distributions, and the response variable is assumed to be completely observed. We derive the E- and M-steps of the EM algorithm with non-ignorable missing covariate data. For categorical covariates, we derive a closed form expression for the E- and M-steps of the EM algorithm for obtaining the maximum likelihood estimates (MLEs). For continuous covariates, we use a Monte Carlo version of the EM algorithm to obtain the MLEs via the Gibbs sampler. Computational techniques for Gibbs sampling are proposed and implemented. The parametric form of the assumed missing data mechanism itself is not 'testable' from the data, and thus the non-ignorable modelling considered here can be viewed as a sensitivity analysis concerning a more complicated model. Therefore, although a model may have 'passed' the tests for a certain missing data mechanism, this does not mean that we have captured, even approximately, the correct missing data mechanism. Hence, model checking for the missing data mechanism and sensitivity analyses play an important role in this problem and are discussed in detail. Several simulations are given to demonstrate the methodology. In addition, a real data set from a melanoma cancer clinical trial is presented to illustrate the methods proposed. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Worcester Polytech Inst, Worcester, MA 01609 USA. RP Ibrahim, JG (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. NR 22 TC 117 Z9 119 U1 1 U2 15 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 1369-7412 J9 J ROY STAT SOC B JI J. R. Stat. Soc. Ser. B-Stat. Methodol. PY 1999 VL 61 BP 173 EP 190 DI 10.1111/1467-9868.00170 PN 1 PG 18 WC Statistics & Probability SC Mathematics GA 165TT UT WOS:000078538500012 ER PT J AU Chen, MH Ibrahim, JG Yiannoutsos, C AF Chen, MH Ibrahim, JG Yiannoutsos, C TI Prior elicitation, variable selection and Bayesian computation for logistic regression models SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY LA English DT Article DE Gibbs sampling; logistic regression; normal prior; posterior distribution; prior distribution; selection of variables ID GENERALIZED LINEAR-MODELS AB Bayesian selection of variables is often difficult to carry out because of the challenge in specifying prior distributions for the regression parameters for all possible models, specifying a prior distribution on the model space and computations. We address these three issues for the logistic regression model. For the first, we propose an informative prior distribution for variable selection. Several theoretical and computational properties of the prior are derived and illustrated with several examples. For the second, we propose a method for specifying an informative prior on the model space, and for the third we propose novel methods for computing the marginal distribution of the data. The new computational algorithms only require Gibbs samples from the full model to facilitate the computation of the prior and posterior model probabilities for all possible models. Several properties of the algorithms are also derived. The prior specification for the first challenge focuses on the observables in that the elicitation is based on a prior prediction y(0) for the response vector and a quantity a(0) quantifying the uncertainty in y(0). Then, Y-0 and a(0) are used to specify a prior for the regression coefficients semi-automatically. Examples using real data are given to demonstrate the methodology. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Worcester Polytech Inst, Worcester, MA 01609 USA. RP Ibrahim, JG (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 665 Huntington Ave, Boston, MA 02115 USA. EM ibrahim@jimmy.harvard.edu NR 31 TC 55 Z9 55 U1 0 U2 4 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 1369-7412 J9 J ROY STAT SOC B JI J. R. Stat. Soc. Ser. B-Stat. Methodol. PY 1999 VL 61 BP 223 EP 242 DI 10.1111/1467-9868.00173 PN 1 PG 20 WC Statistics & Probability SC Mathematics GA 165TT UT WOS:000078538500015 ER PT J AU Weller, EA Feuer, EJ Frey, CM Wesley, MN AF Weller, EA Feuer, EJ Frey, CM Wesley, MN TI Parametric relative survival regression using generalized linear models with application to Hodgkin's lymphoma SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE parametric model; relative survival; Weibull generalized linear model ID CHEMOTHERAPY; DISEASE; RATES AB Changes in survival rates during 1940-1992 for patients with Hodgkin's disease are studied by using population-based data. The aim of the analysis is to identify when the breakthrough in clinical trials of chemotherapy treatments started to increase population survival rates, and to find how long it took for the increase to level off, indicating that the full population effect of the breakthrough had been realized. A Weibull relative survival model is used because the model parameters are easily interpretable when assessing the effect of advances in clinical trials. However, the methods apply to any relative survival model that falls within the generalized linear models framework. The model is fitted by using modifications of existing software (SAS, GLIM) and profile likelihood methods. The results are similar to those from a cause-specific analysis of the data by Feuer and co-workers. Survival started to improve around the time that a major chemotherapy breakthrough (nitrogen mustard, Oncovin, prednisone and procarbazine) was publicized in the mid-1960s but did not level off for 11 years. For the analysis of data where the cause of death is obtained from death certificates, the relative survival approach has the advantage of providing the necessary adjustment for expected mortality from causes other than the disease without requiring information on the causes of death. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. Geisinger Med Ctr, Danville, PA 17822 USA. Informat Management Syst, Silver Spring, MD USA. RP Weller, EA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. EM eweller@jimmy.harvard.edu NR 25 TC 7 Z9 7 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0035-9254 J9 J R STAT SOC C-APPL JI J. R. Stat. Soc. Ser. C-Appl. Stat. PY 1999 VL 48 BP 79 EP 89 DI 10.1111/1467-9876.00141 PN 1 PG 11 WC Statistics & Probability SC Mathematics GA 165XD UT WOS:000078546400007 ER PT J AU Lipsitz, SR Ibrahim, JG Parzen, M AF Lipsitz, SR Ibrahim, JG Parzen, M TI A degrees-of-freedom approximation for a t-statistic with heterogeneous variance SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES D-THE STATISTICIAN LA English DT Article DE homogeneous variance; linear model; ordinary least squares ID REGRESSION; HETEROSKEDASTICITY; ESTIMATORS AB Ordinary least squares is a commonly used method for obtaining parameter estimates for a linear model. When the variance is heterogeneous, the ordinary least squares estimate is unbiased, but the ordinary least squares variance estimate may be biased, Various jackknife estimators of variance have been shown to be consistent for the asymptotic variance of the ordinary least squares estimator of the parameters. In small samples, simulations have shown that the coverage probabilities of confidence intervals using the jackknife variance estimators are often low. We propose a finite sample degrees-of-freedom approximation to use with the t-distribution, which, in simulations, appears to raise the coverage probabilities closer to the nominal level. We also discuss an 'estimated generalized least squares estimator', in which we model and estimate the variance, and use the estimated variance in a weighted regression. Even when the variance is modelled correctly, the coverage can be low in small samples, and, in terms of the coverage probability, one appears better off using ordinary least squares with a robust variance and our degrees-of-freedom approximation. An example with real data is given to demonstrate how potentially misleading conclusions may arise when the degrees-of-freedom approximation is not used. C1 Harvard Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Chicago, Chicago, IL 60637 USA. RP Ibrahim, JG (reprint author), Harvard Sch Publ Hlth, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. NR 15 TC 6 Z9 6 U1 1 U2 3 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0039-0526 J9 J ROY STAT SOC D-STA JI J. R. Stat. Soc. Ser. D-Stat. PY 1999 VL 48 BP 495 EP 506 DI 10.1111/1467-9884.00207 PN 4 PG 12 WC Statistics & Probability SC Mathematics GA 263CU UT WOS:000084105700004 ER PT J AU Mitchell, JD Mathisen, DJ Wright, CD Wain, JC Donahue, DM Moncure, AC Grillo, HC AF Mitchell, JD Mathisen, DJ Wright, CD Wain, JC Donahue, DM Moncure, AC Grillo, HC TI Clinical experience with carinal resection SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 78th Annual Meeting of the American-Association-for-Thoracic-Surgery CY MAY 03-06, 1998 CL BOSTON, MASSACHUSETTS SP Amer Assoc Thorac Surg ID TRACHEAL SLEEVE PNEUMONECTOMY; BRONCHOGENIC-CARCINOMA; MANAGEMENT AB Objective: Pathologic processes that involve the carina pose a tremendous challenge to thoracic surgeons. Although techniques have been developed to allow primary resection and reconstruction, few institutions have accumulated sufficient experience to allow meaningful conclusions about the indications and the morbidity and mortality rates for this type of surgery. Methods: Since 1962, 135 patients have undergone 143 carinal resections (134 primary resection, 9 re-resection) at our institution. Indications for carinal resection included bronchogenic cancer (58 patients), other airway neoplasms (60 patients), and benign or inflammatory strictures (16 patients). Thirty-seven patients (28%) had a history of prior lung or airway surgery not involving the carina, Carinal resection without pulmonary resection was accomplished in 52 patients; 57 patients had carinal pneumonectomy (44 right, 13 left); 14 patients had carinal plus lobar resection, and 11 patients had carinal resection after pneumonectomy (9 left, 2 right). There were 15 different modes of reconstruction, based on the type and extent of resection, Techniques were used to reduce anastomotic tension. Results: The operative mortality rate in the 134 patients after primary carinal resection was 12.7%, Adult respiratory distress syndrome was responsible for 9 early deaths. Predominant predictors of operative death included postoperative mechanical ventilation (P = .001), length of resected airway (P = .03), and development of anastomotic complications (P = .04), Mortality rates varied by the type of procedure and the indication for resection, Left carinal pneumonectomy was associated with a high operative mortality rate (31%), Complications were noted in 52 patients (39%), including atrial arrhythmias (20 patients) and pneumonia (11 patients). Anastomotic complications, both early and late, were seen in a total of 23 patients (17%) and resulted in death or surgical reintervention in 21 patients (91%). The operative mortality rate for carinal re-resection was 11.1%. Conclusions: Carinal resection with primary reconstruction may be accomplished with acceptable mortality rates, but the underlying pathologic process and chance for long-term survival must be carefully considered before the operation is recommended, especially in the case of left carinal pneumonectomy, Anastomotic complications exact a heavy toll on involved patients, Careful patient selection and meticulous anesthetic and surgical technique remain the key to minimizing morbidity and mortality rates. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Gen Thorac Surg Unit, Boston, MA 02114 USA. RP Mathisen, DJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Gen Thorac Surg Unit, Blake Bldg 1570, Boston, MA 02114 USA. NR 15 TC 72 Z9 75 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JAN PY 1999 VL 117 IS 1 BP 39 EP 52 DI 10.1016/S0022-5223(99)70468-X PG 14 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 154PU UT WOS:000077898200012 PM 9869757 ER PT J AU Sugarbaker, DJ Flores, RM Jaklitsch, MT Richards, WG Strauss, GM Carson, JM DeCamp, MM Swanson, SJ Bueno, R Lukanich, JM Baldini, EH Mentzer, SJ AF Sugarbaker, DJ Flores, RM Jaklitsch, MT Richards, WG Strauss, GM Carson, JM DeCamp, MM Swanson, SJ Bueno, R Lukanich, JM Baldini, EH Mentzer, SJ TI Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: Results in 183 patients SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 78th Annual Meeting of the American-Association-for-Thoracic-Surgery CY MAY 03-06, 1998 CL BOSTON, MASSACHUSETTS SP Amer Assoc Thorac Surg ID LUNG-CANCER; INTRAPERITONEAL CHEMOTHERAPY; UNITED-STATES; MULTIMODALITY THERAPY; PHOTODYNAMIC THERAPY; BIWEEKLY PACLITAXEL; 1-HOUR INFUSION; OVARIAN-CANCER; PHASE-I; CISPLATIN AB Objectives: Our aim was to identify prognostic variables for long-term postoperative survival in trimodality management of malignant pleural mesothelioma. Methods: From 1980 to 1997, 183 patients underwent extrapleural pneumonectomy followed by adjuvant chemotherapy and radiotherapy. Results: Forty-three women and 140 men (age range 31-76 years) had a median follow-up of 13 months. The perioperative mortality rate was 3.8 % (7 deaths) and the morbidity, 50%. Survival in the 176 remaining patients was 38% at 2 years and 15% at 5 years (median 19 months). Univariate analysis identified 3 prognostic variables associated with improved survival: epithelial cell type (52% 2-year survival, 21% 5-year survival, 26-month median survival; P =.0001), negative resection margins (44% at 2 years, 25% at 5 years, median 23 months; P =.02), and extrapleural nodes without metastases (42% at 2 years, 17% at 5 years, median 21 months; P =.004). Using the Cox proportional hazards, the relative risk of death was calculated for nonepithelial cell type (OR 3.0, CI 2.0-4.5; P < .0001), positive resection margins (OR 1.7, CI 1.2-2.6; P =.0082), and metastatic extrapleural nodes (OR 2.0, CI 1.3-3.2;P =.0026). Thirty-one patients with 3 positive variables had the best survival (68% 2-year survival, 46% 5-year survival, median 51 months; P =.013). A previously published staging system using these variables stratified survival (P <.05). Conclusions: (1) Multimodality therapy including extrapleural pneumonectomy is feasible in selected patients with malignant pleural mesotheliomas, (2) pre-resectional evaluation of extrapleural nodes may select patients for radical therapy, (3) microscopic resection margins affect long-term survival, highlighting the need for further investigation of locoregional control, and (4) patients with epithelial, margin-negative, extrapleural node-negative resection had extended survival. C1 Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Surg Serv, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Univ Massachusetts, Worcester, MA 01605 USA. RP Sugarbaker, DJ (reprint author), Brigham & Womens Hosp, Div Thorac Surg, 75 Francis St, Boston, MA 02115 USA. NR 43 TC 545 Z9 557 U1 3 U2 10 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD JAN PY 1999 VL 117 IS 1 BP 54 EP 63 DI 10.1016/S0022-5223(99)70469-1 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 154PU UT WOS:000077898200014 PM 9869758 ER PT J AU Szekely, LA Thompson, BT Woolf, A AF Szekely, LA Thompson, BT Woolf, A TI Use of partial liquid ventilation to manage pulmonary complications of acute verapamil-sustained release poisoning SO JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY LA English DT Article ID CHANNEL BLOCKER OVERDOSE; CALCIUM; INGESTION; GLUCAGON; TOXICITY AB Introduction: Verapamil is a papaverine-derived calcium channel blocker widely used for the treatment of hypertension and supraventricular tachyarrhythmias. It is one of the leading agents involved in pharmaceutical poisoning-related deaths among adults.(1,2) Case Report: We report a case of severe sustained-release verapamil poisoning associated with respiratory failure in an adult man who survived after receiving 4 days of partial liquid ventilation as a part of his medical management. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Childrens Hosp, Sch Med, Massachusetts Poison Control Syst, Boston, MA 02115 USA. RP Woolf, A (reprint author), Massachusetts Poison Control Ctr, 300 Longwood Ave, Boston, MA 02115 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0731-3810 J9 J TOXICOL-CLIN TOXIC JI J. Toxicol.-Clin. Toxicol. PY 1999 VL 37 IS 4 BP 475 EP 479 PG 5 WC Toxicology SC Toxicology GA 230KJ UT WOS:000082250100006 PM 10465244 ER PT J AU Taft, CT Stern, AS King, LA King, DW AF Taft, CT Stern, AS King, LA King, DW TI Modeling physical health and functional health status: The role of combat exposure, posttraumatic stress disorder, and personal resource attributes SO JOURNAL OF TRAUMATIC STRESS LA English DT Article DE posttraumatic stress disorder; combat exposure; functional health; hardiness; social support ID VIETNAM THEATER VETERANS; PERCEIVED SOCIAL SUPPORT; PSYCHIATRIC-DISORDER; TRAUMATIC EVENTS; NATURAL DISASTER; SEX-DIFFERENCES; CAUSAL MODEL; A BEHAVIOR; HARDINESS; PREVALENCE AB This study examined associations of combat exposure and posttraumatic stress disorder (PTSD) with physical health conditions and also incorporated hardiness and social support as mediators and functional health status as an outcome. Data were derived from 1,632 male and female Vietnam veterans who participated in the National Vietnam Veterans Readjustment Study. Path analysis revealed that hardiness and social support operated primarily as intermediary variables between combat exposure and PTSD, and PTSD emerged as the pivotal variable explaining physical health conditions and functional health status. Gender-based differences in means and patterns of associations among variables were found. The results stress the importance of assessing trauma in clinical settings as a meaningful determinant of health outcomes. C1 Dept Vet Affairs Med Ctr 116B-3, Natl Ctr PTSD, Womens Hlth Sci Div, Boston, MA 02130 USA. Dept Vet Affairs Med Ctr 116B-3, Natl Ctr PTSD, Behav Sci Div, Boston, MA 02130 USA. RP King, LA (reprint author), Dept Vet Affairs Med Ctr 116B-3, Natl Ctr PTSD, Womens Hlth Sci Div, 150 S Huntington Ave, Boston, MA 02130 USA. EM KING.LYNDA@BOSTON.VA.GOV NR 69 TC 88 Z9 88 U1 3 U2 7 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD JAN PY 1999 VL 12 IS 1 BP 3 EP 23 DI 10.1023/A:1024786030358 PG 21 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 164JY UT WOS:000078461500002 PM 10027139 ER PT J AU Abbott, WM AF Abbott, WM TI Presidential address: Legend, leadership, legacy SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 52nd Annual Meeting of the Society-for-Vascular-Surgery CY JUN 07-10, 1998 CL SAN DIEGO, CALIFORNIA SP Soc Vasc Surg C1 Massachusetts Gen Hosp, Div Vasc Surg, Boston, MA 02114 USA. RP Abbott, WM (reprint author), Massachusetts Gen Hosp, Div Vasc Surg, 15 Parkman St,ACC 458, Boston, MA 02114 USA. NR 12 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 JAN PY 1999 VL 29 IS 1 BP 1 EP 7 DI 10.1016/S0741-5214(99)70344-7 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 156RU UT WOS:000078016500001 PM 9882785 ER PT J AU Debiasi, RL Squier, MKT Pike, B Wynes, M Dermody, TS Cohen, JJ Tyler, KL AF Debiasi, RL Squier, MKT Pike, B Wynes, M Dermody, TS Cohen, JJ Tyler, KL TI Reovirus-induced apoptosis is preceded by increased cellular calpain activity and is blocked by calpain inhibitors SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSFECTED SCHWANN-CELLS; EXPERIMENTAL BRAIN INJURY; FACTOR-KAPPA-B; PROTEASE INHIBITORS; MYELIN MCALPAIN; MOLECULAR-BASIS; THIOL PROTEASE; NERVOUS-SYSTEM; GROWTH-FACTORS; DNA-SYNTHESIS AB The cellular pathways of apoptosis have not been fully characterized; however, calpain, a cytosolic calcium-activated cysteine protease, has been implicated in several forms of programmed cell death. Reoviruses induce apoptosis both in vitro and in vivo and serve as a model for studying virus-induced cell death. We investigated the potential role of calpain in reovirus-induced apoptosis in vitro by measuring calpain activity as well as evaluating the effects of calpain inhibitors, L929 cells were infected with reovirus type 3 Abney (T3A), and calpain activity, measured as cleavage of the fluorogenic calpain substrate Suc-Leu-Leu-Val-Tyr-AMC, was monitored. There was a 1.6-fold increase in calpain activity in T3A-infected cells compared to mock-infected cells; this increase was completely inhibited by preincubation with calpain inhibitor I (N-acetyl-leucyl-leucyl-norleucinal [aLLN]), an active site inhibitor. Both aLLN and PD150606, a specific calpain inhibitor that interacts with the calcium-binding site, inhibited reovirus-induced apoptosis in L929 cells by 54 to 93%. Apoptosis induced by UV-inactivated reovirus was also reduced 65 to 69% by aLLN, indicating that inhibition of apoptosis by calpain inhibitors is independent of effects on viral replication. We conclude that calpain activation is a component of the regulatory cascade in reovirus-induced apoptosis. C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pediat Infect Dis, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Immunol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO 80262 USA. Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Elizabeth B Lamb Ctr Pediat Res, Nashville, TN 37232 USA. RP Tyler, KL (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol, B-182,4200 E 9th Ave, Denver, CO 80262 USA. EM Ken.Tyler@UCHSC.edu OI Tyler, Kenneth/0000-0003-3294-5888 FU NIA NIH HHS [1RO1AG14071]; NIAID NIH HHS [AI38296, R01 AI038296, R37 AI038296] NR 76 TC 77 Z9 78 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 1999 VL 73 IS 1 BP 695 EP 701 PG 7 WC Virology SC Virology GA 146YP UT WOS:000077461700076 PM 9847375 ER PT J AU Shen, HM Cheng, T Preffer, FI Dombkowski, D Tomasson, MH Golan, DE Yang, O Hofmann, W Sodroski, JG Luster, AD Scadden, DT AF Shen, HM Cheng, T Preffer, FI Dombkowski, D Tomasson, MH Golan, DE Yang, O Hofmann, W Sodroski, JG Luster, AD Scadden, DT TI Intrinsic human immunodeficiency virus type 1 resistance of hematopoietic stem cells despite coreceptor expression SO JOURNAL OF VIROLOGY LA English DT Article ID PROGENITOR CELLS; HIV-1 ENTRY; IN-VIVO; THYMOCYTE DEPLETION; NONDIVIDING CELLS; HUMAN-LYMPHOCYTES; GENE-EXPRESSION; HIGH-TITER; INFECTION; CD4 AB Interactions of human immunodeficiency virus type 1 (HIV-1) with hematopoietic stem cells may define restrictions on immune reconstitution following effective antiretroviral therapy and affect stent cell gene therapy strategies for AIDS. In the present study, we demonstrated mRNA and cell surface expression of HIV-1 receptors CD I and the chemokine receptors CCR-5 and CXCR-4 in fractionated cells representing multiple stages of hematopoietic development. Chemokine receptor function was documented in subsets of cells by calcium flux in response to a cognate ligand, Productive infection by HIV-1 via these receptors was observed with the notable exception of stem cells, in which case the presence of CD4, CXCR-4, and CCR-5, as documented by single-cell analysis for expression and function, was insufficient for infection. Neither productive infection, transgene expression, nor virus entry was detectable following exposure of stem cells to either wild-type HIV-1 or lentivirus constructs pseudotyped in HIV-1 envelopes of macrophage-tropic, T-cell-tropic, or dualtropic specificity. Successful entry into stem cells of a vesicular stomatitis virus G protein-pseudotyped HIV-I construct demonstrated that the resistance to HIV-1 was mediated at the level of virus cell membrane fusion and entry. These data define the hematopoietic stem cell as a sanctuary cell which is resistant to HIV-1 infection by a mechanism independent of receptor and coreceptor expression that suggests a novel means of cellular protection from HIV-1. C1 Massachusetts Gen Hosp, Ctr AIDS Res, Boston, MA 02129 USA. Massachusetts Gen Hosp, MGH Canc Ctr, Div Infect Dis, Boston, MA 02129 USA. Massachusetts Gen Hosp, MGH Canc Ctr, Div Hematol Oncol, Boston, MA 02129 USA. Brigham & Womens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Med Sch, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA USA. Harvard Med Sch, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA USA. Harvard Med Sch, Dept Pathol, Boston, MA USA. RP Scadden, DT (reprint author), Massachusetts Gen Hosp, Ctr AIDS Res, Bldg 149,13th St,Rm 5212D, Boston, MA 02129 USA. EM scadden.david@mgh.harvard.edu FU NHLBI NIH HHS [HL 55718, R01 HL032854, R37 HL032854, R01 HL044851, P50 HL054785, HL 44851, HL 32854]; NIAID NIH HHS [T32 AI007387] NR 43 TC 66 Z9 67 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 1999 VL 73 IS 1 BP 728 EP 737 PG 10 WC Virology SC Virology GA 146YP UT WOS:000077461700080 PM 9847379 ER PT J AU Morgan, WW Richardson, A Sharp, ZD Walter, CA AF Morgan, WW Richardson, A Sharp, ZD Walter, CA TI Application of exogenously regulatable promoter systems to transgenic models for the study of aging SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID INDUCIBLE GENE-EXPRESSION; TRANSCRIPTION FACTOR-TFIIB; MAMMALIAN-CELLS; IN-VIVO; ENHANCER PROMOTER; ACTIVATION DOMAIN; EUKARYOTIC CELLS; SKELETAL-MUSCLE; MICE; TETRACYCLINE AB Transgenic mouse and gene knockout technologies offer powerful tools for dissecting the roles of specific genes in the process of aging. The interpretation of the results of such studies is limited, however by the fact that the gene of interest is over- or underexpressed throughout the life span of the animal model. Among other problems, this situation makes it difficult to separate the effects that a specific gene has on embryological development from those that it may exert on Me subsequent maturation and aging of the animal. It is also not possible with these methods alone to alter the expression of genes ill an age-dependent fashion and to assess the effects of these alterations on the aging process. This capacity would be of particular interest in studying genes which are thought to have a role in regulating physiological homeostasis. Because they offer the opportunity to activate or render inactive the expression of genes at will, exogenously regulatable promoter systems, particularly when used in combination with traditional transgenic or gene knockout approaches, provide a new and potentially very powerful tool for studying the effect of selected genes on aging. This review discusses the merits and limitations of Be application of either the tetracycline-regulatable promoter system, the RU486-inducible promoter system, or the ecdysone-inducible promoter system to exogenously regulate the expression of a transcriptionally linked gene and to thus assess the effect of that gene on aging. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Mol Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Inst Biotechnol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. RP Morgan, WW (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78284 USA. EM morgan@UTHSCSA.edu FU NIA NIH HHS [1PO1 AG14674, P03 AG13319]; NIDDK NIH HHS [DK52543] NR 68 TC 13 Z9 14 U1 0 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 JAN PY 1999 VL 54 IS 1 BP B30 EP B40 DI 10.1093/gerona/54.1.B30 PG 11 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 159GE UT WOS:000078163200006 PM 10026653 ER PT J AU Prasad, PV Epstein, FH AF Prasad, PV Epstein, FH TI Changes in renal medullary pO(2) during water diuresis as evaluated by blood oxygenation level-dependent magnetic resonance imaging: Effects of aging and cyclooxygenase inhibition SO KIDNEY INTERNATIONAL LA English DT Article DE radiology; hypoxia; renal injury; acute renal failure; medullary oxygenation; BOLD-MRI ID THICK ASCENDING LIMB; ATPASE ACTIVITY; PROSTAGLANDIN-E2; FAILURE; RAT; HYPOXIA; INJURY AB Background. Hypoxia of the renal medulla has been implicated in the development of renal injury, particularly acute renal failure, and its regulation in humans may therefore be relevant to certain renal disorders. Changes in oxygenation of the renal medulla can now be monitored noninvasively with blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI). Using this method, water diuresis has been shown to improve medullary oxygenation in young persons. Urinary excretion of prostaglandin E-2 (PGE(2)) likewise increases during water diuresis in younger but not in older people. We used BOLD MRI to measure the effects of aging and of inhibiting prostaglandin synthetase on the renal response to water diuresis in healthy human subjects. Methods. Nine younger (25 to 31 years) and nine older (59 to 79 years) female volunteers were studied with BOLD MRI during antidiuresis in the postabsorptive state and during water diuresis. Simultaneously, urinary excretion of PGE(2) was determined. PG synthetase was inhibited by administering ibuprofen. Results. Renal medullary oxygenation, initially low, greatly improved during diuresis in younger subjects, whereas PGE(2) excretion increased. In older women, however, water diuresis elicited no change in oxygenation of renal medulla or PGE(2) excretion. Ibuprofen inhibited excretion of PGE(2) and blocked the increase in medullary oxygenation normally produced by water diuresis in the young. Conclusions. The increase in oxygenation of the renal medulla accompanying water diuresis depends on PGE(2) synthesis. Attenuation of renal PGE(2) synthesis in older people is probably responsible, at least in part, for the loss of the ability to improve medullary oxygenation that younger subjects possess. Inability to improve renal medullary oxygenation might predispose to hypoxic renal injury in older patients. C1 Beth Israel Deaconess Med Ctr E, Dept Radiol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Prasad, PV (reprint author), Beth Israel Deaconess Med Ctr E, Dept Radiol, AN 234,330 Brookline Ave, Boston, MA 02215 USA. OI Prasad, Pottumarthi/0000-0002-4214-5465 FU NCRR NIH HHS [M01-RRO-1032]; NIDDK NIH HHS [DK 18078, DK 53221, R01 DK053221, R01 DK053221-02, R01 DK053221-04] NR 22 TC 97 Z9 104 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 JAN PY 1999 VL 55 IS 1 BP 294 EP 298 DI 10.1046/j.1523-1755.1999.00237.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 150LC UT WOS:000077665500028 PM 9893139 ER PT J AU Ingelfinger, JR AF Ingelfinger, JR TI Men's kidneys are from Mars and women's, from Venus SO KIDNEY INTERNATIONAL LA English DT Editorial Material DE gender; disease progression; renin-angiotensin system; hyperfiltration ID CHRONIC-RENAL-FAILURE; HEMODYNAMICS; RATS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ingelfinger, JR (reprint author), Massachusetts Gen Hosp, ACC-709 Pediat Nephrol,15 Parkman St, Boston, MA 02114 USA. NR 13 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JAN PY 1999 VL 55 IS 1 BP 336 EP 337 DI 10.1046/j.1523-1755.1999.00263.x PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 150LC UT WOS:000077665500035 PM 9893146 ER PT J AU Ellenberger, MA Corning, BF AF Ellenberger, MA Corning, BF TI The animal care and IACUC offices: United or divided? SO LAB ANIMAL LA English DT Article AB Administrative support of the Animal Care Program and the IACUC is generally based on two major models: the same administrative team or two separate units. The authors, each of whom is a director of a facility that follows one of these models, discuss the advantages and disadvantages of each. C1 Massachusetts Gen Hosp, Ctr Comparat Resources, Boston, MA 02114 USA. RP Ellenberger, MA (reprint author), Tufts Univ, New England Med Ctr, Div Lab Anim Med, NEMC 112,171 Harrison Ave, Boston, MA 02111 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD JAN PY 1999 VL 28 IS 1 BP 44 EP 47 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA 157DF UT WOS:000078043900011 ER PT J AU Nielsen, GP Stemmer-Rachamimov, AO Ino, Y Rosenberg, AE Louis, DN AF Nielsen, GP Stemmer-Rachamimov, AO Ino, Y Rosenberg, AE Louis, DN TI Malignant transformation of neurofibroma in NF-1 patients is associated with loss of p16 protein expression SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 58 BP 13A EP 13A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600066 ER PT J AU Rosenberg, AE Bhan, AK Liebsch, N Keel, SB Nielsen, GP AF Rosenberg, AE Bhan, AK Liebsch, N Keel, SB Nielsen, GP TI Chondrosarcoma of the skull base: An immunohistochemical study of 107 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 64 BP 14A EP 14A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600072 ER PT J AU Rosenberg, AE Nielsen, GP Keel, SB Jacoby, LB MacCollin, M AF Rosenberg, AE Nielsen, GP Keel, SB Jacoby, LB MacCollin, M TI The pathology of schwannomatosis: A study of 20 tumors from 11 patients with molecular analysis of the NF2 gene. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 63 BP 14A EP 14A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600071 ER PT J AU Wehrli, BM Nielsen, GP Rosenberg, AE O'Connell, JX AF Wehrli, BM Nielsen, GP Rosenberg, AE O'Connell, JX TI Soft tissue giant cell tumor: A clinicopathologic study of 16 benign and malignant variants. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Vancouver Gen Hosp, Vancouver, BC, Canada. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 67 BP 15A EP 15A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600075 ER PT J AU Oyama, T Maluf, H Sano, T Kashiwabara, K AF Oyama, T Maluf, H Sano, T Kashiwabara, K TI Atypical cystic lobules of the breast SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Gunma Univ, Sch Med, Dept Pathol, Gunma, Japan. Washington Univ, Sch Med, Dept Pathol, St Louis, MO USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 148 BP 28A EP 28A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600156 ER PT J AU Tulecke, M Connolly, J Silver, B Recht, A Harris, J Schnitt, S AF Tulecke, M Connolly, J Silver, B Recht, A Harris, J Schnitt, S TI Extent of margin involvement and risk of local recurrence (LR) in patients with invasive breast cancer treated with conservative surgery and radiation therapy (CS+RT). SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Beth Israel Deaconess Med Ctr, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. Harvard Univ, 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 166 BP 31A EP 31A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600174 ER PT J AU House, SL Quist, WC Aretz, HT Schreiber, AD AF House, SL Quist, WC Aretz, HT Schreiber, AD TI Serum lipids and arterial plaque load are altered independently by exogenous estrogen and progesterone in hypercholesterolemic male rabbits SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. DIDMC, Boston, MA USA. Univ Penn, Sch Med, Philadelphia, PA 19104 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 198 BP 37A EP 37A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600206 ER PT J AU Amrikachi, M Ramzy, I Rone, R Green, LK AF Amrikachi, M Ramzy, I Rone, R Green, LK TI Fine needle aspiration features of gynecomastia: Possible pitfalls in cytodiagnosis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Baylor Coll Med, Methodist Hosp, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. Severance & Associates, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 215 BP 40A EP 40A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600223 ER PT J AU Faquin, WC Cooper, TL Pilch, BZ AF Faquin, WC Cooper, TL Pilch, BZ TI Fine needle aspiration biopsy of spindle cell lesions of the head and neck. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 234 BP 43A EP 43A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600242 ER PT J AU Dahiya, M Slominski, A Carlson, A Wojcik, EM Wharton, J Bahkos, R Nickoloff, BJ AF Dahiya, M Slominski, A Carlson, A Wojcik, EM Wharton, J Bahkos, R Nickoloff, BJ TI Desmoplastic malignant melanoma: Expression of POMC derived antigens, tyrosinase, and DNA content SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Loyola Univ, Ctr Med, Maywood, IL 60153 USA. Albany Med Ctr, Albany, NY 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 315 BP 56A EP 56A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600323 ER PT J AU Duncan, LM Deeds, J Duprat, L Cronin, F Morgan, J Kauffman, M AF Duncan, LM Deeds, J Duprat, L Cronin, F Morgan, J Kauffman, M TI Primary tumor down-regulation of melastatin mRNA correlates with melanoma metastasis and death. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Millennium Predict 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 317 BP 57A EP 57A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600325 ER PT J AU King, R Weilbaecher, K McGill, G Halaban, R Cooley, E Mihm, MC Fisher, DE AF King, R Weilbaecher, K McGill, G Halaban, R Cooley, E Mihm, MC Fisher, DE TI Microphthalmia transcription factor: a highly sensitive and specific nuclear marker for malignant melanoma. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dana Farber Canc Inst, Boston, MA 02114 USA. Albany Med Ctr, Albany, CA USA. Yale Univ, Sch Med, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 331 BP 59A EP 59A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600339 ER PT J AU Murphy, M Signoretti, S Kadin, ME Loda, M AF Murphy, M Signoretti, S Kadin, ME Loda, M TI Detection of clonal T-cell receptor gamma gene rearrangements in paraffin-embedded early CTCL by non-radioactive PCR-SSCP. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 345 BP 61A EP 61A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600353 ER PT J AU North, PE Waner, MW Mizeracki, A Mihm, MC AF North, PE Waner, MW Mizeracki, A Mihm, MC TI GLUT1 is a specific marker for juvenile hemangiomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Univ Arkansas Med Sci, Little Rock, AR USA. Arkansas Childrens Hosp, Little Rock, AR 72202 USA. Harvard Univ, Boston, MA 02115 USA. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 346 BP 61A EP 61A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600354 ER PT J AU Zubovits, J Yu, L Duncan, L AF Zubovits, J Yu, L Duncan, L TI S100, NK1/C3, HMB-45 and MART1 in metastatic melanoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 371 BP 66A EP 66A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600379 ER PT J AU Erickson, LA Jin, L Goellner, JR Zukerberg, LR Lloyd, RV AF Erickson, LA Jin, L Goellner, JR Zukerberg, LR Lloyd, RV TI Proliferative activity and cyclin D1 expression in Hurthle cell neoplasms. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. Massachusetts Gen Hosp, Dept Pathol, 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 378 BP 67A EP 67A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600386 ER PT J AU Yantiss, RK Rosenberg, AE AF Yantiss, RK Rosenberg, AE TI Gastrointestinal stromal tumor vs. intra-abdominal fibromatosis involving the bowel wall: A clinically significant differential diagnosis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 497 BP 87A EP 87A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600505 ER PT J AU Ayala, T Pins, A Cubilla, AL AF Ayala, T Pins, A Cubilla, AL TI Epithelial lesions associated with invasive squamous cell carcinoma of the penis. A study of 152 resected specimens SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Univ Nacl Asunc, Asuncion, Paraguay. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 506 BP 88A EP 88A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600514 ER PT J AU Cubilla, AA Philip, AT Amin, MB Cohen, C Rodriques, I Caballero, C Young, RH AF Cubilla, AA Philip, AT Amin, MB Cohen, C Rodriques, I Caballero, C Young, RH TI Cytokeratin subset distribution in histologic variants of squamous cell carcinoma (SCC) of the penis SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Univ Nacl Ascunc, Asuncion, Paraguay. Emory Univ Hosp, Atlanta, GA 30322 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 529 BP 92A EP 92A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600537 ER PT J AU Cubilla, AL Velazquez, E Pins, A Reuter, V AF Cubilla, AL Velazquez, E Pins, A Reuter, V TI Histologic classification, regional metastasis and outcome in 61 patients with primary resection of penile carcinomas SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Univ Nacl Asunc, Asuncion, Paraguay. NYU, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 530 BP 92A EP 92A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600538 ER PT J AU Philip, AT Amin, MB Cubilla, AA Young, RH AF Philip, AT Amin, MB Cubilla, AA Young, RH TI Secondary tumors of the penis: A study of 16 cases. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Emory Univ Hosp, Atlanta, GA 30322 USA. Univ Natl Asunc, Ascuncion, Paraguay. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 601 BP 104A EP 104A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600609 ER PT J AU Philip, AT Amin, MB Cubilla, AA Cohen, C Rodriguez, I Caballero, C Young, RH AF Philip, AT Amin, MB Cubilla, AA Cohen, C Rodriguez, I Caballero, C Young, RH TI Prognostic parameters in squamous cell carcinoma (SCC) of the penis. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Emory Univ Hosp, Atlanta, GA 30322 USA. Univ Nacl Ascunc, Ascuncion, Paraguay. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 600 BP 104A EP 104A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600608 ER PT J AU Quinn, TR Oliva, E Amin, MB Ehle, JN Epstein, JI Srigley, JR Young, RH AF Quinn, TR Oliva, E Amin, MB Ehle, JN Epstein, JI Srigley, JR Young, RH TI Primary malignant melanoma of the urethra. A clinicopathologic analysis of 13 cases. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Johns Hopkins Hosp, Baltimore, MD 21287 USA. Emory Univ, Atlanta, GA 30322 USA. Indiana Univ, Indianapolis, IN 46204 USA. Credit Valley Hosp, Mississauga, ON, 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 606 BP 105A EP 105A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600618 ER PT J AU Ulbright, TM Srigley, JR Reuter, VE Wojno, K Roth, LM Young, RH AF Ulbright, TM Srigley, JR Reuter, VE Wojno, K Roth, LM Young, RH TI Sex cord-stromal tumors of the testis with entrapped germ cells: A mimic of mixed germ cell/sex cord-stromal tumor SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Indiana Univ, Bloomington, IN 47405 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Michigan, Ann Arbor, MI 48109 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 629 BP 109A EP 109A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600641 ER PT J AU Velazquez, E Rodriguez, I Caballero, C Ocampos, S Ayala, E Pins, A Reuter, V Cubilla, AL AF Velazquez, E Rodriguez, I Caballero, C Ocampos, S Ayala, E Pins, A Reuter, V Cubilla, AL TI Verruciform tumors of the penis. Histologic classification of 68 cases. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Univ Nacl Asunc, Asuncion, Paraguay. NYU, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 630 BP 109A EP 109A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600642 ER PT J AU Vollmer, RT Kantoff, PW Dawson, NA Vogelzang, NJ AF Vollmer, RT Kantoff, PW Dawson, NA Vogelzang, NJ TI The relative velocity of serum PSA predicts prognosis in hormone refractory prostate cancer. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Durham, NC USA. VA Med Ctr, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. Univ Chicago, Chicago, IL 60637 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 631 BP 109A EP 109A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600643 ER PT J AU Dadmanesh, F Young, RH Clement, PB AF Dadmanesh, F Young, RH Clement, PB TI Polypoid endometriosis (PE) - A clinicopathological study of 15 cases. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Vancouver Hosp, Dept Pathol, Vancouver, BC, Canada. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 665 BP 115A EP 115A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600677 ER PT J AU Eichhorn, JH Clement, PB Young, RH Scully, RE AF Eichhorn, JH Clement, PB Young, RH Scully, RE TI Mesodermal adenosarcoma of the ovary: A study of 37 cases. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Vancouver Hosp & Hlth Sci Ctr, Vancouver, BC V5Z 1M9, Canada. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 673 BP 116A EP 116A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600685 ER PT J AU Nucci, MR Young, RH Fletcher, CDM AF Nucci, MR Young, RH Fletcher, CDM TI Cellular pseudosarcomatous fibroepithelial polyps of the lower female genital tract: An underrecognized lesion often misdiagnosed as sarcoma SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 701 BP 121A EP 121A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600713 ER PT J AU Oliva, E Young, RH Clement, PB Scully, RE AF Oliva, E Young, RH Clement, PB Scully, RE TI Fibrous and myxoid variants of endometrial stromal tumors of the uterus. A clinicopathologic analysis of 11 cases. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Vancouver Hosp & Hlth Sci Ctr, Vancouver, BC V5Z 1M9, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 703 BP 121A EP 121A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600715 ER PT J AU Turnnir, RT Young, RH Churg, A Ross, M Clement, PB AF Turnnir, RT Young, RH Churg, A Ross, M Clement, PB TI Peritoneal mesotheliomas (PMs) in women - A clinicopathologic analysis of 36 cases. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Univ British Columbia, Vancouver Hosp & Hlth Sci Ctr, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 732 BP 126A EP 126A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600744 ER PT J AU Cuadra-Garcia, I Harris, NI Proulx, GM Wu, CL Wang, CC Pilch, BZ Ferry, JA AF Cuadra-Garcia, I Harris, NI Proulx, GM Wu, CL Wang, CC Pilch, BZ Ferry, JA TI Sinonasal lymphoma: An analysis of 57 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Hosp Oncol, Inst Mexicano Del Segura Social, Mexico City, DF, Mexico. Massachusetts Gen Hosp, Boston, MA 02114 USA. Roswell Pk Canc Inst, Buffalo, 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 785 BP 135A EP 135A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600797 ER PT J AU Murphy, M Moreira, G Signoretti, S Soung, P Sherburne, B Loda, M AF Murphy, M Moreira, G Signoretti, S Soung, P Sherburne, B Loda, M TI Cdc25A and p27(Kipl) expression in human non-Hodgkin's lymphomas. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 836 BP 143A EP 143A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600848 ER PT J AU Wang, S Rosenwald, IB Hutzler, MJ Pihan, GA Schmidt, EV Savas, L Woda, BA AF Wang, S Rosenwald, IB Hutzler, MJ Pihan, GA Schmidt, EV Savas, L Woda, BA TI Expression of the eukaryotic translation initiation factors 4E and 2 alpha in non-Hodgkins lymphomas. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Univ Massachusetts, Med Ctr, Worcester, MA USA. 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 863 BP 148A EP 148A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600875 ER PT J AU Wu, CL Wang, RJ Kawai, T Wang, F Harris, NL Sachs, DH Cosimi, AB Colvin, RB AF Wu, CL Wang, RJ Kawai, T Wang, F Harris, NL Sachs, DH Cosimi, AB Colvin, RB TI Post-transplant lymphoproliferative disorder in non-human primates SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 871 BP 149A EP 149A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600883 ER PT J AU Mauiyyedi, S Della Pelle, P Saidman, S Collins, AB Pascual, M Tolkoff-Rubin, N Schneeberger, E Colvin, RB AF Mauiyyedi, S Della Pelle, P Saidman, S Collins, AB Pascual, M Tolkoff-Rubin, N Schneeberger, E Colvin, RB TI C4d deposits in peritubular capillaries (PTC) in chronic renal allograft rejection (CR). SO LABORATORY INVESTIGATION 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 914 BP 156A EP 156A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600926 ER PT J AU Mauiyyedi, S Williams, WW Tolkoff-Rubin, N Schneeberger, EE Colvin, RB AF Mauiyyedi, S Williams, WW Tolkoff-Rubin, N Schneeberger, EE Colvin, RB TI Glomerulopathy in chronic cyclosporine toxicity (CsAT) in non-renal transplant cases. SO LABORATORY INVESTIGATION 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 913 BP 156A EP 156A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600925 ER PT J AU vanGorder, M Della Pelle, P Henson, JW Sachs, DH Cosimi, AB Colvin, RB AF vanGorder, M Della Pelle, P Henson, JW Sachs, DH Cosimi, AB Colvin, RB TI A novel polyomavirus causes interstitial nephritis, ureteritis and enteritis in immunosuppressed cynomolgus monkeys SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Little Co Mary Hosp, Torrance, 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 928 BP 158A EP 158A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600940 ER PT J AU Chang, H Odze, R Compton, C AF Chang, H Odze, R Compton, C TI Focal exocrine differentiation in pancreatic endocrine tumors. SO LABORATORY INVESTIGATION 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 943 BP 161A EP 161A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376600955 ER PT J AU de la Monte, SM Gemelli, B Brown, NV Wands, JR AF de la Monte, SM Gemelli, B Brown, NV Wands, JR TI Aspartyl (asparaginyl) beta hydroxylase (AAH) expression marks invasiveness of primary malignant CNS neoplasms. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 1000 BP 170A EP 170A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376601012 ER PT J AU de la Monte, SM Luong, T Wands, JR AF de la Monte, SM Luong, T Wands, JR TI Mitochondrial DNA damage as a novel mechanism of cell loss in Alzheimer's disease (AD). SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 1001 BP 171A EP 171A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376601013 ER PT J AU Khuu, H Conner, M Shultz, J Vanderkwaak, T Alvarez, R Curiel, D Siegal, GP AF Khuu, H Conner, M Shultz, J Vanderkwaak, T Alvarez, R Curiel, D Siegal, GP TI Coxsackie-adenovirus receptor (CAR) is a universal marker for ovarian tumors of epithelial derivation. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Univ Alabama, Birmingham, AL USA. Birmingham VAMC, Birmingham, AL USA. RI Siegal, Gene/A-8653-2009 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 1030 BP 175A EP 175A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376601042 ER PT J AU Ligon, KL Roberts, D Weremowicz, S Quade, B AF Ligon, KL Roberts, D Weremowicz, S Quade, B TI Identification of lethal fetal leukemias and distinction of fetal from maternal origin. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 1054 BP 179A EP 179A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376601066 ER PT J AU Cai, YC Roggli, VL Mark, E Xu, X Cagle, PT Seaver, S Savas, L Fraire, AE AF Cai, YC Roggli, VL Mark, E Xu, X Cagle, PT Seaver, S Savas, L Fraire, AE TI Epidermal growth factor receptor (EGFR) in reactive mesothelial proliferations, epithelial malignant mesothelioma and carcinoma of lung: A study of 114 cases SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Duke Univ, Durham, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Massachusetts, Sch Med, Worcester, 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 1069 BP 182A EP 182A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376601081 ER PT J AU Dickersin, GR Selig, M Rosenberg, AE Nielsen, GP AF Dickersin, GR Selig, M Rosenberg, AE Nielsen, GP TI Hyalinizing spindle cell tumor with giant rosettes. An ultrastructural study. SO LABORATORY INVESTIGATION 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 LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 1148 BP 195A EP 195A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376601160 ER PT J AU Dickersin, GR Rubin, B Selig, M Rosenberg, AE Nielsen, GP AF Dickersin, GR Rubin, B Selig, M Rosenberg, AE Nielsen, GP TI Ultrastructural findings in keratin positive Ewing's sarcoma/PNET. SO LABORATORY INVESTIGATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, 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 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JAN PY 1999 VL 79 IS 1 MA 1147 BP 195A EP 195A PG 1 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 162YZ UT WOS:000078376601159 ER PT J AU Machens, HG Morgan, JR Berthiaume, F Weich, HA Funke, M Rohde, U Siemers, F Berger, AC AF Machens, HG Morgan, JR Berthiaume, F Weich, HA Funke, M Rohde, U Siemers, F Berger, AC TI Functional angiogenesis in the rat epigastric island flap after genetic modification of fibroblasts is ischemia-dependent SO LANGENBECKS ARCHIVES OF SURGERY LA German DT Article ID RECOMBINANT RETROVIRUSES AB Background: Our previous studies have shown that angiogenesis can be induced in flap tissue by means of genetic modification and transplantation of isogenic cells. Methods: Isogenic rat fibroblasts (female Lewis inbreds) were grown, harvested, cultured and retrovirally transfected to produce PD GF-AA, an angiogenetically active protein. Stable gene expression was monitored by PDGF-AA ELISA. 80 animals were divided into 2 groups (I and II) with each 4 subgroups with 10 animals (I.I.-I.IV and II.I-II.IV). The angiogenic target was a 7 x 7 cm epigastric island flap, based on the right inferior epigastric pedicle. This flap represents after elevation and replacement into its wound bed a flap necrosis model for the non-pedicled left flap side. Group I received nap treatment 1 week prior to flap elevation by injection of a test substance into its panniculus carnosus: 10(7) GMFB (genetically modified fibroblasts) plusl ml DMEM as medium (I.I), 10(7) NMFB (non modified fibroblasts) plus 1 ml medium (I.II), 1 ml DMEM (I.III) and 1 ml NaCl 0.9% as a control (I.IV). Group II had the same flap treatment at the day of flap elevation. All flaps were sutured back and the animals provided with an autocannibalism protector. 7 days later, the flaps were harvested, the amount of necrosis measured and histologically/immunhistochemically examined. Results: In vitro the GMFB produced up th 560 - times more PDGF-AA than the NMFB for at least 6 cell generations. In vivo Group II.I developed significantly less flap necrosis compared to all other groups, including group I.I. Accordingly, only group II.I gave histological and immunhistochemical evidence for massive angiogenesis within the flap tissue. Fibroblasts persisted in all flaps of groups I.I,I.II.,II.I. and II.II without major inflammatory reaction. Conclusion: 1. After retroviral gene transfer isogenic rat fibroblasts produce high amounts of PDGF-AA. 2. Both GMFB and NMFB can be successfully transplanted into the panniculus carnosus in this model. 3. PDGF-AA produced by GMFB can induce flap angiogenesis only under ischemic conditions in this model. 4. PDGF-AA induced angiogenesis results in significantly higher flap survival in this model. C1 Med Hsch Hannover, Klin Plast Hand & Wiederherstellungschirurg, Hannover, Germany. Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Shriners Burns Inst, Boston, MA 02114 USA. Gesell Biomed Forsch, Braunschweig, Germany. RP Machens, HG (reprint author), Med Hsch Hannover, Klin Plast Hand & Wiederherstellungschirurg, Hannover, Germany. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1435-2443 J9 LANGENBECK ARCH SURG JI Langenbecks Arch. Surg. PY 1999 SU 1 BP 137 EP 143 PG 7 WC Surgery SC Surgery GA 184GE UT WOS:000079601800029 ER PT J AU Heckenkamp, J Schmitz-Rixen, T Adili, F Leszczynski, D LaMuraglia, GM AF Heckenkamp, J Schmitz-Rixen, T Adili, F Leszczynski, D LaMuraglia, GM TI Effects of ionizing irradiation on vascular smooth muscle cells and matrix: Implications for inhibiting post-interventional restenosis SO LANGENBECKS ARCHIVES OF SURGERY LA German DT Article ID HYPERPLASIA AB Background: Ionizing irradiation (gamma-RT) has been shown to inhibit post-interventional vascular restenosis but there is limited understanding about the underlying mechanisms. Methods: gamma-RT (10, 20 Gy) were applied to vascular smooth muscle cells (SMC) in vitro and to cell culture plates coated with extracellular matrix. Cell viability (tetrazolium salt), proliferation (H-3-thymidine), collagen synthesis (H-3-proline), collagen I mRNA expression (RT-PCR) and conditioned media experiments were used to asses gamma-RT effects on the vascular fibroproliferative response. Results: gamma-RT reduced cellular proliferation to 24% +/- 2.7 (10 Gy) and 31% +/- 3.0 (20 Gy), controls: 100% +/- 5.3; p < 0.0001, but did not affect metabolic activity. Stimulation with calf serum increased mitochondrial activity (162% +/- 8.2 (10 Gy) and 150% +/- 9.7 (20 Gy); p < 0.0001). Collagen synthesis decreased after 7 days (55% +/- 5.5, controls: 100% +/- 8.4), but was also stimulable with calf serum (81% +/- 5.8; p < 0.001). Collagen I mRNA expression did not change in all groups. gamma-RT did not affect cell and matrix associated growth factors. Conclusions: These data suggest that gamma-RT may inhibit restenosis by inducing growth arrest of smooth muscle cells. However, irradiated cells continue to respond to growth factor stimulation and can increase their collagen production. gamma-RT with in vivo used doses does not interfere with growth factors leading to the vascular fibroproliferative response. C1 Univ Cologne, Klin & Poliklin Visceral & Gefasschirurg, D-50931 Cologne, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Vasc Surg,Wellman Labs Photomed, Boston, MA USA. Univ Frankfurt, Schwerpunkt Gefasschirurg, Frankfurt, Germany. RP Heckenkamp, J (reprint author), Univ Cologne, Klin & Poliklin Visceral & Gefasschirurg, Joseph Stelzmann Str 9, D-50931 Cologne, Germany. NR 6 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1435-2443 J9 LANGENBECK ARCH SURG JI Langenbecks Arch. Surg. PY 1999 SU 1 BP 759 EP 764 PG 6 WC Surgery SC Surgery GA 184GE UT WOS:000079601800151 ER PT S AU Kollias, N Tian, WD Zonios, G Brancaleon, L Gillies, R AF Kollias, N Tian, WD Zonios, G Brancaleon, L Gillies, R BE Anderson, RR Bartels, KE Bass, LS Bornhop, DJ Garrett, CG Gregory, KW Kollias, N Lui, H Malek, RS Perlmutter, AP Reidenbach, HD Reinisch, L Robinson, DS Tate, LP Trowers, EA TI UV radiation at the fluorescence excitation maxima produces significant changes in the fluorescence of skin SO LASERS IN SURGERY: ADVANCED CHARACTERIZATION, THERAPEUTICS, AND SYSTEMS IX, PROCEEDINGS OF SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Lasers in Surgery - Advanced Characterization, Therapeutic, and Systems IX CY JAN 23-24, 1999 CL SAN JOSE, CA SP SPIE, Int Biomed Opt Soc ID AUTOFLUORESCENCE AB Fluorescence excitation spectra of skin (human and animal models) have been determined to be stable and reproducible. Three major bands dominate the wavelength range 280-400 nm. The major epidermal band due to tryptophan moieties appears at 295+/-5 nm and the major dermal bands due to collagen cross links appear at 335+/-5 nm (pepsin digestible collagen cross links, PDCCL) and at 370+/-5 nm (collagenase digestible collagen cross links, CDCCL). The tryptophan fluorescence intensity has been found to increase with exposure to ultraviolet radiation; the UVB wavelengths (280-320 nm) are more effective than the UVA wavelengths (320-400 nm). The PDCCL fluorescence intensity has been found to decrease dramatically with exposure to UVA in a wavelength specific way. The maximum of the action spectrum for this process is centered at the maximum of the excitation spectrum. The fluorescence of the skin recovers within 24 hr, following exposure to UVA from single exposures. Multiple exposures produce permanent changes, in a follow-up of 8 weeks. The changes in the tryptophan fluorescence are probably due to changes in the molecular environment brought about by changes in the electrolyte balance in the epidermis following exposure. The changes in the dermis following UVA exposure appear to be associated with changes in the collagen cross links, either through their association with other dermal species leading to quenching of the fluorescence or by the formation of stronger cross links with a smaller quantum efficiency. As these changes are immediate both alterations may provide the means for in vivo UV dosimetry. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. RP Kollias, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA 02114 USA. NR 10 TC 0 Z9 0 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3060-9 J9 P SOC PHOTO-OPT INS PY 1999 VL 3590 BP 52 EP 55 DI 10.1117/12.350994 PG 4 WC Cardiac & Cardiovascular Systems; Dermatology; Gastroenterology & Hepatology; Optics; Otorhinolaryngology; Surgery; Urology & Nephrology; Veterinary Sciences SC Cardiovascular System & Cardiology; Dermatology; Gastroenterology & Hepatology; Optics; Otorhinolaryngology; Surgery; Urology & Nephrology; Veterinary Sciences GA BN29C UT WOS:000081436000006 ER PT S AU Gonzalez, S Rajadhyaksha, M Anderson, RR AF Gonzalez, S Rajadhyaksha, M Anderson, RR BE Anderson, RR Bartels, KE Bass, LS Bornhop, DJ Garrett, CG Gregory, KW Kollias, N Lui, H Malek, RS Perlmutter, AP Reidenbach, HD Reinisch, L Robinson, DS Tate, LP Trowers, EA TI Confocal imaging of benign and malignant proliferative skin lesions in vivo SO LASERS IN SURGERY: ADVANCED CHARACTERIZATION, THERAPEUTICS, AND SYSTEMS IX, PROCEEDINGS OF SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Lasers in Surgery - Advanced Characterization, Therapeutic, and Systems IX CY JAN 23-24, 1999 CL SAN JOSE, CA SP SPIE, Int Biomed Opt Soc DE psoriasis; basal cell carcinoma; squamous cell carcinoma; microscopy; real-time; confocal microscopy; vital microscopy; confocal imaging; skin imaging; skin morphometrics ID IN-VIVO; KERATINOCYTES; MICROSCOPY AB Near-infrared confocal reflectance microscopy (CM) provides non-invasive real-time images of thin en-face tissue sections with high resolution and contrast. Imaging of cells, nuclei, other organelles, microvessels, and hair follicles has been possible at resolution comparable to standard histology, to a maximum depth of 250-300 mu m in human skin in vivo. We have characterized psoriasis as a prototype of benign proliferative skin conditions, and non-pigmented skin malignancies in vivo (basal and squamous cell carcinomas -BCC, SCC-) based on their unstained, native histologic features using CM. Our data shows that reflectance CM may potentially diagnose and morphometrically evaluate proliferative skin lesions in vivo. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. RP Gonzalez, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3060-9 J9 P SOC PHOTO-OPT INS PY 1999 VL 3590 BP 56 EP 65 DI 10.1117/12.351007 PG 10 WC Cardiac & Cardiovascular Systems; Dermatology; Gastroenterology & Hepatology; Optics; Otorhinolaryngology; Surgery; Urology & Nephrology; Veterinary Sciences SC Cardiovascular System & Cardiology; Dermatology; Gastroenterology & Hepatology; Optics; Otorhinolaryngology; Surgery; Urology & Nephrology; Veterinary Sciences GA BN29C UT WOS:000081436000007 ER PT J AU Gonzalez, S White, WM Rajadhyaksha, M Anderson, RR Gonzalez, E AF Gonzalez, S White, WM Rajadhyaksha, M Anderson, RR Gonzalez, E TI Confocal imaging of sebaceous gland hyperplasia in vivo to assess efficacy and mechanism of pulsed dye laser treatment SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE vascular lesion; in vivo confocal imaging; noninvasive method ID IN-VIVO; MICROSCOPY; SKIN AB Background and Objective: This case demonstrates, for the first time, the use of in vivo confocal imaging to assess the efficacy of laser treatment of a skin lesion with a vascular component. Study Design/Patient and Method A patient with lesions of sebaceous gland hyperplasia was histologically imaged in vivo before and after treatment with a 585 nm pulse dye laser (PDL) by using a near-infrared, confocal reflectance microscope. Hyperplastic sebaceous ducts and sebaceous glands were seen with high resolution in vivo. Prominent dermal vasculature was viewed as well as its selective targeting by PDL. Conclusion: Our results confirm the previously reported successful treatment of sebaceous gland hyperplasia with the 585 nm PDL. Lasers Surg. Med. 25:8-12, 1999. (C) 1999 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed,Dermatol Laser Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dermatol Laser Ctr,Dermatol Dept, Boston, MA 02114 USA. RP Gonzalez, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed,Dermatol Laser Ctr, BHX-630,55 Fruit St, Boston, MA 02114 USA. NR 8 TC 37 Z9 37 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 1999 VL 25 IS 1 BP 8 EP 12 DI 10.1002/(SICI)1096-9101(1999)25:1<8::AID-LSM2>3.0.CO;2-8 PG 5 WC Dermatology; Surgery SC Dermatology; Surgery GA 223CH UT WOS:000081822000002 PM 10421881 ER PT J AU Ross, EV Barnette, DJ Glatter, RD Grevelink, JM AF Ross, EV Barnette, DJ Glatter, RD Grevelink, JM TI Effects of overlap and pass number in CO2, laser skin resurfacing: A study of residual thermal damage, cell death, and wound healing SO LASERS IN SURGERY AND MEDICINE LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the American-Society-of-Laser-Medicine-and-Surgery CY APR 04-06, 1997 CL PHOENIX, ARIZONA SP Amer Soc Laser Med & Surg DE time constant; critical frequency; transition zone; scarring; thermal relaxation time ID CARBON-DIOXIDE LASER; CO2-LASER TISSUE ABLATION; PULSED CO2-LASER; RHYTIDES; DURATION; SURGERY AB Background: Newer CO2 laser systems incorporating short pulse and scanning technology have been used effectively to resurface the skin. As the number of resurfacing cases has increased, hypertrophic scarring has been reported more commonly. Previous dermabrasion and continuous wave CO2 studies have suggested that depth of injury and thermal damage are important predictors of scarring for a given anatomic region. To determine whether rapid overlapping of laser pulses/scans significantly altered wound healing, we examined residual thermal damage, cell death, and histologic and clinical wound healing in a farm pig. Methods and Materials: Two popular CO2 systems were used, with a range of radiant exposures, degrees of overlap, and numbers of passes. Thermal damage was assessed by histology, and dermal cell viability was measured with nitrotetrazolium blue staining. Presence or absence of clinical scarring was determined by textural change and loss of skin markings. Results: We observed that dermal thermal damage did not increase significantly with pass number when performed as in the normal clinical setting (for 2-4 passes); however, by delivering rapidly overlapping pulses and scans, residual thermal damage and cell death depth were increased as much as 100% over areas without immediate overlap of laser impacts. Conclusions: Immediate overlapping of CO2 laser pulses and scans is a significant risk factor in increasing thermal damage, cell death, and possibly scarring. Lasers Surg. Med. 24:103-112, 1999. Published 1999 Wiley-Liss, Inc.dagger C1 USN, Med Ctr, Dept Dermatol, San Diego, CA 92134 USA. Massachusetts Gen Hosp, Dermatol Laser Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Ross, EV (reprint author), USN, Med Ctr, Dept Dermatol, 34800 Bob Wilson Dr, San Diego, CA 92134 USA. NR 32 TC 27 Z9 30 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 1999 VL 24 IS 2 BP 103 EP 112 DI 10.1002/(SICI)1096-9101(1999)24:2<103::AID-LSM5>3.0.CO;2-B PG 10 WC Dermatology; Surgery SC Dermatology; Surgery GA 173WZ UT WOS:000079003900005 PM 10100647 ER PT J AU Parekh, SG Trauner, KB Zarins, B Foster, TE Anderson, RR AF Parekh, SG Trauner, KB Zarins, B Foster, TE Anderson, RR TI Photodynamic modulation of wound healing with BPD-MA and GASP SO LASERS IN SURGERY AND MEDICINE LA English DT Article DE cytokines; rat incisional wound model; photosensitizer; scarring ID INTIMAL HYPERPLASIA; RAT SKIN; THERAPY; LASER; TGF-BETA(1); SENSITIZERS; ANTIBODY; SURGERY AB Background and Objective: Wound healing is an intricate process requiring the orchestration of cells, growth factors, cytokines, and the extracellular matrix. Cytokines, specifically TC;Fp, are believed to be instrumental in sustaining the fibrotic process, which leads to scarring. Photodynamic therapy (PDT) uses potent photosensitizers, which induce a wide range of effects on cells and the extracellular matrix. The influences of PDT on wound healing are not well known. Study Design/Materials and Methods: Seven full-thickness incisional wounds were placed on each of 24 hairless Sprague Dawly rats, three wounds on one flank serving as dark controls and four on the contralateral side treated with PDT. Wounds were created two days before, one hour before, or one hour after red light exposure with an argon ion pumped dye laser. Twelve rats were injected with 0.25 mg/kg or 0.5 mg/kg of the PDT drug, BPD-MA, and the other 12 with 5 mg/kg or 10 mg/kg of the PDT drug, GASP, 3 and 24 hours prior to irradiation of light, respectively. At low doses of both photosensitizers, animals were irradiated with 1, 5, 10, and 20 J/cm(2). At higher doses of BPD-MA and GASP animals were treated with 10, 20, 50, and 100 J/cm2 of light. Wounds were examined each day for 14 days and noted for edema, erythema, inflammation, necrosis, and quality of scarring. Wounds were also photographed at day 0, 2, 5, 8, and 14 post-irradiation. All animals were sacrificed 14 days after irradiation and the wounds were evaluated by light microscopy. Results: Grossly, animals treated with 0.25 mg/kg BPD-MA showed no effect with PDT. Animals treated with 0.5 mg/kg BPD, and 5 and 10 mg/kg GASP showed responses that varied with both light and drug dose. Erythema, edema, inflammation, and necrosis attributed to PDT were all observed, but there was no apparent influence of PDT on either the rate or final appearance of wound healing. Histologically, there were no apparent differences between treated and untreated sites, regardless of the drug, dose of light, or time of irradiation. Conclusion: A single PDT treatment given before or after skin wounds does not apparently alter wound healing even when PDT caused brisk inflammatory reactions. PDT may have effects that were not detected. We conclude that PDT does not greatly influence incisional skin wound healing in the rat model. (C) 1999 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Ellison Sports Med Lab, Boston, MA 02114 USA. RP Anderson, RR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed,Ellison Sports Med Lab, 50 Blossom St, Boston, MA 02114 USA. NR 19 TC 22 Z9 23 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 1999 VL 24 IS 5 BP 375 EP 381 DI 10.1002/(SICI)1096-9101(1999)24:5<375::AID-LSM8>3.0.CO;2-B PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 210QW UT WOS:000081117000008 PM 10406478 ER PT J AU Schultze, JL AF Schultze, JL TI Why do B cell lymphoma fail to elicit clinically sufficient T cell immune responses? SO LEUKEMIA & LYMPHOMA LA English DT Article DE lymphoma; tolerance; anergy; T lymphocyte; CD40 ID NON-HODGKINS-LYMPHOMA; GROWTH-FACTOR-BETA; SIGNAL-TRANSDUCTION MOLECULES; MURINE DENDRITIC CELLS; TUMOR-BEARING MICE; IN-VIVO; IMMUNOGLOBULIN IDIOTYPE; CLASS-II; LYMPHOCYTES-T; TRANSPLANTATION TOLERANCE AB There is no doubt that human B cell lymphoma does not elicit a clinically sufficient T cell mediated immune response that results in tumor rejection. However, the mechanisms leading to this lack of T cell recognition and effector function are still not fully understood. Many potential mechanisms such as "ignorance" including "antigen silencing", "tolerance" including "infectious tolerance" and "anegy" or "immunosuppression" have been identified in different model systems and all these could, in part, account for the lack of immune recognition in B cell lymphoma. Malignant B cells are poor antigen presenting cells and T cells in close proximity to the malignant cells are hyporesponsive with defects in T cell receptor signaling and cytotoxic effector function. This review will discuss recent in vitro findings in context of in vivo data in murine model systems relevant to B cell lymphoma. Understanding these complex defects of anti-lymphoma immune responses should allow us to redefine our immunotherapeutic strategies to overcome these defects and induce clinically sufficient T cell mediated immune responses. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Med, Dept Adult Oncol,Dis Ctr Hematol Oncol, Boston, MA 02115 USA. RP Schultze, JL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Med, Dept Adult Oncol,Dis Ctr Hematol Oncol, 44 Binney St, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 99 TC 9 Z9 9 U1 0 U2 2 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING, BERKS, ENGLAND RG1 8JL SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD JAN PY 1999 VL 32 IS 3-4 BP 223 EP + PG 17 WC Oncology; Hematology SC Oncology; Hematology GA 165FH UT WOS:000078509600003 PM 10037020 ER PT J AU Laposata, M AF Laposata, M TI Fatty acid ethyl esters: Nonoxidative ethanol metabolites with emerging biological and clinical significance SO LIPIDS LA English DT Article; Proceedings Paper CT 3rd Congress of the International-Society-for-the-Study-of-Fatty-Acids-and-Lipids CY JUN 01-05, 1998 CL LYON, FRANCE SP Int Soc Study Fatty Acids & Lipids ID LOW-DENSITY-LIPOPROTEIN; HUMAN-BRAIN; SYNTHASE; PURIFICATION; CELLS; BLOOD; ALCOHOL; ALBUMIN; MARKERS; ORGANS C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,Div Lab Med, Boston, MA 02115 USA. RP Laposata, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,Div Lab Med, Boston, MA 02115 USA. NR 29 TC 16 Z9 16 U1 0 U2 0 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0024-4201 J9 LIPIDS JI Lipids PY 1999 VL 34 SU S BP S281 EP S285 DI 10.1007/BF02562318 PG 5 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 215PA UT WOS:000081389000099 PM 10419178 ER PT J AU Muszbek, L Haramura, G Cluette-Brown, JE Van Cott, EM Laposata, M AF Muszbek, L Haramura, G Cluette-Brown, JE Van Cott, EM Laposata, M TI The pool of fatty acids covalently bound to platelet proteins by thioester linkages can be altered by exogenously supplied fatty acids SO LIPIDS LA English DT Article; Proceedings Paper CT 3rd Congress of the International-Society-for-the-Study-of-Fatty-Acids-and-Lipids CY JUN 01-05, 1998 CL LYON, FRANCE SP Int Soc Study Fatty Acids & Lipids ID GLYCOSYL-PHOSPHATIDYLINOSITOL; PALMITOYLATION; PALMITATE; ACYLATION; RECEPTOR; SIGNAL AB The goals of this investigation were, first, to develop a chemical strategy to identify and quantitate the mass of fatty acid which is covalently bound to proteins by thioester linkage in unactivated platelets, and, second, to determine whether exogeneously added fatty acids can alter the fatty acid composition of thioester bound fatty acids. Studies with radiolabeled fatty acids cannot identify and quantitate the actual fatty acids bound to proteins because they permit;analysis of only the radiolabeled fatty acids added and their metabolites. Therefore, in the absence of metabolic labeling by radiolabeled fatty acids, we isolated the thioester-linked fatty acids from platelet proteins using hydroxylamine at neutral pH to form fatty acid hydroxamates. The hydroxamates were subsequently converted to fatty acid methyl esters by acid methanolysis for quantitation by gas chromatography-mass spectrometry. Using platelet specimens from 14 subjects, 74% of the fatty acid recovered from the unactivated platelet proteins as thioester linked was palmitate. Importantly, however, 22% was stearic acid, and oleate was 4% of the total thioester bound fatty acid. There was minimal variability (2.6-fold at maximum) between the subjects in the amount of the thioester-linked palmitate and thioester-linked stearate. However, there was substantial variability (>100-fold at maximum) between subjects in the amount of thioester-linked oleate. We also demonstrated that incubation of platelets with exogenous fatty acids can alter the profile of fatty acids bound to platelet proteins by thioester linkages. Incubation of platelets with 100 mu M palmitate for 3 h increased the amount of thioester-linked palmitate by up to 26%, and incubation of platelets with 100 CIM stearate increased the amount of thioester;linked stearate up to 30%. In support:of the observation that radiolabeled fatty acids other than palmitate were shown to be capable of binding to platelet proteins by thioester linkage, our results indicate that the fatty acids actually bound to unactivated platelet proteins include a significant amount of stearate, and variable amounts of oleate, as well as palmitate. In addition, the data show that palmitate and stearate can be increased, as a percentage of total protein-bound fatty acid, by incubation with exogenous palmitate and stearate, respectively. C1 Massachusetts Gen Hosp, Clin Labs, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Debrecen Univ Med, Sch Med, Dept Clin Chem, H-4012 Debrecen, Hungary. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Clin Labs, Dept Pathol, Div Lab Med, Room 235,Gray Bldg, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-37454, P30 DK-40561] NR 18 TC 8 Z9 8 U1 0 U2 3 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0024-4201 J9 LIPIDS JI Lipids PY 1999 VL 34 SU S BP S331 EP S337 DI 10.1007/BF02562334 PG 7 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 215PA UT WOS:000081389000115 PM 10419194 ER PT J AU Fraser, PA Lu, LY DeCeulaer, K Schur, PH Fici, D Awdeh, Z Ding, WZ Levitan, E Lew, R Uko, G Gonzalez, C AF Fraser, PA Lu, LY DeCeulaer, K Schur, PH Fici, D Awdeh, Z Ding, WZ Levitan, E Lew, R Uko, G Gonzalez, C TI CD4 TCRBV CDR3 analysis in prevalent SLE cases from two ethnic groups SO LUPUS LA English DT Article DE CD plus Tcells; SLE; disease activity ID SYSTEMIC LUPUS-ERYTHEMATOSUS; RESTRICTED JUNCTIONAL DIVERSITY; CELL-RECEPTOR REPERTOIRE; ANTI-DNA AUTOANTIBODIES; T-HELPER CELLS; RHEUMATOID-ARTHRITIS; HLA-DR; BETA-CHAIN; AFRICAN-AMERICANS; PERIPHERAL-BLOOD AB We examined CD4 + T cell TCRBV-CDR3 transcripts from 19 lupus patients and 16 controls to test the hypothesis that CD4 + TCRBV-CDR3 expression in SLE differs from normals. Within the disease group we also performed exploratory analyses to determine the association between risk of oligoclonality and HLA-DRB specificities and the duration of the CDR3 patterns. Oligoclonal patterns consistent with CDR3 restriction were three times more likely in SLE than in controls (OR = 3.7). TCRBV1, BV4, BV5.1, BV7, BV9, BV18 and BV22 gene segment CDR3 patterns of oligoclonality were seen exclusively among lupus patients. HLA-DRB3 increased the risk of oligoclonal expression in SLE. In four patients studied over time, the pattern of TCRBV-CDR3 expression was stable in a second sample obtained 6-14 months later. The increased frequency of CD4 + T cell TCRBV-CDR3 oligoclonal expression in SLE when compared to controls and the persistence of these patterns are consistent with an expanded pool of autoreactive CD4 T cells in SLE which recognize peptides derived from autoantigens. The association of HLA-DRB3 genes with increased risk of CDR3 oligoclonality among the SLE subjects is compatible with the hypothesis that molecules encoded by HLA-DRB3 may facilitate autoantigen recognition by CD4 T cells. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. Univ W Indies, Univ Hosp, Kingston 7, Jamaica. Vet Gen Hosp, Kaohsiung, Taiwan. RP Fraser, PA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL29883-13]; NIAID NIH HHS [AI42374-02]; NIAMS NIH HHS [AR-43523-03] NR 53 TC 8 Z9 12 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PY 1999 VL 8 IS 4 BP 311 EP 319 DI 10.1191/096120399678847902 PG 9 WC Rheumatology SC Rheumatology GA 209GA UT WOS:000081038800012 PM 10413211 ER PT B AU Hope, BT AF Hope, BT BE Nahas, GG Sutin, KM Harvey, D Agurell, S Pace, N Cancro, R TI Cocaine and a mechanism for long-term changes in gene expression SO MARIHUANA AND MEDICINE LA English DT Proceedings Paper CT Conference on Marihuana and Medicine CY MAR 20-21, 1998 CL NEW YORK UNIV SCH MED, NEW YORK, NY SP Stuart Mott Fdn, Helen Clay Frick Fdn, Jeremiah Milibank Fdn, Astra Pain Control, Swedish Acad Pharm Sci HO NEW YORK UNIV SCH MED ID C-FOS; MOLECULAR MECHANISMS; DRUG-ADDICTION; ACTIVATION; COMPLEX; JUN C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. RP Hope, BT (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 0-89603-593-X PY 1999 BP 213 EP 222 PG 10 WC Substance Abuse; Medicine, Legal; Pharmacology & Pharmacy SC Substance Abuse; Legal Medicine; Pharmacology & Pharmacy GA BM81E UT WOS:000079827200022 ER PT S AU Carroll, M AF Carroll, M BE Melchers, F Potter, M TI Negative selection of self-reactive B lymphocytes involves complement SO MECHANISMS OF B CELL NEOPLASIA 1998 SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Mechanisms of B Cell Neoplasia 1998 CY OCT 04-06, 1998 CL BASEL INST IMMUNOL, BASEL, SWITZERLAND SP Basel Inst Immunol HO BASEL INST IMMUNOL ID TOLERANCE; CELLS; IMMUNITY; MICE; DEFICIENCY; THRESHOLDS; INDUCTION; DELETION C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Carroll, M (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 21 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-65759-2 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1999 VL 246 BP 21 EP 29 PG 9 WC Cell Biology; Immunology; Microbiology SC Cell Biology; Immunology; Microbiology GA BN78A UT WOS:000082904200003 PM 10396035 ER PT S AU Carroll, M AF Carroll, M BE Melchers, F Potter, M TI Role of complement receptors CD21/CD35 in B lymphocyte activation and survival SO MECHANISMS OF B CELL NEOPLASIA 1998 SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Mechanisms of B Cell Neoplasia 1998 CY OCT 04-06, 1998 CL BASEL INST IMMUNOL, BASEL, SWITZERLAND SP Basel Inst Immunol HO BASEL INST IMMUNOL ID FOLLICULAR DENDRITIC CELLS; HUMORAL IMMUNE-RESPONSE; CLASSICAL PATHWAY; GERMINAL-CENTERS; INNATE IMMUNITY; MICE DEFICIENT; ANTIGEN; EXPRESSION; INDUCTION; APOPTOSIS C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Carroll, M (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 27 TC 15 Z9 15 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-65759-2 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1999 VL 246 BP 63 EP 69 PG 7 WC Cell Biology; Immunology; Microbiology SC Cell Biology; Immunology; Microbiology GA BN78A UT WOS:000082904200008 PM 10396040 ER PT S AU Ghia, P Schaniel, C Rolink, AG Nadler, LM Cardoso, AA AF Ghia, P Schaniel, C Rolink, AG Nadler, LM Cardoso, AA BE Melchers, F Potter, M TI Human macrophage-derived chemokine (MDC) is strongly expressed following activation of both normal and malignant precursor and mature B cells SO MECHANISMS OF B CELL NEOPLASIA 1998 SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Mechanisms of B Cell Neoplasia 1998 CY OCT 04-06, 1998 CL BASEL INST IMMUNOL, BASEL, SWITZERLAND SP Basel Inst Immunol HO BASEL INST IMMUNOL ID DENDRITIC CELLS; CC-CHEMOKINE; T-CELLS; MOLECULAR-CLONING; BURKITTS-LYMPHOMA; FUNCTIONAL LIGAND; BETA-CHEMOKINE; CD40 LIGAND; LYMPHOCYTES; CHEMOATTRACTANT C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Ist Ric Cura Canc, Candiolo, Italy. Basel Inst Immunol, Basel, Switzerland. RP Ghia, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Schaniel, Chrisoph/C-9655-2012; Ghia, Paolo/K-7138-2016 OI Ghia, Paolo/0000-0003-3750-7342 FU NCI NIH HHS [P01-CA66996-01, P01-CA68484-02] NR 36 TC 9 Z9 9 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-65759-2 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1999 VL 246 BP 103 EP 110 PG 8 WC Cell Biology; Immunology; Microbiology SC Cell Biology; Immunology; Microbiology GA BN78A UT WOS:000082904200013 PM 10396045 ER PT S AU Rathbun, GA Ziv, Y Lai, JH Hill, D Abraham, RH Shiloh, Y Cantley, LC AF Rathbun, GA Ziv, Y Lai, JH Hill, D Abraham, RH Shiloh, Y Cantley, LC BE Melchers, F Potter, M TI ATM and lymphoid malignancies; Use of oriented peptide libraries to identify novel substrates of ATM critical in downstream signaling pathways SO MECHANISMS OF B CELL NEOPLASIA 1998 SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Mechanisms of B Cell Neoplasia 1998 CY OCT 04-06, 1998 CL BASEL INST IMMUNOL, BASEL, SWITZERLAND SP Basel Inst Immunol HO BASEL INST IMMUNOL ID ATAXIA-TELANGIECTASIA GENE; V(D)J RECOMBINATION; DEFICIENT MICE; KINASE; PHOSPHORYLATION; TRANSPOSITION; DEFECTS; RAG1; P53 C1 Harvard Univ, Sch Med, Ctr Blood Res, Cambridge, MA 02138 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet, Tel Aviv, Israel. Harvard Univ, Sch Med, Beth Israel Deaconess Hosp, Dept Med, Cambridge, MA 02138 USA. Duke Univ, Dept Pharmacol & Canc Biol, Durham, NC 27706 USA. RP Rathbun, GA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Cambridge, MA 02138 USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIGMS NIH HHS [GM57018, R01 GM056203] NR 25 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-65759-2 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1999 VL 246 BP 267 EP 274 PG 8 WC Cell Biology; Immunology; Microbiology SC Cell Biology; Immunology; Microbiology GA BN78A UT WOS:000082904200033 PM 10396065 ER PT S AU Vescio, RA Berenson, JR AF Vescio, RA Berenson, JR BE Melchers, F Potter, M TI The role of human herpesvirus-8, (HHV-8), in multiple myeloma pathogenesis SO MECHANISMS OF B CELL NEOPLASIA 1998 SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Article; Proceedings Paper CT Workshop on Mechanisms of B Cell Neoplasia 1998 CY OCT 04-06, 1998 CL BASEL INST IMMUNOL, BASEL, SWITZERLAND SP Basel Inst Immunol HO BASEL INST IMMUNOL ID SARCOMA-ASSOCIATED HERPESVIRUS; KAPOSIS-SARCOMA; DENDRITIC CELLS; DNA-SEQUENCES; HUMAN-HERPESVIRUS-8; INFECTION; INTERLEUKIN-6; LYMPHOCYTES C1 Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Div Hematol & Oncol, Los Angeles, CA 90024 USA. RP Vescio, RA (reprint author), Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90024 USA. NR 27 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 3-540-65759-2 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 1999 VL 246 BP 403 EP 409 PG 7 WC Cell Biology; Immunology; Microbiology SC Cell Biology; Immunology; Microbiology GA BN78A UT WOS:000082904200049 PM 10396081 ER PT J AU Weissman, JS Haas, JS Fowler, FJ Gatsonis, C Massagli, MP Seage, GR Cleary, P AF Weissman, JS Haas, JS Fowler, FJ Gatsonis, C Massagli, MP Seage, GR Cleary, P TI The stability of preferences for life-sustaining care among persons with AIDS in the Boston health study SO MEDICAL DECISION MAKING LA English DT Article DE life-sustaining care; patient preferences; AIDS ID ADVANCE DIRECTIVES; TREATMENT CHOICES; RELIABILITY; VALIDITY AB Background. Clinicians recognize the importance of eliciting patient preferences for life-sustaining care, yet little is known about the stability of those preferences for patients with serious disease. Objectives. To examine the stability of preferences for life-sustaining care among persons with AIDS and to assess factors associated with changes in preferences. Design. Two patient surveys and medical record reviews, administered four months apart in 1990-1991. Setting. Three health care settings in Boston. Patients. 252 of 505 eligible persons with AIDS who participated in both baseline and follow-up surveys. Main outcome measures. A single question assessing desire for cardiac resuscitation and a scale of preferences for life-extending treatment conditional on hypothetical health states. Results. Approximately one-fourth of the respondents changed their minds about life-sustaining care during a four-month period. Of patients who initially desired cardiac resuscitation, 23% decided to forego it four months later, and of those who initially said they would decline care, 34% later said they would accept it. Of those who initially desired any of the life-extending treatments, 25% decided to forego them four months later, and of those who initially said they would decline life-extending care, 24% later said they would accept some treatment. Patients reporting changes in physical function, pain, or suicide ideation were more likely to modify their desires to be resuscitated (all p less than or equal to 0.05). Patients lacking an advance directive, not completing high school, or becoming more severely ill were more likely to change their preferences on the Life Extension scale (p less than or equal to 0.05). Patients who discussed their preferences with at least one physician were just as likely as others to change desires for cardiac resuscitation. Age, gender, race, emotional health, clinical severity, social support, and site of care were not significant correlates of change for either measure. Conclusions. Health care providers should periodically reassess preferences for life-sustaining care, particularly for patients with progressive disease, given the instability in patient preferences. However, predictors of instability may vary with how preferences are measured. In particular, changes in health status may be related to instability of preferences for certain types of treatments. C1 Massachusetts Gen Hosp, Inst Hlth Policy, Hlth Policy Res & Dev Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Gen Med, Sect Hlth Serv Res, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Gen Med, Clin Epidemiol Sect, Boston, MA 02115 USA. Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. Boston Dept Hlth & Hosp, Inst Urban Hlth Policy & Res, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA. Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. RP Weissman, JS (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, Hlth Policy Res & Dev Unit, 50 Staniford St,9th Floor, Boston, MA 02114 USA. FU AHRQ HHS [HS06239] NR 28 TC 36 Z9 36 U1 3 U2 4 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD JAN-MAR PY 1999 VL 19 IS 1 BP 16 EP 26 DI 10.1177/0272989X9901900103 PG 11 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 156AG UT WOS:000077978800003 PM 9917016 ER PT S AU Warfield, SK Westin, CF Guttmann, CRG Albert, M Jolesz, FA Kikinis, R AF Warfield, SK Westin, CF Guttmann, CRG Albert, M Jolesz, FA Kikinis, R BE Taylor, C Colchester, A TI Fractional segmentation of white matter SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION, MICCAI'99, PROCEEDINGS SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 2nd International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI 99) CY SEP 19-22, 1999 CL CAMBRIDGE, ENGLAND DE automatic segmentation; brain; white matter; multiple sclerosis; Alzheimer's disease; normal aging ID MULTIPLE-SCLEROSIS LESIONS; MR; EVOLUTION; MODEL AB Abnormalities in the white matter of the brain are common to subjects with multiple sclerosis and Alzheimer's disease. They also develop in normal, asymptomatic, subjects and appear more frequently with age. Clinically, it is interesting to be able to differentiate between different disease states and to find markers which allow early diagnosis. Conventional spin echo (CSE) magnetic resonance imaging (MRI) is sensitive to these white matter changes and has frequently been applied to their study. Previous approaches to investigate white matter abnormalities have often been reported to have difficulty distinguishing between normal gray matter and abnormal white matter due to their similar appearance in MRI. Earlier methods have also often generated binary classifications, reporting white matter as either normal or abnormal. We have developed a new approach which first identifies the region of white matter using a template moderated spatially varying classification, and then estimates the degree of white matter abnormality present at each voxel of the white matter. This fractional segmentation allows us to preserve the heterogeneous characteristics of white matter abnormalities and to investigate both focal and diffuse white matter damage. We compute, from the fractional segmentation, a white matter spectrum showing the different levels of white matter damage present in each subject. We applied this automated image segmentation method to over 996 MRI scans of subjects affected by multiple sclerosis, 72 normal aging subjects and 29 scans of subjects with Alzheimer's disease. We investigated the ability to characterize these different subject groups based upon tissue volumes determined by spatially varying classification, and by the fractional segmentation of the white matter of each patient. C1 Harvard Univ, Sch Med, Dept Radiol, Surg Planning Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Warfield, SK (reprint author), Harvard Univ, Sch Med, Dept Radiol, Surg Planning Lab, 75 Francis St, Boston, MA 02115 USA. RI Warfield, Simon/B-3352-2009 NR 16 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-66503-X J9 LECT NOTES COMPUT SC PY 1999 VL 1679 BP 62 EP 71 PG 10 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Medical Laboratory Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Medical Laboratory Technology; Radiology, Nuclear Medicine & Medical Imaging GA BS81S UT WOS:000171179200007 ER PT S AU Betke, M Ko, JP AF Betke, M Ko, JP BE Taylor, C Colchester, A TI Detection of pulmonary nodules on CT and volumetric assessment of change over time SO MEDICAL IMAGE COMPUTING AND COMPUTER-ASSISTED INTERVENTION, MICCAI'99, PROCEEDINGS SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 2nd International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI 99) CY SEP 19-22, 1999 CL CAMBRIDGE, ENGLAND AB We present a computer vision system that automatically detects pulmonary nodules in computed tomography (CT) scans of oncology patients, performs size analysis and assesses for change in volume over time. Thresholding, backtracking, and smoothing algorithms have been developed to recognize the thorax and trace the lung border. The regions within the lung that potentially contain nodules are evaluated for their shape, size, and position. These candidate regions are then characterized as nodules versus other structures by comparing consecutive CT slices in the same study. A preliminary system for the registration of studies has also been developed. It estimates nodule volume in each study and evaluates the volumetric change over time. Our system has been tested on initial and follow-up studies of four patients. Preliminary results were detection of 284 nodules ranging between 1 and 32 mm at various locations and assessment of their volumetric change over time. Our techniques have future applications for determining disease progression, remission, and stability in oncologic patients in addition to coregistration of different modalities within the thorax. C1 Boston Coll, Dept Comp Sci, Boston, MA 02167 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Betke, M (reprint author), Boston Coll, Dept Comp Sci, Boston, MA 02167 USA. NR 6 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-66503-X J9 LECT NOTES COMPUT SC PY 1999 VL 1679 BP 245 EP 252 PG 8 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Medical Laboratory Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Medical Laboratory Technology; Radiology, Nuclear Medicine & Medical Imaging GA BS81S UT WOS:000171179200027 ER PT S AU Duerinckx, AJ Kenagy, JJ Grant, EG AF Duerinckx, AJ Kenagy, JJ Grant, EG BE Blaine, GJ Horii, SC TI Cost analysis of PACS: Fact or fiction? SO MEDICAL IMAGING 1999 - PACS DESIGN AND EVALUATION: ENGINEERING AND CLINICAL ISSUES SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 1999 Conference CY FEB 21-25, 1999 CL SAN DIEGO, CA SP SPIE, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc/Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE ATM; PACS; cost-analysis; patient care; clinical issues ID INCREMENTAL COST; IMPLEMENTATION; RADIOGRAPHY; NETWORK AB Purpose: To analyze the incremental costs of Picture Archiving and Communication Systems (PACS) and Computed radiography (CR) and to evaluate the key factors affecting a cost-analysis for PACS. Methods: The incremental cash flows (costs) associated with the implementation of PACS and CR in a single 600 bed hospital were analyzed. Key aspects of the PACS implementation and purchase were singled out for their potential for cost-savings in a filmless environment. Results: One cost- model using net-present-value (NPV) predicts zero cost after a 9 to 10 year period of semi-filmless operation. Other models not relying on NPV predict similar results. Many important benefits of PACS technology can not be accounted for by these models. Transient changes in the overall costs can be controlled by transitioning to a fully filmless operation within as short a period as possible. Conclusions: Cost analysis of PACS/CR technology is not trivial and many cost-models are incomplete descriptions of reality. Simplistic cost-models to predict the cost-effectiveness of PACS/CR systems are limited and can not predict important benefits from such technology. C1 W Los Angeles Vet Affairs Med Ctr, Serv Radiol, Los Angeles, CA 90073 USA. RP Duerinckx, AJ (reprint author), W Los Angeles Vet Affairs Med Ctr, Serv Radiol, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3134-6 J9 P SOC PHOTO-OPT INS PY 1999 VL 3662 BP 253 EP 262 DI 10.1117/12.352752 PG 10 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BN65S UT WOS:000082493300029 ER PT S AU Venkatakrishnan, V Yavuz, M Niklason, LT Opsahl-Ong, B Han, S Landberg, C Nevin, R Hamberg, L Kopans, DB AF Venkatakrishnan, V Yavuz, M Niklason, LT Opsahl-Ong, B Han, S Landberg, C Nevin, R Hamberg, L Kopans, DB BE Boone, JM Dobbins, JT TI Experimental and theoretical spectral optimization for digital mammography SO MEDICAL IMAGING 1999: PHYSICS OF MEDICAL IMAGING, PTS 1 AND 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 1999 Conference CY FEB 21-25, 1999 CL SAN DIEGO, CA SP SPIE, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiol Hlth, Soc Imaging Sci & Technol, Natl Elect Mfg Assoc/Diagnost Imaging & Therapy Syst Div, Radiol Soc N Amer, Soc Comp Applicat Radiol DE digital mammography; optimum spectra; computer model; signal-to-noise ratio; figure-of-merit; CsI; FFDM; simulation tool; breast phantom; Rhodium target ID DIAGNOSTIC-RADIOLOGY; IMAGING-SYSTEMS; BREAST; NOISE; MOLYBDENUM; DEPENDENCE; INTERVAL; RHODIUM; MODEL; SHAPE AB The detection characteristics of digital x-ray and film-screen mammography systems are different and thus current film-screen techniques are not ideal for digital mammography. Therefore optimum technical parameters required for digital mammography are likely to be different compared with film-screen mammography. The goal of this study is to evaluate the optimum technical parameters for full-field digital mammography by experimental and computer simulation methods. A General Electric Full Field Digital Mammography (FFDM) prototype unit using Cesium lodide (CsI) on an amorphous Silicon photodiode array was used for the experimental measurements. Using breast equivalent phantoms, images were acquired for a set of x-ray target-filters for a range of peak kilovoltage, varying breast composition and thickness, with and without an anti-scatter grid. The signal-to-noise ratio (SNR) and figure-of-merit (FOM) were determined for simulated calcification and mass targets, independently by the two methods. The. results for noise, contrast, SNR and FOM were compared and agree within 5% and 6% respectively. Combined results are presented for the case of 50% glandular-50% adipose tissue breast composition using the grid and for the: calcification target. Based on the FOM approach, preliminary results suggest that a Rhodium target-filter combination will: be beneficial for higher breast thickness and for denser breasts. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Venkatakrishnan, V (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 21 TC 11 Z9 11 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3131-1 J9 P SOC PHOTO-OPT INS PY 1999 VL 3659 BP 142 EP 149 DI 10.1117/12.349487 PG 8 WC Engineering, Biomedical; Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BN32Q UT WOS:000081632400014 ER PT J AU Mauceri, T Biggs, P Beatty, J Flynn, D AF Mauceri, T Biggs, P Beatty, J Flynn, D TI Scatter and attenuation measurements at distances greater than 10 cm from an Ir-192 source SO MEDICAL PHYSICS LA English DT Article DE brachytherapy; Ir-192; scatter/attenuation algorithms ID BRACHYTHERAPY SOURCES; I-125 AB Most algorithms developed by various investigators for use in brachytherapy treatment planning have typically been designed to calculate the dose within a 10 cm range of a radiation source. These algorithms predict the dose well at distances <10 cm from the source but were not developed and should not be utilized to predict the dose at distances >10 cm. On the contrary, treatment planning systems and manual calculations will produce erroneous results when dose points >10 cm are calculated using these algorithms. The spread in the data generated by the above algorithms is 16% at 15 cm and 42% at 20 cm. Physical measurements were performed at distances between 5 and 50 cm from a high activity Ir-192 source in water. The measured data correlated well with the predicted data from 5 to 10 cm, which had a 5% spread. Beyond 10 cm the measured data fell central to the range of the predicted data, with the spread of the predicted data increasing from 5% to 80% with increasing distance from the source. The measured data was fitted with a model incorporating a buildup factor and an attenuation factor. The best fit values are in reasonable agreement with those obtained by two of the investigators, Thomason and Tripathi. (C) 1999 American Association of Physicists in Medicine. [S0094-2405(99)01001-9]. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Div Radiat Biophys, Boston, MA 02114 USA. RP Mauceri, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Div Radiat Biophys, Boston, MA 02114 USA. NR 12 TC 2 Z9 2 U1 0 U2 0 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JAN PY 1999 VL 26 IS 1 BP 97 EP 99 DI 10.1118/1.598481 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 159VP UT WOS:000078196000013 PM 9949404 ER PT S AU Weaver, DR AF Weaver, DR BE Olcese, J TI The roles of melatonin in development SO MELATONIN AFTER FOUR DECADES: AN ASSESSMENT OF ITS POTENTIAL SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT Hanseatic Endocrine Conference on Melantonin after 4 Decades CY AUG 27-30, 1998 CL HAMBURG, GERMANY SP Deutsch Forsch Gemeinsch, GEFE eV, Deutsch Gesell Endokrinol, IHF, Lundbeck A S, Bristol Myers Squibb, SmithKline Beecham Fdn, Schering AG, Becton Dickinson, Boehringer Mannheim, Buhlmann Labs AG, Genecraft, Sigma Aldrich, Dianova GmbH, IBL GmbH, Stockgrand Ltd, Servier ID HAMSTER PHODOPUS-SUNGORUS; WESTERN SPOTTED SKUNK; PERIPUBERTAL REPRODUCTIVE DEVELOPMENT; FETAL SUPRACHIASMATIC NUCLEI; PHOTOPERIODIC INFORMATION; MATERNAL TRANSFER; SIBERIAN HAMSTERS; PLASMA MELATONIN; DELAYED IMPLANTATION; DJUNGARIAN HAMSTERS C1 Massachusetts Gen Hosp, Serv Pediat, Lab Dev Chronobiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Weaver, DR (reprint author), Massachusetts Gen Hosp, Serv Pediat, Lab Dev Chronobiol, GRJ 1226, Boston, MA 02115 USA. NR 90 TC 11 Z9 11 U1 0 U2 1 PU KLUWER ACADEMIC / PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-46134-X J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 1999 VL 460 BP 199 EP 214 PG 16 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BQ61T UT WOS:000088969600022 PM 10810515 ER PT J AU Sandberg, WS Dubois, BW Miller, KW AF Sandberg, WS Dubois, BW Miller, KW TI Lipid membrane and ligand-gated ion channels in general anesthetic action SO MEMBRANE PERMEABILITY SE CURRENT TOPICS IN MEMBRANES LA English DT Review ID NICOTINIC ACETYLCHOLINE-RECEPTOR; PROTEIN-KINASE-C; ACID TYPE-A; MEYER-OVERTON HYPOTHESIS; LONG-CHAIN ALCOHOLS; GABA(A) RECEPTOR; RICH MEMBRANES; STEREOSPECIFIC ACTIONS; VOLATILE ANESTHETICS; CHLORIDE CURRENTS C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02114 USA. RP Sandberg, WS (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NR 131 TC 5 Z9 5 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 1063-5823 J9 CURR TOP MEMBR PY 1999 VL 48 BP 311 EP 350 PG 40 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA BN74G UT WOS:000082776900010 ER PT J AU Balis, UJ Behnia, K Dwarakanath, B Bhatia, SN Sullivan, SJ Yarmush, ML Toner, M AF Balis, Ulysses J. Behnia, Kamelia Dwarakanath, Bharath Bhatia, Sangeeta N. Sullivan, Susan J. Yarmush, Martin L. Toner, Mehmet TI Oxygen Consumption Characteristics of Porcine Hepatocytes SO METABOLIC ENGINEERING LA English DT Article DE Oxygen uptake rate; hepatocytes; bioreactor; bioartificial liver; digital signal processing; porcine AB Oxygen uptake rate (OUR) of hepatocytes is an important parameter for the design of bioartificial liver assist (BAL) devices. Porcine hepatocytes were cultured in a specially constructed measurement chamber with an incorporated mixing system and a Clark polarographic oxygen electrode. Signal noise associated with conventional Clark electrode implementations was circumvented by the combination of real time digital numerical averaging and subsequent finite impulse response (FIR) spectral filtering. Additional software allowed for the automated generation of cellular oxygen consumption coefficients, namely, V(max) and K(0.5), adding a high degree of objectivity to parameter determination. Optimization of the above numerical techniques identified a 0.1 Hz/200 data point sample size and a 0.004 Hz cutoff frequency as ideal parameters. V(max) values obtained for porcine hepatocytes during the first two weeks of culture showed a maximal consumption of 0.9 nmole/sec/10(6) cells occurring on Day 4 post seeding, and a gradual decrease to 0.31 nmole/sec/10(6) cells by Day 15. K(0.5) values increased from 2 mm Hg on Day 2 to 8 mm Hg by Day 8, with gradual subsequent decrease to 4 mm Hg by Day 15. The V.. and K(0.5) values measured for porcine cells were higher than maximal values for rat hepatocytes (V(max): 0.43 nmole/sec/10(6) cells, K(0.5): 5.6 mmHg) and thus may necessitate significantly altered BA L device design conditions to ensure no oxygen limitations. Finally, these results highlight the need for species specific characterization of cellular function for optimal BAL device implementations. (C) 1999 Academic Press C1 [Balis, Ulysses J.; Behnia, Kamelia; Dwarakanath, Bharath; Bhatia, Sangeeta N.; Yarmush, Martin L.; Toner, Mehmet] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. [Balis, Ulysses J.; Behnia, Kamelia; Dwarakanath, Bharath; Bhatia, Sangeeta N.; Yarmush, Martin L.; Toner, Mehmet] Shriners Burns Hosp, Boston, MA 02114 USA. [Sullivan, Susan J.] Organogenesis Inc, Canton, MA 02114 USA. RP Balis, UJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. EM mtoner@sbi.org FU Organogenesis, Inc.; Whitaker Foundation FX This work was partially supported by grants from Organogenesis, Inc., and The Whitaker Foundation. We are grateful for insightful consultation and technical assistance from Joseph LeDoux, Kyongbum Lee, Ned Jastromb, Christopher Connolly, and Paul Gregory. NR 33 TC 81 Z9 83 U1 2 U2 13 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 JAN PY 1999 VL 1 IS 1 BP 49 EP 62 DI 10.1006/mben.1998.0105 PG 14 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA V19EA UT WOS:000208054500005 PM 10935754 ER PT J AU Atwood, CS Huang, XD Moir, RD Tanzi, RE Bush, AI AF Atwood, CS Huang, XD Moir, RD Tanzi, RE Bush, AI TI Role of free radicals and metal ions in the pathogenesis of Alzheimer's disease SO METAL IONS IN BIOLOGICAL SYSTEMS, VOL 36 SE METAL IONS IN BIOLOGICAL SYSTEMS LA English DT Review ID AMYLOID-BETA-PROTEIN; HORMONE-RELEASING HORMONE; ISOLATED HYPOTHALAMIC GRANULES; CEREBROSPINAL-FLUID FERRITIN; NEUTRON-ACTIVATION ANALYSIS; ZINC-CONTAINING NEURONS; BLOOD-BRAIN-BARRIER; HEREDITARY CERULOPLASMIN DEFICIENCY; SEROTONIN BINDING-PROTEINS; BOVINE FRONTAL-CORTEX C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Genet & Aging Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Genet & Aging Unit, Boston, MA 02114 USA. RP Atwood, CS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Genet & Aging Unit, Boston, MA 02114 USA. RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 NR 317 TC 130 Z9 135 U1 2 U2 14 PU MARCEL DEKKER PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0161-5149 J9 MET IONS BIOL SYST PY 1999 VL 36 BP 309 EP 364 PG 56 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA BM76L UT WOS:000079715100010 PM 10093929 ER PT J AU Makrigiorgos, GM AF Makrigiorgos, GM TI Detection of chromatin-associated hydroxyl radicals generated by DNA-bound metal compounds and antitumor antibiotics SO METAL IONS IN BIOLOGICAL SYSTEMS, VOL 36 SE METAL IONS IN BIOLOGICAL SYSTEMS LA English DT Review ID SUPEROXIDE-DEPENDENT FORMATION; INSTITUTES-OF-HEALTH; HYDROGEN-PEROXIDE; MAMMALIAN-CELLS; ELECTROCHEMICAL DETECTION; LIQUID-CHROMATOGRAPHY; CHEMICAL PATHOLOGY; SECTION WORKSHOP; DAMAGE; OXYGEN C1 Harvard Univ, Sch Med, Dept Radiat Oncol, Joint Ctr Radiat Therapy, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02215 USA. RP Makrigiorgos, GM (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Joint Ctr Radiat Therapy, 330 Brookline Ave, Boston, MA 02215 USA. FU PHS HHS [R01 63334, K04 69296] NR 74 TC 1 Z9 1 U1 0 U2 0 PU MARCEL DEKKER PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0161-5149 J9 MET IONS BIOL SYST PY 1999 VL 36 BP 521 EP 545 PG 25 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA BM76L UT WOS:000079715100016 PM 10093935 ER PT S AU Ferrigno, P Silver, PA AF Ferrigno, P Silver, PA BE Sullivan, KF Kay, SA TI Analysis of nuclear transport in vivo SO METHODS IN CELL BIOLOGY, VOL 58: GREEN FLUORESCENT PROTEINS SE Methods in Cell Biology LA English DT Review ID GREEN-FLUORESCENT PROTEIN; MESSENGER-RNA EXPORT; SPINDLE POLE BODY; SACCHAROMYCES-CEREVISIAE; BUDDING YEAST; IN-VIVO; PORE DISTRIBUTION; POLY(A)(+) RNA; GENE ENCODES; DYNAMICS C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM pamela_silver@dfci.harvard.edu NR 44 TC 12 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL ROAD, LONDON NW1 7DX, ENGLAND SN 0091-679X BN 0-12-676075-6 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 1999 VL 58 BP 107 EP 122 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BQ96S UT WOS:000165166500007 PM 9891377 ER PT J AU Paw, BH Zon, LI AF Paw, BH Zon, LI TI Primary fibroblast cell culture SO METHODS IN CELL BIOLOGY, VOL 59 SE METHODS IN CELL BIOLOGY LA English DT Review ID ZEBRAFISH; RERIO; FISH; EMBRYOS; INVITRO; LINES C1 Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. RP Paw, BH (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. NR 16 TC 12 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X J9 METHOD CELL BIOL PY 1999 VL 59 BP 39 EP 43 PG 5 WC Cell Biology SC Cell Biology GA BQ13J UT WOS:000087259200004 PM 9891354 ER PT J AU Parker, LH Zon, LI Stainier, DYR AF Parker, LH Zon, LI Stainier, DYR TI Vascular and blood gene expression SO METHODS IN CELL BIOLOGY, VOL 59 SE METHODS IN CELL BIOLOGY LA English DT Review ID TRANSCRIPTION FACTOR GATA-1; EMBRYONIC STEM-CELLS; ENDOTHELIAL-CELLS; ERYTHROID DEVELOPMENT; ZEBRAFISH EMBRYO; CARDIOVASCULAR-SYSTEM; HEMATOPOIETIC-CELLS; MONOCLONAL-ANTIBODY; BINDING PROTEIN; AVIAN EMBRYO C1 Univ Calif San Francisco, Dept Biochem & Biophys, Program Dev Biol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biochem & Biophys, Program Human Genet, San Francisco, CA 94143 USA. Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. RP Parker, LH (reprint author), Univ Calif San Francisco, Dept Biochem & Biophys, Program Dev Biol, San Francisco, CA 94143 USA. NR 75 TC 13 Z9 13 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X J9 METHOD CELL BIOL PY 1999 VL 59 BP 313 EP + PG 26 WC Cell Biology SC Cell Biology GA BQ13J UT WOS:000087259200017 PM 9891367 ER PT J AU Serluca, FC Fishman, MC AF Serluca, FC Fishman, MC TI Cell lineage tracing in heart development SO METHODS IN CELL BIOLOGY, VOL 59 SE METHODS IN CELL BIOLOGY LA English DT Review ID CARDIOVASCULAR-SYSTEM; ZEBRAFISH EMBRYO; XENOPUS-LAEVIS; FATE MAP; EXPRESSION; ORGANS; FIELD; STAGE; GENE C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. RP Serluca, FC (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL49579] NR 18 TC 6 Z9 6 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X J9 METHOD CELL BIOL PY 1999 VL 59 BP 359 EP 365 PG 7 WC Cell Biology SC Cell Biology GA BQ13J UT WOS:000087259200019 PM 9891369 ER PT S AU Beal, MF AF Beal, MF BE Brown, GC Nicholls, DG Cooper, CE TI Mitochondria, NO and neurodegeneration SO MITOCHONDRIA AND CELL DEATH SE Biochemical Society Symposia LA English DT Article; Proceedings Paper CT Biochemical-Society Symposium on Mitochondria and Cell Death CY JUL, 1998 CL SHEFFIELD UNIV, SHEFFIELD, ENGLAND SP Biochem Soc HO SHEFFIELD UNIV ID AMYOTROPHIC-LATERAL-SCLEROSIS; TOCOPHEROL TRANSFER PROTEIN; CU,ZN SUPEROXIDE-DISMUTASE; MOTOR-NEURON DISEASE; STRIATAL EXCITOTOXIC LESIONS; SPORADIC ALZHEIMERS-DISEASE; TRIPLET-REPEAT EXPANSION; HUNTINGTONS-DISEASE; OXIDATIVE DAMAGE; ENERGY-METABOLISM AB A role for mitochondrial dysfunction in neurodegenerative disease is gaining increasing support. Mitochondrial dysfunction may be linked to neurodegenerative diseases through a variety of different pathways, including free-radical generation, impaired calcium buffering and the mitochondrial permeability transition. This can lead to both apoptotic and necrotic cell death. Recent evidence has shown that there is a mitochondrial defect in Friedreich's ataxia, which leads to increased mitochondrial iron content, that appears to be linked to increased free-radical generation. There is evidence that the point mutations in superoxide dismutase which are associated with amyotrophic lateral sclerosis may contribute to mitochondrial dysfunction. There is also evidence for bioenergetic defects in Huntington's disease. Studies of cybrid cell lines have implicated mitochondrial defects in both Parkinson's disease and Alzheimer's disease. If mitochondrial dysfunction plays a role in neurodegenerative diseases then therapeutic strategies such as coenzyme Q(10) and creatine may be useful in attempting to slow the disease process. C1 Massachusetts Gen Hosp, Neurochem Lab, Neurol Serv, WRN 408, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Beal, MF (reprint author), Massachusetts Gen Hosp, Neurochem Lab, Neurol Serv, WRN 408, Boston, MA 02114 USA. FU NIA NIH HHS [AG11337]; NINDS NIH HHS [NS31579, NS16367] NR 94 TC 6 Z9 7 U1 0 U2 1 PU PORTLAND PRESS LTD PI LONDON PA 59 PORTLAND PL, LONDON W1N 3AJ, ENGLAND SN 0067-8694 BN 1-85578-125-5 J9 BIOCHEM SOC SYMP JI Biochem. Soc. Symp. PY 1999 VL 66 BP 43 EP 54 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BP10N UT WOS:000084132600005 PM 10989656 ER PT J AU Gergely, J AF Gergely, J TI Professor Ebashi's impact on the study of the regulation of striated muscle contraction SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE troponin; tropomyosin; thin filament regulation; Ca2+ ID TERNARY TROPONIN COMPLEX; SKELETAL-MUSCLE; THIN FILAMENT; CONFORMATIONAL TRANSITION; MEDIATED REGULATION; BIOLOGICAL-ACTIVITY; INHIBITORY REGION; PEPTIDE COMPLEX; CA2+ REGULATION; X-RAY AB The field of striated muscle regulation has changed tremendously over the last forty years. Many of the problems solved by Dr. Ebashi and by those stimulated by him offer new challenges for future generations of scientists. Many questions remain to be solved, and it should give particular pleasure to Dr. Ebashi to see how the seeds sown by him and his colleagues have now grown into a beautiful tree that bears rich fruit at present and will continue to do so for a long time in the future. (Mol Cell Biochem 190: 5-8, 1999). C1 Boston Biomed Res Inst, Muscle Res Grp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Gergely, J (reprint author), Boston Biomed Res Inst, Muscle Res Grp, 220 Staniford St, Boston, MA 02114 USA. NR 57 TC 0 Z9 1 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD JAN PY 1999 VL 190 IS 1-2 BP 5 EP 8 DI 10.1023/A:1006987223644 PG 4 WC Cell Biology SC Cell Biology GA 172TZ UT WOS:000078942000002 PM 10098964 ER PT J AU Wang, ZY Goldstein, A Zong, RT Lin, DJ Neufeld, EJ Scheuermann, RH Tucker, PW AF Wang, ZY Goldstein, A Zong, RT Lin, DJ Neufeld, EJ Scheuermann, RH Tucker, PW TI Cux/CDP homeoprotein is a component of NF-mu NR and represses the immunoglobulin heavy chain intronic enhancer by antagonizing the bright transcription activator SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Review ID CCAAT DISPLACEMENT PROTEIN; MATRIX-ATTACHMENT REGIONS; MUTUALLY EXCLUSIVE INTERACTION; CHROMOSOMAL LOOP ANCHORAGE; SUPPRESSOR SITES FLANKING; SENSORY ORGAN IDENTITY; TISSUE-SPECIFIC GENE; DNA-BINDING PROTEIN; B-CELL SPECIFICITY; GAMMA-GLOBIN GENE AB Nuclear matrix attachment regions (MARs) flanking the immunoglobulin heavy chain intronic enhancer (E mu) are the targets of the negative regulator, NF-mu NR, found in non-B and early pre-B cells. Expression library screening with NF-mu NR binding sites yielded a cDNA clone encoding an alternatively spliced form of the Cux/CDP homeodomain protein. Cux/CDP fulfills criteria required for NF-mu NR identity. It is expressed in non-B and early pre-B cells but not mature B cells. It binds to NF-mu NR binding sites within E mu with appropriate differential affinities. Antiserum specific for Cux/CDP recognizes a polypeptide of the predicted size in affinity-purified NF-mu NR preparations and binds NF-mu NR complexed with DNA. Cotransfection with Cux/CDP represses the activity of E mu via the MAR sequences in both B and non-B cells. Cux/CDP antagonizes the effects of the Bright transcription activator at both the DNA binding and functional levels. We propose that Cux/CDP regulates cell-type-restricted, differentiation stage-specific E mu enhancer activity by interfering with the function of nuclear matrix-bound transcription activators. C1 Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr, Lab Mol Pathol, Dallas, TX 75235 USA. Univ Texas, Inst Mol & Cellular Biol, Austin, TX 78712 USA. Univ Texas, Dept Microbiol, Austin, TX 78712 USA. Childrens Hosp, Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Scheuermann, RH (reprint author), Univ Texas, SW Med Ctr, Dept Pathol, 5323 Harry Hines Blvd, Dallas, TX 75235 USA. RI Neufeld, Ellis/F-9331-2011 FU NCI NIH HHS [CA31534, R01 CA031534]; NHLBI NIH HHS [HL49196]; NIGMS NIH HHS [GM50329] NR 101 TC 64 Z9 68 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 1999 VL 19 IS 1 BP 284 EP 295 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 150DE UT WOS:000077647100027 PM 9858552 ER PT J AU Lahoz, EG Liegeois, NJ Zhang, PM Engelman, JA Horner, J Silverman, A Burde, R Roussel, MF Sherr, CJ Elledge, SJ DePinho, RA AF Lahoz, EG Liegeois, NJ Zhang, PM Engelman, JA Horner, J Silverman, A Burde, R Roussel, MF Sherr, CJ Elledge, SJ DePinho, RA TI Cyclin D- and E-dependent kinases and the p57(KIP2) inhibitor: Cooperative interactions in vivo SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID LENS-SPECIFIC EXPRESSION; CELL-CYCLE; RETINOBLASTOMA PROTEIN; TRANSGENIC MICE; CHLORAMPHENICOL ACETYLTRANSFERASE; GROWTH SUPPRESSION; PHASE-TRANSITION; MAMMALIAN-CELLS; G(1) CYCLINS; MOUSE LENS AB This study examines in vivo the role and functional interrelationships of components regulating exit from the G(1) resting phase into the DNA synthetic (S) phase of the cell cycle. Our approach made use of several key experimental attributes of the developing mouse lens, namely its strong dependence on pRb in maintenance of the postmitotic state, the down-regulation of cyclins D and E and up-regulation of the p57(KIP2) inhibitor in the postmitotic lens fiber cell compartment, and the ability to target transgene expression to this compartment. These attributes provide an ideal in vivo context in which to examine the consequences of forced cyclin expression and/or of loss of p57(KIP2) inhibitor function in a cellular compartment that permits an accurate quantitation of cellular proliferation and apoptosis rates in situ. Here, we demonstrate that, despite substantial overlap in cyclin transgene expression levels, D-type and E cyclins exhibited clear functional differences in promoting entry into S phase. In general, forced expression of the D-type cyclins was more efficient than cyclin E in driving lens fiber cells into S phase. In the ease of cyclins D1 and D2, ectopic proliferation required their enhanced nuclear localization through CDK4 coexpression. High nuclear levels of cyclin E and CDK2, while not sufficient to promote efficient exit from G(1), did act synergistically with ectopic cyclin D/CDK4. The functional differences between D-type and E cyclins was most evident in the p57(KIP2)-deficient lens wherein cyclin D overexpression induced a rate of proliferation equivalent to that of the pRb null lens, while overexpression of cyclin E did not increase the rate of proliferation over that induced by the loss of p57(KIP2) function. These in vivo analyses provide strong biological support for the prevailing view that the antecedent actions of cyclin D/CDK4 act cooperatively with cyclin E/CDK2 and antagonistically with p57(KIP2) to regulate the G(1)/S transition in a cell type highly dependent upon pRb. C1 Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA. St Jude Childrens Res Hosp, Howard Hughes Med Inst, Memphis, TN 38105 USA. St Jude Childrens Res Hosp, Dept Tumor Cell Biol, Memphis, TN 38105 USA. Baylor Coll Med, Howard Hughes Med Inst, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Baylor Coll Med, Verna & Marrs McLean Dept Biochem, Houston, TX 77030 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St M463, Boston, MA 02115 USA. NR 61 TC 37 Z9 37 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 1999 VL 19 IS 1 BP 353 EP 363 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 150DE UT WOS:000077647100034 ER PT J AU Kaneki, M Kharbanda, S Pandey, P Yoshida, K Takekawa, M Liou, JR Stone, R Kufe, D AF Kaneki, M Kharbanda, S Pandey, P Yoshida, K Takekawa, M Liou, JR Stone, R Kufe, D TI Functional role for protein kinase C beta as a regulator of stress-activated protein kinase activation and monocytic differentiation of myeloid leukemia cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ESTER-INDUCED DIFFERENTIATION; SIGNAL-TRANSDUCTION PATHWAYS; EARLY GROWTH RESPONSE-1; NIH 3T3 CELLS; IONIZING-RADIATION; JUN EXPRESSION; MACROPHAGE DIFFERENTIATION; OKADAIC ACID; ONCOGENE EXPRESSION; GENE-TRANSCRIPTION AB Human myeloid leukemia cells respond to 12-O-tetradecanoylphorbol-13-acetate (TPA) and other activators of protein kinase C (PRC) with induction of monocytic differentiation. The present studies demonstrated that treatment of U-937 and HL-60 myeloid leukemia cells,vith TPA, phorbol-12,13-dibutyrate, or bryostatin 1 was associated with the induction of stress-activated protein kinase (SAPK). In contrast, TPA-resistant TUR and HL-525 cell variants deficient in PKC beta failed to respond to activators of PKC with the induction of SAPK. A direct role for PKC beta in TPA-induced SAPK activity in TUR and HL-525 tells that stably express PKC beta was confirmed. We showed that TPA induced the association of PKC beta with MEK kinase 1 (MEKK-1), an upstream effector of the SAPK/ERK kinase 1 (SEK1)-->SAPK cascade. The results also demonstrated that PKC beta phosphorylated and activated MEKK-1 in vitro. The functional role of MEKK-1 in TPA-induced SAPK activity was further supported by the demonstration that the expression of a dominant negative MEKK-1 mutant abrogated this response. These findings indicate that PKC beta activation is necessary for activation of the MEK-1-->SEK1-->SAPK cascade in the TPA response of myeloid leukemia cells. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA68252, R01 CA042802, CA42802] NR 64 TC 60 Z9 61 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN PY 1999 VL 19 IS 1 BP 461 EP 470 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 150DE UT WOS:000077647100045 PM 9858570 ER PT S AU Sheng, M Pak, DT AF Sheng, M Pak, DT BE Rudy, B Seeburg, P TI Glutamate receptor anchoring proteins and the molecular organization of excitatory synapses SO MOLECULAR AND FUNCTIONAL DIVERSITY OF ION CHANNELS AND RECEPTORS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Molecular and Functional Diversity of Ion Channels and Receptors CY MAY 14-17, 1998 CL NEW YORK, NEW YORK SP NY Acad Sci, ICAGEN, Inc, F Hoffmann-La Roche, CNS Dept, Merck Res Labs, Natl Inst Neurol Disorders & Stroke, Natl Inst Hlth, Natl Sci Fdn, Amer Heart Assoc, Axon Instruments Inc, Bristol-Myers Squibb Pharmaceut Inst, Glaxo Wellcome, Hoechst Marion Roussel Inc, Lilly REs Labs, Neurex Corp, Parke Davis Pharmaceut Res Div, Roche Biosci, Sibia, Neurosci Inc, SmithKline Beecham Labs ID POSTSYNAPTIC DENSITY PROTEIN; TUMOR-SUPPRESSOR PROTEIN; NITRIC-OXIDE SYNTHASE; NMDA RECEPTOR; GUANYLATE KINASES; DISCS-LARGE; PDZ-DOMAIN; HIPPOCAMPAL-NEURONS; CLUSTERING ACTIVITY; PSD-95 FAMILY AB Ionotropic glutamate receptors are concentrated at postsynaptic sites in excitatory synapses. The cytoplasmic C-terminal tail of certain glutamate receptor subunits interact with specific PDZ domain-containing proteins. NMDA receptor NR2 subunits bind to the PSD-95 family of proteins, whereas AMPA receptor subunits GluR2/3 bind to GRIP. These interactions may underlie the clustering, targeting, and immobilization of the glutamate receptors at postsynaptic sites. By virtue of their multiple protein-binding domains (e.g., three PDZs in PSD-95 and seven PDZs in GRIP), PSD-95 and GRIP can function as multivalent proteins that organize a specific cytoskeletal and signaling complex associated with each class of glutamate receptor. The network of protein-protein interactions mediated by these abundant PDZ proteins is likely to contribute significantly to the molecular scaffold of the postsynaptic density. C1 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 Sheng, M (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Wellman 423,50 Blossom St, Boston, MA 02114 USA. NR 60 TC 86 Z9 87 U1 1 U2 5 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-176-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 868 BP 483 EP 493 DI 10.1111/j.1749-6632.1999.tb11317.x PG 11 WC Biochemistry & Molecular Biology; Biophysics; Multidisciplinary Sciences; Neurosciences SC Biochemistry & Molecular Biology; Biophysics; Science & Technology - Other Topics; Neurosciences & Neurology GA BN31T UT WOS:000081584300049 PM 10414325 ER PT S AU Bradley, SR Standaert, DG Levey, AI Conn, PJ AF Bradley, SR Standaert, DG Levey, AI Conn, PJ BE Rudy, B Seeburg, P TI Distribution of group III mGluRs in rat basal ganglia with subtype-specific antibodies SO MOLECULAR AND FUNCTIONAL DIVERSITY OF ION CHANNELS AND RECEPTORS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Molecular and Functional Diversity of Ion Channels and Receptors CY MAY 14-17, 1998 CL NEW YORK, NEW YORK SP NY Acad Sci, ICAGEN, Inc, F Hoffmann-La Roche, CNS Dept, Merck Res Labs, Natl Inst Neurol Disorders & Stroke, Natl Inst Hlth, Natl Sci Fdn, Amer Heart Assoc, Axon Instruments Inc, Bristol-Myers Squibb Pharmaceut Inst, Glaxo Wellcome, Hoechst Marion Roussel Inc, Lilly REs Labs, Neurex Corp, Parke Davis Pharmaceut Res Div, Roche Biosci, Sibia, Neurosci Inc, SmithKline Beecham Labs ID ACTIVATION C1 Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. RP Bradley, SR (reprint author), Emory Univ, Sch Med, Dept Pharmacol, Rollins Res Bldg,Room 5160,1510 Clifton Rd, Atlanta, GA 30322 USA. RI Conn, Peter/D-7848-2012; Levey, Allan/F-2104-2011; OI Levey, Allan/0000-0002-3153-502X; Standaert, David/0000-0003-2921-8348 NR 5 TC 43 Z9 44 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-176-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 868 BP 531 EP 534 DI 10.1111/j.1749-6632.1999.tb11322.x PG 4 WC Biochemistry & Molecular Biology; Biophysics; Multidisciplinary Sciences; Neurosciences SC Biochemistry & Molecular Biology; Biophysics; Science & Technology - Other Topics; Neurosciences & Neurology GA BN31T UT WOS:000081584300054 PM 10414330 ER PT S AU Guo, ZM Richardson, A AF Guo, ZM Richardson, A BE Bohr, VA Clark, BFC Stevnsner, T TI Effects of aging and dietary restriction on DNA repair SO MOLECULAR BIOLOGY OF AGING SE ALFRED BENZON SYMPOSIUM SERIES LA English DT Proceedings Paper CT 44th Alfred Benzon Symposium on Molecular Biology of Aging CY JUN 14-18, 1998 CL ROYAL DANISH ACAD SCI & LETTERS, COPENHAGEN, DENMARK SP Royal Danish Acad Sci & Letters HO ROYAL DANISH ACAD SCI & LETTERS ID AGE-RELATED DECREASE; CALORIC RESTRICTION; SOMATIC MUTATION; CELLS; DAMAGE; MICE; RATS; FIBROBLASTS; IRRADIATION; HEPATOCYTES C1 Univ Texas, Hlth Sci Ctr, Ctr Geriatr Res Educ & Clin, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. RP Guo, ZM (reprint author), Univ Texas, Hlth Sci Ctr, Ctr Geriatr Res Educ & Clin, S Texas Vet Hlth Care Syst, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 44 TC 0 Z9 0 U1 0 U2 0 PU MUNKSGAARD PI COPENHAGEN K PA 35 NORRE SOGADE POSTBOX 2148, DK-1016 COPENHAGEN K, DENMARK SN 0105-3639 BN 87-16-12176-7 J9 ALFRED BENZON SYMP S PY 1999 VL 44 BP 362 EP 372 PG 11 WC Biochemistry & Molecular Biology; Geriatrics & Gerontology SC Biochemistry & Molecular Biology; Geriatrics & Gerontology GA BP88U UT WOS:000086496400027 ER PT J AU Hanstein, B Liu, H Yancisin, MC Brown, M AF Hanstein, B Liu, H Yancisin, MC Brown, M TI Functional analysis of a novel estrogen receptor-beta isoform SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID NUCLEAR-RECEPTOR; ER BETA; COACTIVATOR; IDENTIFICATION; ACTIVATION; PROTEINS; COMPLEX; GENE; SUPERFAMILY; CLONING AB A new level of complexity has recently been added to estrogen signaling with the identification of a second estrogen receptor, ER beta. By screening a rat prostate cDNA library, we detected ER beta as well as a novel isoform that we termed ER beta 2. ER beta 2 contains an in-frame inserted exon of 54 nucleotides that results in the predicted insertion of 18 amino acids within the ER beta hormone-binding domain. We also have evidence for the expression of both ER beta 1 and ER beta 2 in human cell lines. Competition ligand binding analysis of bacterially expressed fusion proteins revealed an 8-fold lower affinity of ER beta 2 for 17 beta-estradiol (E-2) [dissociation constant (K-d similar to 8 nM)] as compared with ER beta 1 (K-d similar to 1 nM). In vitro transcribed and translated ER beta 1 and ER beta 2 bind specifically to a consensus estrogen responsive element in a gel mobility shift assay. Furthermore, we show heterodimerization of ER beta 1 and ER beta 2 with each other as well as with ER alpha. In affinity interaction assays for proteins that associate specifically with the hormone-binding domain of these receptors, we demonstrate that the steroid receptor coactivator SRC-1 interacts in an estrogen-dependent manner with ER alpha and ER beta 1, but not with ER beta 2. In cotransfection experiments with expression plasmids for ER alpha, ER beta 1, and ER beta 2 and an estrogen-responsive element-containing luciferase reporter, the dose response of ER beta 1 to E-2 was similar to that of ER alpha although the maximal stimulation was approximately 50%. In contrast, ER beta 2 required 100- to 1000-fold greater E-2 concentrations for maximal activation. Thus, ER beta 2 adds yet another facet to the possible cellular responses to estrogen. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Brown, M (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. EM myles_brown@dfci.harvard.edu OI Brown, Myles/0000-0002-8213-1658 FU NCI NIH HHS [CA-57374] NR 29 TC 115 Z9 118 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JAN PY 1999 VL 13 IS 1 BP 129 EP 137 DI 10.1210/me.13.1.129 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 153EA UT WOS:000077819100011 PM 9892018 ER PT J AU Ho, SC Rajagopalan, S Chaudhuri, S Shieh, CC Brenner, MB Pillai, S AF Ho, SC Rajagopalan, S Chaudhuri, S Shieh, CC Brenner, MB Pillai, S TI Membrane anchoring of calnexin facilitates its interaction with its targets SO MOLECULAR IMMUNOLOGY LA English DT Article DE calnexin; immunoglobulins; lymphocyte tyrosine kinase ID HISTOCOMPATIBILITY COMPLEX-MOLECULES; RETICULUM CHAPERONE CALNEXIN; KINASE-II PHOSPHORYLATION; ENDOPLASMIC-RETICULUM; TYROSINE KINASE; P-GLYCOPROTEIN; CELL-LINE; G-PROTEIN; ASSOCIATION; CALRETICULIN AB Calnexin, a chaperone that resides in the endoplasmic reticulum, participates in the quality control function of this compartment. Many glycoproteins in the process of folding associate transiently with this chaperone via interactions involving the recognition of their mono-glucosylated glycans. Some misfolded proteins which are retained in the endoplasmic reticulum exhibit prolonged association with calnexin. We have examined whether the transmembrane and cytoplasmic domains of calnexin influence the association of this chaperone with its targets. Interactions of wild type and truncated calnexin with a glycoprotein that is retained in the endoplasmic reticulum (the lymphocyte tyrosine kinase, Ltk), with membrane IgM heavy chains, and with the MHC class I heavy chain protein were investigated. A soluble calnexin molecule lacking the transmembrane domain and cytoplasmic tail does not associate with any of these proteins. When a heterologous transmembrane domain is fused to the lumenal portion of calnexin, this membrane-bound protein can bind Ltk, IgM heavy chains, and MHC class I heavy chain proteins. These results suggest that calnexin must be membrane-anchored in order to recognize its substrates. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol & Immunol, Cambridge, MA 02139 USA. RP Pillai, S (reprint author), Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Boston, MA 02129 USA. FU NCI NIH HHS [CA 69618]; NIAID NIH HHS [AI 33507] NR 55 TC 6 Z9 6 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JAN PY 1999 VL 36 IS 1 BP 1 EP 12 DI 10.1016/S0161-5890(99)00018-8 PG 12 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 181TR UT WOS:000079459000001 PM 10369415 ER PT J AU Forman, SA Zhou, Q AF Forman, SA Zhou, Q TI Novel modulation of a nicotinic receptor channel mutant reveals that the open state is stabilized by ethanol SO MOLECULAR PHARMACOLOGY LA English DT Article ID ACETYLCHOLINE-RECEPTOR; ANESTHETICS; ACTIVATION; TORPEDO; SENSITIVITY; MUTATIONS; ALCOHOLS; BLOCK AB Ethanol enhances the gating of a family of related ligand-gated ion channels including nicotinic acetylcholine, serotonin type 3, gamma-aminobutyric acid-A, and glycine receptors. This common action may reflect shared molecular and kinetic mechanisms. In all of these receptors, ethanol enhances multichannel currents elicited with low agonist concentrations, but not with high agonist concentrations. A single mutation in the nicotinic receptor beta subunit, beta T2631, causes ethanol to enhance multichannel currents elicited with both low and high acetylcholine concentrations. Based on the ratios of acetylcholine EC(50)s in the presence and absence of ethanol, this mutant's sensitivity to enhancement is similar to wild type. Ethanol enhancement of beta T2631 receptor activation shows no voltage dependence. In the presence of ethanol, the apparent single-channel conductance of the beta T2631 receptor is reduced and the apparent channel lifetime is lengthened. Both the 28% increase in maximal current and the 2-fold reduction in EC50 observed at 300 mM ethanol are quantitatively predicted by simulation of a simple kinetic scheme in which ethanol increases by 4-fold the ratio of microscopic opening rate (beta) to closing rate (alpha) for acetylcholine-bound beta T2631 receptors. We conclude that ethanol enhancement of beta T2631 currents reflects stabilization of its open-channel state relative to agonist-bound closed states. Ethanol effects in wild-type receptors can also be explained by this mechanism. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Forman, SA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, CLN-3, Boston, MA 02114 USA. EM forman@helix.mgh.harvard.edu FU NIAAA NIH HHS [1-K21-AA00206] NR 25 TC 32 Z9 33 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JAN PY 1999 VL 55 IS 1 BP 102 EP 108 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 156UV UT WOS:000078021200013 PM 9882703 ER PT J AU Standaert, DG AF Standaert, DG TI NMDA receptors and nitric oxide synthase SO MOLECULAR PSYCHIATRY LA English DT Editorial Material ID DENSITY PROTEIN PSD-95; POSTSYNAPTIC DENSITY; GLUTAMATE RECEPTORS; NERVOUS-SYSTEM; MESSENGER-RNA; RAT-BRAIN; SUBUNIT; EXPRESSION; FAMILY; DOMAIN AB NMDA glutamate receptors stimulate synthesis of nitric oxide in the brain. Neurons containing nitric oxide synthase have NMDA receptors with distinct properties, suggesting the possibility of targeted therapeutic modulation. C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Standaert, DG (reprint author), Massachusetts Gen Hosp, Neurol Serv, Warren 408,Fruit St, Boston, MA 02114 USA. OI Standaert, David/0000-0003-2921-8348 NR 22 TC 7 Z9 7 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JAN PY 1999 VL 4 IS 1 BP 13 EP 14 DI 10.1038/sj.mp.4000437 PG 2 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 157ZW UT WOS:000078092400003 PM 10089001 ER PT J AU Karet, FE Finberg, KE Nelson, RD Nayir, A Mocan, H Sanjad, SA Rodriguez-Soriano, J Santos, F Cremers, CWRJ Di Pietro, A Hoffbrand, BI Winiarski, J Bakkaloglu, A Ozen, S Dusunsel, R Goodyer, P Hulton, SA Wu, DK Skvorak, AB Morton, CC Cunningham, MJ Jha, V Lifton, RP AF Karet, FE Finberg, KE Nelson, RD Nayir, A Mocan, H Sanjad, SA Rodriguez-Soriano, J Santos, F Cremers, CWRJ Di Pietro, A Hoffbrand, BI Winiarski, J Bakkaloglu, A Ozen, S Dusunsel, R Goodyer, P Hulton, SA Wu, DK Skvorak, AB Morton, CC Cunningham, MJ Jha, V Lifton, RP TI Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness SO NATURE GENETICS LA English DT Article ID DIFFERENTIAL EXPRESSION; INNER-EAR; HETEROGENEITY; ASSOCIATION; EXCHANGER; CHILDREN; ISOFORM; CELLS; DNA AB H+-ATPases are ubiquitous in nature; V-ATPases pump protons against an electrochemical gradient, whereas F-ATPases reverse the process, synthesizing ATP. We demonstrate here that mutations in ATP6B1, encoding the B-subunit of the apical proton pump mediating distal nephron acid secretion, cause distal renal tubular acidosis, a condition characterized by impaired renal acid secretion resulting in metabolic acidosis. Patients with ATP6B1 mutations also have sensorineural hearing loss; consistent with this finding, we demonstrate expression of ATP6B1 in cochlea and endolymphatic sac. Our data, together with the known requirement for active proton secretion to maintain proper endolymph pH, implicate ATP6B1 in endolymph pH homeostasis and in normal auditory function. ATP6B1 is the first member of the H+-ATPase gene family in which mutations are shown to cause human disease. C1 Yale Univ, Sch Med, Boyer Ctr Mol Med, Howard Hughes Med Inst, New Haven, CT 06510 USA. Yale Univ, Sch Med, Boyer Ctr Mol Med, Dept Genet, New Haven, CT 06510 USA. Yale Univ, Sch Med, Boyer Ctr Mol Med, Dept Med, New Haven, CT 06510 USA. Univ Utah, Hlth Sci Ctr, Dept Pediat, Salt Lake City, UT USA. Univ Istanbul, Dept Pediat Nephrol, Istanbul, Turkey. Karadeniz Tekn Univ, Dept Pediat Nephrol, Trabzon, Turkey. King Faisal Specialist Hosp & Res Ctr, Dept Pediat, Riyadh 11211, Saudi Arabia. Hosp Cruces, Dept Pediat, Bilbao, Spain. Univ Oviedo, Div Pediat Nephrol, Oviedo, Spain. Acad Ziekenhuis, Dept Otorhinolaryngol, Nijmegen, Netherlands. Serv Osped Rilievo Nazl, Serv Nefrol Pediat, Naples, Italy. Whittington Hosp, Dept Nephrol, London N19 5NF, England. Karolinska Inst, Dept Pediat, Huddinge, Sweden. Hacettepe Univ, Dept Pediat Nephrol, Ankara, Turkey. Erciyes Univ, Dept Pediat Nephrol, Kayseri, Turkey. Montreal Childrens Hosp, Div Pediat Nephrol, Montreal, PQ H3H 1P3, Canada. Childrens Hosp, Dept Nephrol, Birmingham B16 8ET, W Midlands, England. Natl Inst Deafness & Other Commun Disorders, Rockville, MD USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Postgrad Inst Med Educ & Res, Dept Nephrol, Chandigarh 160012, India. RP Lifton, RP (reprint author), Yale Univ, Sch Med, Boyer Ctr Mol Med, Howard Hughes Med Inst, 295 Congress Ave, New Haven, CT 06510 USA. EM richard.lifton@yale.edu RI Cremers, C.W.R.J./L-4254-2015 FU NIDCD NIH HHS [DCO3402]; Wellcome Trust NR 41 TC 411 Z9 430 U1 0 U2 10 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 JAN PY 1999 VL 21 IS 1 BP 84 EP 90 DI 10.1038/5022 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 155RT UT WOS:000077960700014 PM 9916796 ER PT J AU Edelmann, W Cohen, PE Kneitz, B Winand, N Lia, M Heyer, J Kolodner, R Pollard, JW Kucherlapati, R AF Edelmann, W Cohen, PE Kneitz, B Winand, N Lia, M Heyer, J Kolodner, R Pollard, JW Kucherlapati, R TI Mammalian MutS homologue 5 is required for chromosome pairing in meiosis SO NATURE GENETICS LA English DT Article ID DNA MISMATCH REPAIR; NONPOLYPOSIS COLORECTAL-CANCER; COLON-CANCER; CROSSING-OVER; GENE; MUTATION; MICE; MSH2; RECOMBINATION; ASSOCIATION AB MSH5 (MutS homologue 5) is a member of a family of proteins known to be involved in DNA mismatch repair(1,2). Germline mutations in MSH2, MLH1 and GTBP (also known as MSH6) cause hereditary non-polyposis colon cancer (HNPCC) or Lynch syndrome(3-8). Inactivation of Msh2, Mlh1, Gtmbp (also known as Msh6) or Pms2 in mice leads to hereditary predisposition to intestinal and other cancers(9-14). Early studies in yeast revealed a role for some of these proteins, including Msh5, in meiosis(15-17). Gene targeting studies in mice confirmed roles for Mlh1 and Pms2 in mammalian meiosis(12-14,18). To assess the role of Msh5 in mammals, we generated and characterized mice with a null mutation in Msh5 Msh5(-/-) mice are viable but sterile. Meiosis in these mice is affected due to the disruption of chromosome pairing in prophase I. We found that this meiotic failure leads to a diminution in testicular size and a complete loss of ovarian structures, Our results show that normal Msh5 function is essential for meiotic progression and, in females, gonadal maintenance. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10461 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Edelmann, W (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Cell Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. FU NCI NIH HHS [CA 67944, CA 76329, N01-CN-65031] NR 30 TC 252 Z9 259 U1 2 U2 6 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 JAN PY 1999 VL 21 IS 1 BP 123 EP 127 DI 10.1038/5075 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 155RT UT WOS:000077960700023 PM 9916805 ER PT J AU Wang, JM Wilhelmsson, H Graff, C Li, H Oldfors, A Rustin, P Bruning, JC Kahn, CR Clayton, DA Barsh, GS Thoren, P Larsson, NG AF Wang, JM Wilhelmsson, H Graff, C Li, H Oldfors, A Rustin, P Bruning, JC Kahn, CR Clayton, DA Barsh, GS Thoren, P Larsson, NG TI Dilated cardiomyopathy and atrioventricular conduction blocks induced by heart-specific inactivation of mitochondrial DNA gene expression SO NATURE GENETICS LA English DT Article ID KEARNS-SAYRE SYNDROME; SKELETAL-MUSCLE; DEVELOPMENTAL REGULATION; MESSENGER-RNAS; IN-VIVO; DEFICIENCY; DELETIONS; DISEASE; MICE; TRANSCRIPTION AB Mutations of mitochondrial DNA (mtDNA) cause several well-recognized human genetic syndromes with deficient oxidative phosphorytation(1-4) and may also have a role in ageing and acquired diseases of old age(5). We report here that hallmarks of mtDNA mutation disorders can be reproduced in the mouse using a conditional mutation strategy tl manipulate the expression of the gene encoding mitochondrial transcription factor A (Tfam, previously named mtTFA), which regulates transcription and replication of mtDNA (refs 6,7). Using a loxP-flanked Tfam allele (Tfam(loxP); ref. 8) in combination with a cre-recombinase transgene under control of the muscle creatinine kinase promoter(9,10), we have disrupted Tfam in heart and muscle. Mutant animals develop a mosaic cardiac-specific progressive respiratory chain deficiency, dilated cardiomyopathy, atrioventricular heart conduction blocks and die at 2-4 weeks of age. This animal model reproduces biochemical, morphological and physiological features of the dilated cardiomyopathy of Kearns-Sayre syndrome(1-4). Furthermore, our findings provide genetic evidence that the respiratory chain is critical for normal heart function. C1 Karolinska Hosp, Dept Mol Med, Ctr Mol Med L8 02, S-17176 Stockholm, Sweden. Karolinska Hosp, Dept Woman & Child Hlth, S-17176 Stockholm, Sweden. Sahlgrenska Hosp, Dept Pathol, S-41345 Gothenburg, Sweden. Hop Necker Enfants Malad, Unite Rech Handicaps Genet Enfant, INSERM U393, F-75015 Paris, France. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. Stanford Univ, Sch Med, Howard Hughes Med Inst, Dept Pediat & Genet, Stanford, CA 94305 USA. Karolinska Inst, Dept Physiol & Pharmacol, S-17177 Stockholm, Sweden. RP Larsson, NG (reprint author), Karolinska Hosp, Dept Mol Med, Ctr Mol Med L8 02, S-17176 Stockholm, Sweden. EM nils-goran.larsson@cmm.ki.se RI graff, caroline/A-2545-2009 FU NIGMS NIH HHS [R37-GM33088-28] NR 30 TC 238 Z9 249 U1 1 U2 4 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 JAN PY 1999 VL 21 IS 1 BP 133 EP 137 DI 10.1038/5089 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 155RT UT WOS:000077960700025 PM 9916807 ER PT J AU Eskandar, EN Assad, JA AF Eskandar, EN Assad, JA TI Dissociation of visual, motor and predictive signals in parietal cortex during visual guidance SO NATURE NEUROSCIENCE LA English DT Article ID LATERAL INTRAPARIETAL AREA; PURSUIT; SYSTEM AB The role of the posterior parietal cortex (PPC) in the visual guidance of movements was studied in monkeys trained to use a joystick to guide a spot to a target. Visual and motor influences were dissociated by transiently occluding the spot and by varying the relationship between the direction of joystick and spot movements. We found a strong segregation of function in PPC during visual guidance. Neurons in area MST were selectively modulated by the direction of visible moving stimuli, whereas neurons in area MIP were selectively modulated by the direction of hand movement. In contrast, the selectivity of cells in the lateral intraparietal area (LIP) did not directly depend on either visual input or motor output, but rather seemed to encode a predictive representation of stimulus movement. These predictive signals may be an important link in visuomotor transformations. C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. RP Assad, JA (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, 220 Longwood Ave, Boston, MA 02115 USA. EM jassad@hms.harvard.edu NR 17 TC 115 Z9 116 U1 0 U2 8 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JAN PY 1999 VL 2 IS 1 BP 88 EP 93 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 163MK UT WOS:000078409300018 PM 10195185 ER PT J AU Stehman-Breen, C Alpers, CE Fleet, WP Johnson, RJ AF Stehman-Breen, C Alpers, CE Fleet, WP Johnson, RJ TI Focal segmental glomerular sclerosis among patients infected with hepatitis C virus SO NEPHRON LA English DT Article DE focal segmental glomerular sclerosis; hepatitis C virus; heroin nephropathy ID MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS; RENAL-DISEASE; NEPHROPATHY; GLOMERULOSCLEROSIS AB This study describes the occurence of hepatitis C virus (HCV) infection in the setting of focal segmental glomerular sclerosis (FSGS). All patients with the pathologic diagnosis of idiopathic FSGS between 1992 and 1996 at the University of Washington Hospitals were examined using a retrospective cohort study design. FSGS was determined by renal biopsy in the absence of secondary causes. Demographic, laboratory, and outcome data were collected in a standardized fashion. Six patients (50%) were infected with HCV. Patients with HCV infection and FSGS were primarily Black (67%), hypertensive (100%), had a history of intravenous drug abuse (83%), and had normal liver enzymes. Those with HCV infection and a history of IVDA appeared clinically and histologically similar to previously described cases of 'heroin nephropathy'. We demonstrate that there is a high prevalence of HCV infection in our population of patients with idiopathic FSGS. Although this may simply reflect an epiphenomenon, we propose that HCV infection may play a role in the development of FSGS in a predisposed host. C1 Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98195 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Stehman-Breen, C (reprint author), VA Puget Sound Healthcare Syst, 1660 S Columbian Way,Mailstop 111A, Seattle, WA 98108 USA. EM cos@u.washington.edu FU NIDDK NIH HHS [DK 07721] NR 22 TC 41 Z9 41 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-2766 J9 NEPHRON JI Nephron PD JAN PY 1999 VL 81 IS 1 BP 37 EP 40 DI 10.1159/000045243 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 162HU UT WOS:000078340700006 PM 9884417 ER PT J AU Meyer, JW Makris, N Bates, JF Caviness, VS Kennedy, DN AF Meyer, JW Makris, N Bates, JF Caviness, VS Kennedy, DN TI MRI-based topographic parcellation of human cerebral white matter I. Technical foundations SO NEUROIMAGE LA English DT Article ID CORTEX AB We describe a virtually automatic comprehensive parcellation of the human cerebral central white matter, which is based upon T1-weighted MRI scans. The system, which is "rule-based," is developed from prior anatomic studies of the human brain and experimental studies of connectivity in animals as elaborated in the companion manuscript. Boundaries which delineate anatomic subregions of the white matter are computed from the geometric features of anatomic landmarks visible in the imaging data. The fiber systems of the central white matter are ordered topographically into three compartments, reflecting the inferred arrangements of principal neural systems pathways. These include an outer radiate (fibers principally radially aligned), an intermediate sagittal (fibers principally sagittally aligned), and deep bridging (fibers bridging hemispheres or cortex and deep structures) compartments. Each of these compartments is secondarily parcellated into smaller units to increase the anatomic specificity and spatial resolution of the system. The principal intended uses for this system of anatomic subdivision are for the volumetric characterization of forebrain white matter in normal and abnormal brains and for precision and specificity of localization in focal lesion-deficit correlation studies. (C) 1999 Academic Press. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Ctr Morphometri Anal, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, NMR Ctr, Boston, MA 02114 USA. RP Meyer, JW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Ctr Morphometri Anal, Boston, MA 02114 USA. RI Kennedy, David/H-3627-2012 FU NIDA NIH HHS [DA09467]; NINDS NIH HHS [NS34189, NS27950] NR 24 TC 43 Z9 44 U1 0 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN PY 1999 VL 9 IS 1 BP 1 EP 17 DI 10.1006/nimg.1998.0383 PG 17 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 165GN UT WOS:000078512700001 PM 9918725 ER PT J AU Makris, N Meyer, JW Bates, JF Yeterian, EH Kennedy, DN Caviness, VS AF Makris, N Meyer, JW Bates, JF Yeterian, EH Kennedy, DN Caviness, VS TI MRI-Based topographic parcellation of human cerebral white matter and nuclei II. Rationale and applications with systematics of cerebral connectivity SO NEUROIMAGE LA English DT Review ID POSTERIOR PARIETAL CORTEX; HUMAN CORPUS-CALLOSUM; RHESUS-MONKEY; BASAL GANGLIA; CORTICOSTRIATAL PROJECTIONS; CORTICOTHALAMIC CONNECTIONS; HIPPOCAMPAL-FORMATION; MACAQUE MONKEY; MACACA-FASCICULARIS; PREFRONTAL CORTEX AB We describe a system for parcellation of the human cerebral white matter and nuclei, based upon magnetic resonance images. An algorithm for subdivision of the cerebral central white matter according to topographic criteria is developed in the companion manuscript. In the present paper we provide a rationale for this system of parcellation of the central white matter and we extend the system of cerebral parcellation to include principal subcortical gray structures such as the thalamus and the basal ganglia. The volumetric measures of the subcortical gray and white matter parcellation units in 20 young adult brains are computed and reported here as well. In addition, with the comprehensive system for cerebral gray and white matter structure parcellation as reference, we formulate a systematics of forebrain connectivity. The degree to which functionally specific brain areas correspond to topographically specific areas is an open empirical issue. The resolution of this issue requires the development of topographically specific anatomic analyses, such as presented in the current system, and the application of such systems to a comprehensive set of functional-anatomic correlation studies in order to establish the degree of structural-functional correspondence. This system is expected to be applied in both cognitive and clinical neuroscience as an MRI-based topographic systematics of human forebrain anatomy with normative volumetric reference and also as a system of reference for the anatomic organization of specific neural systems as disrupted by focal lesions in lesion-deficit correlations. (C) 1999 Academic Press. C1 Harvard Univ, Sch Med, Ctr Morphometr Anal, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Boston, MA 02114 USA. Colby Coll, Dept Psychol, Waterville, ME 04901 USA. RP Makris, N (reprint author), Harvard Univ, Sch Med, Ctr Morphometr Anal, Dept Neurol, Boston, MA 02114 USA. RI Kennedy, David/H-3627-2012 FU NIDA NIH HHS [DA09467]; NINDS NIH HHS [P01 NS27950, NS27950] NR 121 TC 160 Z9 163 U1 0 U2 10 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN PY 1999 VL 9 IS 1 BP 18 EP 45 DI 10.1006/nimg.1998.0384 PG 28 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 165GN UT WOS:000078512700002 PM 9918726 ER PT S AU Maynard, KI Quinones-Hinojosa, A Malek, JY AF Maynard, KI Quinones-Hinojosa, A Malek, JY BE Trembly, B Slikker, W TI Neuroprotection against ischemia by metabolic inhibition revisited - A comparison of hypothermia, a pharmacologic cocktail and magnesium plus mexiletine SO NEUROPROTECTIVE AGENTS: FOURTH INTERNATIONAL CONFERENCE SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 4th International Conference on Neuroprotective Agents - Clinical and Experimental Aspects CY NOV 15-19, 1998 CL ANNAPOLIS, MD SP US FDA, Natl Ctr Toxicol Res, Dept Vet Affairs Med Ctr ID FOCAL CEREBRAL-ISCHEMIA; MAGNETIC-RESONANCE SPECTROSCOPY; ENERGY-METABOLISM; MILD HYPOTHERMIA; BRAIN-DAMAGE; PROTECTIVE THERAPY; RABBIT RETINA; CNS ISCHEMIA; NITRIC-OXIDE; BLOOD-FLOW AB Previous studies have suggested that metabolic inhibition is neuroprotective, but little evidence has been provided to support this proposal, Using the in vitro rabbit retina preparation as an established model of the central nervous system (CNS), we measured the rate of glucose utilization and lactate production, and the light-evoked compound action potentials (CAPs) as indices of neuronal energy metabolism and electrophysiologic function, respectively. We examined the effect of three (3) treatments options: hypothermia (i.e., 33 degrees C and 30 degrees C), a six-member pharmacologic "cocktail" (tetrodotoxin (0.1 mu M), 2-amino- 4-phosphonobutyric acid (20 mu M), 2-amino-5-phosphonovaleric acid (1 mM), amiloride (1 mM), magnesium (10 mM) and lithium (10 mM)) and the combination of magnesium (Mg(2+) 1 mM) and mexiletine (Mex, 300 mu M) on in vitro rabbit retinas, to see if there is a correlation between neuronal energy metabolism during ischemia (simulated by the reduction of oxygen from 95% to 15% and glucose from 6 mM to 1 mM), and the subsequent recovery of function. Hypothermia and the "cocktail" significantly inhibited both the rate of glucose utilization and lactate production, whereas Mg(2+) and/or Mex showed only a nonsignificant tendency toward a reduction, compared to control retinas, Recovery of light-evoked CAPs was significantly improved in hypothermia and cocktail-treated retinas, as well as with retinas exposed to the combination of Mg(2+) plus Mex, but not with Mg(2+) or Mex alone, relative to control retinas. A linear regression analysis of the % recovery of function versus the % reduction in the rate of glucose utilization during ischemia showed a significant correlation (r(2) = 0.80, correlation coefficient = 0.9, p < 0.05) between these two parameters. This and other data discussed provide convincing evidence that there is a correlation between metabolic inhibition, achieved during ischemia, and neuroprotection. C1 Massachusetts Gen Hosp, Neurophysiol Lab, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Maynard, KI (reprint author), Massachusetts Gen Hosp, Neurophysiol Lab, Neurosurg Serv, Edwards 414, Boston, MA 02114 USA. EM Maynard@helix.mgh.harvard.edu NR 67 TC 13 Z9 13 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-223-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 890 BP 240 EP 254 DI 10.1111/j.1749-6632.1999.tb07999.x PG 15 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BP50F UT WOS:000085330700022 PM 10668430 ER PT J AU Nagamoto, HT Adler, LE McRae, KA Huettl, P Cawthra, E Gerhardt, G Hea, R Griffith, J AF Nagamoto, HT Adler, LE McRae, KA Huettl, P Cawthra, E Gerhardt, G Hea, R Griffith, J TI Auditory P50 in schizophrenics on clozapine: Improved gating parallels clinical improvement and changes in plasma 3-methoxy-4-hydroxyphenylglycol SO NEUROPSYCHOBIOLOGY LA English DT Article DE auditory evoked potential; schizophrenia; clozapine; sensory gating; 3-methoxy-4-hydroxyphenylglycol; homovanillic acid ID CATECHOLAMINE METABOLISM; TREATMENT RESPONSE; NEUROPHYSIOLOGICAL EVIDENCE; PSYCHIATRIC-INPATIENTS; HALOPERIDOL TREATMENT; STIMULATION INTERVAL; CEREBROSPINAL-FLUID; NOREPINEPHRINE; PSYCHOSIS; DEFICIT AB Schizophrenic patients have decreased inhibition of the P50 auditory evoked potential response to the second of two paired click stimuli delivered 500 ms apart. This deficit in inhibitory gating does not change during treatment with typical neuroleptics. We recently reported that neuroleptic-resistant schizophrenics had enhanced P50 gating after 1 month of clozapine treatment, if they responded with decreased clinical symptoms. This study reports the outcome of more prolonged treatment. Ten treatment-refractory schizophrenic patients were studied at baseline, after 1 month on clozapine, and again after 15 +/- 6.1 (SD) months of clozapine treatment. Eight subjects reached a clinically stable improved state, at which time they had significantly improved P50 auditory gating. One patient had a return of impaired gating after stopping clozapine, as did another during a clinical relapse. Decreasing plasma 3-methoxy-4-hydroxyphenylglycol levels with clozapine treatment were correlated with improved P50 gating and improved Brief Bsychiatric Rating Scale-positive scores. This study provides further evidence that improved P50 gating in schizophrenic patients treated with clozapine coincides with clinical improvement and that this improvement can be sustained for at least 1 year. C1 Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Dept Psychiat, Denver, CO USA. RP Adler, LE (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Psychiat, C-268-71,4200 E 9th Ave, Denver, CO 80262 USA. FU NIMH NIH HHS [1 RO1 MH-50787] NR 62 TC 85 Z9 86 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0302-282X J9 NEUROPSYCHOBIOLOGY JI Neuropsychobiology PY 1999 VL 39 IS 1 BP 10 EP 17 DI 10.1159/000026553 PG 8 WC Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 161XA UT WOS:000078313900002 PM 9892854 ER PT J AU Mendola, JD Corkin, S AF Mendola, JD Corkin, S TI Visual discrimination and attention after bilateral temporal-lobe lesions: A case study SO NEUROPSYCHOLOGIA LA English DT Article DE pattern; perception; IT; achromatopsia; prosopagnosia; attention ID LATERAL GENICULATE-NUCLEUS; STATE DEPENDENT ACTIVITY; EXTRASTRIATE AREA V4; INFEROTEMPORAL LESIONS; CONTRAST SENSITIVITY; RHESUS-MONKEYS; MACAQUE MONKEY; CORTEX; NEURONS; COLOR AB We studied a woman (Case I)who acquired achromatopsia, prosopagnosia, and memory loss after sustaining bilateral temporal-lobe lesions. Given her symptoms and locus of lesion, the affected area may be related to the monkey visual area IT. In order to examine her deficits, we assessed her basic discrimination capacities in several domains. She performed normally when stimuli differed in contrast, size, or motion, her performance was abnormal for patterned targets, and was markedly impaired when the patterned targets were less prominent than distracters. This impairment decreased with practice. These symptoms partially resemble the deficits that have been found in monkeys with lesions in Visual cortical area V4. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. MIT, Clin Res Ctr, Cambridge, MA 02139 USA. RP Mendola, JD (reprint author), Massachusetts Gen Hosp, NMR Ctr, 149 13th St 2301, Charlestown, MA 02129 USA. EM janine@nmr.mgh.harvard.edu FU NCRR NIH HHS [RR00088]; NIGMS NIH HHS [T32GM07484]; NIMH NIH HHS [T32MH15761] NR 60 TC 9 Z9 9 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD JAN PY 1999 VL 37 IS 1 BP 91 EP 102 PG 12 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 148TL UT WOS:000077548900011 PM 9920475 ER PT J AU Allen, DN Goldstein, G Aldarondo, F AF Allen, DN Goldstein, G Aldarondo, F TI Neurocognitive dysfunction in patients diagnosed with schizophrenia and alcoholism SO NEUROPSYCHOLOGY LA English DT Article ID NEUROPSYCHOLOGICAL TEST-PERFORMANCE; SUBSTANCE-ABUSE; PREVALENCE; DISORDERS; SYMPTOMS; BRAIN AB The authors administered the Halstead-Reitan Neuropsychological Test Battery to schizophrenic groups with (n = 54) and without (n = 217)coexisting alcoholism, nonschizophrenic groups with alcoholism (n = 231), and a patient comparison group (n = 145) to determine the extent of additive cognitive impairment in schizophrenia associated with alcoholism and to compare cognitive function in alcoholism and schizophrenia. The additive effects of alcoholism on cognitive dysfunction in schizophrenia were subtle but were consistently identifiable. Cognitive dysfunction in alcoholism was less severe than in schizophrenia with or without alcoholism. The magnitude of additive effects of alcoholism on cognitive dysfunction in schizophrenia was age related with a significant interaction between age and presence or absence of alcoholism on a global index of cognitive dysfunction. C1 VA Pittsburgh Healthcare Syst, Highland Dr Div, Psychol Serv 151R, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. RP Allen, DN (reprint author), VA Pittsburgh Healthcare Syst, Highland Dr Div, Psychol Serv 151R, 7180 Highland Dr, Pittsburgh, PA 15206 USA. NR 38 TC 35 Z9 37 U1 2 U2 5 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD JAN PY 1999 VL 13 IS 1 BP 62 EP 68 DI 10.1037/0894-4105.13.1.62 PG 7 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 162HA UT WOS:000078338800008 PM 10067777 ER PT J AU Elman, I Goldstein, DS Eisenhofer, G Folio, J Malhotra, AK Adler, CM Pickar, D Breier, A AF Elman, I Goldstein, DS Eisenhofer, G Folio, J Malhotra, AK Adler, CM Pickar, D Breier, A TI Mechanism of peripheral noradrenergic stimulation by clozapine SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE schizophrenia; norepinephrine; clozapine; catecholamine; fluphenazine; spillover ID PLASMA-CATECHOLAMINES; NOREPINEPHRINE; SCHIZOPHRENIA; HUMANS; EFFICACY; PATTERN; ACID; FATE AB Elevated plasma norepinephrine (NE) levels is a relatively consistent clinical effect of clozapine. Plasma NE levels reflect an interplay of release, reuptake, metabolism, and excretion. To explore the mechanism of clozapine-induced plasma NE elevation, we measured arterial plasma levels of NE and other catechols during intravenous infusion of tritium-labeled NE (H-3-NE) in schizophrenic patients treated with clozapine, fluphenazine, or placebo. Clozapine treated patients had markedly higher levels of NE than did the patients treated with fluphenazine or placebo. NE spillover averaged move than three times higher in clozapine-treated patients; whereas NE clearance did not differ among the groups. Production of H-3-dihydroxyphenylglycol (H-3-DHPG), a purely intraneuronal metabolite of H-3-NE in clozapine-treated patients was normal, indicating that clozapine did not affect neuronal uptake of NE. Because plasma levels of DHPG and dihydroxyphenylacetic acid (DOPAC), deaminated metabolites of catecholamines, in clozapine-treated patients were normal, clozapine also did not seem to inhibit intraneuronal monoamine oxidase (MAO). High plasma NE levels in clozapine-treated patients, therefore, resulted from increased NE spillover rather than decreased reuptake, metabolism, or clearance. [Neuropsychopharmacology 20:29-34, 1999] Published by Elsevier Science Inc. C1 NIMH, Expt Therapeut Branch, NIH, Bethesda, MD USA. NIMH, Clin Neurosci Branch, NIH, Bethesda, MD USA. RP Elman, I (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, W End House,16 Blossom St, Boston, MA 02114 USA. NR 30 TC 29 Z9 29 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 1999 VL 20 IS 1 BP 29 EP 34 DI 10.1016/S0893-133X(98)00047-5 PG 6 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 141LH UT WOS:000077145100004 PM 9885782 ER PT J AU Rothe, F Huang, PL Wolf, G AF Rothe, F Huang, PL Wolf, G TI Ultrastructural localization of neuronal nitric oxide synthase in the laterodorsal tegmental nucleus of wild-type and knockout mice SO NEUROSCIENCE LA English DT Article DE NADPH-diaphorase histochemistry; immunocytochemistry; mutant mouse; electron microscopy ID NADPH-DIAPHORASE ACTIVITY; RAT-BRAIN; SUBCELLULAR-LOCALIZATION; CYTOCHROME-P-450 REDUCTASE; ENDOTHELIAL-CELLS; BLOOD-VESSELS; ELECTRON; LIGHT; IMMUNOREACTIVITY; EXPRESSION AB The cellular and subcellular distribution of neuronal nitric oxide synthase and its related reduced P-nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase activity was compared in wild-type and homozygous knockout mice, in which the gene for neuronal nitric oxide synthase has been disrupted, resulting in a lack of the predominant splice isoform a. In the laterodorsal tegmental nucleus, used as a model structure, the cholinergic principal neurons also exhibited an intensive neuronal nitric oxide synthase immunoreactivity. Using the tetrazolium salt 2-(2'-benzothiazolyl)-5-styryl-3-(4'-phthalhydrazidyl)-tetrazolium chloride (BSPT), these neurons were filled with NADPH-diaphorase reaction product, whereas the equivalent neurons of knockout mice showed, if at all, only traces of neuronal nitric oxide synthase immunoreactivity in parallel to a diminished NADPH-diaphorase labelling. Subcellularly, the neuronal nitric oxide synthase-related diaminobenzidine product was, apparently owing to diffusion artifact, more or less evenly distributed in the cytosol of the neuronal perikarya and dendrites of wild-type mice. In contrast, the BSPT reaction product formazan was closely and discretely attached to endocellular membranes. In the intensely NADPH-diaphorase stained neurons of wild-type mice, 85% of the mitochondria were, at least partly, labelled for BSPT-formazan, whilst in the equivalent neurons of mutant mice, only 13% of mitochondria were NADPH-diaphorase positive. Related to the NADPH-diaphorase activity in the principal neurons of wild-type mice, only 10% of membranes of the endoplasmic reticulum, 27% of mitochondrial membranes and 26% of the nuclear envelope exhibited NADPH-diaphorase activity in the mutant mice. Our findings with the BSPT histochemistry suggest that residues of NADPH-diaphorase positivity in mutant mice are attributed to the alternative splice isoforms beta and/or gamma of neuronal nitric oxide synthase. The splice isoform a is located predominantly at the membranes of the endoplasmic reticulum. (C) 1999 IBRO. Published by Elsevier Science Ltd. C1 Univ Magdeburg, Inst Med Neurobiol, D-39120 Magdeburg, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. RP Rothe, F (reprint author), Univ Magdeburg, Inst Med Neurobiol, Leipziger Str 44, D-39120 Magdeburg, Germany. FU NINDS NIH HHS [NS-33335] NR 58 TC 26 Z9 27 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 94 IS 1 BP 193 EP 201 DI 10.1016/S0306-4522(99)00263-8 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 239EH UT WOS:000082755500021 PM 10613509 ER PT J AU Fink, KB Andrews, LJ Butler, WE Ona, VO Li, M Bogdanov, M Endres, M Khan, SQ Namura, S Stieg, PE Beal, MF Moskowitz, MA Yuan, J Friedlander, RM AF Fink, KB Andrews, LJ Butler, WE Ona, VO Li, M Bogdanov, M Endres, M Khan, SQ Namura, S Stieg, PE Beal, MF Moskowitz, MA Yuan, J Friedlander, RM TI Reduction of post-traumatic brain injury and free radical production by inhibition of the caspase-1 cascade SO NEUROSCIENCE LA English DT Article DE caspase-1; interleukin-1 beta-converting enzyme; apoptosis; DNA fragmentation; TUNEL; caspase inhibition ID INTERLEUKIN-1-BETA CONVERTING-ENZYME; TROPHIC FACTOR WITHDRAWAL; APOPTOTIC CELL-DEATH; NEURONAL APOPTOSIS; IL-1-BETA-CONVERTING ENZYME; MEDIATED APOPTOSIS; MAMMALIAN HOMOLOG; FAMILY PROTEASES; TRANSGENIC MICE; GENE CED-3 AB Necrotic and apoptotic cell death both play a role mediating tissue injury following brain trauma. Caspase-1 (interleukin-1 beta converting enzyme) is activated and oligonucleosomal DNA fragmentation is detected in traumatized brain tissue. Reduction of tissue injury and free radical production following brain trauma was achieved in a transgenic mouse expressing a dominant negative inhibitor of caspase-1 in the brain. Neuroprotection was also conferred by pharmacological inhibition of caspase-1 by intracerebroventricular administration of the selective inhibitor of caspase-1, acetyl-Tyr-Val-Ala-Asp-chloromethylketone or the non-selective caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone. These results indicate that inhibition of caspase-1-like caspases reduces trauma-mediated brain tissue injury. In addition, we demonstrate an in vivo functional interaction between interleukin-1 beta converting enyzme-like caspases and free radical production pathways, implicating free radical production as a downstream mediator of the caspase cell death cascade. (C) 1999 IBRO. Published by Elsevier Science Ltd. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg,Neurosurg Serv, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Univ Bonn, Sch Med, Dept Pharmacol, D-53113 Bonn, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv & Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Neurosurg Serv, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Friedlander, RM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg,Neurosurg Serv, 75 Francis St, Boston, MA 02115 USA. RI Moskowitz, Michael/D-9916-2011; Friedlander, Robert/A-2845-2016 OI Friedlander, Robert/0000-0003-4423-9219 NR 53 TC 71 Z9 76 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 94 IS 4 BP 1213 EP 1218 DI 10.1016/S0306-4522(99)00345-0 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 256PW UT WOS:000083735000019 PM 10625061 ER PT J AU Berezovska, O McLean, P Knowles, R Frosh, M Lu, FM Lux, SE Hyman, BT AF Berezovska, O McLean, P Knowles, R Frosh, M Lu, FM Lux, SE Hyman, BT TI Notch1 inhibits neurite outgrowth in postmitotic primary neurons SO NEUROSCIENCE LA English DT Article DE Notch1; CBF1; numb; primary neurons; neurite outgrowth; transfection ID CAENORHABDITIS-ELEGANS; ALZHEIMERS-DISEASE; ACTIVATED NOTCH; CELL FATES; DROSOPHILA; GENE; EXPRESSION; NUMB; NEUROGENESIS; TRANSCRIPTION AB Notch plays an important role in cell fate decisions in uncommitted proliferative cells, including neurogenesis, but is believed to not have a role in postmitotic cells. We have shown previously that Notch1 is highly expressed in embryonal mouse and human brain, but surprisingly it continues to be expressed at low levels in the adult brain. The function of Notch1 in postmitotic neurons in mammals is unknown. To better understand the potential role of Notch1 in mature central nervous system neurons we studied the effect of Notch1 transfection on neurite outgrowth in primary neocortex hippocampal neurons. Transfection at two days in vitro with full length Notch1 inhibited neurite outgrowth. Transfection at five to six days in vitro, after neurite outgrowth was established, led to apparent regression of neurites. These effects were enhanced when truncated constitutively active forms of Notch1 were introduced. Co-transfection with Numb, a physiological inhibitor of Notch, blocked Notch's effect on neurite outgrowth. We also examined whether Notch1 could activate C-promoter binding factor (CBF1) transcription factor using C-promoter binding factor-luciferase constructs, and demonstrated that this signal transduction pathway is present and can be activated in postmitotic neurons. Our results show that in postmitotic neurons Notch1 influences neurite morphology, and can activate its native signal transduction pathway. These data strongly suggest that Notch1 may play a physiologically important role in the central nervous system beyond neurogenesis. (C) 1999 IBRO. Published by Elsevier Science Ltd. C1 CND Brigham & Womens Hosp, Div Neuropathol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Alzheimers Res Unit, Charlestown, MA 02129 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Alzheimers Res Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG 11337, AG 14744, R01 AG15379] NR 47 TC 160 Z9 164 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 93 IS 2 BP 433 EP 439 DI 10.1016/S0306-4522(99)00157-8 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 222FL UT WOS:000081772800003 PM 10465425 ER PT J AU Gordon, JT Kaminski, DM Rozanov, CB Dratman, MB AF Gordon, JT Kaminski, DM Rozanov, CB Dratman, MB TI Evidence that 3,3 ',5-triiodothyronine is concentrated in and delivered from the locus coeruleus to its noradrenergic targets via anterograde axonal transport SO NEUROSCIENCE LA English DT Article DE chemical lesion; DSP-4; immunohistochemistry; thyroid hormone; tyrosine hydroxylase ID DOPAMINE-BETA-HYDROXYLASE; RAT CEREBRAL-CORTEX; THYROID-HORMONE; HIPPOCAMPAL-FORMATION; CERULEUS NEURONS; HYPOTHYROID RATS; NERVOUS-SYSTEM; MESSENGER-RNA; BRAIN; DSP-4 AB Recent immunohistochemical studies of rat brain triiodothyronine reveal heaviest localization in locus coeruleus perikarya. The cellular distribution is similar to that observed in concomitant studies of tyrosine hydroxylase immunohistochemistry: heavy clumps of immunoreactive triiodothyronine are distributed within locus coeruleus cytosol and in cell processes, leaving cell nuclei unstained. At the same time, in locus coeruleus targets, cell nuclei as well as surrounding neuropil are prominently triiodothyronine labeled. These observations, combined with diverse evidence Linking thyroid hormone with norepinephrine at many levels of physiological and pathophysiological function, led to the hypothesis that the locus coeruleus binds and accumulates triiodothyronine and delivers the hormone via anterograde axonal transport to postsynaptic locus coeruleus targets, where nuclear triiodothyronine receptors are densely concentrated. Furthermore, the hypothesis predicts that destruction of locus coeruleus nerve terminals would interrupt this neural route of triiodothyronine delivery and prevent or reduce triiodothyronine labeling of nuclear receptors in noradrenergic target cells. To test this formulation, we gave the specific locus coeruleus lesioning agent, N-(2-chloroethyl)-N-2-bromobenzylamine hydrochloride (DSP-4), to adult male rats and examined their brains three, five and seven days thereafter by triiodothyronine and, in alternate sections, tyrosine hydroxylase immunohistochemistry. Treatment with DSP-4 resulted in specific and selective reduction in tyrosine hydroxylase and triiodothyronine immunohistochemical labeling in cell nuclei and in nerve cell processes within the neuropil of the hippocampus and cerebral cortex at all time periods examined. The results demonstrate that full occupancy of locus coeruleus target cells by triiodothyronine requires the presence of intact locus coeruleus projections and supports the proposal that, like norepinephrine, triiodothyronine delivery to noradrenergic targets occurs through delivery by locus coeruleus terminals. These findings, provide strong support for earlier proposals that triiodothyronine functions as a co-transmitter with norepinephrine in addition to or as part of its genomic role in the cells receiving noradrenergic innervation. (C) 1999 IBRO. Published by Elsevier Science Ltd. C1 Vet Affairs Med Ctr, Med Res Serv, Philadelphia, PA 19104 USA. Med Coll Penn & Hahnemann Univ, Dept Med, Philadelphia, PA 19129 USA. RP Vet Affairs Med Ctr, Med Res Serv, Univ & Woodland Ave, Philadelphia, PA 19104 USA. FU NIMH NIH HHS [NIMH 45252] NR 59 TC 36 Z9 38 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 93 IS 3 BP 943 EP 954 DI 10.1016/S0306-4522(99)00146-3 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 226KG UT WOS:000082018700012 PM 10473259 ER PT J AU Teter, B Harris-White, ME Frautschy, SA Cole, GM AF Teter, B Harris-White, ME Frautschy, SA Cole, GM TI Role of apolipoprotein E and estrogen in mossy fiber sprouting in hippocampal slice cultures SO NEUROSCIENCE LA English DT Article DE apolipoprotein E; estrogen; neurite sprouting; Alzheimer's disease ID DENSITY-LIPOPROTEIN RECEPTOR; E-DEFICIENT MICE; SYNAPTIC PLASMA-MEMBRANES; RAT SCIATIC-NERVE; E GENE-EXPRESSION; ALZHEIMERS-DISEASE; ORGANOTYPIC CULTURES; LONG-TERM; NEURITE OUTGROWTH; FASCIA DENTATA AB A role for apolipoprotein E is implicated in regeneration of synaptic circuitry after neural injury. The in vitro mouse organotypic hippocampal slice culture system shows Timm's stained mossy fiber sprouting into the dentate gyrus molecular layer in response to deafferentation of the entorhinal cortex. We show that cultures derived from apolipoprotein E knockout mice are defective in this sprouting response; specifically, they show no sprouting in the: dorsal region of the dentate gyrus, yet retain sprouting in the ventral region. Dorsal but not ventral sprouting in cultures from C57Bl/6J mice is increased 75% by treatment with 100 pM 17 beta-estradiol; this response is blocked by both progesterone and tamoxifen. These results show that neuronal sprouting is increased by estrogen in the same region where sprouting is dependent on apolipoprotein E. Sprouting may be stimulated by estrogen through its up-regulation of apolipoprotein E expression leading to increased recycling of membrane lipids for use by sprouting neurons. Estrogen and apolipoprotein E may therefore interact in their modulation of both Alzheimer's disease risk and recovery from CNS injury. C1 Greater Los Angeles Vet Healthcare Syst, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Dept Med, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Dept Neurol, Sepulveda, CA 91343 USA. RP Teter, B (reprint author), Greater Los Angeles Vet Healthcare Syst, Sepulveda, CA 91343 USA. FU NIA NIH HHS [P50 AG016570, R01 AG010685, AG-10415] NR 84 TC 55 Z9 57 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 91 IS 3 BP 1009 EP 1016 DI 10.1016/S0306-4522(98)00630-7 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 195JV UT WOS:000080248000016 PM 10391478 ER PT J AU Zhu, JJ Uhlrich, DJ Lytton, WW AF Zhu, JJ Uhlrich, DJ Lytton, WW TI Burst firing in identified rat geniculate interneurons SO NEUROSCIENCE LA English DT Article DE thalamus; inhibition; vision; epilepsy ID NEOCORTICAL PYRAMIDAL NEURONS; NUCLEUS-RETICULARIS THALAMI; RECEPTOR-MEDIATED RESPONSES; ACTIVATED CATION CURRENT; RELAY NEURONS; IN-VITRO; ACTION-POTENTIALS; PATCH-CLAMP; BRAIN-STEM; ELECTROPHYSIOLOGICAL PROPERTIES AB We used whole-cell patch recording to study 102 local interneurons in the rat dorsal lateral geniculate nucleus in vitro. Input impedance with this technique (607.0 +/- 222.4 M Omega) was far larger than that measured with sharp electrode techniques, suggesting that interneurons may be more electrotonically compact than previously believed. Consistent and robust burst firing was observed in all interneurons when a slight depolarizing boost was given from a potential at, or slightly hyperpolarized from, resting membrane potential. These bursts had some similarities to the low-threshold spike described previously in other thalamic neuron types. The bursting responses were blocked by Ni+, suggesting that the low-threshold calcium current I-T, responsible for the low-threshold spike, was also involved in interneuron burst firing. Compared to the low-threshold spike of thalamocortical cells, however, the interneuron bursts were of relatively long duration and low intraburst frequency. The requirement for a depolarizing boost to elicit the burst is consistent with previous reports of a depolarizing shift of the I-T activation curve of interneurons relative to thalamocortical cells, a finding we confirmed using voltage-clamp. Voltage-clamp study also revealed an additional long-lasting current that could be tentatively identified as the calcium activated non-selective cation current, I-CAN, based on reversal potential and on pharmacological characteristics. Computer simulation of the interneuron burst demonstrated that its particular morphology is likely due to the interaction of I-T and I-CAN. In the slice, bursts could also be elicited by stimulation of the optic tract, suggesting that they may occur in response to natural stimulation. Synaptically triggered bursts were only partially blocked by Ni+, but could then be completely blocked by further addition of (+/-)-2-amino-5-phosphonopentanoic acid. The existence of robust bursts in this cell type suggests an additional role for interneurons in sculpting sensory responses by feedforward inhibition of thalamocortical cells. The low-threshold spike is a mechanism whereby activity in a neuron is dependent on a prior lack of activity in that same neuron. Understanding of the low-threshold spike in the other major neuron types of the thalamus has brought many new insights into how thalamic oscillations might be involved in sleep and epilepsy. Our description of this phenomenon in the interneurons of the thalamus suggests that these network oscillations might be even more complicated than previously believed. (C) 1999 IBPO. Published by Elsevier Science Ltd. C1 Univ Wisconsin, Dept Neurol, Neurosci Training Program, Madison, WI 53706 USA. William S Middleton Mem Vet Hosp, Madison, WI 53706 USA. Univ Wisconsin, Dept Anat, Neurosci Training Program, Madison, WI 53706 USA. RP Lytton, WW (reprint author), Univ Wisconsin, Dept Neurol, Neurosci Training Program, Madison, WI 53706 USA. NR 91 TC 48 Z9 50 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 91 IS 4 BP 1445 EP 1460 DI 10.1016/S0306-4522(98)00665-4 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 198RK UT WOS:000080437600024 PM 10391450 ER PT J AU Clatworthy, AE Stockinger, W Christie, RH Schneider, WJ Nimpf, J Hyman, BT Rebeck, GW AF Clatworthy, AE Stockinger, W Christie, RH Schneider, WJ Nimpf, J Hyman, BT Rebeck, GW TI Expression and alternate splicing of apolipoprotein E receptor 2 in brain SO NEUROSCIENCE LA English DT Article DE ApoE; immunochemistry; RT-PCR; neuron; Alzheimer's disease ID DENSITY-LIPOPROTEIN RECEPTOR; AMYLOID PRECURSOR PROTEIN; CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; NEURITE OUTGROWTH; GENETIC ASSOCIATION; CEREBROSPINAL-FLUID; MESSENGER-RNA; BETA; CELLS AB Apolipoprotein E isoforms affect the risk of developing Alzheimer's disease. Apolipoprotein E-associated risk may be related to its binding to and clearance by cell surface receptors, including members of the low-density lipoprotein receptor family. We examined the brain expression of the most recently identified member of this receptor family, apolipoprotein E receptor 2, in human brain and placenta. We analysed apolipoprotein E receptor 2 messenger RNA by reverse transcription-polymerase chain reaction and apolipoprotein E receptor 2 protein by immunohistochemistry. Four exons of the apolipoprotein E receptor 2 message were alternately spliced in both fetal and adult brain tissue. Exon 5, encoding three of the seven ligand binding repeats, was absent in the apolipoprotein E receptor 2 messenger RNA examined. Apolipoprotein E receptor 2 messages lacking exon 8, encoding an epidermal growth factor precursor repeat, exon 15, encoding the O-glycosylation region, or exon 18, encoding a cytoplasmic domain, were also present as minor splice variants in the brain and placenta. No differences were observed in the pattern of apolipoprotein E receptor 2 splicing between control and Alzheimer brains. Immunohistochemistry of mouse brain showed that apolipoprotein E receptor 2 was expressed in neurons throughout the brain, with strong expression in pyramidal neurons of the hippocampus, granule cells of the dentate gyrus, cortical neurons and Purkinje cells of the cerebellum. Thus, apolipoprotein E receptor 2 is the fourth apolipoprotein E receptor identified on neuronal cells. (C) 1999 IBRO. Published by Elsevier Science Ltd. C1 Massachusetts Gen Hosp, Alzheimer Res Unit, Boston, MA 02129 USA. Univ Vienna, Vienna, Austria. Bioctr, Dept Mol Genet, Vienna, Austria. RP Rebeck, GW (reprint author), Massachusetts Gen Hosp, Alzheimer Res Unit, 149 13th St, Boston, MA 02129 USA. FU NIA NIH HHS [AG05134, AG12406, AG14473] NR 45 TC 40 Z9 42 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 90 IS 3 BP 903 EP 911 DI 10.1016/S0306-4522(98)00489-8 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 182TY UT WOS:000079515300018 PM 10218790 ER PT J AU Facchinetti, F Sasaki, M Cutting, FB Zhai, P MacDonald, JE Reif, D Beal, MF Huang, PL Dawson, TM Gurney, ME Dawson, VL AF Facchinetti, F Sasaki, M Cutting, FB Zhai, P MacDonald, JE Reif, D Beal, MF Huang, PL Dawson, TM Gurney, ME Dawson, VL TI Lack of involvement of neuronal nitric oxide synthase in the pathogenesis of a transgenic mouse model of familial amyotrophic lateral sclerosis SO NEUROSCIENCE LA English DT Article DE copper/zinc superoxide dismutase; transgenic mice; amyotrophic lateral sclerosis; nitric oxide; peroxynitrite; AR-R 17,477 ID FOCAL CEREBRAL-ISCHEMIA; SUPEROXIDE-DISMUTASE MUTATION; MOTOR-NEURON; TYROSINE NITRATION; INCREASED 3-NITROTYROSINE; DEFICIENT MICE; INFARCT VOLUME; NOS INHIBITOR; CELL-DEATH; L-ARGININE AB A subset of familial cases of amyotrophic lateral sclerosis are linked to missense mutations in copper/zinc superoxide dismutase type 1. Patients with missense mutations in copper/zinc superoxide dismutase type 1 develop a paralytic disease indistinguishable from sporadic amyotrophic lateral sclerosis through an unknown toxic gain of function. Nitric oxide reacts with the superoxide anion to form the strong oxidant, peroxynitrite, which participates in neuronal injury in a variety of model systems. Peroxynitrite is an alternate substrate for copper/zinc superoxide dismutase type 1, causing catalytic nitration of tyrosine residues in other proteins. Mutations in copper/zinc superoxide dismutase type 1 may disrupt the active site of the enzyme and permit greater access of peroxy nitrite to copper, leading to increased nitration by peroxynitrite of critical cellular targets. To investigate whether neuronal-derived nitric oxide plays a role in the pathogenesis of familial amyotrophic lateral sclerosis, we examined the effects of three different nitric oxide synthase inhibitors: a non-selective nitric oxide synthase inhibitor, nitro-L-arginine methyl ester; a relatively selective inhibitor of neuronal nitric oxide synthase, 7-nitroindazole; and a novel highly selective neuronal nitric oxide synthase inhibitor, AK-R 17,477, in transgenic mice expressing a familial amyotrophic lateral sclerosis-linked mutant human copper/zinc superoxide dismutase type 1 (Gly --> Ala at position 93; G93A) containing a high transgene copy number and a low transgene copy number. AR-R 17,477, but not nitro-l-arginine methyl ester or 7-nicroindazole, significantly prolonged survival in both the high and low transgene transgenic mice. To determine whether neuronal nitric oxide synthase is involved in the pathogenesis resulting from the familial amyotrophic lateral sclerosis copper/zinc superoxide dismutase type 1 mutation, we produced mice with the copper/zinc superoxide dismutase type 1 mutation which lack the neuronal nitric oxide synthase gene. The transgenic mice expressing a familial amyotrophic lateral sclerosis-linked mutant human copper/zinc superoxide dismutase type 1 on neuronal nitric oxide synthase null background do not live significantly longer than transgenic mice expressing a familial amyotrophic lateral sclerosis-linked mutant human copper/zinc superoxide dismutase type 1. Western blot analysis indicates the presence of two neuronal nitric oxide synthase-like immunoreactive bands in spinal cord homogenates of the neuronal nitric oxide synthase null mice, and residual neuronal nitric oxide synthase catalytic activity ( greater than 7%) is detected in the spinal cord of the transgenic mice expressing a familial amyotrophic lateral sclerosis-linked mutant human copper/zinc superoxide dismutase type 1 on neuronal nitric oxide synthase null background. This amount of residual activity probably does not account for lack of protection afforded by the disrupted neuronal nitric oxide synthase gene in the familial amyotrophic lateral sclerosis-linked mutant human copper/zinc superoxide dismutase type 1 mice. Immunological nitric oxide synthase is not detected in the copper/zinc superoxide dismutase type 1 mutant mice at several different ages, thus excluding immunological nitric oxide synthase as a contributor to the pathogenesis of familial amyotrophic lateral sclerosis. Levels of neuronal nitric oxide synthase as well as Ca2+-dependent nitric oxide synthase catalytic activity in the copper/zinc superoxide dismutase type 1 mutant mice do not differ from wild type mice. Endothelial nitric oxide synthase levels may be decreased in the copper/zinc superoxide dismutase type 1 mutant mice. Together, these results do not support a significant role for neuronal-derived nitric oxide in die pathogenesis of familial amyotrophic lateral sclerosis transgenic mice. (C) 1999 IBRO. Published by Elsevier Science Ltd. C1 Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21287 USA. Pharmacia & Upjohn Inc, Cent Nervous Syst Dis Res Unit, Kalamazoo, MI 49001 USA. Astra Arcus USA, Div Biol, Rochester, NY 14602 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp E, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Dawson, VL (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurol, 600 N Wolfe St,Carnegie 214, Baltimore, MD 21287 USA. OI Dawson, Valina/0000-0002-2915-3970 FU NINDS NIH HHS [NS 33277, NS 01578, NS 33142] NR 69 TC 68 Z9 68 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 1999 VL 90 IS 4 BP 1483 EP 1492 DI 10.1016/S0306-4522(98)00492-8 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 184UE UT WOS:000079631500031 PM 10338314 ER PT J AU Augood, SJ Waldvogel, HJ Munkle, MC Faull, RLM Emson, PC AF Augood, SJ Waldvogel, HJ Munkle, MC Faull, RLM Emson, PC TI Localization of calcium-binding proteins and GABA transporter (GAT-1) messenger RNA in the human subthalamic nucleus SO NEUROSCIENCE LA English DT Article DE Parkinson's disease; neurodegenerative disease; basal ganglia; parvalbumin; calbindin; calretinin ID GLUTAMIC-ACID DECARBOXYLASE; IN-SITU HYBRIDIZATION; BASAL GANGLIA; SUBSTANTIA-NIGRA; RAT-BRAIN; HUNTINGTONS-DISEASE; FUNCTIONAL-ANATOMY; EXTERNAL PALLIDUM; NEURONAL-ACTIVITY; GLOBUS-PALLIDUS AB The distribution of messenger RNA encoding the human GAT-1 (a high-affinity GABA transporter) was investigated in the subthalamic nucleus of 10 neurologically normal human post mortem cases. Further, the distribution of messenger RNA and protein encoding the three neuronally expressed calcium-binding proteins (calbindin D28k, parvalbumin and calretinin) was similarly investigated using in situ hybridization and immunohistochemical techniques. Cellular sites of calbindin D28k, parvalbumin, calretinin and GAT-1 messenger RNA expression were localized using human-specific oligonucleotide probes radiolabelled with [S-35]dATP. Sites of protein localization were visualized using specific anti-calbindin D28k, anti-parvalbumin and anti-calretinin antisera. Examination of emulsion-coated tissue sections processed for in situ hybridization revealed an intense signal for GAT-1 messenger RNA within the human subthalamic nucleus, indeed the majority of Methylene Blue-counterstained cells were enriched in this transcript. Further, a marked heterogeneity was noted with regard to the expression of the messenger RNA's encoding the three calcium-binding proteins; this elliptical nucleus was highly enriched in parvalbumin messenger RNA-positive neurons and calretinin mRNA-positive cells but not calbindin messenger RNA-positive cells. Indeed, only an occasional calbindin messenger RNA-positive cell was detected within the mediolateral extent of the nucleus. In marked contrast, numerous parvalbumin messenger RNA-positive cells and calretinin messenger RNA-positive cells were detected and they were topographically distributed; parvalbumin messenger RNA-positive cells were highly enriched in the dorsal subthalamic nucleus extending mediolaterally; calretinin messenger RNA-positive cells were more enriched ventrally although some degree of overlap was apparent. Computer-assisted analysis of the average cross-sectional somatic area of parvalbumin, calretinin and GAT-I messenger RNA-positive neurons revealed them all to be in the range of 300 mu m(2). The unique patterns of calcium-binding protein gene expression were similarly reflected at the protein level; an abundance of parvalbumin- and calretinin-immunopositive neurons were observed whereas only occasional intensely-labelled calbindin-immunopositive fibres were seen, no calbindin-immunopositive cells were detected. Single and double labelling studies show that parvalbumin-immunopositive neurons were mainly localized in the dorsal region of the nucleus, and calretinin-immunopositive neurons were mainly localized in the ventral region although there was overlap with double-labelled neurons located in the middle and dorsal regions. The significance of these findings, in particular the expression of GAT-1, a high-affinity GABA uptake protein, for basal ganglia signalling is discussed. (C) 1998 IBRO. Published by Elsevier Science Ltd. C1 Babraham Inst, Dept Neurobiol, Cambridge CB2 4AT, England. Univ Auckland, Fac Med & Hlth Sci, Dept Anat Radiol, Auckland 1, New Zealand. RP Augood, SJ (reprint author), Massachusetts Gen Hosp, Warren 408, Boston, MA 02114 USA. FU Wellcome Trust NR 47 TC 24 Z9 25 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD JAN PY 1999 VL 88 IS 2 BP 521 EP 534 DI 10.1016/S0306-4522(98)00226-7 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 130EJ UT WOS:000076506700017 PM 10197772 ER PT J AU Zaroff, JG Rordorf, GA Newell, JB Ogilvy, CS Levinson, JR AF Zaroff, JG Rordorf, GA Newell, JB Ogilvy, CS Levinson, JR TI Cardiac outcome in patients with subarachnoid hemorrhage and electrocardiographic abnormalities SO NEUROSURGERY LA English DT Article DE electrocardiography; heart disease; subarachnoid hemorrhage AB OBJECTIVE: Approximately 25% of patients with subarachnoid hemorrhage (SAH) have electrocardiographic (ECC) abnormalities consistent with myocardial ischemia or myocardial infarction (MI), and their cardiac prognosis remains unclear. The objective of this study was to determine the cardiac and all-cause mortality rate of a series of patients with SAH with ECC changes consistent with ischemia or MI. METHODS: Using an existing database of patients with SAH and predetermined ECG criteria for ischemia or MI, a study group of patients with abnormal ECG results within 3 days of presentation and before aneurysm surgery was identified. Database patients without abnormal ECC results served as a control group. Cardiac mortality, defined as death resulting from arrhythmia, congestive heart failure, or cardiogenic shock, was assessed by chart review. RESULTS: Of 439 patients with SAH in the database, 58 met the criteria for the study group. Forty-one of these patients were treated neurosurgically. No deaths resulting from cardiac causes occurred, and 20 patients died as a result of noncardiac causes. In a multivariable analysis, age older than 65 years and Hunt and Hess grade of at least 3 were predictive of all-cause mortality. ECG abnormalities, however, were not a statistically significant predictor. CONCLUSION: In patients with SAH and ECG readings consistent with ischemia or MI, the risk of death resulting from cardiac causes is low, with or without aneurysm surgery. The ECG abnormalities are associated with more severe neurological injury but are not independently predictive of all-cause mortality. C1 Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Unit, Boston, MA 02114 USA. RP Zaroff, JG (reprint author), Univ Calif San Francisco, Div Cardiol, 505 Parnassus Ave, San Francisco, CA 94143 USA. NR 11 TC 80 Z9 83 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JAN PY 1999 VL 44 IS 1 BP 34 EP 39 DI 10.1097/00006123-199901000-00013 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 152AD UT WOS:000077752300013 PM 9894961 ER PT J AU Magge, S Chapman, P Barnes, P Feany, M AF Magge, S Chapman, P Barnes, P Feany, M TI Spinal lipoma controversy SO NEUROSURGERY LA English DT Article ID NATURAL-HISTORY C1 Brigham & Womens Hosp, Dept Neurosurg, Neurosurg Serv, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Neurosurg Serv, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Magge, S (reprint author), Brigham & Womens Hosp, Dept Neurosurg, Neurosurg Serv, 75 Francis St, Boston, MA 02115 USA. NR 18 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD JAN PY 1999 VL 44 IS 1 BP 186 EP 192 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 152AD UT WOS:000077752300101 ER PT J AU Ghogawala, Z Ogilvy, CS AF Ghogawala, Z Ogilvy, CS TI Intramedullary cavernous malformations of the spinal cord SO NEUROSURGERY CLINICS OF NORTH AMERICA LA English DT Article ID VASCULAR MALFORMATIONS; CLINICAL PRESENTATION; ANGIOMAS; HEMANGIOMA; DIAGNOSIS AB Cavernous malformations of the spinal cord are extremely rare lesions. The 58 reported cases in the English literature and 9 of the authors' own cases are reviewed. The clinical presentation, patient characteristics, radiographic appearance, and histopathologic features are reviewed. The optimal surgical management and outcomes of treatment for intramedullary spinal cord cavernous malformations are discussed in detail. C1 Massachusetts Gen Hosp, Dept Cerebrovasc Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ogilvy, CS (reprint author), Massachusetts Gen Hosp, Dept Cerebrovasc Surg, Boston, MA 02114 USA. NR 28 TC 20 Z9 20 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 1042-3680 J9 NEUROSURG CLIN N AM JI Neurosurg. Clin. N. Am. PD JAN PY 1999 VL 10 IS 1 BP 101 EP + PG 12 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 328PF UT WOS:000087858700008 PM 9855652 ER PT J AU Meguid, MM Abcouwer, SF AF Meguid, MM Abcouwer, SF TI Molecular nutrition SO NUTRITION LA English DT Editorial Material C1 SUNY Hlth Sci Ctr, Dept Surg, Surg & Neurosci Program, Syracuse, NY 13210 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Meguid, MM (reprint author), SUNY Hlth Sci Ctr, Dept Surg, Surg & Neurosci Program, 750 E Adams St, Syracuse, NY 13210 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 JAN PY 1999 VL 15 IS 1 BP 53 EP 53 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 154JC UT WOS:000077884900011 ER PT J AU Abcouwer, SF Souba, WW AF Abcouwer, SF Souba, WW TI Is glutamine a pretender to the throne? SO NUTRITION LA English DT Editorial Material ID SUPPLEMENTED PARENTERAL-NUTRITION; CRITICALLY ILL PATIENTS; DOUBLE-BLIND; MUSCLE; PREVENT; SURGERY C1 Massachusetts Gen Hosp, Surg Oncol Res Labs, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Abcouwer, SF (reprint author), Massachusetts Gen Hosp, Surg Oncol Res Labs, Boston, MA 02114 USA. OI Abcouwer, Steven F/0000-0003-2580-1288 NR 17 TC 5 Z9 5 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 JAN PY 1999 VL 15 IS 1 BP 71 EP 72 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 154JC UT WOS:000077884900021 PM 9918074 ER PT J AU Aronson, WJ Tymchuk, CN Elashoff, RM McBride, WH McLean, C Wang, HJ Heber, D AF Aronson, WJ Tymchuk, CN Elashoff, RM McBride, WH McLean, C Wang, HJ Heber, D TI Decreased growth of human prostate LNCaP tumors in SCID mice fed a low-fat, soy protein diet with isoflavones SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID UNITED-STATES; CANCER CELLS; GENISTEIN; RISK; AMERICAN; WHITES; IMMIGRANTS; PRODUCTS; ANTIGEN; BLACKS AB Epidemiological studies suggest that high intake of dietary fat is a risk factor for the development of clinical prostate cancer. Soy protein has also been proposed to play a role in the prevention of prostate cancer, and one of the isoflavones in soy protein, genistein, inhibits the growth of human prostate cancer cell lines in vitro. This study was designed to evaluate whether altering dietary fat, soy protein, and isoflavone content affects the growth rate of a human androgen-sensitive prostate cancer cell line (LNCaP) grown in severe-combined immunodeficient (SCID) mice. SCID mice were randomized into four dietary groups. high-fat (42.0 kcal%) + casein, high-fat (42.0 kcal%) + soy protein + isoflavone extract, low-fat (12.0 kcal%) + casein, and low-fat (12.0 kcal%) + soy protein + isoflavone extract. After two weeks on these diets, the mice were injected subcutaneously with 1 x 10(5) LNCaP tumor cells and placed in separate cages (I mouse/cage) to strictly control caloric intake. Isocaloric diets were given 3 days/wk, and tumor sizes were measured once per week. The tumor growth rates were slightly reduced in the group that received the low-fat + soy protein + isoflavone extract diet compared with the other groups combined (p < 0.05). In addition, the final tumor weights were reduced by 15% in the group that received the low-fat + soy protein + isoflavone extract diet compared with the other groups combined (p < 0.05). In this xenograft model for prostate cancer, there were statistically significant effects on tumor growth rate and final tumor weight attributable to a low-fat + soy protein + isoflavone extract diet. C1 Univ Calif Los Angeles, Dept Urol, Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Physiol Sci, Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Biostat, Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Radiol Sci, Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Ctr Human Nutr, Sch Med, Los Angeles, CA 90095 USA. W Los Angeles Vet Adm Med Ctr, Los Angeles, CA 90073 USA. RP Aronson, WJ (reprint author), Univ Calif Los Angeles, Dept Urol, Sch Med, Box 951738, Los Angeles, CA 90095 USA. FU NCI NIH HHS [CA-42710-11, CA-42710-12] NR 29 TC 49 Z9 52 U1 1 U2 2 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 1999 VL 35 IS 2 BP 130 EP 136 DI 10.1207/S15327914NC352_6 PG 7 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 284RL UT WOS:000085346200006 PM 10693166 ER PT B AU Maratos-Flier, E AF Maratos-Flier, E BE Bray, GA Ryan, DH TI The role of melanin-concentrating hormone and the lateral hypothalamus in the regulation of eating behavior SO NUTRITION, GENETICS, AND OBESITY SE PENNINGTON CENTER NUTRITION SERIES LA English DT Proceedings Paper CT Symposium on Nutrition, Genetics, and Obesity CY MAR 01-03, 1998 CL NJ SP Pennington Biomed Res Ctr ID RAT-BRAIN; ALPHA-MSH; MICE; MCH; LOCALIZATION; ANTAGONIST; RECEPTOR; OBESITY; PROTEIN; PEPTIDE AB Melanin-concentrating hormone (MCH) is a 19 amino acid peptide expressed in the lateral hypothalamus. Melanin-concentrating hormone expression is increased in the ob/ob mouse and increases in both normal and ob/ob mice with fasting. Intracerebroventricular injection of MCH stimulates eating behavior in rats indicating that MCH functions as a lateral hypothalamic orexigenic factor. Melanin-concentrating hormone appears to act in an opposite manner to a-melanocyte-stimulating hormone (MSH), a known inhibitor of eating. Interestingly this opposite action is also seen in fish melanophores. When administered simultaneously MCH and MSH eating will be either induced or inhibited depending on the relative dose. The potential importance of the lateral hypothalamus as appetite center has recently been underscored by the discovery of orexin/hyprocretin, another appetite-stimulating peptide with expression limited to the lateral hypothalamus. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. RP Maratos-Flier, E (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. NR 32 TC 0 Z9 0 U1 0 U2 0 PU LOUISIANA STATE UNIV PRESS PI BATON ROUGE PA BATON ROUGE, LA 70803 USA BN 0-8071-2407-9 J9 PENN CTR N PY 1999 VL 9 BP 406 EP 417 PG 6 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA BN28X UT WOS:000081434900022 ER PT S AU Walker, WA Dai, DW AF Walker, WA Dai, DW BE Ziegler, EE Lucas, A Moro, GE TI Protective nutrients for the immature gut SO NUTRITION OF THE VERY LOW BIRTHWEIGHT INFANT SE NESTLE NUTRITION WORKSHOP SERIES PEDIATRIC PROGRAM LA English DT Proceedings Paper CT 43rd Nestle Nutrition Workshop CY 1998 CL WARSAW, POLAND ID NEONATAL NECROTIZING ENTEROCOLITIS; CHAIN FATTY-ACIDS; BACTERIAL TOXIN INTERACTION; HUMAN COLONIC MICROBIOTA; RAT SMALL-INTESTINE; BOTTLE-FED INFANTS; HUMAN-MILK; GASTROINTESTINAL-TRACT; ESCHERICHIA-COLI; FECAL FLORA C1 Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Mucosal Immunol Lab, Boston, MA 02114 USA. RP Walker, WA (reprint author), Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Mucosal Immunol Lab, Boston, MA 02114 USA. NR 73 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0742-2806 BN 0-7817-2215-2 J9 NESTLE NUTR WORKS SE PY 1999 VL 43 BP 179 EP 197 PG 19 WC Pediatrics SC Pediatrics GA BU50U UT WOS:000176201000012 ER PT J AU Pitris, C Goodman, A Boppart, SA Libus, JJ Fujimoto, JG Brezinski, ME AF Pitris, C Goodman, A Boppart, SA Libus, JJ Fujimoto, JG Brezinski, ME TI High-resolution imaging of gynecologic neoplasms using optical coherence tomography SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID BIOPSY AB Background: A modality capable of imaging the female reproductive tract, at or near the cellular level, could lead to the detection of diseases at earlier stages than currently possible. Optical coherenece tomography achieves high resolutions in the cellular range (4-20 mu m) and could accomplish that level of detection. Method: Optical coherence tomography imaging of gynecologic tissue was studied in vitro on normal and neoplastic human cervical and uterine tissue. Experience: The structures of the normal ectocervix and endocercrix, including epithelium, basal membrane, and glands, were identified clearly. These findings were compared with changes associated with carcinoma in situ and invasive carcinoma. The optical coherence tomography images of the uterus also showed changes between microstructural features of normal tissue and endometrial adenocarcinoma. Conclusion: Optical coherence tomography of tissue microstructures showed potential for powerful, minimally invasive assessment of the female reproductive tract at a resolution greater than any current clinical imaging method. (C) 1999 by The American College of Obstetricians and Gynecologists. C1 MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Kings Coll, Wilkes Barre, PA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Pitris, C (reprint author), MIT, Dept Elect Engn & Comp Sci, 50 Vassar St,Room 36-347, Cambridge, MA 02139 USA. RI Boppart, Stephen/C-7338-2009; OI Pitris, Costas/0000-0002-5559-1050 FU NCI NIH HHS [NIH-9-RO1-CA75289-01]; NEI NIH HHS [NIH-9-RO1-EY11289-13]; NIAMS NIH HHS [NIH-RO1-AR44812-01] NR 15 TC 101 Z9 103 U1 0 U2 0 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 JAN PY 1999 VL 93 IS 1 BP 135 EP 139 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 154JF UT WOS:000077885200027 PM 9916971 ER PT S AU Tuch, DS Wedeen, VJ Dale, AM George, JS Belliveau, JW AF Tuch, DS Wedeen, VJ Dale, AM George, JS Belliveau, JW BE Chen, CT Lee, RC Shih, JX Zhong, MH TI Conductivity mapping of biological tissue using diffusion MRI SO OCCUPATIONAL ELECTRICAL INJURY: AN INTERNATIONAL SYMPOSIUM SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 3rd International Conference on Electrical Injury and Safety CY OCT 26-28, 1998 CL SHANGHAI, PEOPLES R CHINA SP Univ Chicago, Elect Trauma Res Program, Shanghai Elect Power Hosp, China Burn Assoc, China Hydro Elect Power Med Sci Assoc, Cooper Bussmann, EI Dupont DeNemours & Co, US Electr Power Res Inst, Integra Lifesci, China Med Assoc, Shanghai Branch, Soc Phys regulat Biol & Med, US Natl Sci Fdn, Univ Chicago, Off Continuing Med Educ, Westaim Biomed Corp C1 Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. MIT, Dept Nucl Engn, Cambridge, MA 02139 USA. Univ Calif Los Alamos Natl Lab, Biophys Grp, Los Alamos, NM USA. RP Tuch, DS (reprint author), Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. RI Dale, Anders/A-5180-2010 NR 6 TC 51 Z9 54 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-232-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 888 BP 314 EP 316 DI 10.1111/j.1749-6632.1999.tb07965.x PG 3 WC Emergency Medicine; Public, Environmental & Occupational Health; Multidisciplinary Sciences; Rehabilitation SC Emergency Medicine; Public, Environmental & Occupational Health; Science & Technology - Other Topics; Rehabilitation GA BP20J UT WOS:000084392200031 PM 10842642 ER PT J AU Eagan, SM Jacobs, RJ Demers-Turco, PL AF Eagan, SM Jacobs, RJ Demers-Turco, PL TI Study of luminance effects on pinhole test results for visually impaired patients SO OPTOMETRY AND VISION SCIENCE LA English DT Article DE pinhole test; visual acuity; low-vision; refraction; retinal illuminance ID CLINICAL RESEARCH; ACUITY; SCHEINER,CHRISTOPH; ILLUMINATION; CHARTS; EYE AB Purpose. The visual acuity of visually impaired patients has been reported to improve after a refraction, despite pinhole test results that show a decline or no change in acuity. Our aim was to investigate whether the pinhole-induced reduction in retinal illuminance accounted for these unreliable predictions of best-corrected acuity. Methods. Participants were 64 adult patients referred for low-vision rehabilitation. Neutral density filters reproduced the pinhole-induced luminance loss, allowing pinhole test and postrefraction acuities to be measured at essentially equivalent levels of retinal illuminance. The following data were collected in random order from each subject's better eye: (1) habitual visual acuity, (2) habitual visual acuity with filter, (3) habitual visual acuity with pinhole, (4) best-corrected/postrefraction visual acuity, (5) postrefraction visual acuity with filter. Results. On average, the pinhole test under-estimated postrefraction visual acuity by six letters (95% confidence limits = +/- 20). The pinhole test underestimated postrefraction visual acuity with the filter by two letters (95% confidence limits = +/- 16). Among subjects whose acuity improved with the pinhole test (N = 24), 83% experienced better postrefraction visual acuity. Among subjects whose acuity declined or remained unchanged with the pinhole test (N = 40), 50% achieved better postrefraction visual acuity. Conclusions. The pinhole-induced luminance loss contributed to inadequate predictions of postrefraction visual acuity. Pinhole test results were enormously variable, underestimating and overestimating postrefraction visual acuity. The pinhole test was less reliable when improvements in postrefraction visual acuity were small. Visually impaired patients deserve periodic refractions, and the pinhole test result should not be used as a dichotomizer for clinical decisions regarding the need for a refraction. C1 Massachusetts Eye & Ear Infirm, Vis Rehabil Serv, Boston, MA 02114 USA. RP Eagan, SM (reprint author), 190 High St, Boston, MA 02110 USA. OI Jacobs, Robert/0000-0001-6709-1785 NR 35 TC 6 Z9 7 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-5488 J9 OPTOMETRY VISION SCI JI Optom. Vis. Sci. PD JAN PY 1999 VL 76 IS 1 BP 50 EP 58 DI 10.1097/00006324-199901000-00028 PG 9 WC Ophthalmology SC Ophthalmology GA 163VT UT WOS:000078427600018 PM 10030615 ER PT J AU Stowell, CP Chandler, H Jove, M Guilfoyle, M Wacholtz, MC AF Stowell, CP Chandler, H Jove, M Guilfoyle, M Wacholtz, MC TI An open-label, randomized study to compare the safety and efficacy of perioperative epoetin alfa with preoperative autologous blood donation in total joint arthroplasty SO ORTHOPEDICS LA English DT Article ID ORTHOPEDIC-SURGERY; COST-EFFECTIVENESS; VEIN-THROMBOSIS; TRANSFUSION; MANAGEMENT; ULTRASOUND; REINFUSION; ACCURACY; BENEFIT; CELLS AB A multicenter, randomized, open-label, parallel-group study was conducted to compare the safety and efficacy of perioperative recombinant human erythropoietin (Epoetin alfa) with the safety and efficacy of preoperative autologous donation(PAD) in total joint arthroplasty. A total of 490 patients scheduled for total joint (i.e., hip or knee) surgery and having hemoglobin (Hb) levels greater than or equal to 11 to less than or equal to 13 g/dL were randomized to receive weekly doses of subcutaneous Epoetin alfa on preoperative Days -21, -14, and -7, and on the day of surgery, or to participate in a PAD program. The mean baseline Hb level in both groups was 12.3 +/- 0.6 g/dL, increasing to 13.8 g/dL in the Epoetin alfa-treated group and decreasing to 11.1 g/dL in the PAD group before or on the day of surgery. In the PAD group, 156/219 (71.2%) patients were transfused with autologous blood, and 42/219 (19.2%) patients were transfused with allogeneic blood. A smaller proportion, 27/209 (12.9%) patients, in the Epoetin alfa-treated group were transfused with allogeneic blood (P = .078 compared with the PAD group). Moreover, patients in the PAD group received a total of 325 units of blood (79 allogeneic units and 246 autologous units) compared with patients in the Epoetin alfa group who received a total of 54 units of blood. The mean postoperative Hb level was 11.0 g/dL in the Epoetin alfa-treated group and 9.2 g/dL in the PAD group. Compared with the PAD arm, mean Hb levels measured preoperatively, postoperatively on Day 1, and at discharge visits were significantly greater in the Epoetin alfa-treated arm (P < .0001). C1 Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02214 USA. Atlanta Knee & Sports Med, Decatur, GA USA. RW Johnson Pharmaceut Res Inst, Raritan, NJ 08869 USA. RP Stowell, CP (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, 55 Fruit St, Boston, MA 02214 USA. NR 41 TC 48 Z9 48 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD JAN PY 1999 VL 22 IS 1 SU S BP S105 EP S112 PG 8 WC Orthopedics SC Orthopedics GA 159AP UT WOS:000078149900003 PM 9927110 ER PT J AU Li, KK Teknos, TN Lai, A Lauretano, AM Joseph, MP AF Li, KK Teknos, TN Lai, A Lauretano, AM Joseph, MP TI Traumatic optic neuropathy: Result in 45 consecutive surgically treated patients SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID NERVE DECOMPRESSION; INDIRECT INJURY; MANAGEMENT; BLINDNESS AB The management of traumatic optic neuropathy remains controversial. In this report, we present the results of 45 patients treated with extracranial optic nerve decompression after at least 12 to 24 hours of corticosteroid therapy without improvement. Vision improved in 32 patients after surgery (71%), and the mean percentage of improvement from preoperative visual deficit was 40.7% +/- 6.9% (median improvement 41.2%). Worsening of vision occurred in none of the patients as a result of the surgery, and no intraoperative or postoperative complications were encountered. We present a treatment protocol for traumatic optic neuropathy with the use of megadose corticosteroids and optic nerve decompression. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol Head & Neck Surg, Boston, MA USA. RP Li, KK (reprint author), Facial Reconstruct Surg, 750 Welch Rd,Suite 317, Palo Alto, CA 94304 USA. NR 26 TC 24 Z9 30 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JAN PY 1999 VL 120 IS 1 BP 5 EP 11 DI 10.1016/S0194-5998(99)70362-1 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 156TN UT WOS:000078018300002 PM 9914542 ER PT J AU Kieff, DA Bhattacharyya, N Siegel, NS Salman, SD AF Kieff, DA Bhattacharyya, N Siegel, NS Salman, SD TI Selection of antibiotics after incision and drainage of peritonsillar abscesses SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID MANAGEMENT AB Despite the fact that peritonsillar abscess is the most common complication of acute tonsillitis, the treatment of peritonsillar abscess remains controversial. One element of controversy is the choice of antibiotics after drainage of the abscess. In an attempt to assess the effect of antibiotic choice on the treatment of peritonsillar abscess, we conducted a retrospective review of records from patients with peritonsillar abscess treated with incision and drainage. Our review identified 103 patients, comprising two groups: 58 patients treated with broad-spectrum intravenous antibiotics and 45 patients treated with intravenous penicillin alone. These patients were hospitalized after incision and drainage, and therefore their clinical courses and responses to therapy could be rigorously assessed. Characterization of illness based on patient age, temperature, and white blood cell count revealed similar severity of illness between the two groups. Comparison of clinical outcomes with respect to hours hospitalized (mean 44.3 +/- 6.6 and 38.3 +/- 7.1 hours, 95% confidence interval, for broad-spectrum and penicillin groups, respectively) and mean hours febrile (16.9 +/- 5.0 and 13.3 +/- 4.2 hours, 95% confidence interval) were not statistically significantly different (p = 0.222 and 0.269, respectively) between groups, indicating that broad-spectrum antibiotics failed to show greater efficacy than penicillin in the treatment of these patients. The microbiologic characteristics of these infections, failures of therapy, and complication rates were similar to those reported in the literature. These results suggest that intravenous penicillin remains an excellent choice for therapy in cases of peritonsillar abscess requiring parenteral antibiotics after drainage. C1 Harvard Univ, Sch Med, Joint Ctr Otolaryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. RP Bhattacharyya, N (reprint author), Harvard Univ, Sch Med, Joint Ctr Otolaryngol, 333 Longwood Ave, Boston, MA 02115 USA. NR 11 TC 25 Z9 27 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JAN PY 1999 VL 120 IS 1 BP 57 EP 61 DI 10.1016/S0194-5998(99)70370-0 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 156TN UT WOS:000078018300011 PM 9914550 ER PT S AU Holt, JR Vollrath, MA Eatock, RA AF Holt, JR Vollrath, MA Eatock, RA BE Cohen, B Hess, BJM TI Stimulus processing by type II hair cells in the mouse utricle SO OTOLITH FUNCTION IN SPATIAL ORIENTATION AND MOVEMENT SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Otolith Function in Spatial Orientation and Movement - Symposium in Memory of Volker Henn CY MAY 18-19, 1998 CL ZURICH, SWITZERLAND SP Zurich Univ Hosp, Betty & David Koetser Fdn Brain Res ID ELECTRICAL RESONANCE; DISCHARGE PROPERTIES; MEMBRANE-PROPERTIES; VESTIBULAR NERVE; RANA-CATESBEIANA; BULL-FROG; ADAPTATION; CURRENTS; COCHLEA; TRANSDUCTION AB In type II and neonatal hair cells in the mouse utricle, the receptor potentials evoked by low-frequency sinusoidal deflections of the hair bundle are attenuated by adaptation of the mechanoelectrical transduction current and the voltage-dependent activation of a large potassium (K)-selective outwardly rectifying conductance, g(DR). These processes may contribute to high-pass filtering of the responses of some utricular afferents to sinusoidal linear accelerations below 2 Hz. Depolarizing receptor potentials are more attenuated by g(DR) than are hyperpolarizing receptor potentials. It may therefore reduce nonlinear distortion introduced by mechanoelectrical transduction, which generates larger depolarizing currents than hyperpolarizing currents. The discharge properties of utricular afferents vary according to whether they innervate the striolar or extrastriolar zones of the sensory epithelium. Regional variation in hair-cell properties is likely to contribute. Preliminary results suggest that the outwardly rectifying K conductances of type II cells are slower and larger in the striola than in the extrastriola, consistent with regional variation in the relative numbers of delayed rectifier and A-current K channels. C1 Baylor Coll Med, Bobby R Alford Dept Otorhinolaryngol & Communicat, Houston, TX 77030 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurobiol, Boston, MA 02114 USA. Howard Hughes Med Inst, Boston, MA 02114 USA. Baylor Coll Med, Div Neurosci, Houston, TX 77030 USA. RP Eatock, RA (reprint author), Baylor Coll Med, Bobby R Alford Dept Otorhinolaryngol & Communicat, Houston, TX 77030 USA. RI Eatock, Ruth/F-6404-2013 FU NIDCD NIH HHS [DC02290] NR 26 TC 18 Z9 18 U1 0 U2 5 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-217-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 871 BP 15 EP 26 DI 10.1111/j.1749-6632.1999.tb09172.x PG 12 WC Multidisciplinary Sciences; Neurosciences; Otorhinolaryngology SC Science & Technology - Other Topics; Neurosciences & Neurology; Otorhinolaryngology GA BN24W UT WOS:000081273000002 PM 10372060 ER PT S AU Van de Water, TR Staecker, H Halterman, MW Federoff, HJ AF Van de Water, TR Staecker, H Halterman, MW Federoff, HJ BE Henderson, D Salvi, RJ Quaranta, A McFadden, SL Burkard, RF TI Gene therapy in the inner ear - Mechanisms and clinical implications SO OTOTOXICITY: BASIC SCIENCE AND CLINICAL APPLICATIONS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Ototoxicity - Basic Science and Clinical Applications CY JUN 18-20, 1998 CL BARI, ITALY SP SUNY Buffalo, Ctr Hearing & Deafness, Audiol & Otol Ctr, Abbott Labs, Amgen Inc, AMPLIFON, Univ Bari, Audiol & Otol Pilot Ctr Mediterranean Countries, Bristol Meyers Sqibb Co, Deafness Res Fdn, Genetech Inc, Merck & Co Inc, Sepracor Inc ID ADENOASSOCIATED VIRUS; IN-VIVO; AUDITORY NEURONS; GUINEA-PIG; BDNF; NEUROTROPHINS; DEGENERATION; EXPRESSION; COCHLEA; NT-3 AB The application of gene therapy to the inner ear is an emerging field of study, Most studies report the expression of marker genes (e.g., galactosidase) within the tissues of the cochlea. The first biologic response of an inner ear tissue (i.e,, auditory neurons) to transduction by a gene therapy vector expressing a therapeutic gene (a herpes amplicon vector containing a BDNF gene) was observed in spiral explants obtained from early postnatal rat cochleae. This study was important because it demonstrated the feasibility of a gene augmentation approach to treat traumatized cochleae, long-term expression of transduced or transfected genes in cochlear tissues have been obtained with adenovirus, adeno-associated virus, and herpes amplicon vectors. The herpes amplicon vector (i.e., HSVbdnflac) that evoked a biologic response in vitro has also been successfully used to support the survival of auditory neurons in vivo following loss of the auditory hair cells (i.e., loss of trophic factor). Gene therapy has been successfully applied to the cochlea of a laboratory animal, and future studies will define the types of vectors and therapeutic genes that will work best for the treatment of inner ear diseases in the clinic. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Otolaryngol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10461 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Univ Rochester, Sch Med & Dent, Div Mol Med & Gene Therapy, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Dept Microbiol & Immunol, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA. RP Van de Water, TR (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Otolaryngol, Kennedy Ctr Room 302,1410 Pelham Pkwy S, Bronx, NY 10461 USA. OI Staecker, Hinrich/0000-0002-0348-3015 FU NIMH NIH HHS [F30 MH012305, F30 MH012305-03] NR 27 TC 24 Z9 24 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-204-5 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 884 BP 345 EP 360 DI 10.1111/j.1749-6632.1999.tb08653.x PG 16 WC Multidisciplinary Sciences; Otorhinolaryngology SC Science & Technology - Other Topics; Otorhinolaryngology GA BP20H UT WOS:000084392100028 PM 10842605 ER PT J AU Acworth, IN Bogdanov, MB McCabe, DR Beal, MF AF Acworth, IN Bogdanov, MB McCabe, DR Beal, MF TI Estimation of hydroxyl free radical levels in vivo based on liquid chromatography with electrochemical detection SO OXIDANTS AND ANTIOXIDANTS, PT B SE METHODS IN ENZYMOLOGY LA English DT Review ID NITRIC-OXIDE SYNTHASE; 3-NITROPROPIONIC ACID NEUROTOXICITY; EXCITOTOXICITY IN-VIVO; AROMATIC HYDROXYLATION; OXIDATIVE STRESS; LIPID-PEROXIDATION; SUPEROXIDE; BRAIN; SALICYLATE; MICE C1 Massachusetts Coll Pharm, Dept Pharmacol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. ESA Inc, Chelmsford, MA USA. RP Acworth, IN (reprint author), Massachusetts Coll Pharm, Dept Pharmacol, Boston, MA 02115 USA. NR 46 TC 29 Z9 29 U1 2 U2 7 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 1999 VL 300 BP 297 EP 313 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BM67Q UT WOS:000079432700031 PM 9919532 ER PT S AU Jenkins, BG Chen, YI Kuestermann, E Makris, NM Nguyen, TV Kraft, E Brownell, AL Rosas, HD Kennedy, DN Rosen, BR Koroshetz, WJ Beal, MF AF Jenkins, BG Chen, YI Kuestermann, E Makris, NM Nguyen, TV Kraft, E Brownell, AL Rosas, HD Kennedy, DN Rosen, BR Koroshetz, WJ Beal, MF BE Blass, JP McDowell, FH TI An integrated strategy for evaluation of metabolic and oxidative defects in neurodegenerative illness using magnetic resonance techniques SO OXIDATIVE/ENERGY METABOLISM IN NEURODEGENERATIVE DISORDERS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Oxidative/Energy Metabolism in Neuridegenerative Disorders CY MAR 19-22, 1999 CL NEW YORK, NEW YORK SP New York Acad Sci, Winifred Masterson Burke Med Res Inst Inc, NIA, NIH, MitoKor, Amer Fed Aging Res, Warner Lambert Co, Parke Davis Pharmaceut Res ID CEREBRAL BLOOD-VOLUME; AMYOTROPHIC-LATERAL-SCLEROSIS; STRIATAL EXCITOTOXIC LESIONS; POSITRON-EMISSION-TOMOGRAPHY; TOXIN 3-NITROPROPIONIC ACID; DIFFERENT FIELD STRENGTHS; BRAIN ENERGY-METABOLISM; IN-VIVO C-13-NMR; PARKINSONS-DISEASE; HUNTINGTONS-DISEASE AB The number of physiologic and metabolic phenomena amenable to analysis using magnetic resonance (MR) techniques is increasing every year. MR techniques tan now evalutate tissue parameters relevant to TCA. cyclemetabolism, anerobic glycolysis, ATP levels, blood-brain barrier permeability, macrophage infiltration, cytotoxic edema, spreading depression, cerebral blood now and volume, and neurotransmitter function. The paramagnetic nature of certain oxidation states of iron leads to the ability to map out brain function using deoxyhemoglobin as an endogenous contrast agent, and also allows for mapping of local tissue iran concentrations. Zn addtion to these metabolic parameters, the number of ways to generate anatomic contrast using MR is also expanding; and In addition to conventional anatomic scans, mapping of axonal fiber tracts can also be performed using the anisotropy of eater diffusion, rt strategy for integration of these multifarious parameters in a comprehensive neurofunctional exam in neurodegenerative illness is outlined in this paper. The goals of the integrated exam, as applied to a given neurodegenerative illness, can be subdivided into three categories: etiology, natural history, and therapeutic end points, The consequences of oxidative stress and/or mitochondrial dysfunction are explored in the contest of the various parameters that can be measured using the integrated MR exam. C1 Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Jenkins, BG (reprint author), Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Kennedy, David/H-3627-2012 NR 144 TC 12 Z9 12 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-209-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 893 BP 214 EP 242 DI 10.1111/j.1749-6632.1999.tb07828.x PG 29 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Multidisciplinary Sciences; Neurosciences; Ornithology SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Science & Technology - Other Topics; Neurosciences & Neurology; Zoology GA BP50E UT WOS:000085330600017 PM 10672240 ER PT S AU Kekelidze, T Khait, I Togliatti, A Benzycry, J Mulkern, R Holtzman, D AF Kekelidze, T Khait, I Togliatti, A Benzycry, J Mulkern, R Holtzman, D BE Blass, JP McDowell, FH TI Maturational changes in rabbit brain phosphocreatine and creatine kinase SO OXIDATIVE/ENERGY METABOLISM IN NEURODEGENERATIVE DISORDERS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Oxidative/Energy Metabolism in Neuridegenerative Disorders CY MAR 19-22, 1999 CL NEW YORK, NEW YORK SP New York Acad Sci, Winifred Masterson Burke Med Res Inst Inc, NIA, NIH, MitoKor, Amer Fed Aging Res, Warner Lambert Co, Parke Davis Pharmaceut Res ID MAGNETIC-RESONANCE; RAT C1 Brigham & Womens Hosp, Dept Radiol, LMRC, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kekelidze, T (reprint author), Brigham & Womens Hosp, Dept Radiol, LMRC, 221 Longwood Ave, Boston, MA 02115 USA. FU NINDS NIH HHS [NS 10176, NS 26371] NR 8 TC 2 Z9 2 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-209-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1999 VL 893 BP 309 EP 313 DI 10.1111/j.1749-6632.1999.tb07844.x PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Multidisciplinary Sciences; Neurosciences; Ornithology SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Science & Technology - Other Topics; Neurosciences & Neurology; Zoology GA BP50E UT WOS:000085330600033 PM 10672256 ER PT J AU Pekary, AE Sattin, A Lloyd, RL AF Pekary, AE Sattin, A Lloyd, RL TI Electroconvulsive seizures increase levels of pGlu-Glu-Pro-NH2 (EEP) in rat brain SO PEPTIDES LA English DT Article DE EEP; TRH; HPLC; radioimmunoassay; forced swim test; electroconvulsive seizures; rat brain; blood-brain barrier; affective disorders; antidepressant ID THYROTROPIN-RELEASING-HORMONE; PYROGLUTAMYL-GLUTAMYL-PROLINEAMIDE; CENTRAL-NERVOUS-SYSTEM; FORCED SWIMMING TEST; CEREBROSPINAL-FLUID; TRH RECEPTORS; PEPTIDE; PITUITARY; PRECURSOR; INSULIN AB We have previously reported that electroconvulsive seizures (ECS) increases the level of prepro-TRH-derived peptides in hippocampus, amygdala and pyriform cortex but not the striatum of male rats and that this increase is significantly correlated with reduced immobility (increased swimming) in the Porsolt forced swim test. An abstract by Mabrouk and Bennett published in 1993 described increased locomotor activity in rats following IP injection of TRH (pGlu-His-Pro-NH2) and EEP (pGlu-Glu-Pro-NH2). We have examined the effect of three daily transcorneal ECS on the levels of EEP in various brain regions and their correlation with results from the Porsolt forced swim test. The EEP level (ng/g wet weight) was measured by RIA in 6 brain regions: amygdala (AY), hippocampus (HC), pyriform cortex (PYR), anterior cortex (AC), striatum (STR) and motor cortex (MC). ECS significantly increased EEP levels in AY, HC and PYR. The increased swim behavior following ECS, as measured in the Porsolt test, correlated significantly with the EEP levels in HC and MC within individual subjects. Intraperitoneal (IP) injection of EEP (1.0 mg/kg) resulted in a rapid and sustained rise in EEP levels throughout the brain and a clearance half-time from blood of 2.0 h. Intracardiac injection of 0.5 mg EEP resulted in a peak EEP level in CSF at 2 h followed by a t(1/2) of 0.35 h. A 3 compartment model for EEP transport from blood into CSF and then brain was developed. This model revealed a 1.75 h delay in the transit time of EEP from blood to CSF followed by rapid clearance from the CSF but long retention time within various brain tissues. We conclude that (1) ECS significantly increases EEP levels in limbic regions, but not in striatum, of the rat brain, (2) EEP, like TRH, is a potential mediator of the antidepressant effect of ECS and (3) EEP, after IP or IV administration, is readily taken up by, and has a long residence time in, brain tissue. (C) 1999 by Elsevier Science Inc. C1 W Los Angeles VA Med Ctr, Res Serv, Los Angeles, CA 90073 USA. W Los Angeles VA Med Ctr, Psychiat Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Sch Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90073 USA. Univ Minnesota, Dept Psychol, Duluth, MN 55812 USA. RP Pekary, AE (reprint author), W Los Angeles VA Med Ctr, Res Serv, Los Angeles, CA 90073 USA. NR 60 TC 22 Z9 22 U1 0 U2 0 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 PY 1999 VL 20 IS 1 BP 107 EP 119 DI 10.1016/S0196-9781(98)00140-5 PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 174HG UT WOS:000079028200014 PM 10098631 ER PT J AU Kosoyan, HP Wei, JY Tache, Y AF Kosoyan, HP Wei, JY Tache, Y TI Intracisternal sauvagine is more potent than corticotropin-releasing factor to decrease gastric vagal efferent activity in rats SO PEPTIDES LA English DT Article DE corticotropin-releasing factor receptor antagonist; intracisternal; vagus; parasympathetic nervous system; sauvagine; gastric vagal efferent activity ID STRESS-RELATED ALTERATIONS; COLONIC MOTOR FUNCTION; NERVOUS-SYSTEM; CRF; BRAIN; HORMONE; INHIBITION; ANTAGONIST; NUCLEUS; PROSTAGLANDIN AB Consecutive intracisternal (ic) injections of corticotropin-releasing factor (CRF) (21, 63, and 126 pmol, ic) or sauvagine (2.1, 6.3, and 21 pmol, ic) decreased gastric vagal efferent multiunit discharge (GVED) to 82%, 75% and 69% and 71%, 40% and 21%, respectively, from preinjection basal levels (taken as 100%). The inhibitory action was dose related (magnitude and duration of the response, 7-45 min). The CRF antagonist, [D-Phe(12),Nle(21,38),C-alpha-MeLeu(37)]-rCRF(12-41) (6.25 nmol, ic) increased GVED by 43.5 +/- 4.3% and blocked the decrease in GVED induced by CRF (21 pmol, ic) for >90 min with a complete recovery after 3 h. Vehicles (injected intracisternally) had no effect. These data indicate that: 1) CRF injected intracisternally decreases GVED through the activation of CRF receptors and sauvagine is more potent than CRF to inhibit GVED; and 2) endogenous CRF exerts an inhibitory tone on basal GVED in urethane-anesthetized rats undergoing surgery. (C) 1999 Elsevier Science Inc. All rights reserved. C1 W Los Angeles Vet Adm Med Ctr, Digest Dis Res Ctr, CURE, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Div Digest Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Inst Brain Res, Los Angeles, CA 90073 USA. RP Kosoyan, HP (reprint author), W Los Angeles Vet Adm Med Ctr, Digest Dis Res Ctr, CURE, Bldg 115,Rm 203,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-41301, DK-33061] NR 48 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 0196-9781 J9 PEPTIDES JI Peptides PY 1999 VL 20 IS 7 BP 851 EP 858 DI 10.1016/S0196-9781(99)00072-8 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 228XX UT WOS:000082163700010 PM 10477086 ER PT J AU Park, JY Ha, SW King, GL AF Park, JY Ha, SW King, GL TI The role of protein kinase C activation in the pathogenesis of diabetic vascular complications SO PERITONEAL DIALYSIS INTERNATIONAL LA English DT Article; Proceedings Paper CT VIIIth Congress of the International-Society-for-Peritoneal-Dialysis (ISPD 98, SEOUL) CY AUG 23-26, 1998 CL SEOUL, SOUTH KOREA SP Int Soc Peritoneal Dialysis DE protein kinase C; diabetes; vascular complications ID ELEVATED GLUCOSE-LEVELS; NITRIC-OXIDE SYNTHASE; RETINAL CIRCULATION; GROWTH-FACTOR; IN-VIVO; RATS; EXPRESSION; MECHANISM; CELLS; BETA AB Many vascular diseases in diabetes are known to be associated with the activation of the diacylglycerol (DAG)protein kinase C (PKC) pathway. The major source of DAG that is elevated in diabetes is de novo synthesis from glycolytic intermediates. Among the various PKC isoforms, the p-isoform has been shown to be persistently activated in diabetic animals. Multiple lines of evidence have shown that many vascular alterations in diabetes - such as a decrease in the activity of Na+-K+-adenosine triphosphatase (Na+-K+-ATPase), and increases in extracellular matrix, cytokines, permeability, contractility, and cell proliferation - are caused by activation of PKC. Inhibition of PKC by two different kinds of PKC inhibitors, LY333531,a selective PKC-P-isoform inhibitor, and d-alpha-tocopherol, were able to prevent or reverse the various vascular dysfunctions in diabetic rats. These results have also provided in vivo evidence that DAG-PKC activation could be responsible for the hyperglycemia-induced vascular dysfunctions in diabetes. Clinical studies are now being performed to clarify the pathogenic roles of the DAG-PKC pathway in developing vascular complications in diabetic patients. C1 Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr, Boston, MA 02215 USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr, Boston, MA 02215 USA. FU NEI NIH HHS [EY05110] NR 29 TC 31 Z9 31 U1 0 U2 0 PU MULTIMED INC PI TORONTO PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA SN 0896-8608 J9 PERITON DIALYSIS INT JI Perit. Dial. Int. PY 1999 VL 19 SU 2 BP S222 EP S227 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 225QU UT WOS:000081972900038 PM 10406523 ER PT B AU Beal, MF AF Beal, MF BE Krieglstein, J TI Mitochondria in neuronal death in vivo SO PHARMACOLOGY OF CEREBRAL ISCHEMIA 1998 LA English DT Proceedings Paper CT 7th International Symposium on the Pharmacology of Cerebral Ischemia CY JUL 27-29, 1998 CL MARBURG, GERMANY SP Deutsch Foesch Gemeinsch, Bonn, Philipps Univ, Marburg, Biotrend Chemikalien GmbH, Koln, Gesell Med Sondentechnik mbH, Mielkendorg, Hoechst Marion Roussel, Bad Soden, Janssen-Cilag, Neuss, Knoll AG, Ludwigshafen, Perimed AB, Jarfalla, Willmar Schwabe Arzneimmittel GmbH, Karlsruhe, Tech & Sci Equipment GmbH, Bad Homburg ID AMYOTROPHIC-LATERAL-SCLEROSIS; PERMEABILITY TRANSITION PORE; NMR MAGNETIZATION-TRANSFER; COMPLEX-I DEFECT; HUNTINGTONS-DISEASE; CREATINE-KINASE; PARKINSONS-DISEASE; CYTOCHROME-C; H-1-NMR SPECTROSCOPY; FRIEDREICHS-ATAXIA C1 Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. RP Beal, MF (reprint author), Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. NR 56 TC 0 Z9 0 U1 0 U2 0 PU MEDPHARM GMBH SCIENTIFIC PUBL PI STUTTGART PA BIRKENWALDSTRASSE 44, D-7000 STUTTGART, GERMANY BN 3-88763-070-X PY 1999 BP 105 EP 111 PG 7 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Peripheral Vascular Disease SC Neurosciences & Neurology; Pharmacology & Pharmacy; Cardiovascular System & Cardiology GA BN55B UT WOS:000082191900010 ER PT B AU Moskowitz, MA Dalkara, T AF Moskowitz, MA Dalkara, T BE Krieglstein, J TI Caspase-mediated cell death in cerebral ischemia SO PHARMACOLOGY OF CEREBRAL ISCHEMIA 1998 LA English DT Proceedings Paper CT 7th International Symposium on the Pharmacology of Cerebral Ischemia CY JUL 27-29, 1998 CL MARBURG, GERMANY SP Deutsch Foesch Gemeinsch, Bonn, Philipps Univ, Marburg, Biotrend Chemikalien GmbH, Koln, Gesell Med Sondentechnik mbH, Mielkendorg, Hoechst Marion Roussel, Bad Soden, Janssen-Cilag, Neuss, Knoll AG, Ludwigshafen, Perimed AB, Jarfalla, Willmar Schwabe Arzneimmittel GmbH, Karlsruhe, Tech & Sci Equipment GmbH, Bad Homburg ID INTERLEUKIN-1-BETA CONVERTING-ENZYME; DNA FRAGMENTATION; ARTERY OCCLUSION; CYTOCHROME-C; PROTEIN-KINASE; BRAIN-DAMAGE; BCL-X; APOPTOSIS; ACTIVATION; FAMILY C1 Harvard Univ, Sch Med,Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Dept Neurol & Neurosurg Serv, Charlestown, MA 02129 USA. RP Moskowitz, MA (reprint author), Harvard Univ, Sch Med,Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Dept Neurol & Neurosurg Serv, 149 13th St,Room 6403, Charlestown, MA 02129 USA. NR 52 TC 0 Z9 0 U1 0 U2 0 PU MEDPHARM GMBH SCIENTIFIC PUBL PI STUTTGART PA BIRKENWALDSTRASSE 44, D-7000 STUTTGART, GERMANY BN 3-88763-070-X PY 1999 BP 269 EP 275 PG 7 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Peripheral Vascular Disease SC Neurosciences & Neurology; Pharmacology & Pharmacy; Cardiovascular System & Cardiology GA BN55B UT WOS:000082191900027 ER PT B AU Endres, M Laufs, U Liao, JK Moskowitz, MA AF Endres, M Laufs, U Liao, JK Moskowitz, MA BE Krieglstein, J TI Specific upregulation of endothelial nitric oxide synthase and its potential importance to cerebral ischemia SO PHARMACOLOGY OF CEREBRAL ISCHEMIA 1998 LA English DT Proceedings Paper CT 7th International Symposium on the Pharmacology of Cerebral Ischemia CY JUL 27-29, 1998 CL MARBURG, GERMANY SP Deutsch Foesch Gemeinsch, Bonn, Philipps Univ, Marburg, Biotrend Chemikalien GmbH, Koln, Gesell Med Sondentechnik mbH, Mielkendorg, Hoechst Marion Roussel, Bad Soden, Janssen-Cilag, Neuss, Knoll AG, Ludwigshafen, Perimed AB, Jarfalla, Willmar Schwabe Arzneimmittel GmbH, Karlsruhe, Tech & Sci Equipment GmbH, Bad Homburg ID BLOOD-FLOW; MICE; EXPRESSION; PATHWAY; CELLS AB Currently, stroke prophylaxis is limited to agents that block platelet aggregation or the clotting cascade. We demonstrate that 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors (statins), commonly used cholesterol lowering agents, protect against ischemic brain injury by a novel mechanism involving the selective upregulation of endothelial nitric oxide synthase (eNOS). Statin pretreatment augments cerebral blood flow, reduces cerebral infarct size, and improves neurological function in normocholesterolemic mice. The upregulation of eNOS by statins is reversed by cotreatment with L-mevalonate and by the downstream isoprenoid, geranylgeranylpyrophosphate but not by farnesylpyrophosphate, and is not associated with changes in serum cholesterol levels. The stroke protection and blood flow effects of statins are absent in eNOS knockout mice indicating that eNOS upregulation by statins is the predominant mechanism by which these agents protect against brain injury. Our results suggest that statins provide a novel prophylactic treatment strategy for increasing blood flow and reducing infarct size during cerebral ischemia. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Boston, MA 02114 USA. RP Endres, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Boston, MA 02114 USA. NR 30 TC 0 Z9 0 U1 0 U2 1 PU MEDPHARM GMBH SCIENTIFIC PUBL PI STUTTGART PA BIRKENWALDSTRASSE 44, D-7000 STUTTGART, GERMANY BN 3-88763-070-X PY 1999 BP 299 EP 307 PG 9 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Peripheral Vascular Disease SC Neurosciences & Neurology; Pharmacology & Pharmacy; Cardiovascular System & Cardiology GA BN55B UT WOS:000082191900030 ER PT B AU Sugimori, H Finklestein, SP AF Sugimori, H Finklestein, SP BE Krieglstein, J TI Update on growth factor treatment for stroke SO PHARMACOLOGY OF CEREBRAL ISCHEMIA 1998 LA English DT Proceedings Paper CT 7th International Symposium on the Pharmacology of Cerebral Ischemia CY JUL 27-29, 1998 CL MARBURG, GERMANY SP Deutsch Foesch Gemeinsch, Bonn, Philipps Univ, Marburg, Biotrend Chemikalien GmbH, Koln, Gesell Med Sondentechnik mbH, Mielkendorg, Hoechst Marion Roussel, Bad Soden, Janssen-Cilag, Neuss, Knoll AG, Ludwigshafen, Perimed AB, Jarfalla, Willmar Schwabe Arzneimmittel GmbH, Karlsruhe, Tech & Sci Equipment GmbH, Bad Homburg ID FOCAL CEREBRAL-ISCHEMIA; RECEPTOR MESSENGER-RNA; RAT; EXPRESSION; INFARCTION; NEURONS; RECOVERY C1 Massachusetts Gen Hosp, CNS, Growth Factor Res Lab, Boston, MA 02114 USA. RP Sugimori, H (reprint author), Massachusetts Gen Hosp, CNS, Growth Factor Res Lab, Boston, MA 02114 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU MEDPHARM GMBH SCIENTIFIC PUBL PI STUTTGART PA BIRKENWALDSTRASSE 44, D-7000 STUTTGART, GERMANY BN 3-88763-070-X PY 1999 BP 329 EP 332 PG 4 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Peripheral Vascular Disease SC Neurosciences & Neurology; Pharmacology & Pharmacy; Cardiovascular System & Cardiology GA BN55B UT WOS:000082191900033 ER PT S AU Mehta, A Dreyer, KJ Thrall, J AF Mehta, A Dreyer, KJ Thrall, J BE Seibert, JA Filipow, LJ Andriole, KP TI Integrated medical imaging: Web browsers and the future of image distribution SO PRACTICAL DIGITAL IMAGING AND PACS SE MEDICAL PHYSICS MONOGRAPHS LA English DT Proceedings Paper CT American-Association-of-Physicists-in-Medicine Summer School CY JUN 26-JUL 01, 1999 CL SONOMA STATE UNIV, ROHNERT PK, CA SP Amer Assoc Physicists Med HO SONOMA STATE UNIV C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Mehta, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MEDICAL PHYSICS PUBLISHING PI MADISON PA 4513 VERNON BLVD, MADISON, WI 53705 USA SN 0163-1802 BN 0-944838-20-0 J9 MED PHYS MG PY 1999 IS 25 BP 361 EP 367 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BN53D UT WOS:000082157700015 ER PT J AU Schmalzried, TP Brown, IC Amstutz, HC Engh, CA Harris, WH AF Schmalzried, TP Brown, IC Amstutz, HC Engh, CA Harris, WH TI The role of acetabular component screw holes and or screws in the development of pelvic osteolysis SO PROCEEDINGS OF THE INSTITUTION OF MECHANICAL ENGINEERS PART H-JOURNAL OF ENGINEERING IN MEDICINE LA English DT Article DE hip replacement; acetabulum; wear; osteolysis ID HIP-REPLACEMENT; WEAR; KNEE AB Anecdotal reporting of osteolysis around cementless modular acetabular components with holes through the metal shell and/or iliac fixation screws has raised concern that such designs may generate excessive particulate debris andior permit direct access of particulate debris to iliac bone. To address this issue, incidence data are reported on 513 total hip replacements from six different single-surgeon series of total hip arthroplasties performed with six different porous ingrowth acetabular components. With follow-up ranging from 40 to 108 months, a total of 45 pelvic osteolytic lesions were observed (8.8 per cent). Pelvic osteolysis was seen nearly as frequently in the ischium and pubis (21 lesions) as it was in the ilium (24 lesions). It was not possible to explain ischial and pubic osteolysis by holes and/or screws through the acetabular component shell. There was no direct correlation between the presence of screw holes or screws and the incidence of pelvic osteolysis. The incidence of pelvic osteolysis around modular components with holes through the shell was 4.5 per cent (14 of 313 hips). The incidence of pelvic osteolysis with solid-shell components was 15.5 per cent (31 of 200). The incidence of pelvic osteolysis around acetabular reconstructions with screws was 2.3 per cent (3 of 133). The incidence of pelvic osteolysis in reconstructions without screws was 11.1 per cent (32 of 380). The incidence of pelvic osteolysis in one-piece acetabular components (polyethylene pre-fixed in the metal shell) was 12.7 per cent (21 of 165) and the incidence of pelvic osteolysis with the modular components was 6.9 per cent (24 of 348). In each comparison, the incidence of pelvic osteolysis was actually lower in the group assumed to be at increased risk. Based on this review there does not appear to be a direct relationship between holes and/or screws through an acetabular component and the development of pelvic osteolysis. The incidence of pelvic osteolysis was associated with larger head diameters and longer follow-up. While screw holes may provide an access channel in specific cases, the present data indicate that the simple elimination of holes through the acetabular shell will not eliminate pelvic osteolysis. Regardless of other acetabular component design features, joint fluid and polyethylene wear particles from the femoral-acetabular articulation can gain access to bone behind an acetabular component via the peripheral implant-bone interface through regions without sufficient contact or tissue ingrowth. The development of pelvic osteolysis is multifactorial and includes the total volumetric wear of polyethylene as well as specific features of the acetabular component design and reconstruction technique. C1 Joint Replacement Inst, Los Angeles, CA 90007 USA. Harbor UCLA Med Ctr, Torrance, CA 90509 USA. Anderson Orthopaed Res Inst, Arlington, VA USA. Massachusetts Gen Hosp, Orthopaed Biomech Lab, Boston, MA 02114 USA. RP Joint Replacement Inst, 2400 S Flower St, Los Angeles, CA 90007 USA. NR 21 TC 26 Z9 26 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0954-4119 EI 2041-3033 J9 P I MECH ENG H JI Proc. Inst. Mech. Eng. Part H-J. Eng. Med. PY 1999 VL 213 IS H2 BP 147 EP 153 DI 10.1243/0954411991534861 PG 7 WC Engineering, Biomedical SC Engineering GA 196TP UT WOS:000080323900005 PM 10333686 ER PT S AU Spiegelman, B Castillo, G Hauser, S Puigserver, P AF Spiegelman, B Castillo, G Hauser, S Puigserver, P BE GuyGrand, B TI Regulation of energy balance by PPAR gamma and its coactivators SO PROGRESS IN OBESITY RESEARCH: 8 SE PROGRESS IN OBESITY RESEARCH LA English DT Proceedings Paper CT 8th International Congress on Obesity CY AUG 29-SEP 03, 1998 CL PARIS, FRANCE SP Int Assoc Study Obesity ID PROLIFERATOR-ACTIVATED RECEPTOR; ENHANCER-BINDING-PROTEIN; PROMOTES ADIPOCYTE DIFFERENTIATION; PEROXISOME PROLIFERATOR; GENE-EXPRESSION; TRANSCRIPTION FACTOR; C/EBP-ALPHA; ECTOPIC EXPRESSION; ADIPOSE EXPRESSION; NUCLEAR RECEPTORS C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Spiegelman, B (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 62 TC 1 Z9 1 U1 0 U2 0 PU JOHN LIBBEY & CO PI LONDON PA 13 SMITHS YARD, SUMMERLEY ST, LONDON SW18 4HR, ENGLAND SN 0962-7936 BN 0-86196-581-7 J9 PROG OBES R PY 1999 BP 39 EP 46 PG 8 WC Anatomy & Morphology; Endocrinology & Metabolism; Public, Environmental & Occupational Health; Nutrition & Dietetics SC Anatomy & Morphology; Endocrinology & Metabolism; Public, Environmental & Occupational Health; Nutrition & Dietetics GA BP16V UT WOS:000084261200005 ER PT S AU van Kammen, DP McAllister-Sistilli, CG Kelley, ME Gurklis, JA Yao, JK AF van Kammen, DP McAllister-Sistilli, CG Kelley, ME Gurklis, JA Yao, JK BE Muller, N TI Methodological concerns in the study of the immune system in schizophrenia SO PSYCHIATRY, PSYCHOIMMUNOLOGY, AND VIRUSES SE KEY TOPICS IN BRAIN RESEARCH LA English DT Proceedings Paper CT 3rd Expert Meeting in Psychoneuroimmunology CY 1997 CL MUNICH, GERMANY ID HALOPERIDOL WITHDRAWAL; SERUM INTERLEUKIN-6; PLASMA-LEVELS; HUMAN BLOOD; CYTOKINE; DEPRESSION; CLOZAPINE; RECEPTOR; RELAPSE; IL-6 AB Background. Studies of immune measures in schizophrenia have shown differences with control subjects on a number of measures. However, immune measures are often not detectable in the serum or CSF of human samples and in many studies it is not clear how this was dealt with in the analysis. Methods. CSF IL-6 was measured by ELISA in 61 drug free male schizophrenic (DSM-IIIR) patients and 25 well-screened healthy male control subjects. Serum IL-6 was measured in 43 of the 61 patients, and in 16 control subjects. Data were analyzed with and without non-detectable values to determine if this affected the results. Results. Using a value of "0" for non-detectable values resulted in significant differences between patients and controls in plasma interleukin-6. However, if these values were treated as missing, the difference was not significant. Conclusions. The treatment of non-detectable immune measures has demonstrable effects on the analysis and interpretation of the results. C1 Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP van Kammen, DP (reprint author), RW Johnson Pharmaceut Res Inst, Global Clin Res & Dev, 920 Route 202,Room 2312,POB 300, Raritan, NJ 08869 USA. NR 23 TC 3 Z9 3 U1 1 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, A-1201 VIENNA, AUSTRIA SN 0934-1420 BN 3-211-83249-1 J9 KEY TOP BRAIN RES PY 1999 BP 63 EP 69 PG 7 WC Immunology; Neurosciences; Psychiatry; Virology SC Immunology; Neurosciences & Neurology; Psychiatry; Virology GA BN34Z UT WOS:000081678600007 ER PT J AU Heimberg, RG Horner, KJ Juster, HR Safren, SA Brown, EJ Schneier, FR Liebowitz, MR AF Heimberg, RG Horner, KJ Juster, HR Safren, SA Brown, EJ Schneier, FR Liebowitz, MR TI Psychometric properties of the Liebowitz Social Anxiety Scale SO PSYCHOLOGICAL MEDICINE LA English DT Article ID NATIONAL-COMORBIDITY-SURVEY; PHOBIA SCALE; PLACEBO; DISORDER; SAMPLE; MOCLOBEMIDE; PHENELZINE AB Background. The present study provides data on the reliability, validity and treatment sensitivity of the Liebowitz Social Anxiety Scale (LSAS), one of the most commonly used clinician-administered scales for the assessment of social phobia. Method. Three hundred and eighty-two patients from several studies of the treatment of social phobia were evaluated. An independent assessor administered the LSAS to each patient prior to the initiation of treatment. Patients also completed other measures of social anxiety and avoidance, although the specific measures varied across samples. Results. The LSAS and its subscales were normally distributed and demonstrated excellent internal consistency. The convergent validity of the LSAS was demonstrated via significant correlations with other commonly-used measures of social anxiety and avoidance. These correlations also tended to be larger than correlations with measures of depression, especially after treatment. However, the pattern of correlations of LSAS subscales with one another and with the other measures suggest that the fear subscales and the avoidance subscales may not be sufficiently distinct in clinical samples. The LSAS was also demonstrated to be sensitive to the effects of pharmacological treatments of social phobia over time and in comparison to double-blind pill placebo. Conclusion. The LSAS appears to be a reliable, valid and treatment sensitive measure of social phobia. Further study of the LSAS, both in samples with severe social phobia and in community samples, is needed. C1 Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA USA. SUNY Albany, Albany, NY 12222 USA. New York State Psychiat Inst, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Heimberg, RG (reprint author), Temple Univ, Dept Psychol, Weiss Hall,1701 N 13th St, Philadelphia, PA 19122 USA. FU NIMH NIH HHS [MH40121, MH44119, MH47831] NR 61 TC 356 Z9 363 U1 9 U2 65 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD JAN PY 1999 VL 29 IS 1 BP 199 EP 212 DI 10.1017/S0033291798007879 PG 14 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 165KK UT WOS:000078519800021 PM 10077308 ER PT J AU O'Sullivan, RL Phillips, KA Keuthen, NJ Wilhelm, S AF O'Sullivan, RL Phillips, KA Keuthen, NJ Wilhelm, S TI Near-fatal skin picking from delusional body dysmorphic disorder responsive to fluvoxamine SO PSYCHOSOMATICS LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; NEUROTIC EXCORIATIONS; IMAGINED UGLINESS; DRUG-TREATMENT; FLUOXETINE; THERAPY C1 Butler Hosp, Providence, RI 02906 USA. Brown Univ, Sch Med, Dept Psychiat & Human Behav, Providence, RI 02912 USA. RP O'Sullivan, RL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bdlg 149,13th St, Charlestown, MA 02129 USA. NR 19 TC 42 Z9 42 U1 1 U2 4 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 1999 VL 40 IS 1 BP 79 EP 81 PG 3 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 160LV UT WOS:000078232900012 PM 9989126 ER PT J AU Hamner, M Hunt, N Gee, J Garrell, R Monroe, R AF Hamner, M Hunt, N Gee, J Garrell, R Monroe, R TI PTSD and automatic implantable cardioverter defibrillators SO PSYCHOSOMATICS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; QUALITY-OF-LIFE; VENTRICULAR ARRHYTHMIAS; MYOCARDIAL-INFARCTION; ANXIETY; RESPONSES; SYMPTOMS C1 Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. RP Hamner, M (reprint author), Ralph H Johnson Vet Affairs Med Ctr, 109 Bee St, Charleston, SC 29401 USA. NR 24 TC 21 Z9 21 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD JAN-FEB PY 1999 VL 40 IS 1 BP 82 EP 85 PG 4 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 160LV UT WOS:000078232900013 PM 9989127 ER PT J AU Monga, U Kerrigan, AJ Thornby, J Monga, TN AF Monga, U Kerrigan, AJ Thornby, J Monga, TN TI Prospective study of fatigue in localized prostate cancer patients undergoing radiotherapy SO RADIATION ONCOLOGY INVESTIGATIONS LA English DT Article DE fatigue; prostate cancer; radiotherapy ID EPWORTH SLEEPINESS SCALE; QUALITY-OF-LIFE; FUNCTIONAL ASSESSMENT; THERAPY; RADIATION; CHEMOTHERAPY; DEPRESSION; DIAGNOSIS; DISTRESS AB The objectives were to (1) prospectively evaluate fatigue utilizing validated instruments in patients with localized prostate cancer, and (2) examine the relationships between fatigue, depression, quality of life, and sleep disturbance. The instruments used included: Piper Fatigue Scale, Beck Depression Inventory, Epworth Sleepiness Scale, and Functional Assessment of Cancer Therapy for Prostate Scale. Data on cancer stage, prostate specific antigen levels, hematocrit, patient's body weight and radiation dosage were recorded. Patients were evaluated preradiotherapy, middle of radiotherapy, completion of radiotherapy, and at 4-5 weeks follow-up. Thirty-six veterans with localized prostate cancer were studied. Mean age was 66.9 years (range 55-79). Duration of treatment was 7-8 weeks. Univariate procedure and Wilcoxon Signed Rank-test mere used to examine changes in pretreatment scores for each of the three subsequent study periods. To adjust for multiple comparisons Bonferroni test was used. Spearman Correlations were calculated among parameters. No significant changes were noted in mean scores of hematocrit and body weight during the study period. On the Piper Fatigue Scale, adjusted for multiple comparisons, the median scores were significantly higher at completion of radiotherapy as compared with preradiotherapy values. Three patients (8%) were experienced fatigue according to Piper Fatigue Scale before treatment as compared to nine patients (25%) at completion of radiotherapy. On Prostate Cancer Specific and Physical Well Being subscales of the Functional Assessment for Prostate Cancer Therapy, the scores were significantly lower at middle and completion of radiotherapy than at pretreatment. At preradiotherapy, middle of radiotherapy, completion of radiotherapy and follow-up evaluation, patients scoring higher on the Piper Fatigue Scale were more likely to report a poorer quality of Physical Well Being on Functional Assessment of Cancer Therapy for Prostates. No significant changes were noted in the Beck Depression Inventory and Epworth Sleepiness Scale scores during treatment. Eight patients scored 10 or more on the Beck Depression Inventory before starting radiotherapy, suggesting depressive symptomatology. Of these, only seven patients scored 10 or more at completion of treatment. The incidence of fatigue is lower in our study than in previously published data. A relationship exists between fatigue scores and physical well being subscale scores. Higher scores on the Piper Fatigue Scale at the completion of radiotherapy, as well as no changes on depression and sleepiness scales, suggest that fatigue may not be the result of depression or sleep disturbance. Based upon our previous work, we propose that the physical expression of fatigue may be secondary to a decline in neuromuscular efficiency and enhanced muscle fatigue. Published 1999 Wiley-Liss, Inc.(dagger). C1 Houston VA Med Ctr, Dept Radiat Oncol, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Houston VA Med Ctr, Psychol Serv, Houston, TX USA. Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. Houston VA Med Ctr, Dept Family & Community Med, Houston, TX USA. Houston VA Med Ctr, Dept Phys Med & Rehabil, Houston, TX USA. RP Monga, U (reprint author), VA Med Ctr, Radiotherapy Serv 190, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 34 TC 64 Z9 64 U1 1 U2 3 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1065-7541 J9 RADIAT ONCOL INVESTI JI Radiat. Oncol. Investig. PY 1999 VL 7 IS 3 BP 178 EP 185 DI 10.1002/(SICI)1520-6823(1999)7:3<178::AID-ROI7>3.0.CO;2-0 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 233DP UT WOS:000082410500007 PM 10406060 ER PT J AU Chmura, SJ Advani, SJ Kufe, DW Weichselbaum, RR AF Chmura, SJ Advani, SJ Kufe, DW Weichselbaum, RR TI Strategies for enhancing viral-based gene therapy using ionizing radiation SO RADIATION ONCOLOGY INVESTIGATIONS LA English DT Review DE gene therapy; radiotherapy; chemotherapy; herpes; virus; p53 ID THYMIDINE KINASE GENE; HERPES-SIMPLEX VIRUS-1; TUMOR NECROSIS FACTOR; HUMAN GLIOMA-CELLS; IN-VIVO; CYTOSINE DEAMINASE; CANCER-CELLS; P53 GENE; SELECTIVE ENHANCEMENT; SKIN FIBROBLASTS AB Many gene-therapy strategies under investigation aim to increase the efficacy of current cancer-treatment regimens. Promising results have been obtained in the laboratory and early clinical trials using viral-based motifs specifically designed to enhance the efficacy of ionizing radiation or chemotherapy. These strategies fall into two general categories: replication-incompetent viral shuttle vectors for the delivery of specific genes encoding a chemo/radiation modulator and attenuated replication-competent viruses with proposed replicative advantages in tumor cells. In this review, we discuss the rational, molecular mechanisms, and clinical application of these strategies with particular focus on recent research applying these viral-based strategies to improve the therapeutic index of ionizing radiation. (C) 1999 Wiley-Liss, Inc. C1 Univ Chicago, Dept Radiat & Cellular Oncol, Div Biol Sci, Chicago, IL 60637 USA. Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Weichselbaum, RR (reprint author), Univ Chicago Hosp, Dept Radiat Oncol, 5841 S Maryland Ave,MC 1089, Chicago, IL 60637 USA. NR 66 TC 17 Z9 17 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1065-7541 J9 RADIAT ONCOL INVESTI JI Radiat. Oncol. Investig. PY 1999 VL 7 IS 5 BP 261 EP 269 DI 10.1002/(SICI)1520-6823(1999)7:5<261::AID-ROI1>3.0.CO;2-V PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 253RA UT WOS:000083568500001 PM 10580895 ER PT J AU Weber, AL Romo, LV Sabates, NR AF Weber, AL Romo, LV Sabates, NR TI Pseudotumor of the orbit - Clinical, pathologic, and radiologic evaluation SO RADIOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID TOLOSA-HUNT SYNDROME; WEGENERS GRANULOMATOSIS; INTRACRANIAL EXTENSION; PAINFUL OPHTHALMOPLEGIA; BONE DESTRUCTION; SARCOIDOSIS; MYOSITIS; INVOLVEMENT; DISEASE; MANIFESTATIONS AB Pseudotumor, Graves' disease, and lymphoproliferative disease are the most common ophthalmologic disease entities requiring evaluation by CT and MR imaging. A history of acute onset, pain, swelling, proptosis, and response to steroids are the classical findings. The radiologic findings are categorized according to location into dacryoadenitis, myositis, and sclerouveitis, with and without associated infiltrations. The inflammatory infiltrate, which is composed of polymorphic leukocytes, lymphocytes, and plasma cells interspersed with a variable amount of fibrovascular tissue, may be diffuse or localized. The preferred radiologic method used for assessment of pseudotumor is CT. MR imaging, however, is indicated for evaluation of the Tolosa-Hunt syndrome, which is characterized by an inflammatory infiltrate in the orbital apex and cavernous sinus leading to cranial nerve involvement with ophthalmoplegia. The clinical and radiologic constellation of findings allows a definitive diagnosis in most cases. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol,Sect Neuroradiol, Boston, MA 02115 USA. Univ Missouri, Eye Fdn Kansas City, Dept Ophthalmol, Kansas City Sch Med,Truman Med Ctr, Kansas City, MO 64110 USA. RP Weber, AL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Radiol, 243 Charles St, Boston, MA 02114 USA. NR 71 TC 82 Z9 89 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-8389 J9 RADIOL CLIN N AM JI Radiol. Clin. N. Am. PD JAN PY 1999 VL 37 IS 1 BP 151 EP + DI 10.1016/S0033-8389(05)70084-1 PG 19 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 164JF UT WOS:000078459800010 PM 10026735 ER PT J AU Kopans, DB AF Kopans, DB TI The breast cancer screening controversy and the National Institutes of Health Consensus Development Conference on breast cancer screening for women ages 40-49 SO RADIOLOGY LA English DT Article DE breast neoplasms; breast radiography, utilization; editorials ID RANDOMIZED CONTROLLED TRIALS; POSITIVE PREDICTIVE VALUE; PREMENOPAUSAL WOMEN; COST-EFFECTIVENESS; STATISTICAL POWER; FAMILY HISTORY; SAMPLE-SIZE; MAMMOGRAPHY; YOUNGER; BENEFIT C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Kopans, DB (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ambulatory Care Bldg,Suite 219,15 Parkman St, Boston, MA 02114 USA. NR 70 TC 17 Z9 17 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 1999 VL 210 IS 1 BP 4 EP 9 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 150YC UT WOS:000077692800004 PM 9885578 ER PT J AU Rao, PM Novelline, R AF Rao, PM Novelline, R TI Case 6: Primary epiploic appendagitis SO RADIOLOGY LA English DT Article DE abdomen, abnormalities; diagnosis please; epiploic appendices ID CT FINDINGS; US C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Rao, PM (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 6 TC 16 Z9 22 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 1999 VL 210 IS 1 BP 145 EP 148 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 150YC UT WOS:000077692800028 PM 9885599 ER PT J AU Gonzalez, RG Schaefer, PW Buonanno, FS Schwamm, LH Budzik, RF Rordorf, G Wang, B Sorensen, AG Koroshetz, WJ AF Gonzalez, RG Schaefer, PW Buonanno, FS Schwamm, LH Budzik, RF Rordorf, G Wang, B Sorensen, AG Koroshetz, WJ TI Diffusion-weighted MR imaging: Diagnostic accuracy in patients imaged within 6 hours of stroke symptom onset SO RADIOLOGY LA English DT Article DE brain, ischemia; brain, MR; magnetic resonance (MR), comparative studies; magnetic resonance (MR), diffusion study ID MAGNETIC-RESONANCE; CEREBRAL-ISCHEMIA; T2-WEIGHTED MRI; BRAIN; WATER AB PURPOSE: To evaluate the diagnostic accuracy of diffusion-weighted magnetic resonance (MR) imaging performed within 6 hours of the onset of stroke symptoms. MATERIALS AND METHODS: The authors reviewed the patient records and images from all patients hospitalized in a 10-month period in whom diffusion-weighted imaging was performed within 6 hours of the onset of strokelike symptoms (n = 22). Analyses included comparison of the initial interpretation of the diffusion-weighted images with the final clinical diagnosis; blinded reviews of computed tomographic (CT) scans and conventional and diffusion-weighted images; and determination of lesion contrast-to-noise ratios (CNRs). RESULTS: Diffusion-weighted images indicated stroke in 14 patients, all of whom had a final diagnosis of acute stroke. Diffusion-weighted images were negative in eight patients, all of whom had a final clinical diagnosis other than stroke (100% sensitivity, 100% specificity, chi(2) = 23.00, P < .0001). Blinded reviews yielded 100% sensitivity and 86% specificity for diffusion-weighted MR imaging (chi(2) = 15.43, P < .0005); 18% sensitivity and 100% specificity for conventional MR imaging (chi(2) = 2.85, P > .2); and 45% sensitivity and 100% specificity for CT (chi(2) = 4.40, P > .10). Lesion percentage CNRs were 77% for diffusion-weighted imaging, 5.5% for CT, 9.8% for T2-weighted MR imaging, and 3.1% for proton-density-weighted MR imaging (P < .002 for diffusion-weighted imaging vs others). CONCLUSION: Diffusion-weighted MR imaging is highly accurate for diagnosing stroke within 6 hours of symptom onset and is superior to CT and conventional MR imaging. C1 Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Gonzalez, RG (reprint author), Massachusetts Gen Hosp, Div Neuroradiol, GRB 285,Fruit St, Boston, MA 02114 USA. OI Schwamm, Lee/0000-0003-0592-9145 FU NINDS NIH HHS [NS34626] NR 21 TC 351 Z9 365 U1 1 U2 5 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 1999 VL 210 IS 1 BP 155 EP 162 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 150YC UT WOS:000077692800030 PM 9885601 ER PT S AU Eng, C AF Eng, C BE Conn, PM TI The role of PTEN, a phosphatase gene, in inherited and sporadic nonmedullary thyroid tumors SO RECENT PROGRESS IN HORMONE RESEARCH, VOL 54: PROCEEDINGS OF THE 1998 CONFERENCE SE RECENT PROGRESS IN HORMONE RESEARCH LA English DT Article; Proceedings Paper CT 54th Meeting of Recent Progress in Hormone Research CY 1998 CL STEVENSON, WASHINGTON SP Endocrine Soc ID RILEY-RUVALCABA-SYNDROME; MULTIPLE HAMARTOMA SYNDROME; BANNAYAN-ZONANA-SYNDROME; COWDEN-DISEASE; GERMLINE MUTATIONS; BREAST-CANCER; GROWTH-FACTOR; SUPPRESSOR; HEMANGIOMAS; ASSOCIATION AB PTEN/MMACI/TEP1, a tumor suppressor gene located on 10q23.3, encodes an almost ubiquitously expressed dual-specificity phosphatase. Germline mutations in PTEN have been found in the majority of cases of sporadic and familial Cowden syndrome (CS), an autosomal dominant inherited cancer syndrome characterised by multiple hamartomas and benign and malignant disease of the thyroid and breast. Interestingly, germline mutations in PTEN have also been found in about 50% of a related but distinct disorder, Bannayan-Ruvalcaba-Riley syndrome (BRR), which is characterised by neonatal-onset macrocephaly, mental retardation, Hashimoto's thyroiditis, lipomatosis, haemangiomas, hamartomatous polyps, and pigmented macules of the glans penis. Somatic PTEN mutation has been described to a greater or lesser extent in various benign and malignant tumor types. Somatic deletions have been described in follicular adenomas of the thyroid and papillary thyroid carcinomas. C1 Harvard Univ, Sch Med,Dept Adult Oncol, Dana Farber Canc Inst,Translat Res Lab, Dept Med,Charles A Dana Human Canc Genet Unit, Boston, MA 02115 USA. RP Eng, C (reprint author), Ohio State Univ, Ctr Comprehens Canc, Human Canc Genet Program, Clin Canc Genet Lab, 420 W 12th Ave,690C MRF, Columbus, OH 43210 USA. OI Eng, Charis/0000-0002-3693-5145 NR 40 TC 20 Z9 21 U1 1 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4410 USA SN 0079-9963 BN 0-879225-33-6 J9 RECENT PROG HORM RES PY 1999 VL 54 BP 441 EP 453 PG 13 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA BR61K UT WOS:000166956400017 PM 10548886 ER PT J AU Meissner, HH Santiago, SM Koyal, SN Riemer, A Stein, M Goldman, MD Williams, AJ AF Meissner, HH Santiago, SM Koyal, SN Riemer, A Stein, M Goldman, MD Williams, AJ TI Characteristics of nasal airflow and the effect of a nasal dilator in normal human subjects SO RESPIRATION PHYSIOLOGY LA English DT Article DE air flow, nasal; mammals, humans; resistance, nasal; upper airways, nasal resistance, air flow ID OBSTRUCTIVE SLEEP-APNEA; FLOW; RESISTANCE AB Nasal resistance contributes to negative airway pressure during breathing. We sought to define normal patterns of nasal Bow and the effects of mechanical dilatation and splinting of the nares on flow during forced inspiration and expiration. Maximal inspiratory and expiratory flow volume loops (FVL) were determined in 17 normal subjects. Oral FVL were obtained with nares clamped and nasal FVL through a mask with and without dilatation of nares using a plastic splint (Nozovent(R)). Oral FVL were normal in all. Two patterns of nasal FVL were observed: one indicating 'variable' extrathoracic obstruction, the other indicating 'fixed' extrathoracic obstruction. Maximal inspiratory flow at 50% of vital capacity (FIF50) was improved by the Nozovent(R) only in those with a 'variable' pattern (FIF50 (L/sec): 1.54 +/- 0.3 to 1.86 +/- 0.5; P < 0.05, versus 1.92 +/- 0.3 to 2.21 +/- 0.3; P = 0.5), In subjects with a fixed pattern, failure of dilatation of the nares to increase flow suggests that the site of inspiratory Bow limitation is within the bony nostril. (C) 1999 Elsevier Science B.V. All rights reserved. C1 W Los Angeles Vet Affairs Med Ctr, Div Pulm & Crit Care Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA. St Thomas Hosp, Lane Fox Resp Unit, London SE1 7EH, England. RP Meissner, HH (reprint author), W Los Angeles Vet Affairs Med Ctr, Div Pulm & Crit Care Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 13 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0034-5687 J9 RESP PHYSIOL JI Respir. Physiol. PD JAN 1 PY 1999 VL 115 IS 1 BP 95 EP 101 DI 10.1016/S0034-5687(98)00100-5 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 191GX UT WOS:000080015500009 PM 10344418 ER PT J AU Vorwerk, CK Bonheur, J Kreutz, MR Dreyer, EB Laev, H AF Vorwerk, CK Bonheur, J Kreutz, MR Dreyer, EB Laev, H TI GM1 ganglioside administration protects spinal neurons after glutamate excitotoxicity SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE LA English DT Article DE ganglioside; glutamate; spinal cord; in vitro; LDH; immunohistochemistry ID CONCUSSIVE BRAIN INJURY; EXCITATORY AMINO-ACIDS; CORD INJURY; MONOSIALOGANGLIOSIDE GM1; EXTRACELLULAR LEVELS; IN-VIVO; NEUROTOXICITY; RAT; ISCHEMIA; CELLS AB Injury of the nervous system initiates a cascade of signal transduction including a rise in extracellular glutamate which leads to subsequent secondary neuronal loss. Excitotoxicity is known to play a crucial role in cell death during spinal cord trauma. Gangliosides, particularly monosialogangliosides (GM1), are protective against various neurological insults, including excitotoxicity. Gangliosides may improve outcome following human spinal cord injury in humans. To further explore the relationship between excitotoxicity and GM1, dissociated murine spinal cord preparations were exposed to glutamate (0.5 mM) with the subsequent administration of GM1 (80 mu M) at 8 and 13 days in culture. The addition of GM1 30 minutes after exposure to glutamate significantly reduced neuronal damage and preserved membrane structure and integrity. These results demonstrate that post-treatment with GM1 gangliosides after glutamate-induced excitotoxicity is effective in protecting spinal cord neurons. C1 Vet Adm, Dept Ophthalmol, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. Otto von Guericke Univ, Inst Med Psychol, AG Mol & Cell Neurobiol, D-39118 Magdeburg, Germany. Leibniz Inst Neurobiol, Dept Neurochem Mol Biol, D-39118 Magdeburg, Germany. New York State Psychiat Inst, Div Neurosci, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. RP Vorwerk, CK (reprint author), Vet Affairs Med Ctr, Univ & Woodland Ave, Philadelphia, PA 19104 USA. NR 37 TC 9 Z9 10 U1 0 U2 3 PU IOS PRESS PI AMSTERDAM PA VAN DIEMENSTRAAT 94, 1013 CN AMSTERDAM, NETHERLANDS SN 0922-6028 J9 RESTOR NEUROL NEUROS JI Restor. Neurol. Neurosci. PY 1999 VL 14 IS 1 BP 47 EP 51 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 194FV UT WOS:000080182200004 ER PT J AU Brazitikos, PD D'Amico, DJ Tsinopoulos, IT Stangos, NT AF Brazitikos, PD D'Amico, DJ Tsinopoulos, IT Stangos, NT TI Primary vitrectomy with perfluoro-n-octane use in the treatment of pseudophakic retinal detachment with undetected retinal breaks SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article; Proceedings Paper CT 21st Meeting of the Club-Jules-Gonin CY AUG 28-SEP 01, 1998 CL EDINBURGH, SCOTLAND SP Club Jules Gonin DE perfluoro-n-octane; perfluoro-n-octane-air exchange; pseudophakic retinal detachment; retinal breaks; pars plana vitrectomy ID PARS-PLANA VITRECTOMY; PROLIFERATIVE VITREORETINOPATHY; PNEUMATIC RETINOPEXY; CATARACT-SURGERY; COMPLICATIONS; MANAGEMENT; BUCKLE AB Purpose: This report describes the results of a prospective trial to evaluate the efficacy of pars plana vitrectomy (PPV) in conjunction with perfluoro-n-octane (PFO) as initial treatment of pseudophakic retinal detachment (RD) with no breaks diagnosed preoperatively. Methods: Fourteen consecutive eyes presenting with pseudophakic RD in which retinal breaks could not be identified preoperatively underwent primary PPV, internal microsurgical identification of the retinal breaks with endoillumination and noncontact wide angle viewing system, PFO retinal reattachment, transscleral cryopexy or endolaser treatment of breaks, PFO-air exchange, and final injection of 20% sulfur hexafluoride. In five eyes, a scleral buckle was also used. Mean follow-up period was 18 months. Results: In 13 of the 14 eyes in which no breaks had been identified preoperatively, breaks were diagnosed during surgery. Perfluoro-n-octane retinal attachment facilitated accurate microscopic treatment of retinal breaks. The retina was reattached with a single operation in all eyes. Eleven eyes had final visual acuity of 20/60 or better. Complications were minimal. Conclusions: Pars plana vitrectomy in conjunction with PFO expression of subretinal fluid is effective in the initial treatment of pseudophakic RD with no preoperative diagnosis of retinal breaks. C1 Democritus Univ Thrace, Dept Ophthalmol, Alexandroupolis, Greece. Blue Cross Clin Thessaloniki, Salonika, Greece. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Brazitikos, PD (reprint author), 10 Agias Sophias St, Salonika 54622, Greece. NR 33 TC 44 Z9 45 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PY 1999 VL 19 IS 2 BP 103 EP 109 PG 7 WC Ophthalmology SC Ophthalmology GA 403KV UT WOS:000167041800002 PM 10213234 ER PT J AU Arawia, MA Nayak, RC AF Arawia, MA Nayak, RC TI Circulating antipericyte autoantibodies in diabetic retinopathy SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE autoantibody; autoimmunity; capillary complications; diabetic retinopathy; microvessel; pericyte ID CARDIOVASCULAR AUTONOMIC NEUROPATHY; ANTI-ADRENAL MEDULLARY; ALDOSE REDUCTASE GENE; PROLIFERATIVE RETINOPATHY; MICROVASCULAR PERICYTES; VASCULAR COMPLICATIONS; GANGLIOSIDE ANTIGEN; IMMUNE-COMPLEXES; CELL ANTIBODIES; DEVELOPING IDDM AB Purpose: A number of reports suggest that autoimmune mechanisms may play a role in diabetic microangiopathy, and the existence of circulating antiendothelial cell autoantibodies in diabetic retinopathy has been reported. Because capillary pericyte injury/dysfunction is considered to be an early event in the pathogenesis of diabetic retinopathy and pericyte "drop out" or loss is considered pathognomonic in diabetic retinopathy, we screened diabetic sera for the presence of circulating antipericyte autoantibodies. Methods: Diabetic sera were screened for the presence of antipericyte autoantibodies by indirect immunofluorescence on tissue cultured bovine retinal pericytes, Analysis of autoantibody prevalence data was performed with 2 x 2 contingency tables analyzed using Fisher's exact test. Results: Diabetic subjects were found to have autoantibodies to microvascular pericytes in their circulation. The prevalence of these antibodies declines with increasing severity of retinopathy. A peak of antibody prevalence was seen at 5-10 years' duration of diabetes. These autoantibodies were found in both Type I and Type II diabetics and in prediabetics. Conclusions: The finding of antipericyte autoantibodies in the circulation of a subpopulation of diabetic subjects suggests that the immune system may play a role in the early pathophysiology of diabetic retinopathy in some patients. These results may contribute to understanding why retinopathy progresses in some patients despite consistent reduction of blood sugar. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Elliott P Joslin Res Labs, Boston, MA 02115 USA. RP Nayak, RC (reprint author), Tufts Univ, New England Med Ctr, Sch Med, Dept Physiol, Box 8103,750 Washington St, Boston, MA 02111 USA. NR 74 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PY 1999 VL 19 IS 5 BP 390 EP 400 PG 11 WC Ophthalmology SC Ophthalmology GA 403KY UT WOS:000167042100005 ER PT J AU Weissgold, DJ Gragoudas, ES Kent, C Amrein, PC Dickersin, GR AF Weissgold, DJ Gragoudas, ES Kent, C Amrein, PC Dickersin, GR TI Choroidal metastasis from olfactory neuroblastoma (esthesioneuroblastoma) SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article ID NEURO-BLASTOMA C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. Univ Vermont, Coll Med, Retina Serv, Dept Ophthalmol, Burlington, VT USA. Massachusetts Eye & Ear Infirm, Pathol Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Ophthalmol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Gragoudas, ES (reprint author), Massachusetts Eye & Ear Infirm, Retina Serv, 243 Charles St, Boston, MA 02114 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PY 1999 VL 19 IS 5 BP 459 EP 462 PG 4 WC Ophthalmology SC Ophthalmology GA 403KY UT WOS:000167042100020 PM 10546948 ER PT J AU Sarraf, D Gin, T Yu, F Brannon, A Owens, SL Bird, AC AF Sarraf, D Gin, T Yu, F Brannon, A Owens, SL Bird, AC TI Long-term drusen study SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE age-related macular degeneration; choroidal neovascularization; drusen; drusen grading; high-risk drusen; geographic atrophy; Kaplan-Meier ID DISCIFORM MACULAR DEGENERATION; RETINAL-PIGMENT EPITHELIUM; RISK-FACTORS; 2ND EYE; PROGNOSIS; NEOVASCULARIZATION; ABNORMALITIES; PREVALENCE; EVOLUTION AB Purpose: To determine the yearly incidence of visual loss in the fellow eyes of patients with unilateral neovascular age-related macular degeneration (ARMD) and to assess the drusen characteristics portending the greatest risk for this outcome. Methods: A total of 101 patients with unilateral exudative ARMD and drusen only in the fellow eye were entered into the study and prospectively followed up to 9 years. Visual acuity, color fundus photography, fluorescein angiography, and grading of drusen characteristics were obtained for each patient on entry into the study. Patients were followed at annual intervals with color fundus photography. The study endpoint was the development of choroidal neovascularization (CNV) or geographic atrophy (GA) in the fellow eye. Results: Yearly incidence rates for the development of an endpoint lesion were between 5 and 14%. The risk of CNV peaked at 4 years and dissipated thereafter. Longer follow-up was associated with a slightly increased incidence of GA. Greater drusen number was most highly associated with the development of an endpoint lesion. Drusen size and confluence were also significant. Conclusions: The risk of CNV in patients with ARMD is heralded by an increase in the number, size, and confluence of drusen. This risk eventually declines and is followed by later increased risk of GA. C1 Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Ophthalmol Sect, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. Royal Victoria Hosp, Dept Ophthalmol, Melbourne, Vic, Australia. Univ Calif Los Angeles, Med Ctr, Jules Stein Eye Inst, Ctr Eye Epidemiol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA USA. Moorfields Eye Hosp, London, England. RP Sarraf, D (reprint author), Univ Calif Los Angeles, Sch Med, Jules Stein Eye Inst, 100 Stein Plaza, Los Angeles, CA 90095 USA. NR 25 TC 33 Z9 33 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PY 1999 VL 19 IS 6 BP 513 EP 519 DI 10.1097/00006982-199911000-00006 PG 7 WC Ophthalmology SC Ophthalmology GA 403KZ UT WOS:000167042200006 PM 10606451 ER PT B AU Rizzo, JF Loewenstein, J Wyatt, J AF Rizzo, JF Loewenstein, J Wyatt, J BE Hollyfield, JG Anderson, RE LaVail, MM TI Development of an epiretinal electronic visual prosthesis - The Harvard Medical School Massachusetts Institute of Technology Research Program SO RETINAL DEGENERATIVE DISEASES AND EXPERIMENTAL THERAPY LA English DT Proceedings Paper CT 8th International Symposium on Retinal Degeneration CY JUL 20-25, 1998 CL SCHLUCHSEE, GERMANY SP Fdn Fighting Blindness, Retinal Preservat Fdn, Deutsch Forsch Gemeinschaft, Pro Retina, CIBA Vis ID ELECTRICAL-STIMULATION; RETINA; PHOTORECEPTORS AB Diseases of the retina and optic nerve are common causes of irreversible blindness. Given the lack of effective treatments, several laboratories are utilizing micro-electronic technology to develop either a cortical or retinal prosthesis. Each strategy offers certain advantages, but both face numerous and formidable challenges. Consequently, a, clinically useful device of either type is still conceptual. The technological means to build prostheses are available but the ultimate obstacle is the integration of the technology with the brain. This review primarily focuses on our efforts to develop a retinal prosthesis. In particular we address the two problems that we believe to be most challenging: I) need to demonstrate that retinal stimulation can produce "useful" vision in a blind patient, and 2) need to demonstrate long-term biocomopatibility of an implanted device in an animal. Brindley produced crude visual sensations by stimulating the visual cortex in a blind patient 32 years ago.(1) This early success coupled with the broad therapeutic potential of a cortical prosthesis to treat blindness caused by damage of either the retina or optic nerve has made this pursuit attractive to many scientists. Developing a cortical prosthesis that remains functional and biocompatible for prolonged periods of time is a difficult task and progress has not surprisingly been slow.(2) The convoluted surface of the mobile brain and the need for penetration of the subsurface layer of the visual cortex increase the difficulty of maintaining a stable interface. The potential risks of neurosurgery are also a formidable if not simply a psychological barrier for patients. Although few patients have been tested, the research teams have concentrated on improving the electrode arrays and other tools that will hopefully improve results in the future. Alternative sites for a visual prosthesis include the lateral geniculate body, which has the disadvantage of being located deep within the brain which creates even greater surgical risk, and the optic nerve. The latter is more accessible but the density of axons would make it difficult to activate them in small clusters that might potentially generate focal perceptions of light. Partly because of these considerations nearly ten years ago we initiated an effort to develop a retinal prosthesis. Our interest in working more peripherally was stimulated in part by the occurrence of relatively common causes of blindness that spare the retinal ganglion cells,(2) by the increasing sophistication and miniaturization of micro-electronics, and by the success of cochlear implants.(3) Working within the eye, however, is a formidable challenge and there are numerous limitations. Compared to the inner ear, the eye is prone to chronic inflammatory reactions, its nerve tissue (i.e. the retina) can relatively easily detach and become non-functional and the potential for a devastating infection make it untenable to have wires that penetrate the eye. Mechanical stabilization of a prosthesis on the retinal surface is difficult and fraught with potential danger to the retina. There is also the added possibility that epiretinal implantation may stimulate formation of surface membranes that could dislodge the device and create a barrier of high electrical resistance between the electrodes and the cells we intend to stimulate. Lastly, many blinding diseases destroy the output (retinal ganglion) cells or their axons, which would preclude use of a retinal prosthesis and therefore reduce the number of potential patients. Nevertheless we believe the quest for a retinal prosthesis is justifiable. Two major blinding diseases, retinitis pigmentosa and macular degeneration, currently have little effective treatment. In both diseases there is evidence of relative preservation of retinal ganglion cells,(4,5) at least until the end-stage in the case of retinitis pigmentosa. There are large numbers of patients with these diseases who could potentially benefit from a retinal prosthesis, which unlike other forms of developing therapies might be able to restore function rather than halting or slowing progression. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Rizzo, JF (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 9 TC 12 Z9 12 U1 1 U2 4 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA BN 0-306-46193-5 PY 1999 BP 463 EP 469 DI 10.1007/978-0-585-33172-0_43 PG 7 WC Medicine, Research & Experimental; Ophthalmology SC Research & Experimental Medicine; Ophthalmology GA BQ63L UT WOS:000089018400043 ER PT J AU Castillo, PR Reinoso, MA AF Castillo, PR Reinoso, MA TI Respiratory dysfunction associated with acute cerebrovascular events SO REVISTA ECUATORIANA DE NEUROLOGIA LA English DT Review ID MECHANICAL VENTILATION; ISCHEMIC STROKE; INTUBATION C1 Baylor Coll Med, Pulm & Crit Care Med Sect, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Houston, TX 77030 USA. NR 39 TC 3 Z9 3 U1 0 U2 0 PU SOCIEDAD ECUATORIANA NEUROLOG PI GUAYAQUIL PA REVISTA ECUATORIANA NEUROLOGIA PO BOX (09-01) 3734, GUAYAQUIL, ECUADOR SN 1019-8113 J9 REV ECUAT NEUROL JI Rev. Ecuat. Neurol. PY 1999 VL 8 IS 1-2 BP 18 EP 22 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 229MU UT WOS:000082199000004 ER PT J AU Kern, RS Green, MF Marshall, BD Wirshing, WC Wirshing, D McGurk, SR Marder, SR Mintz, J AF Kern, RS Green, MF Marshall, BD Wirshing, WC Wirshing, D McGurk, SR Marder, SR Mintz, J TI Risperidone versus haloperidol on secondary memory: Can newer medications aid learning? SO SCHIZOPHRENIA BULLETIN LA English DT Article DE risperidone; haloperidol; verbal learning; memory; California Verbal Learning Test (CVLT) ID PSYCHIATRIC-SYMPTOMS; NEUROPSYCHOLOGICAL FUNCTION; SCHIZOPHRENIC-PATIENTS; CLOZAPINE; DEFICITS; NEUROLEPTICS; PERFORMANCE; MANAGEMENT; SEROTONIN; SKILLS AB The introduction of the new generation of antipsychotic medications for the treatment of schizophrenia has been accompanied by a growing interest in the neurocognitive effects of these drugs. The present study compared the effects of risperidone and haloperidol on secondary memory in a group of treatment-resistant schizophrenia patients. The study design included a baseline phase and two double-blind phases in which patients were randomly assigned to medication under two different dose conditions (fixed dose and flexible dose). Secondary memory was assessed at baseline, fixed-dose, and flexible-dose phases, using the California Verbal Learning Test (CVLT). Six measures were selected, which formed three factors (general verbal learning ability, retention, and learning strategy). Risperidone-treated patients showed greater improvement than haloperidol-treated patients in general verbal learning ability, a finding characterized by significant treatment effects on CVLT measures of learning acquisition, recall consistency, and recognition memory. After controlling for benztropine status, differences on the measures of learning acquisition and recall consistency remained significant, and differences in recognition memory weakened slightly (p = 0.07). No significant treatment effects were noted on retention or learning strategy. These findings suggest that risperidone may exert a facilitating effect on the acquisition of new verbal information, an effect that does not appear to be due to the activation of semantic encoding strategies. C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Schizophrenia Inpatient & Treatment Unit, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Ctr Res Treatment & Rehabil Psychosis, Methodol & Stat Support Unit, Los Angeles, CA 90024 USA. Las Posadas Serv Ctr, Camarillo, CA USA. Mt Sinai Sch Med, New York, NY 10029 USA. RP Kern, RS (reprint author), W Los Angeles Vet Affairs Med Ctr, Schizophrenia Inpatient & Treatment Unit, 11301 Wilshire Blvd,MIRECC 210A, Los Angeles, CA 90073 USA. NR 40 TC 76 Z9 76 U1 2 U2 2 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 1999 VL 25 IS 2 BP 223 EP 232 PG 10 WC Psychiatry SC Psychiatry GA 203QQ UT WOS:000080718700005 PM 10416728 ER PT J AU Craver, JC Pogue-Geile, MF AF Craver, JC Pogue-Geile, MF TI Familial liability to schizophrenia: A sibling study of negative symptoms SO SCHIZOPHRENIA BULLETIN LA English DT Article DE negative symptoms; family study; genetics; anhedonia; schizophrenia ID SCHIZOTYPAL PERSONALITY-DISORDER; PERCEPTUAL ABERRATION; SOCIAL COMPETENCE; HEDONIC CAPACITY; ROSCOMMON FAMILY; TWINS; ANHEDONIA; RISK; RELATIVES; TRAITS AB Negative symptoms are important features in schizophrenia, so in milder form they might also serve as indicators of "unexpressed" liability to schizophrenia among patients' adult relatives without schizophrenia. To address this question, we assessed negative symptoms in 39 stable schizophrenia or schizoaffective outpatients, 39 of their siblings, 38 well control probands, and 38 of their siblings. Negative symptom measures included standard behavior ratings of the core negative symptoms of affective flattening and alogia, as well as a self-report measure of social anhedonia. As expected, even stable outpatients with schizophrenia exhibited significantly more negative symptoms than control probands and control siblings. However, negative behavioral symptoms of affective flattening, alogia, and anhedonia did not significantly differentiate the siblings of the schizophrenia patients from the control probands or their siblings, although there were some trends for anhedonia. The findings suggest that core negative symptoms of observed affective flattening and poverty of speech are not likely to be useful as strong indicators of "unexpressed" liability to schizophrenia. C1 Univ Pittsburgh, Dept Psychol, Clin Psychol Program, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Hlth Serv, Cambridge, MA 02138 USA. RP Pogue-Geile, MF (reprint author), Univ Pittsburgh, Dept Psychol, Clin Psychol Program, 4015 OHara St, Pittsburgh, PA 15260 USA. FU NCRR NIH HHS [RR07084]; NIMH NIH HHS [MH-30915, MH-43666] NR 56 TC 12 Z9 12 U1 0 U2 2 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 1999 VL 25 IS 4 BP 827 EP 839 PG 13 WC Psychiatry SC Psychiatry GA 266WV UT WOS:000084324000016 PM 10667751 ER PT J AU Qi, HL Rand, MD Wu, XH Sestan, N Wang, WY Rakic, P Xu, T Artavanis-Tsakonas, S AF Qi, HL Rand, MD Wu, XH Sestan, N Wang, WY Rakic, P Xu, T Artavanis-Tsakonas, S TI Processing of the Notch ligand delta by the metalloprotease kuzbanian SO SCIENCE LA English DT Article ID CELL FATE; DROSOPHILA; RECEPTOR; PROTEIN; SERRATE; CHOICE AB Signaling by the Notch surface receptor controls cell fate determination in a broad spectrum of tissues. This signaling is triggered by the interaction of the Notch protein with what, so far, have been thought to be transmembrane ligands expressed on adjacent cells. Here biochemical and genetic analyses show that the ligand Delta is cleaved on the surface, releasing an extracellular fragment capable of binding to Notch and acting as an agonist of Notch activity. The ADAM disintegrin metalloprotease Kuzbanian is required for this processing event. These observations raise the possibility that Notch signaling in vivo is modulated by soluble forms of the Notch ligands. C1 Yale Univ, Sch Med, Boyer Ctr Mol Med, Howard Hughes Med Inst,Dept Genet, New Haven, CT 06536 USA. Fudan Univ, Inst Genet, Shanghai 200433, Peoples R China. Yale Univ, Sch Med, Boyer Ctr Mol Med, Neurobiol Sect, New Haven, CT 06536 USA. RP Artavanis-Tsakonas, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS14841, NS26084] NR 21 TC 354 Z9 358 U1 0 U2 9 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 JAN 1 PY 1999 VL 283 IS 5398 BP 91 EP 94 DI 10.1126/science.283.5398.91 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 155ZH UT WOS:000077976600057 PM 9872749 ER PT B AU Marder, S AF Marder, S BE Gattaz, WF Hafner, H TI Treatment research and the causes of schizophrenia SO SEARCH FOR THE CAUSES OF SCHIZOPHRENIA, VOL IV: BALANCE OF THE CENTURY LA English DT Proceedings Paper CT 4th Symposium on the Search for the Causes of Schizophrenia CY NOV, 1998 CL GUARUJA, BRAZIL ID RISPERIDONE C1 W Los Angeles Vet Affairs Med Ctr, Psychiat Dept 116A, Los Angeles, CA 90073 USA. RP Marder, S (reprint author), W Los Angeles Vet Affairs Med Ctr, Psychiat Dept 116A, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Gattaz, Wagner/C-4456-2012 NR 9 TC 0 Z9 0 U1 0 U2 0 PU STEINKOPFF DARMSTADT PI BERLIN 33 PA C/O SPRINGER VERLAG, HEIDELBERGER PLATZ 3, 1000 BERLIN 33, GERMANY BN 3-7985-1172-1 PY 1999 BP 367 EP 370 PG 4 WC Psychiatry SC Psychiatry GA BN88P UT WOS:000083329200027 ER PT J AU Aslam, N Palevsky, PM AF Aslam, N Palevsky, PM TI Real-time ultrasound for placement of dialysis catheters: A new standard of care SO SEMINARS IN DIALYSIS LA English DT Editorial Material ID INTERNAL JUGULAR-VEIN; LANDMARK-GUIDED TECHNIQUE; ACUTE HEMODIALYSIS ACCESS; VENOUS CATHETERS; CANNULATION; COMPLICATIONS; INSERTION C1 VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA. RP Palevsky, PM (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, Room 4N173,Univ Dr Div, Pittsburgh, PA 15240 USA. NR 18 TC 3 Z9 4 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD JAN-FEB PY 1999 VL 12 IS 1 BP 1 EP 4 DI 10.1046/j.1525-139X.1999.t01-1-12103.x PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 160FT UT WOS:000078220300001 ER PT J AU Williams, ME Roshan, B AF Williams, ME Roshan, B TI Role of the new oral hypoglycemic drugs in the diabetic patient with ESRD SO SEMINARS IN DIALYSIS LA English DT Article ID LOWERS BLOOD-PRESSURE; INSULIN-RESISTANCE; LACTIC-ACIDOSIS; RENAL-FAILURE; GLUCOSE-TOLERANCE; METFORMIN THERAPY; MELLITUS; ACARBOSE; PHARMACOKINETICS; TROGLITAZONE C1 Beth Israel Deaconess Med Ctr, Renal Unit, Boston, MA USA. RP Williams, ME (reprint author), Joslin Diabet Ctr, Renal Unit, 1 Joslin Pl, Boston, MA 02215 USA. EM mwilliams@joslin.harvard.edu NR 84 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD JAN-FEB PY 1999 VL 12 IS 1 BP 25 EP 31 DI 10.1046/j.1525-139X.1999.t01-5-00001.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 160FT UT WOS:000078220300010 ER PT J AU Stevenson, F Anderson, KC AF Stevenson, F Anderson, KC TI Introduction: Immunotherapy for multiple myeloma - Insights and advances SO SEMINARS IN HEMATOLOGY LA English DT Editorial Material ID CELLS C1 Southampton Univ Hosp Trust, Tenovus Lab, Southampton, Hants, England. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Stevenson, F (reprint author), Southampton Univ Hosp Trust, Tenovus Lab, Southampton, Hants, England. NR 9 TC 3 Z9 3 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JAN PY 1999 VL 36 IS 1 SU 3 BP 1 EP 2 PG 2 WC Hematology SC Hematology GA 160NP UT WOS:000078237000001 PM 9989481 ER PT J AU Anderson, KC Hamblin, TJ Traynor, A AF Anderson, KC Hamblin, TJ Traynor, A TI Management of multiple myeloma today SO SEMINARS IN HEMATOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; RANDOMIZED TRIAL; CHEMOTHERAPY; MELPHALAN; CYCLOPHOSPHAMIDE; VINCRISTINE; THERAPY C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Royal Bournemouth Hosp, Dept Haematol & Oncol, Bournemouth, Dorset, England. Northwestern Univ, Chicago, IL 60611 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, 44 Binney St,Room DL189, Boston, MA 02115 USA. NR 23 TC 36 Z9 40 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 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JAN PY 1999 VL 36 IS 1 SU 3 BP 3 EP 8 PG 6 WC Hematology SC Hematology GA 160NP UT WOS:000078237000002 PM 9989482 ER PT J AU Berenson, JR Bergsagel, PL Munshi, N AF Berenson, JR Bergsagel, PL Munshi, N TI Initiation and maintenance of multiple myeloma SO SEMINARS IN HEMATOLOGY LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; BONE-MARROW; KAPOSIS-SARCOMA; GROWTH-FACTOR; ANGIOGENESIS; GENE; TRANSLOCATIONS; PROGRESSION; EXPRESSION; PATHWAY C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Cornell Univ, Med Ctr, New York Hosp, Dept Med,Div Hematol, New York, NY 10021 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. RP Berenson, JR (reprint author), W Los Angeles Vet Affairs Med Ctr, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Bergsagel, Peter/A-7842-2011 OI Bergsagel, Peter/0000-0003-1523-7388 NR 29 TC 14 Z9 15 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JAN PY 1999 VL 36 IS 1 SU 3 BP 9 EP 13 PG 5 WC Hematology SC Hematology GA 160NP UT WOS:000078237000003 PM 9989483 ER PT J AU Anderson, KC Lust, JA AF Anderson, KC Lust, JA TI Role of cytokines in multiple myeloma SO SEMINARS IN HEMATOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; INTERLEUKIN-6 SECRETION; HERPESVIRUS-INFECTION; DENDRITIC CELLS; STROMAL CELLS; ADHESION; APOPTOSIS; TUMOR; LYMPHOCYTES; ACTIVATION C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Div Hematol, Rochester, MN USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, 44 Binney St,Room DL189, Boston, MA 02115 USA. NR 42 TC 32 Z9 32 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JAN PY 1999 VL 36 IS 1 SU 3 BP 14 EP 20 PG 7 WC Hematology SC Hematology GA 160NP UT WOS:000078237000004 PM 9989484 ER PT J AU Hart, DNJ Schultze, JL Stewart, AK AF Hart, DNJ Schultze, JL Stewart, AK TI Presentation of tumor antigens SO SEMINARS IN HEMATOLOGY LA English DT Article ID DENDRITIC CELLS; T-CELLS; REGRESSION; MODEL; VIVO C1 Mater Med Res Inst, Brisbane, Qld 4101, Australia. Dana Farber Canc Inst, Boston, MA USA. Toronto Gen Hosp, Toronto, ON, Canada. RP Hart, DNJ (reprint author), Mater Med Res Inst, Raymond Terrace, S Brisbane, Qld 4101, Australia. RI Schultze, Joachim/D-7794-2011; Hart, Derek/B-9505-2014 OI Schultze, Joachim/0000-0003-2812-9853; NR 23 TC 11 Z9 12 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 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JAN PY 1999 VL 36 IS 1 SU 3 BP 21 EP 25 PG 5 WC Hematology SC Hematology GA 160NP UT WOS:000078237000005 PM 9989485 ER PT J AU Kraft, M Arellano, RS Mueller, PR AF Kraft, M Arellano, RS Mueller, PR TI Conscious sedation for the non-anesthesiologist: A primer SO SEMINARS IN INTERVENTIONAL RADIOLOGY LA English DT Review DE anesthesia; conscious sedation; interventional radiology ID INTERVENTIONAL RADIOLOGY AB The basic requirements for the use of conscious sedation in interventional radiology procedures are described. The basic requirements necessary for the correct performance of procedures with intravenous anesthesia are outlined. The drugs used for these procedures are listed. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Kraft, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NR 8 TC 5 Z9 5 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0739-9529 J9 SEMIN INTERVENT RAD JI Semin. Interv. Radiol. PY 1999 VL 16 IS 2 BP 89 EP 98 DI 10.1055/s-0028-1082194 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 209TF UT WOS:000081064400003 ER EF